Protein solubility plays a vital role in pharmaceutical research and production yield. [SEP]Definitions: protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. protein sequence defined as following: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION..", "label": "yes"}
{"id": "converted_328", "sentence1": "Can sorafenib activate AMPK?", "sentence2": "Here, we identify sorafenib as an activator of AMP-activated protein kinase (AMPK), in a manner that involves either upstream LKB1 or CAMKK2. , Persistent activation of AMPK by sorafenib finally led to the impairment of glucose metabolism both in MCF-7 and SKBR3 cells as well as in the highly glycolytic MDA-MB-231 cells, resulting in cell death., Here, we identify sorafenib as an activator of AMP-activated protein kinase (AMPK), in a manner that involves either upstream LKB1 or CAMKK2, Sorafenib synergizes with metformin in NSCLC through AMPK pathway activation., Persistent activation of AMPK by sorafenib finally led to the impairment of glucose metabolism both in MCF-7 and SKBR3 cells as well as in the highly glycolytic MDA-MB-231 cells, resulting in cell death. This previously unrecognized long-term effect of sorafenib was mediated by AMPK-dependent inhibition of the mTORC1 pathway.[SEP]Relations: Metformin has relations: drug_drug with Sorafenib, drug_drug with Sorafenib. Definitions: AMPK defined as following: Catalysis of the reaction: [3-hydroxy-3-methylglutaryl-CoA reductase (NADPH)] + ATP = [3-hydroxy-3-methylglutaryl-CoA reductase (NADPH)] phosphate + ADP. [EC:2.7.11.31, MetaCyc:2.7.1.109-RXN]. metformin defined as following: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289). mTORC1 defined as following: A protein complex that is involved in the both serine/threonine phosphorylation and the regulation of protein synthesis in response to cellular stress.. Sorafenib defined as following: A synthetic compound targeting growth signaling and angiogenesis. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway that controls cell division and proliferation; in addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, thereby blocking tumor angiogenesis.. NSCLC defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. sorafenib defined as following: A synthetic compound targeting growth signaling and angiogenesis. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway that controls cell division and proliferation; in addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, thereby blocking tumor angiogenesis..", "label": "yes"}
{"id": "converted_2476", "sentence1": "Can canagliflozin cause euglycemic diabetic ketoacidosis?", "sentence2": "CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose>500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. , Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia., Canagliflozin raised the risk of amputations and the rate of fractures in the CANVAS trial, although more data are necessary before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis seems to be minimal when the drugs are prescribed properly., Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern., However, some serious side effects, including severe anion gap metabolic acidosis and euglycemic diabetic ketoacidosis (DKA), have been reported. , At present, the Food and Drug Administration (FDA) has only approved three medications (canagliflozin, dapagliflozin and empagliflozin) in this drug class for the management of Type 2 diabetes. In May 2015, the FDA issued a warning of ketoacidosis with use of this drug class., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., Nonconvulsive Status Epilepticus in Elderly Patients Receiving SSRIs; Euglycemic Diabetic Ketoacidosis Associated with Canagliflozin Use in a Type 1 Diabetic Patient; Duloxetine-Induced Galactorrhea; Canagliflozin-Associated Severe Hypercalcemia and Hypernatremia; Vemurafenib-Induced Fanconi Syndrome., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin., We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin., Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. , Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., In this article, we present a case of a 50-year-old woman with type 2 diabetes who developed euglycemic DKA after initiating therapy with canagliflozin. , SGLT2 inhibitors such as canagliflozin may predispose patients not only to diabetic ketoacidosis but also to prolonged glucosuria., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.
, We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., CONCLUSION Treatment with canagliflozin was associated with development of euglycemic ketoacidosis., Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.., Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin.[SEP]Relations: diabetes mellitus, noninsulin-dependent has relations: disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus. Metformin has relations: contraindication with metabolic acidosis, contraindication with metabolic acidosis. diabetic ketoacidosis has relations: disease_disease with type 2 diabetes mellitus, disease_disease with type 2 diabetes mellitus. Empagliflozin has relations: drug_drug with Canagliflozin, drug_drug with Canagliflozin. Dapagliflozin has relations: drug_drug with Canagliflozin, drug_drug with Canagliflozin. Definitions: renal defined as following: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.. SSRIs defined as following: Any agent that increases the extracellular level of the neurotransmitter serotonin (5-HT) by inhibiting its reuptake into the presynaptic cell. Increased level in the synaptic cleft prolongs the action of 5-HT on the postsynaptic receptor. This type of agent is typically used as an antidepressant and in the treatment of anxiety disorders and some personality disorders. They are also typically effective and used in treating some cases of insomnia.. metformin defined as following: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289). DKA defined as following: A life-threatening complication of diabetes mellitus, primarily of TYPE 1 DIABETES MELLITUS with severe INSULIN deficiency and extreme HYPERGLYCEMIA. It is characterized by KETOSIS; DEHYDRATION; and depressed consciousness leading to COMA.. ketones defined as following: Organic compounds containing a carbonyl group =C=O bonded to two hydrocarbon groups.. Canagliflozin defined as following: A C-glucoside with a thiophene ring that is an orally available inhibitor of sodium-glucose transporter 2 (SGLT2) with antihyperglycemic activity. Canagliflozin is also able to reduce body weight and has a low risk for hypoglycemia.. ketoacidosis defined as following: Acidosis resulting from accumulation of ketone bodies. [HPO:probinson]. sodium-glucose cotransporter 2 defined as following: The founding member of the sodium glucose transport proteins. It is predominately expressed in the INTESTINAL MUCOSA of the SMALL INTESTINE.. acetone defined as following: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis.. empagliflozin defined as following: An orally available competitive inhibitor of sodium-glucose co-transporter 2 (SGLT2; SLC5A2) with antihyperglycemic activity. Upon oral administration, empagliflozin selectively and potently inhibits SGLT2 in the kidneys, thereby suppressing the reabsorption of glucose in the proximal tubule. Inhibition of SGLT2 increases urinary glucose excretion by the kidneys, resulting in a reduction of plasma glucose levels in an insulin-independent manner. Inhibition of SGLT2 in the kidneys also suppresses the renal reabsorption of 1,5-anhydroglucitol (1,5AG). This lowers serum 1,5AG and neutrophil 1,5-anhydroglucitol-6-phosphate (1,5AG6P) levels, which may improve neutropenia and neutrophil dysfunction in patients with glycogen storage disease type Ib (GSD Ib). SGLT2, a transport protein exclusively expressed in the proximal renal tubules, mediates approximately 90% of renal glucose reabsorption from tubular fluid.. dapagliflozin defined as following: A selective sodium-glucose co-transporter subtype 2 (SGLT2) inhibitor with antihyperglycemic activity. Dapagliflozin selectively and potently inhibits SGLT2 compared to SGLT1, which is the cotransporter of glucose in the gut.. Hypernatremia defined as following: Higher than normal levels of sodium in the circulating blood.. SGLT2 defined as following: Human SLC5A2 wild-type allele is located in the vicinity of 16p11.2 and is approximately 8 kb in length. This allele, which encodes sodium/glucose cotransporter 2 protein, plays a role in sodium-dependent glucose transport. Mutation of the gene is associated with renal glucosuria.. glucosuria defined as following: The appearance of an abnormally large amount of GLUCOSE in the urine, such as more than 500 mg/day in adults. It can be due to HYPERGLYCEMIA or genetic defects in renal reabsorption (RENAL GLYCOSURIA).. woman defined as following: An adult, female human.. Type 2 diabetes defined as following: A type of diabetes mellitus that is characterized by insulin resistance or desensitization and increased blood glucose levels. This is a chronic disease that can develop gradually over the life of a patient and can be linked to both environmental factors and heredity.. Hypercalcemia defined as following: Abnormally high level of calcium in the blood.. amputations defined as following: The surgical removal of part of, or all of, a limb or other appendage or outgrowth of the body.. metabolic acidosis defined as following: Increased acidity in the blood secondary to acid base imbalance. Causes include diabetes, kidney failure and shock.. fractures defined as following: A traumatic injury to the bone in which the continuity of the bone is broken..", "label": "yes"}
{"id": "converted_2016", "sentence1": "Is ocular melanosis a risk factor for uveal melanoma?", "sentence2": "Ocular/oculodermal (oculo[dermal]) melanocytosis is a congenital periocular pigmentary condition that can lead to the development of uveal melanoma, estimated at 1 in 400 affected patients., Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma. Ophthalmic surveillance, every 6 or 12 months is important, in patients with ocular melanocytosis for early detection of high risk diseases., One of about 400 patients with ODM followed for life is estimated to develop uveal melanoma. Excessive melanocytes in the uveal tract in ODM may provide the biologic basis for susceptibility to the development of uveal melanoma. Patients with ODM should be monitored ophthalmoscopically, especially during the susceptible period, for the development of uveal melanoma. The authors suggest that a national registry of ODM patients be created and prospective data collected to better assess the risk of developing uveal melanoma., In the white population, an association between oculo(dermal) melanocytosis (ODM) and uveal melanoma is well recognized. , Malignant melanomas may arise in the uveal tract, the conjunctiva, the skin of the eyelid, or the orbit. Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions. , Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions., Phacomatosis pigmentovascularis of cesioflammea type in 7 patients: combination of ocular pigmentation (melanocytosis or melanosis) and nevus flammeus with risk for melanoma., In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.DISCUSSION: Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma., Association of ocular and oculodermal melanocytosis with the rate of uveal melanoma metastasis: analysis of 7872 consecutive eyes., Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions, In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma, In this study, patients with melanocytosis who developed uveal melanoma were found to have double the risk for metastasis compared with those without melanocytosis.To determine the relationship of oculo(dermal) melanocytosis to the prognosis of patients with uveal melanoma.Retrospective chart review of 7872 patients with uveal melanoma treated at the Ocular Oncology Service, Wills Eye Institute, from August 25, 1970, through August 27, 2008.Enucleation, plaque radiotherapy, local resection, or thermotherapy.Metastasis and death.Of 7872 patients with uveal melanoma, oculo(dermal) melanocytosis was present in 230 (3%), By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009). , In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma., Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions., CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis., By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009)., CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis.[SEP]Relations: melanocytic neoplasm has relations: disease_disease with melanoma, disease_disease with melanoma. Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. eyelid defined as following: Each of the upper and lower folds of SKIN which cover the EYE when closed.. melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. ocular melanocytosis defined as following: A congenital abnormality characterized by the presence of an increased population of non-proliferating hyperpigmented melanocytes in the sclera, iris, ciliary body, choroid, and orbit. Patients present with hyperchromic heterochromia.. Malignant melanomas defined as following: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445). melanocytes defined as following: Mammalian pigment cells that produce MELANINS, pigments found mainly in the EPIDERMIS, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called MELANOSOMES. The large non-mammalian melanin-containing cells are called MELANOPHORES.. nevus flammeus defined as following: A vascular malformation of developmental origin characterized pathologically by ectasia of superficial dermal capillaries, and clinically by persistent macular erythema. In the past, port wine stains have frequently been termed capillary hemangiomas, which they are not; unfortunately this confusing practice persists: HEMANGIOMA, CAPILLARY is neoplastic, a port-wine stain is non-neoplastic. Port-wine stains vary in color from fairly pale pink to deep red or purple and in size from a few millimeters to many centimeters in diameter. The face is the most frequently affected site and they are most often unilateral. (From Rook et al., Textbook of Dermatology, 5th ed, p483). uveal defined as following: The pigmented vascular coat of the eyeball, consisting of the CHOROID; CILIARY BODY; and IRIS, which are continuous with each other. (Cline et al., Dictionary of Visual Science, 4th ed). PAM defined as following: A group of autosomal dominant inherited non-dystrophic myotonias caused by mutations of the SCN4A gene, resulting in sodium muscle channelopathy. They are characterized by muscle stiffness, which worsens by ingestion of potassium-rich food. This group includes myotonia fluctuans, myotonia permanens, and acetazolamide-responsive myotonia.. Phacomatosis pigmentovascularis defined as following: A rare skin disease characterized by the co-occurrence of a widespread vascular nevus (typically nevus flammeus) and a pigmentary nevus, potentially associated with a variety of other cutaneous nevi, and with or without extracutaneous (most commonly central nervous system, ocular, or musculoskeletal) involvement. Several subtypes are distinguished based on phenotypic characteristics.. eyes defined as following: The organ of sight constituting a pair of globular organs made up of a three-layered roughly spherical structure specialized for receiving and responding to light.. ocular defined as following: Subdivision of face which has as its direct parts orbital cavity and its content and eyelids..", "label": "yes"}
{"id": "converted_181", "sentence1": "Is the abnormal dosage of ultraconserved elements disfavored in cancer cells?", "sentence2": "Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells., We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs. In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched. This observation raises the possibility that CNVs that arise somatically and are relatively newly formed are less likely to have established a CNV profile that is depleted for UCEs. Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. In support of this latter explanation, somatic CNVs that are not associated with disease are depleted for UCEs. Finally, we show that it is possible to observe the CNVs of induced pluripotent stem (iPS) cells become depleted of UCEs over time, suggesting that depletion may be established through selection against UCE-disrupting CNVs without the requirement for meiotic divisions., Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state.[SEP]Relations: malignant giant cell tumor has relations: disease_disease with cancer, disease_disease with cancer. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. human defined as following: Members of the species Homo sapiens.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "no"}
{"id": "converted_4559", "sentence1": "Is there an association between pyostomatitis vegetans and Crohn's disease?", "sentence2": "Among the main oral manifestations of IBD are cobblestoning of the oral mucosa, labial swellings with vertical fissures, pyostomatitis vegetans, angular cheilitis, perioral erythema, and glossitis. , Pyostomatitis Vegetans: A Clue for Diagnosis of Silent Crohn's Disease., We present a case of Pyostomatitis vegetans involving gingiva and oral mucosa with no skin lesion which led to the diagnosis of Crohn's disease to emphasize important role of dentists in diagnosis of rare oral lesions and management of patients' systemic disease., Moreover, in both CD and UC, there occur several other inflammatory skin conditions such as erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa, chronic oral aphthous disease, Sweet syndrome, pyostomatitis vegetans, and bowel-associated dermatosis-arthritis syndrome. , Diffuse mucosal swelling, cobblestone mucosa, localised mucogingivitis, deep linear ulceration, fibrous tissue tags, polyps, nodules, pyostomatitis vegetans, and aphthous-like ulcers have been described in Crohn's disease. , Aphthous stomatitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD., Pyostomatitis vegetans (PV) is a rare, chronic mucocutaneous disorder associated with inflammatory bowel disease (IBD). Oral lesions of PV are distinct and present as multiple white or yellow pustules with an erythematous base that coalesce and undergo necrosis to form a typical \"snail tracks\" appearance. Two cases of PV associated with IBD--one with Crohn's disease (CD) and the other with ulcerative colitis (UC) are reported., Oral involvement during IBD includes several types of lesions: the most common are aphthae; uncommon lesions include, among others, pyostomatitis vegetans and granulomatous lesions of CD. , Pyostomatitis vegetans (PV) is a rare condition characterized by pustules that affect the oral mucosa. It is a highly specific marker for inflammatory bowel disease and its correct recognition may lead to the diagnosis of ulcerative colitis or Crohn's disease. , matitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD. In differe, on-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesio, ment during IBD includes several types of lesions: the most common are aphthae; uncommon lesions include, among others, pyostomatitis vegetans and granulomatous lesions of CD. Starting wit, s ulcers, pyostomatitis vegetans, cobblestoning and gingivitis are important oral findings frequently observed in IBD patients. Their p, e main oral manifestations of IBD are cobblestoning of the oral mucosa, labial swellings with vertical fissures, pyostomatitis vegetans, angular cheilitis, perioral erythema, and glossitis. In this sen, Pyostomatitis vegetans is frequently associated with chronic inflammatory bowel diseases and can, thus, give a diagnostic hint at an existing ulcerative colitis or Crohns disease., Oral Crohn's disease and pyostomatitis vegetans. An unusual association., [Pyostomatitis vegetans and Crohn's disease. A specific association of 2 diseases]., osis of Crohn's disease. Clinical manifestations improved dramatically with prednisone.DISCUSSION: This case of pyostomatitis-pyodermatitis vegetans involved several aspects rarely reported in the literature: a) the cutaneomucosal signs were inaugural; b) the association with Crohn's disease; c) the presence of lesions to the genital mucosa; d) the unusual localization , Pyostomatitis vegetans is a specific marker for ulcerative colitis and Crohn's disease., The pathogenetic interrelationship between pyostomatitis vegetans and Crohn's disease is discussed., Successful treatment with infliximab and methotrexate of pyostomatitis vegetans associated with Crohn's disease., Infliximab and methotrexate may be a promising treatment for the rare cases of pyostomatitis vegetans associated with Crohn's disease., INTRODUCTION: Pyostomatitis vegetan (PV) is often associated with chronic inflammatory bowel disease (IBD).OBSERVATION: Tw[SEP]Relations: Methotrexate has relations: contraindication with inflammatory bowel disease, contraindication with inflammatory bowel disease. inflammatory bowel disease has relations: disease_phenotype_positive with Crohn's disease, disease_phenotype_positive with Crohn's disease, disease_phenotype_positive with Crohn's disease, disease_phenotype_positive with Crohn's disease. Pustule has relations: disease_phenotype_positive with pyoderma gangrenosum, disease_phenotype_positive with pyoderma gangrenosum. Oral ulcer has relations: disease_phenotype_positive with inflammatory bowel disease, disease_phenotype_positive with inflammatory bowel disease. Definitions: lesions defined as following: A localized pathological or traumatic structural change, damage, deformity, or discontinuity of tissue, organ, or body part.. methotrexate defined as following: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.. erythema nodosum defined as following: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy.. pyoderma gangrenosum defined as following: An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown.. angular cheilitis defined as following: Inflammation of the skin at the corners of the mouth characterized by redness, fissures or crusts.. UC defined as following: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.. inflammatory bowel diseases defined as following: Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.. pustules defined as following: A circumscribed and elevated skin lesion filled with purulent material.. ulcers defined as following: A lesion on the surface of the skin or a mucous surface, produced by the sloughing of inflammatory necrotic tissue.. oral mucosa defined as following: Lining of the ORAL CAVITY, including mucosa on the GUMS; the PALATE; the LIP; the CHEEK; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous EPITHELIUM covering muscle, bone, or glands but can show varying degree of keratinization at specific locations.. Sweet syndrome defined as following: Condition characterized by large, rapidly extending, erythematous, tender plaques on the upper body usually accompanied by fever and dermal infiltration of neutrophilic leukocytes. It occurs mostly in middle-aged women, is often preceded by an upper respiratory infection, and clinically resembles ERYTHEMA MULTIFORME. Sweet syndrome is associated with LEUKEMIA.. gingiva defined as following: Oral tissue surrounding and attached to TEETH.. glossitis defined as following: Inflammation of the tongue.. infliximab defined as following: A chimeric monoclonal antibody to TNF-ALPHA that is used in the treatment of RHEUMATOID ARTHRITIS; ANKYLOSING SPONDYLITIS; PSORIATIC ARTHRITIS and CROHN'S DISEASE.. prednisone defined as following: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.. perioral erythema defined as following: Erythema (Redness of the skin caused by hyperemia of the capillaries in the lower layers of the skin) localized to the region surrounding the mouth. []. tags defined as following: Cardboard, metal, or plastic markers used for object (e.g., medical device, container with clinical samples) and/or personal (e.g., health emergency patients, accident victims) identification and/or classification.. necrosis defined as following: A finding indicating the presence of cellular necrosis in a tissue specimen.. fibrous tissue defined as following: A tissue composed of bundles of collagenous white fibers between which are rows of connective tissue cells.. gingivitis defined as following: Inflammation of gum tissue (GINGIVA) without loss of connective tissue.. IBD defined as following: Gastrointestinal symptoms characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause.. hidradenitis suppurativa defined as following: A chronic suppurative and cicatricial disease of the apocrine glands occurring chiefly in the axillae in women and in the groin and anal regions in men. It is characterized by poral occlusion with secondary bacterial infection, evolving into abscesses which eventually rupture. As the disease becomes chronic, ulcers appear, sinus tracts enlarge, fistulas develop, and fibrosis and scarring become evident.. PV defined as following: A myeloproliferative disorder of unknown etiology, characterized by abnormal proliferation of all hematopoietic bone marrow elements and an absolute increase in red cell mass and total blood volume, associated frequently with splenomegaly, leukocytosis, and thrombocythemia. Hematopoiesis is also reactive in extramedullary sites (liver and spleen). In time myelofibrosis occurs..", "label": "yes"}
{"id": "converted_3370", "sentence1": "Is Nivolumab (Opdivo) a PD-L1 inhibitor?", "sentence2": "Fatal Myocarditis Following Treatment with the PD-1 Inhibitor Nivolumab, PD-1 inhibitor nivolumab (Opdivo), programmed cell death protein 1 (PD-1)-blocking antibodies nivolumab or pembrolizumab , An improvement in the understanding of the role of the immune system in tumor immunosurveillance has led to the development of the programmed death-1 ( PD-1 ) immune checkpoint inhibitor nivolumab ( Opdivo) . , Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy.[SEP]Definitions: PD-1 defined as following: Human PDCD1 wild-type allele is located in the vicinity of 2q37.3 and is approximately 9 kb in length. This allele, which encodes programmed cell death protein 1, plays a role in the modulation of both apoptosis and cellular immunity. Mutation of the gene is associated with systemic lupus erythematosus type 2.. immune checkpoint inhibitor defined as following: An agent that inhibits any of the immune checkpoint inhibitory proteins.. squamous non-small cell lung cancer defined as following: A squamous cell carcinoma that arises from the lung. It is characterized by the presence of large malignant cells. It includes the clear cell and papillary variants of squamous cell carcinoma.. Nivolumab defined as following: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T-cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.. Myocarditis defined as following: Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.. NSCLC defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. PD-L1 defined as following: Human CD274 wild-type allele is located in the vicinity of 9p24 and is approximately 20 kb in length. This allele, which encodes programmed cell death 1 ligand 1 protein, plays a role in the regulation of T cell stimulation and proliferation..", "label": "no"}
{"id": "converted_4190", "sentence1": "Do honey contain diastases/amylases?", "sentence2": "A new rapid method for the determination of honey diastase activity using direct potentiometric principles has been proposed. , The major alpha-amylase in honey was characterized. , Separation of honey amylase[SEP]", "label": "yes"}
{"id": "converted_4283", "sentence1": "Is AZD9668 a VEGF mRNA drug?", "sentence2": "AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in patients with COPD., AZD9668 is a reversible and selective inhibitor of NE, well tolerated at doses of 60 mg bid during Phase I/IIa development.[SEP]Definitions: bid defined as following: Two times per day, at unspecified times.. neutrophil elastase defined as following: This gene plays a role in innate host defense.. COPD defined as following: A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.. VEGF defined as following: Human VEGFA wild-type allele is located within 6p12 and is approximately 16 kb in length. This allele, which encodes vascular endothelial growth factor A protein, plays a role in several processes related to vasculature function, including angiogenesis. The allele is also involved in endothelial cell growth cell migration and apoptotic inhibition..", "label": "no"}
{"id": "converted_3708", "sentence1": "Does ESN364 activate the hypothalamic-pituitary-gonadal axis?", "sentence2": "Oral administration of the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion, leading to a restrained decrease in ovarian hormone levels in women.[SEP]Definitions: NK3R defined as following: Human TACR3 wild-type allele is located within 4q25 and is approximately 130 kb in length. This allele, which encodes neuromedin K receptor protein, plays a role in the modulation of receptor interactions involving the neuropeptide tachykinin..", "label": "no"}
{"id": "converted_3580", "sentence1": "Can discharge destinations be accurately predicted using the Risk Assessment and Prediction Tool (RAPT)?", "sentence2": "CONCLUSION: Our analysis identified age, lower lumbar/lumbosacral surgery, and RAPT walk score as independent predictors of discharge to SNF, and demonstrated superior predictive power compared with the total RAPT Score when combined in a novel grading scale. , PURPOSE: The aim of this study was to evaluate the value of conventional factors, the Risk Assessment and Predictor Tool (RAPT) and performance-based functional tests as predictors of delayed recovery after total hip arthroplasty (THA)., CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort. , The RAPT allows for identification of patients who are likely to be discharged home or to rehabilitation, which may facilitate preoperative planning of postoperative care. Additionally, it identifies intermediate-risk patients and could be used to implement targeted interventions to facilitate discharge home in this group of patients., RESULTS: Overall predictive accuracy was 78%. , OBJECTIVE: To assess the relevance of the RAPT (Risk Assessment and Prediction Tool), among a cohort of patients undergoing total hip arthroplasty (THA)., CONCLUSION: This study confirmed the usefulness of the RAPT to help in patient orientation decision after total hip arthroplasty. , CONCLUSIONS\n\nThe RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., RAPT scores<6 and >10 (of 12) predicted with >90% accuracy discharge to inpatient rehabilitation and home, respectively., The RAPT allows for identification of patients who are likely to be discharged home or to rehabilitation, which may facilitate preoperative planning of postoperative care., The Risk Assessment and Prediction Tool (RAPT) is a preoperative survey constructed to predict discharge disposition after total joint arthroplasty (TJA)., CONCLUSIONS The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., The Risk Assessment and Prediction Tool (RAPT) is a preoperative survey constructed to predict discharge disposition after total joint arthroplasty (TJA)., A low RAPT score is reported to indicate a high risk of needing any form of inpatient rehabilitation after TJA, including short-term nursing facilities., CONCLUSIONS\nThe RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., BACKGROUND: The Risk Assessment and Prediction Tool (RAPT) is used to predict patient discharge disposition after total joint arthroplasty., CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort.[SEP]", "label": "yes"}
{"id": "converted_878", "sentence1": "Is dichlorphenamide effective for periodic paralysis?", "sentence2": "BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP)., In one study dichlorphenamide (DCP) vs placebo was tested in two groups of participants: 42 with hypokalemic periodic paralysis (HypoPP) and 31 with hyperkalemic periodic paralysis (HyperPP), based on clinical criteria. Thirty-four of 42 participants with hypokalemic periodic paralysis completed both treatment phases. For the 34 participants having attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.02) and severity-weighted attack rate (P = 0.01) on DCP relative to placebo were statistically significant. , AUTHORS' CONCLUSIONS: The largest included study that met our inclusion criteria suggested that DCP was effective in the prevention of episodic weakness in both hypokalemic and hyperkalemic periodic paralyses., For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis. , Chronically, acetazolamide, dichlorphenamide, or potassium-sparing diuretics decrease attack frequency and severity but are of little value acutely. , In the HypoPP trial, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and 11 of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects. We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP., Diclofenamid has now already been administered for 2 years. It is well tolerated and has suppressed further attacks., Three patients with Hypokalemic Periodic Paralysis (HOPP)-associated progressive interattack muscle weakness, who became unresponsive or worsened by acetazolamide, responded favorably to dichlorophenamide, a more potent carbonic anhydrase inhibitor. Dichlorophenamide in single-blind placebo-controlled trials, considerably improved functional strength in two of the patients and had a moderate but definite effect in the third., Dichlorophenamide should be considered as an alternate to acetazolamide in the treatment of patients with HOPP-associated interattack muscle weakness who have become unresponsive or worsened by acetazolamide., Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP)., For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis., BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. , Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP)., For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis. A second trial, comparing dichlorphenamide with acetazolamide versus placebo, is currently in progress., Despite our better understanding of the pathogenesis of these disorders, current treatments are largely empirical and the evidence in favor of specific therapy largely anecdotal. For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis.[SEP]Definitions: Acetazolamide defined as following: One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337). HypoPP defined as following: An autosomal dominant familial disorder characterized by recurrent episodes of skeletal muscle weakness associated with falls in serum potassium levels. The condition usually presents in the first or second decade of life with attacks of trunk and leg paresis during sleep or shortly after awakening. Symptoms may persist for hours to days and generally are precipitated by exercise or a meal high in carbohydrates. (Adams et al., Principles of Neurology, 6th ed, p1483). Dichlorophenamide defined as following: A carbonic anhydrase inhibitor that is used in the treatment of glaucoma.. HyperPP defined as following: An autosomal dominant familial disorder which presents in infancy or childhood and is characterized by episodes of weakness associated with hyperkalemia. During attacks, muscles of the lower extremities are initially affected, followed by the lower trunk and arms. Episodes last from 15-60 minutes and typically occur after a period of rest following exercise. A defect in skeletal muscle sodium channels has been identified as the cause of this condition. Normokalemic periodic paralysis is a closely related disorder marked by a lack of alterations in potassium levels during attacks of weakness. (Adams et al., Principles of Neurology, 6th ed, p1481). carbonic anhydrase defined as following: A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of CARBON DIOXIDE from the tissues to the LUNG. EC 4.2.1.1.. Periodic defined as following: Applies to a sign, symptom, or other manifestation that recurs with a fixed time interval, i.e., the symptom-free periods are always of the same length. []. DCP defined as following: Des-gamma carboxyprothrombin (622 aa, ~70 kDa) is encoded by the human F2 gene. This protein is involved in blood coagulation. This form of prothrombin is not efficiently converted to the active enzyme thrombin because it lacks gamma-carboxyglutamyl residues. These modified glutamyl residues are absent because of either vitamin K deficiency or inhibition of vitamin K activity that, in turn, inhibits the enzyme that carboxylates these residues, vitamin K-dependent gamma-carboxylase.. paralysis defined as following: A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45). dichlorphenamide defined as following: A carbonic anhydrase inhibitor that is used in the treatment of glaucoma..", "label": "yes"}
{"id": "converted_4444", "sentence1": "Can epigenetic modifications be heritable?", "sentence2": "Epigenetic alterations (epimutations) could thus contribute to heritable variation within populations and be subject to evolutionary processes such as natural selection and drift. [SEP]", "label": "yes"}
{"id": "converted_362", "sentence1": "Is there a package in R/bioconductor for classification of alternative splicing?", "sentence2": "spliceR: an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data., Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential., spliceR uses the full-length transcript output from RNA-seq assemblers to detect single or multiple exon skipping, alternative donor and acceptor sites, intron retention, alternative first or last exon usage, and mutually exclusive exon events. For each of these events spliceR also annotates the genomic coordinates of the differentially spliced elements, facilitating downstream sequence analysis. For each transcript isoform fraction values are calculated to identify transcript switching between conditions. Lastly, spliceR predicts the coding potential, as well as the potential nonsense mediated decay (NMD) sensitivity of each transcript., Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential., Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential. , Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.[SEP]Definitions: spliceR defined as following: A device designed to join pieces of a material into a continuous length.. transcript defined as following: The initial RNA molecule produced by transcription.. RNA-seq defined as following: A procedure that can determine the nucleotide sequence for all of the RNA transcripts in an individual.. alternative splicing defined as following: A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different..", "label": "yes"}
{"id": "converted_2063", "sentence1": "Is Melioidosis caused by the bacterium Burkholderia pseudomallei?", "sentence2": "Burkholderia pseudomallei, the causative agent of melioidosis,, What drives the occurrence of the melioidosis bacterium Burkholderia pseudomallei in domestic gardens?, Landscape changes influence the occurrence of the melioidosis bacterium Burkholderia pseudomallei in soil in northern Australia., Out of the ground: aerial and exotic habitats of the melioidosis bacterium Burkholderia pseudomallei in grasses in Australia., Melioidosis, caused by the gram-negative bacterium Burkholderia pseudomallei, is a common cause of community-acquired sepsis in Southeast Asia and Northern Australia., Melioidosis is a suppurative chronic infection caused by a gramnegative bacterium, Burkholderia pseudomallei., Melioidosis is an infection caused by the gram-negative bacterium Burkholderia pseudomallei., Melioidosis is an infectious disease caused by a saprophytic bacterium, Burkholderia pseudomallei., Melioidosis is an infectious disease caused by the Gram-negative bacterium Burkholderia pseudomallei., Melioidosis is a pyogenic infection with high mortality caused by the bacterium Burkholderia pseudomallei., Melioidosis is a tropical infectious disease caused by the gram-negative bacterium Burkholderia pseudomallei., Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei., Melioidosis is a rare tropical disease caused by infection with the bacterium Burkholderia pseudomallei., The mechanisms involved in the pathogenesis of melioidosis, caused by the intracellular bacterium Burkholderia pseudomallei, are unclear., Melioidosis is an emerging tropical infection caused by the intracellular bacterium Burkholderia pseudomallei, and is associated with high mortality rates., Melioidosis is an increasingly recognised cause of sepsis and death across South East Asia and Northern Australia, caused by the bacterium Burkholderia pseudomallei, Melioidosis, an infection caused by the gram-negative bacterium Burkholderia pseudomallei, is an important cause of pneumonia, skin infection, sepsis, and death in Southeast Asia and Australia, but is exceedingly rare in North America, The Gram-negative bacterium Burkholderia pseudomallei is able to survive and replicate within leukocytes and causes melioidosis, an important cause of pneumonia-derived community-acquired sepsis in Southeast Asia, Melioidosis, a lethal tropical infection that is endemic in southeast Asia and northern Australia, is caused by the saprophytic Gram-negative bacterium Burkholderia pseudomallei, Melioidosis is an emerging infectious disease caused by the soil bacterium Burkholderia pseudomallei, Melioidosis is a tropical disease of high mortality caused by the environmental bacterium, Burkholderia pseudomallei, Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a bacterium endemic in Southeast Asia and northern Australia, Melioidosis is a life-threatening infection caused by the Gram-negative bacterium Burkholderia pseudomallei, mainly found in Southeast Asia, Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a dreadful disease common in South-East Asia and Northern Australia and is characterized by chronic suppurative lesions and pneumonia, Melioidosis is caused by the environmental bacterium Burkholderia pseudomallei and can present with severe sepsis, Melioidosis is an emerging infectious disease of humans and animals in the tropics caused by the soil bacterium Burkholderia pseudomallei. , Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei. , Melioidosis, infection caused by the Gram-negative bacterium Burkholderia pseudomallei, is a common cause of sepsis in northeast Thailand. , Melioidosis is a potentially fatal disease caused by the bacterium, Burkholderia pseudomallei. , BACKGROUND: The soil-dwelling saprophyte bacterium Burkholderia pseudomallei is the cause of melioidosis, a severe disease of humans and animals in southeast Asia and northern Australia. , Melioidosis is an endemic disease caused by the bacterium Burkholderia pseudomallei. , Melioidosis is a severe infection caused by the gram-negative bacterium, Burkholderia pseudomallei, that is endemic in Southeast Asia. , Melioidosis, infection caused by the Gram-negative bacterium Burkholderia pseudomallei, is a common cause of sepsis in northeast Thailand., Melioidosis is a clinically diverse disease caused by the facultative intracellular Gram-negative bacterium, Burkholderia pseudomallei., Melioidosis is caused by the environmental bacterium Burkholderia pseudomallei and can present with severe sepsis., Melioidosis is a severe infection caused by the gram-negative bacterium, Burkholderia pseudomallei, that is endemic in Southeast Asia., Melioidosis, a lethal tropical infection that is endemic in southeast Asia and northern Australia, is caused by the saprophytic Gram-negative bacterium Burkholderia pseudomallei., Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicemia to chronic localized illness or latent infection., Melioidosis, an often fatal infectious disease in Northeast Thailand, is caused by skin inoculation, inhalation or ingestion of the environmental bacterium, Burkholderia pseudomallei., Melioidosis is an infection caused by Gram-negative bacterium, Burkholderia pseudomallei., Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a dreadful disease common in South-East Asia and Northern Australia and is characterized by chronic suppurative lesions and pneumonia., Largely due to its recognition as a biological threat agent, current knowledge on melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, has increased tremendously over the last years., Melioidosis is an endemic disease caused by the bacterium Burkholderia pseudomallei., Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei., Melioidosis is a potentially fatal disease caused by the bacterium, Burkholderia pseudomallei., Melioidosis is a disease of humans and animals that is caused by the saprophytic bacterium Burkholderia pseudomallei., Melioidosis is an emerging infectious disease of humans and animals in the tropics caused by the soil bacterium Burkholderia pseudomallei., The soil-dwelling saprophyte bacterium Burkholderia pseudomallei is the cause of melioidosis, a severe disease of humans and animals in southeast Asia and northern Australia., Melioidosis is an often fatal infectious disease affecting humans and animals in tropical regions and is caused by the saprophytic environmental bacterium Burkholderia pseudomallei., We have recently shown that during melioidosis, a severe infection caused by the gram-negative bacterium Burkholderia pseudomallei, TLR2 but not TLR4 impacts the immune response of the intact host in vivo., It is caused by the bacterium Burkholderia pseudomallei, which can infect many organs of the body, including the brain, and results in neurological symptoms., Melioidosis is a frequent cause of severe sepsis in Southeast Asia caused by the gram-negative bacterium Burkholderia pseudomallei., What drives the occurrence of the melioidosis bacterium Burkholderia pseudomallei in domestic gardens?, The Gram-negative bacterium Burkholderia pseudomallei is the causative agent of melioidosi, The environmental bacterium Burkholderia pseudomallei causes the infectious disease melioidosis with a high case-fatality rate in tropical and subtropical regions., Burkholderia pseudomallei is a soil-dwelling bacterium and the cause of melioidosis, Melioidosis, an infectious disease caused by the Gram-negative bacterium Burkholderia pseudomallei,, Melioidosis is a frequently fatal infectious disease caused by the soil dwelling Gram-negative bacterium Burkholderia pseudomallei. , Burkholderia pseudomallei, an environmental bacterium that causes the deadly disease melioidosis, , Melioidosis is an important public health problem in Southeast Asia and Northern Australia. This disease is caused by the gram-negative bacilli, Burkholderia pseudomallei, Melioidosis, caused by Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast-Asi, Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei, Melioidosis is a disease of humans caused by opportunistic infection with the soil and water bacterium Burkholderia pseudomallei.[SEP]Relations: Pneumonia has relations: disease_phenotype_positive with melioidosis, disease_phenotype_positive with melioidosis. Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. organs defined as following: A unique macroscopic (gross) anatomic structure that performs specific functions. It is composed of various tissues. An organ is part of an anatomic system or a body region. Representative examples include the heart, lung, liver, spleen, and uterus.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. humans defined as following: Members of the species Homo sapiens.. TLR2 defined as following: Human TLR2 wild-type allele is located within 4q32 and is approximately 18 kb in length. This allele, which encodes toll-like receptor 2 protein, is involved in pathogen recognition, cytokine mediation and innate immunity.. opportunistic infection defined as following: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression.. TLR4 defined as following: Human TLR4 wild-type allele is located within 9q32-q33 and is approximately 11 kb in length. This allele, which encodes toll-like receptor 4 protein, is involved in pathogen recognition, signal transduction and innate immunity. Mutations in the gene are associated with differences in LPS responsiveness.. pneumonia defined as following: Infection of the lung often accompanied by inflammation.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. melioidosis defined as following: A disease of humans and animals that resembles GLANDERS. It is caused by BURKHOLDERIA PSEUDOMALLEI and may range from a dormant infection to a condition that causes multiple abscesses, pneumonia, and bacteremia.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. Burkholderia pseudomallei defined as following: A species of gram-negative, aerobic bacteria that causes MELIOIDOSIS. It has been isolated from soil and water in tropical regions, particularly Southeast Asia..", "label": "yes"}
{"id": "converted_2791", "sentence1": "Is erythropoietin effective for treatment of amyotrophic lateral sclerosis?", "sentence2": "This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.METHODS: Analyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes., CONCLUSIONS: RhEPO 40,000 IU fortnightly did not change the course of ALS., At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline.[SEP]Definitions: NIV defined as following: A type of mechanical ventilation procedure that uses a non-invasive means, such as a face mask or nasal mask, to deliver oxygenated air into the lungs.. ALS defined as following: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94). IU defined as following: Relating to the cavity of the uterus as the intended site of administration.. erythropoietin defined as following: This gene is involved in the regulation of red blood cell production and function.. amyotrophic lateral sclerosis defined as following: An inherited form of amyotrophic lateral sclerosis, usually inherited in an autosomal dominant pattern, caused by mutation(s) in the SOD1 gene, encoding superoxide dismutase..", "label": "no"}
{"id": "converted_3834", "sentence1": "Does the use of bDMARDs during pregnancy impact neonatal development?", "sentence2": "Exposure to bDMARDs during pregnancy does not seem to interfere with post-natal development up to infancy., Long-term follow-up data about newborns exposed to bDMARDs during pregnancy are however scarce. [SEP]", "label": "no"}
{"id": "converted_3006", "sentence1": "Is galcanezumab effective for treatment of migraine?", "sentence2": "Importance: Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention., Conclusions and Relevance: Monthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies. , PURPOSE OF REVIEW: Monoclonal antibodies (mAbs) targeting the calcitonin-gene-related peptide (CGRP) pathway have been developed for episodic and chronic migraine prevention, either through binding the CGRP ligand (eptinezumab, fremanezumab, galcanezumab) or the CGRP receptor (erenumab)., Background Safety findings from a Phase 2b study of galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, for prevention of migraine (NCT02163993) are reported here., Safety of galcanezumab in patients with episodic migraine: A randomized placebo-controlled dose-ranging Phase 2b study., Currently, there is considerable excitement regarding monoclonal antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene-related peptide receptor (erenumab). To date, these monoclonal antibodies have shown promising efficacy in clinical trials, with no major safety concerns. If ongoing long-term studies show that their efficacy can be maintained, this may herald a new era for effective antimigraine therapies., CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. , Four monoclonal antibodies (mAbs) targeting the CGRP pathway are currently under evaluation for the prevention of episodic and chronic migraine: eptinezumab (ALD403), fremanezumab (TEV-48125), galcanezumab (LY2951742), and erenumab (AMG334). , Introduction Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide, used for migraine prevention., Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial., Galcanezumab induced a robust, dose-dependent, and durable inhibition of capsaicin-induced increase in DBF, supporting the continued clinical development of galcanezumab for prophylaxis in migraine patients., The efficacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis.Based on the results of this meta-analysis, CGRP monoclonal antibodies significantly reduced the monthly migraine days and acute migraine-specific medication. , Importance\nGalcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention., Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine., BACKGROUND\nGalcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine., BACKGROUND\nGalcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (≤6-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning., CONCLUSION\nTwelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days., CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks., Conclusions and Relevance\nMonthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies., Importance Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention., BACKGROUND Galcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (≤6-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning., BACKGROUND Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine., Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly MHDs compared to placebo (placebo -2.7, galcanezumab 120 mg -4.8, galcanezumab 240 mg -4.6) (
CONCLUSIONS: Both doses of galcanezumab were superior to placebo in reducing the number of monthly MHDs., Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.
CLINICALTRIALSGOV IDENTIFIER: NCT02614261.
CLASSIFICATION OF EVIDENCE: This interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.
, In September 2018, the US FDA approved galcanezumab as a once-monthly subcutaneous injection for the preventive treatment of migraine in adults., This article summarizes the milestones in the development of galcanezumab leading to its first approval for the preventive treatment of migraine in adults.
, Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine., This article summarizes the milestones in the development of galcanezumab leading to its first approval for the preventive treatment of migraine in adults., Twelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days.[SEP]Relations: Fremanezumab has relations: drug_drug with Galcanezumab, drug_drug with Galcanezumab. Definitions: monoclonal antibodies defined as following: Antibodies produced by a single clone of cells.. CGRP defined as following: A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.. calcitonin gene-related peptide receptor defined as following: Cell surface proteins that bind CALCITONIN GENE-RELATED PEPTIDE with high affinity and trigger intracellular changes which influence the behavior of cells. CGRP receptors are present in both the CENTRAL NERVOUS SYSTEM and the periphery. They are formed via the heterodimerization of the CALCITONIN RECEPTOR-LIKE PROTEIN and RECEPTOR ACTIVITY-MODIFYING PROTEIN 1.. CGRP receptor antagonists defined as following: Pharmacologic agents that block NOCICEPTIVE PAIN signaling from CALCITONIN GENE-RELATED PEPTIDE RECEPTORS. They may be useful for the treatment of pain associated with MIGRAINE DISORDERS and OSTEOARTHRITIS.. calcitonin gene-related peptide defined as following: This gene is involved in the regulation of bone incorporation and blood calcium and phosphate levels.. migraine defined as following: A common, severe type of vascular headache often associated with increased sympathetic activity, resulting in nausea, vomiting, and light sensitivity.. Class I defined as following: A grading of angina such that ordinary physical activity, such as walking or climbing stairs, does not cause angina. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation.. humanized monoclonal antibody defined as following: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.. monoclonal antibody defined as following: A humanized monoclonal antibody directed against parathyroid hormone-related protein (PTH-rP). As a poly-hormone with diverse biological roles, PTH-rP is expressed by normal tissues, acting in local tissue environments in a variety of ways; it is commonly overexpressed by breast, prostate, and other cancers, acting systemically by promoting bone resorption, inhibiting calcium excretion from the kidney, inducing hypercalcemia, and possibly playing a role in the formation of bony metastases. By blocking the effects of PTH-rP on calcium metabolism, monoclonal antibody CAL may inhibit cancer-related hypercalcemia. (NCI04).", "label": "yes"}
{"id": "converted_1367", "sentence1": "Is HER2 active only when it dimerizes?", "sentence2": "HER activation is driven by the formation of various dimer complexes between members of this receptor family., rtuzumab is the first humanized monoclonal antibody in a new class of drugs, the HER dimerization inhibitors, approved by the Food and Drug, Pertuzumab is a novel anti-HER2 monoclonal antibody, which blocks HER2 dimerization with other ligand-activated HER family members. Here, we explored the complement-mediated anti-tumor effects of trastuzumab and pertuzumab on HER2-positive tumor cells of various histological origins., ays. In this study, we report that an anti-HER2 monoclonal antibody (HER2Mab), which blocks HER2 dimerization with HER3, induces HER3 dimerization with EGFR in both low and high HER2 expressing cancer cells., Recent evidence from both basic and clinical studies suggests that ERBB3 (HER3) serves as a key activator of downstream signaling through dimerization with other ERBB proteins and plays a critical role in the widespread clinical resistance to EGFR and HER2 targeting cancer therapies. , HER3 intracellular domains play a crucial role in HER3/HER2 dimerization and activation of downstream signaling pathways., Dimerization among the EGFR family of tyrosine kinase receptors leads to allosteric activation of the kinase domains of the partners., Our results show that quantification of HER dimerization provides information about receptor activation that cannot be obtained by quantification of single receptors. , Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. It was recently approved by the US FDA for use in combination with trastuzumab and docetaxel for patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. , he HER dimerization status may be more important than HER receptor expression per se in determining sensitivity or resistance to a given therapeutic agen, and HER2 dimerization inhibitors, One of the mechanisms by which tumor cell proliferation can be inhibited consists in hampering HER2 dimerization by targeting its extracellular domain with specific antibodies. , Pertuzumab, a humanized monoclonal antibody, is the first HER2 dimerization inhibitor. It binds to the dimerization site on the HER2 domain and prevents ligand-driven pairing of HER2 with other HER receptors, thus inhibiting tumor cell growth and survival, Pertuzumab, another monoclonal antibody, is a HER2 dimerization inhibitor that binds to a different epitope on HER2 than trastuzumab and inhibits HER2 dimer formation with other HER family members such as HER3 and HER1. [SEP]Relations: ERBB3 has relations: protein_protein with EGFR, protein_protein with EGFR. EGFR has relations: protein_protein with ERBB3, protein_protein with ERBB3. transmembrane receptor protein tyrosine kinase activity has relations: molfunc_protein with ERBB3, molfunc_protein with EGFR, molfunc_protein with ERBB3, molfunc_protein with EGFR. Definitions: HER defined as following: A Niger-Congo Bantu language spoken by the Herero and Mbanderu peoples in Namibia and Botswana.. ERBB3 defined as following: This gene is involved in signal transduction pathways that result in cellular proliferation or differentiation. The gene has also been associated with numerous cancers.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. HER2 defined as following: Human ERBB2 wild-type allele is located in the vicinity of 17q21.1 and is approximately 29 kb in length. This allele, which encodes receptor tyrosine-protein kinase erbB-2 protein, plays a role in EGF receptor signal transduction pathways and cellular growth. Amplification or overexpression of this gene is involved in the progression of several forms of cancer, including breast and ovarian tumors.. trastuzumab defined as following: A humanized monoclonal antibody against the ERBB-2 RECEPTOR (HER2). As an ANTINEOPLASTIC AGENT, it is used to treat BREAST CANCER where HER2 is overexpressed.. tumor cell defined as following: Cells of, or derived from, a tumor.. HER1 defined as following: This gene is involved in the epidermal growth factor signal transduction pathway.. monoclonal antibody defined as following: A humanized monoclonal antibody directed against parathyroid hormone-related protein (PTH-rP). As a poly-hormone with diverse biological roles, PTH-rP is expressed by normal tissues, acting in local tissue environments in a variety of ways; it is commonly overexpressed by breast, prostate, and other cancers, acting systemically by promoting bone resorption, inhibiting calcium excretion from the kidney, inducing hypercalcemia, and possibly playing a role in the formation of bony metastases. By blocking the effects of PTH-rP on calcium metabolism, monoclonal antibody CAL may inhibit cancer-related hypercalcemia. (NCI04). EGFR family defined as following: A family of structurally related cell-surface receptors that signal through an intrinsic PROTEIN-TYROSINE KINASE. The receptors are activated upon binding of specific ligands which include EPIDERMAL GROWTH FACTORS, and NEUREGULINS.. HER3 defined as following: A cell surface protein-tyrosine kinase receptor that is specific for NEUREGULINS. It has extensive homology to and can heterodimerize with the EGF RECEPTOR and the ERBB-2 RECEPTOR. Overexpression of the erbB-3 receptor is associated with TUMORIGENESIS.. pertuzumab defined as following: A humanized recombinant monoclonal antibody directed against the extracellular dimerization domain of the HER-2 tyrosine kinase receptor. Binding of the antibody to the dimerization domain of the HER-2 tyrosine kinase receptor protein directly inhibits the ability of the HER-2 tyrosine kinase receptor protein (the most common pairing partner) to dimerize with other HER tyrosine kinase receptor proteins; inhibiting receptor protein dimerization prevents the activation of HER signaling pathways, resulting in tumor cell apoptosis. (NCI04). humanized monoclonal antibody defined as following: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.. docetaxel defined as following: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER.. extracellular domain defined as following: Any part of a transmembrane protein that projects into the environment surrounding a cell.. tyrosine kinase receptors defined as following: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.. epitope defined as following: Sites on an antigen that interact with specific antibodies..", "label": "yes"}
{"id": "converted_4587", "sentence1": "Does atemoya juice inhibit the CYP1A2 enzyme?", "sentence2": "Atemoya juice significantly inhibited CYP1A2 activity in human liver microsomes, but not the activities of CYP2C9 and CYP3A., This suggests that the intake of an excess amount of atemoya juice is necessary to cause a change in the pharmacokinetics of phenacetin when the IC50 values for CYP1A2 inhibition by atemoya and fluvoxamine are taken into account[SEP]Relations: Phenacetin has relations: drug_protein with CYP2C9, drug_protein with CYP2C9. Fluvoxamine has relations: drug_protein with CYP2C9, drug_protein with CYP2C9. Definitions: CYP2C9 defined as following: A cytochrome P-450 subtype that has specificity for acidic XENOBIOTICS. It oxidizes a broad range of important clinical drugs that fall under the categories of NONSTEROIDAL ANTI-INFLAMMATORY AGENTS; HYPOGLYCEMIC AGENTS; ANTCOAGULANTS; and DIURETICS.. phenacetin defined as following: A phenylacetamide that was formerly used in ANALGESICS but nephropathy and METHEMOGLOBINEMIA led to its withdrawal from the market. (From Smith and Reynard, Textbook of Pharmacology,1991, p431). fluvoxamine defined as following: A selective serotonin reuptake inhibitor that is used in the treatment of DEPRESSION and a variety of ANXIETY DISORDERS.. CYP3A defined as following: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.. human defined as following: Members of the species Homo sapiens..", "label": "yes"}
{"id": "converted_4145", "sentence1": "Is atenolol metabolized by CYP2D6?", "sentence2": "The study analysed the prescribing and dispensing of CYP2D6 drugs (metoprolol, donepezil, galantamine, codeine, tamoxifen) together with CYP2D6-blocking SSRIs (paroxetine/fluoxetine) or SSRIs without significant CYP2D6 inhibition (citalopram/escitalopram/sertraline), and the related prescribing of CYP2D6-independent comparator drugs (atenolol, rivastigmine, propoxyphene, anastrozole).[SEP]Definitions: propoxyphene defined as following: The d-isomer of synthetic diphenyl propionate derivative propoxyphene, with narcotic analgesic effect. This agent mimics the effects of the endogenous opiate dextropropoxyphene, by binding to mu receptors located throughout the central nervous system. The binding results in GTP to GDP exchanges on the mu-G-protein complex, by which effector adenylate cyclase is inactivated thereby decreasing intracellular cAMP. This, in turn, inhibits the release of various nociceptive neurotransmitters, such as substance P, gamma-aminobutyric acid (GABA), dopamine, acetylcholine, noradrenaline, vasopressin, and somatostatin. In addition, dextropropoxyphene closes N-type voltage-gated calcium channels and opens calcium-dependent inwardly rectifying potassium channels. This results in hyperpolarization, thereby reducing neuronal excitability, which further decreases the perception of pain.. SSRIs defined as following: Any agent that increases the extracellular level of the neurotransmitter serotonin (5-HT) by inhibiting its reuptake into the presynaptic cell. Increased level in the synaptic cleft prolongs the action of 5-HT on the postsynaptic receptor. This type of agent is typically used as an antidepressant and in the treatment of anxiety disorders and some personality disorders. They are also typically effective and used in treating some cases of insomnia.. donepezil defined as following: The hydrochloride salt of a piperidine derivative with neurocognitive-enhancing activity. Donepezil reversibly inhibits acetylcholinesterase, thereby blocking the hydrolysis of the neurotransmitter acetylcholine and, consequently, increasing its activity. This agent may improve neurocognitive function in Alzheimer's disease, reduce sedation associated with opioid treatment of cancer pain, and improve neurocognitive function in patients who have received radiation therapy for primary brain tumors or brain metastases.. galantamine defined as following: A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders.. codeine defined as following: An opioid analgesic related to MORPHINE but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough.. tamoxifen defined as following: One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.. rivastigmine defined as following: A carbamate-derived reversible CHOLINESTERASE INHIBITOR that is selective for the CENTRAL NERVOUS SYSTEM and is used for the treatment of DEMENTIA in ALZHEIMER DISEASE and PARKINSON DISEASE.. metoprolol defined as following: A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.. atenolol defined as following: A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to PROPRANOLOL, but without a negative inotropic effect.. CYP2D6 defined as following: Cytochrome P450 2D6 (497 aa, ~56 kDa) is encoded by the human CYP2D6 gene. This protein plays a role in flavoprotein metabolism..", "label": "no"}
{"id": "converted_1526", "sentence1": "Is there an association between presenteeism and depression?", "sentence2": "Presenteeism was positively associated with severity of depression (Health and Work Performance Questionnaire, P < 0.0001; WPAI, P < 0.0001)., Statistically significant correlations (0.32-0.53) were found between presenteeism and increasing disability, fatigue, depression, anxiety, and reduced quality of life. , Presenteeism was associated with increasing fatigue, depression, anxiety, and reduced quality of life., Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers. , BACKGROUND: Subthreshold depression is highly prevalent in the general population and causes great loss to society especially in the form of reduced productivity while at work (presenteeism)., Two major causes of worker presenteeism (reduced on-the-job productivity as a result of health problems) are musculoskeletal pain and mental health issues, particularly depression. , Pain and depression were significantly associated with presenteeism. Pr, Survey adjusted multivariable logistic regression assessed classification of 12-month, depression-related presenteeism on the basis of socio-demographic, financial, work and health factors. , RESULTS: The LPT from absenteeism and presenteeism (reduced performance while present at work) was significantly higher among the MDD group., BACKGROUND: Depression is reported to be a major cause of illness-related sub-optimal work performance (presenteeism). , BACKGROUND: It is amply documented that mood disorders adversely affect job satisfaction, workforce productivity, and absenteeism/presenteeism. , The difference in productivity loss due to impaired presenteeism was significantly different between the two groups, but the productivity loss due to absenteeism was not. , Disease activity (OR 3.24, 95% CI 1.11-9.48) and depression (OR 3.22, 95% CI 1.22-8.48) were associated with absenteeism, while depression (OR 5.69, 95% CI 1.77-18.27, disease activity (OR 3.97, 95% CI 1.76-8.98), anxiety (OR 3.90, 95% CI 1.83-8.31), self-efficacy (OR 0.71, 95% CI 0.58-0.86), and increasing age (OR 1.04 per year, 95% CI 1.00-1.08) were associated with presenteeism. , Depression, in particular, appears to be associated with employment, absenteeism, and presenteeism, and should therefore be prioritized in clinical practice., Depression frequently causes unemployment, absenteeism, and presenteeism, which results in significantly reduced productivity., Presenteeism and absenteeism were significantly worse for the depression group at each time point (p < or = .001). In cross-sectional models, presenteeism was associated with more severe depression symptoms, poorer general physical health, psychologically demanding work, the interaction ofpsychologically demanding work with depression, and less job control (r2 range = .33-.54)., Chronic conditions such as depression/anxiety, obesity, arthritis, and back/neck pain are especially important causes of productivity loss. Comorbidities have significant non-additive effects on both absenteeism and presenteeism., RESULTS: At baseline, all presenteeism measures were sensitive to differences between those with (N=69) and without (N=363) depression/anxiety., Depression and anxiety were more consistently associated with \"presenteeism\" (that is, lost productivity while at work) than with absenteeism, whether this was measured by cutback days or by direct questionnaires., RESULTS: Substantial research exists about anxiety and depression costs, such as performance and productivity, absenteeism, presenteeism, disability, physical disability exacerbation, mental health treatment, increased medical care costs, exacerbating of physical illness, and studies of mental health care limitations and cost-offset., The author discusses the etiology and potential solutions for managing this new component in the productivity equation and in addressing depression, the major contributor to presenteeism., For employees who are currently depressed, recent research evidence has demonstrated that pharmacotherapy can have a dramatic and positive effect on lost productivity, absenteeism, and presenteeism., Among participants who were still employed, those with depression had significantly more job turnover, presenteeism, and absenteeism. , Only depression affected both absenteeism-presenteeism and critical incidents. , CONCLUSIONS: Depressive disorders in the workplace persist over time and have a major effect on work performance, most notably on \"presenteeism,\" or reduced effectiveness in the workplace. , The negative effects of depression include those on patients' occupational functioning, including absenteeism, presenteeism, and reduced opportunities for educational and work success. , The remitted group demonstrated a significant improvement in productivity (particularly presenteeism) when compared with the new visit group (Z = -3.29, p = 0.001)., Depression in workers leads to significant absenteeism, \"presenteeism\" (diminished capacity due to illness while still present at work), and significantly increased medical expenses in addition to the costs of psychiatric care. , Significant predictors of presenteeism and activity impairment at follow-up (controlled for gender, age, spondyloarthritis subgroups and presenteeism at baseline) were presenteeism at baseline, poor quality of life, worse disease activity, decreased physical function, lower self-efficacy pain and symptom, higher scores of anxiety, depression, smoking and low education level, and for activity impairment also female sex. , \" Pain and depression were significantly associated with presenteeism., Only depression affected both absenteeism-presenteeism and critical incidents., Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers.[SEP]Relations: anxiety disorder has relations: disease_disease with anxiety, disease_disease with anxiety. Definitions: arthritis defined as following: Acute or chronic inflammation of JOINTS.. MDD defined as following: Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5). musculoskeletal pain defined as following: Discomfort stemming from muscles, LIGAMENTS, tendons, and bones.. Depressive disorders defined as following: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.. depressed defined as following: An emotional state characterized by feelings of sadness, emptiness, and/or tearfulness.. anxiety defined as following: Persistent and disabling ANXIETY.. fatigue defined as following: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.. illness defined as following: A state of ill health, bodily malfunction, or discomfort.. presenteeism defined as following: Reporting for work despite feeling ill.. mood disorders defined as following: Those disorders that have a disturbance in mood as their predominant feature..", "label": "yes"}
{"id": "converted_1466", "sentence1": "Is the HRC Ser96Ala variant associated with sudden cardiac death in patients with dilated cardiomyopathy?", "sentence2": "The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM., The Ser96Ala (S96A) mutation within the histidine rich Ca(2+) binding protein (HRC) has recently been linked to cardiac arrhythmias in idiopathic dilated cardiomyopathy patients, potentially attributable to an increase in spontaneous Ca(2+) release events., A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy., The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers., HRC has been linked with familiar cardiac conduction disease and an HRC polymorphism was shown to associate with malignant ventricular arrhythmias in the background of idiopathic dilated cardiomyopathy., A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy, The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM., The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers, The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy., These findings indicate that the HRC Ser96Ala variant increases the propensity of arrhythmogenic Ca(2+) waves in the stressed failing heart, suggesting a link between this genetic variant and life-threatening ventricular arrhythmias in human carriers.[SEP]Relations: Ventricular arrhythmia has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. Sudden death has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. Definitions: ventricular arrhythmia defined as following: An electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.. variant defined as following: An alteration or difference from a norm or standard.. human defined as following: Members of the species Homo sapiens.. sarcoplasmic reticulum defined as following: A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.. dilated cardiomyopathy defined as following: Cardiomyopathy which is characterized by dilation and contractile dysfunction of the left and right ventricles. It may be idiopathic, or it may result from a myocardial infarction, myocardial infection, or alcohol abuse. It is a cause of congestive heart failure.. polymorphism defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. ventricular arrhythmias defined as following: A disorder characterized by an electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.. cardiac arrhythmias defined as following: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.. sudden death defined as following: The abrupt cessation of all vital bodily functions, manifested by the permanent loss of total cerebral, respiratory, and cardiovascular functions.. DCM defined as following: A chlorinated methotrexate derivative. Dichloromethotrexate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylates and inhibiting DNA and RNA synthesis. This agent is metabolized and excreted by the liver. (NCI04). sudden cardiac death defined as following: Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005).", "label": "yes"}
{"id": "converted_3003", "sentence1": "Is verubecestat effective for Alzheimer’s Disease?", "sentence2": " The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in AD treatment., This reaction was applied to the preparation of verubecestat, which is currently undergoing clinical evaluation for the treatment of Alzheimer's disease., Verubecestat is an inhibitor of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) being evaluated in clinical trials for the treatment of Alzheimer's disease. , CONCLUSIONS: Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. , Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease.Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. , CONCLUSIONS\nVerubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events., Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events.[SEP]Definitions: BACE1 defined as following: Beta-secretase 1 (501 aa, ~56 kDa) is encoded by the human BACE1 gene. This protein plays a role in the proteolysis of ectodomains of membrane proteins.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65..", "label": "no"}
{"id": "converted_370", "sentence1": "Is intense physical activity associated with longevity?", "sentence2": "Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners., Death rates declined with increased levels of total activity (estimated in kilocalories), and declined also with increased intensity of effort measured as from none, to light, to moderately vigorous or vigorous sports play. Death rates at any given quantity of physical exercise were lower for men playing moderately intense sports than for less vigorous men., he purpose of this study was to investigate if jogging, which can be very vigorous, is associated with increased all-cause mortality in men and women., This long-term study of joggers showed that jogging was associated with significantly lower all-cause mortality and a substantial increase in survival for both men and women., Light activities (<4 multiples of resting metabolic rate (METs)) were not associated with reduced mortality rates, moderate activities (4-<6 METs) appeared somewhat beneficial, and vigorous activities (> or =6 METs) clearly predicted lower mortality rates (p, trend = 0.72, 0.07, and <0.001, respectively)., These data demonstrate a graded inverse relationship between total physical activity and mortality. Furthermore, vigorous activities but not nonvigorous activities were associated with longevity., The capacity for prolonged and vigorous physical exercise, particularly if the exercise is recreational, is a strong indicator of longevity.[SEP]Definitions: Death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions..", "label": "yes"}
{"id": "converted_402", "sentence1": "Is paroxetine effective for treatment of premenstrual dysphoric disorder?", "sentence2": "To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE)., All SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and clomipramine) were effective in reducing premenstrual symptoms., Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults., Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication., When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects., Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD., All these women had significant improvements in the HAMA, HAMD, CGI, and PRISM calendar. The rate of response to paroxetine treatment lay between 50% and 78.6% in the continuous-treatment group, and 37.5-93.8% in the intermittent-treatment group, as determined at the study end-point., The present results indicate that paroxetine is effective in both continuous and intermittent treatment of oriental PMDD women, and that the effects of active treatment lasted for six consecutive treatment menstrual cycles., Paroxetine CR is approved for the treatment of major depression, social anxiety disorder, panic disorder and premenstrual dysphoric disorder in adults., Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%., Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms., Daily Record of Severity of Problems scores were lower in the paroxetine group compared with the placebo group, although the differences were not statistically significant., However, the mean on-treatment Inventory of Depressive Symptomatology (clinician-rated) score for the paroxetine group was 17.9 +/- 8.3 compared with 31.5 +/- 11.2 in the placebo group (adjusted mean difference = 13.6, P = 0.009)., Response (Clinical Global Impressions Scale score of 1 or 2) occurred in 70% of subjects randomized to paroxetine CR and 10% of those assigned to placebo (chi2(1) = 7.5, P = 0.006)., The US Food and Drug Administration and Health Canada recently approved paroxetine for the treatment of premenstrual dysphoric disorder., Patients treated with either dose of paroxetine CR demonstrated significantly greater improvements on the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood scores) and on the majority of secondary efficacy measures compared with patients randomly assigned to placebo., For the treatment of PMDD, luteal phase dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well tolerated., A statistically significant difference was observed in favor of paroxetine CR 25 mg versus placebo on the VAS-Mood (adjusted mean difference = -12.58 mm, 95% CI = -18.40 to -6.76; p < .001) and for paroxetine CR 12.5 mg versus placebo (adjusted mean difference = -7.51 mm, 95% CI = -13.40 to -1.62; p = .013)., Paroxetine CR doses of 12.5 mg/day and 25 mg/day are effective in treating PMDD and are well tolerated., At end point, subjects treated with paroxetine CR (12.5 mg and 25 mg) demonstrated significant improvement in VAS-Mood scores compared with those who received placebo (paroxetine CR 12.5 mg mean treatment difference vs. placebo, -8.7 mm; 95% CI, -15.7, -1.7; p =.015; paroxetine CR 25 mg mean treatment difference vs. placebo, -12.1 mm; 95% CI, -18.9, -5.3; p <.001)., Both doses of paroxetine CR 12.5 mg and 25 mg daily are effective and well tolerated in patients who suffer from PMDD., Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration., In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD])., Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive- compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache., Studies having compared the efficiency of antidepressants according to their serotonin activity (paroxetine or sertraline versus maprotiline, that is a selective noradrenaline re-uptake inhibitor), showed that serotonin re-uptake inhibitors were significantly more efficient on all symptoms than maprotiline, that was not more efficient than placebo., Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache., Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache., The effects of active treatment were marked by the first active cycle with luteal phase 17-item Hamilton Rating Scale for Depression scores decreasing from 14.9 (+/- 5.3) to 8.2 (+/- 4.9) in the first, 7.8 (+/- 5.1) in the second, and 7.8 (+/- 6.8) in the third active treatment cycles (F[1,13] = 17.6; p < 0.0001)., The most conservative measure, the Clinical Global Impression (CGI), revealed that 7 of 14 patients had a complete response (CGI = 1 or 2) whereas 4 patients had a partial response (CGI = 3)., These open trial findings are consistent with the notion that paroxetine is effective in the acute phase for the treatment of PDD., The rating of premenstrual irritability, depressed mood, increase in appetite, and anxiety/tension was markedly lower during treatment with paroxetine than before, and this reduction in symptomatology appeared unabated for the entire treatment period.[SEP]Relations: Maprotiline has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Drospirenone has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Fluvoxamine has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Ethinylestradiol has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Sertraline has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Serotonin has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Citalopram has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Norepinephrine has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Fluoxetine has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Clomipramine has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. major affective disorder has relations: contraindication with Paroxetine, contraindication with Paroxetine. Definitions: premenstrual dysphoric disorder defined as following: A condition in which a woman suffers from severe depression, irritability, and tension before MENSTRUATION. Premenstrual dysphoric disorder (PMDD) may involve a wide range of physical or emotional symptoms, which are more severe and debilitating than those seen with premenstrual syndrome (PMS), and which include at least one mood-related symptom. Symptoms usually stop when, or shortly after, menstruation begins.. post-traumatic stress disorder defined as following: A class of traumatic stress disorders with symptoms that last more than one month.. maprotiline defined as following: A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use.. SSRIs defined as following: Any agent that increases the extracellular level of the neurotransmitter serotonin (5-HT) by inhibiting its reuptake into the presynaptic cell. Increased level in the synaptic cleft prolongs the action of 5-HT on the postsynaptic receptor. This type of agent is typically used as an antidepressant and in the treatment of anxiety disorders and some personality disorders. They are also typically effective and used in treating some cases of insomnia.. traumatic stress disorder defined as following: Anxiety disorders manifested by the development of characteristic symptoms following a psychologically traumatic event that is outside the normal range of usual human experience. Symptoms include re-experiencing the traumatic event, increased arousal, and numbing of responsiveness to or reduced involvement with the external world. Traumatic stress disorders can be further classified by the time of onset and the duration of these symptoms.. drospirenone defined as following: A synthetic spironolactone analogue and progestin with progestational and anti-mineralocorticoid activity. Drospirenone binds to the progesterone receptor, the resulting complex becomes activated and binds to specific sites on DNA. This results in a suppression of LH activity and an inhibition of ovulation as well as an alteration in the cervical mucus and endometrium. This leads to an increased difficulty of sperm entry into the uterus and implantation. This drug is used in oral contraceptives.. antidepressants defined as following: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.. fluvoxamine defined as following: A selective serotonin reuptake inhibitor that is used in the treatment of DEPRESSION and a variety of ANXIETY DISORDERS.. Paroxetine defined as following: A serotonin uptake inhibitor that is effective in the treatment of depression.. panic disorder defined as following: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait.. ethinyl estradiol defined as following: A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.. PDD defined as following: A category of developmental disorders characterized by impaired communication and socialization skills. The impairments are incongruent with the individual's developmental level or mental age. These disorders can be associated with general medical or genetic conditions.. sertraline defined as following: A selective serotonin uptake inhibitor that is used in the treatment of depression.. serotonin defined as following: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.. citalopram defined as following: A furancarbonitrile that is one of the SELECTIVE SEROTONIN REUPTAKE INHIBITORS used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from TARDIVE DYSKINESIA in preference to tricyclic antidepressants, which aggravate dyskinesia.. noradrenaline defined as following: A synthetic phenylethylamine that mimics the sympathomimetic actions of the endogenous norepinephrine. Norepinephrine acts directly on the alpha- and beta-adrenergic receptors. Clinically, norepinephrine is used as a peripheral vasoconstrictor that causes constriction of arterial and venous beds via its alpha-adrenergic action. It is also used as a potent inotropic and chronotropic stimulator of the heart mediated through its beta-1 adrenergic action.. irritability defined as following: Abnormal or excessive excitability with easily triggered anger, annoyance, or impatience.. fluoxetine defined as following: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.. clomipramine defined as following: A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.. obsessive-compulsive disorder defined as following: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension.. PD defined as following: A score of 4 or 5 on a 5-point PET scale with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment.. social phobia defined as following: An anxiety disorder characterized by an intense, irrational fear of one or more social or performance situations in which the individual believes that he or she will be scrutinized by others. Exposure to social situations immediately provokes an anxiety response. In adults, the social phobia is recognized as excessive or unreasonable.. SAD defined as following: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (PHOTOTHERAPY), during the season of recurrence.. depressed mood defined as following: An emotional state characterized by feelings of sadness, emptiness, and/or tearfulness.. MDD defined as following: Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5). paroxetine defined as following: A serotonin uptake inhibitor that is effective in the treatment of depression..", "label": "yes"}
