test.json

{"id": "converted_0", "sentence1": "Can losartan reduce brain atrophy in Alzheimer's disease?", "sentence2": "INTERPRETATION: 12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease.", "label": "no"}
{"id": "converted_6", "sentence1": "Is PRP-40 regulation of microexons a conserved phenomenon?", "sentence2": "PRP-40 regulation of neuronal microexons is therefore a widely conserved phenomenon.", "label": "yes"}
{"id": "converted_7", "sentence1": "Is casimersen effective for the treatment of Duchenne muscular dystrophy?", "sentence2": "Casimersen received its first approval on 25\u00a0February 2021, in the USA, for the treatment of DMD in patients who have a confirmed mutation of the DMD gene that is amenable to exon\u00a045 skipping. , he approval, granted under the US FDA Accelerated Approval Program, was based on an observed increase in dystrophin production in skeletal muscle in patients treated with casimersen", "label": "yes"}
{"id": "converted_9", "sentence1": "Is medical hydrology the same as Spa therapy?", "sentence2": "hydrotherapy,\" \"balneotherapy,\" \"spa therapy,\" \"spa treatment,\" \"creno-balneotherapy,\" \"water treatments,\" and \"aqua therapy,\" o, Spa therapy is an integral part of the treatment of burn scars. The objective of this systematic review is to provide an overview of the spa therapy used in the treatment of burn scars and analyze its effects reported in clinical studies. We used the PRISMA checklist and queried 8 scientific databases from August 2019 to July 2020 for articles referenced with the specific key words: (burn) AND ((spa) OR (crenotherap*) OR (sulfur bath) OR (balneo*) OR (hydrotherap*) OR (mineral water) OR (thermal water) OR (spring water) OR (health resort medicine)), Soon after qualification, Fortescue Fox (1858-1940) began practice in a Scottish spa where he acquired a lifelong interest in chronic disorders, especially arthritis. He worked to improve the status of spa medicine, recasting it as medical hydrology, He worked to improve the status of spa medicine, recasting it as medical hydrology.,  He worked to improve the status of spa medicine, recasting it as medical hydrology.", "label": "no"}
{"id": "converted_11", "sentence1": "Is eteplirsen effective for the treatment of Duchenne muscular dystrophy?", "sentence2": "Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p\u200a<\u200a0.01) and significantly attenuated rates of pulmonary decline vs. natural history patients (FVC%p change: -3.3 vs. -6.0 percentage points annually, p\u200a<\u200a0.0001)., At Years 3 and 4, eteplirsen-treated patients demonstrated markedly greater mean 6MWT than controls (difference in change from baseline of 132 m [95%CI (29, 235), p\u200a=\u200a0.015] at Year 3 and 159\u200am [95%CI (66, 253), p\u200a=\u200a0.002] at Year 4), At Year 4, a significantly greater proportion of eteplirsen-treated patients were still ambulant versus controls (10/12 vs 3/11; p\u200a=\u200a0.020),  In this retrospective matched control study, eteplirsen treatment resulted in attenuation of ambulatory decline over a 4-year observation period, supporting long-term benefit in patients with DMD.", "label": "yes"}
{"id": "converted_16", "sentence1": "Does CIDEB mutation protect from liver disease?", "sentence2": "Germline Mutations in CIDEB and Protection against Liver Disease., We also found that variants in CIDEB, which encodes a structural protein found in hepatic lipid droplets, had a protective effect. , CONCLUSIONS: Rare germline mutations in CIDEB conferred substantial protection from liver disease.", "label": "yes"}
{"id": "converted_19", "sentence1": "Is North Star Ambulatory Assessment score a reliable clinical outcome for disease progression assessment in Duchenne Muscular Dystrophy?", "sentence2": "The results showed a significant difference in the NSAA score between the deletion and nonsense groups at the age of 3 years (P\u2009=\u20090.04)., The boys were evaluated with standardized assessments at the screening and baseline visits at 32 sites in 5 countries (US, UK, Canada, Italy, Germany). Assessments included timed rise from floor, timed 10\u202fm walk/run, six-minute walk distance, North Star Ambulatory Assessment (NSAA) and forced vital capacity (FVC). Mean age at baseline was 5.9 years (range 4.1-8.1 years). Test-retest reliability was high for functional assessments, regardless of time lag between assessments (up to 90 days) and for the majority of age groups. Correlations were strong among the functional measures and timed tests, less so with FVC., The North Star Ambulatory Assessment (NSAA) is a validated 17-item functional rating scale and widely used to assess motor function in boys with Duchenne muscular dystrophy (DMD)., hese exploratory analyses reveal additional approaches to interpreting the NSAA data beyond just change in NSAA total score. These observations also highlight the importance of reporting items as \"not obtainable\" for a patient with a temporary/transient physical disability that impacts their ability to perform the NSAA test., measurement. All analyses were performed using the Rasch Unidimensional Measurement Model.RESULTS: Overall, Rasch analysis supported the NSAA as being a reliable (high Person Separation Index of 0.91) and valid (good targeting, little misfit, no reversed thresholds) measure of ambul, We hypothesised that boys with DMD could be clustered into groups sharing similar trajectories of ambulatory function over time, as measured by the North Star Ambulatory Assessment (NSAA) total score., INTRODUCTION: The North Star Ambulatory Assessment (NSAA) tool is a key instrument for measuring clinical outcomes in patients with Duchenne muscular dy, The North Star Ambulatory Assessment is a functional scale specifically designed for ambulant boys affected by Duchenne muscular dystrophy (DMD).,  North Star Ambulatory Assessment in Brazilian Portuguese is a reliable and valid instrument to measure functional capacity in boys with Duchenne muscular dystrophy., Functional variability among boys with Duchenne muscular dystrophy (DMD) is well recognised and complicates interpretation of clinical studies. We hypothesised that boys with DMD could be clustered into groups sharing similar trajectories of ambulatory function over time, as measured by the North Star Ambulatory Assessment (NSAA) total score.", "label": "yes"}
