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Does deletion of cohesin change gene expression?
The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ~ 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression...
Do MAIT cells have a role in multiple myeloma?
Yes, MAIT cells may represent new immunotherapeutic targets for treatment of Multiple Myeloma and other malignancies
Author information: (1)Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, 3010, Australia. (2)Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia. (3)ARC Centre of Excellence in Advanc...
What is ProSavin?
ProSavin, a lentiviral vector based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease. It has been shown to be well tolerated in a Phase I/II first-in-human study, with significant improvements in motor behavior from baseline at 1 year. Moderate impro...
BACKGROUND: Parkinson's disease is typically treated with oral dopamine replacement therapies; however, long-term treatment leads to motor complications and, occasionally, impulse control disorders caused by intermittent stimulation of dopamine receptors and off-target effects, respectively. We aimed to assess the ...
Are stretch enhancers transcribed more than super-enhancers?
No. Super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers.
Super-enhancers and stretch enhancers represent classes of transcriptional enhancers that have been shown to control the expression of cell identity genes and carry disease- and trait-associated variants. Specifically, super-enhancers are clusters of enhancers defined based on the binding occupancy of master transc...
What is Q-SYMBIO?
Q-SYMBIO is a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality] that assessed coenzyme Q10 as adjunctive treatment of chronic heart failure. METHOD: Patients with moderate to severe HF were randomly ...
What is the function of the NIPBL factor in genome conformation?
The NIPBL protein stimulates cohesin's ABC-like ATPase and is essential for loading cohesin onto chromosomes.. NIPBL recruits histone deacetylases to mediate local chromatin modifications.
Cohesin regulates sister chromatid cohesion during the mitotic cell cycle with Nipped-B-Like (NIPBL) facilitating its loading and unloading. In addition to this canonical role, cohesin has also been demonstrated to play a critical role in regulation of gene expression in nondividing cells. Heterozygous mutations in ...
Is mesothelioma caused by asbestos exposure?
Yes, mesothelioma is caused by asbestos exposure.
OBJECTIVE: Maligt pleural mesothelioma in rural Turkey frequently results from environmental exposure to tremolite asbestos or fibrous zeolite (erionite). The aim of this study was to determine the CT features of maligt pleural mesothelioma in patients exposed to asbestos or erionite. MATERIALS AND METHODS: The CT s...
Which diagnostic test is approved for coronavirus infection screening?
Real-time reverse transcription-PCR (rRT-PCR) is mostly used as the lab test for screening coronaviral infection.
BACKGROUND: An outbreak of severe acute respiratory syndrome (SARS) began in Canada in February 2003. The initial diagnosis of SARS was based on clinical and epidemiological criteria. During the outbreak, molecular and serologic tests for the SARS-associated coronavirus (SARS-CoV) became available. However, without ...
What is Xanamem?
UE2343 was identified as a potent, orally bioavailable, brain-penetrant 11b-HSD1 inhibitor and selected for clinical studies. Reducing glucocorticoid exposure in the brain via intracellular inhibition of the cortisol-regenerating enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) has emerged as a therapeutic str...
Can nrf2 activation lead to resistance to radiotherapy?
Resistance to chemoradiotherapy is a major obstacle to successful treatment of glioblastoma. Recently, the role of NF-E2-related factor 2 (Nrf2) in enhancing chemoradiation sensitivity has been reported in several types of cancers. Blocking Nrf2 activation may be a promising method enhancing chemoradiation sensitivity ...
Cancer stem cells (CSCs) express high levels of drug efflux transporters and antioxidant genes, and are therefore believed to be responsible for cancer recurrence following chemo/radiotherapy intervention. In this study, we investigated the role of NF-E2-related factor 2 (NRF2), a master regulator of antioxidant ge...
Are there interactions between short and long noncoding RNAs?
Yes. Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions.
Which molecule is inhibited by encorafenib?
Encorafenib is a BRAF inhibitor. It is a promising therapy for metastatic or inoperable melanoma with a BRAF mutation.
PURPOSE: To test second-line personalized medicine combination therapies, based on genomic and proteomic data, in patient-derived xenograft (PDX) models. EXPERIMENTAL DESIGN: We established 12 PDXs from BRAF inhibitor-progressed melanoma patients. Following expansion, PDXs were analyzed using targeted sequencing and...
What is the basis of the capture Hi-C experimental protocol?
Capture Hi-C (CHi-C) allows high-resolution analysis of targeted regions of the genome by incorporating a sequence capture step into a Hi-C protocol. Capture Hi-C (CHi-C) enriches standard Hi-C libraries for regions of biological interest, for example by specifically targeting gene promoters, aiding identification of b...
Genome-wide association studies have identified more than 70 common variants that are associated with breast cancer risk. Most of these variants map to non-protein-coding regions and several map to gene deserts, regions of several hundred kilobases lacking protein-coding genes. We hypothesized that gene deserts har...
What is the role of Scc2/Nipbl?
Scc2 (Nipbl) stimulates cohesin's ABC-like ATPase and is essential for loading cohesin onto chromosomes. Scc2 also binds dynamically to chromatin, principally through an association with cohesin. Scc2's movement within chromatin is consistent with a 'stop-and-go' or 'hopping' motion. A low diffusion coefficient, a low ...
The cohesin complex mediates DNA-DNA interactions both between (sister chromatid cohesion) and within chromosomes (DNA looping). It has been suggested that intra-chromosome loops are generated by extrusion of DNAs through the lumen of cohesin's ring. Scc2 (Nipbl) stimulates cohesin's ABC-like ATPase and is essentia...
