Supernumerary mandibular right central primary incisor
. 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.. Membrane defined as following: A device that is made from or resembles a thin flexible sheet of material.. necrosis defined as following: A finding indicating the presence of cellular necrosis in a tissue specimen.. 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.. 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.. PM defined as following: A suppurative infection of muscle.. phosphatidylserine defined as following: A phospholipid with a polar serine found in phosphoester linkage to diacylglycerol.. rupture defined as following: Forcible or traumatic tear or break of an organ or other soft part of the body.. cell membranes defined as following: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells..", "label": "yes"} {"id": "converted_76", "sentence1": "Are LOQ and LOD the same?", "sentence2": "The limit of detection (LoD) and limit of quantitation (LoQ) , Missing values caused by the limit of detection or quantification (LOD/LOQ) were widely observed in mass spectrometry, Limits of detection (LOD) and quantification (LOQ) at 10 and 20\u2009ng/g were achieved,, The quantitative parameters of sensor for silver ion are determined as the limit of detection (LOD) 5.95\u00a0\u00d7\u00a010-7 M, and limit of quantitation (LOQ) 1.98\u00a0\u00d7\u00a010-8 M in the linear range, Real-time PCR (qPCR) is the principal technique for the quantification of pathogen biomass in host tissue, yet no generic methods exist for the determination of the limit of quantification (LOQ) and the limit of detection (LOD) in qPCR., * Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) are terms used to describe the smallest concentration of a measurand that can be reliably measured by an analytical procedure., The linear range of glyoxylic acid concentration is 0-0.028\u2009M. The limits of detection (LOD) and quantitation (LOQ) are 0.0019\u2009M and 0.00577\u2009M, respectively., Results indicated that the dynamic ranges of three fur-bearing animals were all from 1% to 90%; the limit of detection (LOD) and limit of quantification (LOQ) for three fur-bearing animals were same, with LOD 0.1% (w/w) and LOQ 1% (w/w)., Limit of detection (LQD)/limit of quantitation (LOQ): comparison of the empirical and the statistical methods exemplified with GC-MS assays of abused drugs., The limits of detection (LOD) and quantitation (LOQ) were 0.6 and 2.1 microg/L, respectively., tion is important for the analysis of aflatoxin in hazelnuts. The limit of detection (LOD) and limit of quantification (LOQ) are two important paramet, Limits of detection (LOD) and quantitation (LOQ) for UV detection are 1 and 2 mg/L, respectively., The limit of detection (LOD) for any analytical procedure, the point at which analysis is just feasible, may be determined by a statistical approach based on measuring replicate blank (negative) samples or by an empirical approach, consisting of measuring progressively more dilute concentrations of analyte. The limit of quantitation (LOQ), or concentration at which quantitative results can be reported with a high degree of confidence, may likewise be determined by either approach. We used both methods to determine LOD and LOQ for forensic gas chromatographic-mass spectrometric (GC-MS) analyses of abused drugs. The statistically determined LOD and LOQ values for these assays underestimated the LOD because of th[SEP]Relations: Glyoxylic acid has relations: drug_protein with SLC16A3, drug_protein with SLC16A3. Definitions: aflatoxin defined as following: Furano-furano-benzopyrans that are produced by ASPERGILLUS from STERIGMATOCYSTIN. They are structurally related to COUMARINS and easily oxidized to an epoxide form to become ALKYLATING AGENTS. Members of the group include AFLATOXIN B1; aflatoxin B2, aflatoxin G1, aflatoxin G2; AFLATOXIN M1; and aflatoxin M2..", "label": "no"} {"id": "converted_84", "sentence1": "Do machine learning-based methods outperform statistical methods for survival analysis?", "sentence2": "Our results reveal that machine-learning-based models such as random survival forests, gradient boosted survival model, and survival support vector machine can outperform the traditional statistical methods, i.e., Cox proportional hazard model., DeepSurv models consistently outperformed CoxPH; both approaches performed best when provided with all the datasets. , This analysis revealed that survival analysis models outperformed binary classification models for risk assessment, and the performance of the survival analysis methods-Cox model regularized with ridge penalty (Cox-Ridge) and partial least squares (PLS) regression for Cox model (Cox-PLS)-were generally more robust than the other methods., Then, we demonstrate that the resulting method, referred to as ELMCoxBAR, can outperform some other state-of-art survival prediction methods such as L1 - or L2 -regularized Cox regression, random survival forest with various splitting rules, and boosted Cox model, in terms of its predictive performance using both simulated and real world datasets., Furthermore, machine learning approaches have been adapted for survival analysis, to fit nonlinear and complex interaction effects between predictors, and achieve more accurate prediction of individual survival probability., We review traditional survival methods and regularization methods, with various penalty functions, for the analysis of high-dimensional genomics, and describe machine learning techniques that have been adapted to survival analysis., Furthermore, although machine learning and data mining methods are based on statistics, most such techniques do not address the biologist's requirement for sound mathematical confidence measures., BACKGROUND: Machine learning-based risk prediction models may outperform traditional statistical models in large datasets with many variables, by identifying both novel predictors and the complex interactions between them, BACKGROUND: Over the recent years, machine learning methods have been increasingly explored in cancer prognosis because of the appearance of improved machine learning algorithms. These algorithms can use censored data for modeling, such as support vector machines for survival analysis and random survival forest (RSF). However, it is still debated whether traditional (Cox proportional haz[SEP]Relations: centromere clustering at the mitotic interphase nuclear envelope has relations: bioprocess_bioprocess with centromere clustering, bioprocess_bioprocess with centromere clustering, bioprocess_bioprocess with mitotic cell cycle process, bioprocess_bioprocess with mitotic cell cycle process, bioprocess_bioprocess with chromosome attachment to the nuclear envelope, bioprocess_bioprocess with chromosome attachment to the nuclear envelope. Definitions: vector defined as following: Any DNA molecule capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. They are or are derived from plasmids, bacteriophages, or viruses and are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain genetic markers to facilitate their selective recognition.. L2 defined as following: Human PPFIBP1 wild-type allele is located in the vicinity of 12p12.1 and is approximately 172 kb in length. This allele, which encodes liprin-beta-1 protein, is involved in the modulation of protein-protein interactions.. RSF defined as following: Human RSF1 wild-type allele is located in the vicinity of 11q14.1 and is approximately 155 kb in length. This allele, which encodes remodeling and spacing factor 1 protein, plays a role in transcriptional repression, transcriptional co-activation and nucleosome assembly controlled by the RSF chromatin remodeling complex. The RSF1 gene is overexpressed in high-grade ovarian serous carcinoma.. L1 defined as following: A long interspersed element (LINE) found in mammals. The LINE-1 element is the only active LINE in humans and is approximately 6,000 base pairs long. This nucleotide sequence consists of two non-overlapping open reading frames (ORF) flanked by a 5' untranslated region (UTR), which contains a strong RNA polymerase II promoter sequence, and target side duplications. The first ORF encodes a 500 amino acid, ~40 kDa leucine zipper-containing RNA-binding protein. The second ORF encodes an ~150 kDa protein that has endonuclease and reverse transcriptase activity. Increased LINE-1 copy number is associated with cancer and neuropathy..", "label": "yes"} {"id": "converted_90", "sentence1": "Was erythropoietin effective for optic neuritis in the TONE trial?", "sentence2": "INTERPRETATION: Erythropoietin as an adjunct to corticosteroids conveyed neither functional nor structural neuroprotection in the visual pathways after optic neuritis. [SEP]Relations: Optic neuritis has relations: drug_effect with Epirubicin, drug_effect with Epirubicin, drug_effect with Paroxetine, drug_effect with Paroxetine, drug_effect with Ethionamide, drug_effect with Ethionamide, drug_effect with Doxorubicin, drug_effect with Doxorubicin, drug_effect with Allopurinol, drug_effect with Allopurinol. Definitions: corticosteroids defined as following: HORMONES produced by the ADRENAL CORTEX, including both steroid and peptide hormones. The major hormones produced are HYDROCORTISONE and ALDOSTERONE.. Erythropoietin defined as following: This gene is involved in the regulation of red blood cell production and function.. optic neuritis defined as following: Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as MULTIPLE SCLEROSIS, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis).. erythropoietin defined as following: This gene is involved in the regulation of red blood cell production and function..", "label": "no"} {"id": "converted_92", "sentence1": "Is COVID-19 caused by the Omicron variant less severe than infection caused by other variants?", "sentence2": "Omicron appears to lead to a milder illness for patients compared with previous COVID-19 variants., Most of those infected with Omicron experience symptoms, and the Omicron variant appears to lead to less severe disease. However, this does not mean that all the infected experience an Omicron infection as mild., In this study, symptoms of COVID-19 tended to be milder than described for previous SARS-CoV2 variants., These early national data suggest that omicron is associated with a two-thirds reduction in the risk of COVID-19 hospitalisation compared with delta., Globally, SARS CoV-2 omicron variant has led to a notable increase of COVID-19 diagnoses, although with less severe clinical manifestations and decreased hospitalizations., One of the newest variants is Omicron, which shows an increase in its transmissibility, but also reportedly reduces hospitalization rates and shows milder symptoms, such as in those who have been vaccinated., Here we compared 3-day risks of emergency department (ED) visit, hospitalization, intensive care unit (ICU) admission, and mechanical ventilation in patients who were first infected during a time period when the Omicron variant was emerging to those in patients who were first infected when the Delta variant was predominant., First time SARS-CoV-2 infections occurring at a time when the Omicron variant was rapidly spreading were associated with significantly less severe outcomes than first-time infections when the Delta variant predominated., After propensity-score matching for demographics, socio-economic determinants of health, comorbidities, medications and vaccination status, the 3-day risks in the Emergent Omicron cohort outcomes were consistently less than half those in the Delta cohort: ED visit: 4.55% vs. 15.22% (risk ratio or RR: 0.30, 95% CI: 0.28-0.33); hospitalization: 1.75% vs. 3.95% (RR: 0.44, 95% CI: 0.38-0.52]); ICU admission: 0.26% vs. 0.78% (RR: 0.33, 95% CI:0.23-0.48); mechanical ventilation: 0.07% vs. 0.43% (RR: 0.16, 95% CI: 0.08-0.32)., The Omicron is highly transmissible and is spreading faster than any previous variant, but may cause less severe symptoms than previous variants., The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort., The adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0\u00b756 (95% CI 0\u00b754-0\u00b758); for hospital admission and death, HR estimates were 0\u00b741 (0\u00b739-0\u00b743) and 0\u00b731 (0\u00b726-0\u00b737), respectively., The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age., The Omicron variant (B.1.1.529) is estimated to be more transmissible than previous strains of SARS-CoV-2 especially among children, potentially resulting in croup which is a characteristic disease in children., A significant difference between the age-specific susceptibility to the Omicron and that to the pre-Omicron variants was found in the younger age group. The rise in susceptibility to the Omicron/pre-Delta variant was highest in the 10-15 years age group (5.28 times [95% CI, 4.94-5.60]), and the rise in susceptibility to the Omicron/Delta variant was highest in the 15-19 years age group (3.21 times [95% CI, 3.12-3.31]), whereas in those aged 50 years or more, the susceptibility to the Omicron/pre-Omicron remained stable at approximately twofold., Even after adjusting for contact pattern, vaccination status, and waning of vaccine effectiveness, the Omicron variant of SARS-CoV-2 tends to propagate more easily among children than the pre-Omicron strains., Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care., We found that infections caused by the Omicron variant caused significantly less morbidity, including admission to the hospital and requirement for oxygen supplementation, and significantly less mortality than those caused by the Delta variant., Early work suggests that infections caused by the Omicron variant may be less severe than those caused by the Delta variant., The Omicron is highly transmissible and is spreading faster than any previous variant, but may cause less severe symptoms than previous variants., Early reports of Omicron variant confirmed patients indicated less severe disease course compared with the disease caused by previously encountered variants with absence of data regarding cardiac involvement by Omicron, However, we found that infections by Omicron were significantly less severe than those caused by Delta and other previous variants., Severe acute respiratory syndrome coronavirus 2 infection from the Omicron variant in children/adolescents is less severe than infection from the Delta variant., Omicron variant infection is associated with significantly lower severity of disease compared with the Delta variant., In the general population, illness after infection with the SARS-CoV-2 Omicron variant is less severe compared with previous variants.[SEP]Relations: Rotavirus infection has relations: disease_disease with Reoviridae infectious disease, disease_disease with Reoviridae infectious disease. Cessation of head growth has relations: disease_phenotype_positive with Angelman syndrome due to maternal 15q11q13 deletion, disease_phenotype_positive with Angelman syndrome due to maternal 15q11q13 deletion, disease_phenotype_positive with Angelman syndrome due to paternal uniparental disomy of chromosome 15, disease_phenotype_positive with Angelman syndrome due to paternal uniparental disomy of chromosome 15, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to a point mutation. NDUFB6 has relations: anatomy_protein_present with Ammon's horn, anatomy_protein_present with Ammon's horn. Definitions: variants defined as following: An alteration or difference from a norm or standard.. death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. croup defined as following: Narrowing of the larynx, commonly occuring during viral respiratory tract infections, in particular in children, leads to symptoms such as hoarseness, a barking cough, stridor, and sometimes dyspnea and respiratory failure. [LMU:mgriese, PMID:31680234]. 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.. COVID-19 defined as following: A viral disorder generally characterized by high FEVER; COUGH; DYSPNEA; CHILLS; PERSISTENT TREMOR; MUSCLE PAIN; HEADACHE; SORE THROAT; a new loss of taste and/or smell (see AGEUSIA and ANOSMIA) and other symptoms of a VIRAL PNEUMONIA. In severe cases, a myriad of coagulopathy associated symptoms often correlating with COVID-19 severity is seen (e.g., BLOOD COAGULATION; THROMBOSIS; ACUTE RESPIRATORY DISTRESS SYNDROME; SEIZURES; HEART ATTACK; STROKE; multiple CEREBRAL INFARCTIONS; KIDNEY FAILURE; catastrophic ANTIPHOSPHOLIPID ANTIBODY SYNDROME and/or DISSEMINATED INTRAVASCULAR COAGULATION). In younger patients, rare inflammatory syndromes are sometimes associated with COVID-19 (e.g., atypical KAWASAKI SYNDROME; TOXIC SHOCK SYNDROME; pediatric multisystem inflammatory disease; and CYTOKINE STORM SYNDROME). A coronavirus, SARS-CoV-2, in the genus BETACORONAVIRUS is the causative agent.. coronavirus defined as following: Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE).. 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_95", "sentence1": "Should be used bexarotene for relapsing-remitting multiple sclerosis?", "sentence2": "INTERPRETATION: We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. [SEP]Relations: multiple sclerosis has relations: disease_disease with relapsing-remitting multiple sclerosis, disease_disease with relapsing-remitting multiple sclerosis. Bexarotene has relations: drug_effect with Lymphocytosis, drug_effect with Lymphocytosis, drug_drug with Reteplase, drug_drug with Reteplase, drug_drug with Aprepitant, drug_drug with Aprepitant, drug_drug with Repaglinide, drug_drug with Repaglinide. 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). bexarotene defined as following: A rexinoid (an RXR-binding ligand), tetrahydronaphthalene derivative and RETINOID X RECEPTOR antagonist that is used in the treatment of CUTANEOUS T-CELL LYMPHOMA..", "label": "no"} {"id": "converted_97", "sentence1": "Can analgesics or antipyretics be taken for side effects following COVID-19 vaccination?", "sentence2": "Analgesics or antipyretic medications are often used to alleviate vaccine side effects, but their effect on immunogenicity remains uncertain. Few studies have assessed the effect of analgesics/antipyretics on vaccine immunogenicity and reactogenicity. Some studies revealed changes in certain immune response parameters post-vaccination when analgesics/antipyretics were used either prophylactically or therapeutically. Still, there is no evidence that these changes impact vaccine efficacy. Specific data on the impact of analgesic/antipyretic medications on immunogenicity of COVID-19 vaccines are limited. However, available data from clinical trials of licensed vaccines, along with recommendations from public health bodies around the world, should provide reassurance to both healthcare professionals and vaccine recipients that short-term use of analgesics/antipyretics at non-prescription doses is unlikely to affect vaccine-induced immunity., Although fever is part of the normal inflammatory process after immunisation, prophylactic antipyretic drugs are sometimes recommended to allay concerns of high fever and febrile convulsion. We assessed the effect of prophylactic administration of paracetamol at vaccination on infant febrile reaction rates and vaccine responses., Although febrile reactions significantly decreased, prophylactic administration of antipyretic drugs at the time of vaccination should not be routinely recommended since antibody responses to several vaccine antigens were reduced., Antibody geometric mean concentrations (GMCs) were significantly lower in the prophylactic paracetamol group than in the no prophylactic paracetamol group after primary vaccination for all ten pneumococcal vaccine serotypes, protein D, antipolyribosyl-ribitol phosphate, antidiphtheria, antitetanus, and antipertactin., Worldwide, paracetamol is administered as a remedy for complaints that occur after vaccination. Recently published results indicate that paracetamol inhibits the vaccination response in infants when given prior to vaccination., One month after the second booster vaccination, the anti-HBs level in the prophylactic paracetamol group was significantly lower (p = 0.048) than the level in the control group (4257 mIU/mL vs. 5768 mIU/mL). The anti-HBs level in the therapeutic paracetamol group (4958 mIU/mL) was not different (p = 0.34) from the level in the control group. Only prophylactic paracetamol treatment, and not therapeutic treatment, during vaccination has a negative influence on the antibody concentration after hepatitis B vaccination in adults. These findings prompt to consider therapeutic instead of prophylactic treatment to ensure maximal vaccination efficacy and retain the possibility to treat pain and fever after vaccination., Analgesics or antipyretic medications are often used to alleviate vaccine side effects, but their effect on immunogenicity remains uncertain., Some studies revealed changes in certain immune response parameters post-vaccination when analgesics/antipyretics were used either prophylactically or therapeutically., While antipyretic analgesics are widely used to ameliorate vaccine adverse reactions, their use has been associated with blunted vaccine immune responses., However, available data from clinical trials of licensed vaccines, along with recommendations from public health bodies around the world, should provide reassurance to both healthcare professionals and vaccine recipients that short-term use of analgesics/antipyretics at non-prescription doses is unlikely to affect vaccine-induced immunity., Specific data on the impact of analgesic/antipyretic medications on immunogenicity of COVID-19 vaccines are limited., Analgesics or antipyretic medications are often used to alleviate vaccine side effects, but their effect on immunogenicity remains uncertain., Some studies revealed changes in certain immune response parameters post-vaccination when analgesics/antipyretics were used either prophylactically or therapeutically., Specific data on the impact of analgesic/antipyretic medications on immunogenicity of COVID-19 vaccines are limited.[SEP]Relations: BCG vaccine has relations: drug_drug with Lopinavir, drug_drug with Lopinavir, drug_drug with Mirvetuximab Soravtansine, drug_drug with Mirvetuximab Soravtansine, drug_drug with Paritaprevir, drug_drug with Paritaprevir, drug_drug with Etravirine, drug_drug with Etravirine, drug_drug with Alovudine F-18, drug_drug with Alovudine F-18. Definitions: 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].", "label": "yes"} {"id": "converted_101", "sentence1": "Is OXLUMO (lumasiran) used for the treatment of primary hyperoxaluria?", "sentence2": "Lumasiran (Oxlumo\u2122) is a subcutaneously administered small interfering RNA (siRNA) targeting the mRNA for hydroxyacid oxidase 1 gene (HAO1; encodes glycolate oxidase) and was developed by Alnylam Pharmaceuticals for the treatment of primary hyperoxaluria type 1 (PH1)., OXLUMO (lumasiran) for the treatment of primary hyperoxaluria,, Conjugation of oligonucleotide therapeutics, including small interfering RNAs (siRNAs) or antisense oligonucleotides, to N-acetylgalactosamine (GalNAc) ligands has become the primary strategy for hepatocyte-targeted delivery, and with the recent approvals of GIVLAARI (givosiran) for the treatment of acute hepatic porphyria, OXLUMO (lumasiran) for the treatment of primary hyperoxaluria, and Leqvio (inclisiran) for the treatment of hypercholesterolemia, the technology has been well validated clinically., In this context we discuss nedosiran (Dicerna Pharmaceuticals, Inc.) and lumasiran (Alnylam Pharmaceuticals), which are both novel RNAi therapies for primary hyperoxaluria that selectively reduce hepatic expression of lactate dehydrogenase and glycolate oxidase respectively, reducing hepatic oxalate production and urinary oxalate levels., On 23 November 2020, lumasiran was approved in the USA for the treatment of adult and paediatric patients with PH1., Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1., On 19 November 2020, lumasiran received its first global approval in the EU for the treatment of PH1 in all age groups., Efforts made to develop pharmacological treatments succeeded with the biotechnological agent lumasiran, a siRNA product against glycolate oxidase, which has become the first effective therapy to treat PH1., Phase 3 trial of lumasiran for primary hyperoxaluria type 1: A new RNAi therapeutic in infants and young children., Several new drugs have been approved to treat rare genetic disorders: setmelanotide for certain conditions causing obesity; lumasiran for primary hyperoxaluria type 1, a kidney disorder; and lonafarnib for two diseases that cause premature aging., Lumasiran in the Management of Patients with Primary Hyperoxaluria Type 1: From Bench to Bedside., The effect of lumasiran therapy for primary hyperoxaluria type 1 in small infants., Lumasiran was recently approved in the treatment of primary hyperoxaluria type 1 and nedosiran is in the approval process., SIONS: Lumasiran had an acceptable safety profile and reduced urinary oxalate excretion in all patients with primary hyperoxaluria type 1 to near-normal levels.CLINI, Lumasiran is an RNA interference (RNAi) therapeutic agent that reduces hepatic oxalate production, which has been recently approved for the treatment of PH1., RATIONALE & OBJECTIVE: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and a[SEP]Relations: primary hyperoxaluria has relations: contraindication with Sodium sulfate, contraindication with Sodium sulfate, contraindication with Sodium sulfate, contraindication with Sodium sulfate, contraindication with Phenylpropanolamine, contraindication with Phenylpropanolamine, contraindication with Phenylpropanolamine, contraindication with Phenylpropanolamine, contraindication with Orlistat, contraindication with Orlistat. Definitions: hepatic defined as following: Pertaining to, affecting, or associated with the liver.. kidney disorder defined as following: Pathological processes of the KIDNEY or its component tissues.. acute hepatic porphyria defined as following: Porphyria of doss or deficiency of delta-aminolevulinic acid dehydratase (DALAD) is an extremely rare form of acute hepatic porphyria (see this term) characterized by neuro-visceral attacks without cutaneous manifestations.. hypercholesterolemia defined as following: A laboratory test result indicating an increased amount of cholesterol in the blood.. lonafarnib defined as following: A synthetic tricyclic derivative of carboxamide with antineoplastic properties. Lonarfanib binds to and inhibits farnesyl transferase, an enzyme involved in the post-translational modification and activation of Ras proteins. Ras proteins participate in numerous signalling pathways (proliferation, cytoskeletal organization), and play an important role in oncogenesis. Mutated ras proteins have been found in a wide range of human cancers. (NCI04). urinary defined as following: The duct which coveys URINE from the pelvis of the KIDNEY through the URETERS, BLADDER, and URETHRA.. antisense oligonucleotides defined as following: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.. Primary Hyperoxaluria Type 1 defined as following: Recessively inherited primary hyperoxaluria due to alanine-glyoxylate aminotransferase (AGXT) deficiency.. N-acetylgalactosamine defined as following: The N-acetyl derivative of galactosamine.. product defined as following:Participant material that is brought forth (produced) in the act (e.g., specimen in a specimen collection, access or drainage in a placement service, medication package in a dispense service). It does not matter whether the material produced had existence prior to the service, or whether it is created in the service (e.g., in supply services the product is taken from a stock).
