{"id":"5c58a74e86df2b917400000d","question":"Is Baloxavir effective for influenza?","context":"Baloxavir marboxil (Xofluza\u2122; baloxavir) is an oral cap-dependent endonuclease inhibitor that has been developed by Roche and Shionogi. The drug blocks influenza virus proliferation by inhibiting the initiation of mRNA synthesis. In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections.  This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections. Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. BACKGROUND: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents. CONCLUSIONS: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. A single oral dose of baloxavir is usually well tolerated; it hastens alleviation of influenza symptoms and shortens the duration of viral shedding. Japan was the first country to approve baloxavir marboxil as a treatment for influenza. This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections.<br> In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections.","answer":"yes"}
{"id":"5be44bef133db5eb78000014","question":"Are there microbes in human breast milk?","context":"Contrary to long-held dogma, human milk is not sterile. Instead, it provides infants a rich source of diverse bacteria, particularly microbes belonging to the Staphylococcus, Streptococcus, and Pseudomonas genera. The origins of the bacteria in milk are thought to include the maternal gastrointestinal tract (via an entero-mammary pathway) and through bacterial exposure of the breast during nursing.","answer":"yes"}
{"id":"5c61bacae842deac67000001","question":"Is cariprazine effective for treatment of bipolar disorder?","context":"BACKGROUND: We evaluated the safety\/tolerability of longer-term open-label treatment with cariprazine in patients who had responded to cariprazine for acute bipolar mania. Clinically relevant response and remission outcomes in cariprazine-treated patients with bipolar I disorder. Cariprazine is FDA approved for the acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults. DISCUSSION: Cariprazine-treated patients with bipolar I disorder attained clinically significant improvement in manic symptoms as shown by significantly greater rates of response and remission versus placebo; improvement in manic symptoms did not induce depressive symptoms. OBJECTIVE: Cariprazine, a dopamine D3\/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. <b>BACKGROUND<\/b>: Cariprazine was approved for treating schizophrenia and bipolar disorder, and currently is being evaluated for treating depression in clinical trials in the United States.","answer":"yes"}
{"id":"5c55d75807647bbc4b000008","question":"Is Bobble head doll syndrome associated with hydrocephalus?","context":"The first is a 14-year-old boy with BHDS associated with aqueductal obstruction and triventricular hydrocephalus secondary to a tectal tumor. Brain magnetic resonance imaging showed a large suprasellar arachnoid cyst extending into the third ventricle, with obstructive hydrocephalus, characteristic of bobble-head doll syndrome.  MRI Scan showed a large contrast-enhanced lesion in the region of the third ventricle along with gross hydrocephalus.  Bobble-head doll syndrome is usually associated with dilation of the third ventricle, but is rarely associated with posterior fossa disease.PATIENT: We describe an infant with fetal hydrocephalus and an arachnoid cyst of the posterior fossa. All the patients presented a psychomotor retardation due to an obstructive hydrocephalus.  Suprasellar arachnoid cysts can have varied presentations with signs and symptoms of obstructive hydrocephalus, visual impairment, endocrinal dysfunction, gait ataxia and rarely bobble-head doll movement. We present three cases with bobble-head doll syndrome associated with a large suprasellar arachnoid cyst and obstructive hydrocephalus, which were treated with endoscopic cystoventriculocisternostomy and marsupialization of the cyst.","answer":"yes"}
{"id":"5be44f50133db5eb78000017","question":"Can breastfeeding confer protection from type I diabetes?","context":"In the neonate and infant, among other benefits, lactation confers protection from future both type 1 and type 2 diabetes.","answer":"yes"}
{"id":"5be47bff133db5eb78000018","question":"Can pets affect infant microbiomed?","context":"Since there is some evidence that pets also alter the gut microbial composition of infants, changes to the gut microbiome are putative pathways by which pet exposure can reduce these risks to health. The impact of pet ownership varies under different birth scenarios; however, in common, exposure to pets increased the abundance of two bacteria, Ruminococcus and Oscillospira, which have been negatively associated with childhood atopy and obesity. As a common effect in all birth scenarios, pre- and postnatal pet exposure enriched the abundance of Oscillospira and\/or Ruminococcus (P\u2009<\u20090.05) with more than a twofold greater likelihood of high abundance. Among vaginally born infants with maternal intrapartum antibiotic prophylaxis exposure, Streptococcaceae were substantially and significantly reduced by pet exposure (P\u2009<\u20090.001, FDRp\u2009=\u20090.03), reflecting an 80% decreased likelihood of high abundance (OR 0.20, 95%CI, 0.06-0.70) for pet exposure during pregnancy alone and a 69% reduced likelihood (OR 0.31, 95%CI, 0.16-0.58) for exposure in the pre- and postnatal time periods. Exposure to household furry pets influences the gut microbiota of infant at 3-4\u00a0months following various birth scenarios.","answer":"yes"}
{"id":"5be48282133db5eb7800001b","question":"Is there any association between the human gut microbiome and depression?","context":"Moreover, recent findings are suggestive of the possibility that dysregulation of the enteric microbiota (i.e., dysbiosis) and associated bacterial translocation across the intestinal epithelium may be involved in the pathophysiology of stress-related psychiatric disorders, particularly depression.","answer":"yes"}