{"id": "converted_22", "sentence1": "Have chimeric antigen receptor (CAR)-T cell therapies been approved for the treatment of B cell malignancies?", "sentence2": "Engineered T cells have achieved success in the treatment of blood cancers, with four chimeric antigen receptor (CAR)-T cell therapies now approved for the treatment of B cell malignancies based on their unprecedented efficacy in clinical trials. ", "label": "yes"}
{"id": "converted_23", "sentence1": "Is golodirsen effective for the treatment of Duchenne muscular dystrophy?", "sentence2": "Golodirsen is a provisionally approved PMO-based drug for approx. 8% of all DMD patients amenable to exon 53 skipping. , This article summarizes the milestones in the development of golodirsen leading to this first approval for DMD., n December 2019, intravenous golodirsen received its first global approval in the USA for the treatment of DMD in patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping, based on positive results from a phase I/II clinical trial, To date, four PMOs, including eteplirsen, casimersen, viltolarsen, and golodirsen, have been conditionally approved by the FDA for the treatment of DMD., Golodirsen increased dystrophin protein (16.0-fold; P\u2009<\u20090.001) and exon skipping (28.9-fold; P\u2009<\u20090.001)., This study provides evidence for golodirsen biologic activity and long-term safety in a declining DMD population and suggests functional benefit versus external controls. ", "label": "yes"}
{"id": "converted_24", "sentence1": "Is Baricitinib effective for Alopecia Areata?", "sentence2": "Thus far, it has been approved for the treatment of rheumatoid arthritis (RA); however, an increasing number of studies have suggested that baricitinib can be used to treat dermatological diseases, such as atopic dermatitis (AD), psoriasis, vitiligo, and alopecia areata. , We reviewed the application, efficacy, side effects, precautions, limitations and prospect of baricitinib in atopic dermatitis, psoriasis, vitiligo and alopecia areata (AA) in recent 5 years including clinical trials and case reports. , Two Phase 3 Trials of Baricitinib for Alopecia Areata., CONCLUSIONS: In two phase 3 trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo with respect to hair regrowth at 36 weeks. ", "label": "yes"}
{"id": "converted_25", "sentence1": "Anemia is not associated with chronic kidney failure", "sentence2": "This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure, Anaemia is a common manifestation ofa chronic kidney failure. , The hormone deficiency that underlies anemia in chronic kidney failure can now be corrected, We call this interrelationship between congestive heart failure, chronic kidney insufficiency, and anemia the Cardio-Renal Anemia syndrome., Anemia is a major problem in patients with chronic kidney insufficiency., Correction of the anemia with erythropoietin and intravenous iron led to a marked improvement in patients' functional status and their cardiac function, and to a marked fall in the need for hospitalization and for high-dose diuretics; renal function usually improved or at least stabilized., The anemia is very often associated with chronic kidney disease (CKD)., The role of anemia in congestive heart failure and chronic kidney insufficiency: the cardio renal anemia syndrome., While iron deficiency is often stated as a cause of anemia in chronic renal failure prior to end-stage renal disease, its relative contribution is debated., Anemia in chronic renal failure is predominantly caused by diminished erythropoietin synthesis by diseased kidneys., We infer that impaired utilization of iron may be a significant factor in the anemia of chronic renal failure., BACKGROUND: Kidney failure causes anemia and is associated with a very high risk of coronary heart di, BACKGROUND: Kidney failure is known to cause anemia, which is associated with a higher risk of cardiac failure an, The correction of anemia in patients with the combination of chronic kidney disease and congestive heart failure may prevent progression of both conditions., BACKGROUND: Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin, In patients with CKD, anemia is often caused by decreased erythropoietin production relative to hemoglobin levels., Clearly more work is needed to clarify the relationship between anemia, CKD and CHF., Use of EPOGEN for treatment of anemia associated with chronic renal failure.,  Heart failure, anemia and chronic renal failure are mutually related., Uremic Toxins Affect Erythropoiesis during the Course of Chronic Kidney Disease: A Review.,  Partial, but not complete, correction of anemia is associated with improved outcomes in patients with CKD.,  The high prevalence of anemia in chronic kidney disease is explained by a combination of erythropoietin and iron deficiency.,  Many advanced chronic kidney disease patients have both anemia and chronic heart failure.,  In conclusion, anemia is associated with a rapid decrease in kidney function in patients with heart failure, particularly in those with underlying CKD.,  This analysis was conducted to evaluate whether anemia is a risk factor for kidney function decrease in patients with heart failure., Anemia as a risk