What is the chromosomal location of the LDL receptor gene associated with autosomal dominant Familial Hypercholesterolemia?
Familial hypercholesterolemia (FH) is an autosomal dominant inherited metabolic disorder resulting in advanced vascular atherosclerosis and premature death, primarily from coronary artery disease. The primary defect is a mutation in the gene encoding for the plasma LDL receptor located on the short arm of chromosome 19
Clinical familial hypercholesterolemia has been shown to result from mutations in 2 genes, the low density lipoprotein (LDL) receptor on chromosome 19 and apolipoprotein B on chromosome 2. However, we have recently described a Utah pedigree in which linkage to both genes was clearly excluded. A multipoint linkage a...
Can brain derived exosomes carry APP molecules?
Yes, small lipid vesicles called exosomes, secreted in the extracellular milieu by cortical neurons, carry endogenous APP
Alzheimer's disease (AD) is the most common form of dementia and is associated with the deposition of the 39- to 43-amino acid beta-amyloid peptide (Abeta) in the brain. C-terminal fragments (CTFs) of amyloid precursor protein (APP) can accumulate in endosomally derived multivesicular bodies (MVBs). These intracell...
List the most common cancers after a radiation exposure?
well-known increase in leukaemia, increases in solid cancer such as cancers of the lung, breast, stomach and thyroid have also been demonstrated.
Within months of Roentgen's discovery of X rays, severe adverse effects were reported, but not well publicized. As a result, over the next two decades, fluoroscope operators suffered lethal skin carcinomas. Later, case reports appeared concerning leukemia in radiation workers, and infants born with severe mental re...
Which are the main G1/S transcription factors in yeast?
MBF/SBF is the major transcriptional repressor of G1/S genes in Saccharomyces cerevisiae.
We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast. We have now found that Skn7 associates with Mbp1, the DNA-binding component of the G1-S transcription factor DSC1/MBF. SKN7 and MBP1 show several genetic interactions....
What is Hemochromatosis?
Hereditary hemochromatosis (HH) is a group of genetic iron overload disorders that manifest with various symptoms, including hepatic dysfunction, diabetes, and cardiomyopathy.
Hemochromatosis is a common disorder characterized by excess iron absorption and accumulation of iron in tissues. Usually hemochromatosis is inherited in an autosomal recessive pattern and is caused by mutations in the HFE gene. Less common non-HFE-related forms of hemochromatosis have been reported and are caused ...
What molecules are the multidrug transporter MDR3 targeting?
Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator.
The ATP-binding cassette transporter ABCB4/MDR3 is critical for biliary phosphatidylcholine (PC) excretion at the canalicular membrane of hepatocytes. Defective ABCB4 gene expression and protein function result in various cholestatic liver and bile duct injuries. Thyroid hormone receptor (THR) is a major regulator ...
What is the role of the Hof1-Cyk3 interaction in yeast?
In Saccharomyces cerevisiae, it is well established that Hof1, Cyk3, and Inn1 contribute to septum formation and cytokinesis. There is also evidence that they interact physically.
List features of the SAM syndrome.
SAM syndrome is characterized by severe dermatitis, multiple allergies and metabolic wasting. It is caused by mutations in the desmoglein 1 gene (DSG1).
Monoallelic desmoglein 1 mutations have been known for many years to cause striate palmoplantar keratoderma, but only recently, biallelic loss-of-function mutations were associated with a new disorder, designated as SAM syndrome (comprising severe dermatitis, multiple allergies and metabolic wasting) in two consang...
What does the Smith–Waterman algorithm do?
The Smith-Waterman algorithm performs local sequence alignments.
The Smith-Waterman algorithm for local sequence alignment is one of the most important techniques in computational molecular biology. This ingenious dynamic programming approach was designed to reveal the highly conserved fragments by discarding poorly conserved initial and terminal segments. However, the existing ...
Is SATB1 positioned close to AT-rich sequences?
Yes, SATB1 is preferentially located at the start of an AT-rich sequence and is associated with other, more diffuse AT- rich sequences in the genome.
A cis-acting DNA regulatory element 3' to the A gamma-globin gene contains eight distinct regions of DNA-protein interaction distributed over 750 bp of DNA. The sequences of two foot-printed regions (sites I and IV) are A-T rich and generate a highly retarded complex on gel shift analysis with nuclear extract from h...
Describe the Java Adverse Drug Event (JADE) tool
The Java Adverse Drug event (Jade) is a tool for medical researchers to explore adverse drug events using health insurance plans and drug-drug interactions.
BACKGROUND: The Joint Asia Diabetes Evaluation (JADE) Program is a web-based program incorporating a comprehensive risk engine, care protocols, and clinical decision support to improve ambulatory diabetes care. METHODS: The JADE Program uses information technology to facilitate healthcare professionals to create a d...
Which drugs were tested in the CheckMate 227 clinical trial?
CheckMate-227 clinical trial tested ipilimumab plus nivolumab for the treatment of non-small cell lung cancer.
The monoclonal antibodies ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have shown remarkable antitumor activity in an increasing number of cancers. When combined, ipilimumab and nivolumab have demonstrated superior activity in patients with metastatic melanoma (CHECKMATE-067). Here we describe the preclinical...
What is known about PAI-1 in longevity in humans?