{"id":"5c2f8127133db5eb78000032","question":"Are whole-genome duplications more divergent than small-scale duplications in yeast?","context":"Also, we observe that transporter and glycolytic genes have a higher probability to be retained in duplicate after WGD and subsequent gene loss, both in the model as in S. cerevisiae, which leads to an increase in glycolytic flux after WGD We show that the retention of genes in duplicate in the model, corresponds nicely with those retained in duplicate after the ancestral WGD in S. cerevisiae Thus, our model confirms the hypothesis that WGD has been important in the adaptation of yeast to the new, glucose-rich environment that arose after the appearance of angiosperms. Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts. The results uncover the WGD as a major source for the evolution of a complex interconnected block of transcriptional pathways. These selected pairs, both WGD and SSD, tend to have decelerated functional evolution, have higher propensities of co-clustering into the same protein complexes, and share common interacting partners. Moreover, we find additional transcriptional profiles that are suggestive of neo- and subfunctionalization of duplicate gene copies. These patterns are strongly correlated with the functional dependencies and sequence divergence profiles of gene copies. Functional and transcriptional divergence between the copies after gene duplication has been considered the main driver of innovations . Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts. Empirical data shows that whole-genome duplications (WGDs) are more likely to be retained than small-scale duplications (SSDs), though their relative contribution to the functional fate of duplicates remains unexplored.","answer":"yes"}
{"id":"5c34794fda8336e21a000001","question":"Do yeast LTR give rise to circular DNA?","context":"Circular retrotransposition products generated by a LINE retrotransposon Formation of Extrachromosomal Circular DNA from Long Terminal Repeats of Retrotransposons in Saccharomyces cerevisiae Ty eccDNA can arise from the circularization of extrachromosomal linear DNA during the transpositional life cycle of retrotransposons, or from circularization of genomic Ty DNA Circularization may happen through nonhomologous end-joining (NHEJ) of long terminal repeats (LTRs) flanking Ty elements, by Ty autointegration, or by LTR-LTR recombination We have recently shown that yeast LTR elements generate circular DNAs through recombination events between their flanking long terminal repeats (LTRs). Similarly, circular DNAs can be generated by recombination between LTRs residing at different genomic loci, in which case the circular DNA will contain the intervening sequence. A recent study on circular DNAs in yeast found that transposable element sequence residing in circular structures mostly corresponded to full-length transposable elements.","answer":"yes"}
{"id":"5c644c3de842deac67000018","question":"Is cohesin linked to myeloid differentiation?","context":"Consistent with a role for inflammatory signals in promoting myeloid differentiation of hematopoietic stem and progenitor cells (HPSCs), cohesin mutations in HSPCs led to reduced inflammatory gene expression and increased resistance to differentiation-inducing inflammatory stimuli. These findings uncover an unexpected dependence of inducible gene expression on cohesin, link cohesin with myeloid differentiation, and may help explain the prevalence of cohesin mutations in human acute myeloid leukemia. Consistent with a role for inflammatory signals in promoting myeloid differentiation of hematopoietic stem and progenitor cells (HPSCs), cohesin mutations in HSPCs led to reduced inflammatory gene expression and increased resistance to differentiation-inducing inflammatory stimuli. These findings uncover an unexpected dependence of inducible gene expression on cohesin, link cohesin with myeloid differentiation, and may help explain the prevalence of cohesin mutations in human acute myeloid leukemia.<br>","answer":"yes"}
{"id":"5be49287133db5eb7800001e","question":"Is pembrolizumab effective against Ewing's sarcoma?","context":"None of the 13 patients with Ewing's sarcoma had an objective response.  Between March 13, 2015, and Feb 18, 2016, we enrolled 86 patients, 84 of whom received pembrolizumab (42 in each disease cohort) and 80 of whom were evaluable for response (40 in each disease cohort).","answer":"no"}
{"id":"5be94b87133db5eb78000020","question":"Can gene therapy restore auditory function?","context":"Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c. We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.","answer":"yes"}
{"id":"5c58447f07647bbc4b000021","question":"Is the PINES framework being used for the prediction of coding variants?","context":"PINES: phenotype-informed tissue weighting improves prediction of pathogenic noncoding variants. Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding Element Scoring), which predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner. PINES enables analyses to be customized towards genomic annotations from cell types of the highest relevance given the phenotype of interest. We illustrate that PINES identifies functional noncoding variation more accurately than methods that do not use phenotype-weighted knowledge, while at the same time being flexible and easy to use via a dedicated web portal. Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding Element Scoring), which predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner. We illustrate that PINES identifies functional noncoding variation more accurately than methods that do not use phenotype-weighted knowledge, while at the same time being flexible and easy to use via a dedicated web portal.<br> PINES enables analyses to be customized towards genomic annotations from cell types of the highest relevance given the phenotype of interest.","answer":"no"}
{"id":"5c647c52e842deac6700001c","question":"Is erythropoietin effective for treatment of amyotrophic lateral sclerosis?","context":"This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.METHODS: Analyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes. CONCLUSIONS: RhEPO 40,000\u2005IU fortnightly did not change the course of ALS. At 12\u2005months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23\u2005h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline.","answer":"no"}
{"id":"5c6638717c78d69471000012","question":"Is celecoxib effective for treatment of amyotrophic lateral sclerosis?","context":"NTERPRETATION: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. A biological effect of celecoxib was not demonstrated in the cerebrospinal fluid. Further studies of celecoxib at a dosage of 800 mg\/day in ALS are not warranted. Prostaglandin E(2) levels in cerebrospinal fluid were not elevated at baseline and did not decline with treatment.<br><b>INTERPRETATION<\/b>: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe.","answer":"no"}
{"id":"5c531e887e3cb0e231000018","question":"Are ultraconserved enhancers important for normal development?","context":"Ultraconserved Enhancers Are Required for Normal Development. However, initial deletion studies in mice revealed that loss of such extraordinarily constrained sequences had no immediate impact on viability. Here, we show that ultraconserved enhancers are required for normal development.  Here, we show that ultraconserved enhancers are required for normal development.","answer":"yes"}