{"id": "converted_1778", "sentence1": "Is NADPH oxidase 5 expressed in rodents?", "sentence2": "Because the Nox5 gene is absent in rodents, we generated transgenic mice expressing human Nox5 in a podocyte-specific manner (Nox5(pod+)). , The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents. , The data document that the NOX5 gene was expressed in cells of lagomorphs unlike rodents, making the rabbit an interesting model to study NOX5 functions., Nox5 was lost in rodents, and Nox3, which functions in the inner ear in gravity perception, emerged the most recently, corresponding to full-time adaptation of vertebrates to land. , NOX expression patterns in animals are complex and ancestral NOXes, NOX5-like isoforms and DUOXes are generally found. But there are exceptions; for example rodents lack NOX5 and Caenorhabditis elegans expresses only DUOXes., The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents., The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents, NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents., But there are exceptions; for example rodents lack NOX5 and Caenorhabditis elegans expresses only DUOXes., Because the Nox5 gene is absent in rodents, we generated transgenic mice expressing human Nox5 in a podocyte-specific manner (Nox5(pod+))., The data document that the NOX5 gene was expressed in cells of lagomorphs unlike rodents, making the rabbit an interesting model to study NOX5 functions., The most recently identified member of the Nox family, Nox5, has for the most part been overlooked in renal disease, partly owing to its absence from the rodent genome.[SEP]Definitions: NADPH oxidases defined as following: A family of membrane-associated flavoprotein NADPH-dependent oxidoreductases that catalyze the univalent reduction of OXYGEN to create SUPEROXIDES. Structurally, they are characterized by six N-terminal transmembrane ALPHA-HELICES, a FLAVIN-ADENINE DINUCLEOTIDE (FAD)-binding region, and a C-terminal NADPH-binding region. They are expressed primarily by EPITHELIAL CELLS in gut, kidney, colon, and smooth muscle tissues, as well as GRANULOCYTES and function to transfer electrons across membranes to molecular oxygen. Defects in the production of superoxide ions by some NADPH oxidases result in GRANULOMATOUS DISEASE, CHRONIC.. rodents defined as following: A mammalian order which consists of 29 families and many genera.. reactive oxygen species defined as following: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.. humans defined as following: Members of the species Homo sapiens.. kidney cells defined as following: any of the cells comprising the kidney, functioning in filtering the blood.. renal disease defined as following: Pathological processes of the KIDNEY or its component tissues.. lagomorphs defined as following: An order of small mammals comprising two families, Ochotonidae (pikas) and Leporidae (RABBITS and HARES). Head and body length ranges from about 125 mm to 750 mm. Hares and rabbits have a short tail, and the pikas lack a tail. Rabbits are born furless and with both eyes and ears closed. HARES are born fully haired with eyes and ears open. All are vegetarians. (From Nowak, Walker's Mammals of the World, 5th ed, p539-41). neural defined as following: Of or relating to neurons or the nervous system.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. Caenorhabditis elegans defined as following: A species of nematode that is widely used in biological, biochemical, and genetic studies.. transgenic mice defined as following: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.. vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes..", "label": "no"}
{"id": "converted_4238", "sentence1": "Does daily atemoya juice intake change the pharmacokinetics of CYP1A2 substrates?", "sentence2": "Atemoya juice significantly inhibited CYP1A2 activity in human liver microsomes, but not the activities of CYP2C9 and CYP3A. In spite of this inhibition, preadministration of atemoya had no effect on the pharmacokinetics of phenacetin, a CYP1A2 substrate, in rats. , The results indicate that a daily intake of atemoya would not change the pharmacokinetics of CYP1A2 substrates such as phenacetin as well as CYP2C9- and CYP3A-substrate drugs.[SEP]Relations: Phenacetin has relations: drug_protein with CYP2C9, drug_protein with CYP2C9. Definitions: CYP2C9 defined as following: A cytochrome P-450 subtype that has specificity for acidic XENOBIOTICS. It oxidizes a broad range of important clinical drugs that fall under the categories of NONSTEROIDAL ANTI-INFLAMMATORY AGENTS; HYPOGLYCEMIC AGENTS; ANTCOAGULANTS; and DIURETICS.. phenacetin defined as following: A phenylacetamide that was formerly used in ANALGESICS but nephropathy and METHEMOGLOBINEMIA led to its withdrawal from the market. (From Smith and Reynard, Textbook of Pharmacology,1991, p431). rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. CYP3A defined as following: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.. human defined as following: Members of the species Homo sapiens.. CYP1A2 substrates defined as following: Any substance acted upon by cytochrome P450 1A2..", "label": "no"}
{"id": "converted_1285", "sentence1": "Are EDNRB mutations involved in the development of Hirschsprung disease?", "sentence2": "QTL analysis identifies a modifier locus of aganglionosis in the rat model of Hirschsprung disease carrying Ednrb(sl) mutations, As reported previously, when the same null mutation of the Ednrb gene, Ednrb(sl), was introgressed into the F344 strain, almost 60% of F344-Ednrb(sl/sl) pups did not show any symptoms of aganglionosis, appearing healthy and normally fertile., Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl) mutations, In this study, we found that the null mutation of the Ednrb gene, thought indispensable for enteric neuron development, is insufficient to result in HSCR disease when bred onto a different genetic background in rats carrying Ednrb(sl) mutations., New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease., The aim of this study was to evaluate the implication of the EDN3 and EDNRB genes in a series of patients with Hirschsprung disease from Spain and determinate their mutational spectrum., A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with Hirschsprung disease, Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR., Mutations in genes of the RET receptor tyrosine kinase and endothelin receptor B (EDNRB) signaling pathways have been shown to be associated in HSCR patients. , Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10Dom mouse model of Hirschsprung disease, Molecular genetic analyses have revealed that interactions between mutations in the genes encoding the RET receptor tyrosine kinase and the endothelin receptor type B (EDNRB) are central to the genesis of HSCR, Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease, Thus, genetic interaction between mutations in RET and EDNRB is an underlying mechanism for this complex disorder., EDNRB/EDN3 and Hirschsprung disease type II., Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease, wo susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene and the endothelin B receptor (EDNRB) gene., We conclude that Ednrb loss only in neural crest cells is sufficient to produce the Hirschsprungs disease phenotype observed with genomic Ednrb mutations, EDNRB mutations were detected in 2 of the 13 short-segment HD, The mutations of EDNRB gene and EDN-3 gene are found in the short-segment HD of sporadic Hirschsprung's disease in Chinese population, which suggests that the EDNRB gene and EDN-3 gene play important roles in the pathogenesis of HD, Functional characterization of three mutations of the endothelin B receptor gene in patients with Hirschsprung's disease, Hirschsprung's disease (HSCR) is one the most common congenital intestinal disease. It leads to aganglionic megacolon in the early childhood. Several susceptibility genes have been identified : RET protooncogene and its ligand, glial cell derived neutrophic factor (GDNF), Sox 10, Endothelin-3 (EDN3) and its receptor B (EDNRB). EDNRB mutations are found in 5% of familial or sporadic HSCR, Enteric aganglionosis in Hirschsprung disease has been linked to genes coding for endothelin-3 (EDN3) and the endothelin B receptor (EDNRB), To date, three genes have been identified as susceptibility genes for Hirschsprung's disease (HSCR), the RET proto-oncogene, the endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3), Our data indicate that RET and EDNRB mutations have a role in the aetiology of some sporadically occurring HSCR, Mutations of the endothelin-B receptor and endothelin-3 genes in Hirschsprung's disease, The endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3) have recently been recognized as susceptibility genes for Hirschsprung's disease (HD), These observations confirm that impaired function of the endothelin-B receptor or endothelin-3 is involved in the aetiology of some human HD cases. EDNRB mutations appear to be associated with short-segment HD, in contrast to RET mutations, which are found mainly in long-segment aganglionosis, In addition to mutations in the RET and EDNRB genes, embryonic environmental factors and/or other genetic factors appear to be involved in the development of Hirschsprung disease., Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease., QTL analysis identifies a modifier locus of aganglionosis in the rat model of Hirschsprung disease carrying Ednrb(sl) mutations., Homozygous mutations in the endothelin-B receptor gene (EDNRB) on 13q22 have been identified in humans and mice with Hirschsprung disease type 2 (HSCR2)., A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with Hirschsprung disease., Hitherto however, homozygosity for EDNRB mutations accounted for the HSCR-Waardenburg syndrome (WS) association., These data might suggest that EDNRB mutations could be dosage sensitive: heterozygosity would predispose to isolated HSCR with incomplete penetrance, while homozygosity would result in more complex neurocristopathies associating HSCR and WS features., Highly recurrent RET mutations and novel mutations in genes of the receptor tyrosine kinase and endothelin receptor B pathways in Chinese patients with sporadic Hirschsprung disease., Mutations in genes encoding the RET receptor tyrosine kinase and endothelin receptor type B (EDNRB) are involved in HSCR pathogenesis; however, also important in ENS development are molecules that mediate events that are more restricted than those of RET and EDNRB, act later in development and which might not be HSCR-associated., Several missense mutations of the endothelin-B receptor (EDNRB) associated with Hirschsprung disease have recently been identified., These findings indicate that these missense mutations result in loss of function of EDNRB, and may provide the molecular pathological basis of Hirschsprung disease in some individuals., Manifestation of the disease has been linked to mutations in genes that encode the crucial signals for the development of the enteric nervous system-the RET and EDNRB signalling pathways., In addition to mutations in the RET and EDNRB genes, embryonic environmental factors and/or other genetic factors appear to be involved in the development of Hirschsprung disease, In this study, we investigated whether germline mutations of endothelin receptor B (EDNRB), a gene involved in Hirschsprung disease (HSCR), could also predispose for malignant melanoma (MM), However, the similarity between the distal colonic aganglionosis in Hirschsprung disease and that due to EDN3 or EDNRB mutations led to the hypothesis that levels of expression of these genes might be affected in the absence of mutation, thus causing the Hirschsprung disease phenotype, Our data strongly suggest that EDNRB is involved in predisposition for two different multigenic disorders, HSCR and melanoma.[SEP]Relations: Hirschsprung disease has relations: disease_protein with RET, disease_protein with ECE1, disease_protein with EDN3, disease_protein with EDNRB, disease_protein with SOX10, disease_protein with GDNF, disease_protein with RET, disease_protein with ECE1, disease_protein with EDN3, disease_protein with EDNRB, disease_protein with SOX10, disease_protein with GDNF, disease_protein with RET, disease_protein with ECE1, disease_protein with EDN3, disease_protein with EDNRB, disease_protein with SOX10, disease_protein with GDNF, disease_protein with RET, disease_protein with ECE1, disease_protein with EDN3, disease_protein with EDNRB, disease_protein with SOX10, disease_protein with GDNF, disease_protein with RET, disease_protein with ECE1, disease_protein with EDN3, disease_protein with EDNRB, disease_protein with SOX10, disease_protein with GDNF, disease_protein with RET, disease_protein with ECE1, disease_protein with EDN3, disease_protein with EDNRB, disease_protein with SOX10, disease_protein with GDNF. EDN3 has relations: protein_protein with EDNRB, disease_protein with Hirschsprung disease, protein_protein with EDNRB, disease_protein with Hirschsprung disease. EDNRB has relations: protein_protein with SOX10, disease_protein with Hirschsprung disease, protein_protein with EDN3, protein_protein with SOX10, disease_protein with Hirschsprung disease, protein_protein with EDN3. melanoma has relations: disease_protein with RET, disease_protein with RET. hirschsprung disease, susceptibility to has relations: disease_protein with RET, disease_protein with GDNF, disease_protein with EDNRB, disease_disease with Hirschsprung disease, disease_protein with EDN3, disease_protein with RET, disease_protein with GDNF, disease_protein with EDNRB, disease_disease with Hirschsprung disease, disease_protein with EDN3, disease_protein with RET, disease_protein with GDNF, disease_protein with EDNRB, disease_disease with Hirschsprung disease, disease_protein with EDN3, disease_protein with RET, disease_protein with GDNF, disease_protein with EDNRB, disease_disease with Hirschsprung disease, disease_protein with EDN3. glial cell-derived neurotrophic factor receptor binding has relations: molfunc_protein with GDNF, molfunc_protein with GDNF. ECE1 has relations: disease_protein with Hirschsprung disease, disease_protein with Hirschsprung disease. melanocytic neoplasm has relations: disease_disease with melanoma, disease_disease with melanoma. Definitions: EDNRB defined as following: Endothelin receptor type B (442 aa, ~50 kDa) is encoded by the human EDNRB gene. This protein is involved in vasoconstriction and vasodilation.. receptor tyrosine kinase defined as following: High affinity nerve growth factor receptor (796 aa, ~87 kDa) is encoded by the human NTRK1 gene. This protein is involved in tyrosine phosphorylation, axonogenesis and receptor-mediated signaling.. hearing loss defined as following: Partial or complete loss of the ability to detect or understand sounds resulting from damage to the outer, middle, or inner ear structures. Causes include exposure to loud noise, ear infections, injuries to the ear, genetic, and congenital disorders.. HD defined as following: A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.. EDN3 defined as following: This gene is involved in vasoconstriction.. Ednrb gene defined as following: This gene is involved in cell signaling.. endothelin-3 defined as following: A 21-amino acid peptide that circulates in the plasma, but its source is not known. Endothelin-3 has been found in high concentrations in the brain and may regulate important functions in neurons and astrocytes, such as proliferation and development. It also is found throughout the gastrointestinal tract and in the lung and kidney. (N Eng J Med 1995;333(6):356-63). malignant melanoma defined as following: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445). RET receptor tyrosine kinase defined as following: Receptor protein-tyrosine kinases involved in the signaling of GLIAL CELL-LINE DERIVED NEUROTROPHIC FACTOR ligands. They contain an extracellular cadherin domain and form a receptor complexes with GDNF RECEPTORS. Mutations in ret protein are responsible for HIRSCHSPRUNG DISEASE and MULTIPLE ENDOCRINE NEOPLASIA TYPE 2.. NTN defined as following: This gene plays a role in both inflammatory processes and cellular adhesion.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. RET defined as following: a unit of radiation dose. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. GDNF defined as following: The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE.. Hirschsprung's disease defined as following: Congenital MEGACOLON resulting from the absence of ganglion cells (aganglionosis) in a distal segment of the LARGE INTESTINE. The aganglionic segment is permanently contracted thus causing dilatation proximal to it. In most cases, the aganglionic segment is within the RECTUM and SIGMOID COLON.. glial cell defined as following: The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. neuron defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. RET proto-oncogene defined as following: This gene plays an essential role in neural crest development, cellular growth and differentiation. Mutations in the gene are associated with a variety of neoplasias and carcinomas.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. colonic aganglionosis defined as following: The severe form of Hirschsprung disease, this is characterized by a complete lack of nerve cells in the large intestine, and often a partial lack in the small intestine. The bowel is not stimulated without innervation and obstruction ensues. Surgical intervention is necessary.. neural crest cells defined as following: Neuroectodermal cells of the neural crest. They differentiate into various cell types during EMBRYOGENESIS including craniofacial MESENCHYME; ENDOCRINE CELLS; MELANOCYTES and PERIPHERAL NERVOUS SYSTEM.. locus defined as following: The position of a gene or a chromosomal marker on a chromosome; also, a stretch of DNA at a particular place on a particular chromosome. The use of locus is sometimes restricted to mean regions of DNA that are expressed.. WS defined as following: An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease.. humans defined as following: Members of the species Homo sapiens.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"}
{"id": "converted_3470", "sentence1": "Is overexpression of LY6K associated with better prognosis for non-small cell lung cancer patients?", "sentence2": "Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). , Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035)., Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035).[SEP]Definitions: LY6K defined as following: This gene may be involved in cell growth regulation.. ESCC defined as following: A carcinoma that originates usually from cells on the surface of the middle and lower third of the ESOPHAGUS. Tumor cells exhibit typical squamous morphology and form large polypoid lesions. Mutations in RNF6, LZTS1, TGFBR2, DEC1, and WWOX1 genes are associated with this cancer.. NSCLC defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. testis defined as following: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.. non-small cell lung cancer defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy..", "label": "no"}
{"id": "converted_688", "sentence1": "Is Ctf4 involved in sister chromatid cohesion establishment?", "sentence2": "In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles. Here, we show that each of these factors facilitates cohesin acetylation. Moreover, the absence of Ctf4 and Chl1, but not of the other factors, causes a synthetic growth defect in cells lacking Eco1. Distinct from acetylation defects, sister chromatid cohesion in ctf4Δ and chl1Δ cells is not improved by removing Wapl, Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment, Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1, Influence of the human cohesion establishment factor Ctf4/AND-1, Here, we used Xenopus egg extracts to show that AND-1 and Tim1-Tipin, homologues of Saccharomyces cerevisiae Ctf4 and Tof1-Csm3, respectively, are associated with the replisome and are required for proper establishment of the cohesion observed in the M-phase extracts, These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1, Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion, Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks, WSS1 was also found to interact genetically with SGS1, TOP3, SRS2 and CTF4, which are involved in recombination, repair of replication forks and the establishment of sister chromatid cohesion, The catalytic subunit of budding yeast Polalpha (Pol1p) has been shown to associate in vitro with the Spt16p-Pob3p complex, a component of the nucleosome reorganization system required for both replication and transcription, and with a sister chromatid cohesion factor, Ctf4p, Constituents of the replication fork, such as the DNA polymerase alpha-binding protein Ctf4, contribute to cohesion in ways that are poorly understood, Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3., Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion., Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion., Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks., Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II., Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion., We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint., We show here that CTF8, CTF4 and a helicase encoded by CHL1 are required for efficient sister chromatid cohesion in unperturbed mitotic cells, and provide evidence that Chl1 functions during S-phase., In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis., The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion., Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion., Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment., Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment., Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion, Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3, Establishment of sister chromatid cohesion at the S. cerevisiae replication fork.[SEP]Definitions: MRC1 defined as following: This gene is involved in endocytosis of glycoproteins by macrophages.. Smc3 defined as following: Human SMC3 wild-type allele is located in the vicinity of 10q25 and is approximately 37 kb in length. This allele, which encodes structural maintenance of chromosomes protein 3, is involved in the regulation of chromosome migration during mitosis.. Wapl defined as following: This gene is involved in both DNA replication and sister chromatid cohesion.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. S. cerevisiae defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. spindle defined as following: The array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during mitosis or meiosis and serves to move the duplicated chromosomes apart. [ISBN:0198547684]. TOP3 defined as following: Human TOP3A wild-type allele is located within 17p12-p11.2 and is approximately 41 kb in length. This allele, which encodes DNA topoisomerase 3-alpha protein, is involved in the ATP-independent breakage of negatively supercoiled single-stranded DNA and subsequent passage/rejoining of the broken DNA.. S-phase defined as following: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.. human defined as following: Members of the species Homo sapiens.. catalytic subunit defined as following: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "yes"}
{"id": "converted_903", "sentence1": "Does Rad9 interact with Aft1 in S.cerevisiae?", "sentence2": "Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae., Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ∼2% of the coding genome in the absence of exogenously induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events., Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast, Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae, Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ?2% of the coding genome in the absence of exogenously induced DNA damage. , Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.[SEP]Definitions: centromeres defined as following: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.. genome defined as following: Anatomical set of genes in all the chromosomes.. Rad9 defined as following: Human RAD9A wild-type allele is located within 11q13.1-q13.2 and is approximately 7 kb in length. This allele, which encodes cell cycle checkpoint control protein RAD9A, is involved in the regulation of both DNA repair and cell cycle progression.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine)..", "label": "yes"}
{"id": "converted_824", "sentence1": "is pharmacological treatment of subclinical hypothyroidism effective in reducing cardiovascular events?", "sentence2": "The decision to treat elderly people is still an unresolved clinical challenge--first, due to a lack of appropriately powered randomized controlled trials of L-T4 in sHT patients, examining cardiovascular hard endpoints in various classes of age; and second, because of the negative effects of possible overtreatment., The lack of specific randomized trials enrolling either old or very old subjects, aimed at evaluate the efficacy of hormonal replacement on overall survival and cardiovascular risk reduction along with the negative effects of possible over-treatment, makes the decision to treat older people a still unresolved clinical challenge, In patients with type 2 DM, the presence of SH serves as an additional risk factor for endothelial dysfunction., Treatment of SCH with levothyroxine was associated with fewer IHD events in younger individuals, but this was not evident in older people., Subclinical hyperthyroidism seems to be a risk factor of developing major cardiovascular events, especially stroke in older adults from the general population with normal left ventricular function., SCH appears to influence the postoperative outcome for patients by increasing the development of postoperative atrial fibrillation. However, it is still unproven whether preoperative thyroxine replacement therapy for patients with SCH might prevent postoperative atrial fibrillation after CABG., In CHF patients TSH levels even slightly above normal range are independently associated with a greater likelihood of heart failure progression., In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences between intervention groups., However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. , However, whether SH confers a high risk for cardiovascular disease, and whether LT4 therapy has a long-term benefit that clearly outweighs the risks of overzealous treatment in these individuals, remain topics of controversy.[SEP]Relations: Levothyroxine has relations: contraindication with cardiovascular disease, contraindication with cardiovascular disease. Definitions: L-T4 defined as following: The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.. CHF defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). IHD defined as following: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.. SCH defined as following: A hysterectomy that removes the uterus and leaves the cervix in place..", "label": "no"}
{"id": "converted_1845", "sentence1": "Can the Micro-C XL method achieve mononucleosome resolution?", "sentence2": "We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution, We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution., Micro-C XL: assaying chromosome conformation from the nucleosome to the entire genome., Micro-C XL provides a single assay to interrogate chromosome folding at length scales from the nucleosome to the full genome.[SEP]Definitions: nucleosome defined as following: A complex comprised of DNA wound around a multisubunit core and associated proteins, which forms the primary packing unit of DNA into higher order structures. [GOC:elh]. genome defined as following: Anatomical set of genes in all the chromosomes..", "label": "yes"}
{"id": "converted_297", "sentence1": "Are cyclophilins proteins that bind to prolines?", "sentence2": "Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues., a characteristic of the cyclophilin family of proteins that bind prolines and often act as cis-trans peptidyl-prolyl isomerases. , The cyclophilins are widely expressed enzymes that catalyze the interconversion of the cis and trans peptide bonds of prolines. , an immunophilin on the isomerization of critical prolines that are found in the tCHT1 sequence.[SEP]Definitions: proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. immunophilin defined as following: An enzyme that catalyzes the isomerization of proline residues within proteins. EC 5.2.1.8.. Cyclophilins defined as following: A family of peptidyl-prolyl cis-trans isomerases that bind to CYCLOSPORINS and regulate the IMMUNE SYSTEM. EC 5.2.1.-. cis defined as following: Cytokine-inducible SH2-containing protein (258 aa, ~29 kDa) is encoded by the human CISH gene. This protein is involved in the modulation of signal transduction.. cyclophilins defined as following: A family of peptidyl-prolyl cis-trans isomerases that bind to CYCLOSPORINS and regulate the IMMUNE SYSTEM. EC 5.2.1.-.", "label": "yes"}
{"id": "converted_2780", "sentence1": "Is cariprazine effective for treatment of bipolar disorder?", "sentence2": "BACKGROUND: We evaluated the safety/tolerability of longer-term open-label treatment with cariprazine in patients who had responded to cariprazine for acute bipolar mania., Clinically relevant response and remission outcomes in cariprazine-treated patients with bipolar I disorder., Cariprazine is FDA approved for the acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults., DISCUSSION: Cariprazine-treated patients with bipolar I disorder attained clinically significant improvement in manic symptoms as shown by significantly greater rates of response and remission versus placebo; improvement in manic symptoms did not induce depressive symptoms., OBJECTIVE: Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder., BACKGROUND: Cariprazine was approved for treating schizophrenia and bipolar disorder, and currently is being evaluated for treating depression in clinical trials in the United States.[SEP]Relations: Dopamine has relations: drug_drug with Cariprazine, drug_drug with Cariprazine. Definitions: dopamine defined as following: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.. manic defined as following: An emotional state characterized by marked to extreme elevation of mood with noticeable effect of functioning..", "label": "yes"}
{"id": "converted_1402", "sentence1": "Are there Conserved Noncoding Elements (CNEs) in plant genomes?", "sentence2": "Conservation and functional element discovery in 20 angiosperm plant genomes, The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation, Conserved noncoding sequences highlight shared components of regulatory networks in dicotyledonous plants, Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes, Long identical multispecies elements in plant and animal genomes., Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes, In contrast, among six plant genomes, we only found nonsyntenic LIMEs, Although complex LIMEs were found in both animal and plant genomes, they differed significantly in their composition and copy number, Ultraconserved elements between the genomes of the plants Arabidopsis thaliana and rice, We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp, ultraconserved elements in plants tend to occur in clusters and locate at noncoding regions, the functions of these plant ultraconserved elements and the reasons why they are practically frozen during the evolution of millions of years remain a mystery, Conserved noncoding sequences in the grasses, Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. Grass genes have dramatically fewer and much smaller CNSs than mammalian genes, Conserved noncoding sequences among cultivated cereal genomes identify candidate regulatory sequence elements and patterns of promoter evolution, Surveys for conserved noncoding sequences (CNS) among genes from monocot cereal species were conducted to assess the general properties of CNS in grass genomes and their correlation with known promoter regulatory elements, Comparisons of orthologous maize-rice and maize-sorghum gene pairs identified 20 bp as a minimal length criterion for a significant CNS among grass genes, with few such CNS found to be conserved across rice, maize, sorghum, and barley[SEP]Definitions: cereal defined as following: Seeds from grasses (POACEAE) which are important in the diet.. conservation defined as following: The maintenance of certain characteristics in an unchanged condition.. genomes defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE.. plant genomes defined as following: The genetic complement of a plant (PLANTS) as represented in its DNA.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"}
{"id": "converted_1613", "sentence1": "Do plant genomes contain CpG islands?", "sentence2": "This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants, In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters. In rice, most of these CpG clusters are associated with genes. Rice genes are grouped into one of the five classes according to the position of an associated CpG cluster. Among them, class 1 genes, which harbor a CpG cluster at the 5'-terminus, share similarities with human genes having CpG islands, Segmental distribution of genes harboring a CpG island-like region on rice chromosomes, Highly-expressed Arabidopsis genes had overall a more marked GC-skew in the TSS compared to genes with low expression levels. We therefore propose that the GC-skew around the TSS in some plants and fungi is related to transcription. It might be caused by mutations during transcription initiation or the frequent use of transcription factor-biding sites having a strand preference. In addition, GC-skew is a good candidate index for TSS prediction in plant genomes, where there is a lack of correlation among CpG islands and genes, Preliminary analysis shows that promoter location based on the detection of potential CpG/CpNpG islands in the Arabidopsis genome is not straightforward. Nevertheless, because the landscape of CpG/CpNpG islands differs considerably between promoters and introns on the one side and exons (whether coding or not) on the other, more sophisticated approaches can probably be developed for the successful detection of \"putative\" CpG and CpNpG islands in plants, This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants., These plant CpG-rich clusters satisfied the criteria used for identifying human CpG islands, which suggests that these CpG clusters may be regarded as plant CpG islands., CONCLUSIONS: This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants., In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters., These plant CpG-rich clusters satisfied the criteria used for identifying human CpG islands, which suggests that these CpG clusters may be regarded as plant CpG islands., Unmethylated CpG islands associated with genes in higher plant DNA., This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants., These plant CpG-rich clusters satisfied the criteria used for identifying human CpG islands, which suggests that these CpG clusters may be regarded as plant CpG islands, We screened plant genome sequences, primarily from rice and Arabidopsis thaliana, for CpG islands, and identified DNA segments rich in CpG dinucleotides within these sequences[SEP]Definitions: TSS defined as following: A rare acute life-threatening systemic bacterial noncontagious illness caused by any of several related staphylococcal exotoxins. It is characterized by high fever, hypotension, rash, multi-organ dysfunction, and cutaneous desquamation during the early convalescent period. The toxins affect the host immune system, causing an exuberant and pathological host inflammatory response. Laboratory findings include leukocytosis, elevated prothrombin time, hypoalbuminemia, hypocalcemia, and pyuria.. strand defined as following: The orientation of a genomic element on the double stranded molecule.. sequences defined as following: The sequence of nucleotide residues along a DNA chain.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. chromosomes defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. position defined as following: A reference to the alignment of an object, a particular situation or view of a situation, or the location of an object.. coding defined as following: The activity of implementing rules that are used to map the elements of one set onto the elements of another set, usually on a one-to-one basis.. introns defined as following: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE.. plant DNA defined as following: Deoxyribonucleic acid that makes up the genetic material of plants.. plant genomes defined as following: The genetic complement of a plant (PLANTS) as represented in its DNA.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"}
{"id": "converted_3493", "sentence1": "Is there a BRCA mutation analysis in the Greek population?", "sentence2": "Comprehensive BRCA mutation analysis in the Greek population. Experience from a single clinical diagnostic center., Germline mutations in the BRCA1 and BRCA2 genes are associated with hereditary predisposition to breast and ovarian cancer. Sensitive and accurate detection of BRCA1 and BRCA2 mutations is crucial for personalized clinical management of individuals affected by breast or ovarian cancer, and for the identification of at-risk healthy relatives. We performed molecular analysis of the BRCA1 and BRCA2 genes in 898 Greek families, using Sanger sequencing or Next Generation Sequencing for the detection of small insertion/deletion frameshift, nonsynonymous, truncating and splice-site alterations and MLPA for the detection of large genomic rearrangements. In total, a pathogenic mutation was identified in 12.9% of 898 families analyzed. Of the 116 mutations identified in total 9% were novel and 14.7% were large genomic rearrangements. Our results indicate that different types of mutational events in the BRCA1 and BRCA2 genes are responsible for the hereditary component of breast/ovarian cancer in the Greek population. Therefore the methodology used in the analysis of Greek patients must be able to detect both point and small frameshift mutations in addition to large genomic rearrangements across the entire coding region of the two genes.[SEP]Definitions: frameshift mutations defined as following: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.. BRCA1 defined as following: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.. BRCA2 defined as following: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6). breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. ovarian cancer defined as following: A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas.. coding region defined as following: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"}
{"id": "converted_3749", "sentence1": "Is the TFR1 gene dispensable for erythropoiesis?", "sentence2": "These studies describe how point mutations of the transferrin receptor can cause a microcytic anemia that does not respond to iron therapy and would not be detected by routine iron studies, such as serum ferritin., Ret-He was the only red cell marker affected prior to the onset of brain ID. The clinical practice of using anemia as the preferred biomarker for diagnosis of iron deficiency may need reconsidering., The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats., Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. , aken together, decreasing TfR1 expression during β-thalassemic erythropoiesis, either directly via induced haploinsufficiency or via exogenous apotransferrin, decreases ineffective erythropoiesis and provides an endogenous mechanism to upregulate hepcidin, leading to sustained iron-restricted erythropoiesis and preventing systemic iron overload in β-thalassemic mice., The type 1 transferrin receptor (TfR1) is well known as a key player in erythroid differentiation through its role in iron uptake. , The signaling functions of both TfR1 and TfR2 in erythroid cells were unexpected and these recent findings open a new field of research regarding the last steps of erythroid differentiation and their regulation., Erythropoiesis requires large amounts of iron for hemoglobin synthesis, which is mainly provided by macrophages and the intestines in a transferrin (Tf)-bound form., In humans, hematopoietic erythroid precursor cells express high levels of TFR1 and specifically take up the FTH homopolymer (H-ferritin)., We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice., Soluble transferrin receptor-1 (sTfR1) concentrations are increased in the plasma under two conditions that are associated with increased iron absorption, i.e. iron deficiency and increased erythropoiesis., Hemochromatosis is caused by mutations in HFE, a protein that competes with transferrin (TF) for binding to transferrin receptor 1 (TFR1)., Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) and thus is required for the proper delivery of iron to erythroid progenitors., These findings provide direct evidence that Tfr1 is essential for hematopoiesis through binding diferric transferrin to supply iron to cells.[SEP]Relations: Erythropoietin has relations: drug_protein with EPOR, drug_protein with EPOR. beta thalassemia has relations: disease_protein with EPO, disease_protein with EPO. intestine has relations: anatomy_protein_present with EPOR, anatomy_protein_present with EPOR. Definitions: iron defined as following: homeopathic drug. Tfr1 defined as following: Human TFRC wild-type allele is located in the vicinity of 3q29 and is approximately 33 kb in length. This allele, which encodes transferrin receptor protein 1, is involved in the regulation of cellular uptake of iron via receptor-mediated endocytosis.. transferrin receptor 1 defined as following: Homodimeric human Transferrin Receptors (M28B Peptidase Family) are type II membrane proteins involved in the cellular import of transferrin-bound iron and appear necessary for iron metabolism, cell function, and erythrocyte differentiation. (NCI). erythroid cells defined as following: The series of cells in the red blood cell lineage at various stages of differentiation.. erythroid defined as following: 1) Reddish in color. 2) relating to erythrocytes or their precursors.. EPOR defined as following: Erythropoietin receptor (508 aa, ~55 kDa) is encoded by the human EPOR gene. This protein is involved in signal transduction and erythroblast proliferation and differentiation.. EPO defined as following: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.. transferrin defined as following: Serotransferrin (698 aa, ~77 kDa) is encoded by the human TF gene. This protein is involved in iron sequestration and transport.. transferrin receptor defined as following: This gene plays a role in iron metabolism.. TfR2 defined as following: Transferrin receptor protein 2 (801 aa, ~89 kDa) is encoded by the human TFR2 gene. This protein is involved in the mediation of cellular uptake of transferrin-iron complexes.. beta-thalassemia defined as following: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent.. hepcidin defined as following: Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity.. microcytic anemia defined as following: Anemia in which the red blood cell volume is decreased.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. TF defined as following: A person who was assigned to the male gender at birth based on physical characteristics but who self-identifies psychologically and emotionally as female.. ASP defined as following: Fluid withdrawn from a body cavity, organ, cyst, or tumor.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. point mutations defined as following: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. intestines defined as following: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.. CKD defined as following: Impairment of the renal function secondary to chronic kidney damage persisting for three or more months.. Bcl-xL defined as following: This gene is an apoptotic regulator that can have anti or pro apoptotic effects.. hematopoiesis defined as following: The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).. NGAL defined as following: Human LCN2 wild-type allele is located in the vicinity of 9q34 and is approximately 5 kb in length. This allele, which encodes neutrophil gelatinase-associated lipocalin protein, may be involved in both the modulation of inflammation and the regulation of the transport of hydrophobic substances (ie. retinol, lipopolysaccharide). The expression of this gene may be elevated in many cancers and inflammatory diseases.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. bone marrow-derived mononuclear cells defined as following: A biological sample containing mononuclear cells isolated from the bone marrow of an experimental subject.. humans defined as following: Members of the species Homo sapiens.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "no"}
{"id": "converted_4244", "sentence1": "Is Adamts18 deficiency associated with cancer?", "sentence2": "Adamts18 deficiency promotes colon carcinogenesis by enhancing β-catenin and p38MAPK/ERK1/2 signaling in the mouse model of AOM/DSS-induced colitis-associated colorectal cancer., ADAMTS18 is a novel tumor suppressor and is critical to the pathology of human colorectal cancer. However, the underlying mechanism is not clear. Here we generated an Adamts18-deficient mouse strain as an in vivo model to investigate the role of ADAMTS18 in the pathogenesis of colorectal cancer. In AOM/DSS-induced colitis-associated colorectal cancer, the deficiency of Adamts18 in mice resulted in enhanced tumorigenesis and colon inflammation that could be attributed in part to enhanced nuclear translocation of β-catenin and elevated expression of its downstream target genes, cyclin D1 and c-myc. Moreover, increased p38MAPK and ERK1/2 activities were detected in colon cancer cells from Adamts18-deficient mice. Further studies revealed that ADAMTS18 deficiency reduced intestinal E-cadherin levels in mice, which ultimately led to intestinal barrier dysfunction. These data indicate that Adamts18 deficiency enhances tumorigenesis and intestinal inflammation through elevated Wnt/β-catenin and p38MAPK/ERK1/2 signaling and promotes colon cancer in this mouse model.[SEP]Relations: ADAMTS18 has relations: disease_protein with colorectal cancer, disease_protein with colorectal cancer. malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer. Definitions: colon cancer defined as following: A primary or metastatic malignant neoplasm that affects the colon. Representative examples include carcinoma, lymphoma, and sarcoma.. human defined as following: Members of the species Homo sapiens.. cyclin D1 defined as following: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.. intestinal inflammation defined as following: A reaction characterizeds by capillary dilatation, leukocytic infiltration, redness, heat, pain, swelling localized to the in the intestinal tract. [PMID:9897960]. intestinal defined as following: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.. colon inflammation defined as following: Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.. cancer defined as following: A malignant tumor at the original site of growth..", "label": "yes"}
{"id": "converted_4481", "sentence1": "Can Isradipine slow progression of Early Parkinson Disease?", "sentence2": "Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85)., Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD., ONS: These results are consistent with the recent secondary analysis of the STEADY-PD III clinical trial-suggesting that clinically attainable brain exposure to isradipine may slow early-stage PD progression. © 2021 , These findings suggest that greater exposure to isradipine might slow disease progression., erm treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.Primary Funding So, BACKGROUND: Recent examination of the STEADY-PD III isradipine clinical trial data concluded that early-stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end of t, RESULTS: Isradipine exposures did not correlate with the primary clinical outcome, changes in the antiparkinson therapy-adjusted Unified Parkinson's Disease Rating Scale parts I-III score over 36 months (Spearman rank correlation coefficient, rs : , These findings suggest that greater exposure to isradipine might slow disease progressio, Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage P, However, in a recently completed phase 3 clinical trial, the dihydropyridine (DHP) LTCC inhibitor isradipine failed to slow disease progression in early PD patients, questioning the feasibility of DHPs for PD therapy., BACKGROUND: Recent examination of the STEADY-PD III isradipine clinical trial data concluded that early-stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end o[SEP]Definitions: PD defined as following: A score of 4 or 5 on a 5-point PET scale with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment.. dihydropyridine defined as following: partially saturated derivative of pyridine; binds to and inhibits the voltage-gated calcium channel of skeletal muscle T junctional membranes, the principle molecular transducer of excitation-contraction coupling.. isradipine defined as following: A potent antagonist of CALCIUM CHANNELS that is highly selective for VASCULAR SMOOTH MUSCLE. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure.. ONS defined as following: A clinical nurse specialist that provides a high level of supportive and therapeutic care to cancer patients and their families. The ONS is an excellent resource for current trends in cancer care and therapies.. Parkinson's disease defined as following: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75).", "label": "no"}
{"id": "converted_4478", "sentence1": "Is Phospholemman a membrane protein?", "sentence2": " the transmembrane lipoprotein phospholemman (FXYD1), Phospholemman (FXYD1) is a single-transmembrane protein regulator of Na,K-ATPase, expressed strongly in heart, skeletal muscle, and brain and phosphorylated by protein kinases A and C at Ser-68 and Ser-63, respectively., We previously identified FXYD1 (encoding phospholemman; a protein containing the motif phenylalanine-X-tyrosine-aspartate), a gene encoding a transmembrane modulator of the Na, K-ATPase (NKA) enzyme,[SEP]Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Na defined as following: A wild-type zebrafish line, the stock of which was obtained from an area east of Calcutta in a district called Nadia.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. membrane protein defined as following: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors..", "label": "yes"}
{"id": "converted_3434", "sentence1": "Can CMB305 be used against sarcomas?", "sentence2": "CMB305 induces NY-ESO-1 specific T cell responses in both SS and MRC patients and these patients had excellent overall survival (OS) outcomes in the initial phase I study., Data suggesting this vaccine may improve OS for SS and MRCL patients is exciting but early, and on-going work is testing the impact of CMB305 on patient outcomes., The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients.[SEP]Definitions: T cell defined as following: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.. NY-ESO-1 defined as following: Human CTAG1A wild-type allele is located in the vicinity of Xq28 and is approximately 2 kb in length. This allele, which encodes cancer/testis antigen 1 protein, may play a role in both spermatogeneis and development of the testes. Aberrant expression of this gene is associated with incontinentia pigmenti.. synovial sarcoma defined as following: A malignant neoplasm arising from tenosynovial tissue of the joints and in synovial cells of tendons and bursae. The legs are the most common site, but the tumor can occur in the abdominal wall and other trunk muscles. There are two recognized types: the monophasic (characterized by sheaths of monotonous spindle cells) and the biphasic (characterized by slit-like spaces or clefts within the tumor, lined by cuboidal or tall columnar epithelial cells). These sarcomas occur most commonly in the second and fourth decades of life. (From Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1363). myxoid/round cell liposarcoma defined as following: A liposarcoma characterized by the presence of round non-lipogenic primitive mesenchymal cells and small signet ring lipoblasts within a myxoid stoma with a branching vascular pattern. This category includes hypercellular lesions with round cell morphology, formerly known as round cell liposarcoma.. MRC defined as following: A publicly funded organization that is part of United Kingdom Research and Innovation, and is dedicated to improving human health through world-class medical research.. SS defined as following: Supernumerary mandibular right first primary molar
. sarcomas defined as following: A malignant neoplasm arising exclusively from the soft tissues..", "label": "yes"}
{"id": "converted_2286", "sentence1": "Does a tonsillectomy affect the patient's voice?", "sentence2": " Group B had a better awareness of tooth damage (78% vs 30% of patients, P ≤ .001), voice change (61 vs 19%, P = .005), and burns to lips and mouth (44% vs 8%, P = .005). Finally, 35% more patients from group B rated their understanding of tonsillectomy as good or very good (P = .017)., Some patients complaint for dry throat, foreign body sensation or voice change after tonsillectomy., The percentage of patients who had temporary voice change was 62.7%, and 15.4% had a follow-up clinic visit., There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change., There were no differences in secondary outcomes (analgesic requirements, time to first liquid, and change in voice) across treatment groups., Voice change, reported by approximately 70% of all patients, was the most common complaint, but it resolved in all instances., The incidence rates of voice change, velopharyngeal insufficiency, bleeding, constipation, dehydration, and pain were measured. , Tonsillectomy affects voice performance negatively in adults in short term; however, it does not affect voice performance in long term after surgery., The surgical technique, whether it is cold knife or thermal welding system, does not appear to affect voice and speech in tonsillectomy patients., OBJECTIVE: To evaluate changes in acoustic features of voice after tonsillectomy., Surgical indications for tonsillectomy in the young voice patient are discussed., OBJECTIVE: Our goal was to assess patient perception and acoustic characteristics of voice before and after upper airway surgery., In this report, we examined the change in pharyngeal size and acoustic feature of voice after tonsillectomy., CONCLUSION Tonsillectomy affects voice performance negatively in adults in short term; however, it does not affect voice performance in long term after surgery., Some patients complaint for dry throat, foreign body sensation or voice change after tonsillectomy., Tonsillectomy affects voice performance negatively in adults in short term; however, it does not affect voice performance in long term after surgery.., The surgical technique, whether it is cold knife or thermal welding system, does not appear to affect voice and speech in tonsillectomy patients.., There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change.[SEP]Definitions: voice defined as following: Description:This device can receive voice calls (i.e. talking to another person, or a recording device, or a voice activated computer).. dehydration defined as following: The condition that results from excessive loss of water from a living organism.. dexamethasone defined as following: An anti-inflammatory 9-fluoro-glucocorticoid.. velopharyngeal insufficiency defined as following: Failure of the SOFT PALATE to reach the posterior pharyngeal wall to close the opening between the oral and nasal cavities. Incomplete velopharyngeal closure is primarily related to surgeries (ADENOIDECTOMY; CLEFT PALATE) or an incompetent PALATOPHARYNGEAL SPHINCTER. It is characterized by hypernasal speech.. lips defined as following: Either of the two fleshy, full-blooded margins of the mouth.. burns defined as following: Injuries to tissues caused by contact with heat, steam, chemicals (BURNS, CHEMICAL), electricity (BURNS, ELECTRIC), or the like.. bleeding defined as following: Bleeding or escape of blood from a vessel.. constipation defined as following: Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.. vomiting defined as following: The forcible expulsion of the contents of the STOMACH through the MOUTH..", "label": "yes"}
{"id": "converted_3046", "sentence1": "Does Rhamnose have any effect on aging?", "sentence2": "The monosaccharide analysis showed that rhamnose (Rha) and glucose (Glu) may play vital roles in maintaining the antioxidant and anti-aging activities. , Some of these mechanisms will be reviewed as well as the capacity of fucose- and rhamnose-rich oligo- and polysaccharides (FROP and RROP) to counteract several of the mechanisms involved in skin aging.[SEP]Definitions: glucose defined as following: The determination of the amount of glucose present in a sample.. rhamnose defined as following: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides.. monosaccharide defined as following: Single chain carbohydrates that are the most basic units of CARBOHYDRATES. They are typically colorless crystalline substances with a sweet taste and have the same general formula CnH2nOn..", "label": "yes"}
{"id": "converted_572", "sentence1": "Is phospholamban phosphorylated by Protein kinase A?", "sentence2": "cAMP-dependent protein kinase (PKA) phosphorylation of PLB, phosphorylation of PLN, at either Ser(16) by PKA , Activation of cardiac muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) by beta1-agonists involves cAMP- and PKA-dependent phosphorylation of phospholamban (PLB), which relieves the inhibitory effects of PLB on SERCA2a. , Phospholamban (PLB) is a sarcoplasmic reticulum (SR) protein that when phosphorylated at Ser16 by PKA, phosphorylation of PLB by the Ca2+-calmodulin-dependent protein kinase (CaMK) and cAMP-dependent protein kinase (PKA). , cAMP-dependent protein kinase (PKA)-mediated phospholamban (PLB) phosphorylation at serine-16, Phospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, functioning to modulate contractile force by altering the rate of calcium re-sequestration by the Ca-ATPase. Functionally, inhibition by PLB binding is manifested by shifts in the calcium dependence of Ca-ATPase activation toward higher calcium levels; phosphorylation of PLB by PKA reverses the inhibitory action of PLB., phosphorylation of both PLB residues (Ser16, PKA site, and Thr17, CaMKII site) , Phosphorylation of Ser(16) by PKA, stabilization of the structure of PLB following phosphorylation of Ser(16), Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, and this inhibition is relieved by cAMP-dependent protein kinase (PKA)-mediated phosphorylation. , Two-dimensional tryptic peptide maps of phosphorylated phospholamban indicated that cAMP-dependent protein kinase phosphorylates at a single site, A, and Ca2+-calmodulin-dependent protein kinase phosphorylates at sites C1 and C2 in the low molecular weight form, where A is different from C1 but may be the same as C2., Because SR function is regulated by phosphorylation of phospholamban (PLB), a SR protein phosphorylated by cAMP-dependent protein kinase (PKA) at Ser(16)and Ca(2+)-calmodulin-dependent protein kinase (CaMKII) at Thr(17), the phosphorylation of these residues during ischemia and reperfusion was examined in Langendorff-perfused rat hearts, These changes were associated with reduced protein expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and protein kinase A phosphorylated phospholamban (PLB), which was reduced in HF, but essentially abolished in VD-HF, The data indicate that 1) phosphorylation of phospholamban at Ser16 by cAMP-dependent protein kinase is the main regulator of beta-adrenergic-induced cardiac relaxation definitely preceding Thr17 phosphorylation and 2) the beta-adrenergic-mediated phosphorylation of Thr17 by Ca2+-calmodulin-dependent protein kinase required influx of Ca2+ through the L-type Ca2+ channel, Here we extend this model to explain the reversal of SERCA2a inhibition that occurs after phosphorylation of PLB at Ser(16) by protein kinase A (PKA) and after binding of the anti-PLB monoclonal antibody 2D12, which recognizes residues 7-13 of PLB, Phospholamban is phosphorylated in heart by cAMP-dependent protein kinase, cGMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II (CM-kinase-II) and in smooth muscle cells by cGMP-dependent protein kinase, Phospholamban, the cardiac sarcoplasmic reticulum proteolipid, is phosphorylated by cAMP-dependent protein kinase, by Ca2+/phospholipid-dependent protein kinase, and by an endogenous Ca2+/calmodulin-dependent protein kinase, the identity of which remains to be defined[SEP]Definitions: Phospholamban defined as following: free sarcoplasmic reticulum polymeric proteolipid which modulates sarcoplasmic reticulum function; phosphorylated by cAMP-dependent, calcium-calmodulin-dependent, and calcium-phospholipid-dependent protein kinases.. calcium defined as following: A dietary supplement containing the mineral calcium.. ischemia defined as following: A surgical procedure during which the blood supply to an organ or tissue is interrupted and then later reestablished.. C2 defined as following: Complement C2 (752 aa, ~83 kDa) is encoded by the human C2 gene. This protein is involved in post-translational protein processing and complement activity.. SR defined as following: Human SNCG wild-type allele is located within10q23.2-q23.3 and is approximately 13 kb in length. This allele, which encodes gamma-synuclein protein, plays a role in the modulation of axonal architecture and neurofilament integrity. This gene is highly expessed in advanced breast carcinomas, suggesting a correlation between SNCG overexpression and breast tumor development.. smooth muscle cells defined as following: An elongated spindle-shaped contractile cell, peculiar to an involuntary muscle, containing a single nucleus and longitudinally arranged myofibrils.. protein kinase A defined as following: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. sarcoplasmic reticulum defined as following: A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.. CaMKII defined as following: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.. calcium/calmodulin-dependent protein kinase II defined as following: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277). cGMP-dependent protein kinase defined as following: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.. sarcoplasmic reticulum Ca(2+)-ATPase defined as following: Calcium-transporting ATPases that catalyze the active transport of CALCIUM into the SARCOPLASMIC RETICULUM vesicles from the CYTOPLASM. They are primarily found in MUSCLE CELLS and play a role in the relaxation of MUSCLES.. HF defined as following: Abnormal accumulation of serous fluid in two or more fetal compartments, such as SKIN; PLEURA; PERICARDIUM; PLACENTA; PERITONEUM; AMNIOTIC FLUID. General fetal EDEMA may be of non-immunologic origin, or of immunologic origin as in the case of ERYTHROBLASTOSIS FETALIS.. Protein kinase A defined as following: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition..", "label": "yes"}
{"id": "converted_1878", "sentence1": "Is there alternative polyadenylation during zebrafish development?", "sentence2": "Extensive alternative polyadenylation during zebrafish development., At 2 h post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3' UTRs provide a resource for studying gene regulation during vertebrate development., Extensive alternative polyadenylation during zebrafish development.[SEP]Definitions: zebrafish defined as following: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research.. vertebrate defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes..", "label": "yes"}
{"id": "converted_3754", "sentence1": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "sentence2": "Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance., A recent study demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia., Thus, this review focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD., Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance, tudy demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia. Thus, this , iew focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD. Abbreviations: [SEP]Definitions: Nrf2 defined as following: This gene plays a role in transcriptional regulation.. NAFLD defined as following: A term referring to fatty replacement of the hepatic parenchyma which is not related to alcohol use..", "label": "yes"}
{"id": "converted_3635", "sentence1": "Can LB-100 downregulate miR-33?", "sentence2": "PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation., LB100 profoundly upregulates miR-181b-1, which we show directly binds to the 3' untranslated region of Bcl-2 mRNA leading to its translational inhibition. MiR-181b-1 ectopic overexpression further diminishes Bcl-2 expression leading to suppression of sAML cell growth, and enhancement of DNR cytotoxicity. [SEP]Definitions: Bcl-2 defined as following: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.. PP2A defined as following: PP2A core enzyme consists of a 36-kDa catalytic C subunit and a constant 65-kDa regulatory/structural A subunit that interact with either a B regulatory subunit or with cell signaling molecules, that likely modulate substrate selectivity, catalytic activity, and subcellular localization, yielding the trimeric holoenzyme. Combinations of different subunit isoforms can generate many forms of PP2A, which may differ in substrate specificity, subcellular localization, or tissue specific expression.. daunorubicin defined as following: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS..", "label": "no"}
{"id": "converted_1092", "sentence1": "Does amiodarone affect thyroid hormone receptors in the myocardium?", "sentence2": "AM and Dron affected TR expression in the RA similarly by decreasing TRalpha 1 and beta 1 expression by about 50%, In the LVW, AM and Dron decreased TRbeta 1 and, interestingly, AM increased TRalpha 1., n the apex, AM also increased TRalpha 2., Both in treated and untreated mice, TRalpha2 mRNA had the highest density in mouse heart, whereas TRbeta2 mRNA had the lowest density. Amiodarone dose-dependently downregulated the levels of TRalpha1 and beta1 mRNA in comparison to the control., amiodarone subtype selectively downregulates the TR mRNA levels in mouse myocardium in a dose-dependent manner., Western blot analysis revealed no change in the expression of the ThR protein., Amiodarone and T3, respectively, downregulated T3R alpha 1, T3R beta 1, T3R beta 2 (p < 0.05), but did not affect the levels of T3R alpha 2. Amiodarone and T3, added together, upregulated T3R alpha 2 and T3R beta 1 (p < 0.05) as compared to amiodarone or T3 alone.[SEP]Definitions: TRbeta 1 defined as following: This gene plays a role in receptor signaling and regulation of transcription. It is involved in inner ear development and color vision.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. AM defined as following: Human ATF7IP wild-type allele is located in the vicinity of 12p13.1 and is approximately 133 kb in length. This allele, which encodes activating transcription factor 7-interacting protein 1, plays a role in the modulation of both transcription and histone methylation.. amiodarone defined as following: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.. TR defined as following: Backflow of blood from the RIGHT VENTRICLE into the RIGHT ATRIUM due to imperfect closure of the TRICUSPID VALVE.. myocardium defined as following: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.. thyroid hormone receptors defined as following: Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively..", "label": "yes"}
{"id": "converted_2549", "sentence1": "Are stress granules membraneous?", "sentence2": "PMLOs are different in size, shape, and composition, and almost invariantly contain intrinsically disordered proteins (e.g., eIF4B and TDP43 in stress granules,, Liquid-liquid phase separation (LLPS) of RNA-binding proteins plays an important role in the formation of multiple membrane-less organelles involved in RNA metabolism, including stress granules., Stress granules (SG) are membrane-less compartments involved in regulating mRNAs during stress., In addition to membrane delimited organelles, proteins and RNAs can organize themselves into specific domains. Some examples include stress granules and subnuclear bodies. [SEP]Definitions: proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). organelles defined as following: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the MITOCHONDRIA; the GOLGI APPARATUS; ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.. membrane defined as following: A device that is made from or resembles a thin flexible sheet of material.. TDP43 defined as following: Human TARDBP wild-type allele is located in the vicinity of 1p36.22 and is approximately 13 kb in length. This allele, which encodes TAR DNA-binding protein 43, plays a role in the mediation of both mRNA splicing and DNA transcription. Mutation of the gene is associated with amyotrophic lateral sclerosis type 10.. RNA-binding proteins defined as following: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.. stress granules defined as following: A dense aggregation in the cytosol composed of proteins and RNAs that appear when the cell is under stress. [GOC:ans, PMID:17284590, PMID:17601829, PMID:17967451, PMID:20368989].", "label": "no"}
{"id": "converted_501", "sentence1": "Is Kanzaki disease associated with deficiency in alpha-N-acetylgalactosaminidase?", "sentence2": "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. , Our findings suggest that the association of alpha-NAGA with its substrates is strongly affected by the amino acid substitution at R329 and that the association with GalNAcalpha1-O-Thr is more highly susceptible to structural changes. The residual mutant enzyme in R329W could not associate with GalNAcalpha1-O-Thr and GalNAcalpha1-O-Ser. However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent. Therefore, the urinary ratio of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr was lower and the clinical phenotype was milder in the R329Q mutation. , Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr., Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease)., Structural and immunocytochemical studies on alpha-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease)., We describe the neurologic findings in a patient with alpha-N-acetylgalactosaminidase deficiency (Kanzaki disease)., Three dimensional structural studies of alpha-N-acetylgalactosaminidase (alpha-NAGA) in alpha-NAGA deficiency (Kanzaki disease): different gene mutations cause peculiar structural changes in alpha-NAGAs resulting in different substrate specificities and clinical phenotypes., alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described., Schindler disease and Kanzaki disease are caused by a deficient lysosomal enzyme, alpha-N-acetylgalactosaminidase (E.C.3.2.1.49)., The 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler and Kanzaki diseases., These data suggest that a prototype of alpha-NAGA deficiency in Kanzaki disease and factors other than the defect of alpha-NAGA may contribute to severe neurological disorders, and Kanzaki disease is thought to be caused by a single enzyme deficiency., Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease). , alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described. , Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. Missense mutations, R329W or R329Q were identified in two Japanese Kanzaki patients., Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease)., Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49),, Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr., alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described.[SEP]Definitions: gene mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. Alpha-N-acetylgalactosaminidase defined as following: A hexosaminidase with specificity for terminal non-reducing N-acetyl-D-galactosamine residues in N-acetyl-alpha-D-galactosaminides.. Schindler disease defined as following: A very rare and severe type of NAGA deficiency characterized by infantile neuroaxonal dystrophy.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. angiokeratoma corporis diffusum defined as following: An X-linked inherited metabolic disease caused by a deficiency of lysosomal ALPHA-GALACTOSIDASE A. It is characterized by intralysosomal accumulation of globotriaosylceramide and other GLYCOSPHINGOLIPIDS in blood vessels throughout the body leading to multi-system complications including renal, cardiac, cerebrovascular, and skin disorders.. neurological disorders defined as following: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.. amino acid substitution defined as following: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.. alpha-N-acetylgalactosaminidase defined as following: A hexosaminidase with specificity for terminal non-reducing N-acetyl-D-galactosamine residues in N-acetyl-alpha-D-galactosaminides..", "label": "yes"}
{"id": "converted_388", "sentence1": "Is there an association between borna virus and brain tumor?", "sentence2": "Borna disease virus (BDV), a nonsegmented, negative-strand RNA virus, infects a wide variety of mammalian species and readily establishes a long-lasting, persistent infection in brain cells. , To investigate the biological characteristics of field isolates of Borna disease virus (BDV), as well as to understand BDV infections outside endemic countries, we isolated the virus from brain samples of a heifer with Borna disease in Japan., Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to the certain neuronal populations., In addition, compared to uninfected mixed cultures, activation of microglia in BDV-infected mixed cultures was associated with a significantly greater lipopolysaccharide-induced release of tumor necrosis factor alpha, interleukin 1beta, and interleukin 10. Taken together, the present data are the first in vitro evidence that persistent BDV infection of neurons and astrocytes rather than direct exposure to the virus or dying neurons is critical for activating microglia., Usually, Borna disease virus is not cleared from the brain but rather persists in neural cells., Varied persistent life cycles of Borna disease virus in a human oligodendroglioma cell line., Borna disease virus (BDV) establishes a persistent infection in the central nervous system of vertebrate animal species as well as in tissue cultures. , Thus, our findings show that BDV may have established a persistent infection at low levels of viral expression in OL cells with the possibility of a latent infection., These results suggested that BDV infection may cause direct damage in the developing brain by inhibiting the function of amphoterin due to binding by the p24 phosphoprotein., We describe a model for investigating disorders of central nervous system development based on neonatal rat infection with Borna disease virus, a neurotropic noncytolytic RNA virus. , Borna disease virus (BDV) replicates in brain cells. The neonatally infected rat with BDV exhibits developmental-neuromorphological abnormalities, neuronal cytolysis, and multiple behavioral and physiological alterations. , Borna disease virus (BDV) causes central nervous system (CNS) disease in several vertebrate species, which is frequently accompanied by behavioral abnormalities., Intrinsic responses to Borna disease virus infection of the central nervous system., Immune cells invading the central nervous system (CNS) in response to Borna disease virus (BDV) antigens are central to the pathogenesis of Borna disease (BD). , We report here the partial purification and characterization of cell-free BDV from the tissue culture supernatant of infected human neuroblastoma SKNSH cells., We have used the reverse transcriptase-polymerase chain reaction technique to gain insight into the pathogenesis of encephalitis caused by Borna disease virus (BDV). , In contrast, in the BDV-infected primary mixed cultures, we observed proliferation of microglia cells that acquired the round morphology and expressed major histocompatibility complex molecules of classes I and II.[SEP]Definitions: neural cells defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. Borna disease defined as following: An encephalomyelitis of horses, sheep and cattle caused by BORNA DISEASE VIRUS.. microglia defined as following: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.. behavioral abnormalities defined as following: Troublesome or disruptive behavioral displays.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. tissue cultures defined as following: Originally the maintenance and growth of pieces of explanted tissue (plant or animal) in culture away from the source organism. Now usually refers to the (much more frequently used) technique of cell culture, using cells dispersed from tissues or distant descendants of such cells.. amphoterin defined as following: A 24-kDa HMGB protein that binds to and distorts the minor grove of DNA.. astrocytes defined as following: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from \"star\" cells) are irregularly shaped with many long processes, including those with \"end feet\" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and \"reactive astrocytes\" (along with MICROGLIA) respond to injury.. interleukin 1beta defined as following: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.. tumor necrosis factor alpha defined as following: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. brain cells defined as following: header term for the cells that make up the brain; includes neurons, glia, and other specialized cells in the brain.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. virus defined as following: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. human defined as following: Members of the species Homo sapiens.. encephalitis defined as following: Inflammation of the BRAIN due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see ENCEPHALITIS, VIRAL) are a relatively frequent cause of this condition.. brain tumor defined as following: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain..", "label": "no"}
{"id": "converted_2834", "sentence1": "Is obesity related to cognitive decline?", "sentence2": "The initial results suggests that obese children have higher cognitive scores and that this result is driven by those who are female, non-indigenous and live in an urban region., On the other end of the weight distribution, indigenous children who are severely thin or thin have significantly lower cognitive scores, a relationship that holds after correcting for possible bias and appears to strengthen between ages of five and eight., Obesity is associated with decreased cognitive function, reduced gray matter volume, and impaired white matter integrity in cognition-related brain areas in patients with MDD., The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span, Poor cognitive performance was present in 37% of the sample. General obesity (BMI>or = 25) and poor cognition were strongly associated in the presence of abdominal obesity. Poor cognition was negatively associated with overweight (BMI 23-25) with normal waist circumference., BMI could be used as a candidate risk marker to identify people at higher risk of cognitive deficits, and as an intervention target for modifications of cognitive outcomes., Obesity is a common medical illness that is increasingly recognised as conferring risk of decline in cognitive performance, independent of other comorbid medical conditions., Overweight and obesity are associated with an increased risk of subnormal intellectual performance in young adult males. Subjects with low birth weight and adolescent overweight/obesity are at particular risk of subnormal performance., Impairments in cognitive function have been associated with obesity in both people and rodents., Obesity in the pre-school years was associated with poorer outcomes for some cognitive measures in this study. Stronger relationships between obesity and cognition or educational attainment may emerge later in childhood., There is parallel evidence that people who are overweight or obese tend to perform worse on a variety of cognitive tasks, While research in this area is growing, our knowledge of obesity-related cognitive dysfunction and brain alterations has not yet been synthesized., The present review integrates the recent literature regarding patterns of obesity-related cognitive dysfunction and brain alterations and also indicates potential mechanisms for these neuropathological changes., The review culminates in a preliminary model of obesity-related cognitive dysfunction and suggestions for future research, including the potential reversibility of these changes with weight-loss.