Plasminogen activator inhibitor-1 (PAI-1) has been shown to be a key component of the senescence-related secretome and a direct mediator of cellular senescence. In murine models of accelerated aging, genetic deficiency and targeted inhibition of PAI-1 protect against aging-like pathology and prolong life span. However,...
Gene polymorphisms associated with the plasma levels of fibrinogen, factor VII, and plasminogen activator inhibitor 1 (PAI-1)-hemostasis proteins that help to predict the risk of atherothrombotic disease-were compared in 124 healthy individuals > or = 100 years old and 130 young, healthy individuals to identify gen...
Does metformin alleviate atherosclerosis?
Yes. Metformin has been shown to decrease frequency of atherosclerosis-associated adverse effects in statin-intolerant patients and to slow the pathogenesis of type 2 diabetes mellitus.
BACKGROUND: Metformin and rosiglitazone both improve glycemic control in type 2 diabetes mellitus, however may possess different anti-inflammatory and anti-atherosclerotic properties. We investigated the effects of these medications on high-sensitivity C-reactive protein (hsCRP) and carotid artery intima-media thic...
List side effects of radiation therapy?
radiation-induced tumors radiation necrosis microangiopathy progressive leukencephalopathy pneumonitis disturbance of the blood-brain barrier radionecrosis of brain tissue radiogenic liver damage mucositis colitis osteitis osteoradionecrosis myositis Radiation-induced fibrosis Acute skin reactions
BACKGROUND: Radiation-induced fibrosis (RIF) is one of the severe long-term side effects of radiation therapy (RT) with a crucial impact on the development of postoperative wound healing disorders (WHD). The grades of fibrosis vary between mild to severe depending on individual radiosensitivity. In this study, we ha...
Are CD8+ (cytotoxic) T cells and CD4+ Helper T cells generated in the thyroid and express the T-cell receptor?
Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, These two cell types are derived from common precursors in the thymus.
Mature T cells express either CD4 or CD8 on their surface. Most helper T cells express CD4, which binds to class II major histocompatibility complex (MHC) proteins, and most cytotoxic T cells express CD8, which binds to class I MHC proteins. In the thymus, mature CD4+CD8- and CD4-CD8+ T cells expressing alpha beta ...
What bacteria is associated with Gastric cancer and peptic ulcers?
Helicobacter pylori (H. pylori), a gram-negative microaerophilic bacterial pathogen that colonizes the stomachs of more than half of all humans, is linked to chronic gastritis, peptic ulcers and gastric cancer.
The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. The pathogenesis of H. pylori infection in vivo was studied by adapting fresh clinical isolates of bacteria to colonize the stomachs of mice. A gastric pathology resembling human disease was observed in in...
Is Huntington's disease is caused by expansion of a CTG repeat in the HTT gene on Chromosome 4?
No, Huntington's disease is caused by expansion of a CAG repeat (not CTG) in the HTT gene on Chromosome 4.
Huntington's disease (HD) is an autosomal domit neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat in exon 1 of the huntingtin (htt) gene. Emergence and progression of HD depend on continuous expression of mutant Huntingtin protein (Htt). Therefore, blocking expression of mutant Htt mig...
What is the purpose of the 123 dihydrorhodamine assay?
detection of inheritance pattern in thirty-three mexican males with chronic granulomatous disease
OBJECTIVE: Wegener's granulomatosis (WG) is strongly associated with antineutrophil cytoplasmic autoantibodies (ANCAs) directed against proteinase 3 (PR3). Recent studies have shown that membrane-bound PR3 (mPR3) is differentially expressed and colocalizes with CD177/NB1 on circulating neutrophils. We undertook thi...
What is the mode of action of filgotinib?
Filgotinib is an oral selective Janus kinase 1 (JAK1) inhibitor. It has been tested in patients with rheumatoid arthritis and Chroni's disease, and has been shown to be effective.
OBJECTIVE: The selective Janus kinase 1 inhibitor filgotinib (GLPG0634), which is currently in clinical development for the treatment of rheumatoid arthritis (RA) and Crohn's disease, demonstrated encouraging safety and efficacy profiles in RA patients after 4 weeks of daily dosing. As RA patients might be treated ...
Is Huntington's disease caused by a dominate or recessive gene?
Huntington's Disease (HD) is an autosomal dominant neurodegenerative disease
Huntington's disease (HD) is a late onset, incurable, autosomal domitly-inherited, progressive neuropsychiatric disease, characterised by chorea, changes in personality, mood and behaviour, and dementia. Huntington's disease is a clinical diagnosis. The advent of DNA diagnosis has made predictive, prenatal and prei...
What is RiboTag profiling?
RiboTag is a flexible tool for measuring the translational state of targeted cells in heterogeneous cell cultures.
Is there an increased risk of meningiomas in atomic bomb survivors?
Yes, the incidence of meningiomas is increased in atomic bomb survivors.
Among the Nagasaki atomic-bomb survivors registered at the Scientific Data Center for Atomic-Bomb Disaster, Nagasaki University School of Medicine, 45 cases of surgically treated intracranial meningioma were collected from 6 hospitals with departments of neurosurgery in or near Nagasaki City during the period from ...
What is foliglurax?
Foliglurax is a positive allosteric modulator of the metabotropic glutamate receptor 4. Foliglurax induced a robust and dose-dependent reversal of parkinsonian motor symptoms in macaques, including bradykinesia, tremor, posture, and mobility. Moreover, PXT002331 strongly decreased dyskinesia severity, thus having ther...