{"id":"5c5f12d91a4c55d80b000016","question":"Is chlorotoxin a peptide?","context":"chlorotoxin peptide  Chlorotoxin (CTX) is a 36-amino-acid disulfide-containing peptide derived from the venom of the scorpion Leiurus quinquestriatus. The mature Odontobuthus doriae chlorotoxin peptide has a 35-amino-acid residue and four disulfide bounds.  Chlorotoxin (CTX), a disulfide-rich peptide from the scorpion Leiurus quinquestriatus,","answer":"yes"}
{"id":"5c00f38e133db5eb78000023","question":"Does vesatolimod inhibit TLR7?","context":"Vesatolimod (GS-9620) is an oral agonist of toll-like receptor 7, an activator of innate and adaptive immune responses.","answer":"no"}
{"id":"5c5f21a81a4c55d80b00001c","question":"Is selenocysteine an aminoacid?","context":"Selenocysteine (Sec), a rare genetically encoded amino acid with unusual chemical properties, is of great interest for protein engineering. Selenocysteine (SeC) is a naturally available Se-containing amino acid that displays splendid anticancer activities against several human tumors.","answer":"yes"}
{"id":"5c58923c86df2b9174000005","question":"Is Tecovirimat effective for smallpox?","context":"Oral Tecovirimat for the Treatment of Smallpox. CONCLUSIONS: On the basis of its efficacy in two animal models and pharmacokinetic and safety data in humans, tecovirimat is being advanced as a therapy for smallpox in accordance with the FDA Animal Rule. Background: Tecovirimat (ST-246) is being developed as an antiviral therapeutic for smallpox for use in the event of an accidental or intentional release.  Conclusions: Tecovirimat treatment initiated up to 8 days following a lethal aerosol MPXV challenge improves survival and, when initiated earlier than 5 days after challenge, provides protection from clinical effects of disease, supporting the conclusion that it is a promising smallpox antiviral therapeutic candidate. Tecovirimat: First Global Approval. In July 2018, oral tecovirimat was approved in the USA for the treatment of human smallpox disease caused by variola virus in adults and paediatric patients weighing \u2265\u00a013\u00a0kg. An intravenous formulation of tecovirimat is undergoing phase I development for the treatment of smallpox infection.  Brincidofovir, an oral antiviral in late stage development, has proven effective against orthopoxviruses in vitro and in vivo, has a different mechanism of action from tecovirimat (the only oral smallpox antiviral currently in the US Strategic National Stockpile), and has a resistance profile that reduces concerns in the scenario of a bioterror attack using genetically engineered smallpox. Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection. Tecovirimat appears to be an effective smallpox therapeutic in nonhuman primates, suggesting that it is reasonably likely to provide therapeutic benefit in smallpox-infected humans.","answer":"yes"}
{"id":"5c010e09133db5eb78000024","question":"Can simvastatin alleviate depressive symptoms?","context":"Simvastatin-treated patients experienced significantly more reductions in HDRS scores compared to the placebo group by the end of the trial (p=0.02). Early improvement and response rates were significantly greater in the simvastatin group than the placebo group (p=0.02 and p=0.01, respectively) but remission rate was not significantly different between the two groups (p=0.36). In conclusion, simvastatin seems to be a safe and effective adjuvant therapy for patients suffering from major depressive disorder.","answer":"yes"}
{"id":"5c5f2b771a4c55d80b000020","question":"Is P. gingivalis bacteria found in brain?","context":"studies using animal model of periodontitis and human post-mortem brain tissues from subjects with AD strongly suggest that a gram-negative periodontal pathogen, Porphyromonas gingivalis (Pg) and\/or its product gingipain is\/are translocated to the brain. The polymicrobial dysbiotic subgingival biofilm microbes associated with periodontal disease appear to contribute to developing pathologies in distal body sites, including the brain.","answer":"yes"}
{"id":"5c58ac2286df2b917400000f","question":"Is ibudilast effective for multiple sclerosis?","context":"Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study.  Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis. CONCLUSIONS: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. Specifically, the current evidence regarding treatment of progressive MS with ocrelizumab, simvastatin, ibudilast, alpha-lipoic acid, high-dose biotin, siponimod, and cell-based therapies are discussed. Based on our knowledge of pathophysiology, three therapeutic strategies are proposed: anti-inflammatory (ocrelizumab, siponimod\u2026); remyelinating (opicinumab); and neuroprotective (high-dose biotin, ibudilast, simvastatin\u2026).  Current article provides an overview of the pharmacology of IBD with a focus on preclinical and clinical data supporting its potential neuroprotective benefits for neurological conditions, including multiple sclerosis, neuropathic pain, medication overuse headache, stroke, opioid, alcohol and methamphetamine abuse. Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis. METHODS: SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS. CONCLUSION: SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials. Ibudilast for the treatment of multiple sclerosis. AREAS COVERED: This article reviews various studies looking at ibudilast as a potential therapy for MS. It summarizes prior and current clinical trials of ibudilast in MS as well as its pharmacology.EXPERT OPINION: Although ibudilast has not been found to decrease the focal inflammatory activity in relapsing MS, it was shown to have an effect on preserving brain volume and disability progression. Ibudilast may have a role in the treatment of progressive MS phenotypes. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression.<br><b>CONCLUSIONS<\/b>: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. It summarizes prior and current clinical trials of ibudilast in MS as well as its pharmacology.<br><b>EXPERT OPINION<\/b>: Although ibudilast has not been found to decrease the focal inflammatory activity in relapsing MS, it was shown to have an effect on preserving brain volume and disability progression.","answer":"yes"}
{"id":"5c0114ec133db5eb78000028","question":"Does gepotidacin activate bacterial topoisomerase?","context":"GSK2140944 is a novel bacterial topoisomerase inhibitor in development for the treatment of bacterial infections.","answer":"no"}