, Evidence for the increased prevalence of diabetes and obesity is reviewed as it relates to cognitive decline., These articles indicate that the age of onset of Type 1 diabetes may be relevant to future cognitive function and that disease duration of Type 2 diabetes and sociocultural factors are related to cognitive decline during the aging process., This special issue concludes with a conceptual framework for linking obesity and diabetes with accelerated cognitive decline as related to the aging process., The adverse effects of diabetes and obesity on cognitive functioning are increasingly well recognized., Moreover, these studies show that distressing environmental circumstances can adversely influence neurocognitive dysfunction associated with obesity and diabetes.[SEP]Definitions: rodents defined as following: A mammalian order which consists of 29 families and many genera.. MDD defined as following: Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5). Type 2 diabetes defined as following: A type of diabetes mellitus that is characterized by insulin resistance or desensitization and increased blood glucose levels. This is a chronic disease that can develop gradually over the life of a patient and can be linked to both environmental factors and heredity.. abdominal obesity defined as following: A condition of having excess fat in the abdomen. Abdominal obesity is typically defined as waist circumferences of 40 inches or more in men and 35 inches or more in women. Abdominal obesity raises the risk of developing disorders, such as DIABETES; HYPERTENSION; and METABOLIC SYNDROME.. overweight defined as following: A condition in which body mass index falls between 25 and 29.9.. cognitive decline defined as following: Loss of previously present mental abilities, generally in adults. [HPO:probinson]. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. cognitive deficits defined as following: Disorders characterized by disturbances in mental processes related to learning, thinking, reasoning, and judgment.. neurocognitive dysfunction defined as following: Interference or disruption of cognitive processes. This term encompasses a large number of problems and issues associated with intellectual functioning and information processing. 2005. thin defined as following: Narrow in width, extent or cross-section..", "label": "yes"}
{"id": "converted_672", "sentence1": "Is TREM2 associated with Alzheimer's disease?", "sentence2": "Absence of TREM2 polymorphisms in patients with Alzheimer's disease and Frontotemporal Lobar Degeneration, These data demonstrate that TREM2 coding region is highly conserved, implying a crucial role of this receptor. Further studies, including a functional analysis, are certainly required to clarify the role of TREM2 in neurodegenerative processes, Moreover, a rare TREM2 exon 2 variant (p.R47H) was reported to increase the risk of Alzheimer's disease (AD) with an odds ratio as strong as that for APOEε4, We observed an enrichment of rare variants across TREM2 in both AD and FTD patients compared to controls, most notably in the extracellular IgV-set domain, None of the rare variants individually reached significant association, but the frequency of p.R47H was increased ~ 3-fold in both AD and FTD patients compared to controls, in line with previous reports, Our data corroborate and extend previous findings to include an increased frequency of rare heterozygous TREM2 variations in AD and FTD, and show that TREM2 variants may play a role in neurodegenerative diseases in general., non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD), These data strongly support the important role of p.R47H in AD risk, and suggest that this rare genetic variant is not related to FTD., Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in AD patients, Our results indicate that TREM2 might serve as a novel noninvasive biomarker for AD diagnosis, studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1, This study replicates the association between R47H and Alzheimer's disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant, Moreover, mutation scanning of the five exons of TREM2 failed to detect the presence of novel polymorphisms, A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland, We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers, Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes, rs75932628-T variant of the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD), These results confirm the association between this variant and AD and underline its involvement in early-onset cases, recent studies have reported the association of rs75932628-T in the TREM2 gene with the risk for Alzheimer's disease (AD), Rs75932628-T is a rare nonsynonymous variant (p.R47H) that confers a high risk of AD with an effect size similar to that of the APOE ɛ4 allele, Here, we report the first positive replication study in a Spanish population and confirm that TREM2 rs75932628-T is associated with the risk for AD, works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD), with an odds ratio similar to that of the apolipoprotein E ε4 allele, The reduced function of TREM2 was speculated to be the main cause in the pathogenic effects of this risk variant, and TREM2 is highly expressed in white matter, as well as in the hippocampus and neocortex, which is partly consistent with the pathological features reported in AD brain, indicating the possible involvement of TREM2 in AD pathogenesis, Emerging evidence has demonstrated that TREM2 could suppress inflammatory response by repression of microglia-mediated cytokine production and secretion, which may prevent inflammation-induced bystander damage of neurons, TREM2 also participates in the regulation of phagocytic pathways that are responsible for the removal of neuronal debris, Based on the potential protective actions of TREM2 in AD pathogenesis, targeting TREM2 might provide new opportunities for AD treatment, Under the hypothesis that low-prevalence variants showing moderate-to-high effect size may be associated with risk for sAD, two independent research groups have demonstrated that a rare variant (rs75932628, encoding a substitution of arginine by histidine at residue 47 (R47H), in the TREM2 gene, which encodes the triggering receptor expressed on myeloid cells 2) is significantly associated with an increased susceptibility to sAD, Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD, TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk, evidence suggests that rare genetic variants within the TREM2 gene are associated with increased risk of Alzheimer's disease, These data suggest that a mutational burden in TREM2 may serve as a risk factor for neurodegenerative disease in general, and that potentially this class of TREM2 variant carriers with dementia should be considered as having a molecularly distinct form of neurodegenerative disease, The association of TREM2 variants with AD brings innate immune signaling into the light, affirming innate immunity's role as a significant factor in AD pathogenesis, The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS, Even though we are more at the beginning than at the end of sAD genetics, there is some reason for optimism given the recent identification of novel risk or protective variants (such as rare TREM2 and APP mutations) showing strong statistical associations with sAD[SEP]Relations: neocortex has relations: anatomy_protein_present with TREM2, anatomy_protein_present with APOE, anatomy_protein_present with TREM2, anatomy_protein_present with APOE. major affective disorder has relations: disease_protein with APOE, disease_protein with APOE. inherited neurodegenerative disorder has relations: disease_disease with neurodegenerative disease, disease_disease with neurodegenerative disease. TREM2 has relations: anatomy_protein_present with neocortex, anatomy_protein_present with neocortex. Definitions: neocortex defined as following: The largest portion of the CEREBRAL CORTEX in which the NEURONS are arranged in six layers in the mammalian brain: molecular, external granular, external pyramidal, internal granular, internal pyramidal and multiform layers.. variant defined as following: An alteration or difference from a norm or standard.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. histidine defined as following: An essential amino acid that is required for the production of HISTAMINE.. sAD defined as following: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (PHOTOTHERAPY), during the season of recurrence.. APOE defined as following: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. myeloid cells defined as following: The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).. TREM2 defined as following: Triggering receptor expressed on myeloid cells 2 (230 aa, ~25 kDa) is encoded by the human TREM2 gene. This protein plays a role in macrophage and dendritic cell immune responses.. allele defined as following: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.. region defined as following: The continents and countries situated on those continents; the UNITED STATES and each of the constituent states arranged by region; CANADA and each of its provinces; AUSTRALIA and each of its states; the major bodies of water and major islands on both hemispheres; and selected major cities.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. arginine defined as following: An essential amino acid that is physiologically active in the L-form.. FTD defined as following: The most common clinical form of FRONTOTEMPORAL LOBAR DEGENERATION, this dementia presents with personality and behavioral changes often associated with disinhibition, apathy, and lack of insight.. domain defined as following: A taxonomic category above that of Kingdom.. neurodegenerative disease defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.. polymorphisms defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. TREM2 gene defined as following: This gene plays a role in the activation of immune responses.. dementia defined as following: The presence of dementia in an individual younger than age sixty five.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. substitution defined as following: Definition: Indicates that the subject Act has undergone or should undergo substitution of a type indicated by Act.code.
Rationale: Used to specify \"allowed\" substitution when creating orders, \"actual\" susbstitution when sending events, as well as the reason for the substitution and who was responsible for it.
.", "label": "yes"}
{"id": "converted_3733", "sentence1": "Has saracatinib been tested in clinical trials?", "sentence2": "Saracatinib as a metastasis inhibitor in metastatic castration-resistant prostate cancer: A University of Chicago Phase 2 Consortium and DOD/PCF Prostate Cancer Clinical Trials Consortium Study., A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies., Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer., Metastatic colorectal cancer patients who had received one prior treatment and had measurable disease were enrolled in this phase 2 study., A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease., Herein, we present a Phase Ib trial of the repurposed investigational drug AZD0530, a Src family kinase inhibitor specific for Fyn and Src kinase, for the treatment of patients with mild-to-moderate AD., The study was a 4-week Phase Ib multiple ascending dose, randomized, double-blind, placebo-controlled trial of AZD0530 in AD patients with Mini-Mental State Examination (MMSE) scores ranging from 16 to 26.[SEP]Relations: PPP1R1A has relations: anatomy_protein_present with central nervous system, anatomy_protein_present with central nervous system. malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer. Definitions: Saracatinib defined as following: An orally available 5-, 7-substituted anilinoquinazoline with anti-invasive and anti-tumor activities. Saracatinib is a dual-specific inhibitor of Src and Abl, protein tyrosine kinases that are overexpressed in chronic myeloid leukemia cells. This agent binds to and inhibits these tyrosine kinases and affects cell motility, cell migration, adhesion, invasion, proliferation, differentiation, and survival. Specifically, Saracatinib inhibits Src kinase-mediated osteoclast bone resorption.. Src defined as following: Proto-oncogene tyrosine-protein kinase Src (536 aa, ~60 kDa) is encoded by the human SRC gene. This protein is involved in both receptor-mediated signal transduction and tyrosine phosphorylation.. Fyn defined as following: Tyrosine-protein kinase Fyn (537 aa, ~61 kDa) is encoded by the human FYN gene. This protein is involved in tyrosine phosphorylation, cytoskeleton remodeling and signal transduction.. Src kinase defined as following: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. Prostate Cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. saracatinib defined as following: An orally available 5-, 7-substituted anilinoquinazoline with anti-invasive and anti-tumor activities. Saracatinib is a dual-specific inhibitor of Src and Abl, protein tyrosine kinases that are overexpressed in chronic myeloid leukemia cells. This agent binds to and inhibits these tyrosine kinases and affects cell motility, cell migration, adhesion, invasion, proliferation, differentiation, and survival. Specifically, Saracatinib inhibits Src kinase-mediated osteoclast bone resorption..", "label": "yes"}
{"id": "converted_1345", "sentence1": "Are DNA methylation maps applicable to the diagnosis of non-small-cell lung carcinomas?", "sentence2": "Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples., Analysis of the MethylCap-seq data revealed a strong positive correlation between replicate experiments and between paired tumor/lung samples. We identified 57 differentially methylated regions (DMRs) present in all NSCLC tumors analyzed by MethylCap-seq. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. We also identified DMRs that were specific to two of the major subtypes of NSCLC, adenocarcinomas and squamous cell carcinomas., Collectively, we provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC., Genome-wide DNA methylation profiling of non-small cell lung carcinomas., Genomewide DNA methylation analysis identifies novel methylated genes in non-small-cell lung carcinomas., To identify candidate markers for use in NSCLC diagnosis, we used genomewide DNA methylation maps that we had previously generated by MethylCap and next-generation sequencing and listed the most significant differentially methylated regions (DMRs). The 25 DMRs with highest significance in their methylation scores were selected. The methylation status of these DMRs was investigated in 61 tumors and matching control lung tissues by methylation-specific polymerase chain reaction., We found 12 novel DMRs that showed significant differences between tumor and control lung tissues. We also identified three novel DMRs for each of the two most common NSCLC subtypes, adenocarcinomas and squamous cell carcinomas. We propose a panel of five DMRs, composed of novel and known markers that exhibit high specificity and sensitivity to distinguish tumors from control lung tissues., Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples., It is a very stable and specific modification and therefore in principle a very suitable marker for epigenetic phenotyping of tumors. Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples., Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples. The MethylCap-seq data were validated by bisulfite sequencing and methyl-specific polymerase chain reaction of selected regions., Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples.[SEP]Definitions: adenocarcinomas defined as following: A malignant epithelial tumor with a glandular organization.. squamous cell carcinomas defined as following: A squamous cell carcinoma arising from the oral cavity. It affects predominantly adults in their fifth and sixth decades of life and is associated with alcohol and tobacco use. Human papillomavirus is present in approximately half of the cases. It is characterized by a tendency to metastasize early to the lymph nodes. When the tumor is small, patients are often asymptomatic. Physical examination may reveal erythematous or white lesions or plaques. The majority of patients present with signs and symptoms of locally advanced disease including mucosal ulceration, pain, difficulty with speaking, chewing, and swallowing, bleeding, weight loss, and neck swelling. Patients may also present with swollen neck lymph nodes without any symptoms from the oropharyngeal tumor. The most significant prognostic factors are the size of the tumor and the lymph nodes status.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. NSCLC defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. lung tissues defined as following: Tissue consisting of an external serous coat, subserous areolar tissue and lung parenchyma. The parenchyma is made up of lobules wound together by connective tissue. A primary lobule consists of a terminal bronchiole, respiratory bronchioles, and alveolar ducts, which communicate with many alveoli, each alveolus being surrounded by a network of capillary blood vessels.. modification defined as following: Respond with exceptions, completions and modifications or revisions done before completion
. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. non-small-cell lung carcinomas defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy..", "label": "yes"}
{"id": "converted_2734", "sentence1": "Is p53 a transcription factor?", "sentence2": "As a transcription factor, p53 mainly exerts its tumor suppressive function through transcriptional regulation of many target genes., p53 functions primarily as a sequence-specific transcription factor that controls the expression of hundreds of protein-coding genes and noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs)., p53 is a transcription factor [SEP]Definitions: p53 defined as following: Human TP53 wild-type allele is located in the vicinity of 17p13.1 and is approximately 19 kb in length. This allele, which encodes cellular tumor antigen p53 protein, plays a role in cell cycle regulation during the G0/G1transition. Alterations of the TP53 gene occur as both somatic and germline mutations in human malignancies in select cancer-prone families with Li-Fraumeni syndrome.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. miRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"}
{"id": "converted_2215", "sentence1": "Does the histone chaperone ASF1 interact with histones H1/H2?", "sentence2": "The C terminus of the histone chaperone Asf1 cross-links to histone H3 in yeast and promotes interaction with histones H3 and H4., The central histone H3/H4 chaperone Asf1 comprises a highly conserved globular core and a divergent C-terminal tail. , The histone H3-H4 chaperone Asf1 is involved in chromatin assembly (or disassembly), histone exchange, regulation of transcription, and chromatin silencing in several organisms. , An ASF1-EGFP fusion protein localizes to the nucleus. By tandem-affinity purification/mass spectrometry as well as yeast two-hybrid analysis, we identified histones H3 and H4 as ASF1 interaction partners. , This inhibition requires Asf1 binding to H3-H4 and Rtt109 KAT activity, but not tail acetylation of H3-H4 or K56 acetylation of H3. , Asf1 is a conserved histone H3/H4 chaperone that can assemble and disassemble nucleosomes and promote histone acetylation. , Here we characterize further interactions between budding yeast (Saccharomyces cerevisiae) Asf1 and Set2 using assays of intragenic transcription, H3/H4 posttranslational modification, coding region cross-linking of Asf1 and Set2, and cooccurrence of Asf1 and Set2 in protein complexes. , Consistent with this possibility, we show that Asf1 stimulates Set2 occupancy of the coding region of a highly transcribed gene by a mechanism that depends on Asf1 binding to H3/H4. , Drosophila histones H3 and H4 can also be produced as a soluble (H3H4)(2) heterotetrameric complex if they are co-expressed with the histone chaperone Asf1., Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4., Newly synthesized histones H3-H4 first bind histone chaperone Asf1 and are then transferred to other chaperones for nucleosome assembly, The C terminus of the histone chaperone Asf1 cross-links to histone H3 in yeast and promotes interaction with histones H3 and H4, Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosis, Antisilencing function 1 (ASF1) is a major histone H3-H4 chaperone that deposits histones H3 and H4 onto DNA, Rtt109, a recently discovered histone acetyltransferase (HAT) from Saccharomyces cerevisiae, functions with the histone chaperone Asf1 to acetylate lysine K56 on histone H3 (H3K56), a modification associated with newly synthesized histones, In this issue of Cell, English et al. present the first crystal structure of a histone chaperone (Asf1) bound to histones (the H3/H4 heterodimer), By tandem-affinity purification/mass spectrometry as well as yeast two-hybrid analysis, we identified histones H3 and H4 as ASF1 interaction partners., Anti-silencing function 1 (Asf1) is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair., Analysis of a panel of Asf1 mutations that modulate the ability of Asf1 to bind to histones H3/H4 demonstrates that the histone binding activity of Asf1 is required for the acetylation of Lys-9 and Lys-56 on newly synthesized H3., Thus Rad53 competes with histones H3-H4 and cochaperones HirA/CAF-I for binding to Asf1., Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4., Currently, the best-characterized chaperone-histone interaction is that between the ubiquitous chaperone Asf1 and a dimer of H3 and H4.[SEP]Relations: FGFR1 has relations: cellcomp_protein with nucleus, cellcomp_protein with nucleus. Definitions: chromatin assembly defined as following: The assembly of DNA, histone proteins, other associated proteins, and sometimes RNA, into chromatin structure, beginning with the formation of the basic unit, the nucleosome, followed by organization of the nucleosomes into higher order structures, ultimately giving rise to a complex organization of specific domains within the nucleus. [PMID:20404130]. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. histones defined as following: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.. HAT defined as following: Class of enzymes that catalyze the acetylation of specific lysine residues of histones, proteins that organize eukaryotic DNA into chromatin. Among the proteins that exhibit histone acetyltransferase activity are various transcription factor coactivators. E.C. 2.3.1.48.. H4 defined as following: This gene plays a role in mitogenesis and differentiation.. Set2 defined as following: Human SETD2 is located in the vicinity of 3p21.31 and is approximately 108 kb in length. This allele, which encodes histone-lysine N-methyltransferase SETD2 protein, may play a role in transcriptional activation and epigenetic modification of chromatin.. histone H3 defined as following: Histone H3 is a core subunit of the eukaryotic nucleosome complex. Histones are basic nuclear proteins responsible for the nucleosome structure of chromatin. Repeating nucleosome units contain two molecules each of Histones H2A, H2B, H3, and H4 that form an octamer complex around which approximately 146 base pairs of DNA is wrapped. Linker Histone H1 interacts with DNA between nucleosome units in mediating chromatin compaction into higher order structures. (NCI). chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. nucleosome assembly defined as following: The aggregation, arrangement and bonding together of a nucleosome, the beadlike structural units of eukaryotic chromatin composed of histones and DNA. [GOC:mah]. modification defined as following: Respond with exceptions, completions and modifications or revisions done before completion
. organisms defined as following: A living entity.. nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). dimer defined as following: compound formed by the union of two radicals or two molecules of a simpler compound; a polymer formed from two molecules of a monomer.. coding region defined as following: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR)..", "label": "no"}
{"id": "converted_4011", "sentence1": "Are there small molecule CGRPs under development for the treatment of migraine?", "sentence2": "Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine., Several other small-molecular CGRP receptor antagonists are in earlier stages of development for acute migraine treatment or prevention. [SEP]Definitions: migraine defined as following: A common, severe type of vascular headache often associated with increased sympathetic activity, resulting in nausea, vomiting, and light sensitivity.. CGRP receptor antagonist defined as following: Pharmacologic agents that block NOCICEPTIVE PAIN signaling from CALCITONIN GENE-RELATED PEPTIDE RECEPTORS. They may be useful for the treatment of pain associated with MIGRAINE DISORDERS and OSTEOARTHRITIS..", "label": "yes"}
{"id": "converted_2425", "sentence1": "Are there mammalian promoters with distal enhancer functions?", "sentence2": "Genome-wide characterization of mammalian promoters with distal enhancer functions., Gene expression in mammals is precisely regulated by the combination of promoters and gene-distal regulatory regions, known as enhancers. Several studies have suggested that some promoters might have enhancer functions. However, the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive. Here, by exploiting a high-throughput enhancer reporter assay, we unravel a set of mammalian promoters displaying enhancer activity. These promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters. Extensive CRISPR-Cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci. Our results have important implications for the understanding of complex gene regulation in normal development and disease., Here, by exploiting a high-throughput enhancer reporter assay, we unravel a set of mammalian promoters displaying enhancer activity., Several studies have suggested that some promoters might have enhancer functions., genome wide characterization of mammalian promoters with distal enhancer functions, gene expression in mammals is precisely regulated by the combination of promoters and gene distal regulatory regions known as enhancers several studies have suggested that some promoters might have enhancer functions however the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive here by exploiting a high throughput enhancer reporter assay we unravel a set of mammalian promoters displaying enhancer activity these promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters extensive crispr cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci our results have important implications for the understanding of complex gene regulation in normal development and disease.[SEP]Definitions: mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. genome defined as following: Anatomical set of genes in all the chromosomes.. enhancer defined as following: A 50-150bp DNA sequence that increases the rate of transcription of coding sequences. It may be located at various distances and in either orientation upstream from, downstream from or within a structural gene. When bound by a specific transcription factor it increases the levels of expression of the gene, but is not sufficient alone to cause expression. Distinguished from a promoter, that is alone sufficient to cause expression of the gene when bound.. regulatory regions defined as following: Nucleic acid sequences involved in regulating the expression of genes.. genomic defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA..", "label": "yes"}
{"id": "converted_4157", "sentence1": "Is metoprolol metabolized by CYP2D6?", "sentence2": "Among these beta-blockers atenolol is mainly eliminated by renal excretion, bisoprolol is in part excreted as parent compound via the renal route (50%), the other 50% are hepatically metabolised, whereas metoprolol and carvedilol are metabolised by CYP2D6. [SEP]Definitions: carvedilol defined as following: A carbazole and propanol derivative that acts as a non-cardioselective beta blocker and vasodilator. It has blocking activity for ALPHA 1 ADRENERGIC RECEPTORS and, at higher doses, may function as a blocker of CALCIUM CHANNELS; it also has antioxidant properties. Carvedilol is used in the treatment of HYPERTENSION; ANGINA PECTORIS; and HEART FAILURE. It can also reduce the risk of death following MYOCARDIAL INFARCTION.. metoprolol defined as following: A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.. bisoprolol defined as following: A cardioselective beta-1 adrenergic blocker. It is effective in the management of HYPERTENSION and ANGINA PECTORIS.. CYP2D6 defined as following: Cytochrome P450 2D6 (497 aa, ~56 kDa) is encoded by the human CYP2D6 gene. This protein plays a role in flavoprotein metabolism..", "label": "yes"}
{"id": "converted_1152", "sentence1": "Does thyroid hormone affect cardiac remodeling ?", "sentence2": "Thyroid hormones exert important effects on heart remodeling through mir-208., RV and RA function and mechanics are significantly affected by SHT. l-T4 therapy and 1-year maintenance of euthyroid status improved but did not completely recover RV and RA function and deformation in the SHT patients, which implies that right heart remodeling caused by SHT is not reversible in a 1-year period., These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.[SEP]Definitions: myocyte defined as following: Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal (MUSCLE FIBERS, SKELETAL), cardiac (MYOCYTES, CARDIAC), and smooth (MYOCYTES, SMOOTH MUSCLE). They are derived from embryonic (precursor) muscle cells called MYOBLASTS.. Thyroid hormones defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs..", "label": "yes"}
{"id": "converted_512", "sentence1": "Is vemurafenib effective for hairy-cell leukemia?", "sentence2": "CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia., Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL., The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. , Successful re-treatment of a relapsed V600E mutated HCL patient with low-dose vemurafenib., Recent identification of the recurrent V600E BRAF mutation in a majority of HCL patients has led some teams to evaluate the clinical potential of vemurafenib, a BRAF V600 specific inhibitor in a limited number of refractory HCL patients. Recently, we published the case of an HCL patient successfully treated with a low dose of vemurafenib., We present here the successful retreatment of this patient with a second line of vemurafenib. Our data suggest for the first time that vemurafenib at the dose of 240 mg once a day could be sufficient to maintain a complete hematological remission after an initial induction treatment with low-dose vemurafenib (2 × 240 mg) daily without inducing major toxicity., The discovery of the BRAF mutation has created a therapeutic target exploited by oral inhibitors like vemurafenib and dabrafenib., [Successful use of vemurafenib in a patient with resistant hairy cell leukemia]., The frequent persistence of phosphorylated ERK-positive leukemic cells in bone marrow at the end of treatment suggests bypass reactivation of MEK and ERK as a resistance mechanism.CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. , A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia., A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia., The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option.[SEP]Relations: Vemurafenib has relations: drug_protein with BRAF, drug_protein with BRAF. hairy cell leukemia has relations: disease_protein with BRAF, disease_protein with BRAF. Dabrafenib has relations: drug_protein with BRAF, drug_protein with BRAF. Definitions: MEK defined as following: A dual-specific protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.. vemurafenib defined as following: An orally bioavailable, ATP-competitive, small-molecule inhibitor of BRAF(V600E) kinase with potential antineoplastic activity. Vemurafenib selectively binds to the ATP-binding site of BRAF(V600E) kinase and inhibits its activity, which may result in an inhibition of an over-activated MAPK signaling pathway downstream in BRAF(V600E) kinase-expressing tumor cells and a reduction in tumor cell proliferation. Approximately 90% of BRAF gene mutations involve a valine-to-glutamic acid mutation at residue 600 (V600E); the oncogene protein product, BRAF(V600E) kinase, exhibits a markedly elevated activity that over-activates the MAPK signaling pathway. The BRAF(V600E) gene mutation has been found to occur in approximately 60% of melanomas, and in about 8% of all solid tumors, including melanoma, colorectal, thyroid and other cancers.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. ERK defined as following: A superfamily of PROTEIN SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. HCL defined as following: A neoplastic disease of the lymphoreticular cells which is considered to be a rare type of chronic leukemia; it is characterized by an insidious onset, splenomegaly, anemia, granulocytopenia, thrombocytopenia, little or no lymphadenopathy, and the presence of \"hairy\" or \"flagellated\" cells in the blood and bone marrow.. dabrafenib defined as following: An orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations.. BRAF defined as following: Serine/threonine-protein kinase B-raf (766 aa, ~84 kDa) is encoded by the human BRAF gene. This protein plays a role in protein phosphorylation, mitogenesis and neuronal signal transduction.. hairy-cell leukemia defined as following: A neoplastic disease of the lymphoreticular cells which is considered to be a rare type of chronic leukemia; it is characterized by an insidious onset, splenomegaly, anemia, granulocytopenia, thrombocytopenia, little or no lymphadenopathy, and the presence of \"hairy\" or \"flagellated\" cells in the blood and bone marrow..", "label": "yes"}
{"id": "converted_2903", "sentence1": "Should dacomitinib be used for treatment of glioblastoma patients?", "sentence2": "Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit. , Conclusions: Dacomitinib has a limited single-agent activity in recurrent GB with EGFR amplification., Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit., Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit.[SEP]Definitions: Dacomitinib defined as following: A highly selective, orally bioavailable small-molecule inhibitor of the HER family of tyrosine kinases with potential antineoplastic activity. Dacomitinib specifically and irreversibly binds to and inhibits human Her-1, Her-2, and Her-4, resulting in the proliferation inhibition and apoptosis of tumor cells that overexpress these receptors.. dacomitinib defined as following: A highly selective, orally bioavailable small-molecule inhibitor of the HER family of tyrosine kinases with potential antineoplastic activity. Dacomitinib specifically and irreversibly binds to and inhibits human Her-1, Her-2, and Her-4, resulting in the proliferation inhibition and apoptosis of tumor cells that overexpress these receptors.. glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO).", "label": "no"}
{"id": "converted_4299", "sentence1": "Does αCGRP have amyloidogenic properties?", "sentence2": "αCGRP, another amyloidogenic member of the CGRP family., Therefore, in this work, we investigated the amyloidogenic profile of αCGRP, a 37-residue-long peptide hormone, utilizing both biophysical experimental techniques and Molecular Dynamics simulations. These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the αCGRP polymerization.[SEP]Definitions: CGRP defined as following: A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.. peptide hormone defined as following: OBSOLETE. (Was not defined before being made obsolete). [GOC:ai].", "label": "yes"}
{"id": "converted_1340", "sentence1": "Are there enhancer RNAs (eRNAs)?", "sentence2": "active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription, eRNAs may then facilitate enhancer-promoter interaction or activate promoter-driven transcription, Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers, Enhancer RNAs and regulated transcriptional programs, enhancers have been found to be broadly transcribed, resulting in the production of enhancer-derived RNAs, or eRNAs, The emerging roles of eRNAs in transcriptional regulatory networks, we found certain enhancer RNAs (eRNAs) regulate chromatin accessibility of the transcriptional machinery at loci encoding master regulators of myogenesis (i.e., MyoD/MyoG), thus suggesting their significance and site-specific impact in cellular programming, Enhancer RNAs: the new molecules of transcription, the discovery that distal regulatory elements known as enhancers are transcribed and such enhancer-derived transcripts (eRNAs) serve a critical function in transcriptional activation has added a new dimension to transcriptional regulation, eRNAs reach the heart of transcription, Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation., Since the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed \"enhancer RNAs\" (eRNAs), their putative role in enhancer function has been debated., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs)., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established., In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs)., In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). , A subset of enhancers are occupied by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs termed eRNAs. , Very recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibly by helping recruit and/or stabilize binding of the general transcription machinery to the proximal promoter of their target genes. , In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. , Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis., A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons., Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers,, In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription.[SEP]Definitions: RNA polymerase II defined as following: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. histone H3 defined as following: Histone H3 is a core subunit of the eukaryotic nucleosome complex. Histones are basic nuclear proteins responsible for the nucleosome structure of chromatin. Repeating nucleosome units contain two molecules each of Histones H2A, H2B, H3, and H4 that form an octamer complex around which approximately 146 base pairs of DNA is wrapped. Linker Histone H1 interacts with DNA between nucleosome units in mediating chromatin compaction into higher order structures. (NCI). promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. mRNA transcription defined as following: The cellular synthesis of messenger RNA (mRNA) from a DNA template. [GOC:jl]. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds..", "label": "yes"}
{"id": "converted_4610", "sentence1": "Do RNA binding Proteins that bind to adenine uridine (AU)-rich elements (AREs) in the 5' untranslated region (UTR) of mRNAs (AU-RBPs) regulate the DNA Damage Response?", "sentence2": " We investigated 2 mRNA-binding proteins - HuR and TIAR showing specificity to AU-Rich Element (ARE) sites in 3'UTR of mRNA., Bioinformatics analysis of the human SOD1 mRNA 3' untranslated region (3'UTR) demonstrated the presence of HuD binding adenine-uridine (AU)-rich instability-conferring elements (AREs)., We found that AU-rich element RNA binding protein 1 (AUF1) directly binds to the Cry1 3'UTR and regulates translation of Cry1 mRNA., Adenylate/uridylate-rich elements (AREs) are the most common cis-regulatory elements in the 3'-untranslated region (UTR) of mRNAs, where they fine-tune turnover by mediating mRNA decay., HuR binding to AU-rich elements present in the 3' untranslated region of Classical swine fever virus., Previous reports indicate that distinct RNA sequence in the BDNF 3'UTRs differentially regulates BDNF production in the brain to accommodate neuronal activity changes, conceivably through differential interactions with undefined trans-acting factors that regulate stability and translation of these BDNF mRNA isoforms., The 5' untranslated region (UTR) of CSFV contains the IRES, which is a highly structured element that recruits the translation machinery., Although AU-rich elements (AREs) in the 3'UTR of interleukin-6 (IL-6) mRNA dictate mRNA degradation, the role of TTP in the post-transcriptional regulation of IL-6 gene expression is unclear., We cloned the full-length cDNA of rabbit RGS4, which contains a long 3'-untranslated region (UTR) with several AU-rich elements (AREs)., Luciferase reporter assays demonstrate that HuR specifically regulates FOXO1 expression through AU-rich elements (AREs) within the FOXO1 3' UTR., Additionally, we demonstrated that RNPC1 could bind to PR mRNA via AU-rich elements (AREs) within PR 3'-untranslated region (3'-UTR) and then enhance PR mRNA stability., Here, we find that CXCR4 harbors AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR) that bind and respond to the RNA-binding proteins, tristetraprolin (TTP/ZFP36) and HuR (ELAVL1)., These proteins bind to adenine uridine-rich element (ARE) in the 3'untranslated region of target messenger RNA and stimulate target degradation., t mRNAs. RNA-binding proteins can control mRNA stability by binding to AU- and U-rich elements located in the 3'-untranslated regions (3'-UTRs) of target, y RNA-binding proteins (RBPs) have been shown to recognize and bind to mRNAs that contains AREs generally present in the 3'UTR of mRNAs. RBPs , at AREs in the 3'UTR control TSP-1 mRNA stability and that the RNA binding protein AUF1 participates in this control. These studies suggest t, mber of the Elav family of RNA-binding proteins, has been implicated in this pathway through its binding to adenine and uridine (AU)-rich stability elements (ARE) located in the 3' untranslated regions (3'-UTRs) of the mRNA. Whereas three , Hu proteins are RNA-binding proteins that are implicated in the control of stabilization, nuclear export, and/or translation of specific mRNAs with AU-rich elements (AREs) in the 3'-untranslated region. Th, Post-transcriptional mRNA regulation by RNA binding proteins (RBPs) associated with AU-rich elements (AREs) present in the 3' untranslated region (3'UTR) of specific mRNAs modulates transcript stability and translation in eukaryotic cells., In the 3'-untranslated region, the destabilizing adenine-uridine (AU)-rich elements (AREs) control the expression of several transcripts through interactions with ARE-binding proteins (AUBPs) and RNA degradation machinery., The AU/U-rich element-binding protein HuR has been shown to bind to p53 mRNA 3'UTR and enhance translation in response to DNA-damaging UVC radiation., The AUF1 (hnRNPD) and HuR (ELAV-like) proteins, potential trans-acting factors for regulated mRNA decay, bind in vitro to A+U-rich elements (AREs) found in the 3' untranslated region (3' UTR) of many labile transcripts., NCL binds to the AU-rich element (ARE) in the 3'UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation., We investigated 2 mRNA-binding proteins - HuR and TIAR showing specificity to AU-Rich Element (ARE) sites in 3'UTR of mRNA., Secondly, the degradation of some mRNAs related to immune responses has been reported to be regulated by binding of RNA-binding proteins to adenylate uridylate-rich elements (AU-rich elements, AREs) located in the 3'-untranslated region (3'-UTR)., Here, we review the interplay between six well-known RBPs (TTP, AUF-1, KSRP, HuR, TIA-1, and TIAR) that recognize AU-rich elements (AREs) at the 3' untranslated regions of mRNAs, namely ARE-RBPs., Hu proteins have been shown to bind to AU-rich elements (AREs) in the 3'-untranslated region of unstable mRNAs.[SEP]Relations: C-X-C motif chemokine 12 receptor activity has relations: molfunc_protein with CXCR4, molfunc_protein with CXCR4. protein binding has relations: molfunc_protein with CXCR4, molfunc_protein with BDNF, molfunc_protein with NCL, molfunc_protein with CXCR4, molfunc_protein with BDNF, molfunc_protein with NCL. Definitions: IL-6 defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin-6 (IL-6) with antiapoptotic, proinflammatory, antiinflammatory, proproliferative and proangiogenic activities. IL-6 binds to its receptor (IL-6R), activating a receptor-CD130 receptor complex; the CD130 portion of the complex is a signal transduction protein that activates JAK kinases and Ras-mediated signaling pathways, which in turn activate downstream signaling pathways, resulting in the activation of various transcription factors (STAT, ELK-1, NF-IL-6, etc.) and gene transcription. The physiological effects of IL-6 are complex and varied and include hematopoietic, pyrogenic and thermogenic, proinflammatory, antiinflammatory, proproliferative (anti-apoptotic), and angiogenic effects.. BDNF defined as following: A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994). TIA-1 defined as following: Human TIA1 wild-type allele is located in the vicinity of 2p13 and is approximately 39 kb in length. This allele, which encodes nucleolysin TIA-1 isoform p40, plays a role in both RNA binding and splicing. Mutation of the gene is associated with Welander distal myopathy.. TTP defined as following: Thrombotic thrombocytopenic purpura for which the cause is present from birth.. adenine defined as following: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.. ARE defined as following: A unit of area equal to 100 square meters. Are is a non-SI unit accepted for use with SI.. tristetraprolin defined as following: A ZINC FINGER MOTIF containing transcription factor that was originally identified as one of the IMMEDIATE-EARLY PROTEINS. It shuttles between the CYTOPLASM and the CELL NUCLEUS and is involved in destabilization of mRNAs for TUMOR NECROSIS FACTOR-ALPHA.. RNA sequence defined as following: The sequence of nucleotide residues along an RNA chain.. NCL defined as following: A group of severe neurodegenerative diseases characterized by intracellular accumulation of autofluorescent wax-like lipid materials (CEROID; LIPOFUSCIN) in neurons. There are several subtypes based on mutations of the various genes, time of disease onset, and severity of the neurological defects such as progressive DEMENTIA; SEIZURES; and visual failure.. FOXO1 defined as following: This gene is involved in transcriptional regulation and may play a role in myogenic growth and differentiation.. Cry1 defined as following: This gene plays a role in circadian rhythm.. HuR defined as following: This gene plays a role in the regulation of gene expression.. hnRNPD defined as following: Heterogeneous nuclear ribonucleoprotein D0 (355 aa, ~38 kDa) is encoded by the human HNRNPD gene. This protein is involved in both RNA transport and splicing.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. transcript defined as following: The initial RNA molecule produced by transcription.. CXCR4 defined as following: Combining with the C-X-C motif chemokine 12 (CXCL12) and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. [GOC:bf, PMID:22204316]. IRES defined as following: Sequences within MESSENGER RNA that enable PROTEIN TRANSLATION INITIATION independent of 5' CAPPED RNA.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. eukaryotic cells defined as following: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane.. 3' UTR defined as following: The sequence at the 3' end of messenger RNA that does not code for product. This region contains transcription and translation regulating sequences.. RNA binding proteins defined as following: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.. RNPC1 defined as following: Human RBM38 wild-type allele is located in the vicinity of 20q13.31 and is approximately 18 kb in length. This allele, which encodes RNA-binding protein 38, plays a role in the regulation of mRNA stability.. AUF1 defined as following: Human HNRNPD wild-type allele is located in the vicinity of 4q21 and is approximately 22 kb in length. This allele, which encodes heterogeneous nuclear ribonucleoprotein D0, plays a role in the catabolism of RNA.. Th defined as following: Tyrosine 3-monooxygenase (528 aa, ~59 kDa) is encoded by the human TH gene. This protein plays a role in the synthesis of dopamine from L-tyrosine.. trans-acting factors defined as following: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.. p53 defined as following: Human TP53 wild-type allele is located in the vicinity of 17p13.1 and is approximately 19 kb in length. This allele, which encodes cellular tumor antigen p53 protein, plays a role in cell cycle regulation during the G0/G1transition. Alterations of the TP53 gene occur as both somatic and germline mutations in human malignancies in select cancer-prone families with Li-Fraumeni syndrome.. TSP-1 defined as following: An extracellular matrix glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin. Thrombospondin-1 is believed to play a role in cell migration and proliferation, during embryogenesis and wound repair. Also, it has been studied for its use as a potential regulator of tumor growth and metastasis..", "label": "no"}
{"id": "converted_3829", "sentence1": "Is there any role of genotoxic pks + E. coli in cancer?", "sentence2": "Mutational signature in colorectal cancer caused by genotoxic pks+, Various species of the intestinal microbiota have been associated with the development of colorectal cancer1,2, but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin3. This compound is believed to alkylate DNA on adenine residues4,5 and induces double-strand breaks in cultured cells3. Here we expose human intestinal organoids to genotoxic pks+ E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.[SEP]Relations: malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer. Definitions: luminal defined as following: Relating to the lumen of a blood vessel or other tubular structure.. human defined as following: Members of the species Homo sapiens.. intestinal microbiota defined as following: The collection of microorganisms existing in the intestines of an organism.. adenine defined as following: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. Escherichia coli defined as following: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.. cancer defined as following: A malignant tumor at the original site of growth..", "label": "yes"}
{"id": "converted_1347", "sentence1": "Is the protein product of the cylindromatosis gene (CYLD) a deubiquitinating enzyme?", "sentence2": "CYLD was originally identified as a tumor suppressor gene mutated in familial cylindromatosis, an autosomal dominant predisposition to multiple benign neoplasms of the skin known as cylindromas. The CYLD protein is a deubiquitinating enzyme that acts as a negative regulator of NF-κB and JNK signaling through its interaction with NEMO and TNFR-associated factor 2., CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse cellular processes, ranging from proliferation and differentiation to inflammatory responses, via regulating multiple key signaling cascades such as nuclear factor kappa B (NF-κB) pathway., CYLD is a lysine 63-deubiquitinating enzyme that inhibits NF-κB and JNK signaling., Tumor suppressor gene CYLD is a deubiquitinating enzyme which negatively regulates various signaling pathways by removing the lysine 63-linked polyubiquitin chains from several specific substrates., The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in various aspects of adaptive and innate immune responses. , The cylindromatosis gene (CYLD) was identified as a tumor suppressor gene, which is mutated in familial cylindromatosis (Brooke-Spiegler syndrome), an autosomal-dominant predisposition to multiple tumors of the skin appendages. CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor κB (NF-κB) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-κB activating proteins. , Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling., CYLD is a tumour-suppressor gene that is mutated in a benign skin tumour syndrome called cylindromatosis. The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling., Cyld encodes a 956-amino acid deubiquitinating enzyme (CYLD), which is a negative regulator of nuclear factor kappaB and mitogen-activated protein kinase pathways., The deubiquitinating enzyme CYLD has been identified as a key negative regulator for NF-kappaB. , CYLD, a tumor suppressor gene, has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Loss of the deubiquitinating activity of CYLD is correlated with tumorigenesis., We show that dCYLD encodes a deubiquitinating enzyme that deubiquitinates dTRAF2 and prevents dTRAF2 from ubiquitin-mediated proteolytic degradation., The CYLD gene encodes a deubiquitinating enzyme that removes Lys-63-linked ubiquitin chains from I kappa B kinase signaling components and thereby inhibits NF-kappaB pathway activation., Deubiquitinating enzymes (DUB) form a family of cysteine proteases that digests ubiquitin chains and reverses the process of protein ubiquitination. Despite the identification of a large number of DUBs, their physiological functions remain poorly defined. Here we provide genetic evidence that CYLD, a recently identified DUB, plays a crucial role in regulating the peripheral development and activation of B cells., The cylindromatosis (CYLD) gene was originally identified as a tumor suppressor that is mutated in familial cylindromatosis, an autosomal dominant condition that confers a predisposition to multiple tumors of the skin appendages. CYLD has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Therefore, loss of CYLD function correlates with tumorigenesis., Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-κB signaling pathway and attenuates NF-κB and JNK signaling., The cylindromatosis tumor suppressor gene (Cyld) encodes a deubiquitinating enzyme (CYLD) with immunoregulatory function., The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling., Here, we examined the potential role of the deubiquitinating enzyme CYLD (cylindromatosis), mutation of which has been reported to cause familial cylindromatosis., The deubiquitinating enzyme cylindromatosis (CYLD), loss of which was originally reported to cause a benign human syndrome called cylindromatosis, has been identified as a key negative regulator for NF-kappaB in vitro., The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling., Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-�B signaling pathway and attenuates NF-�B and JNK signaling., Cylindromatosis (CYLD) is a deubiquitinating enzyme that is altered in patients with familial cylindromatosis, a condition characterized by numerous benign adnexal tumors., CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members., Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling, Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-κB signaling pathway and attenuates NF-κB and JNK signaling, The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling, The cylindromatosis tumor suppressor gene (Cyld) encodes a deubiquitinating enzyme (CYLD) with immunoregulatory function, Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-κB signaling pathway and attenuates NF-κB and JNK signaling, The cylindromatosis tumor suppressor gene (Cyld) encodes an enzyme (CYLD) with deubiquitinating activity that has been implicated in the regulation of thymocyte selection in an NF-κB-essential-modulator (NEMO)-dependent manner, Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling, CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor κB (NF-κB) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-κB activating proteins, CYLD, a tumor suppressor gene, has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB, Here, we examined the potential role of the deubiquitinating enzyme CYLD (cylindromatosis), mutation of which has been reported to cause familial cylindromatosis, CYLD has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB[SEP]Relations: Brooke-Spiegler syndrome has relations: disease_protein with CYLD, disease_protein with CYLD. Definitions: CYLD gene defined as following: This gene is involved in protein deubiquitination.. Cyld defined as following: Ubiquitin carboxyl-terminal hydrolase CYLD (956 aa, ~107 kDa) is encoded by the human CYLD gene. This protein is involved in the mediation of protein deubiquitination and the regulation of the cell cycle.. NEMO defined as following: NF-kappa-B essential modulator (419 aa, ~48 kDa) is encoded by the human IKBKG gene. This protein plays a role in the mediation of signal transduction through protein phosphorylation.. cysteine proteases defined as following: A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.. B cells defined as following: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.. TNFR defined as following: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.. nuclear factor kappa B defined as following: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. cylindromas defined as following: Carcinoma characterized by bands or cylinders of hyalinized or mucinous stroma separating or surrounded by nests or cords of small epithelial cells. When the cylinders occur within masses of epithelial cells, they give the tissue a perforated, sievelike, or cribriform appearance. Such tumors occur in the mammary glands, the mucous glands of the upper and lower respiratory tract, and the salivary glands. They are malignant but slow-growing, and tend to spread locally via the nerves. (Dorland, 27th ed). Deubiquitinating enzymes defined as following: Enzymes that remove UBIQUITIN from a protein substrate, including POLYUBIQUITIN, or from other molecules.. CYLD protein defined as following: A deubiquitinase and tumor-suppressor protein that specifically cleaves LYSINE-63-linked polyubiquitin chains and also has endodeubiquitinase activity. It functions to regulate NF-KAPPA B and WNT SIGNALING PATHWAY activity, contributing to cell survival, proliferation, and differentiation. Mutations in the CYLD gene are associated with cases of FAMILIAL CYLINDROMATOSIS.. nuclear factor κB defined as following: A family of proteins that contain 1 DWA/MH1 domain and bind 5'-TTGGCNNNNNGCCAA-3' DNA palindromes in viral and cellular promoters as homodimeric factors capable of activating transcription and replication.. Brooke-Spiegler syndrome defined as following: A rare genetic disease characterized as an inherited skin tumour predisposition syndrome presenting with skin appendage tumours, namely cylindromas, spiradenomas and trichoepitheliomas. tumor suppressor gene defined as following: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.. CYLD defined as following: Ubiquitin carboxyl-terminal hydrolase CYLD (956 aa, ~107 kDa) is encoded by the human CYLD gene. This protein is involved in the mediation of protein deubiquitination and the regulation of the cell cycle..", "label": "yes"}
{"id": "converted_162", "sentence1": "Is there an increased risk for cancer in Dyskeratosis Congenita?", "sentence2": "People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis, Clinical progression of the disease can lead to aplastic anemia (86% of all patients) and to pulmonary or hepatic complications. These patients also have an increased risk of cancer., Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anaemia (DBA), and Shwachman-Diamond syndrome (SDS) comprise major inherited bone marrow failure syndromes (IBMFS). Adverse events include severe bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid tumours (ST), Patients with FA had earlier onset of cancers, need for stem cell transplant, and death; followed by DC; DBA and SDS were mildest. While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients, The findings demonstrate that both FA and DC are major cancer susceptibility syndromes, People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis, Patients with dyskeratosis congenita (DC) have an increased risk of cancer, but also exhibit heightened radiation sensitivity., Dyskeratosis congenita (DC) is characterized by the clinical triad of reticular skin pigmentation, oral leukoplakia, and nail dystrophy associated with bone marrow failure (BMF) and an high risk to develop cancer and pulmonary complications., CONCLUSION: Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients., Point mutations in the DKC1 gene that encodes dyskerin cause the rare inherited syndrome called X-linked dyskeratosis congenita, characterized by a failure of proliferating tissues and increased susceptibility to cancer., Dyskeratosis Congenita (DC) also known as Zinsser-Engman-Cole syndrome is a rare multi-system bone marrow failure syndrome characterised by mucocutaneous abnormalities and an increased predisposition to cancer\"., Dyskeratosis congenita is an inherited syndrome characterised by mucocutaneous features, bone marrow failure, an increased risk of malignancy and other somatic abnormalities., Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients., Epidermal atrophy, hair growth defects, bone marrow failure and increased risk of cancer are also common in DC patients., Telomere dysfunction and tumor suppression responses in dyskeratosis congenita: balancing cancer and tissue renewal impairment., Patients with dyskeratosis congenita (DC) have an increased risk of cancer, but also exhibit heightened radiation sensitivity, Dyskeratosis congenita is a rare condition; however, it is vital to recognise the increased risk of upper aerodigestive tract cancers in these patients, Dyskeratosis congenita is an inherited syndrome characterised by mucocutaneous features, bone marrow failure, an increased risk of malignancy and other somatic abnormalities, While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients, As in Fanconi anemia and dyskeratosis congenita, DBA is both an inherited bone marrow failure syndrome and a cancer predisposition syndrome; cancer risks appear lower in DBA than in Fanconi anemia or dyskeratosis congenita, Severe pancytopenia frequently causes early mortality of DC patients, who have an increased risk of developing oropharyngeal squamous cell carcinoma, Here different aspects of telomere biology, concerning adult stem cells senescence, tumor suppression and cancer are considered in the context of DC, resulting in two translational models: late onset of DC symptoms in telomere-related mutations carriers is a potential indicator of increased cancer risk and differences in tumor suppression capacities among the genetic subgroups are (at least partial) causes of different clinical manifestations of the disease, Point mutations in the DKC1 gene that encodes dyskerin cause the rare inherited syndrome called X-linked dyskeratosis congenita, characterized by a failure of proliferating tissues and increased susceptibility to cancer, Dyskeratosis congenita is a cancer-prone bone marrow failure syndrome caused by aberrations in telomere biology.[SEP]Relations: Pancytopenia has relations: disease_phenotype_positive with bone marrow failure syndrome, disease_phenotype_positive with Shwachman-Diamond syndrome, disease_phenotype_positive with bone marrow failure syndrome, disease_phenotype_positive with Shwachman-Diamond syndrome. Fanconi anemia complementation group has relations: disease_disease with Fanconi anemia, disease_disease with Fanconi anemia. Bone marrow hypocellularity has relations: disease_phenotype_positive with Shwachman-Diamond syndrome, disease_phenotype_positive with bone marrow failure syndrome, disease_phenotype_positive with Shwachman-Diamond syndrome, disease_phenotype_positive with bone marrow failure syndrome. anal canal squamous cell carcinoma has relations: disease_disease with squamous cell carcinoma, disease_disease with squamous cell carcinoma. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. Telomere defined as following: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.. oropharyngeal squamous cell carcinoma defined as following: A squamous cell carcinoma arising from the oropharynx. It predominantly affects adults in their fifth and sixth decades of life and is associated with alcohol and tobacco use. Human papillomavirus is present in approximately half of the cases. It is characterized by a tendency to metastasize early to the lymph nodes. When the tumor is small, patients are often asymptomatic. Physical examination may reveal erythematous or white lesions or plaques. The majority of patients present with locally advanced disease. Signs and symptoms include mucosal ulceration, pain, bleeding, weight loss, neck swelling, and difficulty speaking, chewing, and swallowing. Patients may also present with swollen neck lymph nodes without any symptoms from the oropharyngeal tumor. The most significant prognostic factors are the size of the tumor and the lymph nodes status.. oral leukoplakia defined as following: A white patch seen on the oral mucosa. It is considered a premalignant condition and is often tobacco-induced. When evidence of Epstein-Barr virus is present, the condition is called hairy leukoplakia (LEUKOPLAKIA, HAIRY).. DBA defined as following: Congenital pure red cell aplasia caused by autosomal dominant mutation(s) in the RPS19 gene, encoding 40S ribosomal protein S19.. acute myelogenous leukemia defined as following: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. dyskerin defined as following: H/ACA ribonucleoprotein complex subunit 4 (514 aa, ~58 kDa) is encoded by the human DKC1 gene. This protein is involved in telomerase stabilization and maintenance and the processing of ribosomal RNA.. DKC1 gene defined as following: This gene is involved in both H/ACA small nucleolar RNA ribonucleoprotein assembly and telomerase stabilization and maintenance.. DC defined as following: A predominantly X-linked recessive syndrome characterized by a triad of reticular skin pigmentation, nail dystrophy and leukoplakia of mucous membranes. Oral and dental abnormalities may also be present. Complications are a predisposition to malignancy and bone marrow involvement with pancytopenia. (from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin.. IBMFS defined as following: A group of inherited genetic hematopoietic stem cell disorders characterized by bone marrow failure that involves one or more cell lines. Representative examples include Fanconi anemia, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome.. pancytopenia defined as following: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets.. leukaemia defined as following: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006). SDS defined as following: A patient reported questionnaire composed of rating scales developed to measure the degree of distress experienced by the patient for specific symptoms.. death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. Point mutations defined as following: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.. nail dystrophy defined as following: Deformity or discoloration of a fingernail or toenail.. aplastic anemia defined as following: A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.. myelodysplastic syndrome defined as following: Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.. Fanconi anemia defined as following: Fanconi anemia caused by mutations of the FANCA gene. FANCA gene mutations are the most common cause of Fanconi anemia. This gene provides instructions for making a protein that is involved in the Fanconi anemia (FA) pathway.. bone marrow failure defined as following: A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat. [DDD:wouwehand, HPO:probinson]. Fanconi anaemia defined as following: Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004). Diamond-Blackfan anaemia defined as following: A rare congenital hypoplastic anemia that usually presents early in infancy. The disease is characterized by a moderate to severe macrocytic anemia, occasional neutropenia or thrombocytosis, a normocellular bone marrow with erythroid hypoplasia, and an increased risk of developing leukemia. (Curr Opin Hematol 2000 Mar;7(2):85-94). solid tumors defined as following: A benign or malignant neoplasm arising from tissues that do not include fluid areas. Representative examples include epithelial neoplasms (e.g. lung carcinoma, prostate carcinoma, breast carcinoma, colon carcinoma), and neoplasms arising from the soft tissues and bones (e.g. leiomyosarcoma, liposarcoma, chondrosarcoma, osteosarcoma). Neoplasms originating from the blood or bone marrow (leukemias and myeloproliferative disorders) are not considered solid tumors.. X-linked dyskeratosis congenita defined as following: Dyskeratosis congenita inherited in an X-linked recessive pattern. It is caused by mutations in the DKC1 gene.. MDS defined as following: A rare syndrome caused by deletion of genetic material in the short arm of chromosome 17. It is characterized by an abnormally smooth brain with fewer folds and grooves. It results in intellectual disability, developmental delay, seizures, spasticity, hypotonia, and feeding difficulties. Affected individuals have distinctive facial features that include a prominent forehead, midface hypoplasia, small, upturned nose, low-set ears, small jaw, and thick upper lip.. squamous cell carcinoma defined as following: A squamous cell carcinoma (SCC) arising from the anal canal or the anal margin (perianal skin). Human papillomavirus is detected in the majority of cases. Homosexual HIV-positive men have an increased risk of developing anal squamous cell carcinoma in comparison to the general male population. Symptoms include anal pruritus, discomfort when sitting, pain, change in bowel habit, and bleeding. The prognosis is generally better for anal margin SCC than for anal canal SCC.. BMF defined as following: Bcl-2-modifying factor (184 aa, ~21 kDa) is encoded by the human BMF gene. This protein plays a role in the positive regulation of pro-apoptotic gene products.. Dyskeratosis Congenita defined as following: A predominantly X-linked recessive syndrome characterized by a triad of reticular skin pigmentation, nail dystrophy and leukoplakia of mucous membranes. Oral and dental abnormalities may also be present. Complications are a predisposition to malignancy and bone marrow involvement with pancytopenia. (from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin..", "label": "yes"}