BACKGROUND: Levodopa remains the gold-standard treatment for PD. However, it becomes less effective as the disease progresses and produces debilitating side effects, such as motor fluctuations and l-dopa-induced dyskinesia. Modulation of metabotropic glutamate receptor 4 represents a promising antiparkinsonian appr...
What is the genetic basis for Cornelia de Lange's syndrome?
Mutations in five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural components of cohesin, have been identified.
Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous developmental disorder. Clinical features include growth retardation, intellectual disability, limb defects, typical facial dysmorphism, and other systemic involvement. The increased understanding of the genetic basis of CdLS has led to...
Are gut microbiota profiles altered by irradiation?
Yes, Irradiation profoundly impacted gut microbiota profiles
In rodent studies, the gut microbiota has been implicated in facilitating both radioresistance, by protecting the epithelium from apoptotic responses and radiosensitivity, inducing endothelial apoptotic responses. Despite the observation that large animal models, such as the Chinese Rhesus macaque and the Gottingen...
Is TIM-3 a target for cancer immunotherapy in NSCLC?
Yes. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation.
Immune checkpoints associate with dysfunctional T cells, which have a reduced ability to clear pathogens or cancer cells. T-cell checkpoint blockade may improve patient survival. However, checkpoint molecules on cytokine-induced killer (CIK) cell, a non-specific adoptive immunotherapy, remain unknown. In present st...
How does LB-100 affect the DDR proteins (BRCA1, Chk2, and γH2AX)?
LB100 induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and gH2AX).
Despite early positive response to platinum-based chemotherapy, the majority of ovarian carcinomas develop resistance and progress to fatal disease. Protein phosphatase 2A (PP2A) is a ubiquitous phosphatase involved in the regulation of DNA-damage response (DDR) and cell-cycle checkpoint pathways. Recent studies ha...
What particles is Hadron therapy using?
Hadron therapy is using proton beams.
The use of hadron beams, especially proton beams, in cancer radiotherapy has expanded rapidly in the past two decades. To fully realize the advantages of hadron therapy over traditional x-ray and gamma-ray therapy requires accurate positioning of the Bragg peak throughout the tumor being treated. A half century ago...
Does an interferon (IFN) signature exist for SLE patients?
Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. An IFN-I score (positive or negative), as a measure of IFN-I activation, is assessed using the expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs).
The expression and activation of regulatory factors (IRF) and rinterferon (IFN) response genes were evaluated in a patient treated with autologous hematopoietic stem cell transplant (HSCT) for refractory systemic lupus erythematosus (SLE). In SLE patients, genetic variants of IRF5 and IRF7 have been associated with ...
Is AND-1/Ctf4 essential for proliferation?
Yes. AND-1 fork protection function prevents fork resection and is essential for proliferation.
AND-1/Ctf4 bridges the CMG helicase and DNA polymerase alpha, facilitating replication. Using an inducible degron system in avian cells, we find that AND-1 depletion is incompatible with proliferation, owing to cells accumulating in G2 with activated DNA damage checkpoint. Replication without AND-1 causes fork spee...
Does the BRAFV600E mutation have an effect on clinical response to radioiodine therapy?
Yes, it has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAF(V600E) mutation have a worse prognosis.
PURPOSE: As the most frequent and specific genetic alteration in papillary thyroid carcinoma (PTC), BRAF(V600E) has an intimate relationship with more invasive tumour and higher postoperative recurrence risk in PTC patients. We investigate the effect of radioactive iodine (RAI) therapy on the clinical outcome in PT...
Which phosphatase is inhibited by LB-100?
LB-100 is a phosphatase 2A inhibitor
What are the most common side effects of amantadine ER?
The most common side effects of amantadine ER are hallucination, dizziness, orthostatic hypotension and pedal edema.
Levodopa is the most efficacious treatment for Parkinson's disease (PD). Long-term treatment with levodopa is limited due to dyskinesia. Dyskinesia in PD can be socially and functionally disabling. Extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia. When it ...
Which symptoms comprise Abdominal aortic aneurysm rupture Triad?
Classic triad of Abdominal aortic aneurysm rupture include shock, acute abdominal pain, and pulsatile abdominal mass.
Only 50% of abdominal aortic aneurysms present with the classic triad of hypotension, back pain and a pulsatile abdominal mass. This variability in symptoms can delay diagnosis and treatment. We present the case of a patient presenting with a unique combination of symptoms suggesting that decompression of urinary r...
List symptoms of Allgrove syndrome.
The classical clinical triad of the Allgrove syndrome includes alacrima, achalasia and adrenal insufficiency. It can be also associated with progressive peripheral neuropathy.
Allgrove syndrome (triple A syndrome) is an autosomal recessive disorder characterised by adrenocortical insufficiency, achalasia and alacrima. Patients also suffer from diverse neurological disorders. Allgrove syndrome is caused by mutations in the AAAS gene located at chromosome 12q13, which encodes for a tryptop...
What is water radiolysis?
Water radiolysis involves chemical decomposition of the water molecule into free radicals after exposure to ionizing radiation. These free radicals have deleterious effects on normal cell physiology.
To elucidate microscopic details of proton cancer therapy (PCT), we apply the simplest-level electron nuclear dynamics (SLEND) method to H+ + (H2O)1-6 at ELab = 100 keV. These systems are computationally tractable prototypes to simulate water radiolysis reactions-i.e. the PCT processes that generate the DNA-damaging...
How do the plasma concentrations of amantadine extended release and amantadine immediate release compare?