{"id":"5c5607aa07647bbc4b00000e","question":"Is durvalumab used for lung cancer treatment?","context":"In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy. METHODS: An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC. Durvalumab in non-small-cell lung cancer patients: current developments. Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the \u226525% PD-L1+ population. Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma.  PURPOSE OF REVIEW: The therapeutic armamentarium for advanced non-small-cell lung cancer has evolved considerably over the past years. Immune checkpoint inhibitors targeting programmed cell death-1 such as pembrolizumab and nivolumab or programmed cell death ligand 1 such as atezolizumab, durvalumab and avelumab have shown favorable efficacy results in this patient population in the first-line and second-line setting. In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1\/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT.  ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC. The PACIFIC trial assessing durvalumab after standard chemoradiotherapy for locally advanced NSCLC has already met its primary endpoint and the potential of durvalumab will be reinforced if phase III randomized studies of first-line (MYSTIC trial) and second or subsequent (ARCTIC trial) lines of therapy demonstrate superiority over the current standard of care.<br>","answer":"yes"}
{"id":"5c5f0c5a1a4c55d80b00000f","question":"Is  LRP1 interacting with Urokinase receptor?","context":"Interaction with a complex formed by uPA and its inhibitor PAI-1 induces cell surface down regulation and recycling of the receptor via the clathrin-coated pathway, a process dependent on the association to LRP-1. Here we investigated whether direct interaction between uPAR, a glycosyl-phosphatidylinositol-anchored protein, and LRP, a transmembrane receptor, Direct binding of domain 3 (D3) of uPAR to LRP is required for clearance of uPA-PAI-1-occupied uPAR","answer":"yes"}
{"id":"5c0e838b133db5eb7800002e","question":"Is obesity related to cognitive decline?","context":"The initial results suggests that obese children have higher cognitive scores and that this result is driven by those who are female, non-indigenous and live in an urban region. On the other end of the weight distribution, indigenous children who are severely thin or thin have significantly lower cognitive scores, a relationship that holds after correcting for possible bias and appears to strengthen between ages of five and eight. Obesity is associated with decreased cognitive function, reduced gray matter volume, and impaired white matter integrity in cognition-related brain areas in patients with MDD. The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span Poor cognitive performance was present in 37% of the sample. General obesity (BMI>or = 25) and poor cognition were strongly associated in the presence of abdominal obesity. Poor cognition was negatively associated with overweight (BMI 23-25) with normal waist circumference. BMI could be used as a candidate risk marker to identify people at higher risk of cognitive deficits, and as an intervention target for modifications of cognitive outcomes. Obesity is a common medical illness that is increasingly recognised as conferring risk of decline in cognitive performance, independent of other comorbid medical conditions. Overweight and obesity are associated with an increased risk of subnormal intellectual performance in young adult males. Subjects with low birth weight and adolescent overweight\/obesity are at particular risk of subnormal performance. Impairments in cognitive function have been associated with obesity in both people and rodents. Obesity in the pre-school years was associated with poorer outcomes for some cognitive measures in this study. Stronger relationships between obesity and cognition or educational attainment may emerge later in childhood. There is parallel evidence that people who are overweight or obese tend to perform worse on a variety of cognitive tasks While research in this area is growing, our knowledge of obesity-related cognitive dysfunction and brain alterations has not yet been synthesized. The present review integrates the recent literature regarding patterns of obesity-related cognitive dysfunction and brain alterations and also indicates potential mechanisms for these neuropathological changes. The review culminates in a preliminary model of obesity-related cognitive dysfunction and suggestions for future research, including the potential reversibility of these changes with weight-loss.<br> Evidence for the increased prevalence of diabetes and obesity is reviewed as it relates to cognitive decline. These articles indicate that the age of onset of Type 1 diabetes may be relevant to future cognitive function and that disease duration of Type 2 diabetes and sociocultural factors are related to cognitive decline during the aging process. This special issue concludes with a conceptual framework for linking obesity and diabetes with accelerated cognitive decline as related to the aging process. The adverse effects of diabetes and obesity on cognitive functioning are increasingly well recognized. Moreover, these studies show that distressing environmental circumstances can adversely influence neurocognitive dysfunction associated with obesity and diabetes.","answer":"yes"}
{"id":"5c589ddb86df2b917400000b","question":"Is cabozantinib effective for hepatocellular carcinoma?","context":"However, clinical trials of nonselective kinase inhibitors with c-Met activity (tivantinib, cabozantinib, foretinib, and golvatinib) in patients with HCC have failed so far to demonstrate significant efficacy.  More recently, promising outcomes have also been reported with new agents, such as nivolumab and cabozantinib.  Positive results in recent phase III clinical trials have confirmed the high value of anti-angiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities.  Expert opinion: Based on favorable phase III clinical trial data, sorafenib and lenvatinib are considered promising agents for HCC as first-line systemic chemotherapy. Moreover, regorafenib and cabozantinib are useful second-line therapies after the failure of sorafenib. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. BACKGROUND: Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease.  Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval [CI], 0.63 to 0.92; P=0.005). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P<0.001), and the objective response rates were 4% and less than 1%, respectively (P=0.009). CONCLUSIONS: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo.  Positive phase III-study data have been published for lenvatinib as first-line and cabozantinib as second-line therapy.  More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab).  