factor for kidney function decline in individuals with heart failure., End stage renal disease (ESRD) invariably leads to anemia which has been mainly attributed to compromised release of erythropoietin from the defective kidneys with subsequent impairment of erythropoiesis., Chronic kidney disease (CKD) is a widespread health problem in the world and anaemia of renal origin is a common problem., Anemia is the most common hematologic complication in end-stage renal disease (ESRD). It is ascribed to decreased erythropoietin production, shortened red blood cell (RBC) lifespan, and inflammation., Anemia is one of the most characteristic and visable manifestations of chronic renal failure. Investigators in the past decade have provided a better understanding of this anemia. The etiology of the anemia of chronic renal failure has three facets: first is reduced erythropoietin production by damaged kidneys; second is the presence of inhibitors to red blood cell (RBC) production in uremic serum; and third is red blood cell hemolysis., Cardiovascular disease remains the major cause of mortality in patients with end stage renal disease (ESRD). The pathophysiology of cardiac dysfunction in ESRD is complex and not fully understood. However, it appears that the two major determinants of left ventricular (LV) hypertrophy and dysfunction are anemia and hypertension, both of which are very common in ESRD patients., NGAL, also known as lipocalin 2, is a stress protein located on the cell surface that is known for its involvement in iron transport. This study is aimed to evaluate the correlation between the iron profile and NGAL concentration in serum among chronic kidney disease patients under dialysis in order to find its diagnostic value with regards to iron deficiency anaemia (IDA).", "label": "no"}
{"id": "converted_27", "sentence1": "Is deflazacort more efficient than prednisone/prednisolone for the treatment of Duchenne muscular dystrophy?", "sentence2": "Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P\u2009<\u2009.001 for daily prednisone vs intermittent prednisone using a global test; P\u2009=\u2009.017 for daily deflazacort vs intermittent prednisone using a global test), Among patients with Duchenne muscular dystrophy, treatment with daily prednisone or daily deflazacort, compared with intermittent prednisone alternating 10 days on and 10 days off, resulted in significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and satisfaction with treatment, Deflazacort and prednisone/prednisolone are the current standard of care for patients with Duchenne muscular dystrophy (DMD) based on evidence that they improve muscle strength, improve timed motor function, delay loss of ambulation, improve pulmonary function, reduce the need for scoliosis surgery, delay onset of cardiomyopathy, and increase survival., Evidence from randomized clinical trials, prospective studies, meta-analyses, and post-hoc analyses suggests that patients receiving deflazacort experience similar or slower rates of functional decline compared with those receiving prednisone/prednisolone. , Though Deflazacort and prednisone improve clinical endpoints in Duchenne muscular dystrophy (DMD) patients, Deflazacort produces fewer side effects.,  trial. Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P\u2009<\u2009.001 for daily predn", "label": "no"}
{"id": "converted_29", "sentence1": "Is anaphylaxis a results of mast cell activation?", "sentence2": "Mast cells are important effector cells in allergic inflammatory reactions. The aggregation of the high-affinity IgE receptor (FcepsilonRI) on the surface of mast cells initiates a complex cascade of signaling events that ultimately leads to the release of various mediators involved in allergic inflammation and anaphylactic reactions, During the IgE-mediated anaphylactic reaction mast cells release proteases such as tryptase, histamine and vasoactive mediators, Histamine and other deleterious inflammatory mediators promote vascular permeability and smooth muscle contraction; they are readily released from sensitized mast cells and basophils challenged with antigen. Anaphylaxis may be triggered by a variety of antigens including insect and reptile venom, a variety of drugs, vaccines, and food, Earlier mast cells were only known for their important role in the type 1 allergic reactions (i.e. anaphylaxis or some contact hypersensitivity reactions) , Anaphylaxis results from severe systemic mast cell activation., In IgE-dependent and other examples of anaphylaxis, tissue mast cells and circulating basophilic granulocytes (basophils) are thought to represent major (if not the major) sources of the biologically active mediators that contribute to the pathology and, in unfortunate individuals, fatal outcome, of anaphylaxis., Mast cell activation syndromes presenting as anaphylaxis., PURPOSE OF REVIEW: Mast cell activation syndrome (MCAS) and anaphylaxis are the result of a spontaneous or triggered pathological degranulation of mast cells (MCs) and might have as substrate normal or pathological MCs (increased burden, aberrant MCs or both).RECENT FINDINGS: This review summarizes the most recent evidence on immunoglobulin E (IgE)-mediated and non IgE-mediated mechanisms underlying MC activation and degranulation and highlights the importance of standa, Elevated mast cell mediators such as tryptase and histamine have been reported during episodes, and mast cells are considered the primary cells responsible for driving anaphylaxis in humans., In this chapter, we will describe the mechanisms of mast cell (and basophil) activation in anaphylaxis, with a focus on IgE-dependent activation, which is thought to be responsible for most examples of antigen-induced anaphylaxis in humans., Anaphylaxis is a life-threatening syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation., Some usual clinical manifestations in anaphylaxis, such as angioedema or hypotension, or other less common, such as metrorrhagia, may be explained by the direct effect of the activation of the coagulation and contact system driven by mast cell mediators., Idiopathic anaphylaxis involves mast cell activation (acutely elevated urine histamine or serum tryptase) and activated lymphocytes., When there is activation of mast cells and basophils in anaphylaxis, chemical mediators are detectable., Systemic anaphylaxis arises when mast cells, possibly along with other cell types, are provoked to secrete mediators that evoke a systemic response., Anaphylaxis results from the massive activation of the mast cells (MCs)., Human mast cells, by elaborating vasoactive mediators and cytokines, are the primary effector cells of anaphylaxis.,  Although the mast cell is considered the major effector cell during acute allergic reactions, more recent studies indicate a potentially important and specific role for basophils and their migration which occurs rapidly upon allergen challenge in humans undergoing anaphylaxis., Acute anaphylaxis to small molecule drugs is largely considered to be antibody-mediated with immunogloblin E (IgE) and mast cell activation being key., Anaphylactic Degranulation of Mast Cells: Focus on Compound Exocytosis., Idiopathic Anaphylaxis: A Form of Mast Cell Activation Syndrome.,  A precondition for the unfolding of the anaphylactic shock is the secretion of inflammatory mediators from mast cells in response to an allergen, mostly through activation of the cells via the IgE-dependent pathway.,  Beyond IgE-mediated activation of mast cells/basophils, further mechanisms are involved in the occurrence of anaphylaxis.,  When there is activation of mast cells and basophils in anaphylaxis, chemical mediators are detectable., Extensive activation of mast cells is the major switch that triggers systemic anaphylaxis, resulting in the subsequent release of anaphylactic mediators into circulation., ed in the amplification of the mast cell response during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the critical involvement of , phylaxis in 22-49%. In addition, monoclonal mast cell activation syndrome has been described presenting with anaphylaxis, especially in patients with , ol subjects. The severity of anaphylaxis was associated with mast cell degranulation, increased plasma heparin levels, the intensity of contact system,  types. Finally, we discuss the possible reasons for the mast cell to utilize compound exocytosis during anaphylaxis, the conflicting evidence in diff, w clinical entities, such as the \u03b1-gal anaphylaxis. Anaphylaxis results from the massive activation of the mast cells (MCs). Thus, it is also necessar, ted that mast cell activation and anaphylaxis are negatively regulated by AMP-activated protein kinase (AMPK). However, little is known about the rela, s not affected. Calcium-independent early activation events in mast cell anaphylaxis indicated on inhibitory influence of PK-treatment. Inhibition of , phylaxis in 22-49%. In addition, monoclonal mast cell activation syndrome has been described presenting with anaphylaxis, especially in patients with hymenopter, ol subjects. The severity of anaphylaxis was associated with mast cell degranulation, increased plasma heparin levels, the intensity of contact system activation, and bradykin,  types. Finally, we discuss the possible reasons for the mast cell to utilize compound exocytosis during anaphylaxis, the conflicting evidence in different mast cell models, and the open questions in the field which remain to be a, arepsilonRI) on mast cells. However, the regulatory mechanism of mast cell activation i, s not affected. Calcium-independent early activation events in mast cell anaphylaxis indicated on inhibitory influence , r, Ang-1's function in mast cell activation and anaphylaxis diseases is unknown. The results of our study suggest that Ang-1 decreased lipopolysacchar, \u03b5RI-mediated mast cell activation and anaphylaxis that were insensitive to U0126 or activator 5-aminoimidazole-4-carboxamide-1-\u03b2-4-ribofuranoside, suggesting that the suppression of Fc\u03b5RI signals by the inhibition of the ERK1/2 pathway relies largely on AMPK activation. ERK1/2 controlled AMPK activity by regulating its subcellul, Anaphylaxis results from severe systemic mast cell activation. In addition to IgE-mediated and physical triggers, it may occur with a clonal mast cell, For half a century, it has been known that the mast cell is the cell responsible for the majority of anaphylactic events. Its mediators, taken as a whole, are capable of producing all of the clinical manifestations of these events., Anaphylaxis results from severe systemic mast cell activation. In addition to IgE-mediated and physical triggers, it may occur with a clonal mast cell disease and in an idiopathic fashion without clear provoking factors., Anaphylaxis is a rapidly developing, life-threatening, generalized or systemic allergic reaction that is classically elicited by antigen crosslinking of antigen-specific IgE bound to the high-affinity IgE receptor Fc\u03b5RI on mast cells and basophils., Anaphylaxis is a rapidly evolving, acute, life-threatening reaction that occurs rapidly on contact with a trigger. Anaphylaxis is classically defined as an allergen-driven process that induces specific IgE and the activation of mast cells and basophils through the cross-linking of IgE receptors.", "label": "yes"}