. 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.. Pharmaceuticals 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.. oxalate defined as following: A salt or ester of oxalic acid.. oligonucleotide defined as following: Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed). primary hyperoxaluria defined as following: A genetic disorder characterized by excretion of large amounts of OXALATES in urine; NEPHROLITHIASIS; NEPHROCALCINOSIS; early onset of RENAL FAILURE; and often a generalized deposit of CALCIUM OXALATE. There are subtypes classified by the enzyme defects in glyoxylate metabolism..", "label": "yes"} {"id": "converted_102", "sentence1": "Should patients using inhaled glucocorticoids for asthma or COPD be advised to stop these medications to prevent COVID-19?", "sentence2": "International recommendations suggest maintaining asthma under control to limit exacerbations occurrence, by using all available treatment. The minimum steroid dosage effective to control symptoms should be maintained to avoid exacerbations;, The meta-analysis revealed no significant difference in the risk for the development of a fatal course of COVID-19 with preadmission use of inhaled corticosteroids in patients with COVID-19 relative to non-use of inhaled corticosteroids (pooled odds ratio=1.28; 95% confidence interval 0.73-2.26). Similarly, the meta-analysis observed no significant difference in the risk for the development of a severe course of COVID-19 with preadmission use of inhaled corticosteroids in patients with COVID-19 relative to non-use of inhaled corticosteroids (pooled odds ratio=1.45; 95% confidence interval 0.96-2.20)., Our findings assured the safety of continued use of inhaled corticosteroids during the COVID-19 pandemic., Our study showed that asthma is not associated with worse outcomes of COVID-19, despite the higher need for respiratory support compared with the general population, while the use of ICS allowed for a shorter hospital stay., Patients with asthma in regular therapy with ICS at home had significantly shorter hospital stay compared to those with no treatments (25.2 vs. 11.3 days, p = 0.024)., Evidence from clinical studies indicates that the inhaled corticosteroids (ICS) routinely taken for asthma and COPD could have had a protective role in preventing severe COVID-19 and, therefore, may be a promising treatment for COVID-19., The benefit-risk ratio is however clearly in favor of continuing inhaled corticosteroids in patients with asthma or COPD., Due to its known and important benefits ICS should be prescribed as usual for both asthma and COPD., The available recommendations state that patients with asthma should use inhaled glucocorticosteroids (GCS) on a regular basis., These findings should encourage clinicians to continue ICS therapy for COPD patients during the COVID-19 pandemic., Evidence from clinical studies indicates that the inhaled corticosteroids (ICS) routinely taken for asthma and COPD could have had a protective role in preventing severe COVID-19 and, therefore, may be a promising treatment for COVID-19., The available evidence suggests that severe asthma patients do not have an increased risk of poor COVID-19 outcomes and that it is safe to treat asthmatic patients with inhaled corticosteroids (ICS) and biologics during the pandemic, even though some studies indicate that high doses of ICS may predispose to COVID-19., However, patients with asthma or COPD should continue all prescribed inhaled medications., However, patients with asthma or COPD should continue all prescribed inhaled medications., Additionally, the use of systemic or inhaled glucocorticoids does not appear to increase the risk of severe COVID-19, but there is no evidence guiding the use of biologic therapy., Our study supports the recommendation that patients with chronic pulmonary diseases, including asthma and COPD who require treatment with either inhaled or systemic corticosteroids, should continue their use during the COVID-19 pandemic.[SEP]Relations: asthma has relations: contraindication with Sulfadiazine, contraindication with Sulfadiazine, contraindication with Zinc gluconate, contraindication with Zinc gluconate, contraindication with Ascorbic acid, contraindication with Ascorbic acid, contraindication with Ethinylestradiol, contraindication with Ethinylestradiol, contraindication with Methadyl acetate, contraindication with Methadyl acetate. Definitions: asthmatic defined as following: A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).. COPD defined as following: A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.. ICS defined as following: A technique that is used with flow cytometry to measure cytokine production in isolated cells. Cells are stimulated with an antigen or mitogen, and cytokine secretion is blocked using protein transport inhibitors. The cells are then stained with fluorochrome labeled monoclonal antibodies that target surface markers, fixed and permeabilized, and stained with fluorochrome labeled anti-cytokine monoclonal antibodies prior to analysis by flow cytometry.. asthma defined as following: A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL)..", "label": "no"} {"id": "converted_103", "sentence1": "Is Zanubrutinib a first-generation BTK inhibitor approved by US Food and Drug Administration (FDA)?", "sentence2": "In the United States, zanubrutinib, a next-generation BTK inhibitor, has been approved for treating adults with mantle cell lymphoma who have received at least one prior therapy, for adults with Waldenstr\u00f6m macroglobulinemia, and for adults with relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20-based therapy.[SEP]Relations: mantle cell lymphoma has relations: disease_protein with IKBKB, disease_protein with IKBKB, disease_protein with CTNNB1, disease_protein with CTNNB1, disease_protein with CHEK2, disease_protein with CHEK2, disease_protein with UBR5, disease_protein with UBR5, disease_protein with RAD54B, disease_protein with RAD54B. Definitions: BTK inhibitor defined as following: Any drug or substance that inhibits the activity of tyrosine-protein kinase BTK protein.. mantle cell lymphoma defined as following: A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1)..", "label": "no"} {"id": "converted_105", "sentence1": "Is Cinpanemab effective for Parkinson\u2019s Disease?", "sentence2": "CONCLUSIONS: In participants with early Parkinson's disease, the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over a 52-week period. [SEP]Relations: Parkinson disease has relations: contraindication with Alimemazine, contraindication with Alimemazine, contraindication with Propiomazine, contraindication with Propiomazine, contraindication with Acetophenazine, contraindication with Acetophenazine, contraindication with Promazine, contraindication with Promazine, contraindication with Bethanechol, contraindication with Bethanechol. Definitions: 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_108", "sentence1": "Can CRISPR/Cas12a be used for the detection of EGFR mutations in circulating DNA?", "sentence2": "A CRISPR Test for Rapidly and Sensitively Detecting Circulating EGFR Mutations., The CRISPR-Cas12a system can detect both L858R and T790M with a limit of detection of 0.005% in less than three hours., The CRISPR-Cas12a system could detect L858R in plasma of two lung cancer patients whose tissue biopsies are positive for L858R, and one plasma sample of three lung cancer patients whose tissue biopsies are positive for T790M. , This proof of principle study demonstrates that the CRISPR-Cas12a system could rapidly and sensitively detect circulating EGFR mutations, and thus, has potential prognostic or therapeutic implications.[SEP]Relations: epidermal growth factor receptor binding has relations: molfunc_protein with TGFA, molfunc_protein with TGFA, molfunc_protein with PLSCR1, molfunc_protein with PLSCR1, molfunc_protein with ARF4, molfunc_protein with ARF4, molfunc_protein with EGF, molfunc_protein with EGF, molfunc_protein with RNF126, molfunc_protein with RNF126. Definitions: T790M defined as following: A change in the amino acid residue at position 790 in the epidermal growth factor receptor protein where threonine has been replaced by methionine..", "label": "yes"} {"id": "converted_113", "sentence1": "Is PRP-40 involved in microexon splicing?", "sentence2": "PRP-40 is particularly required for inclusion of neuronal microexons, and our data indicate that PRP-40 is a central regulator of microexon splicing. Microexons can be relieved from PRP-40 dependence by artificially increasing exon size or reducing flanking intron size, indicating that PRP-40 is specifically required for microexons surrounded by conventionally sized introns. Knockdown of the orthologous PRPF40A in mouse neuroblastoma cells causes widespread dysregulation of microexons but not conventionally sized exons. PRP-40 regulation of neuronal microexons is therefore a widely conserved phenomenon.[SEP]Relations: PRPF40A has relations: bioprocess_protein with mRNA splicing, via spliceosome, bioprocess_protein with mRNA splicing, via spliceosome, bioprocess_protein with mRNA cis splicing, via spliceosome, bioprocess_protein with mRNA cis splicing, via spliceosome, protein_protein with SP1, protein_protein with SP1, pathway_protein with mRNA Splicing - Major Pathway, pathway_protein with mRNA Splicing - Major Pathway, protein_protein with RPS9, protein_protein with RPS9. Definitions: 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.. 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..", "label": "yes"} {"id": "converted_115", "sentence1": "Is ocrelizumab effective for primary progressive multiple sclerosis?", "sentence2": "Ocrelizumab (Ocrevus\u00ae) is an intravenously administered, humanized anti-CD20 monoclonal antibody approved for the treatment of adults with relapsing forms of multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS)., When using the anti-CD20 monoclonal antibodies ocrelizumab and ofatumumab in the treatment of MS, it is not necessary to test for NAbs as these occur very infrequently. , Ocrelizumab for multiple sclerosis., BACKGROUND: Ocrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration (FDA) in March 2017 for using in adults with relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS).[SEP]Relations: Ocrelizumab has relations: drug_drug with Pexelizumab, drug_drug with Pexelizumab, drug_protein with MS4A1, drug_protein with MS4A1, drug_drug with Otelixizumab, drug_drug with Otelixizumab, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Urelumab, drug_drug with Urelumab. Definitions: ocrelizumab defined as following: A Fc-modified, humanized monoclonal antibody directed against the B-cell CD20 cell surface antigen, with immunosuppressive activity. Ocrelizumab binds to CD20 on the surfaces of B-cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B-cells overexpressing CD20. The CD20 antigen, a non-glycosylated cell surface phosphoprotein that acts as a calcium ion channel, is found on over 90% of B-cells, B-cell lymphomas, and other lymphoid tumor cells of B-cell origin; it plays an important role in B-cell functioning.. ofatumumab defined as following: A fully human, high-affinity IgG1 monoclonal antibody directed against the B cell CD20 cell surface antigen with potential antineoplastic activity. Ofatumumab binds specifically to CD20 on the surfaces of B cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B cells overexpressing CD20. The CD20 antigen, found on over 90% of B cells, B cell lymphomas, and other B cells of lymphoid tumors of B cell origin, is a non-glycosylated cell surface phosphoprotein that acts as a calcium ion channel; it is exclusively expressed on B cells during most stages of B cell development.. PPMS defined as following: A unit of proportion equal to 10E-6.. relapsing-remitting multiple sclerosis defined as following: The most common clinical variant of MULTIPLE SCLEROSIS, characterized by recurrent acute exacerbations of neurologic dysfunction followed by partial or complete recovery. Common clinical manifestations include loss of visual (see OPTIC NEURITIS), motor, sensory, or bladder function. Acute episodes of demyelination may occur at any site in the central nervous system, and commonly involve the optic nerves, spinal cord, brain stem, and cerebellum. (Adams et al., Principles of Neurology, 6th ed, pp903-914). 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). RMS defined as following: A statistical measure of the magnitude of a set of variable values. The root mean square is the square root of the mean value for the squares of the original values..", "label": "yes"} {"id": "converted_118", "sentence1": "Does silencing of SRRM4 inhibit tumor growth across cancers?", "sentence2": "Silencing of SRRM4 suppresses microexon inclusion and promotes tumor growth across cancers., We show that this silencing is favorable for tumor growth, as decreased SRRM4 expression in tumors is correlated with an increase in mitotic gene expression, and up-regulation of SRRM4 in cancer cell lines dose-dependently inhibits proliferation in vitro and in a mouse xenograft model. Further, this proliferation inhibition is accompanied by induction of neural-like expression and splicing patterns in cancer cells, suggesting that SRRM4 expression shifts the cell state away from proliferation and toward differentiation. We therefore conclude that SRRM4 acts as a proliferation brake, and tumors gain a selective advantage by cutting off this brake.[SEP]Relations: malignant giant cell tumor has relations: disease_disease with cancer, disease_disease with cancer, disease_disease with giant cell tumor of soft tissue, disease_disease with giant cell tumor of soft tissue, disease_disease with malignant giant cell tumor of soft parts, disease_disease with malignant giant cell tumor of soft parts, disease_disease with malignancy in giant cell tumor of bone, disease_disease with malignancy in giant cell tumor of bone, disease_disease with giant cell tumor, disease_disease with giant cell tumor. Definitions: cancer cells defined as following: Cells of, or derived from, a malignant tumor.. 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.. 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..", "label": "no"} {"id": "converted_120", "sentence1": "Is daridorexant effective for insomnia?", "sentence2": "Daridorexant (Quviviq\u2122; Idorsia Pharmaceuticals Ltd.) is an orally administered dual orexin type 1 and type 2 (OX1 and OX2) receptor antagonist (DORA) being developed for the treatment of insomnia., Daridorexant was superior to placebo in reducing wake time after sleep onset (MD\u2009=\u2009-13.26; 95% CI, -15.48 to -11.03; P\u2009<\u20090.00001), latency to persistent sleep (MD\u2009=\u2009-7.23; 95% CI, -9.60 to -4.85; P\u2009<\u20090.00001), with increasing the total sleep time (MD\u2009=\u200914.80; 95% CI, 11.18-18.42; P\u2009<\u20090.00001) and subjective total sleep time (MD\u2009=\u200914.80; 95% CI, 11.18-18.42], P\u2009<\u20090.00001). The 25 mg and 50 mg were the most officious doses. Treatment with daridorexant has resulted in a slightly higher incidence of adverse events [risk ratio (RR)\u2009=\u20091.19; 95% CI, 1.05-1.35;, P\u2009=\u20090.005], specifically somnolence (RR\u2009=\u20091.19; 95% CI, 1.13-3.23; P\u2009=\u20090.005) and fatigue (RR\u2009=\u20092.01; 95% CI, 1.21-3.36; P\u2009=\u20090.007). Daridorexant is superior to placebo in improving sleep quality. [SEP]Relations: Fatigue has relations: drug_effect with Darunavir, drug_effect with Darunavir, drug_effect with Lodoxamide, drug_effect with Lodoxamide, drug_effect with Trimetrexate, drug_effect with Trimetrexate, drug_effect with Stiripentol, drug_effect with Stiripentol, drug_effect with Doxazosin, drug_effect with Doxazosin. Definitions: somnolence defined as following: Compelling urge to sleep.. 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.. insomnia defined as following: A sleep disorder characterized by difficulty in falling asleep and/or remaining asleep..", "label": "yes"} {"id": "converted_124", "sentence1": "Is deucravacitinib effective for psoriasis?", "sentence2": "POETYK PSO-1 and PSO-2 involved 1688 patients with moderate-to-severe psoriasis. After 16\u00a0weeks, in both studies, over 50% of patients treated with deucravacitinib reached PASI75, which was significantly superior to placebo and apremilast. In POETYK PSO-1, these results improved until week 24 and were maintained through week 52, with over 65% of patients achieving PASI75 at this point. A reduction in signs and symptoms was also reported by patients, with greater impact on itch. Deucravacitinib was well tolerated and safe. , INTRODUCTION: Deucravacitinib is an oral, selective tyrosine kinase 2 inhibitor that demonstrated therapeutic benefit in a Phase 2 clinical trial of adults with moderate to severe plaque psoriasis. , CONCLUSION: Deucravacitinib treatment produced early response and similar trends in improvements across multiple efficacy assessments and QoL in moderate to severe plaque psoriasis. , CONCLUSION: Deucravacitinib was superior to placebo and apremilast across multiple efficacy endpoints and was well tolerated in moderate to severe psoriasis.[SEP]Relations: Apremilast has relations: drug_drug with Dacomitinib, drug_drug with Dacomitinib. Pruritus has relations: drug_effect with Sunitinib, drug_effect with Sunitinib, drug_effect with Valdecoxib, drug_effect with Valdecoxib, drug_effect with Lercanidipine, drug_effect with Lercanidipine, drug_effect with Acyclovir, drug_effect with Acyclovir. Definitions: itch defined as following: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.. tyrosine kinase 2 defined as following: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.. apremilast defined as following: An orally bioavailable, small molecule inhibitor of phosphodiesterase 4 (PDE4), with potential anti-inflammatory activity. Upon oral administration, apremilast targets, binds to and inhibits the activity of PDE4, thereby blocking cyclic adenosine monophosphate (cAMP) degradation and increasing intracellular cAMP levels. This may decrease the production of the proinflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha). PDE4 is an enzyme that plays an important role in the degradation of cAMP and in cytokine production in inflammatory cells.. 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..", "label": "yes"} {"id": "converted_126", "sentence1": "Can the epigenetic status of introns affect gene expression?", "sentence2": "Here, we show that the expression of the H3K9 demethylase IBM1 (increase in BONSAI methylation 1) requires DNA methylation. Surprisingly, the regulatory methylated region is contained in an unusually large intron that is conserved in IBM1 orthologues., DNA methylation in an intron of the IBM1 histone demethylase gene stabilizes chromatin modification patterns., Polyadenylation (poly(A) sequencing reveals that AAE complex has a substantial influence on poly(A) site usage of heterochromatin-containing genes, including not only intronic heterochromatin-containing genes but also the genes showing overlap with heterochromatin., Heterochromatin is widespread in eukaryotic genomes and has diverse impacts depending on its genomic context., Combining methylation data with mRNA sequencing revealed that DNA methylation in promoters, introns and exons may have different roles in regulating gene expression., In several eukaryotic organisms, heterochromatin (HC) in the introns of genes can regulate RNA processing, including polyadenylation, but the mechanism underlying this regulation is poorly understood., Here we report that ASI1 and EDM2 form a protein complex in vivo via a bridge protein, ASI1-Immunoprecipitated Protein 1 (AIPP1), which is another RNA recognition motif-containing protein. The complex also may contain the Pol II CTD phosphatase CPL2, the plant homeodomain-containing protein AIPP2, and another BAH domain protein, AIPP3. As is the case with dysfunction of ASI1 and EDM2, dysfunction of AIPP1 impedes the use of distal polyadenylation sites at tested intronic HC-containing genes, such as the histone demethylase gene IBM1, resulting in a lack of functional full-length transcripts., Interestingly, hypomethylation of introns is correlated with higher levels of intron expression in mRNA and the methylation level of an intron is inversely correlated with its retention in mRNA from the gene in which it is located., Regulation of gene expression by DNA methylation in gene promoter regions is well studied; however, the effects of methylation in the gene body (exons and introns) on gene expression are comparatively understudied., Consistent with previous work we found that intragenic methylation is positively correlated with gene expression and that exons are more highly methylated than their neighboring intronic environment.[SEP]Relations: promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription. PDZD11 has relations: bioprocess_protein with maintenance of epithelial cell apical/basal polarity, bioprocess_protein with maintenance of epithelial cell apical/basal polarity, pathway_protein with Biotin transport and metabolism, pathway_protein with Biotin transport and metabolism. Hydrocortisone has relations: drug_effect with Paraparesis, drug_effect with Paraparesis. covalent chromatin modification has relations: bioprocess_bioprocess with DNA methylation-dependent heterochromatin assembly, bioprocess_bioprocess with DNA methylation-dependent heterochromatin assembly. Definitions: chromatin modification defined as following: OBSOLETE. The alteration of DNA or protein in chromatin by the covalent addition or removal of chemical groups. [GOC:mah, GOC:vw]. 