The rapidly changing treatment landscape due to the emergence of new treatment options (sorafenib and lenvatinib equally effective in first line; regorafenib, cabozantinib, and ramucirumab showing OS benefit in second line with nivolumab approved by the FDA based on response rate) underscores the importance of re-assessing the role of the first approved systemic agent in HCC, sorafenib. Rationale for use, clinical trial data, and current recommendations for cabozantinib in renal cell cancer, thyroid cancer, prostate cancer, hepatocellular cancer, and lung cancer are detailed in this article. CONCLUSIONS: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. The most common high-grade events were palmar-plantar erythrodysesthesia (17% with cabozantinib vs. 0% with placebo), hypertension (16% vs. 2%), increased aspartate aminotransferase level (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%).<br><b>CONCLUSIONS<\/b>: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma.Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo.  CONCLUSIONS Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. CONCLUSIONS Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. CONCLUSIONS The tyrosine kinase inhibitors sorafenib (first line) and regorafenib (second line) have been approved for hepatocellular carcinoma, and the immune checkpoint inhibitor nivolumab obtained conditional approval for sorafenib-experienced patients in the United States. The principal advancements in the treatment of hepatocellular carcinoma (HCC) are the use of new systemic treatments such as lenvatinib in first-line treatment and regorafenib, cabozantinib and ramucirumab in second-line treatment due to their benefits in terms of overall survival. Recently, a few systemic chemotherapies proved to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib, cabozantinib, and ramucirumab as second-line therapy. <b>BACKGROUND<\/b>: The approval of the tyrosine kinase inhibitor sorafenib in 2007 marked a milestone in the treatment of hepatocellular carcinoma, as sorafenib was the first systemic therapy to show a survival benefit in patients with advanced hepatocellular carcinoma. We also elaborate the unmet need of biomarkers to guide treatment decisions and discuss the emerging field of immunotherapy in hepatocellular carcinoma.<br><b>CONCLUSIONS<\/b>: The tyrosine kinase inhibitors sorafenib (first line) and regorafenib (second line) have been approved for hepatocellular carcinoma, and the immune checkpoint inhibitor nivolumab obtained conditional approval for sorafenib-experienced patients in the United States. Cabozantinib in the treatment of hepatocellular carcinoma. The approval of the tyrosine kinase inhibitor sorafenib in 2007 marked a milestone in the treatment of hepatocellular carcinoma, as sorafenib was the first systemic therapy to show a survival benefit in patients with advanced hepatocellular carcinoma. Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. More recently, promising outcomes have also been reported with new agents, such as nivolumab and cabozantinib.  Positive phase III-study data have been published for lenvatinib as first-line and cabozantinib as second-line therapy.","answer":"yes"}
{"id":"5c56033607647bbc4b00000c","question":"Is Tisagenlecleucel effective for B-Cell Lymphoma?","context":"The phase II JULIET trial suggests that the CD19-targeting CAR T-cell therapy tisagenlecleucel produces durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. BACKGROUND: In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). CONCLUSIONS: In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects. Chimeric antigen receptor T cells demonstrate efficacy in B-cell malignancies, leading to US Food and Drug Administration approval of axicabtagene ciloleucel (October 2017) and tisagenlecleucel (May 2018) for large B-cell lymphomas after 2 prior lines of therapy. This article reviews data of current diffuse large B-cell lymphoma management, focusing on axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. This article reviews data of current diffuse large B-cell lymphoma management, focusing on axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.<br> The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.<br><b>METHODS<\/b>: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. No differences between response groups in tumor expression of CD19 or immune checkpoint-related proteins were found.<br><b>CONCLUSIONS<\/b>: In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel. This was a milestone in tumor immunology on account of the significant antitumor effect of tisagenlecleucel for the treatment of relapsed\/refractory B-ALL patients. On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed\/refractory B-cell acute lymphoblastic leukemia (B-ALL). Within the last one year, two anti-CD19 CAR T-cell therapy products, axicabtagene ciloleucel and tisagenlecleucel, were approved by the United States Food and Drug Administration for the treatment of relapsed or refractory large B-cell lymphoma after at least two lines of systemic therapy based on multicenter single-arm phase two clinical trials.  On August 30, 2017, the U.S. Food and Drug Administration approved tisagenlecleucel for treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Tisagenlecleucel for the treatment of B-cell acute lymphoblastic leukemia. Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed\/refractory (r\/r) B-cell acute lymphoblastic leukemia (B-ALL).","answer":"yes"}
{"id":"5c76cea17c78d694710000a7","question":"Is ADP-ribosylation a PTM?","context":"ADP-ribosylation is a PTM, in which ADP-ribosyltransferases use nicotinamide adenine dinucleotide (NAD+) to modify target proteins with ADP-ribose Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses. ADP-ribosylation is a post-translational modification (PTM) implicated in several crucial cellular processes, ranging from regulation of DNA repair and chromatin structure to cell metabolism and stress responses.","answer":"yes"}
{"id":"5c56fd7407647bbc4b000013","question":"Does epidural anesthesia for pain management during labor affect the Apgar score of the the infant?","context":"We retrospectively analyzed 93 consecutive single-pregnancy patients who underwent cesarean section with combined spinal-epidural anesthesia. The patients were divided into two groups, depending on the use of 6% HES 130\/0.4: group A (461\u00a0\u00b1\u00a0167\u00a0ml of saline-based HES was administered; 43 patients) and group B (HES not administered; 50 patients). The major outcome was umbilical cord chloride level at delivery. The volume infused from operating room admission until delivery was not significantly different between groups. The umbilical cord chloride level at delivery was statistically significantly higher in group A than in group B, but clinically similar (108\u00a0\u00b1\u00a02 vs. 107\u00a0\u00b1\u00a02\u00a0mmol\/l, P\u00a0=\u00a00.02). No differences were observed in the Apgar score or other umbilical cord laboratory data at delivery (Na+, K+, pH, base excess) CONCLUSION Subarachnoid or epidural sufentanil, in the doses used in this study, associated with local anesthetics, had the same effect on the duration of labor after analgesia and in the Apgar score of newborns. CONCLUSION Subarachnoid or epidural sufentanil, in the doses used in this study, associated with local anesthetics, had the same effect on the duration of labor after analgesia and in the Apgar score of newborns.","answer":"no"}