{"id": "converted_31", "sentence1": "Is viltolarsen effective for the treatment of Duchenne muscular dystrophy?", "sentence2": "Viltolarsen is a phosphorodiamidate morpholino antisense oligonucleotide (PMO) designed to skip exon 53 of the DMD gene\u00a0for the treatment of Duchenne muscular dystrophy (DMD), Viltolarsen restores the reading frame of the DMD gene by skipping \u00a0exon 53\u00a0and produces a truncated but functional form of dystrophin. , After showing hopeful results in pre-clinical trials and several clinical trials across North America and Japan, it received US Food and Drug Administration (FDA) approval for DMD\u00a0in 2020., Viltolarsen restores the reading frame of the DMD gene by skipping \u00a0exon 53\u00a0and produces a truncated but functional form of dystrophin., ucleotide viltolarsen targets exon 53 of the dystrophin gene, and could be an effective treatment for patients with Duchenne muscular dystrophy (DMD)., esulting in an absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, has been shown to increase endogenous dystrophin levels. Herein, long-term (>2 years) functional outcomes in viltolarsen treated pati", "label": "yes"}
{"id": "converted_34", "sentence1": "Can the concept of digital twins be applied in Precision Nutrition?", "sentence2": "The \"Virtual Digital Twins\" Concept in Precision Nutrition, We herein discuss how genetic information combined with longitudinal metabolomic, immune, behavioral, and gut microbial parameters, and bioclinical variables could define a digital replica of oneself, a \"virtual digital twin,\" which could serve to guide nutrition in a personalized manner.", "label": "yes"}
{"id": "converted_38", "sentence1": "Based on clinical trial data, can pioglitazone delay cognitive impairment for people at risk for Alzheimer's disease?", "sentence2": "INTERPRETATION: Pioglitazone did not delay the onset of mild cognitive impairment.", "label": "no"}
{"id": "converted_40", "sentence1": "Does silencing of SRRM4 promote microexon inclusion?", "sentence2": "SRRM4 Expands the Repertoire of Circular RNAs by Regulating Microexon Inclusion., Overexpressing SRRM4, known for regulating ME inclusion in mRNAs critical for neural differentiation, in human HEK293 cells resulted in the biogenesis of over 2000 novel ME-circRNAs, including ME-circEIF4G3, and changes in the abundance of many canonical circRNAs, including circSETDB2 and circLBRA. ", "label": "no"}
{"id": "converted_47", "sentence1": "Is levosimendan effective for amyotrophic lateral sclerosis?", "sentence2": "INTERPRETATION: Levosimendan was not superior to placebo in maintaining respiratory function in a broad population with amyotrophic lateral sclerosis. Although levosimendan was generally well tolerated, increased heart rate and headache occurred more frequently with levosimendan than with placebo., CONCLUSIONS: Levosimendan did not achieve the primary endpoint of improving sitting SVC in ALS. Headache and increased heart rate were increased on levosimendan, although it was otherwise well tolerated. ", "label": "no"}
{"id": "converted_54", "sentence1": "Is Iron deficiency anemia a common complication of chronic kidney disease?", "sentence2": "Intravenous iron therapy is increasingly being used worldwide to treat anemia in chronic kidney disease and more recently iron deficiency in heart failure.,  iron deficiency in patients with chronic kidney disease (CKD), either with or without anaemia. , Iron deficiency, both functional and absolute, is common in patients with chronic kidney disease (CKD), especially those requiring dialysis., Treatment with iron preparations remains one of the main directions in the treatment of anemia in patients with chronic kidney disease., This work presents an update on the management of iron deficiency in patients with chronic renal failure (CRF), either with or without anaemia., ron replacement therapy in the management of anaemia in non-dialysis chronic renal failure patients:, Iron deficiency anemia is a common complication of chronic kidney disease (CKD)., Iron Deficiency Anemia in Chronic Kidney Disease., BACKGROUND: Iron deficiency anemia (IDA) is a common manifestation of chronic kidney disease (CKD), affecting most patients on hemodialysis and imposing a substantial clin, Anemia is a common complication of chronic kidney disease (CKD) in predialysis stage., Anemia is a common and clinically important consequence of chronic kidney disease (CKD)., Among CKD patients, absolute iron deficiency is defined when the transferrin saturation (TSAT) is \u226420% and the serum ferritin concentration is \u2264100 ng/mL among predialysis and peritoneal dialysis patients or \u2264200 ng/mL among hemodialysis patients., BACKGROUND: Iron deficiency anemia is a common complication in patients with chronic kidney di, Iron deficiency anemia (IDA) is a frequent complication of chronic kidney disease (CKD) and is associated with adverse outcomes in these patients., Iron deficiency anemia is a common complication in end-stage renal disease (ESRD) and impairs the therapeutic efficacy of recombinant erythropoietin., Anemia in CKD is associated with an increased risk of morbidity and mortality., BACKGROUND: Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function, cardiovascular events, and mortality.STUDY DESIGN: Double-blind, placebo-controlled, randomized trial.SETTING & PARTICIPANTS: 149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m(2), iron deficiency anemia (hemoglobin, 9.0-12.0 g/dL; transferrin saturation [TSAT]\u2264 30%, serum ferritin \u2264 300 ng/, Anemia resulting from iron and erythropoietin deficiencies is a common complication of advanced chronic kidney disease (CKD)., Iron deficiency is common in individuals with chronic kidney disease and plays a major role in the development of anemia., Iron deficiency anemia is a common occurrence in patients with chronic kidney disease and many patients do not respond well to supplementation with oral iron., However, the diagnosis