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.. 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.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. heterochromatin defined as following: The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE.. 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.. 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.. HC defined as following: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.. 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). 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": "yes"} {"id": "converted_129", "sentence1": "Are Luminopsins a fusion proteins of luminol and Rhodopsin ?", "sentence2": "Bioluminescence-optogenetics is mediated by luminopsin fusion proteins-light-sensing opsins fused to light-emitting luciferases., Here we have expanded and refined the versatility of luminopsin tools by fusing an alternative luciferase variant with high light emission, Gaussia luciferase mutant GLucM23, to depolarizing and hyperpolarizing channelrhodopsins, luminopsins by fusing light-sensing opsins with light-emitting luciferases. , ouse iPS-NPCs were transduced with a novel optochemogenetics fusion protein, luminopsin 3 (LMO3), which consisted of a bioluminescent luciferase, Gaussia luciferase, and an opsin, Volvox Channelrhodopsin 1. , Luminopsins are fusion proteins of luciferase and opsin that allow interrogation of neuronal circuits at different temporal and spatial resolutions by choosing either extrinsic physical or intrinsic biological light for its activation.[SEP]Relations: Opsins has relations: pathway_protein with RHO, pathway_protein with RHO, pathway_protein with RGR, pathway_protein with RGR, pathway_protein with OPN1SW, pathway_protein with OPN1SW, pathway_protein with OPN1MW2, pathway_protein with OPN1MW2, pathway_protein with OPN5, pathway_protein with OPN5. Definitions: variant defined as following: An alteration or difference from a norm or standard.. 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).. luciferase defined as following: Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.. opsin defined as following: Photosensitive proteins expressed in the ROD PHOTORECEPTOR CELLS. They are the protein components of rod photoreceptor pigments such as RHODOPSIN.. luminol defined as following: 5-Amino-2,3-dihydro-1,4-phthalazinedione. Substance that emits light on oxidation. It is used in chemical determinations.. Rhodopsin defined as following: This gene plays a role in vision..", "label": "no"} {"id": "converted_134", "sentence1": "Is there a way to distinguish COVID-19 clinically from other respiratory illnesses, such as influenza?", "sentence2": " Unfortunately, COVID-19 patients have symptoms similar to other common illnesses. Here, we hypothesize the order of symptom occurrence could help patients and medical professionals more quickly distinguish COVID-19 from other respiratory diseases, yet such essential information is largely unavailable., No symptoms are characteristic of a single infectious agent, with flu-like disorders being the most common., We show that although COVID-19 and influenza are different in many ways, there are numerous similarities; thus, in addition to using nucleic acid-based polymerase chain reaction (PCR) and antibody-based approaches, clinicians and epidemiologists should distinguish between the two using their respective characteristics in early stages., An understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare., SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics., Unfortunately, COVID-19 patients have symptoms similar to other common illnesses., Clinical presentation of COVID-19, however, can be difficult to distinguish from other respiratory viral infections., It is difficult to distinguish coronavirus disease-2019 (COVID-19) from other viral respiratory tract infections owing to the similarities in clinical and radiological findings., Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown., Since the symptoms are similar to other respiratory infections, differential diagnosis in travellers arriving from countries with wide-spread COVID-19 must include other more common infections such as influenza and other respiratory tract diseases., Clinical presentation of COVID-19, however, can be difficult to distinguish from other respiratory viral infections., COVID-19 and flu are two respiratory illnesses which share similar clinical symptoms., During influenza season, differentiating other causes of respiratory illness from COVID-19 is difficult, because common clinical manifestations of COVID-19 mimic those of influenza.[SEP]Relations: viral respiratory tract infection has relations: disease_disease with influenza, disease_disease with influenza, disease_disease with respiratory syncytial virus infectious disease, disease_disease with respiratory syncytial virus infectious disease. Respiratory tract infection has relations: phenotype_phenotype with Acute infectious pneumonia, phenotype_phenotype with Acute infectious pneumonia, disease_phenotype_positive with glycogen storage disease, disease_phenotype_positive with glycogen storage disease, disease_phenotype_positive with ALG12-CDG, disease_phenotype_positive with ALG12-CDG. Definitions: coronavirus defined as following: Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE).. viral respiratory tract infections defined as following: A respiratory tract infection caused by a virus. Viruses represent the most common causes of upper and lower respiratory tract infections and include rhinoviruses, influenza viruses, parainfluenza viruses, and respiratory syncytial virus.. respiratory tract diseases defined as following: Diseases involving the RESPIRATORY SYSTEM.. respiratory infections defined as following: Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or diseases..", "label": "no"} {"id": "converted_138", "sentence1": "Can untranslated regions (UTRs) regulate gene expression?", "sentence2": "Previously dismissed as \"junk DNA\", it is the non-coding regions of the genome that are responsible for regulation, facilitating complex temporal and spatial gene expression through the combinatorial effect of numerous mechanisms and interactions working together to fine-tune gene expression. The major regions involved in regulation of a particular gene are the 5' and 3' untranslated regions and introns., Post-transcriptional regulation, via 5'-UTRs (5'-untranslated regions), plays an important role in the control of eukaryotic gene expression., Eukaryotic gene expression is precisely regulated at all points between transcription and translation. In this review, we focus on translational control mediated by the 3'-untranslated regions (UTRs) of mRNAs. mRNA 3'-UTRs contain cis-acting elements that function in the regulation of protein translation or mRNA decay., Now, we are beginning to better appreciate the role of 3'-UTR (untranslated region) cis-elements which harbor not only microRNA but also RNA-binding protein (RBP) binding sites that have significant effect on the stability and translational rate of mRNAs., Many studies using reporter assays have demonstrated that 3' untranslated regions (3'-UTRs) regulate gene expression by controlling mRNA stability and translation., The untranslated regions of mRNAs can determine gene expression by influencing mRNA stability and translational efficiency., In higher eukaryotes, untranslated regions (UTRs) of transcripts are one of the crucial regulators of gene expression (influencing mRNA stability and translation efficiency)., Our results suggest that 3'UTR sequences can function not only in cis to regulate protein expression, but also intrinsically and independently in trans, likely as noncoding RNAs, a conclusion supported by a number of previous genetic studies., The 3' untranslated regions (3'UTRs) of eukaryotic genes regulate mRNA stability, localization and translation., The 5' and 3' untranslated regions of eukaryotic mRNAs (UTRs) play crucial roles in the post-transcriptional regulation of gene expression through the modulation of nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization, and message stability., 3' untranslated regions (UTRs) are known to play an important role in posttranscriptional regulation of gene expression., The 3' untranslated region (3' UTR) can control gene expression by affecting the localization, stability and translation of mRNAs., In higher eukaryotes, untranslated regions (UTRs) of transcripts are one of the crucial regulators of gene expression (influencing mRNA stability and translation efficiency)., Untranslated regions (UTR) play important roles in the posttranscriptional regulation of mRNA processing., Untranslated gene regions (UTRs) play an important role in controlling gene expression., The untranslated regions (UTRs) of mRNA are hotspots for regulatory control., Untranslated regions (UTRs) in eukaryotes play a significant role in the regulation of translation and mRNA half-life, as well as interacting with specific RNA-binding proteins., Untranslated regions (UTRs) of eukaryotic mRNAs play crucial roles in post-transcriptional regulation of gene expression via the modulation of nucleocytoplasmic mRNA transport, translation efficiency, subcellular localization, and message stability., The 5' and 3' untranslated regions (UTRs) regulate crucial aspects of post-transcriptional gene regulation that are necessary for the maintenance of cellular homeostasis. When these processes go awry through mutation or misexpression of certain regulatory elements, the subsequent deregulation of oncogenic gene expression can drive or enhance cancer pathogenesis.[SEP]Relations: rRNA transcription has relations: bioprocess_protein with SPIN1, bioprocess_protein with SPIN1. SLC14A2 has relations: molfunc_protein with urea transmembrane transporter activity, molfunc_protein with urea transmembrane transporter activity. protein binding has relations: molfunc_protein with UTRN, molfunc_protein with UTRN, molfunc_protein with UTF1, molfunc_protein with UTF1, molfunc_protein with UTP15, molfunc_protein with UTP15. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. genome defined as following: Anatomical set of genes in all the chromosomes.. binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. UTRs defined as following: The parts of the messenger RNA sequence that do not code for product, i.e. the 5' UNTRANSLATED REGIONS and 3' UNTRANSLATED REGIONS.. 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.. transcripts defined as following: The initial RNA molecule produced by transcription.. 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.. 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.. 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.. 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.. 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.. 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_139", "sentence1": "Is alternative splicing associated with heart disease?", "sentence2": "We identified >200 significant alternative splicing (AS) events and distinct AS profiles were observed in the right (RV) and left (LV) ventricles in PLN-R14del compared to WT mouse hearts. , Our findings suggest that aberrant splicing may affect Ca2+-homeostasis in the heart, contributing to the increased risk of arrythmogenesis in PLN-R14del ACM.[SEP]Relations: FGFR2 alternative splicing has relations: pathway_protein with POLR2D, pathway_protein with POLR2D, pathway_protein with POLR2G, pathway_protein with POLR2G, pathway_protein with RBFOX2, pathway_protein with RBFOX2, pathway_protein with ESRP2, pathway_protein with ESRP2, pathway_protein with POLR2K, pathway_protein with POLR2K. Definitions: 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.. heart disease defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities..", "label": "yes"} {"id": "converted_140", "sentence1": "Should Intepirdine be used for Alzheimer's disease?", "sentence2": "There were no statistically significant differences between intepirdine and placebo groups (adjusted mean [95% confidence interval]) on the co-primary endpoints ADAS-Cog (-0.36 [-0.95, 0.22], P\u00a0=\u00a00.2249) and ADCS-ADL (-0.09 [-0.90, 0.72], P\u00a0=\u00a00.8260). , Discussion: Intepirdine as adjunctive therapy to donepezil did not produce statistical improvement over placebo on cognition or activities of daily living in mild-to-moderate AD dementia patients., EXPERT OPINION: Despite early positive findings, larger phase-III trials have failed to demonstrate any statistically significant impact on cognition for both idalopirdine and intepirdine, as adjunct to cholinesterase inhibitors.[SEP]Relations: Idalopirdine has relations: drug_drug with Eletriptan, drug_drug with Eletriptan, drug_drug with Poldine, drug_drug with Poldine, drug_drug with Eperisone, drug_drug with Eperisone, drug_drug with Epinastine, drug_drug with Epinastine, drug_drug with Almotriptan, drug_drug with Almotriptan. Definitions: 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.. dementia defined as following: The presence of dementia in an individual younger than age sixty five.. Alzheimer's disease defined as following: Alzheimer's disease with an early onset (starts before the age of 65). It is caused by mutations in the PSEN2 gene..", "label": "no"} {"id": "converted_144", "sentence1": "Is rilonacept effective for pericarditis?", "sentence2": " Concerning acute recurrent pericarditis (RP), an innovative interaction between cardiologists, internists and pediatric rheumatologists led to the intuition of a pivotal role of IL-1 in recurrent pericarditis characterized by an evident inflammatory recurrent phenotype, and recent data have shown the striking efficacy of anakinra and rilonacept in these patients. , Pericarditis is regarded as a stereotypical response to an acute damage of the mesothelial cells of the pericardial layers. NLRP3 inflammasome, a macromolecular structure sensing damage and releasing pro-inflammatory cytokines, is centrally involved as it releases interleukin (IL)-1\u03b2, whose auto-induction feeds an autoinflammatory disease, mostly responsible for recurrences. Colchicine, an inhibitor of NLRP3 inflammasome formation, and IL-1-targeted therapies, such as anakinra and rilonacept, were found to effectively blunt the acute inflammation and reduce the risk for recurrences., Currently, anakinra and rilonacept, have demonstrated beneficial impact in clinical outcomes with a reasonable safety profile in randomized clinical trials. There is still paucity of data regarding the use of canakinumab in the treatment of patients with RP. , Rilonacept: A Newly Approved Treatment for Recurrent Pericarditis., OBJECTIVE: To review the pharmacology, efficacy, and safety of rilonacept for the prevention and treatment of recurrent pericarditis (RP)., CONCLUSION: Rilonacept is a safe, once weekly, subcutaneously administered IL-1 \"trap,\" indicated for the treatment of RP, and reduction in risk of recurrent pericarditis in adults and children \u226512 years of age., Overproduction of both IL-1\u03b1 (released by inflamed/damaged pericardial cells) and IL-1\u03b2 (released by inflammatory cells) is now a well-recognized therapeutic target in patients with recurrent idiopathic pericarditis. Currently, there are three available anti-IL-1 agents: anakinra (recombinant human IL-1Ra), rilonacept (a soluble decoy receptor 'trap', binding both IL-1\u03b1 and IL-1\u03b2), and canakinumab (human monoclonal anti-IL-1\u03b2 antibody). [SEP]Relations: Rilonacept has relations: drug_drug with Permethrin, drug_drug with Permethrin, drug_drug with Teriflunomide, drug_drug with Teriflunomide, drug_drug with Pertussis vaccine, drug_drug with Pertussis vaccine, drug_drug with Perhexiline, drug_drug with Perhexiline, drug_drug with Dofetilide, drug_drug with Dofetilide. Definitions: Colchicine defined as following: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE).. anakinra defined as following: A synthetic form of native human IL-1Ra that has an additional methionine residue at its amino terminus.. mesothelial cells defined as following: A flat cell of mesenchymal origin that forms the superficial layer of the serosal membranes lining the body cavities of the abdomen and thorax.. canakinumab defined as following: A recombinant monoclonal antibody targeting human interleukin-1 beta (IL-1b), with anti-inflammatory and immunomodulating activities. Canakinumab binds IL-1b and prevents the binding of IL-1b to the IL-1 receptor and inhibits IL-1b-mediated signaling. This may suppress inflammatory responses mediated by IL-1b. IL-1b, a proinflammatory cytokine, plays a key role in inflammation.. IL-1 defined as following: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.. Pericarditis defined as following: Inflammation of the PERICARDIUM from various origins, such as infection, neoplasm, autoimmune process, injuries, or drug-induced. Pericarditis usually leads to PERICARDIAL EFFUSION, or CONSTRICTIVE PERICARDITIS.. RP defined as following: Hereditary, progressive degeneration of the retina due to death of ROD PHOTORECEPTORS initially and subsequent death of CONE PHOTORECEPTORS. It is characterized by deposition of pigment in the retina.. pericarditis defined as following: Inflammation of the PERICARDIUM from various origins, such as infection, neoplasm, autoimmune process, injuries, or drug-induced. Pericarditis usually leads to PERICARDIAL EFFUSION, or CONSTRICTIVE PERICARDITIS..", "label": "yes"} {"id": "converted_148", "sentence1": "Is tebentafusp effective for uveal melanoma?", "sentence2": "Tebentafusp (tebentafusp-tebn; Kimmtrak\u00ae) is a first-in-class, bispecific gp100 peptide-HLA-A*02:01 directed T cell receptor (TCR) CD3 T cell engager being developed by Immunocore for the treatment of uveal melanoma and malignant melanoma. , This article summarizes the milestones in the development of tebentafusp leading to this first approval for unresectable or metastatic uveal melanoma., Tebentafusp was granted full approval on January 25th 2022 in the setting of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma., In a large meta-analysis, surgical treatment was associated with 6 months longer median overall survival as compared to conventional chemotherapy and, recently, tebentafusp as first-line treatment at the first interim analysis of a randomized phase III trial likewise provided a 6 months longer median overall survival compared to investigator's choice, mostly pembrolizumab; these treatments currently apply to selected patients. [SEP]Relations: melanoma has relations: contraindication with Entacapone, contraindication with Entacapone, contraindication with Rasagiline, contraindication with Rasagiline, contraindication with Methoxsalen, contraindication with Methoxsalen, contraindication with Amantadine, contraindication with Amantadine, disease_protein with MTPAP, disease_protein with MTPAP. Definitions: TCR defined as following: The nucleotide-excision repair process that carries out preferential repair of DNA lesions on the actively transcribed strand of the DNA duplex. In addition, the transcription-coupled nucleotide-excision repair pathway is required for the recognition and repair of a small subset of lesions that are not recognized by the global genome nucleotide excision repair pathway. [PMID:10197977, PMID:11900249]. 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).", "label": "yes"} {"id": "converted_150", "sentence1": "Is erenumab effective for trigeminal neuralgia?", "sentence2": "INTERPRETATION: Erenumab did not reduce pain intensity compared with placebo in patients with trigeminal neuralgia and CGRP probably does not have an important role in paroxysmal pain., There was no difference between groups in the number of responders at 4 weeks in the intention-to-treat population (14 [35%] of 40 with erenumab vs 18 [45%] of 40 with placebo; estimated effect size -10% [95% CI -31 to 11]; p=0\u00b736). 20 (50%) of 40 participants reported adverse events in each group. [SEP]Relations: trigeminal neuralgia has relations: disease_disease with cranial neuralgia, disease_disease with cranial neuralgia, disease_protein with IL1B, disease_protein with IL1B, disease_protein with MAPK9, disease_protein with MAPK9, disease_protein with TNF, disease_protein with TNF, disease_protein with GRIN1, disease_protein with GRIN1. 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.. trigeminal neuralgia defined as following: A syndrome characterized by recurrent episodes of excruciating pain lasting several seconds or longer in the sensory distribution of the TRIGEMINAL NERVE. Pain may be initiated by stimulation of trigger points on the face, lips, or gums or by movement of facial muscles or chewing. Associated conditions include MULTIPLE SCLEROSIS, vascular anomalies, ANEURYSMS, and neoplasms. (Adams et al., Principles of Neurology, 6th ed, p187).", "label": "no"} {"id": "converted_152", "sentence1": "Can other vaccines be given with COVID-19 vaccine?", "sentence2": "Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need., It is unknown if the efficacy of the coronavirus disease-19 (COVID-19) vaccine is affected by the co-administration of other vaccines. The Centers for Disease Control and Prevention (CDC) has shifted their recommendations recently, allowing for the co-administration of the currently available COVID-19 vaccines with other vaccines. This is based on the experience with non-COVID-19 vaccines, where the immunogenicity and adverse event profiles were generally similar when vaccines are administered simultaneously or alone. , Although the administration of Tdap with COVID-19 vaccine in our case caused delay in immunogenicity, it did not negate the ability of the BNT162B2 mRNA vaccine to elicit an adequate immune response., Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine., In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine.[SEP]Relations: COVID-19 has relations: disease_disease with COVID-19 or sequela, disease_disease with COVID-19 or sequela, disease_disease with Orthocoronavirinae infectious disease, disease_disease with Orthocoronavirinae infectious disease, disease_disease with COVID-19\u2013associated multisystem inflammatory syndrome in children, disease_disease with COVID-19\u2013associated multisystem inflammatory syndrome in children. Rotavirus infection has relations: disease_disease with Reoviridae infectious disease, disease_disease with Reoviridae infectious disease, disease_disease with digestive system infectious disease, disease_disease with digestive system infectious disease. Definitions: BNT162b2 defined as following: A formulation consisting of lipid nanoparticle (LNP) encapsulating a nucleoside modified messenger RNA (modRNA) encoding an optimized form of the full-length severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike glycoprotein (SP), with potential immunizing and anti-COVID-19 activities. Upon injection of tozinameran, the LNPs bind to the plasma membrane of nearby cells and release SARS-CoV-2 SP mRNA into the cell. The mRNA is then translated by the cellular protein translation machinery to produce SARS-CoV-2 SP. This may stimulate the immune system to induce an antibody and T-cell-mediated immune response. This may provide active immunization against SARS-CoV-2 infection. SP, usually found on the surface of SARS-CoV-2, plays an essential role in the infection pathway of the SARS-CoV-2 virus.. coronavirus defined as following: Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE).. Concomitant defined as following: Accessory, accompanying especially in a subordinate or incidental way, occurring or existing during the same period of time.. vaccines defined as following: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases..", "label": "yes"} {"id": "converted_154", "sentence1": "Is music therapy effective for pain management in neonates?", "sentence2": "This review supports the beneficial effects of music-based interventions on the health of preterm infants in a neonatal intensive care unit; however, it also offers suggestions for future studies in order to increase the number of interventions with music therapists, since the results of music therapy approaches were more consistent for physiological and behavioural outcomes., No effect of a musical intervention on stress response to venepuncture in a neonatal population., Our findings did not support the additional benefit of music intervention on neonatal stress response to venepuncture in preterm infants., BF could significantly reduce pain response in healthy-term neonates during heel lance. MT did not enhance the effect of pain relief of BF.