{"id":"5c5f22951a4c55d80b00001d","question":"Is phospholipid hydroperoxide glutathione peroxidase a selenoprotein?","context":"Glutathione peroxidase (Gpx1) is the major selenoprotein in most tissues in animals. The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation. the major selenoprotein expressed by germ cells in the testis, the phospholipid hydroperoxide glutathione peroxidase (PHGPx\/GPx4)","answer":"yes"}
{"id":"5c73aced7c78d69471000087","question":"Is inositol effective for trichotillomania?","context":"Patients assigned to inositol failed to show significantly greater reductions on primary or secondary outcomes measures compared with placebo (all P>0.05). This is the first study assessing the efficacy of inositol in the treatment of trichotillomania, but found no differences in symptom reductions between inositol and placebo. At study endpoint, 42.1% of patients were 'much or very much improved' on inositol compared with 35.3% on placebo. Conclusions \u2022 The review indicates that yoga, aerobic exercise, acupuncture, biofeedback, hypnosis, and inositol and N-acetylcysteine all show promise in the treatment of excoriation disorder and other body-focused repetitive behaviors, such as trichotillomania. Future studies should examine whether inositol may be beneficial in controlling pulling behavior in a subgroup of individuals with trichotillomania.","answer":"no"}
{"id":"5c640fa1e842deac67000011","question":"Is TIAM1 favoring tumor progression in colorectal cancer (CRC)?","context":"Here, we identify TIAM1 as a critical antagonist of CRC progression through inhibiting TAZ and YAP, effectors of WNT signaling. We demonstrate that TIAM1 shuttles between the cytoplasm and nucleus antagonizing TAZ\/YAP by distinct mechanisms in the two compartments. In the cytoplasm, TIAM1 localizes to the destruction complex and promotes TAZ degradation by enhancing its interaction with \u03b2TrCP. Nuclear TIAM1 suppresses TAZ\/YAP interaction with TEADs, inhibiting expression of TAZ\/YAP target genes implicated in epithelial-mesenchymal transition, cell migration, and invasion, and consequently suppresses CRC cell migration and invasion. Importantly, high nuclear TIAM1 in clinical specimens associates with increased CRC patient survival. Together, our findings suggest that in CRC TIAM1 suppresses tumor progression by regulating YAP\/TAZ activity. Together, our findings suggest that in CRC TIAM1 suppresses tumor progression by regulating YAP\/TAZ activity. Nuclear TIAM1 suppresses TAZ\/YAP interaction with TEADs, inhibiting expression of TAZ\/YAP target genes implicated in epithelial-mesenchymal transition, cell migration, and invasion, and consequently suppresses CRC cell migration and invasion. Using an orthotopic xenograft model in nude mice, we confirmed that Tiam1 silencing could reduce tumor growth by subcutaneous injection and could suppress lung and liver metastases of colorectal cancer cells. Together, our findings suggest that in CRC TIAM1 suppresses tumor progression by regulating YAP\/TAZ activity.<br>","answer":"no"}
{"id":"5c663afe7c78d69471000013","question":"Is pacritinib effective for treatment of myelofibrosis?","context":"Pacritinib and its use in the treatment of patients with myelofibrosis who have thrombocytopenia. Pacritinib, a dual JAK2 and FLT3 inhibitor which also inhibits IRAK1, has demonstrated the ability to favorably impact MF-associated splenomegaly and symptom burden, while having limited myelosuppression with manageable gastrointestinal toxicity. Other JAKis, such as fedratinib and pacritinib, proved to be useful in MF.  Conclusions and Relevance: In patients with myelofibrosis and thrombocytopenia, including those with prior anti-JAK therapy, pacritinib twice daily was more effective than BAT, including ruxolitinib, for reducing splenomegaly and symptoms. Developments of JAK inhibitors, such as ruxolitinib, pacritinib, momelotinib, and febratinib enabled the effective management in MF patients.   Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression.  Pacritinib could be a treatment option for patients with myelofibrosis, including those with baseline cytopenias for whom options are particularly limited. Conclusions and Relevance In patients with myelofibrosis and thrombocytopenia, including those with prior anti-JAK therapy, pacritinib twice daily was more effective than BAT, including ruxolitinib, for reducing splenomegaly and symptoms. Expert commentary: Pacritinib has demonstrated promising results in patients with myelofibrosis and thrombocytopenia. Pacritinib, a dual JAK2 and FLT3 inhibitor, improves disease-related symptoms and signs with manageable gastrointestinal toxicity in patients with myelofibrosis with splenomegaly and high-risk features, without causing overt myelosuppression, and therefore may provide an important treatment option for a range of patients with myelofibrosis. Pacritinib is an active agent in patients with MF, offering a potential treatment option for patients with preexisting anemia and thrombocytopenia. Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression. This article examines the role of JAK2 and FLT3 signaling in myelofibrosis and provides an overview of the clinical development of pacritinib as a new therapy for myelofibrosis. Pacritinib appears to be an effective agent for the control of MF-related symptoms and splenomegaly with potentially fewer haematological side-effects when compared with ruxolitinib and seems a particularly promising agent for anaemic and thrombocytopenic patients.  Expert commentary: Pacritinib has demonstrated promising results in patients with myelofibrosis and thrombocytopenia.","answer":"yes"}
{"id":"5c571f7607647bbc4b000017","question":"Can exposure to heavy metals like lead(Pb) or cadmium(Cd) cause changes in DNA methylation patterns in Isoetes sinensis?","context":"DNA methylation in endangered plants after exposure to heavy metals, the Isoetes sinensis, an endangered plant, was stressed with three different concentrations of two heavy metals lead (Pb) and cadmium (Cd) The results showed that the DNA methylated profile of I. sinensis was affected by Pb and Cd stress. The proportion of DNA methylation (including hypermethylation) by both Pb and Cd stresses is nearly equal (39.04% and 39.71%), but the proportion of DNA demethylation by Cd is higher than that by Pb (46.86% than 33.92%). There was no significant difference in the amount of DNA methylation among control check (CK), Pb stress group, and Cd stress group (CK 46.96%, Pb 48.23%, and Cd 48.1%). However, full-methylation level of Pb stress group (28.34%) and Cd stress group (20.25%) was lower than control (33.91%), in contrast, hemi-methylation level Pb stress group (19.89%) and Cd stress group (27.85%) were higher than control (13.04%). Consistently, a dramatic change in DNA methylation patterns was detected in excess Cu-exposed H. verticillata. Hydrilla verticillata employs two different ways to affect DNA methylation under excess copper stress.Because of the accumulation of heavy metals, Hydrilla verticillata (L.f.) Royle, a rooted submerged perennial aquatic herb, is being developed as a potential tool to clean the aquatic ecosystem polluted by heavy metals.  The proportion of DNA methylation (including hypermethylation) by both Pb and Cd stresses is nearly equal (39.04% and 39.71%), but the proportion of DNA demethylation by Cd is higher than that by Pb (46.86% than 33.92%).<br>","answer":"yes"}