{"id": "converted_1391", "sentence1": "Can RNASeq be used for the analysis of nascent transcripts?", "sentence2": "Here, we utilize nascent RNA sequencing to document dosage compensation during transcriptional elongation., Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription, Conversely, the nuclear fraction shows an enrichment of unprocessed RNA compared with total RNA-seq, making it suitable for analysis of nascent transcripts and RNA processing dynamics.[SEP]Definitions: RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed).", "label": "yes"}
{"id": "converted_3241", "sentence1": "Can Enlimomab improve stroke outcomes?", "sentence2": "Treatment with a murine anti-ICAM-1 antibody (enlimomab) has been investigated in patients with acute ischemic stroke in the Enlimomab Acute Stroke Trial (EAST). Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group., The two clinical trials of therapy aimed at limiting the inflammatory response in acute stroke that have been carried out to date, however, have not shown a benefit to such therapy. , en classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They included calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilazad and ebselen, enlimomab, GABA agonist clomethiazole, the sodium channel antagonist fosphenytoin, magnesium, glycine site antagonist GV150526 and piracetam. , BACKGROUND AND PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial. , Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study., ESULTS: At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., CONCLUSIONS: The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome., CONCLUSIONS\n\nThe authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome., There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., RESULTS\n\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004)., The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005)., However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial., There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., RESULTS\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004)., Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group., CONCLUSIONS\nDoses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days., PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial., These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial., These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.[SEP]Definitions: Doses defined as following: A quantity of an agent (such as substance or energy) administered, taken, or absorbed at one time.. ebselen defined as following: A organoselenium compound with anti-inflammatory, anti-oxidant and cytoprotective activity. Ebselen acts as a glutathione peroxidase mimetic and is thereby able to prevent cellular damage induced by reactive oxygen species (ROS). In addition, this agent inhibits the activity of a variety of enzymes including nitric oxide synthase (NOS), 5-lipoxygenase, cyclooxygenase, protein kinase C (PKC), NADPH oxidase and gastric H+/K+-ATPase. Furthermore, ebselen may be neuroprotective due to its ability to neutralize free radicals upon NMDA receptor activation thus, reducing lipoperoxidation mediated by glutamate-induced excitotoxicity.. CDP-choline defined as following: Donor of choline in biosynthesis of choline-containing phosphoglycerides.. ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue.. NMDA receptor defined as following: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). clomethiazole defined as following: A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate GAMMA-AMINOBUTYRIC ACID receptors response and it may also affect glycine receptors.. sodium channel defined as following: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.. fosphenytoin defined as following: A water-soluble phosphate ester prodrug of phenytoin, a hydantoin derivative with anticonvulsant activity. Fosphenytoin is hydrolyzed to phenytoin by phosphatases. Phenytoin exerts its effect mainly by promoting sodium efflux and stabilizes neuronal membranes in the motor cortex. This leads to a suppression of excessive neuronal firing and limits the spread of seizure activity.. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae.. piracetam defined as following: A compound suggested to be both a nootropic and a neuroprotective agent..", "label": "no"}
{"id": "converted_4223", "sentence1": "Has the companion diagnostic HercepTest received FDA approval?", "sentence2": "The FDA-Approved Breast Cancer HER2 Evaluation Kit (HercepTest; Dako) May Miss Some HER2-Positive Breast Cancers., HER2 fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) tests were performed on 52 cases using a US Food and Drug Administration (FDA)-approved kit (HercepTest, FDA kit) and a laboratory-developed test (LDT) with the HercepTest antibody and a Leica Bond automated stainer.[SEP]", "label": "yes"}
{"id": "converted_3226", "sentence1": "Is myc a tumour suppressor gene?", "sentence2": "oncogenic Myc, a master transcription factor that turns on anabolic metabolism to promote cell growth in many cancers. , he MYC oncogene, the proto-oncogene protein c-MYC, however, other genes such as the proto-oncogene c-Myc are promising targets for anticancer therapy[SEP]Definitions: MYC oncogene defined as following: A viral and cellular gene. A proto-oncogene, identified in several avian tumors, encoding a nuclear protein with a leucine zipper motif.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. proto-oncogene protein c-MYC defined as following: Basic helix-loop-helix transcription factors encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.. Myc defined as following: Myc proto-oncogene protein (439 aa, ~49 kDa) is encoded by the human MYC gene. This protein plays a role in the regulation of transcription and cell proliferation.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. tumour suppressor gene defined as following: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible..", "label": "no"}
{"id": "converted_2664", "sentence1": "Is recursive splicing more common in short introns?", "sentence2": "Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together, Cutting a Long Intron Short: Recursive Splicing and Its Implications., Furthermore, we uncover the potential to investigate the multi-step nature of splicing, assessing various types of recursive splicing events, Recursive splicing is a process in which large introns are removed in multiple steps by re-splicing at ratchet points--5' splice sites recreated after splicing., Together, these results indicate that recursive splicing is commonly used in Drosophila, occurs in humans, and provides insight into the mechanisms by which some large introns are removed., Recursive splicing in long vertebrate genes., Moreover, the RS-sites are found in some of the longest introns across vertebrates. , The peculiarities of large intron splicing in animals., These \"large introns\" must be spliced out of the pre-mRNA in a timely fashion, which involves bringing together distant 5' and 3' acceptor and donor splice sites., Using a computational analysis of the genomic sequences, we show that vertebrates lack the proper enrichment of RP-sites in their large introns, and, therefore, require some other method to aid splicing, Subdivision of large introns in Drosophila by recursive splicing at nonexonic elements., Recursive splice sites predicted with highly stringent criteria are found at much higher frequency than expected in the sense strands of introns>20 kb, but they are found only at the expected frequency on the antisense strands, and they are underrepresented within introns<10 kb., These transcripts arise by use of two alternative transcription sites and complex alternative splicing mechanisms and encode proteins with long or short N-terminal domains, complete or incomplete GGL domains, 7 distinct C-terminal domains and a common internal domain where the RGS domain is found., These patterns of enrichment and conservation indicate that recursive splice sites are advantageous in the context of long introns., Many genes with important roles in development and disease contain exceptionally long introns, but special mechanisms for their expression have not been investigated., However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing., The effect of splice site strength was context-dependent and much more significant for the 3' splice site of the longer alternative intron than for the 3' splice site of the shorter alternative intron and the common 5' splice sites; it was also more significant in the rat minigene than in the mouse minigene., Cutting a Long Intron Short: Recursive Splicing and Its Implications., Recursive splicing in long vertebrate genes.[SEP]Definitions: pre-mRNA defined as following: A primary RNA transcript synthesized from a DNA template in eukaryotic nuclei which is post-transcriptionally modified and spliced to produce a mature mRNA.. humans defined as following: Members of the species Homo sapiens.. domain defined as following: A taxonomic category above that of Kingdom.. transcripts defined as following: The initial RNA molecule produced by transcription.. RGS defined as following: A rare autosomal dominant syndrome linked to mutations in the PITX2 gene. It is characterized by abnormalities in the anterior chamber of the eye and underdevelopment of the teeth.. intron defined as following: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.. vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. introns defined as following: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes..", "label": "no"}
{"id": "converted_2423", "sentence1": "Is Solanezumab effective for Alzheimer's Disease?", "sentence2": "An analysis of publicly available data from the Phase II studies for bapineuzumab and solanezumab indicates that neither compound produced compelling evidence of drug-like behavior that would justify their progression into pivotal trials. , Notably, a recent study of solanezumab, an amyloid β monoclonal antibody, raises hope for the further therapeutic potential of immunotherapy, not only in Alzheimer's disease, but also for other neurodegenerative disorders, including Parkinson's disease. , For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer's drug solanezumab which failed to reach statistical significance. , Areas covered: This contradiction prompted us to review all study phases of Intravenous Immunoglobulin (IVIG), Bapineuzumab, Solanezumab, Avagacestat and Dimebolin to shed more light on these recent failures. , Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD., Secondary analyses of EXPEDITION studies suggested a smaller functional effect of solanezumab relative to cognition. An increasing effect of solanezumab over 18 months was shown for cognition and function., RESULTS: In the mild AD population, less cognitive and functional decline was observed with solanezumab (n = 659) versus placebo (n = 663), measured by Alzheimer's Disease Assessment Scale Cognitive subscale, Mini-Mental State Examination, and Alzheimer's Disease Cooperative Study-Activities of Daily Living functional scale Instrumental ADLs. , The promising results obtained with aducanumab and solanezumab against Alzheimer's disease (AD) strengthen the vaccine approach to prevent AD, despite of the many clinical setbacks. , CONCLUSIONS: Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability. , Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing.[SEP]Relations: Bapineuzumab has relations: drug_drug with Solanezumab, drug_drug with Solanezumab. Solanezumab has relations: drug_drug with Bapineuzumab, drug_drug with Bapineuzumab. Definitions: neurodegenerative disorders defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.. monoclonal antibodies defined as following: Antibodies produced by a single clone of cells.. amyloid defined as following: A family of apolipoproteins that are associated with high-density lipoprotein particles in the serum. These proteins may play a role in both the acute-phase of inflammation and in cholesterol transport.. Bapineuzumab defined as following: A humanized monoclonal antibody (IgG1) raised against amyloid beta peptides with Alzheimer disease treatment application. Bapineuzumab recognizes and binds the N-terminal amino acids 1-5 of the amyloid beta peptide, and may be used in a passive immunotherapy treatment.. Solanezumab defined as following: A humanized monoclonal antibody (IgG1) raised against amyloid beta peptides with Alzheimer disease treatment application. Solanezumab recognizes and binds the middle amino acid residues 16-24 of the amyloid beta peptide and may be used in a passive immunotherapy treatment.. Alzheimer's Disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. cognitive decline defined as following: Loss of previously present mental abilities, generally in adults. [HPO:probinson]. Parkinson's disease defined as following: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75). Intravenous Immunoglobulin defined as following: Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA.. humanized monoclonal antibody defined as following: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab..", "label": "no"}
{"id": "converted_3835", "sentence1": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "sentence2": "A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome., To investigate if specific exon 38 or 39 KMT2D missense variants (MVs) cause a condition distinct from Kabuki syndrome type 1 (KS1).METHODS: Multiple individuals, with MVs in exons 38 or 39 of KMT2D that encode a highly conserved region of 54 amino acids flanked by Val3527 and Lys3583, were identified and phenotyped. Functional tests were performed to study their pathogenicity and understand the disease mechanism.RESULTS: The consistent clinical features of the affected individuals, from seven unrelated families, included choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability. The frequency of clinical features, objective software-based facial analysis metrics, and genome-wide peripheral blood DNA methylation patterns in these patients were significantly different from that of KS1. Circular dichroism spectroscopy indicated that these MVs perturb KMT2D secondary structure through an increased disordered to ɑ-helical transition.CONCLUSION: KMT2D MVs located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from KS1. Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism.[SEP]Relations: Hearing impairment has relations: disease_phenotype_positive with Kabuki syndrome, disease_phenotype_positive with Kabuki syndrome. Kabuki syndrome has relations: disease_protein with KMT2D, disease_protein with KMT2D. Intellectual disability has relations: disease_phenotype_positive with Kabuki syndrome, disease_phenotype_positive with Kabuki syndrome. Definitions: athelia defined as following: Absence of one or both mammary glands.. KS1 defined as following: This gene is involved in cellular homeostasis and chemotaxis.. MVs defined as following: A SI derived unit of electric potential and electromotive force that is equal to one million volts.. hearing loss defined as following: Partial or complete loss of the ability to detect or understand sounds resulting from damage to the outer, middle, or inner ear structures. Causes include exposure to loud noise, ear infections, injuries to the ear, genetic, and congenital disorders.. KMT2D defined as following: Histone-lysine N-methyltransferase MLL2 (5262 aa, ~564 kDa) is a transcriptional regulatory protein that is encoded by the human MLL2 gene and has a role in epigenetic transcriptional activation.. thyroid abnormalities defined as following: Pathological processes involving the THYROID GLAND.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. choanal atresia defined as following: A congenital abnormality that is characterized by a blocked CHOANAE, the opening between the nose and the NASOPHARYNX. Blockage can be unilateral or bilateral; bony or membranous.. intellectual disability defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28). exon defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA..", "label": "no"}
{"id": "converted_1105", "sentence1": "Are thyroid hormone receptor alpha1 mutations implicated in thyroid hormone resistance syndrome?", "sentence2": "Mutations in human TRα1 mediate RTH with features of hypothyroidism in particular tissues (e.g. skeleton, gastrointestinal tract), but are not associated with a markedly dysregulated pituitary-thyroid axis., Clinical phenotype of a new type of thyroid hormone resistance caused by a mutation of the TRα1 receptor[SEP]Definitions: hypothyroidism defined as following: A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. TRα1 receptor defined as following: A protein located on the cell surface, or in the cytoplasm, that binds to a specific signaling factor, such as a hormone, antigen, or neurotransmitter, causing a conformational and functional change in the receptor molecule. The ligand-bound receptor then alters its interaction with target molecules, which leads to changes in cellular physiology through modification of the activity of one or more signal transduction pathways.. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. human defined as following: Members of the species Homo sapiens..", "label": "yes"}
{"id": "converted_1370", "sentence1": "Are nucleosomes positioned at DNA replication origins?", "sentence2": "yeast origins are characterized by an asymmetric pattern of positioned nucleosomes flanking the ACS. The origin sequences are sufficient to maintain a nucleosome-free origin; however, ORC is required for the precise positioning of nucleosomes flanking the origin., Here, we identify nucleosome occupancy as a likely candidate to set up ORI distribution, we demonstrate that open chromatin domains, characterized by nucleosome depletion, are preferentially permissive for replication, Nucleosome assembly of the template prevented DNA replication. Replication of chromosomes was severely inhibited at more than two-thirds of physiological nucleosome density[SEP]Definitions: ORC defined as following: A multisubunit complex that is located at the replication origins of a chromosome. [GOC:elh]. ORI defined as following: An Indo-Aryan language that is spoken mostly in eastern India.. chromosomes defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. nucleosomes defined as following: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4.. Nucleosome assembly defined as following: The aggregation, arrangement and bonding together of a nucleosome, the beadlike structural units of eukaryotic chromatin composed of histones and DNA. [GOC:mah].", "label": "no"}
{"id": "converted_34", "sentence1": "Do mutations of AKT1 occur in meningiomas?", "sentence2": "The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas., A mutation in PIK3CA or AKT1 was found in around 9 % of the cases., AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry., AKT1E17K mutations were exclusively seen in meningiomas and occurred in 65 of 958 of these tumors. A strong preponderance was seen in the variant of meningothelial meningioma WHO grade I of basal and spinal localization. In contrast, AKT1E17K mutations were rare in WHO grade II and absent in WHO grade III meningiomas. , We observed strong up-regulation of SFRP1 expression in all meningiomas with AKT1E17K mutation and in HEK293 cells after transfection with mutant AKT1E17K, but not in meningiomas and HEK293 cells lacking this mutation., SMO and AKT1 mutations occur in non-NF2 meningiomas., Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma., Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations., A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways., Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO., A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways., SMO and AKT1 mutations occur in non-NF2 meningiomas, The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas, A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways, Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO, Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations, Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma, A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. , A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. [SEP]Relations: meningothelial meningioma has relations: disease_protein with NF2, disease_protein with AKT1, disease_protein with NF2, disease_protein with AKT1. benign meningioma has relations: disease_protein with AKT1, disease_protein with NF2, disease_protein with AKT1, disease_protein with NF2. neurofibromatosis has relations: disease_protein with NF2, disease_protein with NF2. Definitions: PIK3CA defined as following: This gene is involved in apoptosis, cell growth and angiogenesis.. HEK293 cells defined as following: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.. meningiomas defined as following: A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7). TRAF7 defined as following: This gene is involved in both MAPK signaling and protein ubiquitination.. variant defined as following: An alteration or difference from a norm or standard.. KLF4 defined as following: Krueppel-like factor 4 (470 aa, ~50 kDa) is encoded by the human KLF4 gene. This protein regulates transcription.. AKT1 defined as following: RAC-alpha serine/threonine-protein kinase (480 aa, ~56 kDa) is encoded by the human AKT1 gene. This protein is involved in signal transduction, serine/threonine phosphorylation, apoptosis regulation and neurogenesis.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. meningothelial meningioma defined as following: A WHO grade I meningioma characterized by the presence of tumor cells that form lobules. The tumor cells are generally uniform. Whorls and psammoma bodies are usually not present.. SFRP1 defined as following: This gene is involved in signaling.. SMO defined as following: An Austronesian language spoken mainly in the Samoan islands.. meningioma defined as following: A grade I, slowly growing meningioma. Only a minority of tumors recur following complete resection.. NF2 defined as following: An autosomal dominant disorder characterized by a high incidence of bilateral acoustic neuromas as well as schwannomas (NEURILEMMOMA) of other cranial and peripheral nerves, and other benign intracranial tumors including meningiomas, ependymomas, spinal neurofibromas, and gliomas. The disease has been linked to mutations of the NF2 gene (GENES, NEUROFIBROMATOSIS 2) on chromosome 22 (22q12) and usually presents clinically in the first or second decade of life.. mutant defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. skull base defined as following: The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"}
{"id": "converted_705", "sentence1": "Is Bladder training an effective method to treat urge incontinence ?", "sentence2": "Mindfulness-based stress reduction appears to be a treatment worthy of further study, as in the short term, it is as effective as historical studies of drug treatment and bladder training in reducing urge incontinence and incontinence-related quality of life., All patients, irrespective of the results of cystometry were subsequently treated with oxybutynin 2.5 mg twice daily along with bladder training., Of the 29 patients with stable bladder and symptoms of OAB, 100% cure rate was achieved in 20 (68.9%) and 06 (20.6%) patients respectively. While in 3 patients in both groups, decrease of symptoms upto 75% after 6 months of treatment was observed., Both urodynamically proven unstable and stable bladder showed nearly equal improvement with treatment, There are 3 types of urine incontinence (urge-, stress-, and overflow-incontinence). Another standardization of urinary incontinence follows dysfunctions of the pelvic floor: detrusor muscle-dependent, due to sphincter spasm, prostate gland dependent. Urge incontinence with a dysfunction of the detrusor muscle is the most common type. Mixed types are frequent. Non-drug measures (e.g. pelvic muscle training, bladder training, toilet training are first choice treatments., Treatment of stress, urge and mixed incontinence can usually be commenced in primary care; pelvic floor exercises and bladder training are preferred. If bladder training is not effective for urge incontinence, anticholinergic drugs should be considered., Sixty patients (age 8 to 12 years) with urge incontinence or dysfunctional voiding were evaluated. After a no-treatment control period (average 6 months), patients underwent a 6-day bladder training course, Six months after training completion, 64.1% and 64.7% of the inpatient and outpatient groups with daytime wetting and 51.5% and 17.7% of the inpatient and outpatient groups with nighttime wetting were cured or had improved, Of the inpatient group with urge incontinence, the functional bladder capacity increased by 15%., To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder., CONCLUSIONS: Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen., Bladder training is a modification of bladder drill that is conducted more gradually on an outpatient basis and has resulted in significant reduction of incontinence in older, community-dwelling women., OBJECTIVE: To evaluate the long-term effect of treatment of female incontinence by the general practitioner (pelvic floor exercises, and bladder training) in female urinary incontinence., Stress incontinence and urge incontinence were treated by means of pelvic floor exercises and bladder training respectively, while a mixed incontinence was treated by bladder training followed by pelvic floor exercises. T, The treatment consisted of training of pelvic muscles in stress incontinence and bladder training in urge incontinence, RESULTS: After 3 months the mean frequency of urine loss per week diminished from 21 to 8, and after 12 months to 6 times., Some elders suffering from urge incontinence prefer pelvic muscle exercises to bladder training as the behavioral intervention of choice, for eight out of nine women their continence had improved, both subjectively and objectively., Bladder training is a simple, safe, and effective treatment in the management of mild to moderate forms of urinary incontinence in outpatient populations. It can be used as a first-line treatment or in combination with such other interventions as pelvic muscle exercises, bladder pressure biofeedback, electrical stimulation, and drug therapy, Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence., After 3 months about 60% of the patients were either dry or only mildly incontinent, terodiline group shows this drug to be a valuable adjunct to a bladder regimen in children with urge incontinence, Basing on our experience with 39 patients with severe urge incontinence (in one-quarter of the cases pure urge incontinence, in one-half of the cases mixed incontinence and in a further quarter of the cases neurogenic bladder disorders) a supervised programme (mictiogram) and a well-tried therapy (especially in the Anglo-Saxon countries) consisting of the triad hospitalisation/bladder training/medication therapy are presented. After an average hospitalisation period of 14 days, we were able to achieve a symptom-free state in 94% of the patients., Anamnestic and urodynamical results are evaluated before and after bladder retraining drill (BRD) in women suffering from urge incontinence., We could state that the BRD is a good possibility to realize multistep-therapy of female incontinence., Twenty consecutive female patients with urge incontinence and stable detrusor function on provocative rapid fill CO2-cystometry were treated as out-patients with a bladder training programme and with terodiline/placebo in a double-blind cross-over design., In conclusion, female patients with idiopathic urge incontinence and stable detrusor function did respond to treatment as do female patients with urge incontinence and proven instability., The results of in-patient bladder training in 65 women with frequency, urgency and urge incontinence are reported. There was a good initial response in 88%. By 6 months the response rate had fallen to 38%., Patients with sensory urgency appeared to do better than those with detrusor instability and it is suggested that bladder training may be indicated as primary treatment in sensory urgency., Bladder training and/or biofeedback techniques were used to treat 75 patients with frequency, urgency, nocturia and urge incontinence. Significant improvement or cure was obtained in 70 per cent of enuretic children, and 66 per cent of men and 74 per cent of women with unstable detrusor function.[SEP]Definitions: pelvic muscle defined as following: Muscle (organ) which is a part of the pelvis. Examples: levator ani,. urine incontinence defined as following: Involuntary loss of URINE, such as leaking of urine. It is a symptom of various underlying pathological processes. Major types of incontinence include URINARY URGE INCONTINENCE and URINARY STRESS INCONTINENCE.. drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. bladder defined as following: A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION.. Tolterodine defined as following: A benzhydryl compound and a muscarinic receptor antagonist possessing both antimuscarinic and antispasmodic properties. Both tolterodine and its active metabolite, 5-hydroxymethyltolterodine, competitively blocks muscarinic receptors, thereby inhibiting acetylcholine binding. This antagonistic action results in an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure, indicating an antimuscarinic action on the lower urinary tract. The 5-hydroxymethyl metabolite appears to contribute significantly to the therapeutic effects.. nocturia defined as following: Frequent URINATION at night that interrupts sleep. It is often associated with outflow obstruction, DIABETES MELLITUS, or bladder inflammation (CYSTITIS).. modification defined as following: Respond with exceptions, completions and modifications or revisions done before completion
. Stress incontinence defined as following: Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.. incontinence defined as following: Involuntary passage of stool or urine from the body.. pelvic floor defined as following: Soft tissue formed mainly by the pelvic diaphragm, which is composed of the two levator ani and two coccygeus muscles. The pelvic diaphragm lies just below the pelvic aperture (outlet) and separates the pelvic cavity from the PERINEUM. It extends between the PUBIC BONE anteriorly and the COCCYX posteriorly..", "label": "yes"}
{"id": "converted_3639", "sentence1": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "sentence2": "\"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle, Although traditionally known as \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes., Although traditionally known as \" white forelock , \" poliosis circumscripta , defined as a localized patch of white hair in a group of hair follicles , can involve any hairy area on the body including the scalp , eyebrows , and eyelashes, Although traditionally known as \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes.[SEP]Definitions: eyelashes defined as following: The hairs which project from the edges of the EYELIDS.. eyebrows defined as following: Curved rows of HAIR located on the upper edges of the eye sockets.. scalp defined as following: The outer covering of the calvaria. It is composed of several layers: SKIN; subcutaneous connective tissue; the occipitofrontal muscle which includes the tendinous galea aponeurotica; loose connective tissue; and the pericranium (the PERIOSTEUM of the SKULL)..", "label": "yes"}
{"id": "converted_2407", "sentence1": "Has the proteome of mice hippocampus been analysed?", "sentence2": "We employed a discovery-based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)-exposed C57Bl/6J mice to gain insight into alcohol-induced changes in GluN2B signaling complexes. , We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A+/-mice, a model of the 22q11.2 deletion syndrome. , Molecular alterations in the frontal cortex and hippocampus ofTsc1+/-and control mice, with or without rapamycin treatment, were investigated. A quantitative mass spectrometry-based shotgun proteomic approach (LC-MSE) was employed as an unbiased method to detect changes in protein levels., This dataset reports on the analysis of mouse hippocampus by LC-MS/MS, from mice fed a diet that was either deficient in n-3 FA (n-3 Def) or sufficient in n-3 FA (n-3 Adq). , Using isobaric tags for relative and absolute quantitation (iTRAQ) and proteomic methods, here we identified learning-induced changes in the hippocampal proteome of non-transgenic (NonTg) and 3 × Tg-AD mice, a widely used animal model of AD. [SEP]Relations: DiGeorge syndrome has relations: disease_disease with 22q11.2 deletion syndrome, disease_disease with 22q11.2 deletion syndrome. Definitions: prefrontal cortex defined as following: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the MEDIODORSAL NUCLEUS OF THE THALAMUS. The prefrontal cortex receives afferent fibers from numerous structures of the DIENCEPHALON; MESENCEPHALON; and LIMBIC SYSTEM as well as cortical afferents of visual, auditory, and somatic origin.. hippocampal defined as following: A curved gray matter structure of the temporal lobe lying on the floor of the lateral ventricle of the brain.. frontal cortex defined as following: The grey matter, or outermost layer of the frontal lobe.. 22q11.2 deletion syndrome defined as following: Congenital syndrome characterized by a wide spectrum of characteristics including the absence of the THYMUS and PARATHYROID GLANDS resulting in T-cell immunodeficiency, HYPOCALCEMIA, defects in the outflow tract of the heart, and craniofacial anomalies.. rapamycin defined as following: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties..", "label": "yes"}
{"id": "converted_2782", "sentence1": "Can breastfeeding confer protection from type I diabetes?", "sentence2": "In the neonate and infant, among other benefits, lactation confers protection from future both type 1 and type 2 diabetes.[SEP]", "label": "yes"}
{"id": "converted_3712", "sentence1": "Are stem cell transplants used to treat acute kidney injury?", "sentence2": "Animal studies have shown that mesenchymal stromal cell (MSC) infusions improve acute kidney injury (AKI) outcomes when administered early after ischemic/reperfusion injury or within 24 hours after cisplatin administration., Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients., Risk assessment for acute kidney injury after allogeneic hematopoietic stem cell transplantation based on Acute Kidney Injury Network criteria.[SEP]Definitions: Hematopoietic Stem Cell defined as following: Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood.. MSC defined as following: A naturally occurring organoselenium compound found in many plants, including garlic, onions, and broccoli, with potential antioxidant and chemopreventive activities. Se-Methyl-seleno-L-cysteine (MSC) is an amino acid analogue of cysteine in which a methylselenium moiety replaces the sulphur atom of cysteine. This agent acts as an antioxidant when incorporated into glutathione peroxidase and has been shown to exhibit potent chemopreventive activity in animal models.. cisplatin defined as following: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.. mesenchymal stromal cell defined as following: Non-hematopoietic cells that support HEMATOPOIETIC STEM CELLS in bone marrow. They have also been isolated from other organs and tissues such as adipose tissue, UMBILICAL CORD BLOOD, and WHARTON JELLY and include a subpopulation of multipotent stem cells.. acute kidney injury defined as following: Sudden and sustained deterioration of the kidney function characterized by decreased glomerular filtration rate, increased serum creatinine or oliguria..", "label": "yes"}
{"id": "converted_3471", "sentence1": "Are the members of the KRAB-ZNF gene family promoting gene repression?", "sentence2": " The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation., Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming. Using several expression datasets, we identified KRAB-ZNFs (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency., Further analyses of our data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes., The stem cell zinc finger 1 (SZF1)/ZNF589 protein belongs to the large family of Krüppel-associated box domain-zinc finger (KRAB-ZNF) transcription factors, which are present only in higher vertebrates and epigenetically repress transcription by recruiting chromatin-modifying complexes to the promoter regions of their respective target genes, Because KAP1 is recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism involving KAP1., Interestingly, although most KAP1 binding sites were within core promoter regions, the binding sites near ZNF genes were greatly enriched within transcribed regions of the target gene[SEP]Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. KAP1 defined as following: Human TRIM28 wild-type allele is located in the vicinity of 19q13.43 and is approximately 7 kb in length. This allele, which encodes transcription intermediary factor 1-beta protein, plays a role in protein modification, chromatin remodeling, inhibition of herpesvirus 8-mediated lysis and transcriptional regulation. Mutation of the gene may be associated with familial Wilms tumor.. binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. H3K9me3 defined as following: A post-translationally modified form of histone H3 where the lysine residue at position 9 is trimethylated. This modification is associated with heterochromatin formation and plays a role in embryonic stem cell lineage commitment and maintenance of lineage fidelity.. promoter regions defined as following: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. stem cell defined as following: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells..", "label": "yes"}
{"id": "converted_4351", "sentence1": "Are circRNAs susceptible to degradation by RNase R?", "sentence2": "Currently, an increasing body of evidence has demonstrated that 1) majority of circRNAs are evolutionarily conserved across species, stable, and resistant to RNase R degradation, , Circular RNA (circRNA) has a closed-loop structure, and its 3' and 5' ends are directly covalently connected by reverse splicing, which is more stable than linear RNA., CircRNAs are a kind of closed circular RNA molecule widely existing in transcriptomes. Due to lack of free ends, they are not easily cleaved by RNase R, thus avoiding degradation. , Circular RNAs (circRNAs) are a class of newly-identified non-coding RNA that lack 5' (cap) and 3' (polyadenylation) ends and are linked by a covalent bond to form a closed loop structure. In comparison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3' terminals, Circular RNAs (circRNAs) own unique capabilities to communicate with nucleic acids and ribonucleoproteins and are emerging as indispensable compositions of the regulatory messages encoded in the genome. Due to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs. , RNase R is a strong 3' to 5' exoribonuclease, which efficiently degrades linear RNAs, such as mRNAs and rRNAs; therefore, the circular parts of lariat RNAs and the circRNAs can be segregated from eukaryotic total RNAs by their RNase R resistance., Lariat RNAs and circRNAs are both RNase R resistant RNAs., In comparison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3' terminals., Due to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs., Because circRNAs are not easily degraded by exonuclease RNase R, they can exist more stably in body fluids than linear RNAs., Therefore, it is essential to perform the RT-qPCR validation step only after linear RNAs have been degraded using an exonuclease such as ribonuclease R (RNase R)., is a strong 3' to 5' exoribonuclease, which efficiently degrades linear RNAs, such as mRNAs and rRNAs; therefore, the circular parts of lariat RNAs and the circRNAs can be segregated from eukaryotic total RNAs by their RNase R resistance. Thus, RNase, sion of circRNAs is prevalent in tissues and body fluids,and their abnormal expression is related to tumor progression.circRNAs are stable even under the treatment of RNase R because of their circular conformation.As circRNAs, e to lack of 3' termini, circRNAs are more resistant to degradation by exonuclease RNase R and possess greater stability than linear RNAs. Mo, e circRNAs are not easily degraded by exonuclease RNase R, they can exist more stably in body fluids than linear RNAs. Based, is stable, difficult to cleave and resistant to RNA exonuclease or RNase R degradation. circRN, the unique structures, circRNAs are resistant to exonuclease RNase R and maintain stability more easily than linear RNAs. Rece, rison to linear RNAs, circRNAs are more resistant to exonuclease RNase R-mediated degradation with a much stronger stability due to the absence of 3' terminals. Conseque, RT-PCR analysis showed that sheep circRNAs are resistant to RNase R digestion and are expressed in prenatal and postnatal pituitary glands. GO and , Currently, an increasing body of evidence has demonstrated that 1) majority of circRNAs are evolutionarily conserved across species, stable, and resistant to RNase R degradation, and often exhibit cell-specific, and tissue-specific/developmental-stage-specific expression and can be largely independent of the expression levels of the linear host gene-encoded linear RNAs; 2) the biogenesis of circRNAs via back-splicing is different from the canonical splicing of linear RNAs; 3) circRNA biogenesis is regulated by specific cis-acting elements and trans-acting factors; 4) circRNAs regulate biological and pathological processes by sponging miRNAs, binding to RNA-binding protein (RBP), regulators of splicing and transcription, modifiers of parental gene expression, and regulators of protein translation or being translated into peptides in various diseases; 5) circRNAs have been identified for their enrichment and stability in exosomes and detected in body fluids such as human blood, saliva, and cerebrospinal fluids, suggesting that these exo-circRNAs have potential applications as disease biomarkers and novel therapeutic targets; 6) several circRNAs are regulated by oxidative stress and mediate reactive oxygen species (ROS) production as well as promote ROS-induced cellular death, cell apoptosis, and inflammation; 7) circRNAs have also emerged as important regulators in atherosclerotic cardiovascular disease, metabolic disease, and cancers; 8) the potential mechanisms of several circRNAs have been described in diseases, hinting at their potential applications as novel therapeutic targets., To prove their circularity as well as biochemically enrich these transcripts, it has become standard in the field to use the 3'-5' exonuclease RNase R. Here, we demonstrate that standard protocols involving RNase R can fail to digest >20% of all highly expressed linear RNAs, but these shortcomings can largely be overcome., We propose that such an R-loop dependent ciRNA degradation likely represents a mechanism that on one hand limits ciRNA accumulation by recruiting RNase H1 and on the other hand resolves R-loops for transcriptional elongation at some GC-rich ciRNA-producing loci., As circular RNAs (circRNAs) are resistant to degradation by exonucleases, their abundance relative to linear RNAs can be used as a surrogate marker for mRNA stability in the absence of transcription., The synthetic circular sponge was resistant to digestion with RNase R. Luciferase assays and functional experiments showed that the circular multi-miR sponge was more stable than its linear counterpart., RNAs with highly structured 3' ends, including snRNAs and histone mRNAs, are naturally resistant to RNase R, but can be efficiently degraded once a poly(A) tail has been added to their ends., Thousands of eukaryotic protein-coding genes generate circular RNAs that have covalently linked ends and are resistant to degradation by exonucleases.[SEP]Definitions: inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. CircRNAs defined as following: RNA molecules in which the 3' and 5' ends are covalently joined to form a closed continuous loop. They are resistant to digestion by EXORIBONUCLEASES.. RNase defined as following: An enzyme that catalyzes the endonucleolytic cleavage of pancreatic ribonucleic acids to 3'-phosphomono- and oligonucleotides ending in cytidylic or uridylic acids with 2',3'-cyclic phosphate intermediates. EC 3.1.27.5.. exosomes defined as following: A type of extracellular vesicle, containing RNA and proteins, that is secreted into the extracellular space by EXOCYTOSIS when MULTIVESICULAR BODIES fuse with the PLASMA MEMBRANE.. RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. body fluids defined as following: Liquid components of living organisms.. reactive oxygen species defined as following: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.. transcripts defined as following: The initial RNA molecule produced by transcription.. cerebrospinal fluids defined as following: A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES.. R-loops defined as following: An RNA-DNA hybrid structure formed when newly transcribed RNA remains bound to its DNA template. Stability of R-loops may play a role in GENETIC INSTABILITY.. pituitary glands defined as following: A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM.. trans-acting factors defined as following: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.. metabolic disease defined as following: Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed). miRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. nucleic acids defined as following: High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages.. peptides defined as following: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.. Mo defined as following: A metallic element with the atomic symbol Mo, atomic number 42, and atomic weight 95.95. It is an essential trace element, being a component of the enzymes xanthine oxidase, aldehyde oxidase, and nitrate reductase.. genome defined as following: Anatomical set of genes in all the chromosomes.. human defined as following: Members of the species Homo sapiens.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. RNA-binding protein defined as following: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.. circRNAs defined as following: RNA molecules in which the 3' and 5' ends are covalently joined to form a closed continuous loop. They are resistant to digestion by EXORIBONUCLEASES..", "label": "no"}
{"id": "converted_3380", "sentence1": "Does natalizumab improve disease course of secondary progressive multiple sclerosis?", "sentence2": "INTERPRETATION: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component., In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. , INTERPRETATION\n\nNatalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component., Natalizumab did not achieve a statistically significant primary composite disability outcome in a trial of 887 patients with secondary progressive MS , but it did demonstrate a benefit on a prespecified component of the 9-Hole Peg Test . , INTERPRETATION\nNatalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component., In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS., Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component.[SEP]Definitions: multiple sclerosis defined as following: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903). natalizumab defined as following: A humanized recombinant IgG4 monoclonal antibody directed against the alpha4 subunit of the integrins alpha4beta1and alpha4beta7 with immunomodulating, anti-inflammatory, and potential antineoplastic activities. Natalizumab binds to the alpha4-subunit of alpha4beta1 and alpha4beta7 integrins expressed on the surface of all leukocytes except neutrophils, inhibiting the alpha4-mediated adhesion of leukocytes to counter-receptor(s) such as vascular cell adhesion molecule-1 (VCAM-1); natalizumab-mediated disruption of VCAM-1 binding by these integrins may prevent the transmigration of leukocytes across the endothelium into inflamed parenchymal tissue. Integrins are cellular adhesion molecules (CAMs) that are upregulated in various types of cancer and some autoimmune diseases; alpha4beta1 integrin (VLA4) has been implicated in the survival of myeloma cells, possibly by mediating their adhesion to stromal cells..", "label": "no"}
{"id": "converted_2626", "sentence1": "Can nanoparticles be used for afterglow imaging?", "sentence2": "Ultralong Phosphorescence of Water-Soluble Organic Nanoparticles for In Vivo Afterglow Imaging, Afterglow or persistent luminescence eliminates the need for light excitation and thus circumvents the issue of autofluorescence, holding promise for molecular imaging. However, current persistent luminescence agents are rare and limited to inorganic nanoparticles. This study reports the design principle, synthesis, and proof-of-concept application of organic semiconducting nanoparticles (OSNs) with ultralong phosphorescence for in vivo afterglow imaging. , This study not only introduces the first category of water-soluble ultralong phosphorescence organic nanoparticles but also reveals a universal design principle to prolong the lifetime of phosphorescent molecules to the level that can be effective for molecular imaging.[SEP]Definitions: inorganic defined as following: Relating or belonging to the class of compounds not having a carbon basis.. nanoparticles defined as following: Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging..", "label": "yes"}
{"id": "converted_3440", "sentence1": "Does teplizumab hold promise for diabetes prevention?", "sentence2": "Anti-CD3 teplizumab and anti-CD3 otelixizumab have been shown to provide C-peptide preservation. , Underway are secondary prevention studies with teplizumab and with abatacept., INTERPRETATION: Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in β-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children., Teplizumab therapy for type 1 diabetes., Teplizumab for treatment of type 1 diabetes mellitus., TAKE HOME MESSAGE\n\nIn Phase I/II randomized control trials, in patients with new onset T1D, teplizumab slowed the rate of loss of beta-cell function over 2 years of follow-up., Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial., INTERPRETATION\n\nFindings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in β-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children., Treatment of new onset type 1 diabetes with teplizumab: successes and pitfalls in development., AREAS COVERED\n\nIn this review, we discuss the recent update on clinical data obtained from trials of teplizumab in type 1 diabetes, the drug's postulated mechanism of action and the identification of responders to therapy., CONCLUSIONS Teplizumab is an anti-CD3 human monoclonal antibody with promising activity in treatment of patients with T1DM., The results from the TN-10 teplizumab prevention trial show that the diagnosis of type 1 diabetes can be delayed by treatment with a FcR non-binding monoclonal antibody to CD3 in people at high risk for disease, INTERPRETATION\nFindings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in β-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children., Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders., Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial., The results from the TN-10 teplizumab prevention trial show that the diagnosis of type 1 diabetes can be delayed by treatment with a FcR non-binding monoclonal antibody to CD3 in people at high risk for disease., Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in β-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children., Despite decades of research and clinical trials, no treatment exists yet to prevent or cure T1D. A recent prevention trial using the anti-CD3 antibody teplizumab in individuals at a high risk of developing T1D has provided the first piece of evidence that a safe and transient intervention may be able to delay disease., In this review, we discuss the recent update on clinical data obtained from trials of teplizumab in type 1 diabetes, the drug's postulated mechanism of action and the identification of responders to therapy., Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis.[SEP]Relations: Otelixizumab has relations: drug_drug with Teplizumab, drug_drug with Teplizumab. Muromonab has relations: drug_drug with Teplizumab, drug_drug with Teplizumab. Definitions: C-peptide defined as following: C peptide (31 aa, ~3 kDa) is encoded by the human INS gene. This protein is involved in both signal transduction and the modulation of blood flow.. insulin defined as following: A synthetic or animal-derived form of insulin used in the treatment of diabetes mellitus. Therapeutic insulin is formulated to be short-, intermediate- and long-acting in order to individualize an insulin regimen according to individual differences in glucose and insulin metabolism. Therapeutic insulin may be derived from porcine, bovine or recombinant sources. Endogenous human insulin, a pancreatic hormone composed of two polypeptide chains, is important for the normal metabolism of carbohydrates, proteins and fats and has anabolic effects on many types of tissues.. anti-CD3 antibody defined as following: Any antibody that recognizes the CD3 protein complex.. human defined as following: Members of the species Homo sapiens.. abatacept defined as following: A soluble fusion protein consisting of the extracellular domain of human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1) with immunosuppressive activity. Abatacept binds CD80 and CD86 on antigen presenting cells (APCs), blocking interaction with CD28 on T lymphocytes, which initiates a co-stimulatory signal required for full activation of T lymphocytes.. T1D defined as following: A chronic condition characterized by minimal or absent production of insulin by the pancreas.. FcR defined as following: Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.. CD3 defined as following: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. anti-CD3 defined as following: Anti-CD3 monoclonal antibody that exerts immunosuppressive effects by inducing peripheral T-cell depletion and modulation of the T-cell receptor complex (CD3/Ti).. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "yes"}
{"id": "converted_1507", "sentence1": "Do thyroid hormone receptors change after brain injury?", "sentence2": "For example, the T3 receptor alpha was predominantly expressed in stroke-tissue, indicating that regeneration of nerves in stroke tissue may be facilitated by increased T3 receptor alpha expression., TRα expression was also increased in human infants with IVH. , Thus, in infants with IVH the combined elevation in deiodinase-3 and reduction in deiodinase-2 decreases TH signaling that can be worsened by an increase in unliganded TRα. , A rapid increase of the total number of binding sites for T3 appeared within 30 min of ischemia and reached over 40% by 3 h. During the same 3-h period, the relative binding affinity was reduced by 25%. Upon recirculation after 30 min or 3 h of ischemia, a rapid reversal of measured T3 binding sites occurred, which progressed to 20-30% below the control value by the recirculation period of 3 h. [SEP]Definitions: binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. ischemia defined as following: A surgical procedure during which the blood supply to an organ or tissue is interrupted and then later reestablished.. human defined as following: Members of the species Homo sapiens.. brain injury defined as following: Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs..", "label": "yes"}
{"id": "converted_3486", "sentence1": "Are there lncRNAs that control the extent of neuronal outgrowth?", "sentence2": "Regulation of Neuroregeneration by Long Noncoding RNAs., Here, we profiled gene expression following sciatic nerve crush in mice and identified long noncoding RNAs (lncRNAs) that act in the regenerating neurons and which are typically not expressed in other contexts. We show that two of these lncRNAs regulate the extent of neuronal outgrowth. We then focus on one of these, Silc1, and show that it regulates neuroregeneration in cultured cells and in vivo, through cis-acting activation of the transcription factor Sox11.[SEP]Definitions: cultured cells defined as following: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. Sox11 defined as following: Transcription factor SOX-11 (441 aa, ~47 kDa) is encoded by the human SOX11 gene. This protein is involved in transcriptional repression.. neuroregeneration defined as following: The regrowth of neural tissue following its loss or destruction. [Wikipedia:Neuroregeneration].", "label": "yes"}
{"id": "converted_3768", "sentence1": "Is tocilizumab a tumor necrosis factor inhibitor?", "sentence2": "For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered.[SEP]Definitions: rituximab defined as following: A murine-derived monoclonal antibody and ANTINEOPLASTIC AGENT that binds specifically to the CD20 ANTIGEN and is used in the treatment of LEUKEMIA; LYMPHOMA and RHEUMATOID ARTHRITIS.. tocilizumab defined as following: A recombinant, humanized IgG1 monoclonal antibody directed against the interleukin-6 receptor (IL-6R) with immunosuppressant activity. Tocilizumab targets and binds to both the soluble form of IL-6R (sIL-6R) and the membrane-bound form (mIL-6R), thereby blocking the binding of IL-6 to its receptor. This prevents IL-6-mediated signaling. IL-6, a pro-inflammatory cytokine that plays an important role in the regulation of the immune response, is overproduced in autoimmune disorders, certain types of cancers and possibly various other inflammatory conditions.. tumor necrosis factor inhibitors defined as following: Compounds or agents that bind to and inhibit the synthesis or activity of TUMOR NECROSIS FACTOR-alpha. Such agents are used to treat inflammatory bowel diseases and other inflammatory diseases.. abatacept defined as following: A soluble fusion protein consisting of the extracellular domain of human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1) with immunosuppressive activity. Abatacept binds CD80 and CD86 on antigen presenting cells (APCs), blocking interaction with CD28 on T lymphocytes, which initiates a co-stimulatory signal required for full activation of T lymphocytes.. tumor necrosis factor inhibitor defined as following: Compounds or agents that bind to and inhibit the synthesis or activity of TUMOR NECROSIS FACTOR-alpha. Such agents are used to treat inflammatory bowel diseases and other inflammatory diseases..", "label": "no"}
{"id": "converted_347", "sentence1": "Could the Menzerath-Altmann law be proved mathematically trivial in genomes?", "sentence2": "Here we review the statistical foundations of that test and consider three non-parametric tests based upon different correlation metrics and one parametric test to evaluate if Z ∼ 1/X in genomes. The most powerful test is a new non-parametric one based upon the correlation ratio, which is able to reject Z ∼ 1/X in nine out of 11 taxonomic groups and detect a borderline group. Rather than a fact, Z ∼ 1/X is a baseline that real genomes do not meet. The view of Menzerath-Altmann law as inevitable is seriously flawed., The view of Menzerath-Altmann law as inevitable is seriously flawed., The view of Menzerath-Altmann law as inevitable is seriously flawed., The view of Menzerath-Altmann law as inevitable is seriously flawed.[SEP]Definitions: genomes defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA..", "label": "yes"}
{"id": "converted_2533", "sentence1": "Are paralog genes co-regulated?", "sentence2": "Co-regulation of paralog genes in the three-dimensional chromatin architecture., Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters. These looping interactions can be measured by genome-wide chromatin conformation capture (Hi-C) experiments, which revealed self-interacting regions called topologically associating domains (TADs). We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs. To test this hypothesis, we integrated paralogy annotations with human gene expression data in diverse tissues, genome-wide enhancer-promoter associations and Hi-C experiments in human, mouse and dog genomes. We show that paralog gene pairs are enriched for co-localization in the same TAD, share more often common enhancer elements than expected and have increased contact frequencies over large genomic distances. Combined, our results indicate that paralogs share common regulatory mechanisms and cluster not only in the linear genome but also in the three-dimensional chromatin architecture. This enables concerted expression of paralogs over diverse cell-types and indicate evolutionary constraints in functional genome organization., Paralog genes arise from gene duplication events during evolution, which often lead to similar proteins that cooperate in common pathways and in protein complexes. Consequently, paralogs show correlation in gene expression, We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs., Analysis of the Drosophila melanogaster testes transcriptome reveals coordinate regulation of paralogous genes., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs.
, Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear., Co-regulation of paralog genes in the three-dimensional chromatin architecture., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs.., We show that paralog gene pairs are enriched for co-localization in the same TAD, share more often common enhancer elements than expected and have increased contact frequencies over large genomic distances. , MiRNA genes are often subject to co-evolutionary changes together with their target transcripts, which may be reflected by differences between paralog mouse and primate miRNA/mRNA pairs., We characterize the collapse over time through the distribution of runs of reduced paralog pairs in duplicated segments., In addition, we identified 81 co-regulated regions on the human genome (RIDGEs) by using expression data from all cancers. Some RIDGEs (28%) consist of paralog genes while another subset (30%) are specifically dysregulated in tumors but not in normal tissues., We conclude that the similarity of hoxb3a/Hoxa3 regulatory mechanisms reflect the shared descent of both genes from a single ancestral paralog group 3 gene., Conserved co-regulation and promoter sharing of hoxb3a and hoxb4a in zebrafish., By analyzing paralogs of testis-biased genes, we identified \"co-regulated\" paralogous pairs in which both genes are testis biased, \"anti-regulated\" pairs in which one paralog is testis biased and the other downregulated in testes, and \"neutral\" pairs in which one paralog is testis biased and the other constitutively expressed.[SEP]Definitions: dog defined as following: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065). genome defined as following: Anatomical set of genes in all the chromosomes.. zebrafish defined as following: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. paralog defined as following: A gene related to a similar gene by duplication within a genome.. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. enhancer elements defined as following: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. TADs defined as following: Tietz syndrome is a genetic hypopigmentation and deafness syndrome characterized by congenital profound bilateral sensorineural hearing loss and generalized albino-like hypopigmentation of skin, eyes and hair.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. testis defined as following: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.. testes defined as following: The posterior pair of the quadrigeminal bodies which contain centers for auditory function.. human defined as following: Members of the species Homo sapiens.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others..", "label": "yes"}
{"id": "converted_3788", "sentence1": "Is Semagacestat effective for Alzheimer's Disease?", "sentence2": "However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects. , BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD)., CONCLUSION: In participants with mild to moderate AD, high dose semagacestat treatment was associated with greater severity and faster worsening of NPS in a pattern resembling an agitated depression. , INTRODUCTION: The negative efficacy study examining the γ-secretase inhibitor semagacestat in mild to moderate Alzheimer's disease (AD) included a number of biomarkers of the disease as well as safety outcomes., A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, demonstrated that global inhibition of all γ-secretases causes serious toxicity. , ESULTS: Semagacestat treatment was associated with increased reporting of suspected Notch-related adverse events (gastrointestinal, infection, and skin cancer related). Other relevant safety findings associated with semagacestat treatment included cognitive and functional worsening, skin-related TEAEs, renal and hepatic changes, increased QT interval, and weight loss. , CONCLUSIONS: As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability., RESULTS: The trial was terminated before completion on the basis of a recommendation by the data and safety monitoring board., The ADAS-cog scores worsened in all three groups (mean change, 6.4 points in the placebo group, 7.5 points in the group receiving 100 mg of the study drug, and 7.8 points in the group receiving 140 mg; P=0.15 and P=0.07, respectively, for the comparison with placebo). The ADCS-ADL scores also worsened in all groups (mean change at week 76, -9.0 points in the placebo group, -10.5 points in the 100-mg group, and -12.6 points in the 140-mg group; P=0.14 and P<0.001, respectively, for the comparison with placebo). Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P<0.001 for all comparisons with placebo). , Recently disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo., The recent failure of semagacestat in two large Phase III studies questions the value of γ-secretase inhibitors in treating Alzheimer's disease., ntly disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo. Since, ts from Phase III studies showed that semagacestat failed to slow disease progression, and it was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. Furthermore, sem, rge Phase III clinical trials of semagacestat in mild-to-moderate AD patients were prematurely interrupted because of the observation of a detrimental cognitive and functional effect of the drug. These detrimental ef, BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's d, However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects., However, the preliminary equivocal cognitive results obtained with bapineuzumab as well as the detrimental cognitive effects observed with semagacestat, a potent γ-secretase inhibitor, raise the possibility that targeting Aβ may not be clinically efficacious in AD.[SEP]Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. renal defined as following: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.. NPS defined as following: A syndrome of multiple abnormalities characterized by the absence or hypoplasia of the PATELLA and congenital nail dystrophy. It is a genetically determined autosomal dominant trait.. skin cancer defined as following: A primary or metastatic malignant neoplasm involving the skin. Primary malignant skin neoplasms most often are carcinomas (either basal cell or squamous cell carcinomas) or melanomas. Metastatic malignant neoplasms to the skin include carcinomas and lymphomas.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. bapineuzumab defined as following: A humanized monoclonal antibody (IgG1) raised against amyloid beta peptides with Alzheimer disease treatment application. Bapineuzumab recognizes and binds the N-terminal amino acids 1-5 of the amyloid beta peptide, and may be used in a passive immunotherapy treatment.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. cognitive deficits defined as following: Disorders characterized by disturbances in mental processes related to learning, thinking, reasoning, and judgment.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. weight loss defined as following: The measured decrease in body weight over a specified period of time..", "label": "no"}
{"id": "converted_4514", "sentence1": "Do angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the likelihood of severe COVID-19?", "sentence2": "These findings suggest that the use of ACE-I and ARB is not associated with adverse outcomes and may be associated with improved outcomes in COVID-19, which is immediately relevant to care of the many patients on these medications., There are theoretical concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could increase the risk of severe Covid-19., ACEIs and ARBs were associated with a slight reduction in Covid-19 hospitalization risk compared with treatment with other first-line antihypertensives (OR for ACEIs 0.95, 95% CI 0.92-0.98; OR for ARBs 0.94, 95% CI 0.90-0.97)., There were no meaningful differences in risk for ACEIs compared with ARBs., ACEIs and ARBs were not associated with an increased risk of Covid-19 hospitalization or with hospitalization involving ICU admission, invasive mechanical ventilation, or death., In patients with HTN and COVID-19, neither ACEi nor ARBs were independently associated with mortality., Our data confirm Specialty Societal recommendations, suggesting that treatment with ACEIs or ARBs should not be discontinued because of COVID-19., Random-effects meta-analysis showed ACEI/ARB treatment was significantly associated with a lower risk of mortality in hypertensive COVID-19 patients (odds ratio [OR] = 0.624, 95% confidence interval [CI] = 0.457-0.852, p = .003, I2 = 74.3%)., In addition, the ACEI/ARB treatment was associated with a lower risk of ventilatory support (OR = 0.682, 95% CI = 0.475-1.978, p = .037, I2 = 0.0%). In conclusion, these results suggest that ACEI/ARB medications should not be discontinued for hypertensive patients in the context of COVID-19 pandemic., Use of ACE-I or ARB medications was not associated with increased risk of hospitalization, intensive care unit admission, or death. Compared to patients with charted past medical history, there was a lower risk of hospitalization for patients on ACE-I (odds ratio (OR) 0.43; 95% confidence interval (CI) 0.19-0.97; P = 0.0426) and ARB (OR 0.39; 95% CI 0.17-0.90; P = 0.0270)., The second analysis showed that the use of ACEI and/or ARB did not affect in-hospital mortality (risk ratio [RR] 95% [CI]] = 0.88 [0.64-1.20], p = 0.42). The subgroup analysis by limiting studies of patients with hypertension showed ACEI and/or ARB use was associated with a significant reduction of in-hospital mortality compared with no ACEI or ARB use (RR [CI] = 0.66 [0.49-0.89], p = 0.004). Our analysis demonstrated that ACEI and/or ARB use was associated neither with testing positive rates of COVID-19 nor with mortality of COVID-19 patients., ACEIs/ARBs are protective factors against mortality in COVID-19 patients with HTN, and these agents can be considered potential therapeutic options in this disease., There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes., Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV‑2 infections, There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes, ACEIs and ARBs do not promote a more severe outcome of COVID-19., Meta-analysis showed no significant increase in the risk of COVID-19 infection (odds ratio [OR]: 0.95, 95%CI: 0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR: 0.75, 95%CI: 0.59-0.96) and mortality (OR: 0.52, 95%CI: 0.35-0.79)., Subgroup analyses showed among the general population, ACEI/ARB therapy was associated with reduced severe COVID-19 infection (OR: 0.79, 95%CI: 0.60-1.05) and all-cause mortality (OR: 0.31, 95%CI: 0.13-0.75), and COVID-19 infection (OR: 0.85, 95% CI: 0.66-1.08) were not increased., On the basis of the available evidence, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients., Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs), Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.[SEP]Relations: peptidyl-dipeptidase activity has relations: molfunc_protein with ACE2, molfunc_protein with ACE2. Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. ARB defined as following: A retinal dystrophy with characteristics of central visual loss in the first 2 decades of life, associated with an absent electrooculogram (EOG) light rise and a reduced electroretinogram (ERG). To date less than 20 cases have been described in the world literature. Caused by compound heterozygous or homozygous mutations in the BEST1 gene (11q12) which encodes the chloride ion channel bestrophin-1 (expressed in the retinal pigment epithelium (RPE)). Mutations in BEST1 reduce or abolish the activity of the channel. It has been proposed that ARB may represent the null phenotype of bestrophin-1 in humans. Transmission is autosomal recessive.. angiotensin receptor blockers defined as following: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. ACE2 defined as following: Angiotensin-converting enzyme 2 (805 aa, ~92 kDa) is encoded by the human ACE2 gene. This protein plays a role in both vasodilation and protein cleavage.. angiotensin-converting enzyme defined as following: A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of ANGIOTENSIN I to ANGIOTENSIN II, with increase in vasoconstrictor activity, but no action on angiotensin II. It is also able to inactivate BRADYKININ, a potent vasodilator; and has a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. (From https://www.uniprot.org April 15, 2020).. angiotensin II receptor type 1 blockers defined as following: Agents that antagonize the ANGIOTENSIN II TYPE 2 RECEPTOR.. illness defined as following: A state of ill health, bodily malfunction, or discomfort.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "no"}
{"id": "converted_2947", "sentence1": "Are there tools for reviewing variant calls?", "sentence2": "VIPER: a web application for rapid expert review of variant calls., With the rapid development in next-generation sequencing, cost and time requirements for genomic sequencing are decreasing, enabling applications in many areas such as cancer research. Many tools have been developed to analyze genomic variation ranging from single nucleotide variants to whole chromosomal aberrations. As sequencing throughput increases, the number of variants called by such tools also grows. Often employed manual inspection of such calls is thus becoming a time-consuming procedure. We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application. Analysts can then quickly iterate through variants, apply filters and make decisions based on the generated images and variant metadata. VIPER was successfully employed in analyses with manual inspection of more than 10 000 calls.Availability and implementation: VIPER is implemented in Java and Javascript and is freely available at https://github.com/MarWoes/viper., Variant Review with the Integrative Genomics Viewer., VIPER: a web application for rapid expert review of variant calls.Supplementary data are available at Bioinformatics online., We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application.[SEP]Definitions: variants defined as following: An alteration or difference from a norm or standard..", "label": "yes"}
{"id": "converted_4311", "sentence1": "Does bleomycin cause lung toxicity?", "sentence2": "bleomycin-induced pulmonary fibrosis, bleomycin (BLM)-induced pulmonary , Pulmonary toxicity is a devastating complication of bleomycin chemotherapy. , Bleomycin containing regimen is routinely employed in the treatment of HL. Pulmonary toxicity due to this drug is the most feared side effect in these regimens where the mortality rate is approximately 2%-3%. , Bleomycin might cause pulmonary fibrosis at higher cumulative doses as toxic effect directly to the lungs or most likely in addition by the formation of vascular microthrombi., The comparative pulmonary toxicity induced by bleomycin and talisomycin (former trivial name: tallysomycin A) was evaluated by measuring lung hydroxyproline content., Clinicians should always remember that bleomycin toxicity may lead to fatal complications in patients with comorbid conditions., CONTEXT: The application of bleomycin is limited due to its side effects including lung toxicity., Bleomycin is an antineoplastic agent that causes a dose-related lung fibrosis that limits its therapeutic effectiveness., Acute Lung Toxicity After Intralesional Bleomycin Sclerotherapy., We report a case of a severe acute lung toxicity after a low dose of a second bleomycin intralesional injection in a 5-year-old girl., Renal damage, following cisplatin administration, with subsequent accumulation of bleomycin was the likely cause of the high lung toxicity., Whenever possible, bleomycin should precede cisplatin infusion to minimize the risk of lung toxicity., The most severe form of BLM-induced pulmonary toxicity is lung fibrosis., Results from this study suggest that an excess production of superoxide anions by alveolar macrophages may be the underlying cause of bleomycin pulmonary toxicity., Bleomycin lung toxicity is well established and can manifest as bleomycin-induced pneumonitis, but pneumomediastinum and pneumothorax are very rare complications., High doses of bleomycin administered to patients with lymphomas and other tumors lead to significant lung toxicity in general, and to apoptosis of epithelial cells, in particular. , sis of bleomycin-induced lung toxicity is based on the combination of clinical and radiological features, and requires to rule out differential diagnoses including pneumocystis. \"Bleo, Doxorubicin, bleomycin, vinblastine sulfate, and dacarbazine (ABVD) is associated with severe toxicity in older patients, particularly from bleomycin-induced lung toxicity (BLT). Ther, s studies have proposed that the lung toxicity caused by bleomycin is related to the C-terminal regions of these drugs, which have been shown to closely interact with DNA in metal-bleomycin-DNA complexes. Some o, OBJECTIVES: Bleomycin, etoposide, and cisplatin (BEP) is the most common and successful chemotherapy regimen for germ-cell tumor (GCT) patients, accompanied by a bleomycin-induced dose-dependent lung toxicity in certain pat, e been no respiratory problems attributable to bleomycin lung toxicity in this study compared with four (3 associated with patient deaths) seen in 91 previously treated patients. The relat, Mechanisms of bleomycin-induced lung damage., Previous studies have proposed that the lung toxicity caused by bleomycin is related to the C-terminal regions of these drugs, which have been shown to closely interact with DNA in metal-bleomycin-DNA complexes., g V30 cutoff value of 32% was estimated.CONCLUSION: Bleomycin and RT may cause lung injury , Postmortem lung studies were performed in all six patients and revealed findings compatible with bleomycin-induced lung toxicity., However, the cytotoxic effects of bleomycin cause a number of adverse responses, in particular in the lung and the skin., Bleomycin, a widely used anti-cancer drug, may give rise to pulmonary fibrosis, a serious side effect which is associated with significant morbidity and mortality., Bleomycin is a cancer therapeutic known to cause lung injury which progresses to fibrosis., and repair. Bleomycin pulmonary toxicity is mediated, at least in part, by the generation of active oxy, This report suggests that bleomycin lung toxicity may be reversible if treated aggressively., Although all bleomycin-treated animals had some evidence of lung toxicity, histologic examination of the lungs revealed markedly reduced bleomycin toxicity in the rats exposed to hypoxia., Low temperature inhibits bleomycin lung toxicity in the rat., Results at day 22, 3 wk after bleomycin treatment, showed that airway delivery of liposomes before and after intratracheal administration of bleomycin significantly reduced bleomycin-induced lung toxicity as evidenced by less body weight loss, chronic lung inflammation, and fibrosis as well as improved lung compliance compared with controls., Protective effect of hypoxia on bleomycin lung toxicity in the rat., N-acetyl cysteine (NAC) has recently been shown to have antioxidant properties, and since bleomycin produces pulmonary damage via free oxygen radical toxicity, the possible protective effect of NAC on bleomycin lung toxicity was investigated., All rats treated with bleomycin only had typical changes of bleomycin lung toxicity whereas the animals treated with bleomycin and NAC had minimal pathology., atic compliance on day 15 was severely decreased with bleomycin alone and showed a further significant decrease when granulocyte colony-stimulating factor was added (controls, 3.85 +/- 0.14 mL/kPa; bleomycin, 1.44 +/- 0.06 mL/kPa; and bleomycin + granulocyte colony-stimulating factor, 0.65 +/- 0.09 mL/kPa; control vs. bleomycin, p <.0001; and bleomycin vs. bleomycin + granulocyte colony-stimulating factor, p =.0003). Lung m, Bleomycin sometimes causes fatal pulmonary toxicity, including bleomycin-induced pneumonitis., Bleomycin is an antineoplastic agent causing fatal pulmonary toxicity., Pulmonary toxicity is an important adverse effect of bleomycin treatment., Pulmonary toxicity is the most significant complication of bleomycin administration., It is possible, however, that the low incidence of clinically significant and fatal pulmonary toxicity, as experienced in this group of patients, may be related to the infusion of bleomycin., Bleomycin-mediated pulmonary toxicity: evidence for a p53-mediated response., Occurrence of bleomycin lung toxicity requires an immediate and often permanent discontinuation., All three developed bleomycin induced pulmonary toxicity in the form of pulmonary fibrosis during treatment of the disease., One of the fatal side effect of bleomycin is pulmonary toxicity., Pulmonary Toxicity of Bleomycin - A Case Series from a Tertiary Care Center in Southern India., Bleomycin is potentially capable of inducing a diffuse interstitial fibrosis of the lung, the pathogenesis of which has not yet been elucidated., Intratracheal instillation of bleomycin 1.5 mg resulted in a severe pneumonitis with influx of inflammatory cells into the alveoli as assessed by alveolar lavage, oedema of the alveolar walls, and up to an eight fold increase in the total pulmonary extravascular albumin space, maximal at 72 hours., Development of acute lung injury after the combination of intravenous bleomycin and exposure to hyperoxia in rats., Bleomycin is a highly effective antitumor agent, but pulmonary toxicity, characterized by an acute inflammatory reaction and associated pulmonary edema, limits clinical use of the drug., In this study we investigated bleomycin-induced pulmonary toxicity in patients with germ-cell tumour by means of technetium-99m diethylene triamine penta-acetic acid aerosol scintigraphy.[SEP]Relations: Etoposide has relations: contraindication with pulmonary fibrosis, drug_drug with Doxorubicin, contraindication with pulmonary fibrosis, drug_drug with Doxorubicin. Dacarbazine has relations: drug_drug with Doxorubicin, drug_drug with Doxorubicin. Cisplatin has relations: drug_drug with Doxorubicin, drug_drug with Doxorubicin. Bleomycin has relations: drug_drug with Doxorubicin, drug_drug with Doxorubicin. Vinblastine has relations: drug_drug with Doxorubicin, drug_drug with Doxorubicin. Edema has relations: disease_phenotype_positive with acute lung injury, drug_effect with Doxorubicin, disease_phenotype_positive with acute lung injury, drug_effect with Doxorubicin. Definitions: etoposide defined as following: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.. epithelial cells defined as following: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.. alveoli defined as following: Any of the terminal sacs in the lungs through which gas exchange takes place with the pulmonary capillary blood.. cancer defined as following: A malignant tumor at the original site of growth.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. alveolar macrophages defined as following: Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells.. dacarbazine defined as following: An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564). BEP defined as following: A chemotherapy regimen consisting of bleomycin, etoposide and cisplatin used for the treatment of ovarian and testicular germ cell tumors (GCTs).. lymphomas defined as following: A general term for various neoplastic diseases of the lymphoid tissue.. cisplatin defined as following: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.. pneumomediastinum defined as following: Presence of air in the mediastinal tissues due to leakage of air from the tracheobronchial tree, usually as a result of trauma.. bleomycin defined as following: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.. drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. pulmonary fibrosis defined as following: A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death.. hypoxia defined as following: A disorder characterized by a decrease in the level of oxygen in the body.. ABVD defined as following: A chemotherapy regimen consisting of doxorubicin, bleomycin, vinblastine and dacarbazine, used alone or in combination with radiation therapy, for the primary treatment of Hodgkin lymphoma.. vinblastine sulfate defined as following: The sulfate salt of vinblastine, a natural alkaloid isolated from the plant Catharanthus roseus (Madagascar periwinkle) with antineoplastic properties. Vinblastine disrupts microtubule formation and function during mitosis and interferes with glutamic acid metabolism. (NCI04). N-acetyl cysteine defined as following: The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.. Doxorubicin defined as following: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.. fibrosis defined as following: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.. Pulmonary toxicity defined as following: Toxicity that impairs or damages the lung(s). This condition is often caused by the administration of a pharmaceutical agent that causes damage to the lungs.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. hydroxyproline defined as following: A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.. BLT defined as following: 1. According to Sutherland's model, all the joints in the body are balanced ligamentous articular mechanisms. The ligaments provide proprioceptive information that guides the muscle response for positioning the joint and the ligaments themselves guide the motion of the articular components. (Foundations) 2. First described in \"Osteopathic Technique of William G. Sutherland\", that was published in the 1949 Year Book of Academy of Applied Osteopathy.. pneumothorax defined as following: An accumulation of air or gas in the PLEURAL CAVITY, which may occur spontaneously or as a result of trauma or a pathological process. The gas may also be introduced deliberately during PNEUMOTHORAX, ARTIFICIAL.. pneumocystis defined as following: Pneumonia resulting from infection with Pneumocystis jirovecii, frequently seen in the immunologically compromised, such as persons with AIDS, or steroid-treated individuals, the elderly, or premature or debilitated babies during their first three months. Patients may be only slightly febrile (or even afebrile), but are likely to be extremely weak, dyspneic, and cyanotic. This is a major cause of morbidity among patients with AIDS.. acute lung injury defined as following: A condition of lung damage that is characterized by bilateral pulmonary infiltrates (PULMONARY EDEMA) rich in NEUTROPHILS, and in the absence of clinical HEART FAILURE. This can represent a spectrum of pulmonary lesions, endothelial and epithelial, due to numerous factors (physical, chemical, or biological).. superoxide defined as following: Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.. lung injury defined as following: Damage to any compartment of the lung caused by physical, chemical, or biological agents which characteristically elicit inflammatory reaction. These inflammatory reactions can either be acute and dominated by NEUTROPHILS, or chronic and dominated by LYMPHOCYTES and MACROPHAGES.. hyperoxia defined as following: An abnormal increase in the amount of oxygen in the tissues and organs.. granulocyte colony-stimulating factor defined as following: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines.. liposomes defined as following: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.. HL defined as following: A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.. lungs defined as following: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.. oedema defined as following: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE..", "label": "yes"}
{"id": "converted_2660", "sentence1": "Can GDF15 be a biomarker for metformin treatment?", "sentence2": "Growth Differentiation Factor 15 as a Novel Biomarker for Metformin., GDF15 levels are a biomarker for the use of metformin in people with dysglycemia, and its concentration reflects the dose of metformin.[SEP]Definitions: GDF15 defined as following: Growth/differentiation factor 15 (308 aa, ~34 kDa) is encoded by the human GDF15 gene. This protein plays a role in both tissue differentiation and signal transduction.. metformin defined as following: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289).", "label": "yes"}
{"id": "converted_3184", "sentence1": "Are Crocus sativus compounds being considered against Alzheimer's disease?", "sentence2": "Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer's disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD. , Collectively, findings from this study support the positive effect of Crocus sativus against AD by reducing Aβ pathological manifestations.[SEP]Definitions: Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65..", "label": "yes"}
{"id": "converted_4177", "sentence1": "Should cerebrolysin be used for aneurysmal subarachnoid hemorrhage?", "sentence2": "No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 1.49; 95% confidence interval (CI): 0.43-5.17). Secondary functional outcome measures for favorable six-month recovery i.e. a mRS of 0 to 3 (OR: 3.45; 95% CI 0.79-15.01) were comparable for both groups. Similarly, there was no difference in MOCA neurocognitive performance (p-value: 0.75) and in the incidence of DCI (OR: 0.85 95% CI: 0.28-2.59).CONCLUSIONS: Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. However, the neutral results of this trial suggest that it does not improve the six-month global functional performance of patients., CONCLUSION: Cerebrolysin injection during the acute period of SAH appeared to reduce the mortality rate, especially in poor-grade patients. This study suggests the potential of Cerebrolysin for treating aneurysmal SAH. Further studies are needed to confirm our results.[SEP]Definitions: DCI defined as following: A noninvasive (noninfiltrating) carcinoma of the breast characterized by a proliferation of malignant epithelial cells confined to the mammary ducts or lobules, without light-microscopy evidence of invasion through the basement membrane into the surrounding stroma.. SAH defined as following: A Turkic language spoken by the Yakut people in the Sakha Republic in the Russian Federation..", "label": "no"}
{"id": "converted_1493", "sentence1": "Was modafinil tested for schizophrenia treatment?", "sentence2": "Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study., CONCLUSION: The data suggest that modafinil was a safe adjunctive treatment which improved parkinsonian symptoms and signs in patients with schizophrenia or schizoaffective disorder. , A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions, with pro-mnemonic effects and problem solving improvements. Emotional processing also appears to be enhanced by the drug, although to date there are only a limited number of studies., BACKGROUND: Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. , A review of modafinil and armodafinil as add-on therapy in antipsychotic-treated patients with schizophrenia., It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain., Evidence for the use of modafinil or armodafinil as add-on therapy to antipsychotic drugs to alleviate fatigue, sleepiness and inactivity is inconclusive. One cohort study and one out of two single-dose crossover RCTs in which modafinil addition was studied could demonstrate a positive effect. All five RCTs of modafinil (three RCTs) and armodafinil (two RCTs) addition with a longer study duration could not demonstrate a positive effect. , In RCTs with a treatment duration of 4 weeks or more, however, no positive effect could be demonstrated on cognitive functioning with modafinil and armodafinil addition. Yet, four single-dose crossover RCTs of modafinil addition show significant positive effects on executive functioning, verbal memory span, visual memory, working memory, spatial planning, slowing in latency, impulse control and recognition of faces expressing sadness and sadness misattribution in the context of disgust recognition. The addition of modafinil or armodafinil to an antipsychotic regime, despite theoretical and preclinical considerations, has not been proved to enhance cognitive function, attenuate fatigue, enhance activity, improve negative symptoms and reduce weight in patients with schizophrenia., RATIONAL: In recent years, evidence suggests that modafinil may be useful for certain symptom domains of schizophrenia, especially for the negative and cognitive symptoms. , CONCLUSION: The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms. , Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia., CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil to counteract increased weight and metabolic diseases in patients taking clozapine., Modafinil (2-((diphenylmethyl)sulfinyl)acetamide) is described as an atypical stimulant and is a putative cognition enhancer for schizophrenia, but the precise mechanisms of action remain unclear., Modafinil is a wake-promoting drug that has been shown to improve emotion discrimination in healthy individuals and attention and executive function in schizophrenia. , CONCLUSIONS: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction., Modafinil improves working memory in healthy subjects and individuals diagnosed with schizophrenia and Attention Deficit/Hyperactivity Disorder, though the effects of modafinil have not been evaluated on working memory in methamphetamine-dependent subjects., Modafinil is a psychostimulant approved for treating excessive sleepiness in adults; off-label uses (e.g., treatment of cognitive impairment in schizophrenia, ADHD and age-related dementias) are currently being explored. , CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine., We have previously shown that the amount of movement exhibited by patients with schizophrenia is positively correlated with the volume of left anterior cingulate cortex and that this quantity of movement can be increased by modafinil. , OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability. , RESULTS: One of 4 reviewed studies found a significant effect of modafinil as an alerting agent for antipsychotic-induced fatigue and sedation. Neither of 2 reviewed studies found modafinil to improve negative symptoms of schizophrenia. Three of 6 reviewed studies showed that modafinil may improve short-term memory, attention, and the ability to shift mental sets. , CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia. , Hence, before prescribing modafinil to a schizophrenia patient, the possible risks and benefits of each particular case should be evaluated., Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo., RATIONALE: The wake-promoting agent modafinil selectively improves neuropsychological task performance in healthy volunteers, in adults with attention deficit hyperactivity disorder (ADHD) and in schizophrenia. , Recently, however, modafinil has been shown to improve attentional set-shifting performance in patients with schizophrenia., In addition, modafinil shows initial promise for a variety of off-label indications in psychiatry, including treatment-resistant depression, attention-deficit/hyperactivity disorder, and schizophrenia., There is increasing interest in the use of modafinil to improve cognition in schizophrenia as well as in other disorders such as attention-deficit/hyperactivity disorder., Initial findings indicate that modafinil may lead to better executive functioning and attentional performance in patients with schizophrenia. , CONCLUSIONS: Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms., CONCLUSIONS: Modafinil did not improve cognitive control in all schizophrenia patients., . These data suggest that modafinil increases quantifiable motor behaviour in schizophrenia and may have an impact on avolition., One patient was on treatment with both modafinil and trazodone and reported no change after tapering each in separate discontinuation trials, while another 3 patients were taking sleeping medications and also noted no change after discontinuation., Neuroprotective agents as add-on therapies (e.g., modafinil, erythropoietin, glycine, D-serine, memantine and celecoxib) are currently being evaluated in schizophrenia and related disorders. , In the modafinil (N = 10) and placebo (N = 10) groups, fatigue improved significantly over time (p < .01), but there were no differences between groups on changes in fatigue, positive and negative symptoms, or cognition. , CONCLUSIONS: Modafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation., Modafinil significantly improved overall clinical condition, with 64% and 82% of patients rated as clinically improved at week 4 by a blinded clinician and the investigator respectively., Modafinil significantly improved fatigue (P = 0.025, week 3) and tended to improve cognitive functioning scores. , Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder. , Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD. , Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting., While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia., Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability., The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms., It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain., CONCLUSION: The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms., OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability., CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia., The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms., Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder., While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia, The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms, Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions[SEP]Relations: Modafinil has relations: contraindication with schizoaffective disorder, contraindication with schizoaffective disorder. Armodafinil has relations: contraindication with schizoaffective disorder, contraindication with schizoaffective disorder. Cognitive impairment has relations: disease_phenotype_positive with schizophrenia, disease_phenotype_positive with schizophrenia. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. sleepiness defined as following: Compelling urge to sleep.. schizoaffective disorder defined as following: A disorder in which the individual suffers from both symptoms that qualify as schizophrenia and symptoms that qualify as a mood disorder (e.g., depression or bipolar disorder) for a substantial portion (but not all) of the active period of the illness; for the remainder of the active period of the illness, the individual suffers from delusions or hallucinations in the absence of prominent mood symptoms.. memantine defined as following: AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent.. D-serine defined as following: A non-essential amino acid and dextro isomer of serine with antipsychotic activity. D-serine is a selective full agonist at the glycine site of N-methyl-D-aspartate (NMDA)-type glutamate receptor. Hypofunction of NMDA type of neurotransmission is believed to play a major role in pathophysiology of schizophrenia, therefore, administration of D-serine and subsequent activation of NMDA receptors may alleviate psychotic tendencies.. clozapine defined as following: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.. traumatic brain injury defined as following: A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.. ADHD defined as following: A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-V). multiple sclerosis defined as following: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903). erythropoietin defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous glycoprotein erythropoietin (Epo). Epo promotes the differentiation and maturation of hematopoietic progenitors into erythrocytes; is a mitogen and a chemoattractant for endothelial cells; stimulates activated and differentiated B-cells and enhances B-cell immunoglobulin production and proliferation; and is hypoxia-inducible. (NCI04). modafinil defined as following: A benzhydryl acetamide compound, central nervous system stimulant, and CYP3A4 inducing agent that is used in the treatment of NARCOLEPSY and SLEEP WAKE DISORDERS.. celecoxib defined as following: A pyrazole derivative and selective CYCLOOXYGENASE 2 INHIBITOR that is used to treat symptoms associated with RHEUMATOID ARTHRITIS; OSTEOARTHRITIS and JUVENILE ARTHRITIS, as well as the management of ACUTE PAIN.. fatigue defined as following: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.. armodafinil defined as following: The R-enantiomer of the racemic synthetic agent modafinil with central nervous system (CNS) stimulant and wakefulness-promoting activities. Although the exact mechanism of action has yet to be fully elucidated, armodafinil appears to inhibit the reuptake of dopamine by binding to the dopamine-reuptake pump, which leads to an increase in extracellular dopamine levels in some brain regions. This agent does not bind to or inhibit several receptors and enzymes that may be involved in sleep/wake regulation and is not a direct- or indirect-acting dopamine receptor agonist. Armodafinil has a longer half-life than modafinil.. cognitive deficits defined as following: Disorders characterized by disturbances in mental processes related to learning, thinking, reasoning, and judgment.. trazodone defined as following: A serotonin uptake inhibitor that is used as an antidepressive agent. It has been shown to be effective in patients with major depressive disorders and other subsets of depressive disorders. It is generally more useful in depressive disorders associated with insomnia and anxiety. This drug does not aggravate psychotic symptoms in patients with schizophrenia or schizoaffective disorders. (From AMA Drug Evaluations Annual, 1994, p309). attention deficit disorder defined as following: A mental disorder characterized by inattention, easy distraction, careless mistakes and avoidance of tasks that require sustained mental focus. These behaviors can lead to maladaptive consequences in the affected individual's life.. weight gain defined as following: A question about whether an individual is gaining or has gained weight..", "label": "yes"}
{"id": "converted_2938", "sentence1": "Does Groucho related gene 5 (GRG5) have a role only in late development?", "sentence2": "Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. The malignant characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its pro-oncogenic potential., Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions., Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state decisions.Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. [SEP]Definitions: embryonic defined as following: The entities of developing ANIMALS in early stages.. cancer defined as following: A malignant tumor at the original site of growth.. Embryonic Stem Cell defined as following: Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.. teratomas defined as following: A true neoplasm composed of a number of different types of tissue, none of which is native to the area in which it occurs. It is composed of tissues that are derived from three germinal layers, the endoderm, mesoderm, and ectoderm. They are classified histologically as mature (benign) or immature (malignant). (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1642). multifunctional protein defined as following: This gene is involved in fatty acid oxidation..", "label": "no"}
{"id": "converted_1187", "sentence1": "Is there any link between conserved noncoding elements and alternative splicing in vertebrates?", "sentence2": "Some of the most highly conserved sequences occur in genes encoding RNA binding proteins, particularly the RNA splicing-associated SR genes. Differences in sequence conservation between plants and animals are likely to reflect differences in the biology of the organisms, with plants being much more able to tolerate genomic deletions and whole-genome duplication events due, in part, to their far greater fecundity compared with vertebrates.[SEP]Definitions: vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. organisms defined as following: A living entity.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE.. RNA binding proteins defined as following: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA..", "label": "yes"}
{"id": "converted_4017", "sentence1": "Is eptinezumab a small molecule?", "sentence2": "Eptinezumab-jjmr (referred to as eptinezumab hereafter; Vyepti™) is a humanised monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) and blocks its binding to the receptor. [SEP]Definitions: CGRP defined as following: A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.. calcitonin gene-related peptide defined as following: Calcitonin precursor (141 aa, ~15 kDa) is encoded by the human CALCA gene. This protein plays a role in calcium flux and bone resorption..", "label": "no"}
{"id": "converted_2324", "sentence1": "Are mutations in the nf1 gene associated with memory?", "sentence2": "We hypothesized that NF1 mutations disturb the expression of genes important for memory formation, Our previous work has shown that defective cAMP signaling leads to the learning phenotype in Drosophila Nf1 mutants. In the present report, our experiments showed that in addition to learning, long-term memory was also abolished in Nf1 mutants. , Distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation.[SEP]Relations: neurofibromatosis has relations: disease_protein with NF1, disease_protein with NF1. Definitions: NF1 defined as following: An autosomal dominant inherited disorder (with a high frequency of spontaneous mutations) that features developmental changes in the nervous system, muscles, bones, and skin, most notably in tissue derived from the embryonic NEURAL CREST. Multiple hyperpigmented skin lesions and subcutaneous tumors are the hallmark of this disease. Peripheral and central nervous system neoplasms occur frequently, especially OPTIC NERVE GLIOMA and NEUROFIBROSARCOMA. NF1 is caused by mutations which inactivate the NF1 gene (GENES, NEUROFIBROMATOSIS 1) on chromosome 17q. The incidence of learning disabilities is also elevated in this condition. (From Adams et al., Principles of Neurology, 6th ed, pp1014-18) There is overlap of clinical features with NOONAN SYNDROME in a syndrome called neurofibromatosis-Noonan syndrome. Both the PTPN11 and NF1 gene products are involved in the SIGNAL TRANSDUCTION pathway of Ras (RAS PROTEINS).. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. nf1 gene defined as following: Tumor suppressor genes located on the long arm of human chromosome 17 in the region 17q11.2. Mutation of these genes is thought to cause NEUROFIBROMATOSIS 1, Watson syndrome, and LEOPARD syndrome..", "label": "yes"}
{"id": "converted_4409", "sentence1": "Does addition of valproic acid improve survival of patients with diffuse intrinsic pontine glioma?", "sentence2": "Median event-free survival (EFS) and overall survival (OS) for DIPG were 7.8 (95% CI 5.6-8.2) and 10.3 (7.4-13.4) months, and estimated one-year EFS was 12% (2%-31%). Median EFS and OS for HGG were 9.1 (6.4-11) and 12.1 (10-22.1) months, and estimated one-year EFS was 24% (7%-45%). , CONCLUSION: Addition of VPA and bevacizumab to radiation was well tolerated but did not appear to improve EFS or OS in children with DIPG or HGG., Event-free survival and overall survival of patients not treated with valproic acid were 6.5 and 7.8 months. Accelerated failure time model (a parametric multivariate regression test for time-to-failure data) showed a statistically significant superiority of the median event-free survival of treated patients (6.5 vs. 9.5 months in treated patients; HR 0.54-95 % CI 0.33-0.87; p < 0.05) and also of overall survival (7.8 vs. 13.4 months in treated patients; HR 0.60-95 % CI 0.37-0.98; p = 0.05).[SEP]Definitions: VPA defined as following: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.. DIPG defined as following: A glioma that grows diffusely in the pons. It usually affects children and has a poor prognosis.. bevacizumab defined as following: An anti-VEGF humanized murine monoclonal antibody. It inhibits VEGF RECEPTORS and helps to prevent PATHOLOGIC ANGIOGENESIS.. valproic acid defined as following: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS..", "label": "no"}
{"id": "converted_3231", "sentence1": "Is CD63 an exosomal marker?", "sentence2": "f exosome marker proteins (e.g., CD63, Alix) , CD63 levels and acetylcholinesterase (AChE) activity were used as markers of exosome,, The results demonstrated these exosomes all expressed CD9, CD63, CD81, Alix[SEP]Definitions: exosome defined as following: A type of extracellular vesicle, containing RNA and proteins, that is secreted into the extracellular space by EXOCYTOSIS when MULTIVESICULAR BODIES fuse with the PLASMA MEMBRANE.. CD63 defined as following: Ubiquitously-expressed tetraspanin protein that is found in late ENDOSOMES and LYSOSOMES. It functions in intracellular protein transport and signaling.. CD81 defined as following: A tetraspanin protein that is involved in a variety of cellular functions including BASEMENT MEMBRANE assembly, and in the formation of a molecular complexes on the surface of LYMPHOCYTES.. CD9 defined as following: A subtype of tetraspanin protein that plays a role in cell adhesion, cell motility, and tumor metastasis. It functions in platelet activation and aggregation, the formation of paranodal junctions in neuronal tissue, and the fusion of sperm with egg..", "label": "yes"}
{"id": "converted_1057", "sentence1": "Are there clinical trials on stem cells in multiple sclerosis", "sentence2": "Cells are generally given intravenously. Multiple sclerosis, rheumatoid arthritis and lupus have been successfully treated in human clinical trials, Human multipotent mesenchymal stem cell (MSC) therapies are currently being tested in clinical trials for Crohn's disease, multiple sclerosis, graft-versus-host disease, type 1 diabetes, bone fractures, cartilage damage, and cardiac diseases., Based on these results, several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair, Mesenchymal stem cells (MSC) promote functional recovery in experimental models of central nervous system (CNS) pathology and are currently being tested in clinical trials for stroke, multiple sclerosis and CNS injury., Autologous bone marrow stromal cells (BMSCs) offer significant practical advantages for potential clinical applications in multiple sclerosis (MS). Based on recent experimental data, a number of clinical trials have been designed for the intravenous (IV) and/or intrathecal (ITH) administration of BMSCs in MS patients., Fingolimod is a S1P receptor modulator in MS clinical trials due to systemic anti-inflammatory properties, yet may impact cells within the CNS by crossing the blood-brain barrier., Their development in vitro and their use in vivo in animal models of degenerative neurological disease and recent first efforts in human clinical trials were the topics of a recent international meeting sponsored by the Multiple Sclerosis International Federation and the National Multiple Sclerosis Society on \"Stem Cells & MS: Prospects and Strategies\", Here we discuss key observations and questions emerging from clinical trials of hematopoietic stem cell transplantation for MS, Another possibility to achieve remyelination is the transplantation of myelinating cells into the central nervous system. Proof of principle and demonstration of the functionality were shown in numerous experiments, and a first clinical trial in patients with MS has started, This first trial will show if cell transplantation is a feasible concept in MS and whether the transplanted cells will survive and form new myelin.[SEP]Relations: Rheumatoid arthritis has relations: disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis. Definitions: rheumatoid arthritis defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. human defined as following: Members of the species Homo sapiens.. graft-versus-host disease defined as following: The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.. MSC defined as following: A naturally occurring organoselenium compound found in many plants, including garlic, onions, and broccoli, with potential antioxidant and chemopreventive activities. Se-Methyl-seleno-L-cysteine (MSC) is an amino acid analogue of cysteine in which a methylselenium moiety replaces the sulphur atom of cysteine. This agent acts as an antioxidant when incorporated into glutathione peroxidase and has been shown to exhibit potent chemopreventive activity in animal models.. multiple sclerosis defined as following: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903). Mesenchymal stem cells defined as following: An undifferentiated stromal cell with the ability to develop into the cells that form distinct mesenchymal tissues; such as bone, muscle, connective tissue, blood vessels, and lymphatic tissue.. Fingolimod defined as following: An orally available derivate of myriocin and sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) modulator, with potential anti-inflammatory and immunomodulating activities. Upon oral administration, fingolimod, as a structural analogue of sphingosine, selectively targets and binds to S1PR1 on lymphocytes and causes transient receptor activation followed by S1PR1 internalization and degradation. This results in the sequestration of lymphocytes in lymph nodes. By preventing egress of lymphocytes. fingolimod reduces both the amount of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues. This prevents a lymphocyte-mediated immune response and may reduce inflammation. S1PR1, a G-protein coupled receptor, plays a key role in lymphocyte migration from lymphoid tissues. Fingolimod also shifts macrophages to an anti-inflammatory M2 phenotype, and modulates their proliferation, morphology, and cytokine release via inhibition of the transient receptor potential cation channel, subfamily M, member 7 (TRPM7).. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). myelin defined as following: The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. lupus defined as following: chronic form of cutaneous lupus erythematosus in which the skin lesions mimic those of the systemic form but in which systemic signs are rare; characterized by the presence of discoid skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy; lesions are surrounded by an elevated erythematous border; the condition typically involves the face and scalp, but widespread dissemination may occur.. cardiac diseases defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities.. stem cells defined as following: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells..", "label": "yes"}
{"id": "converted_3263", "sentence1": "Are astrocytes part of the blood brain barrier?", "sentence2": "The blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation., The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL).[SEP]Definitions: pericytes defined as following: Unique slender cells with multiple processes extending along the capillary vessel axis and encircling the vascular wall, also called mural cells. Pericytes are imbedded in the BASEMENT MEMBRANE shared with the ENDOTHELIAL CELLS of the vessel. Pericytes are important in maintaining vessel integrity, angiogenesis, and vascular remodeling.. astrocytes defined as following: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from \"star\" cells) are irregularly shaped with many long processes, including those with \"end feet\" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and \"reactive astrocytes\" (along with MICROGLIA) respond to injury.. basal lamina defined as following: A layer of extracellular matrix found beneath epithelial tissues. It is secreted by epithelial cells and comprised of proteoglycans, laminin and type IV collagen.. BL defined as following: A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.. endothelial cells defined as following: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer..", "label": "yes"}
{"id": "converted_1489", "sentence1": "Is there any role for long noncoding RNAs in adipogenesis?", "sentence2": "Long noncoding RNAs regulate adipogenesis., Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 lncRNAs that are specifically regulated during adipogenesis. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (CEBPα). RNAi-mediated loss of function screens identified functional lncRNAs with varying impact on adipogenesis. Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis., Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 lncRNAs that are specifically regulated during adipogenesis. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (CEBPα). [SEP]Definitions: promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. peroxisome proliferator-activated receptor γ defined as following: TRANSCRIPTION FACTORS that are activated by ligands and heterodimerize with RETINOID X RECEPTORS and bind to peroxisome proliferator response elements in the promoter regions of target genes.. white adipocytes defined as following: Fat cells with light coloration and few MITOCHONDRIA. They contain a scant ring of CYTOPLASM surrounding a single large lipid droplet or vacuole.. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process..", "label": "yes"}
{"id": "converted_384", "sentence1": "Is nintedanib effective for Idiopathic Pulmonary Fibrosis?", "sentence2": "In this review, we present the positive results of recently published clinical trials regarding therapy for IPF, with emphasis on pirfenidone and nintedanib., Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis, In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily., Effects on collagen secretion were compared with those of the drugs nintedanib and pirfenidone, recently approved for IPF., Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. , Most recently, pirfenidone and nintedanib, two compounds with pleiotropic anti-fibrotic properties, have been proven effective in reducing functional decline and disease progression in IPF. , Meningococcal group B vaccine (Trumenba) to prevent more types of invasive meningococcal disease; antihemophilic factor (recombinant), porcine sequence (Obizur) to treat bleeding from acquired hemophilia A; and pirfenidone (Esbriet) and nintedanib (Ofev) for idiopathic pulmonary fibrosis., More importantly, the period ends with the publication of two groundbreaking studies that confirmed that two drugs, pirfenidone and nintedanib, slowed disease progression, leading to a historic approval by the FDA. , Nintedanib (Ofev(®)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. Nintedanib has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for the treatment of IPF, and for the second-line treatment in combination with docetaxel of locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma tumour histology. , This article summarizes the milestones in the development of nintedanib leading to this first approval for IPF., Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis., Nintedanib: a novel therapeutic approach for idiopathic pulmonary fibrosis., Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF)., Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib., These results suggest that nintedanib may impact the progressive course of fibrotic lung diseases such as idiopathic pulmonary fibrosis., Findings from recently published placebo-controlled trials in idiopathic pulmonary fibrosis have established that pirfenidone and nintedanib prevent about 50% of the decline in forced vital capacity typically seen in this disease; future trials are therefore unlikely to use placebo as a control group for ethical reasons., The tyrosine kinase inhibitor nintedanib (BIBF 1120) is in clinical development for the treatment of idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. , Data from the Phase II TOMORROW study suggested that nintedanib 150�mg twice daily had clinical benefits with an acceptable safety profile.METHODS: The INPULSIS� trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150�mg twice daily with placebo in patients with IPF. , Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. , The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. , A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. , Nintedanib (Ofev(�)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. , Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis.[SEP]Definitions: tyrosine kinase defined as following: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.. cancer defined as following: A malignant tumor at the original site of growth.. platelet-derived growth factor defined as following: Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.. vascular endothelial growth factor defined as following: A recombinant therapeutic agent which is chemically identical to or similar to endogenous vascular endothelial growth factor (VEGF). Produced by a wide variety of cell types, endogenous VEGF is a homodimeric, glycosylated protein that is a highly specific mitogen for vascular endothelial cells; significantly influences vascular permeability; appears to play a role in neovascularisation under physiological conditions; is a potent chemoattractant; has pro-coagulatory activities; and is hypoxia-inducible. Therapeutic VEGF may be used to induce angiogenesis in the treatment of ischemic conditions and may have a role in stimulating nerve regeneration. (NCI04). hemophilia A defined as following: A deficiency or abnormality of a blood coagulation factor characterized by the tendency to hemorrhage. Hemophilia is typically a hereditary disorder but, rarely, may be acquired. Inherited coagulation factor-deficient hemophilias include hemophilia A or classic hemophilia (hereditary factor VIII deficiency) hemophilia B or Christmas disease (hereditary factor IX deficiency), and hemophilia C (hereditary factor XI deficiency). Factor VIII inhibitors may occur spontaneously as autoantibodies, resulting in acquired hemophilia known as acquired factor VIII deficiency. Approximately 10% of patients with acquired hemophilia have an underlying malignancy.. Medicinal Products defined as following: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.. VEGF defined as following: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as \"tumor angiogenesis factor\" and \"vascular permeability factor\". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.. collagen defined as following: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).. IPF defined as following: A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change.. pirfenidone defined as following: An orally bioavailable and deuterated form of the synthetic antifibrotic agent pirfenidone, with potential anti-inflammatory and anti-fibrotic activities. Upon administration, deupirfenidone inhibits a variety of pro-inflammatory mediators, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and transforming growth factor-beta (TGF-b). This may reduce fibrosis, inflammation and infection, and may repair the impaired lymphatic flow, decrease lymphedema and restore lymphatic function. In the lungs, deupirfenidone may abrogate impaired lung function, lymphoedema and pulmonary fibrosis.. nintedanib defined as following: An orally bioavailable, indolinone-derived inhibitor of multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs), with potential antiangiogenic, antifibrotic and antineoplastic activities. Upon administration, nintedanib selectively binds to and inhibits vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and colony stimulating factor 1 receptor (CSF1R) tyrosine kinases, which may result in the induction of endothelial cell apoptosis, the reduction in tumor vasculature, the inhibition of tumor cell proliferation and migration, and antifibrotic activity in pulmonary fibrosis. In addition, nintedanib also binds to and inhibits members of the Src family of tyrosine kinases, including Src, Lck and Lyn, and fms-like tyrosine kinase 3 (FLT-3). VEGFR, FGFR, PDGFR and CSF1R RTKs play key roles in tumor angiogenesis, tumor cell proliferation and metastasis, as well as pulmonary fibrosis.. diarrhea defined as following: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.. fibroblast growth factor defined as following: A recombinant therapeutic agent which is chemically identical to or similar to endogenous fibroblast growth factor 1 (FGF-1. Because of the mitogenic and angiogenetic effects of FGF-1 on fibroblasts and endothelial cells, therapeutic FGF-1 has a potential role in wound healing; because FGF-1 has been shown to induce neurogenesis, therapeutic FGF-1 may have a role in nerve regeneration. (NCI04). Human defined as following: Members of the species Homo sapiens.. bleeding defined as following: Bleeding or escape of blood from a vessel.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. docetaxel defined as following: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER.. non-small cell lung cancer defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. tyrosine kinase inhibitor defined as following: Protein kinase inhibitors that inhibit TYROSINE PROTEIN KINASES.. Idiopathic Pulmonary Fibrosis defined as following: A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change..", "label": "yes"}
{"id": "converted_687", "sentence1": "Is the Miller-Fisher syndrome considered to be a variant of Guillain-Barré?", "sentence2": "Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia, We are reporting a rare case of Miller-Fisher (MFS) variant of Guillain-Barré syndrome (GBS) as the first manifestation of SLE in a 41-year-old female, Miller-Fisher syndrome is defined as ophthalmoplegia, ataxia and areflexia. Considered as a variant of Guillain-Barré syndrome, it differs in its clinical presentation and by anti-GQ1b antibody positivity, Guillain-Barré syndrome (GBS) and its variant, Miller Fisher syndrome (MFS), exist as several clinical subtypes with different neurological features and presentations, Using in vitro and in vivo models of the Guillain-Barré syndrome variant, Miller Fisher syndrome, we have shown previously that anti-GQ1b ganglioside antibodies target the presynaptic motor nerve terminal axon and surrounding perisynaptic Schwann cells, thereby mediating destructive injury through deposition of membrane attack complex., Miller Fisher syndrome is a variant of Guillain-Barré syndrome, characterized by ophthalmoplegia, ataxia and areflexia., Miller Fisher syndrome is a localized variant of Guillain-Barré syndrome, characterized by ophthalmoplegia, areflexia and ataxia., Miller Fisher syndrome, a variant of Guillain-Barré syndrome, is associated with IgG antibody to GQ1b ganglioside., Miller Fisher syndrome (MFS), a variant of Guillain-Barré syndrome, is a rare disorder typically characterized by a triad of ataxia, areflexia, and ophthalmoplegia, which may have a highly variable clinical presentation., Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia., The objective of this study was to review the occurrence and clinical features of Guillain-Barré syndrome and its variant, the Miller Fisher syndrome, during TNFalpha antagonist therapy., Miller Fisher variant of Guillain-Barré syndrome masquerading as acute sphenoid sinusitis with orbital apex syndrome., Controversy exists concerning whether Miller Fisher syndrome (MFS) is the result of a predominantly axonal or demyelinating polyneuropathy and whether the Guillain-Barré syndrome variant of acute ataxia and areflexia without ophthalmoplegia, ataxic Guillain-Barré syndrome (atxGBS), has a distinct pathophysiology., Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke's encephalopathy, Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia, Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome, The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system, Miller-Fisher syndrome (MFS) is considered the most common variant of Guillain-Barré syndrome (GBS) and is characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia, Miller Fisher syndrome (MFS), characterized as ataxia, areflexia and ophthalmoplegia, is generally considered as a variant of Guillain-Barré syndrome (GBS), Miller Fisher Syndrome (MFS), which is characterized by ophthalmoplegia, ataxia and tendon areflexia, is generally considered as a clinical variant of Guillain-Barré Syndrome, Miller-Fisher syndrome (MFS), a variant of Guillain-Barré syndrome (GBS) is a self-limiting demyelinating disease of the peripheral nervous system, BACKGROUND: Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome. , BACKGROUND AND OBJECTIVE: Miller-Fisher syndrome (MFS) is considered the most common variant of Guillain-Barré syndrome (GBS) and is characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia. , Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke's encephalopathy. , A recent report described serum anti-GQ1b ganglioside antibodies in Miller Fisher syndrome (MFS), a clinical variant of Guillain-Barré syndrome (GBS)., The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system., Guillain-Barré syndrome (GBS), an acute inflammatory polyneuropathy, is preceded in most cases by an infectious illness, and Campylobacter jejuni, a leading cause of acute gastroenteritis, is the most common antecedent to GBS and its ocular variant, Miller Fisher syndrome (MFS)., Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome., Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome., The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system. A patient with Miller-Fisher syndrome and bilateral demyelinating optic neuropathy suggesting associated central nervous system pathology is presented., Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia,, Miller Fisher syndrome is an uncommon disease and it is a variant of Guillain-Barre syndrome. Miller Fisher syndrome also has rarer variants., Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke's encephalopathy., Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia., Data were separately analysed for Miller Fisher syndrome and other Guillain-Barré syndrome variants., Guillain-Barré syndrome variants alone (excluding Miller Fisher syndrome) accounted for 10.5% of total cases., The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system.[SEP]Definitions: MFS defined as following: An autosomal dominant disorder of CONNECTIVE TISSUE with abnormal features in the heart, the eye, and the skeleton. Cardiovascular manifestations include MITRAL VALVE PROLAPSE; AORTIC ANEURYSM; and AORTIC DISSECTION. Other features include lens displacement (ectopia lentis), disproportioned long limbs and enlarged DURA MATER (dural ectasia). Marfan syndrome (type 1) is associated with mutations in the gene encoding FIBRILLIN-1 (FBN1), a major element of extracellular microfibrils of connective tissue. Mutations in the gene encoding TYPE II TGF-BETA RECEPTOR (TGFBR2) are associated with Marfan syndrome type 2.. variant defined as following: An alteration or difference from a norm or standard.. Campylobacter jejuni defined as following: A species of bacteria that resemble small tightly coiled spirals. Its organisms are known to cause abortion in sheep and fever and enteritis in man and may be associated with enteric diseases of calves, lambs, and other animals.. ataxia defined as following: Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90). IgG antibody defined as following: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.. GBS defined as following: An acute inflammatory autoimmune neuritis caused by T cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. (From Adams et al., Principles of Neurology, 6th ed, pp1312-1314). Wernicke's encephalopathy defined as following: An acute neurological disorder characterized by the triad of ophthalmoplegia, ataxia, and disturbances of mental activity or consciousness. Eye movement abnormalities include nystagmus, external rectus palsies, and reduced conjugate gaze. THIAMINE DEFICIENCY and chronic ALCOHOLISM are associated conditions. Pathologic features include periventricular petechial hemorrhages and neuropil breakdown in the diencephalon and brainstem. Chronic thiamine deficiency may lead to KORSAKOFF SYNDROME. (Adams et al., Principles of Neurology, 6th ed, pp1139-42; Davis & Robertson, Textbook of Neuropathology, 2nd ed, pp452-3). areflexia defined as following: A finding indicating the complete absence of neurological reflexes.. Miller-Fisher syndrome defined as following: A variant of the GUILLAIN-BARRE SYNDROME characterized by the acute onset of oculomotor dysfunction, ataxia, and loss of deep tendon reflexes with relative sparing of strength in the extremities and trunk. The ataxia is produced by peripheral sensory nerve dysfunction and not by cerebellar injury. Facial weakness and sensory loss may also occur. The process is mediated by autoantibodies directed against a component of myelin found in peripheral nerves. (Adams et al., Principles of Neurology, 6th ed, p1313; Neurology 1987 Sep;37(9):1493-8). SLE defined as following: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.. membrane attack complex defined as following: A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the \"membrane attack complex\" or MAC..", "label": "yes"}
{"id": "converted_528", "sentence1": "Is there any software for automated analysis of immuno-histochemistry images?", "sentence2": "The LIM homeobox gene Lhx2 is expressed in cortical progenitors during development and also in the superficial layers of the neocortex in maturity. However, analysis of Lhx2 function at later stages of cortical development has been hampered by severe phenotypes associated with early loss of function. , The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1) mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses., Tissue Transglutaminase (TG2) is a multifunctional enzyme, which amongst other functions, is involved in cell differentiation. Therefore, we hypothesized that TG2 contributes to differentiation of OPCs into OLGs and thereby stimulates remyelination. [SEP]Definitions: TG2 defined as following: Protein-glutamine gamma-glutamyltransferase 2 (687 aa, ~77 kDa) is encoded by the human TGM2 gene. This protein plays a role in both the induction of apoptosis and the formation of covalent bonds between peptide-bound glutamine and various primary amines.. neocortex defined as following: The largest portion of the CEREBRAL CORTEX in which the NEURONS are arranged in six layers in the mammalian brain: molecular, external granular, external pyramidal, internal granular, internal pyramidal and multiform layers.. Egr-1 defined as following: Early growth response protein 1 (543 aa, ~58 kDa) is encoded by the human EGR1 gene. This protein is involved in the modulation of both mitogenesis and differentiation through the transcriptional regulation of specified genes.. Lhx2 defined as following: Human LHX2 wild-type allele is located within 9q33-34.1 and is approximately 22 kb in length. This allele, which encodes the LIM/homeobox protein Lhx2, may play a role in both the modulation of transcription by RNA polymerase II and the development of lymphoid and neural cells.. Tissue Transglutaminase defined as following: Calcium-dependent acyltransferase that catalyzes cross-linking of proteins at a GLUTAMINE in one chain with primary amine such as in LYSINE in another chain. In addition it can also accept monoamine substrates to catalyze post-translational modifications (e.g., protein serotonylation).. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm..", "label": "yes"}
{"id": "converted_2527", "sentence1": "Can doxycycline cause photosensitivity?", "sentence2": "Phototoxicity of Doxycycline: A Systematic Review on Clinical Manifestations, Frequency, Cofactors, and Prevention., BACKGROUND: One of the most important dermatologic side effects of doxycycline is photosensitivity. , While there are many publications on the phototoxicity of tetracyclines in general, only a few exist focusing on doxycycline. , Clinical symptoms vary from light sunburn-like sensation (burning, erythema) to large-area photodermatitis. , CONCLUSION: Evidence base must be improved for giving advice on appropriate prevention measures to travelers taking doxycycline and having a risk of significant sun exposure., Based on the available evidence, our best estimates of absolute effect for mefloquine versus doxycyline were: 2% versus 2% for discontinuation, 12% versus 3% for insomnia, 31% versus 3% for abnormal dreams, 18% versus 1% for anxiety, 11% versus 1% for depressed mood, 4% versus 14% for dyspepsia, 2% versus 19% for photosensitivity, 1% versus 5% for vomiting, and 2% versus 16% for vaginal thrush., Many drugs are responsible for this phototoxic reaction, especially tetracyclines, psoralens, chloramphenicol, non-steroidal anti-inflammatory drugs, fluoroquinolones, and, rarely, doxycycline. , OBJECTIVES: Many patients undergoing long-term doxycycline treatment do not regularly take their treatment because of photosensitivity., Modulation of Melanogenesis and Antioxidant Status of Melanocytes in Response to Phototoxic Action of Doxycycline., Doxycycline is a commonly used tetracycline antibiotic showing the broad spectrum of antibacterial action. However, the use of this antibiotic is often connected with the risk of phototoxic reactions that lead to various skin disorders., The results obtained in vitro may explain the mechanisms of phototoxic reactions that occur in normal human epidermal melanocytes in vivo after exposure of skin to doxycycline and UVA radiation., Treatment with doxycycline is cheap and relatively safe, but gastrointestinal symptoms and photosensitivity reactions can be expected more often than with ceftriaxone.
, OBJECTIVES: Many patients undergoing long-term doxycycline treatment do not regularly take their treatment because of photosensitivity., Photosensitivity reactions and gastrointestinal symptoms were noted more often among patients receiving doxycycline than in those receiving ceftriaxone., Thus, the action spectra of the drug photosensitivity patients were plotted and compared with those of 12 nonphotosensitive control patients: 10 patients were found to be photosensitive in the UVA range; the implicated drugs included quinine, sparfloxacin, amiodarone, doxycycline, mefenamic acid, nalidixic acid, fenbrufen, diclofenac, enalapril, diltiazem and prochlorperazine maleate., One patient on doxycycline was photosensitive in both the UVA and UVB ranges., Treatment with doxycycline is cheap and relatively safe, but gastrointestinal symptoms and photosensitivity reactions can be expected more often than with ceftriaxone., Anti-inflammatory-dose doxycycline should not be used by individuals with known hypersensitivity to tetracyclines or increased photosensitivity, or by pregnant or nursing women (anti-inflammatory-dose doxycycline is a pregnancy category-D medication)., BACKGROUND: One of the most important dermatologic side effects of doxycycline is photosensitivity., One of the most important dermatologic side effects of doxycycline is photosensitivity., One patient experienced mild photosensitivity from doxycycline but continued to take it., Participants in the doxycycline group had a higher incidence of nausea and photosensitivity., Photosensitivity reactions and gastrointestinal symptoms were noted more often among patients receiving doxycycline than in those receiving ceftriaxone.[SEP]Relations: anxiety disorder has relations: disease_disease with anxiety, disease_disease with anxiety. Definitions: tetracyclines defined as following: Any of a group of broad spectrum naphthacene antibiotics isolated from various species of Streptomyces or produced semisynthetically. In bacteria, tetracycline antibiotics block binding of aminoacyl-tRNA to the mRNA-ribosome complex, thereby inhibiting protein synthesis. (NCI05). quinine defined as following: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood.. doxycycline defined as following: A synthetic tetracycline derivative with similar antimicrobial activity.. erythema defined as following: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes.. Melanocytes defined as following: Mammalian pigment cells that produce MELANINS, pigments found mainly in the EPIDERMIS, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called MELANOSOMES. The large non-mammalian melanin-containing cells are called MELANOPHORES.. hypersensitivity defined as following: Heightened emotional reactivity to environmental stimuli, including emotions of others. [PMID:23250816]. mefloquine defined as following: A phospholipid-interacting antimalarial drug (ANTIMALARIALS). It is very effective against PLASMODIUM FALCIPARUM with very few side effects.. amiodarone defined as following: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.. dyspepsia defined as following: Impaired digestion, especially after eating.. psoralens defined as following: Linear forms of furocoumarins.. sparfloxacin defined as following: A fluoroquinolone antibiotic that inhibits bacterial DNA gyrase, thereby inhibiting DNA replication and transcription. Sparfloxacin was withdrawn from the U.S. market due to a high incidence of phototoxicity.. diclofenac defined as following: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.. nalidixic acid defined as following: A synthetic 1,8-naphthyridine antimicrobial agent with a limited bacteriocidal spectrum. It is an inhibitor of the A subunit of bacterial DNA GYRASE.. photosensitivity defined as following: Increased sensitivity of the skin to light exposure.. anxiety defined as following: Persistent and disabling ANXIETY.. prochlorperazine maleate defined as following: The maleate salt form of prochlorperazine, a synthetic, piperazine phenothiazine derivative with antiemetic, antipsychotic, antihistaminic, and anticholinergic activities. Prochlorperazine binds to and blocks the postsynaptic dopamine D2-receptor in the chemoreceptor trigger zone (CTZ) of the brain and may prevent chemotherapy-induced emesis. Prochlorperazine maleate also blocks anticholinergic and alpha-adrenergic receptors. Its antagonistic actions on the alpha-1 adrenergic receptors results in sedation, muscle relaxation, and hypotension.. enalapril defined as following: An angiotensin-converting enzyme inhibitor that is used to treat HYPERTENSION and HEART FAILURE.. diltiazem defined as following: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.. ceftriaxone defined as following: A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears.. Photosensitivity reactions defined as following: A nonimmunologic, chemically induced type of photosensitivity producing a sometimes vesiculating dermatitis. It results in hyperpigmentation and desquamation of the light-exposed areas of the skin.. Cofactors defined as following: Something that must join with another to produce a given result.. vomiting defined as following: The forcible expulsion of the contents of the STOMACH through the MOUTH.. mefenamic acid defined as following: A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase.. depressed mood defined as following: An emotional state characterized by feelings of sadness, emptiness, and/or tearfulness..", "label": "yes"}
{"id": "converted_1751", "sentence1": "Is Thalidomide currently a marketed drug?", "sentence2": "In this retrospective study, pharmacy claims were analyzed for those patients with a diagnosis of MM who received thalidomide,, The Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome,, Thalidomide could relieve clinical symptoms and intestinal mucosal lesions effectively in children with refractory inflammatory bowel disease (IBD) from the pre-clinical study., Thalidomide is now available as an investigational drug in the USA., The STEPStrade mark (System for Thalidomide Education and Prescribing Safety) Program has been developed by Celgene, the commercial manufacturer of thalidomide, to ensure compliance with prescription and usage protocols., New uses of thalidomide., Thalidomide is an anti-angiogenesis agent that currently is being evaluated in the treatment of various types of cancer., The comeback of thalidomide to the legitimate status of a marketed drug came in 1998 when it received FDA approval for the treatment of erythema nodosum leprosum (ENL), Thalidomide is considered the drug of choice for the treatment of ENL, but for other conditions, it is recommended only when resistance to the currently available form of therapy is encountered, Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy, Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. , In 1998, FDA approved the marketing of thalidomide (Thalomid, Celgene). , In 1998 the US Food and Drug Administration approved thalidomide exclusively for the treatment of ENL, and strict conditions were stipulated for its use in order to prevent teratogenic adverse effects., BACKGROUND: The use of thalidomide during the 1950s resulted in teratogenic effects in thousands of infants. Although thalidomide is currently approved for the treatment of a complication of leprosy, it is commercially available to treat other diseases through a controlled distribution system., The comeback of thalidomide to the legitimate status of a marketed drug came in 1998 when it received FDA approval for the treatment of erythema nodosum leprosum (ENL).[SEP]Relations: Erythema nodosum has relations: drug_effect with Thalidomide, drug_effect with Thalidomide. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. cancer defined as following: A malignant tumor at the original site of growth.. thalidomide defined as following: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. leprosy defined as following: leprosy vaccine
. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. anti-angiogenic drug defined as following: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.. ENL defined as following: Human MLLT1 wild-type allele is located in the vicinity of 19p13.3 and is approximately 70 kb in length. This allele, which encodes protein ENL, plays a role in the activation of transcription by RNA polymerase II. Mixed-lineage leukemias are associated with the translocation t(11;19)(q23;p13.3) of the gene with the MLL gene.. lepromatous leprosy defined as following: A chronic communicable infection which is a principal or polar form of LEPROSY. This disorder is caused by MYCOBACTERIUM LEPRAE and produces diffuse granulomatous skin lesions in the form of nodules, macules, or papules. The peripheral nerves are involved symmetrically and neural sequelae occur in the advanced stage.. IBD defined as following: Gastrointestinal symptoms characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause.. POEMS syndrome defined as following: A multisystemic disorder characterized by a sensorimotor polyneuropathy (POLYNEUROPATHIES), organomegaly, endocrinopathy, monoclonal gammopathy, and pigmentary skin changes. Other clinical features which may be present include EDEMA; CACHEXIA; microangiopathic glomerulopathy; pulmonary hypertension (HYPERTENSION, PULMONARY); cutaneous necrosis; THROMBOCYTOSIS; and POLYCYTHEMIA. This disorder is frequently associated with osteosclerotic myeloma. (From Adams et al., Principles of Neurology, 6th ed, p1335; Rev Med Interne 1997;18(7):553-62). Thalidomide defined as following: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action..", "label": "yes"}
{"id": "converted_2668", "sentence1": "Is the protein pelota a ribosomal rescue factor?", "sentence2": "a novel binding partner of the ribosome recycling protein Pelota, n eukaryotes, Pelota (Dom34 in yeast) and Hbs1 are responsible for solving general problems of ribosomal stall in translation. , In eukaryotes, the protein complex of Pelota (yeast Dom34) and Hbs1 translational GTPase recognizes the stalled ribosome containing the defective mRNA.[SEP]Definitions: GTPase defined as following: Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. ribosomal defined as following: Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm..", "label": "yes"}
{"id": "converted_2517", "sentence1": "Does wheat belongs to the genus Avena, yes or no?", "sentence2": "oat seedlings (Avena sativa), wild green-oat (Avena sativa) , Oat (Avena sativa L.), Oat (Avena sativa L.), Avena (Oats), wild oats (Avena fatua L.), oats (genus Avena), Avena sativa L. and A. byzantina C. Koch) , oat (Avena sativa L.)., oat (Avena sativa L.) and wheat (Triticum aestivum[SEP]Definitions: wheat defined as following: plant genus of the family Poaceae that is the source of wheat grain.. Oat defined as following: Catalysis of the reaction: L-ornithine + a 2-oxo acid = L-glutamate 5-semialdehyde + an L-amino acid. [EC:2.6.1.13]. Avena defined as following: Oats, genus of the family POACEAE..", "label": "no"}
{"id": "converted_2862", "sentence1": "Does lucatumumab bind to CD140?", "sentence2": "Lucatumumab is a fully humanized anti-CD40 antibody that blocks interaction of CD40L with CD40 and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC). , Phase I study of the anti-CD40 humanized monoclonal antibody lucatumumab (HCD122) in relapsed chronic lymphocytic leukemia., Saturation of CD40 receptor on CLL cells was uniform at all doses post-treatment but also persisted at trough time points in the 3.0 mg/kg or greater cohorts.[SEP]Definitions: CD40L defined as following: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.. CD40 defined as following: Members of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. They are found on mature B-LYMPHOCYTES, some EPITHELIAL CELLS; and lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.. chronic lymphocytic leukemia defined as following: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.. lucatumumab defined as following: A fully human monoclonal antibody directed against the B-cell surface antigen CD40 with potential antineoplastic activity. Lucatumumab binds to and inhibits CD40, thereby inhibiting CD40 ligand-induced cell proliferation and triggering cell lysis via antibody-dependent cellular cytotoxicity (ADCC) in cells overexpressing CD40. CD40, an integral membrane protein found on the surface of B lymphocytes, is a member of the tumor necrosis factor receptor superfamily and is highly expressed in a number of B-cell malignancies..", "label": "no"}
{"id": "converted_3952", "sentence1": "Has ubrogepant entered clinical phase III trials?", "sentence2": "Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive phase III outcomes for acute treatment of migraine., A population pharmacokinetic model describing the effect of formulations was included in the E-R simulation framework to assess potential dose implications of a formulation switch from phase II to phase III. , The understanding of E-R helped support the dose selection for the phase III clinical trials., The CGRP receptor antagonist ubrogepant, also known as MK-1602, has been recently evaluated in phase III clinical trials for clinical efficacy and long-term safety as an abortive migraine treatment., Two pivotal phase III clinical trials (ACHIEVE I and ACHIEVE II) demonstrated effectiveness and safety of ubrogepant in acute migraine attacks.[SEP]Definitions: migraine defined as following: A common, severe type of vascular headache often associated with increased sympathetic activity, resulting in nausea, vomiting, and light sensitivity..", "label": "yes"}
{"id": "converted_3058", "sentence1": "Is Miller-Dieker syndrome associated with abnormalities of chromosome 1?", "sentence2": "A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion). , Chromosome microdeletions within 17p13.3 can result in either isolated lissencephaly sequence (ILS) or Miller-Dieker syndrome (MDS). , We report a fetus with lissencephaly diagnosed as Miller-Dieker Syndrome postnatally. G banded chromosome analysis revealed 45,X,psu dic(17;Y)(p13;p11.32).ish dic (17;Y)(LIS1-,RARA+, SRY+, DYZ3+) by G-banding analysis using high resolution banding technique. Fetal delayed cortical development will be the findings to perform further investigations including fluorescence in situ hybridization analysis for MDS, a 17p13.3 microdeletion syndrome, pre/postnatally. This will be the first case of MDS with unbalanced translocation between deleted short arm of chromosome 17 and Y chromosome., We report the finding of a 2.5-Mb gene region quadruplication of Chromosome 17p13.3. This region is well characterized for the deletion leading to Miller-Dieker syndrome but has an unclear replication phenotype. , Both deletions have overlapped with the critical region of Miller-Dieker syndrome (MDS) and involved candidate genes such as PAFAH1B1, YWHAE and CRK. In addition, SNP array and FISH analyses on the parental peripheral blood samples demonstrated that both 17p13.3 and 17p13.3p13.2 deletions were of de novo origin., Miller-Dieker syndrome (MDS) is caused by a heterozygous deletion of chromosome 17p13.3 involving the genes LIS1 and YWHAE (coding for 14.3.3ε) and leads to malformations during cortical development., We studied after death a 3-month-old girl whose karyotype was 45,XX,-15,-17,+der(17),t(15;17)(q13;p13.3) and thus combines abnormalities of chromosome 15 associated with the Prader-Willi syndrome and of chromosome 17 associated with the Miller-Dieker syndrome., The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13., The Miller-Dieker syndrome (type I lissencephaly) is a neuronal migration disorder which is associated with microdeletions in the short arm of chromosome 17., Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome., A 15-month-old girl with Miller-Dieker syndrome, a contiguous gene deletion syndrome involving chromosome 17p13.3 and resulting in lissencephaly, was diagnosed with precursor B-cell acute lymphoblastic leukemia., A computed tomography scan revealed evidence of lissencephaly, and chromosomal analysis showed a microdeletion on the short arm of chromosome 17 (17p13.3), confirming the diagnosis as Miller-Dieker syndrome., Familial Miller-Dieker syndrome associated with pericentric inversion of chromosome 17., The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region., Miller-Dieker syndrome (MDS), a disorder manifesting the severe brain malformation lissencephaly (\"smooth brain\"), is caused, in the majority of cases, by a chromosomal microdeletion of the distal short arm of chromosome 17., The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13., Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment., Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome., HIC1 is a candidate tumor suppressor gene which is frequently hypermethylated in human tumors, and its location within the Miller-Dieker syndrome's critical deletion region at chromosome 17p13.3 makes it a candidate gene for involvement in this gene deletion syndrome., A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion)., About 15% of patients with isolated lissencephaly and more than 90% of patients with Miller-Dieker syndrome have microdeletions in a critical 350-kilobase region in chromosome 17p13.3 (ref., Chromosome aberrations in which epilepsy is a major and consistent finding include Angelman syndrome due to loss of the maternal 15q11.2-q12 segment, tetrasomy of the maternal segment 15pter-q13 due to an additional inv dup chromosome, Miller-Dieker syndrome due to deletion of the 17p13.3 segment including the lissencephaly1 gene, ring chromosome 20, and Wolf-Hirschhorn syndrome due to deletion of at least the 4p16.3 segment., Miller-Dieker syndrome and trisomy 5p in a child carrying a derivative chromosome with a microdeletion in 17p13.3 telomeric to the LIS1 and the D17S379 loci., The Miller-Dieker syndrome, a disorder of neuronal migration, is caused by deletions of chromosome 17p13.3., The girl was diagnosed by subtelomeric FISH and array-CGH, showing a 4.43-Mb heterozygous deletion on chromosome 10p that involved 14 genes and a 3.22-Mb single-copy gain on chromosome 17p, which includes the critical region of the Miller-Dieker syndrome and 61 genes., Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome.The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13. , Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment.Microdeletions of chromosome 17p13.3 involving YWHAE present with growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment. , Unbalanced translocation (15;17)(q13;13.3) with apparent Prader-Willi syndrome but without Miller-Dieker syndrome.We studied after death a 3-month-old girl whose karyotype was 45,XX,-15,-17,+der(17),t(15;17)(q13;p13.3) and thus combines abnormalities of chromosome 15 associated with the Prader-Willi syndrome and of chromosome 17 associated with the Miller-Dieker syndrome. , The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region. , A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3.Miller-Dieker syndrome (MDS) is a multiple malformation syndrome characterized by classical lissencephaly and a characteristic facies. , Case Report of Proliferative Peripheral Retinopathy in Two Familial Lissencephaly Infants with Miller-Dieker Syndrome.A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion). , Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome.Profilin is a conserved actin-monomer-binding protein which is found in all eukaryotes, including yeast. , We propose that essentially no loss of 17p material has occurred and confirm previous reports that the critical region for the production of the Miller-Dieker phenotype is located subterminally in the 17p13.3 region.