When it is given at bedtime, it reaches plasma concentration approximately twice the level achieved by amantadine immediate release.
Levodopa is the most efficacious treatment for Parkinson's disease (PD). Long-term treatment with levodopa is limited due to dyskinesia. Dyskinesia in PD can be socially and functionally disabling. Extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia. When it ...
Is the BAGEL algorithm used for arrayed CRISPR screens?
No. BAGEL (Bayesian Analysis of Gene EssentiaLity) is a supervised learning method for analyzing pooled library gene knockout screens. It offers significantly greater sensitivity than current methods, while computational optimizations reduce runtime by an order of magnitude.
BACKGROUND: The adaptation of the CRISPR-Cas9 system to pooled library gene knockout screens in mammalian cells represents a major technological leap over RNA interference, the prior state of the art. New methods for analyzing the data and evaluating results are needed. RESULTS: We offer BAGEL (Bayesian Analysis of ...
What is included in the LACE Index?
The LACE index is a simple tool that includes 4 parameters: Length of stay, Acuity of admission, Comorbidity, and Emergency visits in the previous 6 months. It is used to predict early re-admission after hospital discharge.
Predictive models for hospital readmission rates are in high demand because of the Centers for Medicare & Medicaid Services (CMS) Hospital Readmission Reduction Program (HRRP). The LACE index is one of the most popular predictive tools among hospitals in the United States. The LACE index is a simple tool with 4 par...
Which drugs are included in GI cocktail?
"GI cocktail" is a mixture of liquid antacid, viscous lidocaine, and an anticholinergic.
STUDY OBJECTIVE: To determine practice patterns regarding administration of the "GI cocktail" (a mixture of liquid antacid, viscous lidocaine, and an anticholinergic) in the emergency department in a single hospital and the responses and final dispositions of patients who received the cocktails. DESIGN: A retrospect...
Is AZD5153 active in prostate cancer?
Yes, AZD5153 was shown to be effective in treatment of prostate cancer.
BACKGROUNDS/AIMS: Bromodomain-containing protein 4 (BRD4) overexpression participates in prostate cancer progression by enhancing the transcriptional activity and expression of several key oncogenes. AZD5153 is a novel BRD4 inhibitor. METHODS: Prostate cancer cells were treated with AZD5153. Cell survival was teste...
Is GRG5 involved only in late embryonic mouse development?
No. Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in both early and late embryonic mouse development.
Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches...
Are astronauts in higher risk for developing cancer?
No significant associations between space radiation dose and mortality were found using logistic regression with an internal reference group, adjusting for medical radiation.
Despite years of research, understanding of the space radiation environment and the risk it poses to long-duration astronauts remains limited. There is a disparity between research results and observed empirical effects seen in human astronaut crews, likely due to the numerous factors that limit terrestrial simulat...
Describe the mechanism of action of a drug Elagolix.
Elagolix is a novel, orally active, non-peptide, competitive gonadotropin-releasing hormone (GnRH) receptor antagonist. It is in development for the management of endometriosis with associated pain and heavy menstrual bleeding due to uterine fibroids.
CONTEXT: Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. OBJECTIVE: Our objective was to evaluate the safety, pharmacokinetics, and inhibi...
Describe mechanism of action of volanesorsen.
Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. It has been shown to decrease TGs by 70-80%.
OBJECTIVE: To determine the effects of volanesorsen (ISIS 304801), a second-generation 2'-O-methoxyethyl chimeric antisense inhibitor of apolipoprotein (apo)C-III, on triglyceride (TG) levels and insulin resistance in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized, double-blind, placebo-con...
What is the cyberknife used for?
CyberKnife(r) is a robotic stereotactic radiotherapy system
BACKGROUND: CyberKnife® stereotactic radiosurgery is a new treatment option for uveal melanoma. OBJECTIVE: This review outlines the technique of robot-assisted CyberKnife® therapy, as well as the pros and cons in the treatment of uveal melanoma. METHODS: The study provides a PubMed literature review and own prelimina...
Is Niraparib effective for ovarian cancer?
Yes. Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is approved by the United States Food and Drug Administration and the European Medicines Agency for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy.
Author information: (1)From the Nordic Society of Gynecological Oncology and Rigshospitalet-Copenhagen University Hospital, Copenhagen (M.R.M.), Odense University Hospital (J.H.) and European Network for Gynacological Oncological Trial and Research Unit of General Practice, Institute of Public Health, University of...
Which portal has been developed to explore protein-protein interactions in cancer cell lines?
The OncoPPi Portal has been developed as an interactive web resource that allows investigators to access, manipulate and interpret a high-quality cancer-focused network of protein-protein interactions (PPIs) experimentally detected in cancer cell lines. To facilitate prioritization of PPIs for further biological studie...
MOTIVATION: As cancer genomics initiatives move toward comprehensive identification of genetic alterations in cancer, attention is now turning to understanding how interactions among these genes lead to the acquisition of tumor hallmarks. Emerging pharmacological and clinical data suggest a highly promising role of...
Are genes that escape X-chromosome inactivation related to mental impairment?
Yes. Genes that escape X-inactivation in humans have high intraspecific variability in expression, are associated with mental impairment but are not slow evolving.
Mental retardation affects 2 to 3% of the population and is marked by significant etiological heterogeneity, including genetic and non genetic causes. FRAXA (FMR1) trinucleotide expansion is widely searched in routine screening, but found in only about 2% of the patients tested. Mutations of the MECP2 (methyl-CpG-b...