{"id":"5c57031107647bbc4b000014","question":"Has Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) been reported to be a plasminogen receptor in pathogenic bacteria?","context":"binding of plasminogen (Plg) to bacterial surfaces, as it has been shown that this interaction contributes to bacterial adhesion to host cells, invasion of host tissues, and evasion of the immune system. Several bacterial proteins are known to serve as receptors for Plg including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Moreover, several isoforms of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and galectin (GAL) were identified in both antigenic extracts as plasminogen-binding proteins. Purified GAPDH was found to bind human plasminogen and fibrinogen in Far-Western blot and ELISA-based assays. GAPDH exhibits a high affinity for plasmin and a significantly lower affinity for plasminogen. Moreover, several isoforms of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and galectin (GAL) were identified in both antigenic extracts as plasminogen-binding proteins.","answer":"yes"}
{"id":"5c6549e1e842deac67000022","question":"Can CPX-351 be used for the treatment of tuberculosis?","context":"CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin which has recently been FDA approved for treatment of acute myeloid leukemia (AML).","answer":"no"}
{"id":"5c654c14e842deac67000025","question":"Does lucatumumab bind to CD140?","context":"Lucatumumab is a fully humanized anti-CD40 antibody that blocks interaction of CD40L with CD40 and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC).  Phase I study of the anti-CD40 humanized monoclonal antibody lucatumumab (HCD122) in relapsed chronic lymphocytic leukemia. Saturation of CD40 receptor on CLL cells was uniform at all doses post-treatment but also persisted at trough time points in the 3.0 mg\/kg or greater cohorts.","answer":"no"}
{"id":"5c73ad0b7c78d69471000093","question":"Does simvastatin improve outcomes of aneurysmal subarachnoid hemorrhage?","context":"Randomized controlled trials have shown that simvastatin and intravenous magnesium do not prevent DCI or improve functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Conclusions Simvastatin showed no benefits in decreasing the incidence of vasospasm, DCI, or all-cause mortality after aneurysmal SAH. We conclude that patients with SAH should not be treated routinely with simvastatin during the acute stage. We found no statistically significant effects on vasospasm detected by transcranial cerebral Doppler (relative risk [RR], 0.91; 95% confidence interval [CI], 0.55-1.49), delayed cerebral ischemia (DCI) (RR, 0.85; 95% CI, 0.63-1.14), or all-cause mortality (RR, 1.02; 95% CI, 0.67-1.54). BACKGROUND: Simvastatin might be beneficial to the patients with aneurysmal subarachnoid hemorrhage. However, the results remained controversial.  CONCLUSIONS: Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS\u22642, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage. Current evidence does not support prophylactic use of clazosentan, magnesium, or simvastatin.  Recently, acute simvastatin treatment was not shown to be beneficial in neurological outcome using modified Rankin Scale. CONCLUSIONS: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage. CONCLUSION: This study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients. High-Dose Simvastatin Is Effective in Preventing Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study in Korean Patients. CONCLUSIONS The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage. CONCLUSIONS High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage. Randomized controlled trials have shown that simvastatin and intravenous magnesium do not prevent DCI or improve functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH). CONCLUSIONS Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS\u22642, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage. CONCLUSIONS The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage. CONCLUSIONS High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage. CONCLUSIONS Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS\u22642, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage. There were also no differences in DID, delayed cerebral infarction, favorable mRS outcome, and MMSE scores, and MMSE-assessed cognitive impairment between both groups.<br><b>CONCLUSIONS<\/b>: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.<br>","answer":"no"}
{"id":"5c72aaed7c78d6947100006f","question":"Is pazopanib an effective treatment of glioblastoma?","context":"RESULTS: The six-month progression-free survival (PFS) rates in phase II (n = 41) were 0% and 15% in the PTEN\/EGFRvIII-positive and PTEN\/EGFRvIII-negative cohorts, respectively, leading to early termination.  Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses.","answer":"no"}
{"id":"5c643485e842deac67000015","question":"Are de novo mutations in regulatory elements responsible for neurodevelopmental disorders?","context":"The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism.  Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders.  De novo mutations in regulatory elements in neurodevelopmental disorders.We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences.","answer":"yes"}
{"id":"5c7c0e2fd774d0424000000d","question":"Are phagosomal proteins ubiquitinated?","context":"Phagosomal proteins are ubiquitylated, and ubiquitylation was found to be required for formation of acidic multivesicular structures. membranes of the bacterial phagosome are enriched with ubiquitinated proteins in a way that requires its Dot\/Icm type IV secretion system, suggesting the involvement of effectors in the manipulation of the host ubiquitination machinery.","answer":"yes"}