of iron-deficiency anemia in CKD patients is complicated by the relatively poor predictive ability of easily obtained routine serum iron indices (eg, ferritin and transferrin saturation) and more invasive gold standard measures of iron deficiency (eg, bone marrow iron stores) or erythropoietic response to supplemental iron., Iron deficiency in patients with chronic kidney disease: potential role for intravenous iron therapy independent of erythropoietin., Iron deficiency anemia is common in people with chronic kidney disease (CKD) and its importance in supporting erythropoiesis is unquestioned especially in those patients treated with erythropoietin.,  Limited data suggest that iron deficiency is common in patients with chronic kidney disease with anemia; this lack of iron can hinder the effectiveness of erythropoiesis., Anemia is a frequent complication of kidney disease., Anemia is a common complication of chronic kidney disease., Severe anemia and iron deficiency are common complications in chronic kidney disease., Iron deficiency anemia is common in people with chronic kidney disease (CKD) and its importance in supporting erythropoiesis is unquestioned especiall, Iron deficiency anemia is a common complication of chronic kidney disease (CKD). CKD patients suffer from both absolute and functional iron deficiency,  diabetic nephropathy is a leading cause of CKD. One of the most common complications of CKD is anemia, the frequency and severity of which increase a, Anemia is as a frequent complication in patients with chronic kidney disease, which gains in importance in the treatment of patients with renal diseas, Severe anemia and iron deficiency are common complications in chronic kidney disease. The cause of renal anemia is multifactorial and includes decreas, Anemia is a common complication in patients with chronic kidney disease (CKD), mainly due to inadequate renal production of erythropoietin. In hemodia, o anemia. The other cause of anemia is deficiency of iron. Iron deficiency anemia is common in people with CKD and its importance in supporting erythr, Anemia is as a frequent complication in patients with chronic kidney disease, which gains in importance in the treatment of patients with renal disease.,  development and treat complications including anemia. Anemia is one of the common complication of chronic kidney disease (CKD), which is a significan, The diagnosis of iron deficiency anemia in patients with CKD is complicated due to the relatively low predictive ability of routine serum iron markers (e.g., ferritin and transferrin saturation) and more invasive measurements such as bone marrow iron stores., Anemia is a frequent complication in chronic kidney disease (CKD), and it is often accompanied by various clinical symptoms. The primary cause of anem, Iron deficiency anemia is a common complication of chronic kidney disease (CKD). CKD patients suffer from both absolute and functional iron deficiency., Anemia is a frequent complication during the later stages of chronic kidney disease., Anemia in chronic kidney disease is common and iron deficiency is an important cause., nemia in chronic kidney disease, nemia is common and associated with adverse outcomes in children with chronic kidney disease (CKD, e treatment of anemia in chronic kidney disease., he prevalence of iron deficiency and its contribution to the anemia of end stage renal disease has been extensively studied, but much less is known about the role of iron deficiency in the pathogenesis of the anemia of chronic kidney disease in predialysis patients., nemia in renal disease: diagnosis and manageme, Anemia is a very common clinical problem in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality in these patients., Safety issues with intravenous iron products in the management of anemia in chronic kidney disease.,  Deciding on the appropriate treatment for anemia associated with CKD, nemia in chronic kidney disease, Anemia in ESRD and Earlier Stages of CKD,  Ferumoxytol for Anemia of CKD Trial ,  anemia and reduction of serum phosphate in patients with CKD, Chronic kidney disease (CKD) is a widespread health problem in the world and anemia is a common complication, nemia in diabetic kidney disease - underappreciated but still clinically relevant proble, Anemia in children with chronic kidney disease, nemia in children with chronic kidney disease (CKD) is common secondary to inadequate erythropoietin production, echanisms of anemia in CKD, Anemia is a common feature of CKD associated with poor outcomes., he current management of patients with anemia in CKD is controversial, with recent c, Here, we examine recent insights into the molecular mechanisms underlying anemia of CKD, nemia of Inflammation with An Emphasis on Chronic Kidney Disease,  Treatment of Anemia in Patients with Chronic Kidney Disease, nemia is a common complication of chronic kidney disease (CKD), and its prevalence has shown a tendency to increase in many countries., ythropoietin resistance in the treatment of the anemia of chronic renal failure, esistance to erythropoietin therapy is a common complication of the modern management of anemia in chronic kidney disease, spectrum of anemia in non-dialysis-dependent chronic kidney disease,  retrospective study was conducted over seven years and it aimed to find out various causes of anemia among patients with chronic kidney disease (CKD)., safety and efficacy of ferumoxytol therapy in anemic chronic kidney disease patients., options for the anemia of chronic kidney disease., nemia is a common complication of chronic kidney disease, Urology and nephrology update: anemia of chronic kidney disease., Anemia is associated with chronic kidney disease (CKD) at all stages, and it is nearly universal among patients with stage 5 CKD, nemia in Chronic Kidney Disease: , nemia is a common complication in chronic kidney disease (CKD), and is associated with a reduced quality of life,, Anemia and its predictors among adult non-dialysis chronic kidney disease patients in Southern Ethiopia: a cross-sectional study., Anemia is an adverse outcome and common complication in chronic kidney disease patient, Prevalence of malnutrition and absolute and functional iron deficiency anemia in nondialysis-dependent chronic kidney disease and hemodialysis Algerian patients],  chronic kidney disease, anemia and malnutrition coupled with inflammation as malnutrition-inflammation complex syndrom are common and considered as morbidity-mortality factors, f Anemia in Chronic Kidney Disease: Beyond Erythropoietin, nemia is a frequent comorbidity of chronic kidney disease (CKD) ", "label": "yes"}