Which biological process takes place in nuclear speckles?
Speckles are subnuclear structures that are enriched in pre-messenger RNA splicing factors and are located in the interchromatin regions of the nucleoplasm of mammalian cells. They serve as splicing factor storage sites and play important roles in regulation of pre-mRNA splicing.
Nuclear speckles (speckles) represent a distinct nuclear compartment within the interchromatin space and are enriched in splicing factors. In a previous study (Melcák et al., 2001), it has been shown that the pre-spliceosomal assembly on microinjected splicing-competent precursor mRNA takes place in the speckles, an...
What is the effect of HMGB2 loss on CTCF clustering?
Depletion of the abundant HMGB2 protein occurs early on the path to senescence and coincides with the dramatic spatial clustering of CTCF. Knocking down HMGB2 suffices for senescence-induced CTCF clustering and for loop reshuffling, while ectopically expressing HMGB2 rescues these effects.
Author information: (1)Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany. (2)German Cancer Research Center and Bioquant, 69120 Heidelberg, Germany. (3)School of Physics and Astronomy, University of Edinburgh, EH9 3FD Edinburgh, UK. (4)Institute of Molecular Biology, 55128 Mainz, Ger...
Has LB-100 been tested in clinical trials?
Yes, a phase I trial has been performed to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small-molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors.
Which algorithms have been developed for analysing CRISPR/Cas9 knockout screens data?
HiTSelect and MAGeCK (Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout)
Author information: (1)Institute for Human Genetics, University of California, San Francisco, CA, USA The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA Department of Epidemiology and Biostatistics, University of California, San Francisco...
Which cells are affected in radiation-induced leukemias?
Hemopoietic stem cells, the possible target cells for radiation-induced leukemias.
The host-defense mechanisms against cancers are known to be modulated by changing the environmental factor(s). The spontaneous incidence of myeloid leukemia is about 1% in C3H/He mice, and the incidence increases up to 23.3% when a single dose of radiation, 3 Gy X-ray, is exposed to a whole-body. Since calorie rest...
PDQ39 questionnaires is design for which disease?
PDQ39 is Parkinson's Disease Questionnaire that is used for assessment of quality of life in patients with Parkinson's Disease.
BACKGROUND: The well known global improvement of quality of life (QoL) after bilateral high frequency chronic deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) is in contrast to behavioral disturbances as observed after surgery. Indeed the impact of DBS on physical versus menta...
Is palbociclib effective for glioblastoma?
No. In a clinical trial palbociclib monotherapy was not an effective treatment for recurrent glioblastoma.
INTRODUCTION: Alterations in the CDK4/6-RB signaling pathway are common causes of cell cycle dysregulation in many cancers, including glioblastoma. Palbociclib is an oral inhibitor of CDK4/6, which leads to phosphorylation of RB1 and cell-cycle arrest. We conducted a two-arm study evaluating efficacy and tissue pha...
List five proteins with antioxidant properties?
thioredoxin 1 (Trx1), peroxiredoxin 1 (Prx1), GSH reductase (GSR), phosphatase and tensin homolog (PTEN) superoxide dismutase (SOD)
Arginine is a conditionally essential amino acid. To elucidate the influence of l-arginine on the activation of endogenous antioxidant defence, male Wistar rats were orally administered daily with l-arginine at different levels of 25, 50, 100 mg/100 g body weight. After 7 and 14 days feeding, the antioxidative capa...
Does the Mcm2-Ctf4-Polα axis play a role in transfer of histones to leading strand DNA at the replication forks?
No, the Mcm2-Ctf4-Pola axis facilitates parental histone H3-H4 transfer to lagging strands.
What is Scalp cirsoid aneurysms?
Cirsoid aneurysms are rare arteriovenous malformations of the scalp, which are usually of congenital etiology. They often present as an enlarging pulsatile scalp mass.
BACKGROUND: Cirsoid aneurysms are uncommon arteriovenous fistulas of the scalp. Surgery for these lesions can be difficult; transarterial embolization is rarely curative, while embolization of the venous pouch with permanent agents usually necessitates subsequent surgical removal of the embolic material. The ideal ...
Which gene is frequently involved in autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)?
Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene.
Adult-onset autosomal domit leukodystrophy (ADLD) is a slowly progressive neurological disorder characterized by symmetrical widespread myelin loss in the central nervous system, with a phenotype similar to chronic progressive multiple sclerosis. In this study, we identify a genomic duplication that causes ADLD. Af...
What is the radiation-induced CD8 lymphocyte apoptosis (RILA) assay used for?
Radiation-induced lymphocyte apoptosis (RILA) has been suggested as a predictive assay for adverse late reactions after radiotherapy.
PURPOSE: 454 patients with prostate adenocarcinoma were accidentally overexposed to radiation in Epinal hospital, France, between August 1999 and January 2007. We aimed toevaluate whether radiation-induced CD4 or CD8 T-lymphocyte apoptosis (RILA) correlates with the severity of radiation toxicity. METHODS: Between 2...
What are the puQTLs (promoter-usage Quantitative Trait Loci)?
The identification of genetic variants affecting gene expression, namely expression quantitative trait loci (eQTLs), has contributed to the understanding of mechanisms underlying human traits and diseases. The majority of these variants map in non-coding regulatory regions of the genome and their identification remains...
The identification of genetic variants affecting gene expression, namely expression quantitative trait loci (eQTLs), has contributed to the understanding of mechanisms underlying human traits and diseases. The majority of these variants map in non-coding regulatory regions of the genome and their identification rem...