[SEP]Definitions: MT defined as following: A physical treatment primarily used to treat musculoskeletal pain and disability through physical manipulation of the body..", "label": "no"} {"id": "converted_160", "sentence1": "Is there any association between Tripe palms and cancer?", "sentence2": "ACANTHOSIS NIGRICANS MALIGNA: Symmetrical mainly intertriginous hyperpigmentation with partially verrucous hyperplasia and lichenification mostly in association with gastric adenocarcinoma. Special forms are florid cutaneous papillomatosis and tripe palms., Bladder cancer with AN concomitant with tripe palms (TP) and/or mucosal involvement is relatively rare and, to our knowledge, only seven cases of AN with bladder cancer have been reported in the English literature. , BACKGROUND: Tripe palms (TP) is one of the rare cutaneous paraneoplastic manifestations of various intra-abdominal malignancies. , BACKGROUND: Acanthosis nigricans (AN), Leser-Tr\u00e9lat sign, and tripe palm are all skin diseases. To date, reports of these appearing as a paraneoplastic syndrome in a gastric cancer patient are quite rare., Finally, yet another collection of paraneoplastic skin disorders can associate themselves with anatomically-diverse malignancies (Leser-Trelat syndrome, Trousseau syndrome, dermatomyositis, erythema gyratum repens, hypertrichosis lanuginosa acquisita, papuloerythroderma of Ofuji, tripe palms, and multicentric reticulohistiocytosis). Recognition of these processes by the pathologist can be a valuable step in the characterization of underlying malignant diseases.[SEP]Relations: pustulosis palmaris et plantaris has relations: disease_protein with APOE, disease_protein with APOE, disease_protein with RUNX3, disease_protein with RUNX3, disease_protein with TAGAP, disease_protein with TAGAP, disease_protein with CRP, disease_protein with CRP, disease_protein with LCE3D, disease_protein with LCE3D. Definitions: Bladder cancer defined as following: A primary or metastatic malignant neoplasm involving the bladder.. gastric adenocarcinoma defined as following: An adenocarcinoma arising from the stomach glandular epithelium. Gastric adenocarcinoma is primarily a disease of older individuals. It most commonly develops after a long period of atrophic gastritis and is strongly associated with Helicobacter pylori infection. The lack of early symptoms often delays the diagnosis of gastric cancer. The majority of patients present with advanced tumors which have poor rates of curability. Microscopically, two important histologic types of gastric adenocarcinoma are recognized: the intestinal and diffuse type. The overall prognosis of gastric adenocarcinomas is poor, even in patients who receive a \"curative\" resection (adapted from Sternberg's Surgical Pathology, 3rd ed., 1999).. paraneoplastic syndrome defined as following: In patients with neoplastic diseases a wide variety of clinical pictures which are indirect and usually remote effects produced by tumor cell metabolites or other products.. dermatomyositis defined as following: Dermatomyositis in an adult.. gastric cancer defined as following: A primary or metastatic malignant neoplasm involving the stomach..", "label": "yes"} {"id": "converted_166", "sentence1": "Can Amyotrophic Lateral Sclerosis (ALS) be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene?", "sentence2": "Approximately 2% of amyotrophic lateral sclerosis (ALS) cases are caused by mutations in the super oxide dismutase 1 (SOD1) gene a, . The two most widely studied ALS/FTLD models, super-oxide dismutase 1 (SOD1), A novel mutation of the SOD-1 gene which encodes the enzyme copper-zinc superoxide dismutase was identified in a family manifesting amyotrophic lateral sclerosis (ALS) in three generations., Mutations in the Cu/Zn superoxide dismutase gene (SOD-1) are reported in 20% of familial amyotrophic lateral sclerosis (ALS) cases, but no definite report of a mutation in a \"truly\" sporadic case of ALS has been proved., Copper-zinc superoxide dismutase 1 (SOD1) is one of the most commonly mutated genes in ALS, and more than 160 mutations in SOD1 have been reported., Mutations of the Cu/Zn superoxide dismutase (SOD-1) gene were recently implicated in the pathogenesis of familial amyotrophic lateral sclerosis (ALS)., Over 30 different mutations of SOD-1 have now been identified in families with ALS., A novel mutation of SOD-1 (Gly 108 Val) in familial amyotrophic lateral sclerosis., Approximately 2% of amyotrophic lateral sclerosis (ALS) cases are caused by mutations in the super oxide dismutase 1 (SOD1) gene and transgenic mice for these mutations recapitulate many features of this devastating neurodegenerative disease., Mutations of the gene SOD-1, which encodes the enzyme copper-zinc superoxide dismutase, occur in patients with a familial form of amyotrophic lateral sclerosis (ALS)., Autosomal-dominant familial amyotrophic lateral sclerosis (FALS) is associated with mutation in the gene that encodes Cu/Zn superoxide dismutase (SOD1)., (1996) (Morita, M., Aoki, M., Abe, K., Hasegawa, T., Sakuma, R., Onodera, Y., Ichikawa, N., Nishizawa, M. and Itoyama, Y., A novel two-base mutation in the Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis in Japan., Mutations of the SOD1 gene, which encodes the enzyme copper/zinc superoxide dismutase, are associated with familial amyotrophic lateral sclerosis (ALS)., Familial ALS is associated with mutations in all exons of SOD1: a novel mutation in exon 3 (Gly72Ser)., Here we report tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O2.- to O2 and H2O2 (ref., Familial amyotrophic lateral sclerosis (FALS), a degenerative disorder of motor neurons, is associated with mutations in the Cu/Zn superoxide dismutase gene SOD1 in some affected families., Eight of 38 patients (21%) with familial and 5 of 175 patients (3%) with sporadic amyotrophic lateral sclerosis (ALS) had missense mutations in the SOD-1 gene., The SOD1 gene encoding the superoxide dismutase 1 (SOD1) protein is mutated in approximately 15% of familial amyotrophic lateral sclerosis (ALS) and 3% of sporadic ALS., About 20% of ALS families are associated with mutations in the gene for superoxide dismutase-1 (SOD1) encoded on chromosome 21q22.1., The superoxide dismutase-1 (SOD1) gene is the first gene for familial amyotrophic lateral sclerosis (ALS) with autosomal dominant inheritance., Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) gene have been shown to cause a familial form of amyotrophic lateral sclerosis (SOD1-ALS)., Mutations in the gene encoding Cu/Zn-superoxide dismutase (SOD-1) have been identified in cases of familial amyotrophic lateral sclerosis linked to chromosome 21., Mutations in the Cu, Zn superoxide dismutase (SOD1) gene have been reported in some pedigrees with Familial Amyotrophic Lateral Sclerosis (FALS)., Genetic mutations in Cu/Zn superoxide dismutase (SOD1) have been associated with one kind of familial amyotrophic lateral sclerosis (ALS1)., Accumulated evidence implies that mutations in the gene coding for Cu/Zn superoxide dismutase (SOD) are associated with the pathogenesis of the familial form of amyotrophic lateral sclerosis (ALS)., have reported point mutations in the cytosolic Cu/Zn superoxide dismutase (SOD 1) gene in some families with familial amyotrophic lateral sclerosis (ALS)., All mutations in the human gene for CuZn superoxide dismutase (CuZnSOD) reported to date are associated with the disease amyotrophic lateral sclerosis (ALS)., Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene have been reported to cause adult-onset autosomal dominant amyotrophic lateral sclerosis (FALS)., We report the absence of superoxide dismutase (SOD-1) gene mutations in 30 patients with amyotrophic lateral sclerosis (ALS) including individuals with a confirmed family history of ALS (familial ALS/FALS), ALS with an unclear family history (UFALS) and sporadic ALS (SALS)., A predilection for disease onset in the lower limbs appears to be a distinguishing feature of familial ALS with SOD-1 mutations, and accords with findings in transgenic mouse models., is a new type of SOD1 mutation which may be associated with familial amyotrophic lateral sclerosis.CON, To delineate ALS associated with this particular CuZn-SOD mutation from ALS without mutations, we performed a detailed neurophysiological study of the corticomotoneuronal function using peristimulus time histograms (PSTHs) in eight ALS patients homozygous for the D90A CuZn-SOD mutation., ateral sclerosis (ALS) cases, but no definite report of a mutation in a \"truly\" sporadic case of ALS has been proved. We present the first case of a n, It has been reported that mutations in the superoxide dismutase (SOD) 1 gene can lead to ALS., Mutations in the superoxide dismutase-1 (SOD1) gene have been found in 12%-23% of patients diagnosed with familial ALS., INTRODUCTION: Mutations in the gene encoding the free radical scavenging enzyme CuZn-superoxide dismutase have been associated with amyotrophic lateral sclerosis (ALS), Up to 20% of ALS cases are inherited (familial, fALS) and associated with mutations, usually of the superoxide dismutase type 1 (SOD-1) gene.[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_protein with ALS2, disease_protein with ALS2, disease_protein with SOD1, disease_protein with SOD1, disease_protein with SOD2, disease_protein with SOD2, disease_disease with motor neuron disease, disease_disease with motor neuron disease, disease_protein with JUND, disease_protein with JUND. Definitions: chromosome 21 defined as following: A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.. amyotrophic lateral sclerosis 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). 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.. superoxide dismutase-1 defined as following: A superoxide dismutase (SOD1) that requires copper and zinc ions for its activity to destroy SUPEROXIDE FREE RADICALS within the CYTOPLASM. Mutations in the SOD1 gene are associated with AMYOTROPHIC LATERAL SCLEROSIS-1.. Genetic mutations defined as following: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.. Copper-zinc superoxide dismutase 1 defined as following: This gene plays a role in the detoxification of superoxide radicals in the cytosol.. SOD defined as following: A very rare congenital syndrome characterized by hypoplasia of the optic nerve, impaired vision, absence of the septum pellucidum and hypopituitarism.. SOD1 defined as following: Superoxide dismutase [Cu-Zn] (154 aa, ~16 kDa) is encoded by the human SOD1 gene. This protein is involved in the conversion of superoxides into oxygen and hydrogen peroxide.. 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]. H2O2 defined as following: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.. cytosolic defined as following: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.. SOD-1 defined as following: Catalysis of the reaction: 2 superoxide + 2 H+ = O2 + hydrogen peroxide. [EC:1.15.1.1, GOC:vw, PMID:15064408]. O2 defined as following: A Commissioned Officer O2 is a First Lieutenant in all US military branches except in the Coast Guard and Navy where it is a Lieutenant Junior Grade.. 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.. Gly defined as following: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.. 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.. 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.. 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.. transgenic mice defined as following: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.. motor neurons defined as following: Neurons which send impulses peripherally to activate muscles or secretory cells.. 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.. 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).", "label": "yes"} {"id": "converted_172", "sentence1": "Are any medications available to prevent COVID-19 following exposure?", "sentence2": "Casirivimab/imdevimab (REGN-COV), a cocktail of neutralizing antibodies against the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, was shown to be an effective treatment and post-exposure prophylaxis measure for coronavirus disease 2019 (COVID-19)., The high titer of IgGSP supports the clinical benefit of therapeutic and prophylactic use of REGN-COV from the serological point of view., We collected serological data of patients with COVID-19 who were treated with REGN-COV 1200\u00a0mg (casirivimab 600\u00a0mg/imdevimab 600\u00a0mg)., Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID-19. , Overall, the reliable evidence available does not support the use ivermectin for treatment or prevention of COVID-19 outside of well-designed randomized trials., Currently, evidence on efficacy and safety of ivermectin for prevention of SARS-CoV-2 infection and COVID-19 treatment is conflicting., We report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 (COVID-19)., This study did not meet the primary efficacy endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 versus placebo., This systematic review was performed to determine the population that benefited from prophylactic ivermectin. , Ivermectin was associated with a lower risk of COVID-19 (OR, 0.22; 95% CI, 0.12-0.40) in the pre-exposure population, whereas no protective effect was observed in the post-exposure population (OR, 0.39; 95% CI, 0.09-1.67). In summary, prophylactic ivermectin did not prevent COVID-19 in the post-exposure population. Although the protective effect of ivermectin was shown in the overall and pre-exposure populations, the results were unreliable owing to poor-quality evidence., This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection., Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies., To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection., Chloroquine or hydroxychloroquine has demonstrated no effect on the treatment of hospitalized COVID-19 patients. This study aimed to answer questions related to the use of hydroxychloroquine for pre-exposure or post-exposure prophylaxis of SARS-CoV-2 infection and in the treatment of patients with mild COVID-19 in terms of hospitalization, adverse events, and mortality., The use of hydroxychloroquine for prophylaxis of SARS-CoV-2 infection or treatment of patients with mild COVID-19 is not recommended., No statistically significant differences were found between the hydroxychloroquine and control groups in terms of pre- or post-exposure prophylaxis of SARS-CoV-2 infection., Rapidly emerging SARS-CoV-2 variants jeopardize antibody-based countermeasures. Although cell culture experiments have demonstrated a loss of potency of several anti-spike neutralizing antibodies against variant strains of SARS-CoV-21-3, the in vivo importance of these results remains uncertain., Therefore, many-but not all-of the antibody products with Emergency Use Authorization should retain substantial efficacy against the prevailing variant strains of SARS-CoV-2., Although some individual mAbs showed reduced or abrogated neutralizing activity in cell culture against B.1.351, B.1.1.28, B.1.617.1 and B.1.526 viruses with mutations at residue E484 of the spike protein, low prophylactic doses of mAb combinations protected against infection by many variants in K18-hACE2 transgenic mice, 129S2 immunocompetent mice and hamsters, without the emergence of resistance. , Hydroxychloroquine (HCQ) has been tried against COVID-19 owing to its in vitro virucidal action against SARS-CoV-2, but the role of HCQ as post-exposure prophylaxis (PEP) remains inconclusive.[SEP]Relations: Chloroquine has relations: drug_drug with Sofosbuvir, drug_drug with Sofosbuvir, drug_drug with Gadodiamide, drug_drug with Gadodiamide, drug_drug with Tacrolimus, drug_drug with Tacrolimus, drug_drug with Elbasvir, drug_drug with Elbasvir, drug_drug with Efonidipine, drug_drug with Efonidipine. Definitions: variants defined as following: An alteration or difference from a norm or standard.. ivermectin defined as following: A mixture of mostly avermectin H2B1a (RN 71827-03-7) with some avermectin H2B1b (RN 70209-81-3), which are macrolides from STREPTOMYCES avermitilis. It binds glutamate-gated chloride channel to cause increased permeability and hyperpolarization of nerve and muscle cells. It also interacts with other CHLORIDE CHANNELS. It is a broad spectrum antiparasitic that is active against microfilariae of ONCHOCERCA VOLVULUS but not the adult form.. 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.. Chloroquine defined as following: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.. cell culture defined as following: Any laboratory procedure for growing cells or tissues in vitro.. Hydroxychloroquine defined as following: A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p970). coronavirus defined as following: Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE).. residue defined as following: A single unit within a polymer; a recognizable molecular fragment embedded in a larger molecule.. transgenic mice defined as following: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.. spike protein defined as following: A protein complex comprised of two heavy chains and two light chains. Monoclonal immunoglobulin (M protein) is found in abundance in patients who have multiple myeloma. The protein is not produced in response to an antigen, but it is expressed in malignant plasma cells and excreted into the blood and urine.. SARS-CoV-2 infection defined as following: A viral disorder generally characterized by high FEVER; COUGH; DYSPNEA; CHILLS; PERSISTENT TREMOR; MUSCLE PAIN; HEADACHE; SORE THROAT; a new loss of taste and/or smell (see AGEUSIA and ANOSMIA) and other symptoms of a VIRAL PNEUMONIA. In severe cases, a myriad of coagulopathy associated symptoms often correlating with COVID-19 severity is seen (e.g., BLOOD COAGULATION; THROMBOSIS; ACUTE RESPIRATORY DISTRESS SYNDROME; SEIZURES; HEART ATTACK; STROKE; multiple CEREBRAL INFARCTIONS; KIDNEY FAILURE; catastrophic ANTIPHOSPHOLIPID ANTIBODY SYNDROME and/or DISSEMINATED INTRAVASCULAR COAGULATION). In younger patients, rare inflammatory syndromes are sometimes associated with COVID-19 (e.g., atypical KAWASAKI SYNDROME; TOXIC SHOCK SYNDROME; pediatric multisystem inflammatory disease; and CYTOKINE STORM SYNDROME). A coronavirus, SARS-CoV-2, in the genus BETACORONAVIRUS is the causative agent.. 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": "no"} {"id": "converted_173", "sentence1": "Has RTA 408 received FDA approval?", "sentence2": "Forced overexpression of HO-1, pharmacological activation of HO-1 with the agonists RTA-408 (omaveloxolone, an FDA-approved drug) and RTA-402 repressed cell death, and treatment with HO-1 antagonist SnPP exacerbated the cell death. [SEP]Relations: Protoporphyrin has relations: drug_drug with Tretinoin, drug_drug with Tretinoin, drug_drug with Porfimer sodium, drug_drug with Porfimer sodium, drug_protein with FTL, drug_protein with FTL, drug_drug with Verteporfin, drug_drug with Verteporfin. Definitions: agonists defined as following: An agent that has affinity for a receptor and intrinsic activity at that receptor.. HO-1 defined as following: This gene is involved in heme catabolism and cellular homeostasis.. RTA-408 defined as following: A member of the synthetic oleanane triterpenoid class of compounds and an activator of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2, Nfe2l2), with potential chemopreventive activity. Upon administration, RTA 408 activates the cytoprotective transcription factor Nrf2. In turn, Nrf2 translocates to the nucleus, dimerizes with a small Maf protein (sMaf), and binds to the antioxidant response element (ARE). This induces the expression of a number of cytoprotective genes, including NAD(P)H quinone oxidoreductase 1 (NQO1), sulfiredoxin 1 (Srxn1), heme oxygenase-1 (HO1, HMOX1), superoxide dismutase 1 (SOD1), gamma-glutamylcysteine synthetase (gamma-GCS), thioredoxin reductase-1 (TXNRD1), glutathione S-transferase (GST), glutamate-cysteine ligase catalytic subunit (Gclc) and glutamate-cysteine ligase regulatory subunit (Gclm), and increases the synthesis of the antioxidant glutathione (GSH). Nrf2, a leucine zipper transcription factor, plays a key role in the maintenance of redox balance and cytoprotection against oxidative stress. Check for \"https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C113443\" active clinical trials using this agent. (\"http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C113443\" NCI Thesaurus). RTA defined as following: A group of genetic disorders of the KIDNEY TUBULES characterized by the accumulation of metabolically produced acids with elevated plasma chloride, hyperchloremic metabolic ACIDOSIS. Defective renal acidification of URINE (proximal tubules) or low renal acid excretion (distal tubules) can lead to complications such as HYPOKALEMIA, hypercalcinuria with NEPHROLITHIASIS and NEPHROCALCINOSIS, and RICKETS..", "label": "yes"} {"id": "converted_177", "sentence1": "Can reinfection occur after SARS-CoV-2 infection?", "sentence2": "A precise estimate of the frequency and severity of SARS-CoV-2 reinfections would be critical to optimize restriction and vaccination policies for the hundreds of millions previously infected subjects. We performed a meta-analysis to evaluate the risk of reinfection and COVID-19 following primary infection., Reinfection rates were still 0.66% after \u226512\u2009months from first infection, and the risk was substantially lower among vaccinated subjects (0.32% vs. 0.74% for unvaccinated individuals). During the first 3\u00a0months of Omicron wave, the reinfection rates reached 3.31%., A strong natural immunity follows the primary infection and may last for more than one year, suggesting that the risk and health care needs of recovered subjects might be limited. Although the reinfection rates considerably increased during the Omicron wave, the risk of a secondary severe or lethal disease remained very low., Despite over 140\u00a0million SARS-CoV-2 infections worldwide since the beginning of the pandemic, relatively few confirmed cases of SARS-CoV-2 reinfection have been reported. While immunity from SARS-CoV-2 infection is probable, at least in the short term, few studies have quantified the reinfection risk., Reinfection was an uncommon event (absolute rate 0%-1.1%), with no study reporting an increase in the risk of reinfection over time. Only one study estimated the population-level risk of reinfection based on whole genome sequencing in a subset of patients; the estimated risk was low (0.1% [95% CI: 0.08-0.11%]) with no evidence of waning immunity for up to 7\u00a0months following primary infection. These data suggest that naturally acquired SARS-CoV-2 immunity does not wane for at least 10\u00a0months post-infection. However, the applicability of these studies to new variants or to vaccine-induced immunity remains uncertain., The risk of reinfection increased almost 18-fold following emergence of the Omicron variant compared with Delta., Better understanding of the protective duration of prior SARS-CoV-2 infection against reinfection is needed., This large US population-based study demonstrates that SARS-CoV-2 reinfection is uncommon among individuals with laboratory evidence of a previous infection. Protection from SARS-CoV-2 reinfection is stable up to one year., The duration of protection against reinfection was stable over the median 5 months and up to 1-year follow-up interval., Among >22 million individuals tested February 2020 through April 2021, the relative risk of reinfection among those with prior infection was 87% lower than the risk of infection among individuals without prior infection. This protection was durable for up to a year., The aim of this study was a comparison of antibody level after infection caused by Delta and Omicron variants. The study included 203 persons who underwent mild COVID-19 despite two doses of vaccine. The obtained results indicate that a significantly lower titer was observed in patients with the Omicron variant infection. Therefore, these patients may be at risk of reinfection with new strains of the Omicron variant., SARS-CoV-2 infection does not confer long immunity. However, studies suggest that prior infection is associated with lower risk of reinfection and milder outcomes of recurrent infections., Reinfection with the SARS-CoV-2 Delta variant resulted in fewer hospitalizations compared to the primary Delta infection, suggesting that primary infection may, to some extent, produce at least short lasting protective immunity., The vast majority of anti-spike IgG positive individuals remain anti-spike IgG positive for at least 8 months regardless of initial COVID-19 disease severity. The presence of anti-spike IgG antibodies is associated with a substantially reduced risk of reinfection up to 9 months following asymptomatic to mild COVID-19., Emerging data support detectable immune responses for months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, but it is not yet established to what degree and for how long protection against reinfection lasts., Comparative genomic analysis demonstrates that true reinfection following SARS-CoV-2 infection is possible., Our findings indicate that reinfection results in restricted SARS-CoV-2 replication despite substantial levels of humoral immunity, denoting the potential for transmission through reinfected asymptomatic individuals., Prior to the emergence of antigenically distinct SARS-CoV-2 variants, reinfections were reported infrequently - presumably due to the generation of durable and protective immune responses., It is currently unclear whether the previous infection with SARS-CoV-2 provides protection against reinfection with VOCs., Our case supports the hypothesis that SARS-CoV-2 reinfection may occur once antibody titers decrease or following the emergence of a new variant., Reinfection with SARS-CoV-2 has been well documented, yet little is known about the degree of protection a previous infection provides against reinfection, especially against Variants of Concern (VOC)., Reinfection with SARS-CoV-2 is a strong possibility. This case raises concerns that asymptomatic infections may not provide long-term protective immunity to all patients, which could make them susceptible to reinfection., The rate of reinfection with SARS-CoV-2 is relatively low. The protection against SARS-CoV-2 after natural infection is comparable to that estimated for vaccine efficacy., SARS-CoV-2 reinfection can occur but is a rare phenomenon suggestive of protective immunity against reinfection that lasts for at least a few months post primary infection., Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 months and 5\u00b71 years after peak antibody response, with a median of 16 months., It is currently unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection will remain a rare event, only occurring in individuals who fail to mount an effective immune response, or whether it will occur more frequently when humoral immunity wanes following primary infection.