, A review of the literature revealed five additional patients in three families, who had Miller-Dieker syndrome and an abnormality of 17p., We propose that essentially no loss of 17p material has occurred and confirm previous reports that the critical region for the production of the Miller-Dieker phenotype is located subterminally in the 17p13.3 region., Miller-Dieker syndrome: lissencephaly and monosomy 17p., Thus, we propose that monosomy of distal 17p may be the cause of Miller-Dieker syndrome in some patients., Miller-Dieker syndrome with der(17)t(12;17)(q24.33;p13.3)pat presenting with a potential risk of mis-identification as a de novo submicroscopic deletion of 17p13.3., Most cases of Miller-Dieker syndrome have a de novo deletion involving 17p13.3.[SEP]Relations: tetrasomy has relations: disease_disease with epilepsy, disease_disease with epilepsy. PAFAH1B1 has relations: anatomy_protein_present with cerebral cortex, anatomy_protein_present with cerebral cortex. epilepsy has relations: disease_disease with tetrasomy, disease_disease with ring chromosome 20, disease_disease with Wolf-Hirschhorn syndrome, disease_disease with Angelman syndrome, disease_disease with tetrasomy, disease_disease with ring chromosome 20, disease_disease with Wolf-Hirschhorn syndrome, disease_disease with Angelman syndrome. cerebral cortex has relations: anatomy_protein_present with YWHAE, anatomy_protein_present with CRK, anatomy_protein_present with PAFAH1B1, anatomy_protein_present with YWHAE, anatomy_protein_present with CRK, anatomy_protein_present with PAFAH1B1. Angelman syndrome has relations: disease_disease with epilepsy, disease_disease with epilepsy. Wolf-Hirschhorn syndrome has relations: disease_disease with epilepsy, disease_disease with epilepsy. ring chromosome 20 has relations: disease_disease with epilepsy, disease_disease with epilepsy. Abnormality of the dentition has relations: disease_phenotype_positive with tetrasomy, disease_phenotype_positive with Prader-Willi syndrome, disease_phenotype_positive with tetrasomy, disease_phenotype_positive with Prader-Willi syndrome. Cognitive impairment has relations: disease_phenotype_positive with tetrasomy, disease_phenotype_positive with tetrasomy. congenital nervous system disorder has relations: disease_disease with Angelman syndrome, disease_disease with ring chromosome 20, disease_disease with tetrasomy, disease_disease with Wolf-Hirschhorn syndrome, disease_disease with Angelman syndrome, disease_disease with ring chromosome 20, disease_disease with tetrasomy, disease_disease with Wolf-Hirschhorn syndrome. Definitions: CRK defined as following: Adapter molecule crk (304 aa, ~34 kDa) is encoded by the human CRK gene. This protein is involved in the modulation of signal transduction.. precursor B-cell acute lymphoblastic leukemia defined as following: A type of ALL characterized by elevated levels of B-cell lymphoblasts in the bone marrow and the blood. [NCIT:C8644]. ILS defined as following: A genetic disorder caused by mutations in the LIS1, XLIS, or TUBA1A genes. It results in brain malformation characterized by the underdevelopment or absence of gyri or ridges in the cerebral cortex. Signs and symptoms include epilepsy and mental retardation.. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. tetrasomy defined as following: The possession of four chromosomes of any one type in an otherwise diploid cell.. segment defined as following: One of the parts into which something naturally divides.. 17p13.3 defined as following: A chromosome band present on 17p. PAFAH1B1 defined as following: This gene is involved in the modulation of neuronal migration.. Chromosome defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. epilepsy defined as following: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313). YWHAE defined as following: 14-3-3 protein epsilon (255 aa, ~29 kDa) is encoded by the human YWHAE gene. This protein plays a role in signal transduction.. cerebral cortex defined as following: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.. 17p defined as following: Mandibular left third molar prosthesis
. Profilin defined as following: This gene plays a role in the regulation of actin polymerization.. 4p16.3 defined as following: A chromosome band present on 4p. neuronal migration disorder defined as following: A diverse group of congenital brain developmental disorders characterized by defects in neuronal migration in the brain during early fetal development. The neuronal migration defects result in brain abnormalities that are usually manifested with mental retardation and epilepsy.. Angelman syndrome defined as following: A syndrome characterized by multiple abnormalities, MENTAL RETARDATION, and movement disorders. Present usually are skull and other abnormalities, frequent infantile spasms (SPASMS, INFANTILE); easily provoked and prolonged paroxysms of laughter (hence \"happy\"); jerky puppetlike movements (hence \"puppet\"); continuous tongue protrusion; motor retardation; ATAXIA; MUSCLE HYPOTONIA; and a peculiar facies. It is associated with maternal deletions of chromosome 15q11-13 and other genetic abnormalities. (From Am J Med Genet 1998 Dec 4;80(4):385-90; Hum Mol Genet 1999 Jan;8(1):129-35). deletions defined as following: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.. Y chromosome defined as following: The male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans and in some other male-heterogametic species in which the homologue of the X chromosome has been retained.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Prader-Willi syndrome defined as following: An autosomal dominant disorder caused by deletion of the proximal long arm of the paternal chromosome 15 (15q11-q13) or by inheritance of both of the pair of chromosomes 15 from the mother (UNIPARENTAL DISOMY) which are imprinted (GENETIC IMPRINTING) and hence silenced. Clinical manifestations include MENTAL RETARDATION; MUSCULAR HYPOTONIA; HYPERPHAGIA; OBESITY; short stature; HYPOGONADISM; STRABISMUS; and HYPERSOMNOLENCE. (Menkes, Textbook of Child Neurology, 5th ed, p229). death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. trisomy 5p defined as following: Duplication of the short arm of chromosome 5 most frequently associated with craniofacial, cardiac, renal, and limb abnormalities, and moderate to severe mental retardation. Dandy-Walker malformation (agenesis of the cerebellar vermis, hydrocephalus, and posterior fossa cyst continuous with the fourth ventricle) occurs in some cases. The phenotype is related to the amount of genetic material duplicated and the specific duplicated segment.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. Wolf-Hirschhorn syndrome defined as following: A syndrome caused by large deletions of the telomereic end of the short arm of CHROMOSOME 4 (4p) in Wolf-Hirchhorn syndrome critial regions (WHSCRs). Several candidate genes have been identified including WHSC1 and WHSCH2 which appear to be responsible for the core phenotype and in combination with other linked and unlinked genes determine the severity and inclusion of rarer phenotypes. Most cases have a characteristic cranio-facial defect often referred to as \"Greek helmet face\" - a combined result of MICROCEPHALY, broad forehead, prominent glabella, HYPERTELORISM, high arched eyebrows, short philtrum and micrognathia. In addition there is mental retardation, growth delays, EPILEPSY, and frequently a wide range of midline and skeletal defects, including HYPOSPADIAS; CONGENITAL HEART DEFECTS; CLEFT LIP; CLEFT PALATE; colobomata; CLUBFOOT; clinodactyly; SCOLIOSIS; and KYPHOSIS.. lissencephaly defined as following: A lissencephaly syndrome characterized by smoothness of the surface of the brain (lissencephaly type I) with thickening of the cerebral cortex (pachygyria), absence of gyri and sulci (agyria), microcephaly, mental retardation, low sloping forehead, and prominent nasal bridge.. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. ring chromosome 20 defined as following: A rare condition in which the two arms of chromosome 20 are fused resulting in a ring chromosome. It is characterized by recurrent seizures with an onset in childhood. Additional features my include microcephaly and short stature.. chromosome 17 defined as following: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.. human defined as following: Members of the species Homo sapiens.. chromosome 17p defined as following: Proximal (short) arm of chromosome 17. MDS defined as following: A rare syndrome caused by deletion of genetic material in the short arm of chromosome 17. It is characterized by an abnormally smooth brain with fewer folds and grooves. It results in intellectual disability, developmental delay, seizures, spasticity, hypotonia, and feeding difficulties. Affected individuals have distinctive facial features that include a prominent forehead, midface hypoplasia, small, upturned nose, low-set ears, small jaw, and thick upper lip.. congenital disorder defined as following: existing at, and usually before, birth; referring to conditions that are present at birth, regardless of their causation; inborn metabolism disorders are generally not treed here.. Miller-Dieker syndrome defined as following: A rare syndrome caused by deletion of genetic material in the short arm of chromosome 17. It is characterized by an abnormally smooth brain with fewer folds and grooves. It results in intellectual disability, developmental delay, seizures, spasticity, hypotonia, and feeding difficulties. Affected individuals have distinctive facial features that include a prominent forehead, midface hypoplasia, small, upturned nose, low-set ears, small jaw, and thick upper lip.. chromosome 1 defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification..", "label": "no"}
{"id": "converted_1334", "sentence1": "Is protein Fbw7 a SCF type of E3 ubiquitin ligase?", "sentence2": "FBW7 (F-box and WD repeat domain-containing 7) is the substrate recognition component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box protein)-type ubiquitin ligase., However, very few E3 ubiquitin ligases are known to target G-CSFR for ubiquitin-proteasome pathway. Here we identified F-box and WD repeat domain-containing 7 (Fbw7), a substrate recognizing component of Skp-Cullin-F box (SCF) E3 ubiquitin Ligase physically associates with G-CSFR and promotes its ubiquitin-mediated proteasomal degradation., FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins., F-box and WD repeat domain-containing 7 (FBW7), the substrate-binding subunit of E3 ubiquitin ligase SCF(FBW7) (a complex of SKP1, cullin-1 and FBW7), plays important roles in various physiological and pathological processes., The tumor suppressor Fbxw7 (also known as Sel-10, hCdc4, hAgo, or Fbw7) is an F-box protein that functions as the substrate-recognition subunit of an SCF ubiquitin ligase complex and targets a group of oncoproteins for degradation. , Fbw7 is the substrate recognition component of the Skp1-Cullin-F-box (SCF)-type E3 ligase complex and a well-characterized tumor suppressor that targets numerous oncoproteins for destruction., Fbw7 is a member of F-box family proteins, which constitute one subunit of Skp1, Cul1, and F-box protein (SCF) ubiquitin ligase complex., The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun., Fbxw7 (also known as Fbw7, SEL-10, hCdc4, or hAgo) is the F-box protein subunit of an Skp1-Cul1-F-box protein (SCF)-type ubiquitin ligase complex that plays a central role in the degradation of Notch family members., The Fbxw7 (F-box/WD repeat-containing protein 7; also called CDC4, Sel10, Ago, and Fbw7) component of the SCF (Skp1/Cullin/F-box protein) E3 ubiquitin ligase complex acts as a tumor suppressor in several tissues and targets multiple transcriptional activators and protooncogenes for ubiquitin-mediated degradation., The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase., We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation., The SCF(Fbw7) ubiquitin ligase complex plays important roles in cell growth, survival, and differentiation via the ubiquitin-proteasome-mediated regulation of protein stability., F-box and WD-40 domain protein 7 (Fbw7) provides substrate specificity for the Skp1-Cullin1-F-box protein (SCF) ubiquitin ligase complex that targets multiple oncoproteins for degradation, including cyclin E, c-Myc, c-Jun, Notch, and mammalian target of rapamycin (mTOR)., Mammalian Fbw7 (also known as Sel-10, hCdc4, or hAgo) is the F-box protein component of an SCF (Skp1-Cul1-F-box protein-Rbx1)-type ubiquitin ligase, and the mouse Fbw7 is expressed prominently in the endothelial cell lineage of embryos., The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase, We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation, Here we identified F-box and WD repeat domain-containing 7 (Fbw7), a substrate recognizing component of Skp-Cullin-F box (SCF) E3 ubiquitin Ligase physically associates with G-CSFR and promotes its ubiquitin-mediated proteasomal degradation, FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins[SEP]Relations: F-box domain binding has relations: molfunc_protein with SKP1, molfunc_protein with SKP1. Definitions: F-box/WD repeat-containing protein 7 defined as following: F-box/WD repeat-containing protein 4 (412 aa, ~46 kDa) is encoded by the human FBXW4 gene. This protein plays a role in both the modulation of protein turnover and the regulation of limb development.. CUL1 defined as following: Cullin-1 (776 aa, ~90 kDa) is encoded by the human CUL1 gene. This protein plays a role in protein ubiquitination and cell cycle regulation.. Fbw7 defined as following: Human FBXW7 wild-type allele is located in the vicinity of 4q31.3 and is approximately 91 kb in length. This allele, which encodes F-box/WD-repeat protein 7, is involved in ubiquitin-dependent protein degradation and has been implicated in the maintenance of genomic integrity.. F-box defined as following: The F-box consists of three helices. The H1 helix packs orthogonally with the H2-H3 antiparallel pair. The F-box domain is a 42-48 amino acid conserved domain found at the N-terminus of F-box proteins. F-box proteins act as adaptor components of the modular E3 ubiquitin ligase SCF complex that functions in phosphorylation mediated ubiquitination. The F-box domain mediates interaction with Skp1, which links F-box proteins to a core ubiquitin-ligase complex composed of Rbx1, cdc53/Cul1 and the E2 conjugating enzyme cdc34. The C-terminal region of F-box proteins are also composed of various modular domain that interact with target substrates, often in a phosphorylation dependant manner.. cyclin E defined as following: A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.. E3 ubiquitin ligases defined as following: A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.. SCF defined as following: Kit ligand (273 aa, ~31 kDa) is encoded by the human KITLG gene. This protein is involved in melanogenesis, hematopoiesis and mast cell development, migration and function.. F-box protein defined as following: F-box only protein 3 (471 aa, ~55 kDa) is encoded by the human FBXO3 gene. This protein plays a role in the regulation of substrate specificity of SCF complexes.. hAgo defined as following: F-box/WD repeat-containing protein 7 (707 aa, ~80 kDa) is encoded by the human FBXW7 gene. This protein plays a role in the regulation of protein ubiquitination.. SKP1 defined as following: S-phase kinase-associated protein 1 (163 aa, ~19 kDa) is encoded by the human SKP1 gene. This protein plays a role in the formation of SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complexes.. oncoproteins defined as following: Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. endothelial cell defined as following: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.. c-Jun defined as following: This gene plays a critical role in transcriptional regulation and cellular growth.. ubiquitin ligase complex defined as following: A protein complex that includes a ubiquitin-protein ligase and enables ubiquitin protein ligase activity. The complex also contains other proteins that may confer substrate specificity on the complex. [GOC:jh2, PMID:9529603]. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. protooncogenes defined as following: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.. mTOR defined as following: Serine/threonine-protein kinase mTOR (2549 aa, ~289 kDa) is encoded by the human MTOR gene. This protein is involved in protein phosphorylation, signaling and cell growth.. E3 ubiquitin ligase defined as following: This gene may play a role in the mediation of proteasomal targeting..", "label": "yes"}
{"id": "converted_2085", "sentence1": "Is Musclin a secretory peptide?", "sentence2": "Musclin is a novel skeletal muscle-derived secretory factor,, Musclin has been described as a muscle-derived secretory peptide, responsive to insulin in vivo, and inducing insulin resistance in vitro., Musclin is a type of muscle-secreted cytokine and its increased gene expression induces insulin resistance in type 2 diabetes. , Musclin is a novel skeletal muscle-derived factor found in the signal sequence trap of mouse skeletal muscle cDNAs., Musclin is a novel skeletal muscle-derived secretory factor found in the signal sequence trap of mouse skeletal muscle cDNAs. , Musclin is a novel skeletal muscle-derived secretory factor that was isolated by our group. [SEP]Definitions: insulin defined as following: A synthetic or animal-derived form of insulin used in the treatment of diabetes mellitus. Therapeutic insulin is formulated to be short-, intermediate- and long-acting in order to individualize an insulin regimen according to individual differences in glucose and insulin metabolism. Therapeutic insulin may be derived from porcine, bovine or recombinant sources. Endogenous human insulin, a pancreatic hormone composed of two polypeptide chains, is important for the normal metabolism of carbohydrates, proteins and fats and has anabolic effects on many types of tissues..", "label": "yes"}
{"id": "converted_1486", "sentence1": "Does ventriculoperitoneal shunt improve normal pressure hydrocephalus?", "sentence2": "Clinical improvement depends not only on the capability to restore the cerebrospinal fluid dynamic, but also on the ability of cerebral parenchyma to recover the metabolic function., After shunting, the global CMRglu significantly increased (2.95 ± 0.44 vs 4.38 ± 0.68, p = 10(-7)) in all INPH patients with a mean percentage value of 48.7%. , Our preliminary data show that changes in the CMRglu are promptly reversible after surgery and that there is a relationship between the early metabolic changes and clinical symptoms, independently from the simultaneous changes in the ventricular size. The remarkable and prompt improvement in the global CMRglu and in symptoms may also have important implications for the current concept of \"neuronal plasticity\" and for the cells' reactivity in order to recover their metabolic function., Outcome of shunting in INPH is most often successful when patients are accurately diagnosed, suitably evaluated for surgical candidacy, and managed carefully throughout the preoperative, surgical, and postoperative periods., The decision to perform the only efficient procedure, i.e., a ventricular shunt operation, depends upon a number of established arguments in favor of that procedure. Clinical improvement, which is often spectacular, can then confirm the diagnosis. , During the 1st postoperative year, there was improvement in the condition of 22 patients (96%) who had received a ventricular shunt; 21 of these patients (91%) remained improved until death or for at least 5 years., Shunt treatment showed an effect on cognitive functions of distractibility of attention and motor speed, but not on intelligence of memory. Three patients deteriorated, eleven remained stable and sixteen showed significant improvement on psychological tests, mainly those for attention, motor speed and memory, but rarely did any improvement of intelligence occur.[SEP]Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. cerebrospinal fluid defined as following: A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES..", "label": "yes"}
{"id": "converted_1548", "sentence1": "Is the gene SLC6A2 associated with orthostatic intolerance?", "sentence2": "Orthostatic intolerance is a debilitating syndrome characterized by tachycardia on assumption of upright posture. The norepinephrine (NE) transporter (NET) has been implicated in a genetic form of the disorder. , Thus attenuated baroreflex function and reduced sympathetic outflow may contribute to the orthostatic intolerance of severe NET deficiency., A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters., Recently, our laboratory reported a polymorphism in the human NET (hNET) gene A457P in an individual with the autonomic disorder orthostatic intolerance (OI). , Nonsynonymous single nucleotide polymorphisms (SNPs) in the human NET (hNET) gene that influence transporter function can contribute to disease, such as the nonfunctional transporter, A457P, identified in orthostatic intolerance. , Orthostatic intolerance is not necessarily related to a specific mutation (Ala457Pro) in the human norepinephrine transporter gene., We propose that chromatin-modifying events associated with SLC6A2 gene suppression may constitute a mechanism of POTS., The goal of the present study was to further characterize the role and regulation of the SLC6A2 gene in POTS., In the absence of altered SLC6A2 gene sequence or promoter methylation, this reduced expression was directly correlated with chromatin modifications. We propose that chromatin-modifying events associated with SLC6A2 gene suppression may constitute a mechanism of POTS., A coding mutation in the norepinephrine transporter gene (SLC6A2) sequence has been reported in 1 family kindred only. The goal of the present study was to further characterize the role and regulation of the SLC6A2 gene in POTS.[SEP]Relations: Defective SLC6A2 causes orthostatic intolerance (OI) has relations: pathway_protein with SLC6A2, pathway_protein with SLC6A2. Definitions: SLC6A2 defined as following: Sodium-dependent noradrenaline transporter (617 aa, ~69 kDa) is encoded by the human SLC6A2 gene. This protein plays a role in the reuptake of norepinephrine by presynaptic cells.. OI defined as following: COLLAGEN DISEASES characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. Most types are autosomal dominant and are associated with mutations in COLLAGEN TYPE I.. human defined as following: Members of the species Homo sapiens.. SLC6A2 gene defined as following: This gene plays a role in neurotransmitter recycling.. norepinephrine transporter gene defined as following: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of noradrenergic neurons. They remove NOREPINEPHRINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. The norepinephrine transporter regulates signal amplitude and duration at noradrenergic synapses and is the target of ADRENERGIC UPTAKE INHIBITORS.. mutant defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. Orthostatic intolerance defined as following: Symptoms of cerebral hypoperfusion or autonomic overaction which develop while the subject is standing, but are relieved on recumbency. Types of this include NEUROCARDIOGENIC SYNCOPE; POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME; and neurogenic ORTHOSTATIC HYPOTENSION. (From Noseworthy, JH., Neurological Therapeutics Principles and Practice, 2007, p2575-2576). polymorphism defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. orthostatic intolerance defined as following: Symptoms of cerebral hypoperfusion or autonomic overaction which develop while the subject is standing, but are relieved on recumbency. Types of this include NEUROCARDIOGENIC SYNCOPE; POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME; and neurogenic ORTHOSTATIC HYPOTENSION. (From Noseworthy, JH., Neurological Therapeutics Principles and Practice, 2007, p2575-2576). gene SLC6A2 defined as following: This gene plays a role in neurotransmitter recycling..", "label": "yes"}
{"id": "converted_1876", "sentence1": "Has small pox been eradicated from the world?", "sentence2": "small pox has been eradicated., smallpox is now eradicated, In May 1980 the World Health Assembly in Geneva announced in solemn form the world-wide eradication of the small-pox and gave recommendations to the member countries for concluding measures concerning the small-pox vaccination, the foundation of vaccine reserves and the control of the epidemiological situation in the world., As a result of vaccination, diseases such as polio and measles have been controlled and small pox has been eradicated, Small pox eradication from the world is the perfect example of the role of mass vaccination of the entire community of the universe. , The French owe a lot to this Central Committee of Vaccine, which greatly contributed to fighting small pox and eradicating the disease finally., Small pox eradication from the world is the perfect example of the role of mass vaccination of the entire community of the universe., Also, the vaccine that Jenner used, which decreased the prevalence of Small Pox worldwide in his own time, and later was used to eradicate Small Pox altogether, is discussed in light of recent data.., the only known cases of smallpox happened from an outbreak in Birmingham, England caused by a laboratory accident in the year of 1979. On May the 8 th 1980 the disease was declared as eliminated from the world by the WHO (WHO-Resolution 33.33).[SEP]Definitions: disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "yes"}
{"id": "converted_1974", "sentence1": "Does mTOR regulate the translation of MAPKAPK2?", "sentence2": "mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype., Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro-tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses., Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1., mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype, Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1, Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1., Both Beclin1-PI3KIII and Beclin1-MAPKAPK2 interactions as were remarkably affected by silencing either ATM or MAPK14.ATM promoted IR-induced autophagy via the MAPK14 pathway, mTOR pathway and Beclin1/PI3KIII complexes., mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype.[SEP]Relations: ZFP36L1 has relations: protein_protein with MAPKAPK2, protein_protein with MAPKAPK2. protein binding has relations: molfunc_protein with ZFP36L1, molfunc_protein with MAPKAPK2, molfunc_protein with ATM, molfunc_protein with ZFP36L1, molfunc_protein with MAPKAPK2, molfunc_protein with ATM. Sirolimus has relations: contraindication with cancer, contraindication with cancer. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. SASP defined as following: Thioredoxin (105 aa, ~12 kDa) is encoded by the human TXN gene. This protein plays a role in redox reactions, signaling and immunity.. mTOR defined as following: Serine/threonine-protein kinase mTOR (2549 aa, ~289 kDa) is encoded by the human MTOR gene. This protein is involved in protein phosphorylation, signaling and cell growth.. transcripts defined as following: The initial RNA molecule produced by transcription.. 4EBP1 defined as following: Human EIF4EBP1 wild-type allele is located in the vicinity of 8p12 and is approximately 30 kb in length. This allele, which encodes eukaryotic translation initiation factor 4E-binding protein 1, plays a role in the regulation of both translation and protein-protein interactions.. RNA-binding protein defined as following: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.. mTOR inhibitor defined as following: Agents that inhibit the activity of TOR SERINE-THREONINE KINASES.. MK2 defined as following: MAP kinase-activated protein kinase 2 (400 aa, ~46 kDa) is encoded by the human MAPKAPK2 gene. This protein is involved in stress responsive signaling.. rapamycin defined as following: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties..", "label": "yes"}
{"id": "converted_4488", "sentence1": "Is Algenpantucel-L effective for pancreatic cancer?", "sentence2": " Median (IQR) overall survival was 14.9 (12.2-17.8) months in the standard group (N=158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) (hazard ratio [HR] 1.02, 95% CI 0.66-1.58; P = 0.98). Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% CI 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05).CONCLUSIONS: Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation., CONCLUSIONS: The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A multi-institutional, phase 3 study is ongoing, CONCLUSIONS: The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve surviva, CONCLUSIONS: Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiatio[SEP]Definitions: pancreatic cancer defined as following: A primary or metastatic malignant tumor involving the pancreas. Representative examples include carcinoma and lymphoma.. HR defined as following: The rapid, localized death of plant cells in response to invasion by a pathogen. [ISBN:0582227089]. PDAC defined as following: A rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Only five cases have been reported so far, two of who were siblings. In the three nonfamilial cases, unilateral pulmonary agenesis and microphthalmia were associated with diaphragmatic hernia and pulmonary vessel agenesis. It has been suggested that two different entities can be distinguished: on one hand, the association of anophthalmia-pulmonary hypoplasia with/without anomalies of the face, heart, spleen and uterus, which may be due to a putative autosomal recessive gene with pleiotropic effects; on the other hand, a sporadic association including pulmonary hypoplasia, anophthalmia, unilateral diaphragmatic defect and agenesis of the pulmonary trunk, which may represent the expression of a developmental field defect. There is evidence that syndromic microphthalmia- is caused by homozygous or compound heterozygous mutation in the STRA6 gene on chromosome 15q24..", "label": "no"}
{"id": "converted_1134", "sentence1": "Are Drosophila ultraconserved elements candidate ncRNAs?", "sentence2": "Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs., Here, we report the discovery and characterization of UCEs from 12 sequenced Drosophila species. We identified 98 elements ≥80 bp long with very high conservation across the Drosophila phylogeny. Population genetic analyses reveal that these UCEs are not present in mutational cold spots. Instead we infer that they experience a level of selective constraint almost 10-fold higher compared with missense mutations in protein-coding sequences, which is substantially higher than that observed previously for human UCEs. About one-half of these Drosophila UCEs overlap the transcribed portion of genes, with many of those that are within coding sequences likely to correspond to sites of ADAR-dependent RNA editing. For the remaining UCEs that are in nongenic regions, we find that many are potentially capable of forming RNA secondary structures. Among ten chosen for further analysis, we discovered that the majority are transcribed in multiple tissues of Drosophila melanogaster. We conclude that Drosophila species are rich with UCEs and that many of them may correspond to novel noncoding RNAs., Highly Constrained Intergenic Drosophila Ultraconserved Elements Are Candidate ncRNAs[SEP]Definitions: conservation defined as following: The maintenance of certain characteristics in an unchanged condition..", "label": "yes"}
{"id": "converted_3357", "sentence1": "Is SARS virus interacting with ACE2 encoded protein?", "sentence2": "The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition, The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism., Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, Angiotensin-converting enzyme 2 (ACE2), a relatively new member of the RAS, has drawn extensive attention since 2003, because of the findings that ACE2 is the receptor for SARS Corona virus and that maintenance of normal ACE2 levels in the lung is beneficial for the host to combat inflammatory lung disease., The infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2).[SEP]Relations: peptidyl-dipeptidase activity has relations: molfunc_protein with ACE2, molfunc_protein with ACE2. Definitions: infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. ACE2 defined as following: Angiotensin-converting enzyme 2 (805 aa, ~92 kDa) is encoded by the human ACE2 gene. This protein plays a role in both vasodilation and protein cleavage.. angiotensin-converting enzyme 2 defined as following: A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of ANGIOTENSIN I to ANGIOTENSIN II, with increase in vasoconstrictor activity, but no action on angiotensin II. It is also able to inactivate BRADYKININ, a potent vasodilator; and has a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. (From https://www.uniprot.org April 15, 2020).. SARS defined as following: A species of CORONAVIRUS causing atypical respiratory disease (SEVERE ACUTE RESPIRATORY SYNDROME) in humans. The organism is believed to have first emerged in Guangdong Province, China, in 2002. The natural host is the Chinese horseshoe bat, RHINOLOPHUS sinicus..", "label": "yes"}
{"id": "converted_1971", "sentence1": "Is golimumab effective for ulcerative colitis?", "sentence2": "Initial experience with golimumab in clinical practice for ulcerative colitis., BACKGROUND: Golimumab is a TNF-blocking agent indicated as a second-line therapy in ulcerative colitis., CONCLUSIONS: In this short study, golimumab seems to be an alternative treatment in naive and non-naive anti-TNF ulcerative colitis patients., Cost-Effectiveness Analysis of 1-Year Treatment with Golimumab/Standard Care and Standard Care Alone for Ulcerative Colitis in Poland., OBJECTIVE: The objective of this study was to assess the cost-effectiveness of induction and maintenance treatment up to 1 year of ulcerative colitis with golimumab/standard care and standard care alone in Poland., CONCLUSIONS: The biologic treatment of ulcerative colitis patients with golimumab/standard care is more effective but also more costly compared with standard care alone., Currently, infliximab, adalimumab, and golimumab are available in the East Asian medical market, and these agents have been shown to be effective for inducing and maintaining long-term remission of IBD., Furthermore, upcoming treatments are introduced, such as golimumab, vedolizumab, AJM300, tofacitinib., CONCLUSIONS: No significant differences in efficacy in the maintenance phase between infliximab and golimumab or adalimumab were revealed. Infliximab proved to be more effective than adalimumab but of similar efficacy to that of golimumab in the induction phase., In this review, we will provide a detailed discussion of the three tumor necrosis factor-alpha (TNF-α) inhibitors currently approved for treatment of ulcerative colitis: infliximab, adalimumab, and golimumab., Golimumab, a human anti-TNF antibody, is effective in patients with ulcerative colitis, according to new findings from an international phase III double-blind trial., Golimumab for moderately to severely active ulcerative colitis., Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis., Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis., Subcutaneous golimumab, a fully human monoclonal antibody to tumor necrosis factor-α (TNFα), was evaluated as maintenance therapy in TNFα antagonist-naive adults with moderate-to-severe active ulcerative colitis, despite conventional therapy, who responded to golimumab induction therapy.We performed a phase 3, double-blind trial of patients who completed golimumab induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment, eg, PURSUIT), Golimumab, a human anti-TNF antibody, is effective in patients with ulcerative colitis, according to new findings from an international phase III double-blind trial, The purpose of this review was to describe the management of ulcerative colitis with emphasis on the use of anti-tumor necrosis factor (TNF) agents.Recent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis, Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options, The required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively.This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis, The biosimilar of infliximab is as effective and as safe as its originator in rheumatologic conditions, while a new anti-TNF agent, namely golimumab, has been recently approved for refractory ulcerative colitis, We evaluated subcutaneous golimumab induction therapy in TNF-α antagonist-naïve patients with moderate-to-severe UC despite conventional treatment. , Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options., The purpose of this review was to describe the management of ulcerative colitis with emphasis on the use of anti-tumor necrosis factor (TNF) agents.Recent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis., Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options., The biosimilar of infliximab is as effective and as safe as its originator in rheumatologic conditions, while a new anti-TNF agent, namely golimumab, has been recently approved for refractory ulcerative colitis., The incremental cost-utility ratio of golimumab/standard care compared to the standard care alone is estimated to be 391,252 PLN/QALY gained (93,155 €/QALYG) from public payer perspective and 374,377 PLN/QALY gained (89,137 €/QALYG) from social perspective.The biologic treatment of ulcerative colitis patients with golimumab/standard care is more effective but also more costly compared with standard care alone., The required sample sizes for direct head-to-head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively.This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis., Recently, 2 new antibodies have been approved: golimumab is a new option for ulcerative colitis and with another more selective mechanism of action; vedolizumab could be useful for ulcerative colitis as well as Crohn's disease., The present review summarizes the literature on the role of golimumab, a new anti TNF agent, in ulcerative colitis.Literature search was done on PubMed using the search terms 'golimumab' AND 'ulcerative colitis' from inception till March 2016., The aim of this systematic review was to evaluate the efficacy and safety of biological agents (vedolizumab, abatacept, visilizumab, golimumab) in patients with active moderate to severe ulcerative colitis.This paper was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines., Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options., BACKGROUND & AIMS: Subcutaneous golimumab, a fully human monoclonal antibody to tumor necrosis factor-á (TNFá), was evaluated as maintenance therapy in TNFá antagonist-naive adults with moderate-to-severe active ulcerative colitis, despite conventional therapy, who responded to golimumab induction therapy.METHODS: We performed a phase 3, double-blind trial of patients who completed golimumab induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment, eg, PURSUIT)., BACKGROUND & AIMS: Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) -á, for treatment of ulcerative colitis (UC)., This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis., Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options.., Recent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis., Golimumab for moderately to severely active ulcerative colitis., Initial experience with golimumab in clinical practice for ulcerative colitis., Golimumab was found to be effective and safe in inducing and maintaining clinical remission, clinical response and mucosal healing in patients with UC in the two registration trials., [Golimumab Therapy in Ulcerative Colitis]., Golimumab: clinical update on its use for ulcerative colitis., This review will focus on golimumab therapy in ulcerative colitis., To assess golimumab pharmacokinetics [PK] and exposure-response [ER] in adults with moderate-to-severe ulcerative colitis [UC] from the Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment [PURSUIT] studies.[SEP]Relations: ulcerative colitis (disease) has relations: disease_protein with TNF, disease_protein with TNF. Visilizumab has relations: drug_drug with Vedolizumab, drug_drug with Golimumab, drug_drug with Vedolizumab, drug_drug with Golimumab. Abatacept has relations: drug_drug with Vedolizumab, drug_drug with Golimumab, drug_drug with Vedolizumab, drug_drug with Golimumab. Vedolizumab has relations: drug_drug with Golimumab, drug_drug with Golimumab. Infliximab has relations: drug_protein with TNF, drug_drug with Vedolizumab, drug_drug with Golimumab, drug_protein with TNF, drug_drug with Vedolizumab, drug_drug with Golimumab. Adalimumab has relations: drug_protein with TNF, drug_drug with Golimumab, drug_drug with Vedolizumab, drug_protein with TNF, drug_drug with Golimumab, drug_drug with Vedolizumab. Tofacitinib has relations: drug_drug with Vedolizumab, drug_drug with Golimumab, drug_drug with Vedolizumab, drug_drug with Golimumab. Golimumab has relations: drug_protein with TNF, drug_drug with Vedolizumab, drug_protein with TNF, drug_drug with Vedolizumab. Definitions: Ulcerative Colitis defined as following: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.. visilizumab defined as following: A humanized, non-Fc receptor (FcR)-binding IgG2 monoclonal antibody (MoAb) directed against CD3 with potential immunosuppressive activity. Visilizumab binds to invariant CD3 epsilon, one of the non-covalently-associated subunits of T-cell receptors (TCRs) on activated T-cells. Upon binding to the TCR/CD3 complex, visilizumab induces apoptosis, which may result in the selective clonal deletion of activated pathogenic T-cells. This MoAb is engineered with a substitution at amino acid residues 234 and 237 (Val3Ala) within the IgG2 Fc arm, rendering it unable to bind to type II FcRs; accordingly, this agent is less likely to activate type II FcR-expressing resting T-cells.. ADA defined as following: Catalysis of the reaction: acetaldehyde + CoA + NAD+ = acetyl-CoA + NADH + H+. [EC:1.2.1.10]. ER defined as following: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed). human defined as following: Members of the species Homo sapiens.. abatacept defined as following: A soluble fusion protein consisting of the extracellular domain of human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1) with immunosuppressive activity. Abatacept binds CD80 and CD86 on antigen presenting cells (APCs), blocking interaction with CD28 on T lymphocytes, which initiates a co-stimulatory signal required for full activation of T lymphocytes.. TNF defined as following: A recombinant therapeutic agent which is chemically identical to or similar to one of a number of endogenous tumor necrosis factor (TNF) proteins. TNF family cytokines bind to and activate specific cell-surface receptors, thereby mediating inflammatory processes, cell proliferation, immunity, angiogenesis, and tumor cell cytotoxicity. One primary antitumor effect of TNFs involves stimulation of T cell-mediated antitumor cytotoxicity.. Vedolizumab defined as following: A recombinant humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against the human lymphocyte Peyer's patch adhesion molecule 1 (LPAM-1; alpha4beta7; a4b7), with immunomodulating, anti-inflammatory, and potential antineoplastic activities. Upon administration, vedolizumab selectively binds to integrin a4b7 and prevents the binding of a4b7, expressed on the surface of a subset of T-lymphocytes, to its natural ligand, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is mainly expressed on the surface of gut endothelial cells. This prevents a4b7-mediated signaling, adhesion of lymphocytes to the endothelium and the migration of T-lymphocytes across the endothelium into inflamed gastrointestinal (GI) tissue. By preventing this infiltration to the affected area, inflammation is reduced. The human lymphocyte a4b7 integrin, plays a key role in gastrointestinal (GI) inflammation; it is overexpressed in certain types of cancer cells. The alpha4beta7/MAdCAM-1 signaling pathway plays a critical role in the homing of T-lymphocytes to intestinal tissue.. tumor necrosis factor defined as following: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.. infliximab defined as following: A chimeric monoclonal antibody to TNF-ALPHA that is used in the treatment of RHEUMATOID ARTHRITIS; ANKYLOSING SPONDYLITIS; PSORIATIC ARTHRITIS and CROHN'S DISEASE.. PK defined as following: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.. adalimumab defined as following: A recombinant, human IgG1 monoclonal antibody directed against tumor necrosis factor-alpha (TNF-alpha), with immunomodulating activity. Upon administration, adalimumab binds to TNF-alpha, thereby preventing its binding to the p55 and p75 TNF cell surface receptors and inhibiting TNF-mediated immune responses. TNF-alpha, a pro-inflammatory cytokine, is upregulated in various autoimmune diseases.. IBD defined as following: Gastrointestinal symptoms characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause.. tofacitinib defined as following: An orally available inhibitor of Janus kinases (JAK), with immunomodulatory and anti-inflammatory activities. Upon administration, tofacitinib binds to JAK and prevents the activation of the JAK-signal transducers and activators of transcription (STAT) signaling pathway. This may decrease the production of pro-inflammatory cytokines, such as interleukin (IL)-6, -7, -15, -21, interferon-alpha and -beta, and may prevent both an inflammatory response and the inflammation-induced damage caused by certain immunological diseases. JAK kinases are intracellular enzymes involved in signaling pathways affecting hematopoiesis, immunity and inflammation.. Golimumab defined as following: A human monoclonal antibody directed against the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) with immunosuppressive activity. Golimumab binds to TNF-a, thereby preventing TNF-a-mediated immune responses. TNF-a production is dysregulated in various auto-immune diseases and in cancer.. golimumab defined as following: A human monoclonal antibody directed against the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) with immunosuppressive activity. Golimumab binds to TNF-a, thereby preventing TNF-a-mediated immune responses. TNF-a production is dysregulated in various auto-immune diseases and in cancer.. ulcerative colitis defined as following: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN..", "label": "yes"}
{"id": "converted_3033", "sentence1": "Is there a link between BCL11B haploinsufficiency and syndromic neurodevelopmental delay?", "sentence2": "BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells., Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B. Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency. Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo. A further frameshift mutation was transmitted from a similarly affected mother. Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient. Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice. Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice. Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. In addition, we suggest that missense mutations affecting specific sites within zinc-finger domains might result in distinct and more severe clinical outcomes., Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. , Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay.[SEP]Definitions: frameshift mutations defined as following: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.. BCL11B defined as following: B-cell lymphoma/leukemia 11B (894 aa, ~96 kDa) is encoded by the human BCL11B gene. This protein may play a role in the modulation of p53-mediated signaling, tumor suppression and T cell development.. immune deficiency defined as following: Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.. T lymphocyte defined as following: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.. speech impairment defined as following: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language.. neurodevelopmental disorder defined as following: A childhood disorder that has a neurological basis and manifests as a developmental disability.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. intellectual disability defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28).", "label": "no"}
{"id": "converted_2428", "sentence1": "Is autosomal dominant inheritanced form of Osteogenesis imperfecta caused by mutations in the genes associated with collagen production?", "sentence2": "steogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations inCOL1A1orCOL1A2and show autosomal dominant inheritance,, Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by decreased bone mass and increased fracture risk. The majority of OI cases have an autosomal dominant pattern of inheritance and are usually caused by mutations in genes encoding type I collagen, Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by low bone mass and recurrent fractures. Most OI cases follow an autosomal dominant pattern of inheritance and are attributed to mutations in genes encoding type I collagen (COL1A1/COL1A2). , Osteogenesis imperfecta (OI) is a genetic disorder characterised by low bone mineral density resulting in fractures. 85-90% of patients with OI carry a variant in the type 1 collagen genes, COL1A1 and COL1A2, which follows an autosomal dominant pattern of inheritance., Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders that are characterized by susceptibility to bone fractures, and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Most patients have defects in type I collagen biosynthesis with autosomal-dominant inheritance, but many autosomal-recessive genes have been reported., To investigate mutation of COL1A1 gene and analyze the relationship between genotype and clinical phenotype in a family with osteogenesis imperfecta, Dominant inheritance of osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2, the genes that encode type I collagen,, Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. It exhibits a broad spectrum of clinical severity, ranging from multiple fractures in utero and perinatal death, to normal adult stature and low fracture incidence. Extra-skeletal features of OI include blue sclera, hearing loss, skin hyperlaxity, joint hyperextensibility, and dentinogenesis imperfecta. The proα1(I) and proα2(I) chains of collagen 1 are encoded by the COL1A1 and COL1A2 genes, respectively; quantitative or qualitative defects in type I collagen synthesis usually manifest as types of OI or some sub-types of EDS. The majority of patients (about 90%) with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2, Osteogenesis imperfecta (OI) type I is characterized by bone fragility without significant deformity, osteopenia, normal stature, blue sclerae, and autosomal dominant inheritance. Dermal fibroblasts from most affected individuals produce about half the expected amount of type I collagen, suggesting that the OI type I phenotype results from a variety of mutations which alter the apparent expression of either COL1A1 or COL1A2, the genes encoding the chains of type I collagen., Autosomal dominant osteogenesis imperfecta is caused by mutations in the COL1A2 and COL1A1 genes of type I collagen. , Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure., Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, mainly caused by mutations in the collagen type I genes (COL1A1 and COL1A2)., Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen., In approximately 90% of individuals with osteogenesis imperfecta, mutations in either of the genes encoding the pro-alpha1 or pro-alpha2 chains of type I collagen (COL1A1 or COL1A2) can be identified., Autosomal dominant OI is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen., ext-generation sequencing technology was used to screen a panel of known OI genes.RESULTS: In 41 probands, we identified 28 different disease-causing variants of 9 different known OI genes. Eleven of the variants are novel. Ten of the 28 variants are located in COL1A1, five in COL1A2, three in BMP1, three in FKBP10, two in TMEM38B, two in P3H1, and one each in CRTAP, SERPINF1, and SERPINH1. , Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disorder associated with bone fragility and susceptibility to fractures after minimal trauma. OI type V has an autosomal-dominant pattern of inheritance and is not caused by mutations in the type I collagen genes COL1A1 and COL1A2. , Detection of a high frequency RsaI polymorphism in the human pro alpha 2(I) collagen gene which is linked to an autosomal dominant form of osteogenesis imperfecta., Osteogenesis imperfecta due to recurrent point mutations at CpG dinucleotides in the COL1A1 gene of type I collagen., Osteogenesis imperfecta (OI), commonly known as \"brittle bone disease\", is a dominant autosomal disorder characterized by bone fragility and abnormalities of connective tissue. Biochemical and molecular genetic studies have shown that the vast majority of affected individuals have mutations in either the COL1A1 or COL1A2 genes that encode the chains of type I procollagen. , Osteogenesis imperfecta is normally caused by an autosomal dominant mutation in the type I collagen genes COL1A1 and COL1A2.[SEP]Relations: collagen type I trimer has relations: cellcomp_protein with COL1A2, cellcomp_protein with COL1A1, cellcomp_protein with COL1A2, cellcomp_protein with COL1A1, cellcomp_protein with COL1A2, cellcomp_protein with COL1A1, cellcomp_protein with COL1A2, cellcomp_protein with COL1A1. Hearing impairment has relations: disease_phenotype_positive with dentinogenesis imperfecta, disease_phenotype_positive with dentinogenesis imperfecta. COL1A1 has relations: anatomy_protein_present with connective tissue, protein_protein with COL1A2, anatomy_protein_present with connective tissue, protein_protein with COL1A2. Autosomal dominant inheritance has relations: disease_phenotype_positive with dentinogenesis imperfecta, disease_phenotype_positive with dentinogenesis imperfecta. osteogenesis imperfecta has relations: disease_protein with COL1A2, disease_protein with SERPINH1, disease_protein with SERPINF1, disease_protein with TMEM38B, disease_protein with COL1A1, disease_protein with BMP1, disease_protein with COL1A2, disease_protein with SERPINH1, disease_protein with SERPINF1, disease_protein with TMEM38B, disease_protein with COL1A1, disease_protein with BMP1, disease_protein with COL1A2, disease_protein with SERPINH1, disease_protein with SERPINF1, disease_protein with TMEM38B, disease_protein with COL1A1, disease_protein with BMP1, disease_protein with COL1A2, disease_protein with SERPINH1, disease_protein with SERPINF1, disease_protein with TMEM38B, disease_protein with COL1A1, disease_protein with BMP1. TMEM38B has relations: anatomy_protein_present with connective tissue, anatomy_protein_present with connective tissue. SERPINF1 has relations: anatomy_protein_present with connective tissue, anatomy_protein_present with connective tissue. connective tissue has relations: anatomy_protein_present with COL1A1, anatomy_protein_present with COL1A2, anatomy_protein_present with SERPINH1, anatomy_protein_present with TMEM38B, anatomy_protein_present with BMP1, anatomy_protein_present with SERPINF1, anatomy_protein_present with COL1A1, anatomy_protein_present with COL1A2, anatomy_protein_present with SERPINH1, anatomy_protein_present with TMEM38B, anatomy_protein_present with BMP1, anatomy_protein_present with SERPINF1. Hyperextensibility at elbow has relations: disease_phenotype_positive with dentinogenesis imperfecta, disease_phenotype_positive with dentinogenesis imperfecta. Blue sclerae has relations: disease_phenotype_positive with dentinogenesis imperfecta, disease_phenotype_positive with dentinogenesis imperfecta. SERPINH1 has relations: anatomy_protein_present with connective tissue, anatomy_protein_present with connective tissue. Definitions: variant defined as following: An alteration or difference from a norm or standard.. type I collagen defined as following: The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.. hearing loss defined as following: Partial or complete loss of the ability to detect or understand sounds resulting from damage to the outer, middle, or inner ear structures. Causes include exposure to loud noise, ear infections, injuries to the ear, genetic, and congenital disorders.. COL1A1 defined as following: This gene plays an important structural role in cartilage and mutations in the gene are associated with osteogenesis imperfecta.. collagen defined as following: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).. autosomal dominant inheritance defined as following: A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. [HPO:curators]. Osteogenesis imperfecta defined as following: COLLAGEN DISEASES characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. Most types are autosomal dominant and are associated with mutations in COLLAGEN TYPE I.. trauma defined as following: Nurses in this specialty provide emergency care to patients of all ages. These nurses work to maintain vital signs and prevent complications and death. BMP1 defined as following: Bone morphogenetic protein 1 (986 aa, ~111 kDa) is encoded by the human BMP1 gene. This protein is involved in the processing of collagen fibrils during skeletal development.. SERPINF1 defined as following: This gene is involved in the regulation of cell proliferation.. genotype defined as following: The determination of the DNA sequence of an individual.. connective tissue defined as following: Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. autosomal defined as following: Any chromosome other than a sex chromosome. [GOC:mah]. death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. autosomal dominant defined as following: A rare distal arthrogryposis syndrome with characteristics of multiple pterygia (typically involving the neck, axilla and popliteal areas), joint contractures, ptosis, camptodactyly of the hands with hypoplastic flexion creases, vertebral fusions, severe scoliosis and short stature. There is evidence this disease is caused by heterozygous mutation in the MYH3 gene on chromosome 17p13.. hereditary disorders defined as following: Genetic diseases are diseases in which inherited genes predispose to increased risk. The genetic disorders associated with cancer often result from an alteration or mutation in a single gene. The diseases range from rare dominant cancer family syndrome to familial tendencies in which low-penetrance genes may interact with other genes or environmental factors to induce cancer. Research may involve clinical, epidemiologic, and laboratory studies of persons, families, and populations at high risk of these disorders.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. blue sclerae defined as following: An abnormal bluish coloration of the sclera. [HPO:probinson]. dentinogenesis imperfecta defined as following: Dentinogenesis imperfecta type 2 (DGI-2) is a rare, severe form of dentinogenesis imperfecta (DGI, see this term) and is characterized by weakness and discoloration of all teeth.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. fracture defined as following: A traumatic injury to the bone in which the continuity of the bone is broken.. polymorphism defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. osteopenia defined as following: Decreased calcification or density of bone tissue..", "label": "yes"}
{"id": "converted_4367", "sentence1": "Can bergapten cross the blood-brain barrier?", "sentence2": "Moreover, pharmacokinetic studies showed that bergapten has higher absolute bioavailability and can cross the blood-brain barrier and has a great potential for treating brain disease, but the mechanism needs further clarification to make greater use of its ability to treat brain diseases. [SEP]Definitions: bergapten defined as following: A linear furanocoumarin that has phototoxic and anti-inflammatory properties, with effects similar to METHOXSALEN. It is used in PUVA THERAPY for the treatment of PSORIASIS.. brain disease defined as following: Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM..", "label": "yes"}
{"id": "converted_848", "sentence1": "Is there a pharmacogenetic test for trastuzumab?", "sentence2": "The clinical need for novel approaches to improve drug therapy derives from the high rate of adverse reactions to drugs and their lack of efficacy in many individuals that may be predicted by pharmacogenetic testing., the assessment of the human epidermal growth factor receptor (HER-2) expression for trastuzumab therapy of breast cancer, HER2 positive breast cancer and the use of the drug Herceptin, The dependence on gene copy number or expression levels of HER2 and epidermal growth factor receptor (EGFR) for therapeutic efficacy of trastuzumab and cetuximab (Erbitux), respectively, supports the importance of selecting suitable patient populations based on their pharmacogenetic profile., to explore informed consent issues surrounding the use of the drug Herceptin, widely cited as an example of a novel approach to drug development called pharmacogenetics. Drawing on qualitative semi-structured interviews with 25 UK-based breast cancer specialists, this paper explores Herceptin's disputed epistemological status, as an example of pharmacogenetics or as something out of the ordinary in terms of clinical practice., There have been several success stories in the field of pharmacogenetics in recent years, including the analysis of HER2 amplification for trastuzumab selection in breast cancer, Trastuzumab is standard of care in the treatment of human epidermal growth factor receptor (HER)-2⁺ early and advanced breast cancer., HER-2 overexpression as a predictor of response to trastuzumab, Pharmacogenomic analysis aspires to identify individuals with specific genetic characteristics in order to predict a positive response or reduce a negative response to a therapeutic modality., Assays are available to detect the HER2 protein receptor or copies of the HER2 gene sequence to determine eligibility for Herceptin treatment or adriamycin treatment in node positive patients, respectively., Determining the HER2 status of breast carcinomas is a prerequisite for the use of the monoclonal antibody trastuzumab (Herceptin), which has recently been licensed for the treatment of metastatic disease., Laboratory testing of HER2/neu in breast carcinoma has become vital to patient care following the approval of trastuzumab as the first therapy to target the HER2/neu oncoprotein., Immunohistochemical (IHC) analysis was performed with use of a diagnostic test for the assessment of HER2 overexpression, the HercepTest., To test for HER-2/neu overexpression in patients with non-Hodgkin's lymphoma and the possible role of the recombinant monoclonal anti-HER-2/neu antibody trastuzumab (Herceptin) in the treatment of non-Hodgkin's lymphoma., To evaluate concordance between local and central laboratory HER2 testing results in patients from the North Central Cancer Treatment Group (NCCTG) N9831 adjuvant trial of trastuzumab., These findings support the importance of using high-volume, experienced laboratories for HER2 testing to improve the process of selecting patients likely to benefit from trastuzumab therapy., we measured trastuzumab levels in the serum and in cerebrospinal fluid of metastatic breast cancer patients with brain metastases receiving trastuzumab for HER2-overexpressing metastatic breast cancer. In a pilot study, metastatic breast cancer patients with brain metastases and HER2-overexpressing tumors (HercepTest; Dako, Copenhagen, Denmark) were included., Monitoring of trastuzumab levels in the serum and cerebrospinal fluid may enable individualized therapy strategies in metastatic breast cancer patients with brain metastases, and lead to a better understanding of trastuzumab pharmacokinetics in the cerebrospinal fluid and serum., Biotin-labeled trastuzumab (BiotHER) can be used to test for HER2 by immunohistochemistry., The results support a role for BiotHER testing in better tailoring trastuzumab-based treatments in patients with advanced HER2-amplified breast cancers., response to anti-human epidermal growth factor receptor 2 (HER2) therapy trastuzumab.[SEP]Relations: Cetuximab has relations: drug_drug with Trastuzumab, drug_protein with EGFR, drug_drug with Trastuzumab, drug_protein with EGFR. Definitions: HER-2/neu defined as following: Human Oncogene ErbB2 is a mutated variant of ERBB2 Gene, which encodes ERRB2 Receptor Protein Tyrosine Kinase, a 185-kDa type I membrane glycoprotein similar to EGFR that controls cell growth. Ligand binding increases ERBB2 tyrosine phosphorylation. A heterodimer with ERBB3 and ERBB4, p185ERBB2 is an essential component of the heregulin/neuregulin receptor. ERBB2 forms an IL6-dependent complex with IL6R gp130, resulting in ERBB2 tyrosine phosphorylation and MAPK activation. Oncogene ERBB2 disrupts normal cell function.. Trastuzumab defined as following: A humanized monoclonal antibody against the ERBB-2 RECEPTOR (HER2). As an ANTINEOPLASTIC AGENT, it is used to treat BREAST CANCER where HER2 is overexpressed.. HER2/neu defined as following: Human ERBB2 wild-type allele is located in the vicinity of 17q21.1 and is approximately 29 kb in length. This allele, which encodes receptor tyrosine-protein kinase erbB-2 protein, plays a role in EGF receptor signal transduction pathways and cellular growth. Amplification or overexpression of this gene is involved in the progression of several forms of cancer, including breast and ovarian tumors.. HER-2 defined as following: A cancer vaccine comprised of peptides derived from the extracellular domain of the tumor-associated antigen Her-2/neu with potential antineoplastic activity. HER-2/neu peptide vaccine may induce antibodies with anti-tumor activity and may also elicit a specific CD8 T-cell response against specific tumor cell types. (NCI04). cetuximab defined as following: A chimeric monoclonal antibody that functions as an ANTINEOPLASTIC AGENT through its binding to the EPIDERMAL GROWTH FACTOR RECEPTOR, where it prevents the binding and signaling action of cell growth and survival factors.. HER2 defined as following: A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.. breast carcinoma defined as following: A carcinoma arising from the breast, most commonly the terminal ductal-lobular unit. It is the most common malignant tumor in females. Risk factors include country of birth, family history, menstrual and reproductive history, fibrocystic disease and epithelial hyperplasia, exogenous estrogens, contraceptive agents, and ionizing radiation. The vast majority of breast carcinomas are adenocarcinomas (ductal or lobular). Breast carcinoma spreads by direct invasion, by the lymphatic route, and by the blood vessel route. The most common site of lymph node involvement is the axilla.. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. cerebrospinal fluid defined as following: A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES.. metastatic disease defined as following: A tumor that has spread from its original (primary) site of growth to another site, close to or distant from the primary site. Metastasis is characteristic of advanced malignancies, but in rare instances can be seen in neoplasms lacking malignant morphology.. trastuzumab defined as following: A humanized monoclonal antibody against the ERBB-2 RECEPTOR (HER2). As an ANTINEOPLASTIC AGENT, it is used to treat BREAST CANCER where HER2 is overexpressed..", "label": "yes"}
{"id": "converted_167", "sentence1": "Is CD84 genetically associated with arthritis?", "sentence2": "The SNP is predicted to disrupt transcription factor binding site motifs in the 3' UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1 × 10(-11) in 228 non-RA patients and P = 0.004 in 132 RA patients), Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity, Three members of this gene family, Ly108, Ly9, and CD84, exhibit polymorphisms that strongly influence susceptibility to systemic autoimmunity, notably in mice, but also in some human populations[SEP]Definitions: peripheral blood mononuclear cells defined as following: A peripheral blood cell with a single nucleus. This category includes lymphocytes and monocytes.. Ly108 defined as following: Human SLAMF6 wild-type allele is located in the vicinity of 1q23.2 and is approximately 38 kb in length. This allele, which encodes SLAM family member 6 protein, plays a role as a coreceptor in natural killer cell activation.. Ly9 defined as following: T-lymphocyte surface antigen Ly-9 (655 aa, ~72 kDa) is encoded by the human LY9 gene. This protein is involved in the positive regulation of helper T-cell Th17 differentiation.. allele defined as following: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.. human defined as following: Members of the species Homo sapiens.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. 3' UTR defined as following: The sequence at the 3' end of messenger RNA that does not code for product. This region contains transcription and translation regulating sequences.. polymorphisms defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. SNP defined as following: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.. etanercept defined as following: A recombinant version of soluble human TNF receptor fused to an IgG FC fragment that binds specifically to TUMOR NECROSIS FACTOR and inhibits its binding with endogenous TNF receptors. It prevents the inflammatory effect of TNF and is used to treat RHEUMATOID ARTHRITIS; PSORIATIC ARTHRITIS and ANKYLOSING SPONDYLITIS.. arthritis defined as following: Acute or chronic inflammation of JOINTS..", "label": "yes"}
{"id": "converted_2955", "sentence1": "Are Copy Number Variants (CNVs) depleted in regions of low mappability?", "sentence2": "Human copy number variants are enriched in regions of low mappability., Applying PopSV to 640 human genomes, we find that low-mappability regions are approximately 5 times more likely to harbor germline CNVs, in stark contrast to the nearly uniform distribution observed for somatic CNVs in 95 cancer genomes. In addition to known enrichments in segmental duplication and near centromeres and telomeres, we also report that CNVs are enriched in specific types of satellite and in some of the most recent families of transposable elements. Finally, using this comprehensive approach, we identify 3455 regions with recurrent CNVs that were missing from existing catalogs. In particular, we identify 347 genes with a novel exonic CNV in low-mappability regions, including 29 genes previously associated with disease., Human copy number variants are enriched in regions of low mappability.Copy number variants (CNVs) are known to affect a large portion of the human genome and have been implicated in many diseases. [SEP]Definitions: variants defined as following: An alteration or difference from a norm or standard.. Human defined as following: Members of the species Homo sapiens.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. transposable elements defined as following: Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.. telomeres defined as following: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs..", "label": "no"}
{"id": "converted_3587", "sentence1": "Does Estrogen lead to forkhead FoxA1 activation?", "sentence2": "We showed that CTCF acts upstream of the \"pioneer\" factor FOXA1 in determining the genomic response to estrogen. , Almost all ER-chromatin interactions and gene expression changes depended on the presence of FOXA1 and FOXA1 influenced genome-wide chromatin accessibility, FOXA1 is a key determinant of estrogen receptor function and endocrine response., As such, FOXA1 is a major determinant of estrogen-ER activity and endocrine response in breast cancer cells., Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response., Furthermore, knockdown of FoxA1 expression blocks the association of ER with chromatin and estrogen-induced gene expression demonstrating the necessity of FoxA1 in mediating an estrogen response in breast cancer cells., FoxA1 determines estrogen receptor action in breast cancer progression, Given previous findings from cell lines, FoxA1 appears to play a critical role in this reprogramming of ER binding., FOXA1 expression can independently predict chemosensitivity of ER-positive breast cancer patients., FOXA1 expression could be a prognostic marker in ER-positive breast cancer., The pioneer transcription factor FoxA1 plays an important role in estrogen signaling by opening closed chromatin and promoting recruitment of the estrogen receptor to its target regions in DNA, The phosphomimetic FoxA1 promoted the activation of estrogen signaling, whereas the nonphosphorylatable FoxA1 suppressed its activation.[SEP]Definitions: estrogen receptor alpha defined as following: One of the ESTROGEN RECEPTORS that has marked affinity for ESTRADIOL. Its expression and function differs from, and in some ways opposes, ESTROGEN RECEPTOR BETA.. CTCF defined as following: CCN family member 2 (349 aa, ~38kDa) is encoded by the human CCN2 gene. This protein plays a role in the promotion of proliferation and differentiation of chondrocytes and also mediates heparin- and divalent cation-dependent cell adhesion in many different cell types.. FoxA1 defined as following: This gene plays a role in the modulation of gene expression.. estrogen receptor defined as following: Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. ER defined as following: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed). domain defined as following: A taxonomic category above that of Kingdom.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. cell lines defined as following: Established cell cultures that have the potential to propagate indefinitely.. FOXA1 defined as following: This gene plays a role in the modulation of gene expression.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. Estrogen defined as following: Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds..", "label": "yes"}
{"id": "converted_813", "sentence1": "Does a selective sweep increase genetic variation?", "sentence2": "An East African population that gave rise to non-Africans underwent a selective sweep affecting the subcentromeric region where MTMR8 is located. This and similar sweeps in four other regions of the X chromosome, documented in the literature, effectively reduced genetic diversity of non-African chromosomes, a selective sweep that has removed genetic variation from much of the drive X chromosome., evidence of reduced diversity and an excess of fixed replacement sites, consistent with a species-wide selective sweep., recent independent selective sweeps in AGO2 have reduced genetic variation, episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity, reduced variation or deviations from neutrality that might indicate a recent selective sweep, Consider a genetic locus carrying a strongly beneficial allele which has recently fixed in a large population. As strongly beneficial alleles fix quickly, sequence diversity at partially linked neutral loci is reduced. This phenomenon is known as a selective sweep., a local selective sweep or demographic process that reduced variability, reduced variation (a selective sweep), the mtDNA diversity, but not the nuclear DNA diversity, has been reduced relative to the neutral expectation of molecular evolution, suggesting the action of a selective sweep, Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations., Our observation of reduction in variation at both intragenic and flanking loci of mutant pfcrt gene confirmed the selective sweep model of natural selection in chloroquine resistant P., A selective sweep describes the reduction of linked genetic variation due to strong positive selection., In these situations, adaptation should commonly produce 'soft' selective sweeps, where multiple adaptive alleles sweep through the population at the same time, either because the alleles were already present as standing genetic variation or arose independently by recurrent de novo mutations., CONCLUSIONS: The severe reduction in nucleotide variation at OsAMT1;1 in rice was caused by a selective sweep around OsAMT1;1, which may reflect the nitrogen uptake system under strong selection by the paddy soil during the domestication of rice., A selective sweep describes the reduction of linked genetic variation due to strong positive selection[SEP]Definitions: AGO2 defined as following: Protein argonaute-2 (859 aa, ~97 kDa) is encoded by the human AGO2 gene. This protein plays a role in RNA catabolism.. allele defined as following: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.. human defined as following: Members of the species Homo sapiens.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. mtDNA defined as following: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. genetic locus defined as following: Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.. X chromosome defined as following: The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species..", "label": "no"}
{"id": "converted_2092", "sentence1": "Can valproic acid prolong survival of glioblastoma patients?", "sentence2": "For patients who presented with epilepsy, the use of the antiepileptic drug VPA did not associate with survival when compared with patients who did not receive VPA treatment., This prognostic effect is not solely explained by early diagnosis, and survival is not associated with VPA treatment., Several in vivo and in vitro studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons. The results of several retrospective studies have also indicated potential benefit to improve survival of patients with GBM. Moreover, the promising treatment results of a phase 2 trial of concurrent radiation therapy, temozolomide, and VPA for patients with GBM have been recently reported. , While there have not been any novel anti-GBM therapeutics approved for many years, there has been the gradual accumulation of clinical data suggesting that the widely used anti-convulsant agent, valproic acid (VPA) may significantly prolong survival in GBM patients., Additionally, VPA may result in improved outcomes compared to historical data and merits further study., Several retrospective studies in seizure patients with glioblastoma treated with chemotherapy have provided evidence for a moderately improved survival with the use of valproic acid, possibly due to inhibition of histone deacetylase, Several clinical studies have reported that valproic acid could prolong survival of GBM patients, While there have not been any novel anti-GBM therapeutics approved for many years, there has been the gradual accumulation of clinical data suggesting that the widely used anti-convulsant agent, valproic acid (VPA) may significantly prolong survival in GBM patients, Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma, Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma., Valproic acid use during radiation therapy for glioblastoma associated with improved survival., Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93). , Several retrospective studies in seizure patients with glioblastoma treated with chemotherapy have provided evidence for a moderately improved survival with the use of valproic acid, possibly due to inhibition of histone deacetylase., Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma.To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation T, Several clinical studies have reported that valproic acid could prolong survival of GBM patients., Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93).VPA may be preferred over an EIAED in patients with glioblastoma who require an AED during TMZ-based chemoradiotherapy., The combination of radiotherapy, temozolomide and valproic acid (VPA) has shown some promise in retrospective analyses of patients with glioblastoma, although their mechanisms of action remain unknown.We investigated the in vitro and in vivo effects of pretreating glioma cells with temozolomide and VPA as an immunization strategy to boost an adaptive immune response in a syngeneic mouse model.Temozolomide and VPA induced autophagy in GL261 glioma cells, and caused tumor antigen-specific T-cells to become activated effector T-cells., Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma.[SEP]Definitions: VPA defined as following: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.. GBM defined as following: A sheet of amorphous extracellular material upon which the basal surfaces of epithelial cells rest and is the covering surface of a glomerular capillary, interposed between the cellular elements and the underlying connective tissue.. glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). gliomas defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). temozolomide defined as following: A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA.. histone deacetylase defined as following: Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes.. Cilengitide defined as following: A cyclic Arg-Gly-Asp peptide with potential antineoplastic activity. Cilengitide binds to and inhibits the activities of the alpha(v)beta(3) and alpha(v)beta(5) integrins, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis. (NCI04). epilepsy defined as following: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313). chemoradiotherapy defined as following: Treatment that combines chemotherapy with radiotherapy.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. seizure defined as following: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\". valproic acid defined as following: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS..", "label": "yes"}
{"id": "converted_508", "sentence1": "Does cortical spreading depression appear in ischemic penumbra following ischemic stroke?", "sentence2": "During the subacute phase, the irreversible damage expands into the penumbra: multiple electrical and biological signals are triggered by periinfarct, spreading depression-like depolarizations leading to hypoxia and stepwise increase in lactate., Experimental and clinical studies indicate that waves of cortical spreading depolarization (CSD) appearing in the ischemic penumbra contribute to secondary lesion growth., Analysis of MCA occlusions (MCAOs) revealed a first CSD wave starting off during ischemic decline at the emerging core region, propagating concentrically over large portions of left cortex., Subsequent recurrent waves of CSD did not propagate concentrically but preferentially circled around the ischemic core., In the vicinity of the core region, CSDs were coupled to waves of predominantly vasoconstrictive CBF(LSF) responses, resulting in further decline of CBF in the entire inner penumbra and in expansion of the ischemic core., We conclude that CSDs and corresponding CBF responses follow a defined spatiotemporal order, and contribute to early evolution of ischemic territories., Astrocytes in the metabolically compromised ischemic penumbra-like area showed a long lasting swelling response to spontaneous spreading depolarizations despite rapid dendritic recovery in a photothrombotic occlusion model of focal stroke., Spontaneous spreading depolarizations (SDs) occur in the penumbra surrounding ischemic core., These SDs, often referred to as peri-infarct depolarizations, cause vasoconstriction and recruitment of the penumbra into the ischemic core in the critical first hours after focal ischemic stroke; however, the real-time spatiotemporal dynamics of SD-induced injury to synaptic circuitry in the penumbra remain unknown., We propose that metabolic stress resulting from recurring SDs facilitates acute injury at the level of dendrites and dendritic spines in metabolically compromised tissue, expediting penumbral recruitment into the ischemic core., Although the mechanism remains unknown, SDs show delayed electrophysiological recovery within the ischemic penumbra., Spreading depression-like peri-infarct depolarizations not only characterize but also worsen penumbra conditions in cortical border zones of experimental focal ischemia., We conclude that in focal ischemia, transient peri-infarct depolarizations emerge not only in cortical but also in striatal gray matter, thereby demonstrating the existence of subcortical zones of ischemic penumbra., Spreading depression (SD) has been demonstrated following focal ischemia, and the additional workload imposed by SD on a tissue already compromised by a marked reduction in blood flow may contribute to the evolution of irreversible damage in the ischemic penumbra., While the changes in the glucose-related metabolites persisted during recovery even in anterior portions of the cortex in both groups in the aftermath of the SD, the magnitude of the changes was greater in the penumbra than in the normal cortex., SD appears to impose an equivalent increase in energy demands in control and ischemic brain, but the ability of the penumbra to recover from the insult is compromised., Thus, increasing the energy imbalance in the penumbra after multiple SDs may hasten the deterioration of the energy status of the tissue and eventually contribute to terminal depolarization and cell death, particularly in the penumbra., It is suggested that the limited survival of the penumbra is due to periinfarct depolarizations, which result in repeated episodes of tissue hypoxia, because the increased metabolic workload is not coupled to an adequate increase of collateral blood supply., Transient decreases of the apparent diffusion coefficient (ADC) of water as measured by fast diffusion-weighted imaging (DWI) in the ischemic border zone are thought to reflect cellular swelling associated with spreading depression., Severely delayed recovery time after spreading depression is thought to represent the ischemic penumbra., One current but controversial hypothesis is that this penumbra tissue often eventually dies because of the metabolic stress imposed by multiple cortical spreading depression (CSD) waves, that is, by ischemic depolarizations., After simulated infarction, the model displays the linear relation between final infarct size and the number of CSD waves traversing the penumbra that has been reported experimentally, although damage with each individual wave progresses nonlinearly with time., These findings support the hypothesis that CSD waves play an important causal role in the death of ischemic penumbra tissue., MCAO also triggers periodic periinfarction depolarizing waves (PIDs) in the ischemic penumbra, the territory of salvage., Here, the effects of SD at reduced flow conditions as encountered in the ischemic penumbra are examined., The experiments illustrate how peri-infarct depolarizations may detrimentally affect the penumbra., In the second series of experiments, periinfarct depolarizations (PIDs) were recorded with an extracellular DC electrode at two locations in the ischemic penumbra for the initial 3 h following MCAO., In vivo two-photon microscopy of green fluorescent protein-expressing neurons in this penumbra-like area at risk revealed that SDs were temporally correlated with rapid (<6 s) dendritic beading.[SEP]Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. extracellular defined as following: The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite. [GOC:go_curators]. lactate defined as following: The determination of the amount of lactic acid present in a sample.. dendrites defined as following: Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.. territory defined as following: A constituent administrative district of a nation.. SDs defined as following: A patient reported questionnaire composed of rating scales developed to measure the degree of distress experienced by the patient for specific symptoms.. CBF defined as following: CBF is an alpha/beta heterodimeric transcription factor involved in the transcriptional regulation of several genes important in hematopoiesis. The CBFalpha subunit binds directly to the enhancer core DNA sequence on target genes, whereas the beta subunit does not bind the DNA directly but increases the affinity and stabilizes the binding of the alpha subunit to the DNA.. dendritic spines defined as following: A small, membranous protrusion from a dendrite that forms a postsynaptic compartment, typically receiving input from a single presynapse. They function as partially isolated biochemical and an electrical compartments. Spine morphology is variable:they can be thin, stubby, mushroom, or branched, with a continuum of intermediate morphologies. They typically terminate in a bulb shape, linked to the dendritic shaft by a restriction. Spine remodeling is though to be involved in synaptic plasticity. [GOC:nln]. Astrocytes defined as following: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from \"star\" cells) are irregularly shaped with many long processes, including those with \"end feet\" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and \"reactive astrocytes\" (along with MICROGLIA) respond to injury.. terminal defined as following: Being or situated at an end; occurring at or forming an end.. hypoxia defined as following: A disorder characterized by a decrease in the level of oxygen in the body.. cortex defined as following: Pathological processes of the ADRENAL CORTEX.. MCA defined as following: The largest of the cerebral arteries. It trifurcates into temporal, frontal, and parietal branches supplying blood to most of the parenchyma of these lobes in the CEREBRAL CORTEX. These are the areas involved in motor, sensory, and speech activities.. cortical defined as following: The outer layer of the adrenal gland. It is derived from MESODERM and comprised of three zones (outer ZONA GLOMERULOSA, middle ZONA FASCICULATA, and inner ZONA RETICULARIS) with each producing various steroids preferentially, such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and ANDROSTENEDIONE. Adrenal cortex function is regulated by pituitary ADRENOCORTICOTROPIN.. DC defined as following: A predominantly X-linked recessive syndrome characterized by a triad of reticular skin pigmentation, nail dystrophy and leukoplakia of mucous membranes. Oral and dental abnormalities may also be present. Complications are a predisposition to malignancy and bone marrow involvement with pancytopenia. (from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin.. ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue..", "label": "yes"}
{"id": "converted_4428", "sentence1": "Is there a dependence between chromatin organization and dorsoventral gene expression in Drosophila?", "sentence2": "Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning., Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.[SEP]Definitions: tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. Drosophila defined as following: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology..", "label": "no"}
{"id": "converted_443", "sentence1": "Can we detect DNA strand asymmetries using dinucleotide relative abundance \"genomic signatures\"?", "sentence2": "comparing the heterogeneities of bacterial genomes with respect to strand-independent first- and second-order features, (i) G + C content and (ii) dinucleotide relative abundance,, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes., dinucleotide relative abundance values (the genomic signature), The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome., The profile is computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling). , The genome signatures (dinucleotide relative abundance values), Early biochemical experiments measuring nearest neighbor frequencies established that the set of dinucleotide relative abundance values (dinucleotide biases) is a remarkably stable property of the DNA of an organism., the set of dinucleotide biases constitutes a 'genomic signature' that can discriminate sequences from different organisms., the set of dinucleotide odds ratio (relative abundance) values constitute a signature of each DNA genome, Dinucleotide relative abundance extremes: a genomic signature., The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome., Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes., Comparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement)., Dinucleotide relative abundances (i.e., dinucleotide representations normalized by the component nucleotide frequencies) are consonant with respect to the leading and lagging strands[SEP]Definitions: Dinucleotide defined as following: A group of compounds which consist of a nucleotide molecule to which an additional nucleoside is attached through the phosphate molecule(s). The nucleotide can contain any number of phosphates.. bacterial genomes defined as following: The genetic complement of a BACTERIA as represented in its DNA.. genome defined as following: Anatomical set of genes in all the chromosomes.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. organisms defined as following: A living entity.. dinucleotide defined as following: A group of compounds which consist of a nucleotide molecule to which an additional nucleoside is attached through the phosphate molecule(s). The nucleotide can contain any number of phosphates..", "label": "no"}
{"id": "converted_758", "sentence1": "Is PLK2 involved in alpha-synuclein phosphorylation in the nervous system?", "sentence2": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system, Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons, PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay, Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo, specific knockdown of PLK2 expression by transduction with short hairpin RNA constructs or by knock-out of the plk2 gene reduced p-Ser-129 levels, These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system., These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system., Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons., Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system., PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay., Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (α-syn) phosphorylating polo-like kinase 2 (PLK2)., Also, due to the dominant mode of α-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and α-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD., To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice., This PLK2-mediated neuroprotective effect is also dependent on PLK2 activity and α-synuclein phosphorylation., PLK2-mediated degradation of α-synuclein requires both phosphorylation at S129 and PLK2/α-synuclein complex formation., Overexpression of only PLK2 increased phosphorylation of aggregated α-syn at S129, which likely is due to increased phosphorylation of soluble α-syn, which then was incorporated into aggregates., Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons., PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay., Unlike other kinases reported to partially phosphorylate alpha-syn at Ser-129 in vitro, phosphorylation by PLK2 and PLK3 is quantitative (, Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo., These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system, Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo, PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay, To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice, Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology[SEP]Relations: Parkinson disease has relations: disease_protein with LRRK2, disease_protein with LRRK2. Definitions: Plk-2 defined as following: Serine/threonine-protein kinase PLK2 (685 aa, ~78 kDa) is encoded by the human PLK2 gene. This protein is involved in cell cycle progression, centriole duplication and serine/threonine phosphorylation.. serine defined as following: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. PLK3 defined as following: Serine/threonine-protein kinase PLK3 (646 aa, ~72 kDa) is encoded by the human PLK3 gene. This protein is involved in protein phosphorylation and cell cycle regulation.. alpha-synuclein defined as following: A synuclein that is a major component of LEWY BODIES and plays a role in SYNUCLEINOPATHIES, neurodegeneration and neuroprotection.. LRRK2 defined as following: Leucine-rich repeat serine/threonine-protein kinase 2 (2527 aa, ~286 kDa) is encoded by the human LRRK2 gene. This protein may play a role in protein phosphorylation.. Polo-like kinase 2 defined as following: This gene is involved in normal cell division.. leucine rich repeat kinase 2 defined as following: Leucine-rich repeat serine/threonine-protein kinase 1 (2015 aa, ~225 kDa) is encoded by the human LRRK1 gene. This protein is involved in serine/threonine phosphorylation and osteoclast resorption of bone.. Parkinson's disease defined as following: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75). polo-like kinase 2 defined as following: This gene plays a role in mitotic regulation.. PD defined as following: A score of 4 or 5 on a 5-point PET scale with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment.. PLK defined as following: Serine/threonine-protein kinase PLK1 (603 aa, ~68 kDa) is encoded by the human PLK1 gene. This protein is involved in protein phosphorylation and the regulation of both cell cycle progression and cytokinesis.. PLK2 defined as following: This gene is involved in normal cell division..", "label": "yes"}
{"id": "converted_3024", "sentence1": "Is deletion at 6q24.2-26 associated with longer survival of patients with high-grade serous ovarian carcinoma (HGSOCs)?", "sentence2": "Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients., We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95%CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95%CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life., Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life., OBJECTIVE\nWe aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients., OBJECTIVE We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients., Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life.
, OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.
METHODS: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays., We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.[SEP]Definitions: GTF2H5 defined as following: General transcription factor IIH subunit 5 (71 aa, ~8 kDa) is encoded by the human GTF2H5 gene. This protein is involved in both nucleotide excision repair and RNA polymerase II-mediated transcription.. region defined as following: The continents and countries situated on those continents; the UNITED STATES and each of the constituent states arranged by region; CANADA and each of its provinces; AUSTRALIA and each of its states; the major bodies of water and major islands on both hemispheres; and selected major cities.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"}
{"id": "converted_1691", "sentence1": "Is STAT3 transcription factor regulated by mTORC1?", "sentence2": "Mechanistically, mTORC1 mediated IL-6-induced Stat3 activation in intestinal epithelial cells to stimulate the expression of downstream targets essential for cell proliferation and tissue regeneration. Therefore, mTORC1 signaling critically protects against inflammatory bowel disease through modulation of inflammation-induced Stat3 activity., we demonstrated that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1α mRNA transcription, Mechanistically, mTORC1 signaling was activated by excess amino acids, which then positively regulated Notch1 expression through the activation of the signal transducer and activator of transcription 3 (STAT3)., Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process, Furthermore, we demonstrated that STAT3 is directly phosphorylated by mTORC1 on Ser727 during hypoxia, promoting HIF-1α mRNA transcription. mTORC1 also regulates HIF-1α synthesis on a translational level via co-operative regulation of both initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase-1 (S6K1), whereas HIF-1α degradation remains unaffected, Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process. , TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade., Mechanistically, mTORC1 signaling was activated by excess amino acids, which then positively regulated Notch1 expression through the activation of the signal transducer and activator of transcription 3 (STAT3). , Suppression of the mTORC1/STAT3/Notch1 pathway by activated AMPK prevents hepatic insulin resistance induced by excess amino acids., Here, we review the connections between mTORC1 and gene transcription by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PPARγ, PPARα, HIF1α, YY1–PGC1α and TFEB. We also discuss the importance of these transcription factors in mediating the effects of mTORC1 on various cellular processes in physiological and pathological contexts.[SEP]Relations: inflammatory bowel disease has relations: disease_protein with STAT3, disease_protein with STAT3. transcription factor binding has relations: molfunc_protein with STAT3, molfunc_protein with STAT3. Definitions: TFEB defined as following: Transcription factor EB (476 aa, ~53 kDa) is encoded by the human TFEB gene. This protein plays a role in transcriptional regulation.. S6K1 defined as following: Human RPS6KB1 wild-type allele is located in the vicinity of 17q23.1 and is approximately 57 kb in length. This allele, which encodes ribosomal protein S6 kinase beta-1 protein, plays a role in the regulation of protein phosphorylation.. epithelial cells defined as following: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.. 4E-BP1 defined as following: Eukaryotic translation initiation factor 4E-binding protein 1 (118 aa, ~13 kDa) is encoded by the human EIF4EBP1 gene. This protein is involved in the modulation of translation and the sequestration of eukaryotic translation initiation factor 4E.. STAT3 defined as following: Signal transducer and activator of transcription 3 (770 aa, ~88 kDa) is encoded by the human STAT3 gene. This protein plays a role in cytokine signaling and gene expression.. AKT defined as following: Expressed in diverse tissues, Protein Kinase B (AKT/RAC Family) is a group (Alpha, Beta and Gamma) of cytoplasmic serine/threonine enzymes that covalently transfer the terminal, gamma phosphate group from ATP to a variety of substrate proteins and regulate cell signaling responses to insulin, PDGF, and IGF1 (through PI3K) involved in cell survival, cell proliferation, differentiation, apoptosis, glycogen synthesis, and glucose uptake.. mTORC1 defined as following: A protein complex that is involved in the both serine/threonine phosphorylation and the regulation of protein synthesis in response to cellular stress.. AMPK defined as following: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.. hypoxia defined as following: A disorder characterized by a decrease in the level of oxygen in the body.. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process..", "label": "yes"}
{"id": "converted_1219", "sentence1": "Can ferric carboxymaltose be used to treat anemia in inflammatory bowel disease patients?", "sentence2": "Intravenous iron should be preferred where oral iron is poorly tolerated or where it has failed in moderate to severe anemia, and in combination with erythropoietin, Ferric carboxymaltose is much more convenient, and has been shown to be more effective than iron sucrose in a large randomized tria, nemia and iron deficiency anemia are very common in inflammatory bowel disease (IBD, Ferric carboxymaltose was associated with cost savings of 30-44 % per patient per treatment cycle compared to iron sucrose. , Iron deficiency is common in pregnancy, postpartum, inflammatory bowel disease, chronic kidney disease, chronic heart failure, heavy uterine bleeding, cancer and following surgery. We estimate the budget impact (BI) on the Swiss mandatory health insurance associated with substituting iron sucrose (standard) with ferric carboxymaltose (new treatment) using real-life data., reating iron deficiency involves substantial costs to the Swiss MHI which may be reduced by substituting iron sucrose with ferric carboxymaltose., e aim of this study was to observe, in a non-interventional way, how Swedish gastroenterologists adhere to guidelines in IBD outpatients treated with intravenous ferric carboxymaltose (FCM), and the result of treatment, FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis., We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L), e performed a randomized, placebo-controlled trial to determine if administration of ferric carboxymaltose (FCM) prevents anemia in patients with IBD and low levels of serum ferritin, FCM prevents recurrence of anemia in patients with IBD, compared with placebo. , A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose., Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients., Intravenous iron avoids these concerns, especially with the development of ferric carboxymaltose, which allow up to 1000mg to be given rapidly., What is the optimal treatment for anemia in inflammatory bowel disease?, We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen (FCM) with individually calculated iron sucrose (IS) doses in patients with inflammatory bowel disease (IBD) and IDA, Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience, The simpler FCM-based dosing regimen showed better efficacy and compliance, as well as a good safety profile, compared with the Ganzoni-calculated IS dose regimen., Ferric carboxymaltose can be rapidly administered in doses of 15 mg/kg body weight, up to a ceiling dose of 1000 mg. A test dose is not required, and it can be used more widely across a spectrum of iron deficiency and iron deficiency anemia indication, Intravenous iron offers a rapid means of iron repletion and is superior to oral iron in many circumstances, especially in the presence of anemia of chronic disease, where it appears to overcome the block to absorption of iron from the gastrointestinal tract and immobilization of stored iron. The clinical situations where high doses of iron are commonly required are reviewed. These include nondialysis-dependent chronic kidney disease, inflammatory bowel disease, obstetrics, menorrhagia, and anemia associated with cancer and its treatment. , Ferric carboxymaltose can be administered at 15 mg/kg body weight to a maximum dose of 1000 mg, whereas iron isomaltoside 1000 can be administered at 20 mg/kg body weight. The ability to give high doses of iron is important in the context of managing iron deficiency anemia in a number of clinical conditions where demands for iron are high (including chronic blood loss associated with inflammatory bowel disease, menorrhagia, and chronic kidney disease), erric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD, In patients with IBD or PPA, improvements in Hb levels were more rapid with FCM than with FeSulf. , CM improved patient quality of life to an equivalent extent to oral FeSulf in patients with IBD or PPA, and to a greater extent than oral FeSulf in women with AUB, Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses)., he prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%)., novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial., FeCarb is effective and safe in IBD-associated anemia. It is noninferior to FeSulf in terms of Hb change over 12 wk, and provides a fast Hb increase and a sufficient refill of iron stores., Treatment-related adverse events (AEs) occurred in 28.5% of the FeCarb and 22.2% of the FeSulf groups, with discontinuation of study medication due to AEs in 1.5% and 7.9%, respectively., The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group, demonstrating noninferiority (P= 0.6967). , Ferric carboxymaltose prevents recurrence of anemia in patients with inflammatory bowel disease., Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD)., Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD)[SEP]Relations: Phenylpropanolamine has relations: contraindication with inflammatory bowel disease, contraindication with inflammatory bowel disease. Definitions: platelets defined as following: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.. cancer defined as following: A malignant tumor at the original site of growth.. CKD defined as following: Impairment of the renal function secondary to chronic kidney damage persisting for three or more months.. iron defined as following: homeopathic drug. IDA defined as following: A toxic purine analogue. Inosine dialdehyde inhibits ribonucleotide reductase, resulting in decreased synthesis of DNA, RNA, and proteins, and G2/M-phase cell cycle arrest. This agent also forms stable covalent crosslinks in proteins, thereby inhibiting the activity of enzymes involved in nucleic acid synthesis. (NCI04). iron sucrose defined as following: A glucaric acid-iron conjugate that is used in the treatment of IRON-DEFICIENCY ANEMIA, including in patients with chronic kidney disease, when oral iron therapy is ineffective or impractical.. PPA defined as following: A sympathomimetic that acts mainly by causing release of NOREPINEPHRINE but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant.. iron isomaltoside defined as following: An intravenous colloidal solution containing trivalent iron (Fe3+) chelated to isomaltosides, used as iron replacement. The iron in iron isomaltoside 1000 is strongly bound to the carbohydrate particles; each particle contains a trivalent iron core and a carbohydrate shell of isomaltosides which protects and stabilizes the iron core. This results in low levels of free iron and decreases inorganic, unbound iron-related toxicities thereby allowing for administration of higher doses of iron as compared to other iron-containing formulations. Upon parenteral administration and degradation of the carbohydrate shell, the iron in iron isomaltoside 1000 is released and replenishes iron stores.. FCM defined as following: A rare genetic movement disorder with characteristics of autosomal dominant, adult-onset, slowly progressive, multifocal, cortical myoclonus. Patients present somatosensory-evoked, brief, jerky, involuntary movements in the face, arms and legs, associated in most of cases with sustained, multiple, sudden falls without loss of consciousness. Seizures or other neurological deficits, aside from mild cerebellar ataxia late in the course of the illness, are absent. The disease is caused by heterozygous mutation in the NOL3 gene on chromosome 16q22.. menorrhagia defined as following: Excessive uterine bleeding during MENSTRUATION.. chronic disease defined as following: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).. iron dextran defined as following: A complex of ferric oxyhydroxide with dextrans of 5000 to 7000 daltons in a viscous solution containing 50 mg/ml of iron. It is supplied as a parenteral preparation and is used as a hematinic. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1292). IBD defined as following: Gastrointestinal symptoms characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause.. CHF defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. erythropoietin defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous glycoprotein erythropoietin (Epo). Epo promotes the differentiation and maturation of hematopoietic progenitors into erythrocytes; is a mitogen and a chemoattractant for endothelial cells; stimulates activated and differentiated B-cells and enhances B-cell immunoglobulin production and proliferation; and is hypoxia-inducible. (NCI04). Hb defined as following: The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.. AEs defined as following: An instrument that consist of an ultra high vacuum scanning microscope column combined with an electron energy analyzer, which can determine the elemental composition of the outer surface of a sample.. HD defined as following: A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.. iron-deficiency anemia defined as following: Anemia characterized by decreased or absent iron stores, low serum iron concentration, low transferrin saturation, and low hemoglobin concentration or hematocrit value. The erythrocytes are hypochromic and microcytic and the iron binding capacity is increased..", "label": "yes"}
{"id": "converted_2088", "sentence1": "Are cutaneous porphyrias inherited with a recessive pattern?", "sentence2": "Five of the porphyrias are low-penetrance autosomal dominant conditions in which clinical expression results from additional factors that act by increasing demand for haem or by causing an additional decrease in enzyme activity or by a combination of these effects, Molecular mechanisms of dominant expression in porphyria., Variegate porphyria (VP) is an autosomal-dominant disorder that is caused by inheritance of a partial deficiency of the enzyme protoporphyrinogen oxidase (EC 1.3.3.4). It is characterized by cutaneous photosensitivity and/or various neurological manifestations. , The acute porphyrias constitute a group of metabolic disorders engaging enzymes in the haem synthetic chain and generally following dominant inheritance patterns.[SEP]Definitions: metabolic disorders defined as following: Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed). Variegate porphyria defined as following: An autosomal dominant disorder of porphyria-heme metabolism. It is manifested with acute attacks including abdominal pain, vomiting, diarrhea, constipation, seizures, anxiety, and confusion. Patients may experience skin sensitivity to sunlight.. haem defined as following: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.. cutaneous photosensitivity defined as following: Increased sensitivity of the skin to light exposure.. VP defined as following: Vasopressin-neurophysin 2-copeptin (164 aa, ~17 kDa) is encoded by the human AVP gene. This protein is involved in neuropeptide hormone activity.. porphyria defined as following: A group of genetic or acquired metabolic disorders characterized by defects in the enzymes that are involved in the heme synthesis..", "label": "no"}
{"id": "converted_1044", "sentence1": "Does Chromatin Immunoprecipitation (ChIP) show a bias for highly expressed loci?", "sentence2": "However, several issues in the processing and analysis of ChIP-chip data have not been resolved fully, including the effect of background (mock control) subtraction and normalization within and across arrays, Proper normalization is essential for ChIP-chip experiments. The proposed normalization technique can correct systematic errors and compensate for the lack of mock control data, thus reducing the experimental cost and producing more accurate results., Subtraction of the mock (non-specific antibody or no antibody) control data is generally needed to eliminate the bias, but appropriate normalization obviates the need for mock experiments and increases the correlation among replicates, The proposed method can handle several control samples allowing for correction of multiple sources of bias simultaneously, However, the data generated will always contain noise due to e.g. repetitive regions or non-specific antibody interactions, The generation of high copy numbers of DNA fragments as an artifact of the PCR step in ChIP-seq is an important source of bias of this methodology, Here we describe several technical aspects of the ChIP-Seq assay that diminish bias and background noise and allow the consistent generation of high-quality data, This theoretical paper systematically characterizes the biases and properties of ChIP-seq data by comparing 62 separate publicly available datasets, using rigorous statistical models and signal processing techniques, We detected a chromatin-state bias: open chromatin regions yielded higher coverage, which led to false positives if not corrected, This bias had a greater effect on detection specificity than any base-composition bias, This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data, We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods, We investigated the impact of library amplification bias on the identification of allele-specific (AS) molecular events from high-throughput sequencing data derived from chromatin immunoprecipitation assays (ChIP-seq), The 238 loci, termed \"hyper-ChIPable\", were in highly expressed regions with strong polymerase II and polymerase III enrichment signals, and the correlation between transcription level and ChIP enrichment was not limited to these 238 loci but extended genome-wide, The localization of unrelated proteins, including the entire silencing complex, to the most highly transcribed genes was highly suggestive of a technical issue with the immunoprecipitations[SEP]Definitions: proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. ChIP-seq defined as following: A molecular genetic technique that combines chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing to map the binding sites of DNA-associated proteins in a sample of cells. First, crosslinked protein-DNA complexes are isolated using ChIP. Next, the crosslinks are broken, the proteins are removed and the purified DNA is modified with adaptor oligonucleotides to facilitate massively parallel DNA sequencing. Following sequencing, the DNA sequences that are obtained can be mapped to their genomic locations.. repetitive regions defined as following: Nucleotide sequences present in multiple copies in the genome. There are several types of repeated sequences. Interspersed (or dispersed) DNA repeats (Interspersed Repetitive Sequences) are copies of transposable elements interspersed throughout the genome. Flanking (or terminal) repeats (Terminal Repeat Sequences) are sequences that are repeated on both ends of a sequence, for example, the long terminal repeats (LTRs) on retroviruses. Direct terminal repeats are in the same direction and inverted terminal repeats are opposite to each other in direction. Tandem repeats (Tandem Repeat Sequences) are repeated copies which lie adjacent to each other. These can also be direct or inverted. The ribosomal RNA and transfer RNA genes belong to the class of middle repetitive DNA..", "label": "yes"}
{"id": "converted_2024", "sentence1": "Is the enzyme EPRS phosphorylated?", "sentence2": "Phosphorylation of glutamyl-prolyl tRNA synthetase (EPRS) has been investigated extensively in our laboratory for more than a decade, and has served as an archetype for studies of other AARSs., EPRS is dually phosphorylated by cyclin-dependent kinase 5 (Cdk5) at Ser(886) and then by a Cdk5-dependent-AGC kinase at Ser(999); , Diphosphorylated EPRS is released from its residence in the tRNA multisynthetase complex for immediate binding to NS1-associated protein and subsequent binding to ribosomal protein L13a and GAPDH. , Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity.[SEP]Relations: EPRS1 has relations: protein_protein with GAPDH, protein_protein with GAPDH. Definitions: GAPDH defined as following: Glyceraldehyde-3-phosphate dehydrogenase (335 aa, ~36 kDa) is encoded by the human GAPDH gene. This protein is involved in carbohydrate metabolism.. cyclin-dependent kinase 5 defined as following: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.. Cdk5 defined as following: Cyclin-dependent kinase 5 (292 aa, ~33 kDa) is encoded by the human CDK5 gene. This protein plays a role in protein phosphorylation and may be involved in cell cycle regulation..", "label": "yes"}
{"id": "converted_2090", "sentence1": "Can methylenetetrahydrofolate reductase (MTHFR) gene mutations cause homocystinuria?", "sentence2": "Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. , Several mutations seen in methylenetetrahydrofolate reductase (MTHFR) give rise to the formation of hyperhomocysteinemia and homocystinuria, a considerable risk factor for cardiovascular and cerebrovascular disorders, by leading to enzymatic inactivation., At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine., Response to treatment demonstrated B(6)-non-responsive homocystinuria. Molecular study showed compound heterozygous T353 N and D444 N mutations of the cystathionine beta-synthase (CBS) gene, and also a C667T homozygous mutation of the methylenetetrahydrofolate-reductase (MTHFR) gene. , Our case is atypical because of the absence of thromboembolism and the mild phenotype, in spite of being B(6)-non-responsive, and the association of a rare compound heterozygous mutation of the CBS gene and also an homozygous mutation of the MTHFR gene., Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency., Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate and homocysteine metabolism. Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia., Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the regulation of plasma homocysteine levels. MTHFR deficiency, an autosomal recessive disorder, results in homocystinuria and hypomethioninaemia and presents with highly variable symptoms affecting many organs but predominantly the central nervous system. , Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria., Rare mutations in the MTHFR gene have been associated with autosomal recessive MTHFR deficiency leading to homocystinuria., Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria., Five patients suspected of having non-classical homocystinuria due to MTHFR deficiency were examined with respect to their symptoms, MTHFR enzyme activity and genotypes of the MTHFR gene., The results of our study render the full-length characterisation of affected alleles in severe homocystinuria and moderate hyperhomocysteinaemia due to MTHFR deficiency and provide a basis for investigating the regulation of the human MTHFR gene., Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia., Different MTHFR mutations lead either to severe homocystinuria as a multisystem disorder or to moderate hyperhomocysteinaemia, which is a common risk factor for disorders ranging from cardiovasculopathy to spina bifida., We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis., On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR., We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis., Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria, We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis, Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria, The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, The 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinemia, but this polymorphism does not seem to be a risk factor for venous thrombosis, Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM), The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia, We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. , AIM: Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria. , Betaine for treatment of homocystinuria caused by methylenetetrahydrofolate reductase deficiency., Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) with homocystinuria can result in early demise or later-onset neurological impairment, including developmental delay, motor dysfunction, and seizures. , Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR) leads to deficient remethylation of homocysteine and is one of the causes of homocystinuria. , Neurological disturbances have been described in homocystinuria caused by severe MTHFR deficiency. , The 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinemia, but this polymorphism does not seem to be a risk factor for venous thrombosis., Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia., The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia., The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene., Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia., Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria., Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency., On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR.[SEP]Relations: methylenetetrahydrofolate reductase (NAD(P)H) activity has relations: molfunc_protein with MTHFR, molfunc_protein with MTHFR. spina bifida has relations: disease_protein with MTHFR, disease_protein with MTHFR. hyperhomocysteinemia has relations: disease_protein with MTHFR, disease_protein with MTHFR. homocystinuria due to methylene tetrahydrofolate reductase deficiency has relations: disease_protein with MTHFR, disease_protein with MTHFR. Methionine has relations: drug_protein with MTHFR, drug_protein with MTHFR. Definitions: autosomal recessive disorder defined as following: An inherited disorder manifested only when two copies of a mutated gene are present.. MTHFR defined as following: A flavoprotein amine oxidoreductase that catalyzes the reversible conversion of 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. This enzyme was formerly classified as EC 1.1.1.171.. gene mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. spina bifida defined as following: Congenital defects of closure of one or more vertebral arches, which may be associated with malformations of the spinal cord, nerve roots, congenital fibrous bands, lipomas, and congenital cysts. These malformations range from mild (e.g., SPINA BIFIDA OCCULTA) to severe, including rachischisis where there is complete failure of neural tube and spinal cord fusion, resulting in exposure of the spinal cord at the surface. Spinal dysraphism includes all forms of spina bifida. The open form is called SPINA BIFIDA CYSTICA and the closed form is SPINA BIFIDA OCCULTA. (From Joynt, Clinical Neurology, 1992, Ch55, p34). folate defined as following: A cofactor for 1-carbon transfer involved with DNA synthesis.. Betaine defined as following: A naturally occurring compound that has been of interest for its role in osmoregulation. As a drug, betaine hydrochloride has been used as a source of hydrochloric acid in the treatment of hypochlorhydria. Betaine has also been used in the treatment of liver disorders, for hyperkalemia, for homocystinuria, and for gastrointestinal disturbances. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1341). hyperhomocysteinemia defined as following: Condition in which the plasma levels of homocysteine and related metabolites are elevated (>13.9 μmol/l). Hyperhomocysteinemia can be familial or acquired. Development of the acquired hyperhomocysteinemia is mostly associated with vitamins B and/or folate deficiency (e.g., PERNICIOUS ANEMIA, vitamin malabsorption). Familial hyperhomocysteinemia often results in a more severe elevation of total homocysteine and excretion into the urine, resulting in HOMOCYSTINURIA. Hyperhomocysteinemia is a risk factor for cardiovascular and neurodegenerative diseases, osteoporotic fractures and complications during pregnancy.. CBS gene defined as following: This gene plays a role in transsulfuration.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. homocysteine defined as following: A thiol-containing amino acid formed by a demethylation of METHIONINE.. thromboembolism defined as following: Obstruction of a blood vessel (embolism) by a blood clot (THROMBUS) in the blood stream.. methionine defined as following: A preparation of METHIONINE that includes a mixture of D-methionine and L-methionine isomers.. MTHFR gene defined as following: This gene is involved in folate metabolism and methionine biosynthesis.. genotypes defined as following: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.. venous thrombosis defined as following: The formation or presence of a blood clot (THROMBUS) within a vein.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. homocystinuria defined as following: Autosomal recessive inborn error of methionine metabolism usually caused by a deficiency of CYSTATHIONINE BETA-SYNTHASE and associated with elevations of homocysteine in plasma and urine. Clinical features include a tall slender habitus, SCOLIOSIS, arachnodactyly, MUSCLE WEAKNESS, genu varus, thin blond hair, malar flush, lens dislocations, an increased incidence of MENTAL RETARDATION, and a tendency to develop fibrosis of arteries, frequently complicated by CEREBROVASCULAR ACCIDENTS and MYOCARDIAL INFARCTION. (From Adams et al., Principles of Neurology, 6th ed, p979). cerebrospinal fluid defined as following: A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES.. alleles defined as following: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. organs defined as following: A unique macroscopic (gross) anatomic structure that performs specific functions. It is composed of various tissues. An organ is part of an anatomic system or a body region. Representative examples include the heart, lung, liver, spleen, and uterus.. Molecular defined as following: Relating to or produced by or consisting of molecules.. seizures defined as following: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\". gene mutation defined as following: A change in the nucleotide sequence of the TAF1 gene.. FVL defined as following: Human F5 Leiden allele is a variant form of the F5 gene that is located in the vicinity of 1q23 and is approximately 75 kb in length. This allele, which encodes coagulation factor V Leiden protein, is involved in hypercoagulability due to resistance to degradation by activated protein C.. polymorphism defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. methylenetetrahydrofolate reductase defined as following: This gene is involved in folate metabolism and methionine biosynthesis..", "label": "yes"}
{"id": "converted_1874", "sentence1": "Is there an association between Muenke Syndrome and FGFR3 gene mutation?", "sentence2": "RESULTS: Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years)., Muenke is a fibroblast growth factor receptor 3 (FGFR-3)-associated syndrome, which was first described in late 1990 s. , The syndrome is defined molecularly by a unique point mutation c.749C>G in exon 7 of the FGFR3 gene which results to an amino acid substitution p.Pro250Arg of the protein product. , Muenke syndrome caused by point mutation (C749G) in the FGFR3 gene affects 1 in 30,000 newborns and accounts for 25% to 30% of genetic causes of craniosynostosis., Phenotypic variability in two families of Muenke syndrome with FGFR3 mutation., PURPOSE: There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes-that result from mutations in the fibroblast growth factor receptor (FGFR) genes. , Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene., Talocalcaneal coalition in Muenke syndrome: report of a patient, review of the literature in FGFR-related craniosynostoses, and consideration of mechanism., To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3 (P244R)) and compare them with human phenotypes., We show in this study that knock-in mice harboring the mutation responsible for the Muenke syndrome (FgfR3(P244R)) display postnatal shortening of the cranial base along with synchondrosis growth plate dysfunction characterized by loss of resting, proliferating and hypertrophic chondrocyte zones and decreased Ihh expression., Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene., The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes., Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis., Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature., The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes., PURPOSE: The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation., The heterozygous Pro250Arg substitution mutation in fibroblast growth factor receptor 3 (FGFR3), which increases ligand-dependent signalling, is the most common genetic cause of craniosynostosis in humans and defines Muenke syndrome., P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities., Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies., Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene., Muenke syndrome, defined by heterozygosity for a Pro250Arg substitution in fibroblast growth factor receptor 3 (FGFR3), is the most common genetic cause of craniosynostosis in humans., In addition, sensorineural hearing loss is detected in all FgfR3 (P244R) mutant mice as in the majority of Muenke syndrome patients., Genetic testing identifies a pathogenic mutation or chromosomal abnormality in ∼ 21% of cases, but it is likely that further causative mutations remain to be discovered.To identify a shared signature of genetically determined craniosynostosis by comparing the expression patterns in three monogenic syndromes with a control group of patients with non-syndromic sagittal synostosis.Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured, The craniosynostosis syndromes: Apert syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Muenke syndrome, Pfeiffer syndrome and Saethre-Chotzen syndrome can be caused by mutation in either FGFR1, FGFR2, or FGFR3, Identical proline-->arginine gain-of-function mutations in fibroblast growth factor receptor (FGFR) 1 (Pro252Arg), FGFR2 (Pro253Arg) and FGFR3 (Pro250Arg), result in type I Pfeiffer, Apert and Muenke craniosynostosis syndromes, respectively, The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes, Mutation analysis of FGFR-3 revealed a missense mutation in exon 6, c.749 C>G, with a resultant amino acid change from proline to arginine at codon 250 (P250R), in keeping with Muenke syndrome (Am J Hum Genet 1997;60:555-564), In an attempt to delineate functional features separating SCS from Muenkes syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3, Since the Gly380Arg achondroplasia mutation was recognized, similar observations regarding the conserved nature of FGFR mutations and resulting phenotype have been made regarding other skeletal phenotypes, including hypochondroplasia, thanatophoric dysplasia, and Muenke coronal craniosynostosis, Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).Here we report a clinical and molecular study in a large cohort of 125 Portuguese patients with these skeletal disorders. , The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. , P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities. , METHODS: Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured. , Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. , Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). , In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease. , Skeletal analysis of the Fgfr3(P244R) mouse, a genetic model for the Muenke craniosynostosis syndrome., Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene., Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis., Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3)., The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation.[SEP]Relations: Hearing impairment has relations: disease_phenotype_positive with Crouzon syndrome, disease_phenotype_positive with Pfeiffer syndrome, disease_phenotype_positive with achondroplasia, disease_phenotype_positive with thanatophoric dysplasia, disease_phenotype_positive with Crouzon syndrome, disease_phenotype_positive with Pfeiffer syndrome, disease_phenotype_positive with achondroplasia, disease_phenotype_positive with thanatophoric dysplasia. Coronal craniosynostosis has relations: disease_phenotype_positive with Crouzon syndrome, disease_phenotype_positive with Pfeiffer syndrome, disease_phenotype_positive with Crouzon syndrome, disease_phenotype_positive with Pfeiffer syndrome. hypogonadotropic hypogonadism has relations: disease_protein with FGFR1, disease_protein with FGFR1. Beare-Stevenson cutis gyrata syndrome has relations: disease_protein with FGFR1, disease_protein with FGFR1. apert syndrome has relations: disease_protein with TWIST1, disease_protein with FGFR1, disease_protein with TWIST1, disease_protein with FGFR1. Craniofacial dysostosis has relations: disease_phenotype_positive with Crouzon syndrome, disease_phenotype_positive with Crouzon syndrome. Pfeiffer syndrome has relations: disease_protein with TWIST1, disease_protein with FGFR1, disease_protein with TWIST1, disease_protein with FGFR1. Craniosynostosis has relations: disease_phenotype_positive with Jackson-Weiss syndrome, disease_phenotype_positive with craniosynostosis, disease_phenotype_positive with Jackson-Weiss syndrome, disease_phenotype_positive with craniosynostosis. craniosynostosis Fontaine type has relations: disease_disease with craniosynostosis, disease_disease with craniosynostosis. FGFR3 has relations: disease_protein with craniosynostosis, disease_protein with thanatophoric dysplasia, disease_protein with achondroplasia, disease_protein with craniosynostosis, disease_protein with thanatophoric dysplasia, disease_protein with achondroplasia. Jackson-Weiss syndrome has relations: disease_protein with FGFR1, disease_protein with FGFR1. autosomal dominant disease has relations: disease_disease with thanatophoric dysplasia, disease_disease with thanatophoric dysplasia. Definitions: Muenke Syndrome defined as following: A rare autosomal dominant inherited disorder caused by mutations in the FGFR3 gene. It is characterized by premature fusion of cranial bones, resulting in head shape abnormalities, flattened cheekbones, and wide-set eyes.. Fibroblast Growth Factor Receptor 3 defined as following: A fibroblast growth factor receptor with specificity for FIBROBLAST GROWTH FACTORS; HEPARAN SULFATE PROTEOGLYCAN; and NEURONAL CELL ADHESION MOLECULES. Several variants of the receptor exist due to multiple ALTERNATIVE SPLICING of its mRNA. Fibroblast growth factor receptor 1 contains three extracellular IMMUNOGLOBULIN C2-SET DOMAINS and is a tyrosine kinase that transmits signals through the MAP KINASE SIGNALING SYSTEM.. fibroblast growth factor receptor defined as following: A fibroblast growth factor receptor which contains three extracellular IMMUNOGLOBULIN I-SET DOMAINS and is expressed as two isoforms. One receptor isoform is expressed in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform is expressed mainly by EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in craniosynostotic syndromes (e.g., APERT SYNDROME; and CROUZON SYNDROME).. hearing loss defined as following: Partial or complete loss of the ability to detect or understand sounds resulting from damage to the outer, middle, or inner ear structures. Causes include exposure to loud noise, ear infections, injuries to the ear, genetic, and congenital disorders.. sensorineural hearing loss defined as following: Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.. proline defined as following: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.. P250R mutation defined as following: A change in the nucleotide sequence of the ARID1B gene.. FGFR-3 defined as following: Fibroblast growth factor receptor 3 (806 aa, ~88 kDa) is encoded by the human FGFR3 gene. This protein is involved in fibroblast growth factor signaling and skeletal development.. coronal craniosynostosis defined as following: Premature closure of the coronal suture of skull. [HPO:probinson]. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. Hypochondroplasia defined as following: An autosomal dominant disorder that is often caused by a defect in fibroblast growth factor receptor 3, and characterized by short stature, micromelia, and a comparatively large head. The features are milder than those seen in achondroplasia.. thanatophoric dysplasia defined as following: Thanatophoric dysplasia characterized by a normally shaped skull and curved femurs. It is the most common type of thanatophoric dysplasia.. achondroplasia defined as following: An autosomal dominant disorder that is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, GENU VARUM, and trident hand. (Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim, MIM#100800, April 20, 2001). Beare-Stevenson syndrome defined as following: A rare, autosomal dominant inherited disorder caused by mutations in the FGFR2 gene. It is characterized by the premature fusion of the bones of the skull (craniosynostosis) and a skin abnormality called cutis gyrata. The craniosynostosis results in a cloverleaf-shaped skull, wide-set eyes, ear abnormalities, underdeveloped upper jaw, and developmental delays. Cutis gyrata is characterized by a wrinkled skin appearance, especially on the face, near the ears, and on the palms and soles.. FGFR defined as following: Specific molecular sites or structures on cell membranes that react with FIBROBLAST GROWTH FACTORS (both the basic and acidic forms), their analogs, or their antagonists to elicit or to inhibit the specific response of the cell to these factors. These receptors frequently possess tyrosine kinase activity.. craniofacial defined as following: refers to the bones of the skull and face.. Apert syndrome defined as following: An autosomal dominant inherited type of acrocephalosyndactyly caused by mutations in the FGFR2 gene. It is characterized by early closure of the sutures between the skull bones, bulging eyes, low-set ears, fusion of the second, third, and forth fingers, and fusion of the toes.. TWIST1 defined as following: Twist-related protein 1 (202 aa, ~21 kDa) is encoded by the human TWIST1 gene. This protein plays a role in the negative regulation of both transcription and myogenesis.. arginine defined as following: An essential amino acid that is physiologically active in the L-form.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. point mutation defined as following: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.. Arg defined as following: This gene plays a role in signal transduction.. Epilepsy defined as following: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313). chondrocyte defined as following: Polymorphic cells that form cartilage.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. Pfeiffer syndrome defined as following: An autosomal dominant inherited type of acrocephalosyndactyly caused by mutations in the FGFR1 or FGFR2 genes. It is characterized by early closure of the sutures between the skull bones, bulging and wide-set eyes, broad thumbs, big toes, and partial syndactyly in the hands and toes.. craniosynostosis syndromes defined as following: Premature closure of one or more CRANIAL SUTURES. It often results in plagiocephaly. Craniosynostoses that involve multiple sutures are sometimes associated with congenital syndromes such as ACROCEPHALOSYNDACTYLIA; and CRANIOFACIAL DYSOSTOSIS.. P250R defined as following: Human ARID1B wild-type allele is located in the vicinity of 6q25.1 and is approximately 433 kb in length. This allele, which encodes AT-rich interactive domain-containing protein 1B, is involved in both cell type-specific transcriptional regulation and chromatin remodeling.. amino acid substitution defined as following: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.. craniosynostosis defined as following: A form of syndromic craniosynostosis with characteristics of highly variable craniosynostosis with frontal bossing, turribrachycephaly and cloverleaf skull anomaly. Hypoplasia of the supraorbital ridges, cleft palate, extra teeth and limb anomalies has also been described. Associated problems include headache, poor vision, and seizures. Intelligence is normal.. FGFR1 defined as following: Fibroblast growth factor receptor 1 (822 aa, ~92 kDa) is encoded by the human FGFR1 gene. This protein is involved in the regulation of embryonic development, cell proliferation, cell differentiation and cellular migration.. humans defined as following: Members of the species Homo sapiens.. FGFR3 gene defined as following: This gene plays a role in bone development and maintenance and mutations in the gene are associated with craniosynostosis and several types of skeletal dysplasia.. Jackson-Weiss syndrome defined as following: A rare, autosomal dominant inherited disorder caused by mutations in the FGFR2 gene. It is characterized by the premature fusion of the bones of the skull (craniosynostosis) and foot abnormalities. The craniosynostosis results in a malformed skull, widely spaced eyes, and a bulging forehead. The foot abnormalities consist of short and wide first toes, which bend away from the other toes. In addition, syndactyly in some toes may be present. The hands are almost always normal.. cranial base defined as following: The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface.. autosomal dominant disorder defined as following: An inherited disorder that manifests when one copy of a mutated gene is present.. FGFR3 gene mutation defined as following: A change in the nucleotide sequence of the FGFR3 gene..", "label": "yes"}
{"id": "converted_1981", "sentence1": "Does the hERG gene code for a protein which is part of a sodium channel?", "sentence2": " The human ether-à-go-go-related gene (hERG 1a) potassium channel is critical for cardiac repolarization, Human ether-a-go-go-related gene (hERG) channels conduct delayed rectifier K(+) current. , The KvLQT1 and minK genes code the slowly activating, delayed rectifier (Iks) potassium channel, the HERG gene code the rapidly activating, delayed rectifier (Ikr) potassium channel of the heart, while the SCN5A gene codes a cardiac sodium channel., The molecular basis of inherited disorders caused by a mutation in either the gene coding for a particular potassium channel called HERG-or another gene, SCN5A, which codes for the sodium channel and disruption of which results in a loss of inactivation of the Na+ current., The aim of this study was to test whether a recently reported polymorphism in the HERG gene coding for the rapidly activating delayed rectifier K+ channel has influence on myocardial repolarization., Mutations in KvLQT1, minK and HERG genes affects repolarising, rectifier potassium currents, while SCN5A mutations cause delayed inactivation and reopening of the cardiac sodium channel, which initiates the depolarisation of cardiac cells., A human genetic defect associated with 'long Q-T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel., Therefore, matrine and oxymatrine may have the potential to cure LQT2 as a potassium channel activator by promoting hERG channel activation and increasing hERG channel expression., The human delta1261 mutation of the HERG potassium channel results in a truncated protein that contains a subunit interaction domain and decreases the channel expression., HERG (human eag-related gene) encodes an inward-rectifier potassium channel formed by the assembly of four subunits., The human ether-?-go-go-related gene (HERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel in the heart., The human ether-a-go-go-related gene (hERG) encodes the rapidly activating, delayed rectifier potassium channel (IKr) important for cardiac repolarization., Role of glycosylation in cell surface expression and stability of HERG potassium channels., The human ERG protein (HERG or Kv 11.1) encoded by the human ether-a-go-go-related gene (herg) is the pore-forming subunit of the cardiac delayed rectifier potassium current (IKr) responsible for action potential (AP) repolarization, Human ether-a-go-go related gene (herg) encoding HERG K(+) channel has been demonstrated in many previous studies with its association to cell cycle progression and growth in tumor cells, A human genetic defect associated with 'long Q-T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel. , Drug-induced long QT syndrome: hERG K+ channel block and disruption of protein trafficking by fluoxetine and norfluoxetine., OBJECTIVES: The aim of this study was to test whether a recently reported polymorphism in the HERG gene coding for the rapidly activating delayed rectifier K+ channel has influence on myocardial repolarization. , The aim of this study was to test whether the K897T polymorphism of the KCNH2 (HERG) gene coding for the rapidly activating delayed rectifier K+ channel influences cardiac repolarization assessed by principal component analysis (PCA) of T-wave morphology. , The KvLQT1 and minK genes code the slowly activating, delayed rectifier (Iks) potassium channel, the HERG gene code the rapidly activating, delayed rectifier (Ikr) potassium channel of the heart, while the SCN5A gene codes a cardiac sodium channel., All code for subunits of sodium or potassium channels: two a subunits of the potassium channels (QVLQT1 for LQT1, HERG for LQT2), the a subunit of the sodium channel INa (SCN5A for LQT3), and two regulatory subunits of potassium channels (KCNE1 for LQT5 regulating the KvLQT1 channel and MiRP1 regulating HERG)., The corresponding genes code for potassium channels KVLQT1 (LQT1) and HERG (LQT2) and the sodium channel SCN5A (LQT3)., The molecular basis of inherited disorders caused by a mutation in either the gene coding for a particular potassium channel called HERG-or another gene, SCN5A, which codes for the sodium channel and disruption of which results in a loss of inactivation of the Na+ current., There may also be correlation between the strength of binding of the medicinal substance to the potassium channel coded by the HERG gene and prolongation of the QT interval., We demonstrate that the mRNA 3'UTR of ppk29 affects neuronal firing rates and associated heat-induced seizures by acting as a natural antisense transcript (NAT) that regulates the neuronal mRNA levels of seizure (sei), the Drosophila homolog of the human Ether-à-go-go Related Gene (hERG) potassium channel., Mutations in KvLQT1, minK and HERG genes affects repolarising, rectifier potassium currents, while SCN5A mutations cause delayed inactivation and reopening of the cardiac sodium channel, which initiates the depolarisation of cardiac cells., Among the congenital forms, particularly interest is focused on the potassium channel coded by the HERG gene located on chromosome 7 and with a key role in the normal electric cardiac activity., By employing heterologous expression and making comparisons to cells expressing wild-type human-ether-a-go-go-related protein (HERG), a potassium channel that contributes to I(Kr) current in ventricular cardiomyocytes, we demonstrate activation of an elevated endoplasmic reticulum (ER) stress response by the mutant I593R HERG potassium channel implicated in long QT syndrome type 2., Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome., Mutations in the human ether-à-go-go-related gene (HERG), which encodes a delayed-rectifier potassium channel,, s HERG and KvLQT1 potassium channel genes, HERG encodes the cardiac I(Kr) potassium channel., block of the cardiac potassium channel human ether-à-go-go-related gene (hERG) , The human ether-a-go-go-related gene (hERG) encodes the pore-forming α-subunit of the rapidly activating delayed rectifier K(+) channel in the heart, which plays a critical role in cardiac action potential repolarization. , Effects of donepezil on hERG potassium channels., Human ether-a-go-go related-gene K⁺ channels (hERG) participate in the regulation of tumor cell proliferation and apoptosis. HERG channel activity is up-regulated by growth factors, hERG potassium channels, HERG, a K+ channel gene.[SEP]Relations: long QT syndrome has relations: disease_protein with KCNE1, disease_protein with KCNE1, disease_protein with KCNE1, disease_protein with KCNE1, disease_protein with KCNE1, disease_protein with KCNE1, disease_protein with KCNE1, disease_protein with KCNE1. KCNE1 has relations: disease_protein with long QT syndrome, anatomy_protein_present with heart, disease_protein with long QT syndrome, anatomy_protein_present with heart. KCNE2 has relations: disease_protein with long QT syndrome, disease_protein with long QT syndrome. Definitions: LQT5 defined as following: An autosomal dominant condition caused by mutation(s) in the KCNE1 gene, encoding potassium voltage-gated channel subfamily E member 1. It is characterized by a prolonged QT interval that may result in torsade de pointes, ventricular fibrillation and/or sudden cardiac death.. LQT2 defined as following: An autosomal dominant condition caused by mutation(s) in the KCNH2 gene, encoding potassium voltage-gated channel subfamily H member 2. It is characterized by a prolonged QT interval that may result in torsade de pointes, ventricular fibrillation and/or sudden cardiac death.. LQT3 defined as following: An autosomal dominant condition caused by mutation(s) in the SCN5A gene, encoding sodium channel protein type 5 subunit alpha. It is characterized by a prolonged QT interval that may result in torsade de pointes, ventricular fibrillation and/or sudden cardiac death.. SCN5A gene defined as following: This gene is involved in voltage-dependent sodium ion transport.. ER defined as following: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed). LQT1 defined as following: A form of long QT syndrome that is without congenital deafness. It is caused by mutation of the KCNQ1 gene which encodes a protein in the VOLTAGE-GATED POTASSIUM CHANNEL.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. KvLQT1 defined as following: Potassium voltage-gated channel subfamily KQT member 1 (676 aa, ~75 kDa) is encoded by the human KCNQ1 gene. This protein is involved in cardiac repolarization through modulation of potassium ion transport.. fluoxetine defined as following: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.. mutant defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. growth factors defined as following: Growth Factors are extracellular signaling molecules (ligands) involved in control of target cell proliferation, cell survival, and cell differentiation. (NCI). protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. sodium channel defined as following: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. chromosome 7 defined as following: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.. long QT syndrome defined as following: A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.. donepezil defined as following: The hydrochloride salt of a piperidine derivative with neurocognitive-enhancing activity. Donepezil reversibly inhibits acetylcholinesterase, thereby blocking the hydrolysis of the neurotransmitter acetylcholine and, consequently, increasing its activity. This agent may improve neurocognitive function in Alzheimer's disease, reduce sedation associated with opioid treatment of cancer pain, and improve neurocognitive function in patients who have received radiation therapy for primary brain tumors or brain metastases.. tumor cells defined as following: Cells of, or derived from, a tumor.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. human defined as following: Members of the species Homo sapiens.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. polymorphism defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level..", "label": "no"}
{"id": "converted_2179", "sentence1": "Is airplane stroke syndrome a common disease.", "sentence2": "Only 37 cases of stroke during or soon after long-haul flights have been published to our knowledge. , Our centre admitted 5727 stroke patients, of whom 42 (0.73%) had flight-related strokes., The authors report three cases of ischemic stroke in young adults that occurred during or after an airplane flight.[SEP]Definitions: ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810).", "label": "no"}
{"id": "converted_3543", "sentence1": "Does an interferon (IFN) signature exist for SLE patients?", "sentence2": "Interferon regulatory factor 7 activation correlates with the IFN signature and recurrent disease., In SLE post-transplant, recurrent disease activity and induction of IRF7 protein expression correlated with activation of the IFN signature., JAK inhibitor has the amelioration effect in lupus-prone mice: the involvement of IFN signature gene downregulation., We also detected decreased expression of several IFN-signature genes Ifit3 and Isg15 in CD4+ from SLE-prone mice following TOFA and DEXA treatment, and IFIT3 in CD3+ T cells from human patients following immunosuppressant therapy including steroid, respectively, We found that cDCs from prediseased TCSle male mice express the IFN signature as female TCSle cDCs do. Estrogens are necessary but not sufficient to express this IFN signature, but high doses of E2 can compensate for other steroidal components., Conventional DCs from Male and Female Lupus-Prone B6.NZM Sle1/Sle2/Sle3 Mice Express an IFN Signature and Have a Higher Immunometabolism That Are Enhanced by Estrogen., Type I IFN signature in childhood-onset systemic lupus erythematosus, Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. , The IFN-I score (positive or negative), as a measure of IFN-I activation, was assessed using real-time quantitative PCR (RT-PCR) expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs)[SEP]Definitions: Isg15 defined as following: This gene is involved in both protein tagging and cell signaling.. IFI44 defined as following: This gene may play a role in the response to viral infection.. IFITM1 defined as following: Interferon-induced transmembrane protein 1 (125 aa, ~14 kDa) is encoded by the human IFITM1 gene. This protein is involved in interferon-induced antiviral responses.. steroid defined as following: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed). MxA defined as following: Human MX1 wild-type allele is located in the vicinity of 21q22.3 and is approximately 39 kb in length. This allele, which encodes interferon-induced GTP-binding protein Mx1, is involved in the regulation of apoptosis, hydrolysis of GTP, the modulation of interferon-regulated signaling.. E2 defined as following: Isoenergetic transfer of a ubiquitin-like protein (ULP) from one protein to another via the reaction X-SCP + Y -> Y-SCP + X, where both the X-SCP and Y-SCP linkages are thioester bonds between the C-terminal amino acid of SCP and a sulfhydryl side group of a cysteine residue. [GOC:dph]. Interferon type I defined as following: Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).. Interferon regulatory factor 7 defined as following: This gene plays a role in the modulation of the innate immune response against DNA and RNA viruses.. IFIT1 defined as following: Interferon-induced protein with tetratricopeptide repeats 1 (478, ~55 kDa) is encoded by the human IFIT1 gene. This protein plays a role in binding to triphosphorylated, single-stranded viral RNA.. monocytes defined as following: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.. Ly6e defined as following: Human LY6E wild-type allele is located in the vicinity of 8q24.3 and is approximately 4 kb in length. This allele, which encodes lymphocyte antigen Ly-6E protein, is involved in myelopoiesis and signal transduction.. JAK defined as following: A family of intracellular tyrosine kinases that participate in the signaling cascade of cytokines by associating with specific CYTOKINE RECEPTORS. They act upon STAT TRANSCRIPTION FACTORS in signaling pathway referred to as the JAK/STAT pathway. The name Janus kinase refers to the fact the proteins have two phosphate-transferring domains.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. DCs defined as following: Neutral lipid storage disease (NLSD) refers to a group of diseases characterized by a deficit in the degradation of cytoplasmic triglycerides and their accumulation in cytoplasmic lipid vacuoles in most tissues of the body. The group is heterogeneous: currently cases of NLSD with icthyosis (NLSDI/Dorfman-Chanarin disease; see this term) and NLSD with myopathy (NLSDM/neutral lipid storage myopathy; see this term) can be distinguished.. IFN defined as following: Human interferons have been classified into 3 groups: alpha, beta, and gamma. Both alpha- and beta-IFNs, previously designated type I, are acid-stable, but they differ immunologically and in regard to some biologic and physiochemical properties. The IFNs produced by virus-stimulated leukocytes (leukocyte IFNs) are predominantly of the alpha type. Those produced by lymphoblastoid cells are about 90% alpha and 10% beta. Induced fibroblasts produce mainly or exclusively the beta type. The alpha- and beta-IFNs differ widely in amino acid sequence. The gamma or immune IFNs, which are produced by T lymphocytes in response to mitogens or to antigens to which they are sensitized, are acid-labile and serologically distinct from alpha- and beta-IFNs. (from OMIM 147570). CD14 defined as following: Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including MONOCYTES; MACROPHAGES; and some GRANULOCYTES. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.. SLE defined as following: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.. DEXA defined as following: A technique for scanning bone and measuring bone mineral density (BMD). A DXA scanner produces 2 X-ray beams, each with different energy levels. One beam is high energy while the other is low energy. The amount of x-rays that pass through the bone is measured for each beam. This will vary depending on the thickness of the bone. Based on the difference between the 2 beams, the bone density can be measured.. human defined as following: Members of the species Homo sapiens..", "label": "yes"}
{"id": "converted_725", "sentence1": "Is acid alpha-glucosidase the enzyme that causes Pompe disease when mutant?", "sentence2": "Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA)), Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation, Pompe disease is an autosomal recessive myopathic disorder caused by the deficiency of lysosomal acid α-glucosidase (GAA), Acid α-glucosidase deficiency, that is, Pompe disease, is a glycogenosis for which enzyme replacement therapy (ERT) is available, The analysis revealed that the amino acid substitutions causing a processing or transport defect responsible for Pompe disease were widely spread over all of the five domains comprising the acid alpha-glucosidase., Pompe disease is a lysosomal storage disease (LSD) caused by a deficiency in the lysosomal enzyme acid alpha-glucosidase., Glycogen storage disease type II (GSDII; Pompe disease or acid maltase deficiency) is an autosomal recessive disorder caused by lysosomal acid alpha-glucosidase (AalphaGlu) deficiency and manifests predominantly as skeletal muscle weakness., Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease., The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types., Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene., Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen., Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA)., Demonstration of acid alpha-glucosidase in different types of Pompe disease by use of an immunochemical method., Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists., Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy., Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease., Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase., Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease., The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease, Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease, Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme, Although many lysosomal disorders are corrected by a small amount of the missing enzyme, it has been generally accepted that 20-30% of normal acid alpha-glucosidase (GAA) activity, provided by gene or enzyme replacement therapy, would be required to reverse the myopathy and cardiomyopathy in Pompe disease, The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types, As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter, Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome, Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene, Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen, Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme., Structural modeling of mutant alpha-glucosidases resulting in a processing/transport defect in Pompe disease., Replacing acid alpha-glucosidase in Pompe disease: recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers., The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease., Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. , Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease., We describe an improved method for detecting deficiency of the acid hydrolase, alpha-1,4-glucosidase in leukocytes, the enzyme defect in glycogen storage disease Type II (Pompe disease)., Acid alpha-glucosidase (GAA) deficiency causes Pompe disease,, Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase. Trials with recombinant human acid alpha-glucosidase enzyme replacement therapy (ERT) show a decrease in left ventricular mass and improved function., Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy., Pompe disease is caused by the congenital deficiency of the lysosomal enzyme acid alpha-glucosidase., The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease,, Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA). Recently, small molecule pharmacological chaperones have been shown to increase protein stability and cellular levels for mutant lysosomal enzymes and have emerged as a new therapeutic strategy for the treatment of LSDs., Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists., Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase., Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome., Structural modeling of mutant alpha-glucosidases resulting in a processing/transport defect in Pompe disease., Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA)., Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease., Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease., Mutations in alpha-glucosidase cause accumulation of glycogen in lysosomes, resulting in Pompe disease, a lysosomal storage disorder., Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase., Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme.[SEP]Relations: GAA has relations: cellcomp_protein with lysosome, disease_protein with cardiomyopathy, cellcomp_protein with lysosome, disease_protein with cardiomyopathy. Definitions: autosomal recessive disorder defined as following: An inherited disorder manifested only when two copies of a mutated gene are present.. alpha-glucosidase defined as following: Enzymes that catalyze the exohydrolysis of 1,4-alpha-glucosidic linkages with release of alpha-glucose. Deficiency of alpha-1,4-glucosidase may cause GLYCOGEN STORAGE DISEASE TYPE II.. LSD defined as following: Semisynthetic derivative of ergot (Claviceps purpurea). It has complex effects on serotonergic systems including antagonism at some peripheral serotonin receptors, both agonist and antagonist actions at central nervous system serotonin receptors, and possibly effects on serotonin turnover. It is a potent hallucinogen, but the mechanisms of that effect are not well understood.. glycogen defined as following: large branched polysaccharide consisting of glucose residues; the major carbohydrate reserve of animals, stored primarily in liver and muscle, synthesized and degraded for energy as demanded.. amino acid substitutions defined as following: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.. muscle defined as following: Contractile tissue that produces movement in animals.. alpha-1,4-glucosidase defined as following: An enzyme that catalyzes the hydrolysis of terminal 1,4-linked alpha-D-glucose residues successively from non-reducing ends of polysaccharide chains with the release of beta-glucose. It is also able to hydrolyze 1,6-alpha-glucosidic bonds when the next bond in sequence is 1,4.. glycogenosis defined as following: An autosomal recessive disease in which gene expression of glucose-6-phosphatase is absent, resulting in hypoglycemia due to lack of glucose production. Accumulation of glycogen in liver and kidney leads to organomegaly, particularly massive hepatomegaly. Increased concentrations of lactic acid and hyperlipidemia appear in the plasma. Clinical gout often appears in early childhood.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. lysosome defined as following: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed).. ERT defined as following: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, DYSPAREUNIA, and progressive development of OSTEOPOROSIS. This may also include the use of progestational agents in combination therapy.. cardiomyopathy defined as following: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).. Pompe disease defined as following: Glycogen storage disease due to acid maltase deficiency (AMD) is an autosomal recessive trait leading to metabolic myopathy that affects cardiac and respiratory muscles in addition to skeletal muscle and other tissues. AMD represents a wide spectrum of clinical presentations caused by an accumulation of glycogen in lysosomes.. mutant defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. myopathy defined as following: Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.. AAG defined as following: An antineoplastic antibiotic that is structurally similar to the benzoquinone ansamycin antibiotic geldanamycin. A geldanamycin analogue binds to HSP90, a chaperone protein that aids in the assembly, maturation, and folding of proteins. Subsequently, the function of HSP90 is inhibited, leading to the degradation and depletion of client proteins such as kinases and transcription factors involved with cell cycle regulation and signal transduction.. GAA defined as following: A Niger-Congo Kwa language spoken in the capital area of Ghana.. death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. respiratory insufficiency defined as following: Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed). glycogen storage disease II defined as following: An autosomal recessive metabolic disorder due to deficient expression of amylo-1,6-glucosidase (one part of the glycogen debranching enzyme system). The clinical course of the disease is similar to that of glycogen storage disease type I, but milder. Massive hepatomegaly, which is present in young children, diminishes and occasionally disappears with age. Levels of glycogen with short outer branches are elevated in muscle, liver, and erythrocytes. Six subgroups have been identified, with subgroups Type IIIa and Type IIIb being the most prevalent.. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. human defined as following: Members of the species Homo sapiens..", "label": "yes"}
{"id": "converted_390", "sentence1": "Does PU.1 (SPI1) affect NF-kB binding?", "sentence2": "Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs)., Within 1217 bp of upstream sequence, 3 sites for NF-kB, 10 sites for NF-IL6, 15 sites for AP1, 6 sites for AP4, 2 sites for CHOP/CEBP alpha and 1 site for SP1 and PU.1 were identified., As little as 82 bp of upstream sequence gave relatively strong luciferase activity, a region containing both a PU.1 and NF-kB site., Potential transcription regulatory elements, AP1, AP2, AP3, NF-kB and GATA recognition sequences, are located within 523 bp upstream of the p35 gene; however, no TATA box was identified. The p40 subunit gene consists of eight exons. A TATA box is located 30 bp upstream from the transcription start site, and AP1, AP3, GATA, and Pu.1 recognition sequences are located within 690 bp upstream of the p40 gene., Several putative binding sequences for ubiquitous (Sp1, AP-1, AP-2, and NF-kB) and leukocyte-specific (PU.1) transcription factors have been identified in the proximal region of the CD11c promoter which may participate in the regulation of the expression of p150,95., PU.1 is regulated by NF-kappaB through a novel binding site in a 17 kb upstream enhancer element.[SEP]Definitions: PU.1 defined as following: The human SPI1 wild-type allele is located in the vicinity of 11p11.2 and is approximately 24 kb in length. This allele, which encodes transcription factor PU.1 protein, is involved in the activation of transcription by RNA polymerase II.. interferon regulatory factors defined as following: A family of transcription factors that share an N-terminal HELIX-TURN-HELIX MOTIF and bind INTERFERON-inducible promoters to control GENE expression. IRF proteins bind specific DNA sequences such as interferon-stimulated response elements, interferon regulatory elements, and the interferon consensus sequence.. AP2 defined as following: Transcription factor AP-2-alpha (437 aa, ~48 kDa) is encoded by the human TFAP2A gene. This protein plays a role in both transcriptional regulation and lens vesicle morphogenesis.. p150,95 defined as following: A major adhesion-associated heterodimer molecule expressed by MONOCYTES; GRANULOCYTES; NK CELLS; and some LYMPHOCYTES. The alpha subunit is the CD11C ANTIGEN, a surface antigen expressed on some myeloid cells. The beta subunit is the CD18 ANTIGEN.. p40 gene defined as following: Human IL9 wild-type allele is located in the vicinity of 5q31.1 and is approximately 4 kb in length. This allele, which encodes interleukin-9 protein, is involved in hematopoiesis, proliferation stimulation, and apoptotic prevention.. binding site defined as following: A Binding Site Domain is a region of protein that physically interacts stereospecifically, and usually at high affinity, with a specific ligand, substrate, or a specific domain of some complex target biomolecule, such as a protein, lipid, carbohydrate, or nucleic acid. Typically, but not necessarily, the interaction results in protein conformational alteration and functional modification.. NF-kB defined as following: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.. AP1 defined as following: A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.. region defined as following: The continents and countries situated on those continents; the UNITED STATES and each of the constituent states arranged by region; CANADA and each of its provinces; AUSTRALIA and each of its states; the major bodies of water and major islands on both hemispheres; and selected major cities.. AP-2 defined as following: Human TFAP2A wild-type allele is located in the vicinity of 6p24 and is approximately 24 kb in length. This allele, which encodes transcription factor AP-2 alpha protein, plays a role in the modulation of inducible transcription.. TATA box defined as following: A conserved A-T rich sequence which is contained in promoters for RNA polymerase II. The segment is seven base pairs long and the nucleotides most commonly found are TATAAAA.. transcription regulatory elements defined as following: Nucleotide sequences of a gene that are involved in the regulation of GENETIC TRANSCRIPTION.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. sites defined as following: A position in relation to its surroundings.. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process..", "label": "yes"}