{"id": "converted_55", "sentence1": "Can modulation of KCNQ1 splicing prevent arrhythmias?", "sentence2": "Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia.", "label": "yes"}
{"id": "converted_58", "sentence1": "Is trichotillomania encountered with equali frequency in males and females?", "sentence2": "The disease affects mainly female patients, who often deny the habit, and it usually presents with a bizarre pattern nonscarring patchy alopecia with short hair and a negative pull test. ", "label": "no"}
{"id": "converted_64", "sentence1": "Does microexon alternative splicing of small GTPase regulators have implication in central nervous system diseases?", "sentence2": "Microexon alternative splicing of small GTPase regulators: Implication in central nervous system diseases., We further discuss the emerging evidence for dysregulation of the Rho GTPase pathway in CNS diseases and the consequences contributed by the mis-splicing of microexons. ", "label": "yes"}
{"id": "converted_69", "sentence1": "Is prosopagnosia also known as lack of auditory recognition?", "sentence2": "Prosopagnosia is a visual agnosia characterized by an inability to recognize previously known human faces and to learn new faces, Prosopagnosia is a type of visual agnosia with inability to identify faces, usually secondary to brain lesion in associative cortex areas, but there is also a congenital form known as developmental prosopagnosia., These results indicate that, in some subjects with developmental prosopagnosia, the face recognition deficit is not an isolated impairment but is associated with deficits in other domains, such as auditory perception., Prosopagnosia (PA) or face blindness is characterized by a deficiency in identifying familiar faces., The apparent selectivity of agnosia for faces is termed prosopagnosia or face blindness., In recent years, prosopagnosia is defined as the \"loss of ability to recognize the well-acquainted persons like the family members by their physiognomy.\", The patient is unable to recognize faces or cars, consistent with his prosopagnosia and object agnosia, respectively., Anecdotally, it has been reported that individuals with acquired prosopagnosia compensate for their inability to recognize faces by using other person identity cues such as hair, gait or the voice., Visual object agnosia refers to the inability to recognize objects and prosopagnosia to the failure to recognize faces that are well familiar to the patient, when stimuli are visually perceived., Since face recognition is the most powerful source of information for identifying familiar people, patients showing a multimodal defect in people recognition have been sometimes considered as affected by \"prosopagnosia\"-namely, by a form of visual agnosia, specifically affecting face recognition., Prosopagnosia is a selective visual agnosia characterized by the inability to recognize the identity of faces., Prosopagnosia is a rare neurological sign, characterized by disturbance of recognition of faces., INTRODUCTION: The prosopagnosia has generally been defined as an incapacity to recognize familiar faces, or faces previously known, due to certain lesions to certain areas of the ce, Developmental prosopagnosia (DP) is a condition characterised by lifelong face recognition difficulties., BACKGROUND: Developmental prosopagnosia is a disorder of face recognition that is believed to reflect impairments of visual mechanisms. However, voice recognition has rarely been evaluated in developmental pro, Prosopagnosia is a selective impairment of the visual learning and recognition of faces.,  This rarely studied form of prosopagnosia ensures that deficits are limited to face recognition., Prosopagnosia is the inability to recognize someone by the face alone in the absence of sensory or intellectual impairment. In contrast to the acquire", "label": "no"}
{"id": "converted_72", "sentence1": "Do cells undergoing necroptosis show disruption of their cell membranes?", "sentence2": "Necroptosis is a form of caspase-independent programmed cell death that arises from disruption of cell membranes by the mixed lineage kinase domain-like (MLKL) pseudokinase after its activation by the upstream kinases, receptor interacting protein kinase (RIPK)-1 and RIPK3, within a complex known as the necrosome, Thus, cells undergoing necroptosis need to overcome these independent suppressive mechanisms before plasma membrane disruption can occur., Taken together, these results confirm the active role of VLCFAs during necroptosis and point to multiple potential mechanisms of membrane disruption including direct permeabilization via bilayer disruption and permeabilization by targeting of proteins to cellular membranes by fatty acylation., Necroptosis is a form of caspase-independent programmed cell death that arises from disruption of cell membranes by the mixed lineage kinase domain-like (MLKL) pseudokinase after its activation by