[SEP]Relations: Rotavirus infection has relations: disease_disease with Reoviridae infectious disease, disease_disease with Reoviridae infectious disease. RNA Pol II CTD phosphorylation and interaction with CE during HIV infection has relations: pathway_protein with GTF2F2, pathway_protein with GTF2F2, pathway_protein with GTF2H2, pathway_protein with GTF2H2, pathway_protein with GTF2F1, pathway_protein with GTF2F1, pathway_protein with GTF2H4, pathway_protein with GTF2H4. Definitions: variants defined as following: An alteration or difference from a norm or standard.. reinfection defined as following: Infection by the same infectious agent following a recovery. Reinfection may be by a different strain or the same strain.. 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.. coronavirus defined as following: Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE).. 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]. SARS-CoV-2 infection defined as following: A viral disorder generally characterized by high FEVER; COUGH; DYSPNEA; CHILLS; PERSISTENT TREMOR; MUSCLE PAIN; HEADACHE; SORE THROAT; a new loss of taste and/or smell (see AGEUSIA and ANOSMIA) and other symptoms of a VIRAL PNEUMONIA. In severe cases, a myriad of coagulopathy associated symptoms often correlating with COVID-19 severity is seen (e.g., BLOOD COAGULATION; THROMBOSIS; ACUTE RESPIRATORY DISTRESS SYNDROME; SEIZURES; HEART ATTACK; STROKE; multiple CEREBRAL INFARCTIONS; KIDNEY FAILURE; catastrophic ANTIPHOSPHOLIPID ANTIBODY SYNDROME and/or DISSEMINATED INTRAVASCULAR COAGULATION). In younger patients, rare inflammatory syndromes are sometimes associated with COVID-19 (e.g., atypical KAWASAKI SYNDROME; TOXIC SHOCK SYNDROME; pediatric multisystem inflammatory disease; and CYTOKINE STORM SYNDROME). A coronavirus, SARS-CoV-2, in the genus BETACORONAVIRUS is the causative agent..", "label": "yes"} {"id": "converted_185", "sentence1": "Does mutation of ARTEMIS gene causes severe combined immunodeficiency?", "sentence2": "RESULTS: Seven infants were diagnosed with SCID, yielding an incidence of 1 in 22,819 live births. Four of these infants had Artemis-type SCID., Artemis deficiency disrupts development of adaptive immunity and leads to radiosensitive T- B- severe combined immunodeficiency (RS-SCID)., Encouraging data for X-SCID and preclinical work for Artemis-SCID and RAG1-SCID are paving the way for the therapy to become a viable curative treatment option., Pathogenic variants in DCLRE1C encoding Artemis cause T-B-NK+ severe combined immunodeficiency (SCID), and patients with Artemis-deficient SCID (ART-SCID) require definitive therapy with allogeneic hematopoietic cell transplantation (HCT).[SEP]Relations: severe combined immunodeficiency (disease) has relations: disease_protein with STAT5A, disease_protein with STAT5A, disease_protein with STAT1, disease_protein with STAT1, disease_disease with recombinase activating gene 1 deficiency, disease_disease with recombinase activating gene 1 deficiency, disease_protein with ADA, disease_protein with ADA, disease_protein with PNP, disease_protein with PNP. Definitions: DCLRE1C defined as following: This gene is involved in both DNA repair and V(D)J recombination.. Artemis defined as following: Human DCLRE1C wild-type allele is located in the vicinity of 10p13 and is approximately 97 kb in length. This allele, which encodes protein artemis, plays a role in the mediation of both V(D)J recombination and DNA repair via nonhomologous end joining. Mutation of the gene is associated with severe combined immunodeficiency Athabaskan type and Omenn syndrome.. HCT defined as following: The volume of packed RED BLOOD CELLS in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, ANEMIA shows a low value; POLYCYTHEMIA, a high value.. combined immunodeficiency defined as following: A broad classification of inherited disorders presenting at birth that affect both the cell-mediated and humoral aspects of the immune response. Circulating numbers of B lymphocytes, T lymphocytes and NK cells are variable but where present do not function properly. Susceptibility to infection is the primary concern.. Artemis-deficient SCID defined as following: An autosomal recessive condition caused by mutation(s) in the DCLRE1C gene, encoding protein artemis. It is characterized by severe combined immunodeficiency that is T-cell negative, B-cell negative, NK-cell positive. Sensitivity to ionizing radiation and a high incidence of occurrence amongst the Athabascan Indians are also characteristic of this disease.. 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..", "label": "yes"} {"id": "converted_186", "sentence1": "Is Wilson's disease described as an iron storage disease?", "sentence2": "Wilson's disease (WD), an inherited disorder of copper metabolism that mostly affects the liver and brain;, Wilsons disease is a rare autosomal recessive disorder of copper transportation, which is fatal if not treated., Wilsons disease and idiopathic toxicosis are examples of severe chronic liver diseases that are the results of genetic predisposition to the hepatic accumulation of copper., Wilson disease is a genetic copper storage disorder that causes hepatic and neurologic symptoms. , Wilson's disease represents a copper storage disease., Hereditary hemochromatosis and Wilson disease are autosomal recessive storage disorders of iron and copper overload, respectively., Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's disease) are autosomal recessive metabolic disease characterized by progressive liver pathology and subsequent involvement of various other organs., OBJECTIVES: Wilson's disease (WD) is a metabolic disorder leading to hepatic and extrahepatic copper, Wilson's disease (WD) is a rare hereditary disorder of copper metabolism., Wilson's disease, a copper storage disorder, in which biliary copper excretion is reduced, is inherited as an autosomal recessive trait., BACKGROUND & AIMS: Wilson disease is a genetic copper storage disorder that causes hepatic and n, UNLABELLED: Wilson disease (WD) is a rare inherited disorder of copper metabolism, which can lead to severe liver failure and to a variety of neuropsychiatr, Wilson disease (WD) (OMIM# 277900) is an autosomal recessive inherited disorder characterized by excess copper (Cu) storage in different human tissues, such as the brain, liver, and the corneas of the eyes., UNLABELLED: Wilson's disease (WND) and hereditary hemochromatosis (HH) are two metal loading diseases of copper and iron, respectively, and are both recessivel, Wilson's disease is an autosomal recessive inherited disease with congenital copper metabolism disorder, characterized by decreased ceruloplasmin and increased urine copper, which can involve multiple organs., Wilson's disease is an autosomal recessive disease of copper metabolism which is widely recognized as a disease occurring clinically in children, adolescents, and young adults., Hereditary copper-associated hepatitis in dogs resembles Wilson's disease, a copper storage disease in humans., Wilson's disease is a rare inherited disorder of copper metabolism causing severe damage to vital organs., Inherited copper toxic disease, Wilson's disease, is an autosomal recessive disorder arising from a defect in biliary copper excretion., Wilson's disease is a genetic disorder of copper metabolism with a hepatic or neurologic presentation., Wilson's disease is an autosomal recessive disease of abnormal copper metabolism., Hemochromatosis and Wilson's disease are known as iron and copper accumulation disorders, respectively., Wilson's disease represents a copper storage disease., In the new paradigm, Wilson's disease is seen as a hereditary disorder associated with copper intoxication., ve determination of elevated liver iron content. Wilson's disease represents a copper storage disease. Prominent clinical features are hepatomegaly an, Wilson's disease is an autosomal recessive disorder in which the liver does not properly release copper into bile, resulting in prominent copper accumulation in various tissues., Wilson's disease is one such\u00a0hereditary disease\u00a0that creates chaos in tissues, usually the brain and liver, via deposition of abnormal amounts of copper in them., Wilson's disease is rare autosomal-recessive disorder originated on the basis of metabolic copper over-storage., Wilson's disease is an autosomal-recessive disorder of copper metabolism caused by mutations in ATP7B and associated with neurological, psychiatric, ophthalmological and hepatic manifestations., PROJECT: Wilson's disease (WD) is an inherited disorder of copper metabolism characterised by juvenile liver cirrhosis and by neurological symptoms, OBJECTIVE: Wilson's disease (WD) is a hereditary disorder of copper metabolism, Wilson's disease is an autosomal-recessive disorder of copper metabolism with neurological and hepatic presentations., Wilson's disease is an inherited disorder associated with copper accumulation in the liver, brain and other vital organs.[SEP]Relations: hereditary hemochromatosis has relations: disease_disease with disorder of iron metabolism and transport, disease_disease with disorder of iron metabolism and transport, disease_disease with African iron overload, disease_disease with African iron overload. Hepatomegaly has relations: disease_phenotype_positive with Wilson disease, disease_phenotype_positive with Wilson disease, disease_phenotype_positive with glycogen storage disease, disease_phenotype_positive with glycogen storage disease, disease_phenotype_positive with glycogen storage disease due to glycogen branching enzyme deficiency, disease_phenotype_positive with glycogen storage disease due to glycogen branching enzyme deficiency. Definitions: metal defined as following: Electropositive chemical elements characterized by ductility, malleability, luster, and conductance of heat and electricity. They can replace the hydrogen of an acid and form bases with hydroxyl radicals. (Grant & Hackh's Chemical Dictionary, 5th ed). autosomal recessive disorder defined as following: An inherited disorder manifested only when two copies of a mutated gene are present.. primary haemochromatosis defined as following: An inherited metabolic disorder characterized by iron accumulation in the tissues.. WD defined as following: A rare autosomal recessive disease characterized by the deposition of copper in the BRAIN; LIVER; CORNEA; and other organs. It is caused by defects in the ATP7B gene encoding copper-transporting ATPase 2 (EC 3.6.3.4), also known as the Wilson disease protein. The overload of copper inevitably leads to progressive liver and neurological dysfunction such as LIVER CIRRHOSIS; TREMOR; ATAXIA and intellectual deterioration. Hepatic dysfunction may precede neurologic dysfunction by several years.. hepatic defined as following: Pertaining to, affecting, or associated with the liver.. chronic liver diseases defined as following: Hepatic necrosis, inflammation, or scarring due to any cause that persists for more than 6 months. Manifestations may include signs and symptoms of cholestasis, portal hypertension, and/or abnormal liver function tests.. hepatomegaly defined as following: Enlargement of the liver.. 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.. iron defined as following: homeopathic drug. copper defined as following: A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.. ceruloplasmin defined as following: Catalysis of the reaction: 4 Fe2+ + 4 H+ + O2 = 4 Fe3+ + 2 H2O. [RHEA:11148]. psychiatric defined as following: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders.. humans defined as following: Members of the species Homo sapiens.. ATP7B defined as following: Copper-transporting ATPase 2 (1465 aa, ~157 kDa) is encoded by the human ATP7B gene. This protein plays a role in copper ion export.. 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.. metabolic disorder 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). hereditary disorder 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.. bile defined as following: An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.. 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.. liver failure defined as following: Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed). 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.. corneas defined as following: The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous CORNEAL EPITHELIUM; BOWMAN MEMBRANE; CORNEAL STROMA; DESCEMET MEMBRANE; and mesenchymal CORNEAL ENDOTHELIUM. It serves as the first refracting medium of the eye. It is structurally continuous with the SCLERA, avascular, receiving its nourishment by permeation through spaces between the lamellae, and is innervated by the ophthalmic division of the TRIGEMINAL NERVE via the ciliary nerves and those of the surrounding conjunctiva which together form plexuses. (Cline et al., Dictionary of Visual Science, 4th ed). mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. Wilson's disease defined as following: A rare autosomal recessive disease characterized by the deposition of copper in the BRAIN; LIVER; CORNEA; and other organs. It is caused by defects in the ATP7B gene encoding copper-transporting ATPase 2 (EC 3.6.3.4), also known as the Wilson disease protein. The overload of copper inevitably leads to progressive liver and neurological dysfunction such as LIVER CIRRHOSIS; TREMOR; ATAXIA and intellectual deterioration. Hepatic dysfunction may precede neurologic dysfunction by several years..", "label": "no"} {"id": "converted_188", "sentence1": "Is omaveloxolone an activator of NFkB?", "sentence2": "Omaveloxolone (RTA 408) is an activator of Nrf2 and an inhibitor of NF\u03baB, possessing antioxidative and anti-inflammatory activities in mitochondrial bioenergetics.[SEP]Relations: GABPA has relations: protein_protein with NFKBIL1, protein_protein with NFKBIL1, protein_protein with FBXO22, protein_protein with FBXO22, molfunc_protein with DNA-binding transcription activator activity, RNA polymerase II-specific, molfunc_protein with DNA-binding transcription activator activity, RNA polymerase II-specific, protein_protein with RFXANK, protein_protein with RFXANK, protein_protein with FBXO28, protein_protein with FBXO28. Definitions: mitochondrial defined as following: The distribution of mitochondria, including the mitochondrial genome, into daughter cells after mitosis or meiosis, mediated by interactions between mitochondria and the cytoskeleton. [GOC:mcc, PMID:10873824, PMID:11389764]. Omaveloxolone defined as following: A member of the synthetic oleanane triterpenoid class of compounds and an activator of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2, Nfe2l2), with potential chemopreventive activity. Upon administration, omaveloxolone activates the cytoprotective transcription factor Nrf2. In turn, Nrf2 translocates to the nucleus, dimerizes with a small Maf protein (sMaf), and binds to the antioxidant response element (ARE). This induces the expression of a number of cytoprotective genes, including NAD(P)H quinone oxidoreductase 1 (NQO1), sulfiredoxin 1 (Srxn1), heme oxygenase-1 (HO1, HMOX1), superoxide dismutase 1 (SOD1), gamma-glutamylcysteine synthetase (gamma-GCS), thioredoxin reductase-1 (TXNRD1), glutathione S-transferase (GST), glutamate-cysteine ligase catalytic subunit (Gclc) and glutamate-cysteine ligase regulatory subunit (Gclm), and increases the synthesis of the antioxidant glutathione (GSH). Nrf2, a leucine zipper transcription factor, plays a key role in the maintenance of redox balance and cytoprotection against oxidative stress.. RTA defined as following: A group of genetic disorders of the KIDNEY TUBULES characterized by the accumulation of metabolically produced acids with elevated plasma chloride, hyperchloremic metabolic ACIDOSIS. Defective renal acidification of URINE (proximal tubules) or low renal acid excretion (distal tubules) can lead to complications such as HYPOKALEMIA, hypercalcinuria with NEPHROLITHIASIS and NEPHROCALCINOSIS, and RICKETS..", "label": "no"} {"id": "converted_195", "sentence1": "Can Efgartigimod be used for myasthenia gravis?", "sentence2": "Efgartigimod is an FcRn inhibitor recently approved for MG treatment, and rozanolixizumab, nipocalimab and batoclimab are other agents in clinical trial development. , Efgartigimod (efgartigimod alfa-fcab, Vyvgart\u2122) is a first-in-class neonatal Fc receptor antagonist being developed by argenx for the treatment of autoimmune diseases including myasthenia gravis. In December 2021, intravenous efgartigimod received its first approval in the USA for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive., This article summarizes the milestones in the development of efgartigimod leading to this first approval for generalized myasthenia gravis., INTERPRETATION: Efgartigimod was well tolerated and efficacious in patients with generalised myasthenia gravis.[SEP]Relations: myasthenia gravis has relations: contraindication with Orphenadrine, contraindication with Orphenadrine, contraindication with Desflurane, contraindication with Desflurane, contraindication with Brimonidine, contraindication with Brimonidine, contraindication with Fesoterodine, contraindication with Fesoterodine, contraindication with Bendroflumethiazide, contraindication with Bendroflumethiazide. Definitions: MG defined as following: A disorder of neuromuscular transmission characterized by fatigable weakness of cranial and skeletal muscles with elevated titers of ACETYLCHOLINE RECEPTORS or muscle-specific receptor tyrosine kinase (MuSK) autoantibodies. Clinical manifestations may include ocular muscle weakness (fluctuating, asymmetric, external ophthalmoplegia; diplopia; ptosis; and weakness of eye closure) and extraocular fatigable weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles (ocular myasthenia). THYMOMA is commonly associated with this condition.. autoimmune diseases defined as following: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.. 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]. myasthenia gravis defined as following: A disorder of neuromuscular transmission characterized by fatigable weakness of cranial and skeletal muscles with elevated titers of ACETYLCHOLINE RECEPTORS or muscle-specific receptor tyrosine kinase (MuSK) autoantibodies. Clinical manifestations may include ocular muscle weakness (fluctuating, asymmetric, external ophthalmoplegia; diplopia; ptosis; and weakness of eye closure) and extraocular fatigable weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles (ocular myasthenia). THYMOMA is commonly associated with this condition..", "label": "yes"} {"id": "converted_196", "sentence1": "Have Quercetin-biapigenin nanoparticles been shown to be effective in penetrating the blood-brain barrier", "sentence2": "Quercetin-biapigenin nanoparticles are effective to penetrate the blood-brain barrier., The present study aimed to investigate the potential protective effect of quercetin-biapigenin encapsulated into poly(\u0190-polycaprolactone) (PCL) nanoparticles against t-BOOH-induced oxidative stress in several brain cell lines, as well as evaluate the permeability of those active molecules through an in vitro BBB model., As of our knowledge, this is the first report of quercetin-biapigenin PCL-loaded nanoparticle activity in brain cells., Microbubbles in combination with focused ultrasound for the delivery of quercetin-modified sulfur nanoparticles through the blood brain barrier into the brain parenchyma and relief of endoplasmic reticulum stress to treat Alzheimer's disease.[SEP]Relations: blood brain barrier has relations: anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with cell layer, anatomy_anatomy with cell layer. familial Alzheimer disease has relations: disease_protein with PRNP, disease_protein with PRNP, disease_phenotype_positive with Emotional lability, disease_phenotype_positive with Emotional lability, disease_phenotype_positive with Perseveration, disease_phenotype_positive with Perseveration. Definitions: blood-brain barrier 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.. 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.. 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_202", "sentence1": "Is adenosine methylation an epigenetic modification?", "sentence2": "Epigenetic modifications have received increasing attention and have been shown to be extensively involved in kidney development and disease progression. Among them, the most common RNA modification, N6 -methyladenosine (m6 A), has been shown to dynamically and reversibly exert its functions in multiple ways, including splicing, export, decay and translation initiation efficiency to regulate mRNA fate., N6-methyladenosine (m6A) methylation is the most abundant mammalian mRNA modification. m6A regulates RNA processing, splicing, nucleation, translation and stability by transferring, removing and recognizing m6A methylation sites, which are critical for cancer initiation, progression, metabolism and metastasis., The methyltransferase-like 3 (Mettl3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for RNA N6-methyladenosine (m6A) modification, which plays an important role in gene post-transcription modulation., Methylation of the N6 position of adenosine (m6A) is a post-transcriptional epigenetic modification of RNA., N6-methyladenosine (m6A) is a dynamic reversible methylation modification of the adenosine N6 position and is the most common chemical epigenetic modification among mRNA post-transcriptional modifications, including methylation, demethylation, and recognition., N6-adenosine methylation (m6A) is one of the most common modifications on mRNA., N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which is the most prevalent internal modification on eukaryotic mRNA., The N6-methyl adenosine (m6A) is an important epigenetic modification primarily present on mRNA that controls the levels of transcripts and efficiency of translation in eukaryotes.[SEP]Relations: RNA modification has relations: bioprocess_bioprocess with RNA methylation, bioprocess_bioprocess with RNA methylation. Adenosine has relations: drug_drug with Epinastine, drug_drug with Epinastine, drug_effect with Palpitations, drug_effect with Palpitations, drug_drug with 9-Methylguanine, drug_drug with 9-Methylguanine, drug_drug with Anisotropine methylbromide, drug_drug with Anisotropine methylbromide. 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). transcripts defined as following: The initial RNA molecule produced by transcription.. 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.. methyltransferase-like 3 defined as following: This gene is involved in methlyation of mRNA.. adenosine defined as following: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.. RNA modification defined as following: The covalent alteration of one or more nucleotides within an RNA molecule to produce an RNA molecule with a sequence that differs from that coded genetically. [GOC:go_curators, ISBN:1555811337]. modification defined as following:Respond with exceptions, completions and modifications or revisions done before completion