{"id": "converted_28", "sentence1": "Proteomic analyses need prior knowledge of the organism complete genome. Is the complete genome of the bacteria of the genus Arthrobacter available?", "sentence2": "Complete genome sequence of Arthrobacter phenanthrenivorans type strain (Sphe3)., Complete genome sequence and metabolic potential of the quinaldine-degrading bacterium Arthrobacter sp. Rue61a., Here, we described the high quality draft genome sequence, annotations and the features ofArthrobactersp. B6., Complete genome sequence of Arthrobacter sp. ZXY-2 associated with effective atrazine degradation and salt adaptation., We announce here the draft genome sequence ofArthrobactersp. strain EpSL27, isolated from the stem and leaves of the medicinal plantEchinacea purpureaand able to inhibit human-pathogenic bacterial strains. , We report here the 4.6-Mb genome sequence of a nylon oligomer-degrading bacterium,Arthrobactersp. strain KI72., Arthrobacter alpinusR3.8 is a psychrotolerant bacterial strain isolated from a soil sample obtained at Rothera Point, Adelaide Island, close to the Antarctic Peninsula. Strain R3.8 was sequenced in order to help discover potential cold active enzymes with biotechnological applications. [SEP]Definitions: leaves defined as following: Expanded structures, usually green, of vascular plants, characteristically consisting of a bladelike expansion attached to a stem, and functioning as the principal organ of photosynthesis and transpiration. (American Heritage Dictionary, 2d ed). salt defined as following: Sodium chloride used in foods.. stem defined as following: A type of TRANSMISSION ELECTRON MICROSCOPY in which the object is examined directly by an extremely narrow electron beam scanning the specimen point-by-point and using the reactions of the electrons that are transmitted through the specimen to create the image. It should not be confused with SCANNING ELECTRON MICROSCOPY.. bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.. organism defined as following: A living entity.. genome defined as following: Anatomical set of genes in all the chromosomes..", "label": "yes"}
{"id": "converted_2245", "sentence1": "Is there a sequence bias in MNase digestion patterns?", "sentence2": "In addition, unlike MNase, MPE-Fe(II) cleaves nuclear DNA with little sequence bias., These findings collectively indicate that MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias., Micrococcal nuclease does not substantially bias nucleosome mapping., MNase has hitherto been very widely used to map nucleosomes, although concerns have been raised over its potential to introduce bias., These results indicate that biases in nucleosome positioning data collected using MNase are, under our conditions, not significant., Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques., Standardized collection of MNase-seq experiments enables unbiased dataset comparisons., Here, we show that the cutting preference of MNase in combination with size selection generates a sequence-dependent bias in the resulting fragments., We propose that combined MNase/exoIII digestion can be applied to in situ chromatin for unbiased genome-wide mapping of nucleosome positions that is not influenced by DNA sequences at the core/linker junctions., Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques., Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques., These results indicate that biases in nucleosome positioning data collected using MNase are, under our conditions, not significant.., Micrococcal nuclease does not substantially bias nucleosome mapping., We find that maize MNase-hypersensitive (MNase HS) regions localize around active genes and within recombination hotspots, focusing biased gene conversion at their flanks.[SEP]Definitions: DNA sequences defined as following: The sequence of nucleotide residues along a DNA chain.. Micrococcal nuclease defined as following: An enzyme that catalyzes the endonucleolytic cleavage to 3'-phosphomononucleotide and 3'-phospholigonucleotide end-products. It can cause hydrolysis of double- or single-stranded DNA or RNA. (From Enzyme Nomenclature, 1992) EC 3.1.31.1.. nucleosome defined as following: A complex comprised of DNA wound around a multisubunit core and associated proteins, which forms the primary packing unit of DNA into higher order structures. [GOC:elh]. nuclear DNA defined as following: The DNA that is normally located in the nucleus of a eukaryotic cell.. nucleosomes defined as following: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4..", "label": "yes"}
{"id": "converted_2844", "sentence1": "Does epidural anesthesia for pain management during labor affect the Apgar score of the the infant?", "sentence2": " We retrospectively analyzed 93 consecutive single-pregnancy patients who underwent cesarean section with combined spinal-epidural anesthesia. The patients were divided into two groups, depending on the use of 6% HES 130/0.4: group A (461 ± 167 ml of saline-based HES was administered; 43 patients) and group B (HES not administered; 50 patients). The major outcome was umbilical cord chloride level at delivery. The volume infused from operating room admission until delivery was not significantly different between groups. The umbilical cord chloride level at delivery was statistically significantly higher in group A than in group B, but clinically similar (108 ± 2 vs. 107 ± 2 mmol/l, P = 0.02). No differences were observed in the Apgar score or other umbilical cord laboratory data at delivery (Na+, K+, pH, base excess), CONCLUSION\nSubarachnoid or epidural sufentanil, in the doses used in this study, associated with local anesthetics, had the same effect on the duration of labor after analgesia and in the Apgar score of newborns., CONCLUSION Subarachnoid or epidural sufentanil, in the doses used in this study, associated with local anesthetics, had the same effect on the duration of labor after analgesia and in the Apgar score of newborns.[SEP]Definitions: sufentanil defined as following: An opioid analgesic that is used as an adjunct in anesthesia, in balanced anesthesia, and as a primary anesthetic agent.. HES defined as following: A rare hematologic disease characterized by eosinophilia without evidence of clonality persisting for at least six months, for which no underlying cause can be identified. The condition is associated with signs of organ damage and dysfunction. Clinical manifestations are highly variable, depending on the organ systems involved, and include rapidly developing, life-threatening cardiovascular or neurological complications..", "label": "no"}
{"id": "converted_4148", "sentence1": "Is the glucocorticoid receptor a transcription factor?", "sentence2": "GR and KLF4, both pioneer transcription factors,, The glucocorticoid receptor (GR) is a ligand-binding dependent transcription factor that ultimately regulates vital biological processes and inflammation response through specific gene expression control, thus representing a notable drug target to explore. , The glucocorticoid receptor (GR) is a ligand-activated transcription factor that translocates to the nucleus upon hormone stimulation and distributes between the nucleoplasm and membraneless compartments named nuclear foci.[SEP]Relations: nucleoplasm has relations: cellcomp_protein with KLF4, cellcomp_protein with KLF4. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). KLF4 defined as following: Krueppel-like factor 4 (470 aa, ~50 kDa) is encoded by the human KLF4 gene. This protein regulates transcription.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. nucleoplasm defined as following: That part of the nuclear content other than the chromosomes or the nucleolus. [GOC:ma, ISBN:0124325653]. glucocorticoid receptor defined as following: This gene is involved in ligand-activated transcriptional regulation and mutations in the gene are associated with glucocorticoid resistance.. GR defined as following: Glutathione reductase, mitochondrial (522 aa, ~56 kDa) is encoded by the human GSR gene. This protein plays a role in the synthesis of the sulfhydryl form of glutathione.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process..", "label": "yes"}
{"id": "converted_374", "sentence1": "Is desmin an intermediate filament protein involved in Dilated Cardiomyopathy (DCM)?", "sentence2": "Desmin-related myofibrillar myopathy (DRM) is a cardiac and skeletal muscle disease caused by mutations in the desmin (DES) gene. Mutations in the central 2B domain of DES cause skeletal muscle disease that typically precedes cardiac involvement. However, the prevalence of DES mutations in dilated cardiomyopathy (DCM) without skeletal muscle disease is not known., The lack of severe disruption of cytoskeletal desmin network formation seen with mutations in the 1A and tail domains suggests that dysfunction of seemingly intact desmin networks is sufficient to cause DCM., According to the predominant view, desmin mutations cause dilated cardiomyopathy (DCM). We evaluated a family with restrictive cardiomyopathy (RCM) associated with a novel desmin mutation and reviewed recent reports regarding the frequency of RCM in patients with desmin myopathy., Dilated cardiomyopathy (DCM) is characterized by enlargement and dilation of all heart compartments associated with serious decrease of its contractile function. DCM hallmark is the combination of dystrophic and hypertrophic alterations of cardiomyocytes. Since the power output of cardiac cells is directly related to remodeling of their contractile machinery we investigated expression of selected contractile and cytoskeletal proteins in the left ventricle of DCM patients using immunoblotting. The content of the recognized protein markers of cardiomyocyte hypertrophy such as tubulin, desmin and slow skeletal myosin heavy chain isoform, MHCbeta, was significantly elevated in DCM compared to normal myocardium., In contrast, overexpression of desmin filaments by itself is not detrimental to the heart. Although loss-of-function studies have been more limited, ablation of the desmin gene causes mitochondrial dysfunction and apoptosis, resulting in cardiomyopathy in mice. From function studies, abnormal desmin aggregation and disruption of the desmin networks resulting from expression of either mutant desmin or mutant CryAB have been shown to remodel the heart and compromise cardiac function, suggesting their synergistic roles in disease pathogenesis., A missense mutation in the desmin gene (DES) causes DCM in a human family., Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Several lines of evidence suggest impaired vascular function in desmin null animals., Familial DCM is commonly inherited as autosomal dominant trait; less frequently it is autosomal recessive, X-linked or matrilinear. The disease is clinically and genetically heterogeneous. Genes causally linked to this phenotype include dystrophin, dystrophin-associated glycoproteins, actin, desmin, beta-miosin heavy chain, cardiac troponin T, and mitochondrial DNA genes, mostly transfer RNAs., Examination of families has identified so far eight disease genes, namely the dystrophin, tafazzin, cardiac actin, desmin, lamin A/C, delta- sarcoglycan, cardiac beta-myosin heavy chain, and cardiac troponin T gene., Mutations of the desmin, delta-sarcoglycan, the cardiac actin and beta-myosin heavy chain as well as the troponin T gene are known to cause autosomal dominant-dilated cardiomyopathy without other abnormalities., Autosomal dominant DCM is the most frequent form (56% of our cases), and several candidate disease loci have been identified by linkage analysis. Three disease genes are presently known: the cardiac actin gene, the desmin gene, and the lamin A/C gene., Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality. Two genes have been identified for the X-linked forms (dystrophin and tafazzin), whereas three other genes (actin, lamin A/C, and desmin) cause autosomal dominant DCM;, Desmin defects were also recently identified in 1 familial dilated cardiomyopathy., By candidate gene screening, the molecular diagnosis can be provided for dystrophin, DAG, mitochondrial DNA, actin and desmin gene defects., Desmin (z-bands) are partly destroyed in DCM. Anti-desmin antibody titers as indicators of a possible secondary immune response are found high in patients with acute myocarditis declining during reconvalescence and are also elevated in DCM. , Desmin, the muscle-specific intermediate filament protein, is a major target in dilated cardiomyopathy and heart failure in humans and mice, Desmin, the muscle-specific intermediate filament, is involved in myofibrillar myopathies, dilated cardiomyopathy and muscle wasting[SEP]Relations: cytoskeletal protein binding has relations: molfunc_protein with DES, molfunc_protein with DES. Congestive heart failure has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. Cardiomyopathy has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. dilated cardiomyopathy has relations: disease_protein with DES, disease_protein with DES. myofibrillar myopathy has relations: disease_protein with DES, disease_protein with DES. X-linked inheritance has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. muscle contraction has relations: bioprocess_protein with DES, bioprocess_protein with DES. myocardium has relations: anatomy_protein_present with DES, anatomy_protein_present with DES. Definitions: cytoskeletal proteins defined as following: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.. DAG defined as following: A synthetic oil with anti-obesity activity. The enzymatically synthesized isoform, 1,3-isoform diacylglycerol, is suggested to decrease formation of chylomicrons as well as shunting them directly to the liver through the portal vein where they are oxidized. Increased beta-oxidation may enhance body weight loss, suppress body fat accumulation and lower serum triacylglycerol levels through increasing satiety.. antibody defined as following: A protein complex that in its canonical form is composed of two identical immunoglobulin heavy chains and two identical immunoglobulin light chains, held together by disulfide bonds and sometimes complexed with additional proteins. An immunoglobulin complex may be embedded in the plasma membrane or present in the extracellular space, in mucosal areas or other tissues, or circulating in the blood or lymph. [GOC:add, GOC:jl, ISBN:0781765196]. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. cardiomyocytes defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. DCM defined as following: A chlorinated methotrexate derivative. Dichloromethotrexate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylates and inhibiting DNA and RNA synthesis. This agent is metabolized and excreted by the liver. (NCI04). cardiomyopathy defined as following: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).. desmin defined as following: Desmin (470 aa, ~54 kDa) is encoded by the human DES gene. This protein is involved in the regulation of cytoskeletal dynamics in muscle cells.. RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). dilated cardiomyopathy defined as following: Cardiomyopathy which is characterized by dilation and contractile dysfunction of the left and right ventricles. It may be idiopathic, or it may result from a myocardial infarction, myocardial infection, or alcohol abuse. It is a cause of congestive heart failure.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. myofibrillar myopathies defined as following: An inherited or sporadic disorder affecting the skeletal muscles.. X-linked defined as following: A mode of inheritance that is observed for traits related to a gene encoded on the X chromosome. [HPO:curators]. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. autosomal defined as following: Any chromosome other than a sex chromosome. [GOC:mah]. desmin gene defined as following: This gene is involved in the maintenance of muscle cell structure.. dystrophin defined as following: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as SPECTRIN and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa.. lamin A/C gene defined as following: This gene is involved in the architecture of nuclear membrane construction.. contractile defined as following: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.. muscle wasting defined as following: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation.. actin defined as following: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.. CryAB defined as following: This gene is involved in lens formation.. mitochondrial dysfunction defined as following: A functional anomaly of mitochondria. [ORCID:0000-0001-5208-3432]. mitochondrial DNA defined as following: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.. tubulin defined as following: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.. humans defined as following: Members of the species Homo sapiens.. myocardium defined as following: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.. cardiac troponin T defined as following: Troponin T, cardiac muscle (298 aa, ~36 kDa) is encoded by the human TNNT2 gene. This protein plays a role in cardiac muscle contraction.. Dilated Cardiomyopathy defined as following: Cardiomyopathy which is characterized by dilation and contractile dysfunction of the left and right ventricles. It may be idiopathic, or it may result from a myocardial infarction, myocardial infection, or alcohol abuse. It is a cause of congestive heart failure.. intermediate filament protein defined as following: Filaments 7-11 nm in diameter found in the cytoplasm of all cells. Many specific proteins belong to this group, e.g., desmin, vimentin, prekeratin, decamin, skeletin, neurofilin, neurofilament protein, and glial fibrillary acid protein..", "label": "yes"}
{"id": "converted_3706", "sentence1": "Do genes with monoallelic expression contribute proportionally to genetic diversity in humans?", "sentence2": "Genes with monoallelic expression contribute disproportionately to genetic diversity in humans., An unexpectedly large number of human autosomal genes are subject to monoallelic expression (MAE). Our analysis of 4,227 such genes uncovers surprisingly high genetic variation across human populations. This increased diversity is unlikely to reflect relaxed purifying selection. Remarkably, MAE genes exhibit an elevated recombination rate and an increased density of hypermutable sequence contexts. However, these factors do not fully account for the increased diversity. We find that the elevated nucleotide diversity of MAE genes is also associated with greater allelic age: variants in these genes tend to be older and are enriched in polymorphisms shared by Neanderthals and chimpanzees. Both synonymous and nonsynonymous alleles of MAE genes have elevated average population frequencies. We also observed strong enrichment of the MAE signature among genes reported to evolve under balancing selection. We propose that an important biological function of widespread MAE might be the generation of cell-to-cell heterogeneity; the increased genetic variation contributes to this heterogeneity., Genes with monoallelic expression contribute disproportionately to genetic diversity in humans[SEP]Definitions: polymorphisms defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. humans defined as following: Members of the species Homo sapiens.. Neanderthals defined as following: Common name for an extinct species of the Homo genus. Fossils have been found in Europe and Asia. Genetic evidence suggests that limited interbreeding with modern HUMANS (Homo sapiens) took place.. MAE defined as following: A generalized myoclonic-atonic seizure is a type of generalized motor seizure characterized by a myoclonic jerk followed by an atonic motor component. [HPO:jalbers, PMID:28276060, PMID:28276064]. Genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "no"}
{"id": "converted_4138", "sentence1": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "sentence2": "The use of methotrexate in rheumatoid arthritis., Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis., Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis, The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis., Methotrexate (MTX) is currently under study for use in juvenile rheumatoid arthritis. , The rational use of methotrexate in rheumatoid arthritis and other rheumatic diseases., Methotrexate-induced hepatic cirrhosis is less common in rheumatoid arthritis than previously thought, although its occurrence in psoriasis is probably higher than in rheumatoid arthritis. , Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions. , The use of methotrexate in rheumatoid arthritis., Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease., MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival., The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases, A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed., Methotrexate has been used in treatment of rheumatoid arthritis (RA) since the 1980s and to this day is often the first line medication for RA treatment., OBJECTIVE: Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries., Low dose pulse methotrexate (MTX) has become a widely used therapy for rheumatoid arthritis (RA) because of its good response rate profile. With, Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The ai, Patients having rheumatoid arthritis (RA) treated with methotrexate (MTX) are at an increased risk of developing lymphoproliferative disorder (LPD). Epstei, Increasingly, methotrexate (MTX) and sulphasalazine (SASP) are used initially for second-line therapy of rheumatoid arthritis (RA). Althoug, OBJECTIVES: The folate antagonist methotrexate (MTX) has become established as the most commonly used disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA) but is commonly discontinued due to adverse effe, e suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About , BACKGROUND: Treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA) leads to decreased total immunoglobulin (Ig) levels and impairs vaccine-specific IgG antibody levels following pneumococcal vaccinat, In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enro, Methotrexate (MTX) is known as a first-line synthetic disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA)., Biological treatments are expensive and using SC methotrexate can improve disease control in RA patients, thus potentially avoiding or delaying the requirement for future biological treatment., Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries., We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs).M, st covered some but not all of the following areas: baseline \"pre-MTX\" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). R, lectronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. , MTX must at the present time be used only in severe RA, refractory to more than one classical slow acting drug., MTX is as effective in treating RA as the other second line drugs and always more rapidly effective, perhaps because of anti-inflammatory properties., For the low doses used in RA (less than 15 mg/week), MTX is completely and rapidly absorbed with an active process membrane transport., Methotrexate, which is used for RA treatment, causes thrombocytopenia., Methorexate therapy in a patient with rheumatoid arthritis complicated by idiopathic thrombocytopenic purpura., This case shows that methotrexate may be used in patients diagnosed with RA that is associated with ITP under strict monitoring., Here, we report an RA case that also had ITP, which did not decrease in platelet count after methotrexate therapy., We started methotrexate therapy 10 mg per week for treatment of RA, and hydroxychloroquine therapy was stopped due to nonresponse., Methotrexate (MTX) is the anchor treatment for rheumatoid arthritis (RA) and has been very thoroughly studied in many different patient populations, as monotherapy and in combination with various other disease modifying antirheumatic drugs and biologic agents, as they became available., Although rheumatologists have been using methotrexate in the treatment of RA for some time, controlled studies have been needed to establish the safety and efficacy of this agent., Methotrexate is generally the first-line drug for the treatment of RA, psoriatic arthritis and other forms of inflammatory arthritis, and it enhances the effect of most biologic agents in RA., Despite the introduction of numerous biologic agents for the treatment of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, low-dose methotrexate therapy remains the gold standard in RA therapy., A number of studies show the efficacy of methotrexate (MTX) for rheumatoid arthritis (RA) in general., Methotrexate (MTX) is currently the most frequently used drugs in the treatment of rheumatoid arthritis (RA)., Methotrexate (MTX) has been the anchor treatment in rheumatoid arthritis (RA) over the last 15 years, and is used in combination with biologic agents to enhance efficacy over the last decade or so.[SEP]Relations: Methotrexate has relations: contraindication with thrombocytopenia, contraindication with thrombocytopenia. Folic acid has relations: drug_drug with Aminopterin, drug_drug with Aminopterin. Rheumatoid arthritis has relations: disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis. Azathioprine has relations: contraindication with thrombocytopenia, contraindication with thrombocytopenia. thrombocytopenic purpura has relations: disease_disease with thrombocytopenia, disease_disease with thrombocytopenia. Definitions: biologic agents defined as following: Endogenously synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.. methotrexate defined as following: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.. psoriasis defined as following: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.. folic acid defined as following: A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.. SASP defined as following: Thioredoxin (105 aa, ~12 kDa) is encoded by the human TXN gene. This protein plays a role in redox reactions, signaling and immunity.. acute leukemia defined as following: A clonal (malignant) hematopoietic disorder with an acute onset, affecting the bone marrow and the peripheral blood. The malignant cells show minimal differentiation and are called blasts, either myeloid blasts (myeloblasts) or lymphoid blasts (lymphoblasts).. rheumatoid arthritis defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. Aminopterin defined as following: A folic acid derivative used as a rodenticide that has been shown to be teratogenic.. azathioprine defined as following: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed). sulphasalazine defined as following: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907). infliximab defined as following: A chimeric monoclonal antibody to TNF-ALPHA that is used in the treatment of RHEUMATOID ARTHRITIS; ANKYLOSING SPONDYLITIS; PSORIATIC ARTHRITIS and CROHN'S DISEASE.. LPD defined as following: A rare, benign process that affects the peritoneal cavity and is characterized by the formation of multiple small nodules that are composed of well differentiated smooth muscle. It usually affects adults in their late reproductive years. Most patients are asymptomatic. The tumor nodules may regress spontaneously.. ITP defined as following: Thrombocytopenia occurring in the absence of toxic exposure or a disease associated with decreased platelets. It is mediated by immune mechanisms, in most cases IMMUNOGLOBULIN G autoantibodies which attach to platelets and subsequently undergo destruction by macrophages. The disease is seen in acute (affecting children) and chronic (adult) forms.. low-dose defined as following: A reduced quantity of a therapeutic agent prescribed to be taken at one time or at stated intervals.. anti-inflammatory defined as following: Substances that reduce or suppress INFLAMMATION.. folate antagonist defined as following: Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033). disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. rheumatic diseases defined as following: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement.. thrombocytopenia defined as following: An autosomal dominant disorder caused by mutation(s) in the ANKRD26 gene, encoding ANKRD26 protein. Additionally, in one family, a mutation(s) has been identified in the MASTL gene, encoding serine/threonine-protein kinase greatwall. The condition is characterized by mild to moderate bruisability.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated..", "label": "yes"}
{"id": "converted_3340", "sentence1": "Is MLL3 part of the ASCOM complex?", "sentence2": "MLL3 as part of ASCOM complex, MLL3 as part of activating signal cointegrator-2 -containing complex (ASCOM)[SEP]Definitions: MLL3 defined as following: This gene plays a role in both methylation and transcriptional regulation.", "label": "yes"}
{"id": "converted_462", "sentence1": "Does melanoma occur in people of African origin ?", "sentence2": "ALM is the most common type of melanoma amongst Asians, Africans,, ALM develops on palmar, plantar, and subungual skin, and its biology is different from that of other cutaneous melanomas, where sunlight is the major known environmental determinant, We present four albinos with histologic diagnoses of skin cancer, Four Nigerian albinos (two men and two women) with skin cancer, The sites of the lesions included the head [squamous cell carcinoma (SCC) in two patients and basal cell carcinoma (BCC) in one patient] and the upper limb (melanoma, wenty-nine patients (18 males and 11 females) with skin cancer were identified, Kaposi sarcoma associated with HIV represented 81.8 percent of KS cases found. Squamous cell carcinoma (SCC) ranked second and malignant melanoma third, Earlier studies have shown frequent mutations in the BRAF and NRAS genes in cutaneous melanoma, but these alterations have not been examined in the rare category of melanoma from black Africans., In a series of melanomas from black Africans (n=26), only two BRAF mutations (8%) were found, both being different from the common T1799A substitution. Moreover, melanomas from black Africans exhibited mutations in NRAS exon 1 only (12%), whereas NRAS exon 2 mutations were predominant in melanomas from Caucasians. Thus, the frequencies of BRAF and NRAS mutations were particularly low in melanomas from black Africans, supporting a different pathogenesis of these tumors., Malignant melanoma (MM) remains a pediatric rarity world-wide, but perhaps more so in black Africans. To the best of our knowledge, the current report of MM in a two-and-a-half-year-old Nigerian who had a pre-existing congenital giant hairy nevus is probably the first (in an accessible literature) in a black African child., Malignant melanomas in black Africans are predominantly located on the lower extremities, Thus, our findings indicate that melanomas located on the lower extremities in black Africans show several features of aggressiveness; in particular, the proliferative activity was high, and p16 alterations was frequent as evidenced by loss of protein staining. Our findings also indicated that the diagnosis is delayed among black Africans., Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians, but the ratio of their incidence rates of cutaneous malignant melanoma to that of squamous cell carcinoma is larger than the corresponding ratio for Caucasians. (, Albino Africans, as compared with normally pigmented Africans, seem to have a relatively small risk of getting cutaneous malignant melanomas compared to nonmelanomas. This is probably also true for albino and normally pigmented Caucasians., Scant data exists on melanoma in blacks from Africa, The mean age at presentation of the 39 women and 24 men was 60.5 years (range of 30 to 85 years), with a peak incidence in the sixth decade. The foot was the most common site of disease (45 patients). Seven patients had subungual melanoma, seven had primary mucosal lesions, and in six, the primary lesion could not be found., The poor prognosis in black patients in South Africa is the result of delayed presentation with thick primary lesions and advanced disease, The outcome of treatment in 40 black patients (27 women, 13 men; mean age 62.9 years) with plantar melanoma over a 13-year period was analysed, Delay in presentation and locally advanced disease may explain the poor prognosis of plantar melanoma in black South Africans., Eighteen cases of malignant skin tumors seen at the University of Port Harcourt Teaching Hospital over 3 years (1984 to 1987) were analyzed for diagnoses, site of tumors, sex, and age. Seven patients (39%) had malignant melanomas affecting only the soles of the feet, while the same number had squamous cell carcinomas widely distributed in various parts of the body, Non-white populations experienced in general a much lower incidence of melanoma although there was some overlap of white and non-white rates., Populations of African descent were found to have a higher incidence than those of Asiatic origin, but it was concluded that this was due largely to the high frequency of tumours among Africans on the sole of the foot., Pathological features of twenty-one cases of malignant melanoma studied in the University of Nigeria Teaching Hospital, Enugu during the period January, 1974 to December, 1975 are presented. Malignant melanoma accounted for 2.4% of all tumours and 4.5% of all malignant tumours, greatest age incidence being in the fifth to seventh decades., 81% melanomas occurred on the sole of feet validating the hypothesis that the pigmented skin in Africans is resistant to malignant melanoma., This paper reports the incidence of this lesion in association with invasive malignant melanomas of the feet and hands of Black Africans., Follow-up data (over a 3-year period) and the histological appearances of primary lesion were studied and related in 40 Black patients with malignant melanoma., Malignant melanoma of the skin in Blacks in formidable and sinister tumour., The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces., Twenty-one cases of malignant melanoma occurring in the Igbos of Nigeria have been analysed. The site of predilection is the sole of the foot. This result supports the conclusion that Negroes tend to have the disease in the non-pigmented parts., A case of leptomeningeal melanoma in an African child of 7 years is presented together with a survey of pigmentation in the normal African brain.[SEP]Relations: melanoma has relations: disease_protein with BRAF, disease_disease with skin cancer, disease_protein with BRAF, disease_disease with skin cancer. non-cutaneous melanoma has relations: disease_disease with melanoma, disease_disease with melanoma. squamous cell carcinoma of floor of mouth has relations: disease_disease with squamous cell carcinoma, disease_disease with squamous cell carcinoma. melanocytic neoplasm has relations: disease_disease with melanoma, disease_disease with melanoma. anal canal squamous cell carcinoma has relations: disease_disease with squamous cell carcinoma, disease_disease with squamous cell carcinoma. Definitions: plantar defined as following: relating to the sole of the foot. malignant melanomas defined as following: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445). BCC defined as following: A carcinoma involving the basal cells.. skin cancer defined as following: A primary or metastatic malignant neoplasm involving the skin. Primary malignant skin neoplasms most often are carcinomas (either basal cell or squamous cell carcinomas) or melanomas. Metastatic malignant neoplasms to the skin include carcinomas and lymphomas.. NRAS defined as following: Human Oncogene N-RAS is a mutated variant of NRAS Gene (RAS Family), which encodes p21 N-Ras Protein, a monomeric GTPase involved in transmembrane signal transduction that alternates between inactive GDP-bound and active GTP-bound forms. RAS is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase-activating protein. Mitogen-stimulated RAS stabilizes MYC protein and enhances MYC accumulation by the RAS/RAF/MAPK pathway, which appears to inhibit the proteasome-dependent degradation of MYC. Implicated in a variety of human tumors, specific amino acid mutations activate c-RAS and transform cells. Oncogene NRAS disrupts normal cell function.. mucosal lesions defined as following: A pathologic process that affects the mucosa.. BRAF defined as following: Serine/threonine-protein kinase B-raf (766 aa, ~84 kDa) is encoded by the human BRAF gene. This protein plays a role in protein phosphorylation, mitogenesis and neuronal signal transduction.. cutaneous melanoma defined as following: A primary melanoma arising from atypical melanocytes in the skin. Precursor lesions include acquired and congenital melanocytic nevi, and dysplastic nevi. Several histologic variants have been recognized, including superficial spreading melanoma, acral lentiginous melanoma, nodular melanoma, and lentigo maligna melanoma.. squamous cell carcinomas defined as following: A squamous cell carcinoma arising from the oral cavity. It affects predominantly adults in their fifth and sixth decades of life and is associated with alcohol and tobacco use. Human papillomavirus is present in approximately half of the cases. It is characterized by a tendency to metastasize early to the lymph nodes. When the tumor is small, patients are often asymptomatic. Physical examination may reveal erythematous or white lesions or plaques. The majority of patients present with signs and symptoms of locally advanced disease including mucosal ulceration, pain, difficulty with speaking, chewing, and swallowing, bleeding, weight loss, and neck swelling. Patients may also present with swollen neck lymph nodes without any symptoms from the oropharyngeal tumor. The most significant prognostic factors are the size of the tumor and the lymph nodes status.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. aggressiveness defined as following: Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism.. lesions defined as following: A localized pathological or traumatic structural change, damage, deformity, or discontinuity of tissue, organ, or body part.. soles defined as following: The undersurface of the foot.. melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. Kaposi sarcoma defined as following: A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Kaposi's sarcoma occurs spontaneously in Jewish and Italian males in Europe and the United States. An aggressive variant in young children is endemic in some areas of Africa. A third form occurs in about 0.04% of kidney transplant patients. There is also a high incidence in AIDS patients. (From Dorland, 27th ed & Holland et al., Cancer Medicine, 3d ed, pp2105-7) HHV-8 is the suspected cause.. squamous cell carcinoma defined as following: A squamous cell carcinoma (SCC) arising from the anal canal or the anal margin (perianal skin). Human papillomavirus is detected in the majority of cases. Homosexual HIV-positive men have an increased risk of developing anal squamous cell carcinoma in comparison to the general male population. Symptoms include anal pruritus, discomfort when sitting, pain, change in bowel habit, and bleeding. The prognosis is generally better for anal margin SCC than for anal canal SCC.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. Africans defined as following: People native to or inhabitants of AFRICA.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. HIV defined as following: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).. basal cell carcinoma defined as following: A malignant skin neoplasm that seldom metastasizes but has potentialities for local invasion and destruction. Clinically it is divided into types: nodular, cicatricial, morphaic, and erythematoid (pagetoid). They develop on hair-bearing skin, most commonly on sun-exposed areas. Approximately 85% are found on the head and neck area and the remaining 15% on the trunk and limbs. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1471). sites defined as following: A position in relation to its surroundings.. primary lesion defined as following: A term that refers to a pathologic process in its original anatomic site of growth..", "label": "yes"}
{"id": "converted_1599", "sentence1": "Is there any protein that undergoes both mono-ubiquitination and poly-ubiquitination?", "sentence2": "The yeast G protein alpha subunit Gpa1 represents a rare example of a protein that undergoes both mono- and poly-ubiquitination. , Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination., These fingers possess E3 activities of mono-ubiquitination and poly-ubiquitination, respectively, with ubiquitin-conjugating enzyme (E2)-binding capabilities. , Instead of promoting poly-ubiquitination and degradation, we show that Smurf2 actually induces multiple mono-ubiquitination of Smad3 in vivo., mono-ubiquitination of CIITA dramatically increases its transactivity whereas poly-ubiquitination leads to CIITA degradation., This leads to a model in which Lys134 of LDB1 can be either mono-ubiquitinated, leading to stabilization, or poly-ubiquitinated, leading to degradation by the proteasome pathway. , mono-ubiquitination of CIITA increases its transactivity, whereas poly-ubiquitination of CIITA leads to its degradation, PS1 ubiquitination after PI3K inhibition is represented by the multiple mono-ubiquitination, instead of poly-ubiquitination, Our observations support a novel functional relationship between parkin and Hsc/Hsp70 and support the notion that parkin is a multi-purpose E3 ubiquitin ligase capable of modifying proteins either via attachment of alternatively linked poly-ubiquitin chains or through multiple mono-ubiquitination to achieve alternate biological outcomes, our results indicate that Hsp70 facilitates CHIP-mediated poly-ubiquitination of Smad1 whereas it attenuates CHIP-meditated mono-ubiquitination of Smad1., Whereas poly-ubiquitination targets protein substrates for proteasomal degradation, mono-ubiquitination is known to regulate protein trafficking in the endosomal system and to target cargo proteins for lysosomal degradation., Our results suggest that oxidative stress induces not only poly-ubiquitination but also mono-ubiquitination of LDH-A, which may be involved in its lysosomal degradation during unloading., wild type Smad4 is a relatively stable protein that undergoes mono- or oligo-ubiquitination, a modification not linked to protein degradation, These data suggest that oligo-ubiquitination positively regulates Smad4 function, whereas poly-ubiquitination primarily occurs in unstable cancer mutants and leads to protein degradation., We found that Ro52 was strongly conjugated by a single molecule of ubiquitin in cells. Although the biological relevance of this mono-ubiquitination was not defined, the function of Ro52 might be modified by the mono-ubiquitination. We also found that Ro52 was conjugated with poly-ubiquitin chain in cells (poly-ubiquitination)[SEP]Definitions: Ro52 defined as following: This gene is involved in the modulation of protein ubiquitination.. LDH-A defined as following: A member of the LACTATE DEHYDROGENASES isozyme family, Lactate Dehydrogenase 5 is localized to liver and skeletal muscle cells where its expression increases in liver disease and striated muscle trauma respectively.. Gpa1 defined as following: This gene plays a role in protein hormone signaling.. CIITA defined as following: MHC class II transactivator (1130 aa, ~123 kDa) is encoded by the human CIITA gene. This protein plays a role in the expression of HLA class II genes.. Smad3 defined as following: Mothers against decapentaplegic homolog 3 (425 aa, ~48 kDa) is encoded by the human SMAD3 gene. This protein plays a role in the modulation of transforming growth factor (TGF)-beta-mediated signaling and gene expression.. PTEN defined as following: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (403 aa, ~47 kDa) is encoded by the human PTEN gene. This protein plays a role in signaling and as both a dual-specificity phosphoprotein phosphatase and a lipid phosphatase.. PTEN protein defined as following: A lipid phosphatase that contains a C2 DOMAIN and acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. Smurf2 defined as following: E3 ubiquitin-protein ligase SMURF2 (748 aa, ~86 kDa) is encoded by the human SMURF2 gene. This protein is involved in the modulation of SMAD/TGF-beta receptor complex degradation.. Smad4 defined as following: Mothers against decapentaplegic homolog 4 (552 aa, ~60 kDa) is encoded by the human SMAD4 gene. This protein is involved in cytokine signaling and transcription factor activity.. LDB1 defined as following: Human LDB2 wild-type allele is located in the vicinity of 4p16 and is approximately 397 kb in length. This allele, which encodes LIM domain-binding protein 2, plays a role in the modulation of gene transcription.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. mutants defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. cancer defined as following: A malignant tumor at the original site of growth.. Hsp70 defined as following: A family of structurally related proteins that are involved in both protein folding and cellular stress responses. The members of this family are approximately 70 kDa.. parkin defined as following: E3 ubiquitin-protein ligase parkin (465 aa, ~52 kDa) is encoded by the human PRKN gene. This protein may play a role in the ubiquitination of proteins targeted for proteasomal degradation.. p34 defined as following: This gene is involved in both transcription and repair of DNA.. Smad1 defined as following: Human GARS1 wild-type allele is located in the vicinity of 7p14.3 and is approximately 39 kb in length. This allele, which encodes glycine-tRNA ligase protein, is involved in the synthesis of glycyl-tRNA. Mutation of the gene is associated with type 2D Charcot-Marie-Tooth disease and distal hereditary motor neuropathy, type Va.. modification defined as following: Respond with exceptions, completions and modifications or revisions done before completion
. PS1 defined as following: Human PSEN1 wild-type allele is located in the vicinity of 14q24.3 and is approximately 87 kb in length. This allele, which encodes presenilin-1 protein, is involved in the modulation of proteolytic processing. Mutation of the gene is associated with early-onset Alzheimer disease and frontotemporal dementia.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "yes"}
{"id": "converted_2887", "sentence1": "Is the enzyme ERAP2 associated with the disease birdshot chorioretinopathy?", "sentence2": "Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy., BSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands, thus implicating the A*29:02 peptidome in this disease. , A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.[SEP]Relations: ERAP1 has relations: protein_protein with ERAP2, protein_protein with ERAP2. Definitions: BSCR defined as following: A form of chorioretinitis characterized by multiple small, cream-colored LESIONS, symmetrically scattered mainly around the OPTIC DISK. These lesions are the most distinctive sign and often appear at the level of the RETINAL PIGMENT EPITHELIUM but, on occasion, suggest an even deeper infiltration and may ultimately lead to visual loss. An association with HLA-A29 antigen (see HLA-A ANTIGENS) has been observed in nearly all patients.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "yes"}
{"id": "converted_2902", "sentence1": "Is lithium effective for treatment of amyotrophic lateral sclerosis?", "sentence2": "In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results., Despite several positive case reports and short studies, further controlled researches have failed to substantiate any positive effects of lithium exposure in amyotrophic lateral sclerosis. , The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3)., Studies in ALS showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease., BACKGROUND\nLithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival., In a pilot clinical study that we recently published we found that lithium administration slows the progression of Amyotrophic Lateral Sclerosis (ALS) in human patients., BACKGROUND Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival., BACKGROUND A neuroprotective effect of lithium in amyotrophic lateral sclerosis (ALS) has been recently reported., Lithium delays progression of amyotrophic lateral sclerosis.ALS is a devastating neurodegenerative disorder with no effective treatment. , Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial.Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. , INTRODUCTION: Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period., A recently published study also ruled out any possible modest effect.
CONCLUSIONS: There is evidence to suggest that lithium has no short-term benefits in ALS., A comparison of the group of patients treated with lithium+riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time., None of the patients treated with lithium died during the 15 months of the follow-up, and disease progression was markedly attenuated when compared with age-, disease duration-, and sex-matched control patients treated with riluzole for the same amount of time.[SEP]Definitions: amyotrophic lateral sclerosis defined as following: An inherited form of amyotrophic lateral sclerosis, usually inherited in an autosomal dominant pattern, caused by mutation(s) in the SOD1 gene, encoding superoxide dismutase.. human defined as following: Members of the species Homo sapiens.. pioglitazone defined as following: An orally-active thiazolidinedione with antidiabetic properties and potential antineoplastic activity. Pioglitazone activates peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor, thereby inducing cell differentiation and inhibiting cell growth and angiogenesis. This agent also modulates the transcription of insulin-responsive genes, inhibits macrophage and monocyte activation, and stimulates adipocyte differentiation.. riluzole defined as following: A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. neurodegenerative disorder defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures..", "label": "no"}
{"id": "converted_1171", "sentence1": "Is nicotinamide effective for skin cancer prevention?", "sentence2": "Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses., ESULTS: At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39]lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001)., CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients., Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. , In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma., Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. , Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans., These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention., Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers., No noteworthy between-group differences were found with respect to the number or types of adverse events during the 12-month intervention period, and there was no evidence of benefit after nicotinamide was discontinued.CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. , Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses.METHODS: In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. , Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39]lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). , Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients., Nicotinamide has shown potential as a safe and effective intervention for the prevention of malignant and premalignant skin lesions., Nicotinamide, which protected against both UVB and UVA, is a promising agent for skin cancer prevention.[SEP]Relations: skin carcinoma has relations: disease_disease with skin cancer, disease_disease with skin cancer. Definitions: Nicotinamide defined as following: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.. cutaneous melanoma defined as following: A primary melanoma arising from atypical melanocytes in the skin. Precursor lesions include acquired and congenital melanocytic nevi, and dysplastic nevi. Several histologic variants have been recognized, including superficial spreading melanoma, acral lentiginous melanoma, nodular melanoma, and lentigo maligna melanoma.. vitamin B3 defined as following: The determination of the amount of Vitamin B3 present in a sample.. nonmelanoma skin cancers defined as following: A carcinoma that arises from the skin. Representative examples are basal cell carcinoma and squamous cell carcinoma.. humans defined as following: Members of the species Homo sapiens.. keratinocytes defined as following: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.. skin cancer defined as following: A primary or metastatic malignant neoplasm involving the skin. Primary malignant skin neoplasms most often are carcinomas (either basal cell or squamous cell carcinomas) or melanomas. Metastatic malignant neoplasms to the skin include carcinomas and lymphomas.. melanocytes defined as following: Mammalian pigment cells that produce MELANINS, pigments found mainly in the EPIDERMIS, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called MELANOSOMES. The large non-mammalian melanin-containing cells are called MELANOPHORES.. actinic keratoses defined as following: White or pink lesions on the arms, hands, face, or scalp that arise from sun-induced DNA DAMAGE to KERATINOCYTES in exposed areas. They are considered precursor lesions to superficial SQUAMOUS CELL CARCINOMA.. vitamin defined as following: Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body..", "label": "yes"}
{"id": "converted_475", "sentence1": "Can venlafaxine block NET and SERT?", "sentence2": "Treatment for 14 days with 70 mg/kg per day venlafaxine, which inhibits both the NET and SERT, or 10 mg/kg per day phenelzine, a monoamine oxidase inhibitor, produced antidepressant-like effects on behavior without altering NET or SERT expression., Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT., Chronic venlafaxine treatment affected SERT and NET binding differently from paroxetine or desipramine., Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT, Paroxetine and venlafaxine are potent serotonin transporter (SERT) antagonists and weaker norepinephrine transporter (NET) antagonists, Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition, Treatment for 14 days with 70 mg/kg per day venlafaxine, which inhibits both the NET and SERT, or 10 mg/kg per day phenelzine, a monoamine oxidase inhibitor, produced antidepressant-like effects on behavior without altering NET or SERT expression, We then performed the first reported investigation of epistasis between the SERT gene and norepinephrine transporter gene (SLC6A2, alias NET) in AN, as an earlier study suggested that atypical AN responds to the dual serotonin-norepinephrine reuptake inhibitor venlafaxine, Of particular interest were the findings that paroxetine, generally thought of as a selective SERT antagonist, possesses moderately high affinity for the NET and that venlafaxine, which has been described as a "dual uptake inhibitor", possesses weak affinity for the NET, The ratios of measured occupancy ED(50) values (doses at which 50% occupancy occurs) among SERT, NET and DAT sites for duloxetine, venlafaxine, nomifensine, indatraline, DOV 21,947 and DOV 216,303 were consistent with the ratios of the in vitro affinities between these target binding sites, SERT and NET occupancy by venlafaxine and milnacipran in nonhuman primates: a PET study, In this study in nonhuman primates, we aimed to investigate the relationship between SERT and NET affinity by measuring the in vivo occupancy at both transporters of venlafaxine and milnacipran, We hypothesized that venlafaxine would affect monoamine transporters dose-dependently, with low doses causing selective reduction of SERT binding sites and higher doses reducing both SERT and NET binding sites, Comparative studies with clinically used antidepressants showed that venlafaxine possessed a profile similar to S33005 but was less potent. Clomipramine likewise interacted with SERTs and NETs but also with several other receptors types, while citalopram and reboxetine were preferential ligands of SERTs and NETs, respectively. In conclusion, S33005 interacts potently with SERTs and, less markedly, with NETs. , Venlafaxine blocks both serotonin and norepinephrine transporters (SERT and NET), with higher affinity for SERT. Serotonergic effects occur with lower doses, whereas both serotonergic and noradrenergic effects occur with higher doses of venlafaxine., Taken together, the results from this study indicate that the low dose of venlafaxine blocked selectively the reuptake of 5-HT, whereas the high dose blocked the reuptake of both 5-HT and NE. Moreover, an enhancement of serotonergic neurotransmission by venlafaxine was only achieved under conditions whereby the desensitization of the terminal 5-HT(1B) autoreceptor is appended to that of the somatodendritic 5-HT(1A) receptor.[SEP]Relations: Phenelzine has relations: drug_drug with Paroxetine, drug_drug with Clomipramine, drug_drug with Paroxetine, drug_drug with Clomipramine. Paroxetine has relations: drug_drug with Clomipramine, drug_drug with Clomipramine. Serotonin has relations: drug_drug with Clomipramine, drug_drug with Paroxetine, drug_drug with Clomipramine, drug_drug with Paroxetine. Clomipramine has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Citalopram has relations: drug_drug with Clomipramine, drug_drug with Paroxetine, drug_drug with Clomipramine, drug_drug with Paroxetine. Venlafaxine has relations: drug_drug with Clomipramine, drug_drug with Paroxetine, drug_drug with Clomipramine, drug_drug with Paroxetine. Reboxetine has relations: drug_drug with Paroxetine, drug_drug with Clomipramine, drug_drug with Paroxetine, drug_drug with Clomipramine. Nomifensine has relations: drug_drug with Paroxetine, drug_drug with Clomipramine, drug_drug with Paroxetine, drug_drug with Clomipramine. Duloxetine has relations: drug_drug with Clomipramine, drug_drug with Paroxetine, drug_drug with Clomipramine, drug_drug with Paroxetine. Desipramine has relations: drug_drug with Clomipramine, drug_drug with Paroxetine, drug_drug with Clomipramine, drug_drug with Paroxetine. Protein S human has relations: drug_drug with Paroxetine, drug_drug with Paroxetine. Milnacipran has relations: drug_drug with Clomipramine, drug_drug with Paroxetine, drug_drug with Clomipramine, drug_drug with Paroxetine. Definitions: phenelzine defined as following: One of the MONOAMINE OXIDASE INHIBITORS used to treat DEPRESSION; PHOBIC DISORDERS; and PANIC.. binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. Paroxetine defined as following: A serotonin uptake inhibitor that is effective in the treatment of depression.. 5-HT defined as following: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.. Clomipramine defined as following: A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.. citalopram defined as following: A furancarbonitrile that is one of the SELECTIVE SEROTONIN REUPTAKE INHIBITORS used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from TARDIVE DYSKINESIA in preference to tricyclic antidepressants, which aggravate dyskinesia.. venlafaxine defined as following: A synthetic phenethylamine bicyclic derivative with antidepressant activity. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak dopamine reuptake inhibitors. This agent may reduce hormone-related vasomotor symptoms. (NCI04). PET defined as following: An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.. reboxetine defined as following: A morpholine derivative that is a selective and potent noradrenaline reuptake inhibitor; it is used in the treatment of DEPRESSIVE DISORDER.. nomifensine defined as following: An isoquinoline derivative that prevents dopamine reuptake into synaptosomes. The maleate was formerly used in the treatment of depression. It was withdrawn worldwide in 1986 due to the risk of acute hemolytic anemia with intravascular hemolysis resulting from its use. In some cases, renal failure also developed. (From Martindale, The Extra Pharmacopoeia, 30th ed, p266). desipramine defined as following: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.. NET defined as following: This gene plays a role in neurotransmitter recycling.. norepinephrine transporter gene defined as following: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of noradrenergic neurons. They remove NOREPINEPHRINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. The norepinephrine transporter regulates signal amplitude and duration at noradrenergic synapses and is the target of ADRENERGIC UPTAKE INHIBITORS.. monoamine oxidase inhibitor defined as following: A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414). antidepressants defined as following: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.. milnacipran defined as following: A cyclopropanecarboxamide serotonin and norepinephrine reuptake inhibitor (SNRI) that is used in the treatment of FIBROMYALGIA.. human defined as following: Members of the species Homo sapiens..", "label": "yes"}
{"id": "converted_3187", "sentence1": "Do Crocus sativus extracts loosen the blood-brain barrier?", "sentence2": "Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid β Load and Related Toxicity in 5XFAD Mice., In vitro results showed that Crocus sativus extract increases the tightness of a cell-based blood-brain barrier (BBB) model and enhances transport of Aβ. Further in vivo studies confirmed the effect of Crocus sativus extract (50 mg/kg/day, added to mice diet) on the BBB tightness and function that was associated with reduced Aβ load and related pathological changes in 5XFAD mice used as an AD model. Reduced Aβ load could be explained, at least in part, by Crocus sativus extract effect to enhance Aβ clearance pathways including BBB clearance, enzymatic degradation and ApoE clearance pathway.[SEP]Definitions: BBB defined as following: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.. Toxicity defined as following: The finding of bodily harm due to the poisonous effects of something..", "label": "no"}
{"id": "converted_146", "sentence1": "Is SLC22A3 expressed in the brain?", "sentence2": "The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. , The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain., In agreement with this distribution, OCT3/Slc22a3-deficient mice show evidence of altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters., CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF., The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain, The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. , CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF., Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain., CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters., The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission., CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF., Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission., The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain., OCT2-OCT-3 display differential tissue distribution: OCT1 is predominantly found in liver of humans, and liver and kidney in rodents; OCT2 is most strongly expressed in both human and rodent kidney, whereas is OCT3 primarily expressed in placenta, but also more widely detected in various tissues, including brain and lung.[SEP]Relations: POU2F2 has relations: anatomy_protein_present with placenta, anatomy_protein_present with placenta. placenta has relations: anatomy_protein_present with SLC22A3, anatomy_protein_present with SLC22A3. SLC6A6 has relations: anatomy_protein_present with placenta, anatomy_protein_present with placenta. SLC22A3 has relations: anatomy_protein_present with placenta, anatomy_protein_present with placenta. Definitions: OCT2 defined as following: This gene is involved in transcriptional activation and plays a role in mature B cell maintenance.. BBB defined as following: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.. OCT1 defined as following: This gene plays a role in transcriptional activation and modulates immunoglobulin activity.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. CSF defined as following: A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES.. CRT defined as following: Treatment that combines chemotherapy with radiotherapy.. Slc22a3 defined as following: This gene is involved in membrane potential-dependent transport of organic cations.. S-adenosylmethionine defined as following: Physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed). rodents defined as following: A mammalian order which consists of 29 families and many genera.. OCT3 defined as following: This gene plays a role in early mammalian development.. isoform defined as following: Refers to variants of the same protein which can be separated on special conducting media using electrophoresis. The differences may arise from genetically determined differences in primary structure or by modification of the same primary sequence.. organic cation transporter defined as following: Solute carrier family 22 member 1 (554 aa, ~61 kDa) is encoded by the human SLC22A1 gene. This protein is involved in bidirectional cation transport.. organic cation transporter 3 defined as following: Solute carrier family 22 member 3 (556 aa, ~61 kDa) is encoded by the human SLC22A3 gene. This protein is involved in mediating membrane potential-dependent transport of organic cations and may play a role in the disposition of cationic neurotoxins and neurotransmitters in the brain.. GCs defined as following: Ceramide glucosyltransferase (394 aa, ~45 kDa) is encoded by the human UGCG gene. This protein is involved in the glycosylation of N-acylsphingosine.. organs defined as following: A unique macroscopic (gross) anatomic structure that performs specific functions. It is composed of various tissues. An organ is part of an anatomic system or a body region. Representative examples include the heart, lung, liver, spleen, and uterus.. humans defined as following: Members of the species Homo sapiens.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. SLC22A3 defined as following: This gene is involved in membrane potential-dependent transport of organic cations..", "label": "yes"}
{"id": "converted_2186", "sentence1": "Can acupuncture cause spinal epidural hematoma?", "sentence2": "RESULTS: A 54-year-old woman, a 38-year-old woman, and a 60-year-old man with hemiplegia by cervical subdural or epidural hematoma after cervical posterior paraspinal muscle needling without direct invasion (intramuscular stimulation, acupuncture, or intramuscular lidocaine) were observed., Acute spinal subdural hematoma with hemiplegia after acupuncture: a case report and review of the literature., Although acupuncture has been a popular method for the management of pain control, we encountered the first case of SDH after acupuncture.PURPOSE: The purpose of this case report was to present the first case of subdural hematoma after acupuncture and the reasons for the risks of blind cervical acupuncture., SUMMARY OF BACKGROUND DATA: Epidural hematomas after dry needling are quite unusual and only a few cases of epidural hematoma after acupuncture have been reported in the literature., Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc. , Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage., Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc., Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture., However, subarachnoid hemorrhage and spinal epidural hematoma have been reported to occur after acupuncture in the posterior neck., A retrospective case report.The objective of this article is to report an unusual complication of dry needling.Epidural hematomas after dry needling are quite unusual and only a few cases of epidural hematoma after acupuncture have been reported in the literature, Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture, Spinal epidural hematoma is a rare complication associated with pain control procedures such as facet block, acupuncture, epidural injection, etc, Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage, Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture.[SEP]Definitions: hematoma defined as following: A collection of blood outside the BLOOD VESSELS. Hematoma can be localized in an organ, space, or tissue.. SDH defined as following: A flavoprotein containing oxidoreductase that catalyzes the dehydrogenation of SUCCINATE to fumarate. In most eukaryotic organisms this enzyme is a component of mitochondrial electron transport complex II.. subarachnoid hemorrhage defined as following: Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.. lidocaine defined as following: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.. man defined as following: Members of the species Homo sapiens.. epidural defined as following: Administration of the drug in the epidural space, usually at the lumbar level of the spine. The drug must initially cross the dura mater before exerting its effect on the nervous system components. The drug is also subject to uptake into the rich epidural plexus of veins. Uptake and distribution after epidural administration resembles that seen after intramuscular injection. The portion of drug that is not taken into the vascular compartment is available to cross the dura. Hydrophilicity is a major component in the pharmacokinetics of drug transfer into the subdural space.. Spinal epidural hematoma defined as following: A collection of blood into the space between the dura mater and the skull.. intramuscular defined as following: Intramuscular injection is a route of drug administration via injection into muscle tissue. Aqueous or oleaginous solutions and emulsions or suspensions may be administered. Absorption rates, delay in availability of the drug to the systemic circulation, and duration of effect are perfusion-limited, depend on molecular size of the agent, volume, and osmolarity of the drug solution, fat content of the injection site, and patient physical activity.. hemiplegia defined as following: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical SPINAL CORD DISEASES; PERIPHERAL NERVOUS SYSTEM DISEASES; and other conditions may manifest as hemiplegia. The term hemiparesis (see PARESIS) refers to mild to moderate weakness involving one side of the body.. spinal epidural hematoma defined as following: A collection of blood into the space between the dura mater and the skull..", "label": "yes"}
{"id": "converted_3776", "sentence1": "Is MAGE-A3 immunotherapeutic effective for non-small-cell lung cancer?", "sentence2": "INTERPRETATION: Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped., In the overall population, median disease-free survival was 60·5 months (95% CI 57·2-not reached) for the MAGE-A3 immunotherapeutic group and 57·9 months (55·7-not reached) for the placebo group (hazard ratio [HR] 1·02, 95% CI 0·89-1·18; p=0·74). Of the patients who did not receive chemotherapy, median disease-free survival was 58·0 months (95% CI 56·6-not reached) in those in the MAGE-A3 group and 56·9 months (44·4-not reached) in the placebo group (HR 0·97, 95% CI 0·80-1·18; p=0·76). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. , uvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Ba[SEP]Definitions: NSCLC defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. MAGE-A3 defined as following: A peptide cancer vaccine comprised of a peptide derived from the human melanoma antigen A3 (MAGE-A3), with potential immunostimulating and antineoplastic activities. Upon administration, MAGE-A3 peptide vaccine may stimulate the immune system to mount a cytotoxic T-cell (CTL) response against tumor cells expressing MAGE-A3, resulting in tumor cell lysis. MAGE-A3, a tumor-associated antigen (TAA), is overexpressed by a variety of cancer cell types..", "label": "no"}