Which is the main epigenetic difference between poised and constitutive enhancers?
We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone.
Developmental programs are controlled by transcription factors and chromatin regulators, which maintain specific gene expression programs through epigenetic modification of the genome. These regulatory events at enhancers contribute to the specific gene expression programs that determine cell state and the potentia...
What is PRL3-zumab?
PRL3-zumab is a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. PRL3-zumab specifically blocked PRL-3+, but not PRL-3-, orthotopic gastric tumors. In this setting, PRL3-zumab had...
Novel, tumor-specific drugs are urgently needed for a breakthrough in cancer therapy. Herein, we generated a first-in-class humanized antibody (PRL3-zumab) against PRL-3, an intracellular tumor-associated phosphatase upregulated in multiple human cancers, for unconventional cancer immunotherapies. We focused on gas...
Which receptor is inhibited by Tivozanib?
Tivozanib is a selective inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3 tyrosine kinases.
PURPOSE: To assess the maximum tolerated dose (MTD)/dose-limiting toxicities (DLT), safety, pharmacokinetics, and pharmacodynamics of tivozanib, a potent and selective oral VEGF receptor (VEGFR) tyrosine kinase inhibitor. EXPERIMENTAL DESIGN: Dose levels of 1.0, 1.5, and 2.0 mg/d tivozanib for 28 days followed by 14...
Can discharge destinations be accurately predicted using the Risk Assessment and Prediction Tool (RAPT)?
Yes. The Risk Assessment and Prediction Tool (RAPT) appears to be a valuable predictor of discharge destination after orthopedic surgery and neurosurgical procedures.
OBJECTIVE: To assess the relevance of the RAPT (Risk Assessment and Prediction Tool), among a cohort of patients undergoing total hip arthroplasty (THA). METHOD: Prospective study of a cohort of patients evaluated before and after THA. The difference between the postoperative orientation predicted by the RAPT and th...
What is Perturb-seq?
Perturb-seq is a technique that combines single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations to perform many such assays in a pool. Perturb-seq accurately identifies individual gene targets, gene signatures, and cell states affected by individu...
Author information: (1)Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. (2)Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. (3)Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Systems...
What is the content of the REPAIRtoire database?
The REPAIRtoire database collects and organizes the following types of information: (i) DNA damage linked to environmental mutagenic and cytotoxic agents, (ii) pathways comprising individual processes and enzymatic reactions involved in the removal of damage, (iii) proteins participating in DNA repair and (iv) diseases...
REPAIRtoire is the first comprehensive database resource for systems biology of DNA damage and repair. The database collects and organizes the following types of information: (i) DNA damage linked to environmental mutagenic and cytotoxic agents, (ii) pathways comprising individual processes and enzymatic reactions ...
Has amantadine ER been approved by the FDA?
Yes, amantadine ER is an US FDA-approved treatment.
BACKGROUND: Although levodopa is considered the most effective pharmacotherapy for motor symptoms of Parkinson's disease (PD), chronic use is associated with motor complications, including fluctuating response and unpredictable, involuntary movements called dyskinesia. ADS-5102 (amantadine) extended-release (ER) ca...
Can PRL3-zumab inhibit PRL3+ cancer cells in vitro and in vivo?
PRL3-zumab specifically inhibits PRL3+ cancer cells in vivo, but not in vitro.
How rare are CTCs (circulating tumour cells) in the plasma of patients?
Circulating tumour cells (CTCs) are significantly rare entity in the blood of patients with non-small cell lung cancer (NSCLC) patients as well as in other types of cancer. Small-cell lung cancer cells are typically quiescent, whereas CTCs can be up-regulated in response to radiation or chemical agents and may contribu...
The enumeration of circulating tumor cells has long been regarded as an attractive diagnostic tool, as circulating tumor cells are thought to reflect aggressiveness of the tumor and may assist in therapeutic decisions in patients with solid maligcies. However, implementation of this assay into clinical routine has ...
What is gamma sterilization used for?
Gamma sterilization of bone allografts is used as a gold standard method to provide safety against disease transmission. Also, gamma (g)-sterilization has been commonly employed for wide range of products as indicated by the pharmacopoeias.
The long-term clinical success of autologous vein and synthetic vascular grafts are limited because of the development of anastomotic intimal hyperplasia (IH). We have previously published data suggesting that cyclosporine (CyA) may reduce the development of IH in a canine model (Hirko et al., J Vasc Surg 1993;17:8...
Does Estrogen lead to forkhead FoxA1 activation?
The pioneer transcription factor FoxA1 plays an important role in estrogen signaling by opening closed chromatin and promoting recruitment of the estrogen receptor to its target regions in DNA.
Estrogen plays an essential physiologic role in reproduction and a pathologic one in breast cancer. The completion of the human genome has allowed the identification of the expressed regions of protein-coding genes; however, little is known concerning the organization of their cis-regulatory elements. We have mappe...
What is detected by the UV-damaged DNA-binding protein (UV-DDB) complex?
Upon UV irradiation of primate cells, UV-DDB associates tightly with chromatin and is involved in global genomic nucleotide excision repair (NER) in mammalian cells.
Xeroderma pigmentosum (XP) is a heritable human disorder characterized by defects in nucleotide excision repair (NER) and the development of skin cancer. Cells from XP group E (XP-E) patients have a defect in the UV-damaged DNA-binding protein complex (UV-DDB), involved in the damage recognition step of NER. UV-DDB...