. 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.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young..", "label": "yes"} {"id": "converted_204", "sentence1": "Can breastfeeding be used to alleviate the procedural pain in neonates?", "sentence2": "The duration between breastfeeding and heel lance may influence the perception of pain in newborns. Keeping this period short, may reduce the perception of pain., Breastfeeding and mother's heartbeat sounds, which are non-pharmacological pain relief methods, are effective in neonatal pain management. , The best non-pharmacological methods are breastfeeding followed by non-nutritive sucking coupled with sucrose sucking. , Non-pharmacological interventions, particularly breastfeeding and non-nutritive sucking as primary strategies for pain management in neonates are useful strategies to consider.[SEP]", "label": "yes"} {"id": "converted_205", "sentence1": "Can lenacapavir be used for HIV?", "sentence2": "PURPOSE OF REVIEW: This review summarizes available data for lenacapavir, an investigational first-in-class agent that disrupts functioning of HIV capsid protein across multiple steps in the viral life cycle., Lenacapavir (Sunlenca\u00ae) is a long-acting capsid inhibitor of human immunodeficiency virus type\u00a01 (HIV-1) being developed by Gilead Sciences Inc. , In August 2022, lenacapavir received its first approval in the EU for use in combination with other antiretroviral(s) in adults with multi-drug resistant HIV infection, for whom it is otherwise not possible to construct a suppressive anti-viral regimen.[SEP]Definitions: 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)..", "label": "yes"} {"id": "converted_215", "sentence1": "Was prehospital transdermal glyceryl trinitrate effective for stroke in the RIGHT-2 trial?", "sentence2": "INTERPRETATION: Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. , Conclusions- Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. [SEP]Relations: Cerebral hemorrhage has relations: drug_effect with Oxaliplatin, drug_effect with Oxaliplatin, drug_effect with Dabigatran etexilate, drug_effect with Dabigatran etexilate, drug_effect with Trandolapril, drug_effect with Trandolapril, drug_effect with Eptifibatide, drug_effect with Eptifibatide, drug_effect with Alprostadil, drug_effect with Alprostadil. Definitions: GTN defined as following: Gestational Trophoblastic diseases that are malignant. It does not include HYDATIDIFORM MOLE. However, there is a minority of authors that consider the term gestational trophoblastic neoplasia synonymous with gestational trophoblastic disease.. 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). intracerebral hemorrhage defined as following: Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA..", "label": "no"} {"id": "converted_217", "sentence1": "Is omaveloxolone a suppressor of Nrf2?", "sentence2": "The Effects of Two Nrf2 Activators, Bardoxolone Methyl and Omaveloxolone, on Retinal Ganglion Cell Survival during Ischemic Optic Neuropathy., Omaveloxolone (RTA 408) is an activator of Nrf2 and an inhibitor of NF\u03baB, possessing antioxidative and anti-inflammatory activities in mitochondrial bioenergetics.[SEP]Relations: NFE2L2 has relations: protein_protein with RNF4, protein_protein with RNF4, protein_protein with PMF1, protein_protein with PMF1, protein_protein with UBE2E2, protein_protein with UBE2E2, protein_protein with TNNT1, protein_protein with TNNT1, protein_protein with MAF, protein_protein with MAF. Definitions: mitochondrial defined as following: The distribution of mitochondria, including the mitochondrial genome, into daughter cells after mitosis or meiosis, mediated by interactions between mitochondria and the cytoskeleton. [GOC:mcc, PMID:10873824, PMID:11389764]. Nrf2 defined as following: This gene plays a role in transcriptional regulation.. Bardoxolone Methyl defined as following: The methyl ester form of bardoxolone, a synthetic triterpenoid compound with potential antineoplastic and anti-inflammatory activities. Bardoxolone blocks the synthesis of inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2), two enzymes involved in inflammation and carcinogenesis. This agent also inhibits the interleukin-1 (IL-1)-induced expression of the pro-inflammatory proteins matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13) and the expression of Bcl-3; Bcl-3 is an IL-1-responsive gene that preferentially contributes to MMP-1 gene expression.. RTA defined as following: A group of genetic disorders of the KIDNEY TUBULES characterized by the accumulation of metabolically produced acids with elevated plasma chloride, hyperchloremic metabolic ACIDOSIS. Defective renal acidification of URINE (proximal tubules) or low renal acid excretion (distal tubules) can lead to complications such as HYPOKALEMIA, hypercalcinuria with NEPHROLITHIASIS and NEPHROCALCINOSIS, and RICKETS.. Omaveloxolone defined as following: A member of the synthetic oleanane triterpenoid class of compounds and an activator of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2, Nfe2l2), with potential chemopreventive activity. Upon administration, omaveloxolone activates the cytoprotective transcription factor Nrf2. In turn, Nrf2 translocates to the nucleus, dimerizes with a small Maf protein (sMaf), and binds to the antioxidant response element (ARE). This induces the expression of a number of cytoprotective genes, including NAD(P)H quinone oxidoreductase 1 (NQO1), sulfiredoxin 1 (Srxn1), heme oxygenase-1 (HO1, HMOX1), superoxide dismutase 1 (SOD1), gamma-glutamylcysteine synthetase (gamma-GCS), thioredoxin reductase-1 (TXNRD1), glutathione S-transferase (GST), glutamate-cysteine ligase catalytic subunit (Gclc) and glutamate-cysteine ligase regulatory subunit (Gclm), and increases the synthesis of the antioxidant glutathione (GSH). Nrf2, a leucine zipper transcription factor, plays a key role in the maintenance of redox balance and cytoprotection against oxidative stress..", "label": "no"} {"id": "converted_218", "sentence1": "Can salivary cortisol be used to evaluate pain in neonates?", "sentence2": "We observed the increase in SC concentrations in response to painful stimulus. The presence of a correlation between NIPS scores and SC increase suggests that SC can be used as an objective parameter to assess pain in neonates.[SEP]Relations: blood group, lewis system has relations: disease_disease with Mendelian disease, disease_disease with Mendelian disease.", "label": "yes"} {"id": "converted_219", "sentence1": "Does nintedanib improve response rate in patients with bladder cancer?", "sentence2": "INTERPRETATION: The addition of nintedanib to chemotherapy was safe but did not improve the rate of pathological complete response in muscle-invasive bladder cancer.FUNDING: Boehringer Ingelheim.[SEP]Relations: Nintedanib has relations: drug_drug with Nilotinib, drug_drug with Nilotinib, drug_drug with Siltuximab, drug_drug with Siltuximab, drug_drug with Entrectinib, drug_drug with Entrectinib, drug_drug with Neratinib, drug_drug with Neratinib, drug_drug with Ceritinib, drug_drug with Ceritinib. Definitions: 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.. bladder cancer defined as following: A primary or metastatic malignant neoplasm involving the bladder..", "label": "no"} {"id": "converted_229", "sentence1": "Does SRRM4 regulate neuronal-specific microexon splicing of TAF1 mRNA?", "sentence2": "Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100., Knockdown and ectopic expression experiments demonstrate that the neuronal-specific splicing factor SRRM4/nSR100 promotes the inclusion of microexon 34' into TAF1\u00a0mRNA, through the recognition of UGC sequences in the poly-pyrimidine tract upstream of the regulated microexon. [SEP]Relations: Viral Messenger RNA Synthesis has relations: pathway_protein with GTF2F1, pathway_protein with GTF2F1, pathway_protein with RAE1, pathway_protein with RAE1, pathway_protein with POLR2F, pathway_protein with POLR2F, pathway_protein with GTF2F2, pathway_protein with GTF2F2, pathway_protein with POLR2E, pathway_protein with POLR2E. Definitions: TAF1 defined as following: Human TAF1 wild-type allele is located in the vicinity of Xq13.1 and is approximately 164 kb in length. This allele, which encodes transcription initiation factor TFIID subunit 1 protein, is involved in the progression of the G1 phase of the cell cycle, the mediation of acetyltransferase activity and the regulation of ubiquitination.. 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_232", "sentence1": "In twin-twin transfusion syndrome, are the twins identical?", "sentence2": "hey are genetically identical and those with twin-twin transfusion syndrome(TTTS) provide an ideal natural model in whom to study the influence of differing haemodynamic stresses on the developing vascular tre, n twin-to-twin transfusion syndrome (TTTS), genetically identical twins are exposed to different haemodynamic conditions during fetal life, which are considered to be the cause of prenatal and postnatal cardiovascular differences between the donor and the recipient, To test the hypothesis that identical twins show no inter-twin differences in cardiovascular structure or physiology in fetal life unless there has been twin-twin transfusion syndrome., Twin-twin transfusion syndrome (TTTS) is an unusual and serious condition that occurs in twin pregnancies when identical twins share a placenta but develop discordant amniotic fluid volumes., Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twins, which share one single monochorionic placenta., Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twin fetuses sharing one single (monochorionic) placenta., OBJECTIVE: Twin-twin transfusion syndrome (TTTS) is a severe pregnancy complication of monochorionic (identical) twins that results in markedly discordant in utero environments for, BACKGROUND: In twin-to-twin transfusion syndrome (TTTS), genetically identical twins are exposed to different haemodynamic conditions during fetal life, which are considered to be the cause of prenatal and postnatal cardiovascular differences between the donor and the recipient.OBJECTIVE: To assess intertwin differences on childhood cardiac outcome after intrauterine laser coagulation therapy (LC) of severe TTTS.DESIGN AND PATIENTS: Prospective, detailed, echocardiographic follow-up of 31 twin pairs aged 9.95\u00b10.8\u2005years (mean\u00b1SD) with severe TTTS treated by LC, and the comparison with reference values.RESULTS: Cardiac function was normal and did not show intertwin d, Twin-twin transfusion syndrome is a serious complication of monozygotic, monochorionic, diamniotic twins resulting from transplacental vascular communications., Most likely, the identical twin transfusion syndrome produces anoxia and brain damage during early prenatal development in the smaller identical twin., A likely explanation for the association between birthweight and intelligence among identical twins is the identical twin transfusion syndrome which occurs only between some monochorionic identical twin pairs., The twin-twin transfusion syndrome is a rare but severe complication in monozygotic twins., Monochorionic twins are at increased risk for unique complications including twin-twin transfusion syndrome (TTTS), selective intrauterine growth restriction (sIUGR), and twin-reversed arterial perfusion (TRAP) sequence.[SEP]Relations: placenta has relations: anatomy_protein_present with TRIO, anatomy_protein_present with TRIO, anatomy_protein_present with ERVV-2, anatomy_protein_present with ERVV-2, anatomy_protein_present with PTOV1-AS2, anatomy_protein_present with PTOV1-AS2, anatomy_protein_present with SYNC, anatomy_protein_present with SYNC, anatomy_protein_present with CISD2, anatomy_protein_present with CISD2. Definitions: fetal defined as following: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality.. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. TRAP defined as following: A chemotherapy regimen consisting of cytarabine, daunorubicin, prednisone, and thioguanine that may be used in the treatment of acute myeloid leukemia (AML).. twins defined as following: Two individuals derived from two FETUSES that were fertilized at or about the same time, developed in the UTERUS simultaneously, and born to the same mother. Twins are either monozygotic (TWINS, MONOZYGOTIC) or dizygotic (TWINS, DIZYGOTIC).. amniotic fluid defined as following: A clear, yellowish liquid that envelopes the FETUS inside the sac of AMNION. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (AMNIOCENTESIS)..", "label": "yes"} {"id": "converted_236", "sentence1": "Optogenetics refers to the study of gene expression optimization", "sentence2": "Optogenetics allows the experimental manipulation of excitable cells by a light stimulus without the need for technically challenging and invasive procedures., Optogenetics has revolutionized the capability of controlling genetically modified neurons in\u00a0vitro and in\u00a0vivo and has become an indispensable neuroscience tool. Using light as a probe for selective neuronal activation or inhibition and as a means to read out neural activity has dramatically enhanced our understanding of complex neural circuits. , Optogenetics controls neural activity and behavior in living organisms through genetically targetable actuators and light. , This is a review of the current state of optogenetics-based research in the field of ophthalmology and physiology of vision. Optogenetics employs an interdisciplinary approach that amalgamates gene engineering, optics, and physiology. It involves exogenous expression of a light-activated protein in a very particular retinal cell enabling regulation (stimulation vs. inhibition) of its physiological activity, In contrast, optogenetics leverages light-sensitive proteins to control cellular signaling dynamics and target gene expression and, by virtue of precise hardware control over illumination, offers the capacity to interrogate how spatiotemporally varying signals modulate gene regulatory networks and cellular behaviors., As light-gated protein switches, signaling photoreceptors provide the basis for optogenetics, a term that refers to the control of organismal physiology and behavior by light., In this review, we summarize the main optogenetic systems implemented in the budding yeast Saccharomyces cerevisiae, which allow orthogonal control (by light) of gene expression, protein subcellular localization, reconstitution of protein activity, and protein sequestration by oligomerization., Optogenetics is the genetic approach for controlling cellular processes with light., The recently introduced term 'optogenetics' describes a variety of techniques for expressing genes in nerve cells that render them responsive to light., Optogenetic expression systems can provide precise control over gene expression timing, location, and amplitude using light as the inducing agent., Optogenetics refers to the control of biological processes with light., Optogenetics refers to a technique that uses light to modulate neuronal activity with a high spatiotemporal resolution, which enables the manipulation of learning and memory functions in the human brain., In optogenetics, as in nature, sensory photoreceptors serve to control cellular processes by light., Optogenetics refers to the genetic modification of cells to express light-sensitive proteins, which mediate ion flow or secondary signalling cascades upon light exposure., Optogenetics involves the use of genetically encoded and optically active proteins, namely opsins, to control neuronal circuits., (3) A completely different interpretation of optogenetics refers to the light activated expression of a genetically induced construct., Optogenetics is an innovative technique for optical control of cells., Optogenetics refers to techniques that use light to control the cellular activity of targeted cells., basis for optogenetics, a term that refers to the control of organismal physiology and behavior by light. We establish as novel optogenetic tools the , Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels., Optogenetics refers to the control of biological processes with light. The activation of cellular phenomena by defined wavelengths has several advanta, Optogenetics is the use of genetically coded, light-gated ion channels or pumps (opsins) for millisecond resolution control of neural activity.[SEP]Relations: regulation of neural retina development has relations: bioprocess_protein with DLL4, bioprocess_protein with DLL4, bioprocess_protein with PTF1A, bioprocess_protein with PTF1A, bioprocess_bioprocess with regulation of developmental process, bioprocess_bioprocess with regulation of developmental process, bioprocess_protein with SIX3, bioprocess_protein with SIX3. Opsins has relations: pathway_protein with OPN1SW, pathway_protein with OPN1SW. Definitions: nerve 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.. probe defined as following: brand name of methazole herbicide. human defined as following: Members of the species Homo sapiens.. construct defined as following: An abstract or general idea inferred or derived from specific instances.. 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.. opsins defined as following: Photosensitive proteins in the membranes of PHOTORECEPTOR CELLS such as the rods and the cones. Opsins have varied light absorption properties and are members of the G-PROTEIN-COUPLED RECEPTORS family. Their ligands are VITAMIN A-based chromophores.. genetic modification defined as following: Genetic engineering or molecular biology techniques that involve DNA REPAIR mechanisms for incorporating site-specific modifications into a cell's genome.. 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_239", "sentence1": "Was DNX-2401 tested for treatment of Diffuse Intrinsic Pontine Glioma?", "sentence2": "Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma., METHODS: We conducted a single-center, dose-escalation study of DNX-2401, an oncolytic adenovirus that selectively replicates in tumor cells, in patients with newly diagnosed DIPG. , CONCLUSIONS: Intratumoral infusion of oncolytic virus DNX-2401 followed by radiotherapy in pediatric patients with DIPG resulted in changes in T-cell activity and a reduction in or stabilization of tumor size in some patients but was associated with adverse events., Phase I Trial of DNX-2401 for Diffuse Intrinsic Pontine Glioma Newly Diagnosed in Pediatric Patients., OBJECTIVE: To determine the safety, tolerability, and toxicity of an oncolytic adenovirus, DNX-2401, injected into the cerebellar peduncle in pediatric subjects with DIPG and to collect tumor samples of this type of tumor., DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Gliomas: A Case Report., To this aim, we have designed a clinical Phase I trial for newly diagnosed pediatric DIPG to investigate the feasibility, safety, and preliminary efficacy of delivering DNX-2401 into tumors within the pons following biopsy., To our knowledge, this is the first report of intratumoral DNX-2401 for a patient with DIPG in a clinical trial. [SEP]Relations: diffuse intrinsic pontine glioma has relations: disease_disease with childhood brain stem glioma, disease_disease with childhood brain stem glioma. Glioma has relations: disease_phenotype_positive with Nijmegen breakage syndrome, disease_phenotype_positive with Nijmegen breakage syndrome, drug_effect with Aminolevulinic acid, drug_effect with Aminolevulinic acid, disease_phenotype_positive with retinoblastoma, disease_phenotype_positive with retinoblastoma, disease_phenotype_positive with neurofibromatosis, disease_phenotype_positive with neurofibromatosis. Definitions: DIPG defined as following: A glioma that grows diffusely in the pons. It usually affects children and has a poor prognosis.. DNX-2401 defined as following: An adenovirus serotype 5 strain, selectively replication competent in cells defective in the Rb/p16 tumor suppressor pathway, with potential oncolytic activity. Oncolytic adenovirus Ad5-Delta 24RGD contains an integrin binding RGD-4C motif, allowing Coxsackie adenovirus receptor-independent infection of tumor cells, which are often deficient for Coxsackie and adenovirus receptors (CARs). Selectively replication competent in cells that are defective in retinoblastoma gene (Rb) or cyclin-dependent kinase inhibitor-2A (p16), active replication of oncolytic adenovirus Ad5-Delta 24RGD in tumor cells may induce oncolysis or cell lysis. As integral components of the late G1 restriction point, the Rb gene product and p16 are negative regulators of the cell cycle; ovarian cancer cells and non-small cell lung cancer cells may be defective in the Rb/p16 pathway. Check for \"https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C74067\" active clinical trials using this agent. (\"http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C74067\" NCI Thesaurus). 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.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. tumor cells defined as following: Cells of, or derived from, a tumor.. pons defined as following: The front part of the hindbrain (RHOMBENCEPHALON) that lies between the MEDULLA and the midbrain (MESENCEPHALON) ventral to the cerebellum. It is composed of two parts, the dorsal and the ventral. The pons serves as a relay station for neural pathways between the CEREBELLUM to the CEREBRUM.. Glioma 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).", "label": "yes"} {"id": "converted_251", "sentence1": "Is Functional Neurological Disorder (FND) classified as a psychosomatic disorder?", "sentence2": "Challenges to the Diagnosis of Functional Neurological Disorder: Feigning, Intentionality, and Responsibility., he diagnosis of Functional Neurological Disorder (FND) requires differentiation from other neurologic diseases/syndromes, and from the comparatively rare diagnosis of feigning (Malingering and Factitious Disorder), Functional neurological disorder reflects impairments in brain networks leading to distressing motor, sensory and/or cognitive symptoms that demonstrate positive clinical signs on examination incongruent with other conditions. , Functional neurological disorder and somatic symptom disorder in Parkinson's disease., The occurrence of Functional Neurological Disorder (FND) and Somatic Symptom Disorder (SSD) in PD was not commonly accepted until recently, despite some evidence that emerged in the pre and early L-Dopa era. , Maladaptive schemas of patients with functional neurological symptom disorder., he psychological underpinnings of functional neurological symptom disorders (FNSD) remain poorly understood. , disintegration of explicit and implicit information processing in patients with FNSD has previously been suggested; however, this suggestion has so far received little empirical support. Trauma and maladaptive schemas probably reinforce disintegration in FNSD. The present study explored the occurrence of maladaptive schemas and investigated the impact of trauma-related maladaptive schemas in patients with FNSD., Functional neurological symptom disorder (FND) remains a clinical challenge. It is one of the many mimics of cerebrovascular accidents, spinal cord disorders, and lower motor neuron disease. , Previous studies with adults suggest that aberrant communication between neural networks underpins functional neurological disorder (FND). , Functional neurological disorder (FND) is a complex neuropsychiatric disorder characterized by abnormal or atypical sensorimotor, gait, dissociative, or special sensory symptoms in the absence of structural nervous system lesions to explain the symptoms., Functional neurological disorders (FNDs), which are sometimes also referred to as psychogenic neurological disorders or conversion disorder, are common disabling neuropsychiatric disorders with limited treatment options., Functional neurological disorder (FND) is a complex neuropsychiatric condition characterized by the presence of neurological symptoms and signs (either motor or sensory) that cannot be explained by any known medical or mental disease., Functional neurological disorder (FND) is a rare neuropsychiatric illness that commonly presents to the medical setting as opposed to the psychiatric setting., Historically, functional neurological disorder (FND) has been described in psychodynamic terms as the physical manifestation of psychological distress., BACKGROUND: Functional neurological disorders (FNDs) are common but often misdiagnosed.REVIEW SUMMARY: The incidence of FNDs is between 4 and 12 per 100,000, comparable to multiple sclerosis and amyotrophic lateral sclerosis, and it is the second most common dia, Functional Neurological Disorder (FND), otherwise known as Conversion Disorder, is characterized by abnormal sensory or motor symptoms that are determined to be \"incompatible\" with neurological disease., Conversion disorder or functional neurological disorder is a neurological symptom complex originating from psychological factors, which manifests in voluntary motor and sensory functions or as unexplained epilepsy-like seizures., Functional neurological disorder (FND) is characterized by neurological symptoms that cannot be explained by a structural neurological cause., Functional neurological disorder (FND) is a constellation of common neurological symptoms without exact organic pathophysiology., BACKGROUND: Functional neurological disorder (FND) is an elusive disorder characterized by unexplained neurological symptoms alongside aberrant cognitive processing and negative affect, often associated with amygdala reactivity, Functional neurological disorder (FND), previously regarded as a diagnosis of exclusion, is now a rule-in diagnosis with available treatments., Functional neurological disorder (FND) is a common and highly disabling disorder, but its aetiology remains enigmatic.