the upstream kinases, receptor interacting protein kinase (RIPK)-1 and RIPK3, within a complex known as the necrosome., Necroptosis is a form of regulated cell death which results in loss of plasma membrane integrity, release of intracellular contents, and an associated inflammatory response., Here, we show that, during necroptosis, MLKL-dependent calcium (Ca2+) influx and phosphatidylserine (PS) exposure on the outer leaflet of the plasma membrane preceded loss of PM integrity., Membrane Disruption by Very Long Chain Fatty Acids during Necroptosis., The activation of mixed lineage kinase-like (MLKL) by receptor-interacting protein kinase-3 (RIPK3) results in plasma membrane (PM) disruption and a form of\u00a0regulated necrosis, called necroptosis., Necroptosis is a highly inflammatory form of programmed cell death that results from MLKL-mediated disruption of the cell membrane., Necroptosis, a form of programmed cell death, is characterized by the loss of membrane integrity and release of intracellular contents, the execution of which depends on the membrane-disrupting activity of the Mixed Lineage Kinase Domain-Like protein (MLKL) upon its phosphorylation., Here we report that, following sciatic nerve injury, MLKL, a pseudokinase known to rupture cell membranes during necroptotic cell death, is induced and targets the myelin sheath membrane of Schwann cells to promote myelin breakdown., Under conditions of necroptotic cell death, ESCRT-III controls the duration of plasma membrane integrity., Necroptosis induction leads to cell membrane disruption, inflammation and vascularization.,  Both necrosis and necroptosis show similar morphological features and are characterized by an increase in cell volume, cell membrane permeabilization, and rupture that lead to cellular demise.,  Thus, cells undergoing necroptosis need to overcome these independent suppressive mechanisms before plasma membrane disruption can occur., chanisms by which the essential, and possibly terminal, necroptotic effector, MLKL, triggers the disruption of cellular membranes to cause cell lysis., uring necroptosis. We show that MLKL and phosphoMLKL, key for membrane permeabilization, are exclusively acylated during necroptosis. Reducing the lev, anslocates to and disrupts the plasma membrane, thereby causing necroptotic cell lysis. Herein, we show that activation of necroptosis in mouse dermal, Necroptosis is a programmed cell death pathway triggered by activation of receptor interacting protein kinase 3 (RIPK3), which phosphorylates and activates the mixed lineage kinase-like domain pseudokinase, MLKL, to rupture or permeabilize the plasma membrane.,  non-inflammatory process while necrosis triggers inflammation. Recent studies on necroptosis and pyroptosis, two types of programmed necrosis, revealed that plasma membrane rupture is mediated by MLKL channels during necroptosis but depen", "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", "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", "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. ", "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.", "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. ", "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.", "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", "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.", "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.", "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. ", "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.", "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.", "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).", "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.", "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. ", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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). ", "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. ", "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. ", "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.", "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.", "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.", "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.", "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.", "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. ", "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.", "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).", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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. ", "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.", "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.", "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.", "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. ", "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.", "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.", "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. ", "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.", "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.", "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. ", "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", "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.", "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 ", "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.", "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.", "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.", "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).", "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.", "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", "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.", "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).", "label": "no"}