What is the current regulation of eye lens radiation exposure?
The reduction of the dose limit for eye lens from 150 to 20 mSv yr-1 must be implemented by EU member states by February 2018. Consequently, there is a requirement for all employers engaged with work with ionising radiation to have appropriate monitoring arrangements in place by this date to demonstrate that they can m...
The reduction of the dose limit for eye lens from 150 to 20 mSv yr-1 must be implemented by EU member states by February 2018. Consequently, there is a requirement for all employers engaged with work with ionising radiation to have appropriate monitoring arrangements in place by this date to demonstrate that they c...
Does association with the nuclear pore promote gene silencing?
MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing. The nucleoporin Nup358 plays an important role in this process
Tpr is a 267-kDa protein forming coiled coil-dominated homodimers that locate at the nucleoplasmic side of the nuclear pore complex (NPC). The proteins that tether Tpr to this location are unknown. Moreover, the question whether Tpr itself might act as a scaffold onto which other NPC components need to be assembled...
Which methods are used for genome segmentation of gene expression data?
Most of the used methods are variations of Markov Models such as Markov Chain Monte Carlo (MCMC) or Combinatorial methods.
The existence of whole genome sequences makes it possible to search for global structure in the genome. We consider modeling the occurrence frequencies of discrete patterns (such as starting points of ORFs or other interesting phenomena) along the genome. We use piecewise constant intensity models with varying numb...
Which receptor is inhibited by Teprotumumab?
Teprotumumab is a monoclonal inhibitory antibody targeting IGF-1 receptor.
PURPOSE OF REVIEW: In recent years, immunosuppressive therapy, as an alternative to corticosteroids, has been proposed as novel agents which target the various antigens involved in the pathogenesis of Graves' ophthalmopathy. Although the lack of randomized and controlled studies suggests caution in generalizing res...
What is the cause of the disease Xeroderma Pigmentosum?
Mutations in the ERCC1 or ERCC4 genes cause a remarkable array of rare inherited human disorders including specific forms of xeroderma pigmentosum. Individuals with NER-defective xeroderma pigmentosum (XP), in which bulky DNA lesions are not efficiently removed, are cancer-prone and suffer neurodegeneration.
Nucleotide excision repair (NER) in higher organisms repair massive DNA abrasions caused by ultraviolet rays, and various mutagens, where Xeroderma pigmentosum group A (XPA) protein is known to be involved in damage recognition step. Any mutations in XPA cause classical Xeroderma pigmentosum disease. The extent to ...
List Alkaptonuria Triad.
Alkaptonuria is a rare inherited genetic disorder of tyrosine metabolism characterized by a triad of homogentisic aciduria, ochronosis, and arthritis.
Alkaptonuria is a rare autosomal recessive disorder of metabolism caused by deficiency of homogentisic acid oxidase and resulting in accumulation of homogentisic acid in collagenous structures. This causes the classic clinical triad: (1) homogentisic aciduria (urine blackens on standing when oxidized or alkalinized...
Can LB-100 sensitize ovarian carcinoma to cisplatin?
Yes, LB100 sensitizes ovarian carcinoma cells to cisplatin-mediated cytotoxicity.
Despite early positive response to platinum-based chemotherapy, the majority of ovarian carcinomas develop resistance and progress to fatal disease. Protein phosphatase 2A (PP2A) is a ubiquitous phosphatase involved in the regulation of DNA-damage response (DDR) and cell-cycle checkpoint pathways. Recent studies ha...
List T-UCRs that have been implicated in breast cancer
Long non-coding RNAs (lncRNAs) are transcripts longer than 200 bp with no protein-coding capacity. Transcribed ultraconserved regions (T-UCRs) are a type of lncRNA and are conserved among human, chick, dog, mouse and rat genomes. These sequences are involved in cancer biology and tumourigenesis. Overexpression of one s...
Transcribed-ultraconserved regions (T-UCRs) are long non-coding RNAs (lncRNA) encoded by a subset of long ultraconserved stretches in the human genome. Recent studies revealed that the expression of several T-UCRs is altered in cancer and growing evidences underline the importance of T-UCRs in oncogenesis, offering ...
How many different miRNAs can be upregulated by LB-100?
LB-100 has been reported to upregulate one miRNA, namely miR-181b-1.
Author information: (1)Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China. (2)Department of Hematology, Hangzhou First People's Hospital, Hangzhou, 310006, Zhejiang Province, People's Republic of China. (3)Myelodysplastic Syn...
Which T-UCRs have been implicated in gastric cancer?
Uc.160 is significantly down-regulated in gastric carcinomas and can inhibit the tumor growth both in vitro and in vivo, suggesting that uc.160 may be used as a diagnostic marker and therapeutic target of gastric malignancies. Uc.416+A is overexpressed in GC and is associated with cell growth through the regulation of ...
The transcribed-ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs, which are absolutely conserved (100%) between the orthologous regions of the human, rat and mouse genomes. Previous studies have described that several T-UCRs show differential expressions in cancers and might be involved in cancer...
Which disease can be treated with Anifrolumab?
Anifrolumab is a type I interferon (IFN) receptor antagonist that has been shown to be effective for moderate-to-severe systemic lupus erythematosus (SLE).
Systemic lupus erythematosus (SLE) is an autoimmune disease with a polymorphic presentation. The variability in the clinical expression and severity of SLE makes new treatments both essential and challenging to develop. Several biotherapies targeting different pathophysiological pathways have been developed over th...