[SEP]Relations: Parkinson disease has relations: disease_disease with autosomal recessive Parkinson disease, disease_disease with autosomal recessive Parkinson disease, disease_disease with parkinson disease, autosomal dominant, disease_disease with parkinson disease, autosomal dominant. nervous system disorder has relations: disease_disease with psychiatric disorder, disease_disease with psychiatric disorder, disease_disease with Balint syndrome, disease_disease with Balint syndrome. somatoform disorder has relations: disease_disease with psychiatric disorder, disease_disease with psychiatric disorder. Definitions: amygdala defined as following: Almond-shaped group of basal nuclei anterior to the INFERIOR HORN OF THE LATERAL VENTRICLE of the TEMPORAL LOBE. The amygdala is part of the limbic system.. amyotrophic lateral sclerosis 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). 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.. 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). Functional neurological disorders defined as following: A disorder whose predominant feature is a loss or alteration in physical functioning that suggests a physical disorder but that is actually a direct expression of a psychological conflict or need.. neurological disease 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.. 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). L-Dopa defined as following: The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.. SSD defined as following: Persistent difficulty with speech sound production such that it interferes with verbal communication.. 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. cerebrovascular accidents 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). psychosomatic disorder defined as following: A group of disorders characterized by physical symptoms that are affected by emotional factors and involve a single organ system, usually under AUTONOMIC NERVOUS SYSTEM control. (American Psychiatric Glossary, 1988).", "label": "no"} {"id": "converted_252", "sentence1": "Are accessible enhancers necessarily active?", "sentence2": "In this review, it is argued that the relationship between the accessibility and activity of an enhancer is insufficiently described by simply considering open versus closed chromatin, or active versus inactive enhancers. Instead, recent studies focusing on the quantitative nature of accessibility signal reveal subtle differences between active enhancers and their different inactive counterparts: the closed silenced state and the accessible primed and repressed states. While the open structure as such is not a specific indicator of enhancer activity, active enhancers display a higher degree of accessibility than the primed and repressed states., DNA accessibility is thought to be of major importance in regulating gene expression., Accessibility of promoter DNA is not the primary determinant of chromatin-mediated gene regulation., Euchromatin and heterochromatin have very similar accessibilities, suggesting that transcription factors can penetrate heterochromatin. Thus, DNA accessibility is not likely to be the primary determinant of gene regulation., A major goal in the field of transcriptional regulation is the mapping of changes in the binding of transcription factors to the resultant changes in gene expression., Together, these results show many gene expression changes can happen independently of changes in the accessibility of local chromatin in the context of a single-factor perturbation., While the open structure as such is not a specific indicator of enhancer activity, active enhancers display a higher degree of accessibility than the primed and repressed states., Functional enhancers, in contrast with accessible chromatin regions that lack enhancer activity, were enriched for enhancer RNAs (eRNAs) and preferentially interacted in vivo with B cell lineage-determining transcription factors., In this review, it is argued that the relationship between the accessibility and activity of an enhancer is insufficiently described by simply considering open versus closed chromatin, or active versus inactive enhancers., In conclusion, loci identified as active by STARR-seq often overlap with those identified by chromatin accessibility and active epigenetic marking, yet a significant fraction is epigenetically repressed or display condition-specific enhancer activity.[SEP]Relations: transcription factor binding has relations: molfunc_protein with CEBPG, molfunc_protein with CEBPG, molfunc_protein with AHR, molfunc_protein with AHR, molfunc_protein with BCOR, molfunc_protein with BCOR, molfunc_protein with SRY, molfunc_protein with SRY, molfunc_protein with ARNT, molfunc_protein with ARNT. Definitions: heterochromatin defined as following: The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE.. 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.. Euchromatin defined as following: A dispersed and relatively uncompacted form of chromatin that is in a transcription-competent conformation. [PMID:32017156]. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process..", "label": "no"} {"id": "converted_255", "sentence1": "Is Prasinezumab effective for Parkinson\u2019s Disease?", "sentence2": "CONCLUSIONS: Prasinezumab therapy had no meaningful effect on global or imaging measures of Parkinson's disease progression as compared with placebo and was associated with infusion reactions. [SEP]Relations: Parkinson disease has relations: contraindication with Alimemazine, contraindication with Alimemazine, contraindication with Perazine, contraindication with Perazine, contraindication with Pimozide, contraindication with Pimozide, contraindication with Promazine, contraindication with Promazine, contraindication with Prochlorperazine, contraindication with Prochlorperazine. Definitions: 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_260", "sentence1": "Was AAVS3 developed for hemophilia A?", "sentence2": "Phase 1-2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B., BACKGROUND: FLT180a (verbrinacogene setparvovec) is a liver-directed adeno-associated virus (AAV) gene therapy that uses a synthetic capsid and a gain-of-function protein to normalize factor IX levels in patients with hemophilia B[SEP]Relations: hemophilia has relations: disease_disease with acquired hemophilia, disease_disease with acquired hemophilia, disease_disease with factor XI deficiency, disease_disease with factor XI deficiency, disease_protein with F8, disease_protein with F8, contraindication with Indinavir, contraindication with Indinavir, contraindication with Salicylamide, contraindication with Salicylamide. Definitions: hemophilia B defined as following: A deficiency of blood coagulation factor IX inherited as an X-linked disorder. (Also known as Christmas Disease, after the first patient studied in detail, not the holy day.) Historical and clinical features resemble those in classic hemophilia (HEMOPHILIA A), but patients present with fewer symptoms. Severity of bleeding is usually similar in members of a single family. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. Treatment is similar to that for hemophilia A. (From Cecil Textbook of Medicine, 19th ed, p1008). Trial defined as following: Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.. hemophilia A defined as following: This gene plays an important role in blood coagulation..", "label": "no"} {"id": "converted_266", "sentence1": "Does iron regulate oligodendrocyte maturation?", "sentence2": "Developmental iron deficiency (dID) models facilitate the study of specific oligodendrocyte (OL) requirements for their progression to a mature state and subsequent contribution to myelinatio, Ontogenetic oligodendrocyte maturation through gestational iron deprivation: The road not taken., the expression levels of Hes5, Sox10, and Olig1 in dID conditions correlated with an unfavorable OL maturation profile., the current results provide further evidence of dID impact on myelination, keeping OL away from the maturational path., Impaired Postnatal Myelination in a Conditional Knockout Mouse for the Ferritin Heavy Chain in Oligodendroglial Cells., To define the importance of iron storage in oligodendrocyte development and function, the ferritin heavy subunit (Fth) was specifically deleted in oligodendroglial cells., Fth iron storage is essential for early oligodendrocyte development as well as for OPC maturation in the demyelinated adult brain., H-ferritin expression in astrocytes is necessary for proper oligodendrocyte development and myelination., These results indicate that Fth iron storage in astrocytes is vital for early oligodendrocyte development as well as for the remyelination of the CNS., Iron modulates the differentiation of a distinct population of glial precursor cells into oligodendrocytes., Here, using an in vitro cultured differentiation model of oligodendrocytes, we found that both transferrin receptor and ferritin-H are significantly upregulated during oligodendrocyte maturation, implying the essential role of iron in the development of oligodendrocytes., Our results raise the possibility that iron may affect oligodendrocyte development at stages during early embryogenesis rather than during later development., When disrupted, iron homeostasis negatively impacts oligodendrocyte (OLG) differentiation and impairs myelination., These hypotheses are based on the observations that there is a peak in brain iron uptake in vivo that coincides with the period of greatest myelination and that a shortage of iron leads to myelination deficiency., Developmental iron deficiency (dID) models facilitate the study of specific oligodendrocyte (OL) requirements for their progression to a mature state and subsequent contribution to myelination., Iron is an essential trophic element that is required for cell viability and differentiation, especially in oligodendrocytes, which consume relatively high rates of energy to produce myelin., These results indicate that Fth iron storage in astrocytes is vital for early oligodendrocyte development as well as for the remyelination of the CNS., Total iron content in unperfused brain is not significantly different between Mcoln1(-/-) and wild-type littermate mice, suggesting that the observed maturation delay or loss of oligodendrocytes might be caused by impaired iron handling, rather than by global iron deficiency., These data indicate that iron delivered via transferrin and its receptor is intrinsically involved in oligodendrocyte maturation and thus plays a critical role in the onset of myelination.[SEP]Relations: HES5 has relations: bioprocess_protein with negative regulation of oligodendrocyte differentiation, bioprocess_protein with negative regulation of oligodendrocyte differentiation, bioprocess_protein with oligodendrocyte development, bioprocess_protein with oligodendrocyte development, bioprocess_protein with negative regulation of astrocyte differentiation, bioprocess_protein with negative regulation of astrocyte differentiation, bioprocess_protein with negative regulation of stem cell differentiation, bioprocess_protein with negative regulation of stem cell differentiation. protein complex oligomerization has relations: bioprocess_bioprocess with protein trimerization, bioprocess_bioprocess with protein trimerization. Definitions: Hes5 defined as following: This gene may play a role in the regulation of transcription.. 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.. 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.. Fth defined as following: The determination of the amount of ferritin heavy chain in a sample.. iron defined as following: homeopathic drug. oligodendrocytes defined as following: Neuroglial cells that first appear during mid-embryogenesis in the central nervous system of mammals and give rise to OLIGODENDROCYTES. Mitotically-active populations remain through late adulthood and are capable of regenerating MYELIN lost to disease or injury.. transferrin receptor 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). oligodendrocyte defined as following: A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as SATELLITE CELLS, PERINEURONAL of GANGLIA) according to their location. They form the insulating MYELIN SHEATH of axons in the central nervous system.. OPC defined as following: A preparation containing plant-derived polyphenolic bioflavonoids composed of multimers (dimers, trimers, or higher order polymers) of the flavan-3-ol-based monomers catechin and epicatechin, which are extracted from sources rich in these chemicals, such as grape seeds, grape skin and pine bark, with potential anti-oxidant, anti-inflammatory, anti-microbial, anti-cancer and protective activities. Upon oral administration of oligomeric procyanidin complex (OPC), the polyphenols exert anti-oxidant activity by scavenging free radicals, which prevents both the formation of reactive oxygen species (ROS), particularly nitrous oxide (NO), and DNA damage. OPC also inhibits chemical-induced lipid peroxidation. In addition, OPC reduces the production advanced glycation end-products (AGE), decreases AGE accumulation in tissues, and inhibits the progression of AGE/receptor for AGE (RAGE)-mediated inflammatory transduction pathways, which inhibits the activation of pro-inflammatory transcriptional regulators and prevents the secretion of pro-inflammatory cytokines/chemokines. This ultimately prevents inflammatory-driven damage to end organs and may reduce inflammation-induced cancer formation and progression. In addition, OPC inhibits the activity of a variety of enzymes, including xanthine oxidase, collagenase, elastase hyaluronidase and beta-glucuronidase.. 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..", "label": "yes"} {"id": "converted_282", "sentence1": "Are epigenetic changes heritable?", "sentence2": "Epigenetics is defined as heritable changes in gene expression that are, unlike mutations, not attributable to alterations in the sequence of DNA. The predominant epigenetic mechanisms are DNA methylation, modifications to chromatin, loss of imprinting and non-coding RNA., Genome-wide association studies of complex physiological traits and diseases consistently found that associated genetic factors, such as allelic polymorphisms or DNA mutations, only explained a minority of the expected heritable fraction. This discrepancy is known as \"missing heritability\", and its underlying factors and molecular mechanisms are not established. Epigenetic programs may account for a significant fraction of the \"missing heritability.\" Epigenetic modifications, such as DNA methylation and chromatin assembly states, reflect the high plasticity of the genome and contribute to stably alter gene expression without modifying genomic DNA sequences., Epigenetics is defined as heritable changes in gene expression that do not involve a change in DNA sequence., Epigenetics is defined as mitotically and meiotically heritable changes in gene expression that do not involve a change in the DNA sequence., Epigenetic changes refer to heritable changes that may modulate gene expression without affecting DNA sequence., Epigenetic alterations, which, by definition, comprise mitotically and meiotically heritable changes in gene expression that are not caused by changes in the primary DNA sequence, are increasingly being recognized for their roles in carcinogenesis., Unlike heritable genetic changes, which are always associated with mutations in gene sequence, heritable epigenetic changes can be associated with physical or chemical changes in molecules or only changes in the system., Epigenetic alterations are defined as heritable changes in gene expression mediated through mechanisms other than alterations in the DNA sequence itself, including DNA promoter methylation and various histone covalent modifications., Epigenetics refers to heritable phenotypic alterations in the absence of DNA sequence changes, and DNA methylation is one of the extensively studied epigenetic alterations., Epigenetics is defined as heritable changes that affect gene expression without altering the DNA sequence., Epigenetics refers to heritable changes in patterns of gene expression that occur without alterations in DNA sequence., Epigenetic modifications are classified as heritable and reversible chemical modifications of chromatin that do not cause changes in DNA sequence., Epigenetics is the study of changes in gene activity that can be transmitted through cell divisions but cannot be explained by changes in the DNA sequence., First, some epigenetic states are transmitted intergenerationally and affect the phenotype of offspring., One possible but largely unexplored explanation is that exposure to sublethal doses of insecticides may alter epigenetic patterns that are heritable., DNA methylation is one such heritable epigenetic change, which is causally associated with the transcription regulation of many genes in the mammalian genome., As a result, heritable epigenetic changes can include any that can alter a wave such as changes in form, midline, frequency, amplitude, or phase., Epigenetics has been defined as 'a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence' and several epigenetic regulators are recurrently mutated in hematological malignancies., Epigenetic alterations (epimutations) could thus contribute to heritable variation within populations and be subject to evolutionary processes such as natural selection and drift., Some of these epigenetic changes appear to be heritable., First, some epigenetic states are transmitted intergenerationally and affect the phenotype of offspring., First, stress-induced methylation changes are common and are mostly heritable., Epigenetic inheritance systems enable the environmentally induced phenotypes to be transmitted between generations., Epigenetic changes enforced by various environmental and lifestyle factors lead to heritable modifications., Transient epigenetic changes across the entire genome can influence metabolic outcomes and might or might not be heritable., More interestingly, epigenetic changes are reversible heritable changes which pass through generations., However, it is unclear whether the active changes mediated by variations in DNA methyltransferase activity are heritable., Epigenetic modification refers to heritable changes in the genetic material without any changes in the nucleic acid sequence and results in heritable phenotypic changes., Epigenetics refers to the heritable, but reversible, regulation of various biological functions mediated principally through changes in DNA methylation and chromatin structure derived from histone modification., Although epigenetic modifications may contribute substantially to average risk, they will not contribute much to recurrence risk and heritability unless they persist on average for many generations., Epigenetic processes, defined as heritable changes in gene expression that occur without changes to the DNA sequence, have emerged as a promising area of cardiovascular disease research., Epigenetic changes can be defined as stable molecular alterations of a cellular phenotype such as the gene expression profile of a cell that are heritable during somatic cell divisions (and sometimes germ line transmissions) but do not involve changes of the DNA sequence itself., Epigenetic modifications are heritable changes in gene expression not encoded by the DNA sequence., Epigenetics is defined as the study of changes in gene function that are mitotically or meiotically heritable and do not lead to a change in DNA sequence., Epigenetic mechanisms are heritable traits that are mediated by changes in a genetic locus that do not involve a modification at the nucleotide level., ssion, notably during embryonic development. New research indicates that epigenetic factors are heritable, which is why paternal lifestyle may affect [SEP]Relations: Hematological neoplasm has relations: disease_phenotype_positive with platelet disorder, undefined, disease_phenotype_positive with platelet disorder, undefined, disease_phenotype_positive with Muir-Torre syndrome, disease_phenotype_positive with Muir-Torre syndrome, drug_effect with Teniposide, drug_effect with Teniposide, disease_phenotype_positive with aspergillosis, disease_phenotype_positive with aspergillosis. histone modification has relations: bioprocess_protein with PARP2, bioprocess_protein with PARP2. Definitions: chromosome defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. histone modification defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc]. DNA sequence defined as following: The sequence of nucleotide residues along a DNA chain.. genome defined as following: Anatomical set of genes in all the chromosomes.. midline defined as following: E3 ubiquitin-protein ligase Midline-1 (667 aa, ~75 kDa) is encoded by the human MID1 gene. This protein is involved in protein ubiquitination and may influence microtubule dynamics.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. insecticides defined as following: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.. hematological malignancies defined as following: Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.. 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).. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. 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.. 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.. nucleic acid defined as following: High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages..", "label": "yes"} {"id": "converted_292", "sentence1": "Do epigenetic changes change the DNA sequence?", "sentence2": "Epigenetic modifications, such as DNA methylation and chromatin assembly states, reflect the high plasticity of the genome and contribute to stably alter gene expression without modifying genomic DNA sequences., Epigenetics is defined as heritable changes in gene expression that are, unlike mutations, not attributable to alterations in the sequence of DNA., Epigenetic changes are inheritable modifications that can modify the gene expression without changing the DNA sequence. The most common epigenetic alternations consist of DNA methylation and histone modifications., Epigenetic changes refer to heritable changes that may modulate gene expression without affecting DNA sequence., Epigenetic changes are reversible and do not affect the DNA sequence itself but rather control levels of gene expression., Epigenetic changes, or heritable alterations in gene function that do not affect DNA sequence, are rapidly gaining acceptance as co-conspirators in carcinogenesis., Environmentally caused changes in chromosomes that do not alter the DNA sequence but cause phenotypic changes by altering gene transcription are summarized as epigenetics., Epigenetic modifications are heritable changes in gene expression not encoded by the DNA sequence., Epigenetic regulation is referred to as changes in gene function that do not involve changes in the DNA sequence, it is usually accomplished by DNA methylation, histone modifications (repressive marks such as H3K9me, H3K27me, H2Aub, or active marks such as H3K4me, H3K36me, H3Ac), and chromatin remodeling (nucleosome composition, occupancy, and location)., Epigenetics is the study of changes in gene expression or cellular phenotype that do not change the DNA sequence., Epigenetic change, which does not involve alteration to the nucleotide sequence, can also cause changes in gene activity by changing the structure of chromatin through DNA methylation or histone modifications., Epigenetics is defined as mitotically and meiotically heritable changes in gene expression that do not involve a change in the DNA sequence., These modifications, also known as epigenetic code, do not change the DNA sequence but alter the expression level of specific genes., Epigenetic regulation refers to heritable factors of genomic modifications that do not involve changes in DNA sequence., Epigenetics refers to structural modifications to genes that do not change the nucleotide sequence itself but instead control and regulate gene expression., Epigenetics are the heritable changes in gene expression patterns which occur without altering DNA sequence., Epigenetic changes appear briefly and do not involve permanent changes to the primary DNA sequence., Epigenetic changes responding to the environmental and intercellular signals can turn on/off specific genes, but do not modify the DNA sequence., Epigenetic changes are reversible and do not affect the DNA sequence itself but rather control levels of gene expression., Epigenetic regulation refers to heritable changes in gene expression that do not involve any alteration of the DNA sequence., Epigenetic mechanisms, which include DNA methylation, histone modification, and microRNA (miRNA), can produce heritable phenotypic changes without a change in DNA sequence., Epigenetic changes to the genome are biochemical alterations to the DNA that do not change an individual's genome but do change and influence gene expression., e next, which may alter gene expression but which do not involve changes in the primary DNA sequence. These marks include DNA methylation (methylation, Epigenetics, the study of functionally relevant chemical modifications to DNA that do not involve a change in the DNA nucleotide sequence, is at the interface between research and clinical medicine., The accessibility of DNA is regulated by epigenetic processes, including methylation of cytosine. In these circumstances the nucleic sequence of the DNA does not change., Epigenetics is comprised of the stable and heritable (or potentially heritable) changes in gene expression that do not entail a change in DNA sequence.[SEP]Relations: histone modification has relations: bioprocess_protein with PARP2, bioprocess_protein with PARP2, bioprocess_bioprocess with cellular protein modification process, bioprocess_bioprocess with cellular protein modification process, bioprocess_bioprocess with covalent chromatin modification, bioprocess_bioprocess with covalent chromatin modification, bioprocess_protein with MT3, bioprocess_protein with MT3, bioprocess_protein with HLCS, bioprocess_protein with HLCS. Definitions: histone modifications defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc]. microRNA 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.. cytosine defined as following: A pyrimidine base that is a fundamental unit of nucleic acids.. DNA sequence defined as following: The sequence of nucleotide residues along a DNA chain.. genome defined as following: Anatomical set of genes in all the chromosomes.. chromosomes defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. 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).. cellular 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.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. nucleotide sequence defined as following: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.. 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": "no"} {"id": "converted_302", "sentence1": "Can skin picking phenotype present following methylphenidate treatment?", "sentence2": "Newly Developed Skin Picking After Methylphenidate Treatment in Attention Deficit Hyperactivity Disorder: Possible Mechanisms., We describe a case of skin picking developing after methylphenidate therapy for ADHD.[SEP]Relations: Attention deficit hyperactivity disorder has relations: drug_effect with Methylphenidate, drug_effect with Methylphenidate, drug_effect with Dexmethylphenidate, drug_effect with Dexmethylphenidate, disease_phenotype_positive with facial dysmorphism-developmental delay-behavioral abnormalities syndrome due to 10p11.21p12.31 microdeletion, disease_phenotype_positive with facial dysmorphism-developmental delay-behavioral abnormalities syndrome due to 10p11.21p12.31 microdeletion, disease_phenotype_positive with AMED syndrome, digenic, disease_phenotype_positive with AMED syndrome, digenic, disease_phenotype_positive with Niemann-Pick disease, disease_phenotype_positive with Niemann-Pick disease. Definitions: 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).", "label": "yes"} {"id": "converted_305", "sentence1": "Do enhancers have to be close to their gene targets?", "sentence2": "Enhancers are cis-regulatory elements in the genome that cooperate with promoters to control target gene transcription. Unlike promoters, enhancers are not necessarily adjacent to target genes and can exert their functions regardless of enhancer orientations, positions and spatial segregations from target genes., Enhancers are often located many tens of kilobases away from the promoter they regulate, sometimes residing closer to the promoter of a neighboring gene., Many enhancers map quite far from their target genes, on the order of tens or even hundreds of kilobases., Enhancers are intergenic DNA elements that regulate the transcription of target genes in response to signaling pathways by interacting with promoters over large genomic distances., Enhancers have been identified at up to megabase distances from their regulated genes, and/or proximal to or within the introns of unregulated genes., In metazoans transcriptional enhancers and their more complex relatives, locus control regions, are often located at great linear distances from their target genes., Given their distance from the target gene, lack of common motifs, and tissue/cell specificity, enhancer regions are thought to be difficult to predict in DNA sequences., Computational identification of enhancers is difficult because they do not exhibit clear location preference relative to their target gene and also because they lack clearly distinguishing genomic features., Enhancers function independently of their distance and orientation to the promoters of target genes., Until recently, identifying each gene's enhancers had been challenging because enhancers do not occupy prescribed locations relative to their target genes., Computational identification of enhancers is difficult because they do not exhibit clear location preference relative to their target gene and also because they lack clearly distinguishing genomic features., cis-regulatory sequences called enhancers. Enhancers can stimulate gene activity at great genomic distances from their targets, raising questions abou, Enhancer elements are essential for tissue-specific gene regulation during mammalian development. Although these regulatory elements are often distant from their target genes, they affect gene expression by recruiting transcription factors to specific promoter regions., Epigenetic profiling of different tissues and cell-types has identified a large number of non-coding epigenetic regulatory elements ('enhancers') that can be located far away from coding genes., In metazoans, enhancers of gene transcription must often exert their effects over tens of kilobases of DNA. Over the past decade it has become clear that to do this, enhancers come into close proximity with target promoters with the looping away of intervening sequences.[SEP]Relations: GLI proteins bind promoters of Hh responsive genes to promote transcription has relations: pathway_protein with GLI1, pathway_protein with GLI1, pathway_protein with GLI3, pathway_protein with GLI3, pathway_protein with GLI2, pathway_protein with GLI2. transcription factor binding has relations: molfunc_protein with AHR, molfunc_protein with AHR. promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription. 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.. intervening sequences 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.. promoter 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.. DNA sequences defined as following: The sequence of nucleotide residues along a DNA chain.. 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.. 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.. locus control regions defined as following: A regulatory region first identified in the human beta-globin locus but subsequently found in other loci. The region is believed to regulate GENETIC TRANSCRIPTION by opening and remodeling CHROMATIN structure. It may also have enhancer activity.. 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).. 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.. target gene defined as following: A gene proposed to have a primary role in a disease, based upon its known function in other organisms or model systems or based upon its physical proximity to markers linked to a genetic disease.. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young..", "label": "no"} {"id": "converted_306", "sentence1": "Are there any other types of Spinal Muscular Atrophy except for types 1-4?", "sentence2": "Spinal muscular atrophy (SMA) with respiratory distress type 1 (SMARD1) is an exceptionally rare type of SMA., There are no convincing reports of X-linked SMA hitherto. , The total AChE activity was either normal or decreased in the childhood SMA (Type 1), the other SMA groups and disease controls (ALS, X-linked SMA).[SEP]Relations: Spinal muscular atrophy has relations: disease_phenotype_positive with distal spinal muscular atrophy type 3, disease_phenotype_positive with distal spinal muscular atrophy type 3, disease_phenotype_positive with spinal muscular atrophy, facioscapulohumeral type, disease_phenotype_positive with spinal muscular atrophy, facioscapulohumeral type, disease_phenotype_positive with X-linked distal spinal muscular atrophy type 3, disease_phenotype_positive with X-linked distal spinal muscular atrophy type 3, disease_phenotype_positive with spinal muscular atrophy, Ryukyuan type, disease_phenotype_positive with spinal muscular atrophy, Ryukyuan type, phenotype_phenotype with Skeletal muscle atrophy, phenotype_phenotype with Skeletal muscle atrophy. Definitions: SMARD1 defined as following: Spinal muscular atrophy with respiratory distress type 1 is a rare genetic motor neuron disease characterized by severe respiratory distress/respiratory failure in association with diaphragmatic eventration and palsy, as well as progressive, symmetrical, distal-to-proximal muscle weakness and atrophy (in lower limbs especially). Patients typically have a history of intrauterine growth retardation, low birth weight, feeble cry, weak suck and failure to thrive and present with inspiratory stridor, recurrent episodes of dyspnea or apnea, cyanosis and absent deep tendon reflexes. Kyphosis/scoliosis, foot deformities and joint contractures are frequently associated features.. 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). SMA defined as following: A group of disorders marked by progressive degeneration of motor neurons in the spinal cord resulting in weakness and muscular atrophy, usually without evidence of injury to the corticospinal tracts. Diseases in this category include Werdnig-Hoffmann disease and later onset SPINAL MUSCULAR ATROPHIES OF CHILDHOOD, most of which are hereditary. (Adams et al., Principles of Neurology, 6th ed, p1089).", "label": "yes"} {"id": "converted_310", "sentence1": "Is Tilavonemab effective for progressive supranuclear palsy?", "sentence2": "INTERPRETATION: A similar safety profile was seen in all treatment groups. No beneficial treatment effects were recorded. Although this study did not provide evidence of efficacy in progressive supranuclear palsy, the findings provide potentially useful information for future investigations of passive immunisation using tau antibodies for progressive supranuclear palsy.[SEP]", "label": "no"} {"id": "converted_314", "sentence1": "Is SARS-CoV-2 transmitted through breast milk?", "sentence2": "No infectious SARS-CoV-2 in breast milk from a cohort of 110 lactating women., SARS-CoV-2 RNA can be found infrequently in the breastmilk after recent infection, but we found no evidence that breastmilk contains an infectious virus or that breastfeeding represents a risk factor for transmission of infection to infants., This article goes beyond prior small studies to provide evidence that infectious SARS-CoV-2 is not present in the milk of lactating women with recent infection, even when SARS-CoV-2 RNA is detected., Recent SARS-CoV-2 infection or detection of its RNA in human milk is not a contraindication to breastfeeding., Based on the currently available limited evidence and recognizing the benefits of breastfeeding, it may be concluded that if the health of the mother and her newborn allows, direct breastfeeding or extracted breastmilk should be encouraged by the healthcare providers after a careful discussion of the risks of vertical transmission to the mother and her family, Preventive measures should be taken by COVID-19 mothers to prevent droplet transmission of infection to the infants while breastfeeding., Currently, there is no evidence of SARS-CoV-2 transmission through breast milk., The authors could not find evidence for transmission of SARS-CoV-2 from mother to child through breastmilk in the population studied., At present, there is limited information on potential transmission of the infection from mother to child, particularly through breast milk and breastfeeding., However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS-CoV-2) via human milk and/or breastfeeding., However, there is limited published literature related to vertical transmission of any human coronavirus (including SARS-CoV-2) via human milk and/or breastfeeding., and had a benign clinical course. There was no evidence of significant clinical infection during the hospital stay or from outpatient neonatal follow-up data for all the infants included in this study.CONCLUSION: In a small cohort of SARS-CoV-2 positive lactating mothers giving birth at our institution, most of their breast milk samples (95%) contained no detectable virus, and there was no evidence of COVID-19 infection in their breast milk-fed neonates.KEY POINTS: \u00b7 Breast milk may rarely contain detectable SARS-CoV-2 RNA and was not detected in asymptomatic mothers.. \u00b7 Breast milk with detectable SARS-CoV-2 RNA from a symptomatic mother had no clinical significance for her infant.. \u00b7 Breast feeding with appropriate infection control instru, Taken together, our data do not support mother-to-infant transmission of SARS-CoV-2 via milk., th SARS-CoV-2 neutralization. Strong correlations between levels of IgA and IgG to SARS-CoV-2 and seasonal coronaviruses were noted.CONCLUSIONS: Our data do not support maternal-to-child transmission of SARS-CoV-2 via milk; however, risk of transmission v, Currently, there is no evidence of SARS-CoV-2 transmission through breast milk., Whether SARS-CoV-2 was transmitted through breast milk is unknown., No breast milk samples were positive for SARS-CoV-2 and, to date, there is no evidence on the presence of SARS-CoV-2 in breast milk of pregnant women with COVID-19., from 11 women tested negative.INTERPRETATION: Considering the lack of evidence for SARS-CoV-2 transmission through breast milk, breastfeeding counsell[SEP]Relations: Human immunoglobulin G has relations: drug_drug with Sarilumab, drug_drug with Sarilumab, drug_drug with Sarilumab, drug_drug with Sarilumab, drug_protein with FCGR2A, drug_protein with FCGR2A, drug_protein with FCGR2A, drug_protein with FCGR2A. colitis (disease) has relations: disease_protein with NOS2, disease_protein with NOS2. 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). 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.. IgA defined as following: IgA is the immunoglobulin subclass that is associated with antibody-mediated mucosal immunity. It is secreted as dimers into the mucosa and is the most effective isotype at fixing complement by the alternative pathway, even though it lacks the ability to fix complement by the classical pathway. There are two subtypes in the human - IgA1 and IgA2.. human defined as following: Members of the species Homo sapiens.. coronaviruses defined as following: A member of CORONAVIRIDAE which causes respiratory or gastrointestinal disease in a variety of vertebrates.. infectious SARS-CoV-2 defined as following: A viral disorder generally characterized by high FEVER; COUGH; DYSPNEA; CHILLS; PERSISTENT TREMOR; MUSCLE PAIN; HEADACHE; SORE THROAT; a new loss of taste and/or smell (see AGEUSIA and ANOSMIA) and other symptoms of a VIRAL PNEUMONIA. In severe cases, a myriad of coagulopathy associated symptoms often correlating with COVID-19 severity is seen (e.g., BLOOD COAGULATION; THROMBOSIS; ACUTE RESPIRATORY DISTRESS SYNDROME; SEIZURES; HEART ATTACK; STROKE; multiple CEREBRAL INFARCTIONS; KIDNEY FAILURE; catastrophic ANTIPHOSPHOLIPID ANTIBODY SYNDROME and/or DISSEMINATED INTRAVASCULAR COAGULATION). In younger patients, rare inflammatory syndromes are sometimes associated with COVID-19 (e.g., atypical KAWASAKI SYNDROME; TOXIC SHOCK SYNDROME; pediatric multisystem inflammatory disease; and CYTOKINE STORM SYNDROME). A coronavirus, SARS-CoV-2, in the genus BETACORONAVIRUS is the causative agent.. IgG 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..", "label": "no"} {"id": "converted_316", "sentence1": "Is there any treatment for the Facioscapulohumeral Muscular Dystrophy?", "sentence2": "The treatment of FSHD is currently supportive only., Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies.[SEP]Relations: facioscapulohumeral muscular dystrophy has relations: disease_disease with progressive muscular dystrophy, disease_disease with progressive muscular dystrophy, disease_disease with progressive muscular dystrophy, disease_disease with progressive muscular dystrophy, disease_disease with muscular dystrophy, scapulohumeral, disease_disease with muscular dystrophy, scapulohumeral, disease_disease with muscular dystrophy, scapulohumeral, disease_disease with muscular dystrophy, scapulohumeral, contraindication with Succinylcholine, contraindication with Succinylcholine. Definitions: FSHD defined as following: An autosomal dominant degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. The onset of symptoms usually occurs in the first or second decade of life. Affected individuals usually present with impairment of upper extremity elevation. This tends to be followed by facial weakness, primarily involving the orbicularis oris and orbicularis oculi muscles. (Neuromuscul Disord 1997;7(1):55-62; Adams et al., Principles of Neurology, 6th ed, p1420). Facioscapulohumeral muscular dystrophy defined as following: An autosomal dominant form of facioscapulohumeral muscular dystrophy associated with contraction of the D4Z4 macrosatellite repeat.. muscular dystrophy defined as following: A heterogeneous group of inherited MYOPATHIES, characterized by wasting and weakness of the SKELETAL MUSCLE. They are categorized by the sites of MUSCLE WEAKNESS; AGE OF ONSET; and INHERITANCE PATTERNS..", "label": "no"} {"id": "converted_319", "sentence1": "Do all proteins start with methionine?", "sentence2": "The use of several translation initiation codons in a single mRNA, by expressing several proteins from a single gene, contributes to the generation of protein diversity. A small, yet growing, number of mammalian mRNAs initiate translation from a non-AUG codon, in addition to initiating at a downstream in-frame AUG codon. Translation initiation on such mRNAs results in the synthesis of proteins harbouring different amino terminal domains potentially conferring on these isoforms distinct functions., In eukaryotes, it is generally assumed that translation initiation occurs at the AUG codon closest to the messenger RNA 5' cap. However, in certain cases, initiation can occur at codons differing from AUG by a single nucleotide, especially the codons CUG, UUG, GUG, ACG, AUA and AUU. While non-AUG initiation has been experimentally verified for a handful of human genes, the full extent to which this phenomenon is utilized--both for increased coding capacity and potentially also for novel regulatory mechanisms--remains unclear., The removal of N-terminal translation initiator Met by methionine aminopeptidase (MetAP) is often crucial for the function and stability of proteins., Protein synthesis is initiated by methionine in eukaryotes and by formylmethionine in prokaryotes. N-terminal methionine can be co-translationally cleaved by the enzyme methionine aminopeptidase (MAP)., Our understanding of translation underpins our capacity to engineer living systems. The canonical start codon (AUG) and a few near-cognates (GUG, UUG) are considered as the 'start codons' for translation initiation in Escherichia coli., Translation from non-canonical start codons ranged from 0.007 to 3% relative to translation from AUG., Protein synthesis is initiated universally with the amino acid methionine. In Escherichia coli, studies with anticodon sequence mutants of the initiator methionine tRNA have shown that protein synthesis can be initiated with several other amino acids. In eukaryotic systems, however, a yeast initiator tRNA aminoacylated with isoleucine was found to be inactive in initiation in mammalian cell extracts., Our results show that in the presence of the corresponding mutant initiator tRNAs, AGG and GUC can initiate protein synthesis in COS1 cells with methionine and valine, respectively. CAG initiates protein synthesis with glutamine but extremely poorly, whereas UAG could not be used to initiate protein synthesis with glutamine., Methionine is the universal translation start but the first methionine is removed from most mature proteins., Protein synthesis generally starts with a methionine that is removed during translation., Most mature proteins do not retain their initial N-terminal amino acid (methionine in the cytosol and N-formyl methionine in the organelles).[SEP]Relations: Methionine has relations: drug_protein with GLUL, drug_protein with GLUL, drug_protein with MTR, drug_protein with MTR, drug_protein with MSRA, drug_protein with MSRA, drug_protein with MTRR, drug_protein with MTRR, drug_protein with MARS1, drug_protein with MARS1. Definitions: glutamine defined as following: A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.. isoforms 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.. valine defined as following: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.. methionine aminopeptidase defined as following: Aminopeptidases that remove METHIONINE from the amino-terminus of a peptide chain, such as the initiator METHIONINE found on nascent peptide chains.. codons defined as following: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).. methionine defined as following: A preparation of METHIONINE that includes a mixture of D-methionine and L-methionine isomers.. formylmethionine defined as following: Effective in the initiation of protein synthesis. The initiating methionine residue enters the ribosome as N-formylmethionyl tRNA. This process occurs in Escherichia coli and other bacteria as well as in the mitochondria of eucaryotic cells.. 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.. N-terminal amino acid defined as following: The amino acid residing in the first position of a protein or peptide.. 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.. removal defined as following: Shift the position or location of; take out of.. 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.. 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.. isoleucine defined as following: An essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels.. 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.. cytosol defined as following: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.. 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..", "label": "no"}