{"id":"5c73ad327c78d69471000097","question":"Does tremelimumab improve survival of mesothelioma patients?","context":"BACKGROUND: Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study.  INTERPRETATION: The combination of tremelimumab and durvalumab appeared active, with a good safety profile in patients with mesothelioma, warranting further exploration. Biological and clinical considerations rule out the use of tremelimumab as single agent for MM and, more generally, the use of immune checkpoint inhibitors for MM is still largely questionable and not supported by evidences. At the data cutoff date (Jan 24, 2016), 307 (80%) of 382 patients had died in the tremelimumab group and 154 (81%) of 189 patients had died in the placebo group. Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7\u00b77 months (95% CI 6\u00b78-8\u00b79) in the tremelimumab group and 7\u00b73 months (5\u00b79-8\u00b77) in the placebo group (hazard ratio 0\u00b792 [95% CI 0\u00b776-1\u00b712], p=0\u00b741).  INTERPRETATION: Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma. BACKGROUND Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study. INTERPRETATION Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma. Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7\u00b77 months (95% CI 6\u00b78-8\u00b79) in the tremelimumab group and 7\u00b73 months (5\u00b79-8\u00b77) in the placebo group (hazard ratio 0\u00b792 [95% CI 0\u00b776-1\u00b712], p=0\u00b741). BACKGROUND Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study. INTERPRETATION Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma. Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7\u00b77 months (95% CI 6\u00b78-8\u00b79) in the tremelimumab group and 7\u00b73 months (5\u00b79-8\u00b77) in the placebo group (hazard ratio 0\u00b792 [95% CI 0\u00b776-1\u00b712], p=0\u00b741).  <b>BACKGROUND<\/b>: Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study.","answer":"no"}
{"id":"5c6587d77c78d69471000005","question":"Can enasidenib be used for the treatment of acute myeloid leukemia?","context":"In August 2017, the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene\/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation.","answer":"yes"}
{"id":"5c783236d774d04240000001","question":"Is collagen the most abundant human protein?","context":"As the most abundant protein in the body, collagen is essential to maintain the normal structure and strength of connective tissue, such as bones, skin, cartilage, and blood vessels. Collagen is the most abundant protein family in mammals. Collagen is a fibrillar protein that conforms the conjunctive and connective tissues in the human body, essentially skin, joints, and bones. This molecule is one of the most abundant in many of the living organisms due to its connective role in biological structures.","answer":"yes"}
{"id":"5c76be617c78d694710000a5","question":"Is the enzyme ERAP2 associated with the disease birdshot chorioretinopathy?","context":"Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy. BSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands, thus implicating the A*29:02 peptidome in this disease.  A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.","answer":"yes"}
{"id":"5c73ad377c78d6947100009a","question":"Does Panitumumab prolong survival of biliary tract cancer patients?","context":"Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study). CONCLUSIONS: Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer.  No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P\u2009=\u2009.42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P\u2009=\u2009.13).  CONCLUSIONS Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer. CONCLUSIONS Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer. Despite many clinical trials being conducted with molecular targeted agents including erlotinib, cetuximab, panitumumab, bevacizumab, sorafenib, cediranib, trametinib and vandetanib, no agent has shown to be effective for advanced biliary tract cancer. Adding panitumumab to standard protocols does not prolong survival but provokes additional adverse effects.","answer":"no"}
{"id":"5c6582207c78d69471000001","question":"Is lucatumumab a polyclonal antibody?","context":"A phase 1 study of lucatumumab, a fully human anti-CD40 antagonist monoclonal antibody administered intravenously to patients with relapsed or refractory multiple myeloma. In this open-label, multicentre, phase 1 study a fully human anti-CD40 antagonist monoclonal antibody, lucatumumab, was evaluated in patients with relapsed\/refractory multiple myeloma (MM).","answer":"no"}
{"id":"5c662c507c78d6947100000d","question":"Is lithium effective for treatment of amyotrophic lateral sclerosis?","context":"In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results. Despite several positive case reports and short studies, further controlled researches have failed to substantiate any positive effects of lithium exposure in amyotrophic lateral sclerosis.  The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). Studies in ALS showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease. BACKGROUND Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. In a pilot clinical study that we recently published we found that lithium administration slows the progression of Amyotrophic Lateral Sclerosis (ALS) in human patients. BACKGROUND Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. BACKGROUND A neuroprotective effect of lithium in amyotrophic lateral sclerosis (ALS) has been recently reported. Lithium delays progression of amyotrophic lateral sclerosis.ALS is a devastating neurodegenerative disorder with no effective treatment.  Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial.<AbstractText Label=\"BACKGROUND\" NlmCategory=\"BACKGROUND\">Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival.  <b>INTRODUCTION<\/b>: Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period. A recently published study also ruled out any possible modest effect.<br><b>CONCLUSIONS<\/b>: There is evidence to suggest that lithium has no short-term benefits in ALS. A comparison of the group of patients treated with lithium+riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time. None of the patients treated with lithium died during the 15 months of the follow-up, and disease progression was markedly attenuated when compared with age-, disease duration-, and sex-matched control patients treated with riluzole for the same amount of time.","answer":"no"}
{"id":"5c73acea7c78d69471000085","question":"Should dacomitinib be used for treatment of glioblastoma patients?","context":"Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit.  Conclusions: Dacomitinib has a limited single-agent activity in recurrent GB with EGFR amplification. Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit. Expert opinion: Despite the poor global results of Dacomitinib in recurrent GB shown in a phase II trial, some patients had a significant benefit.","answer":"no"}
{"id":"5c6d7bb57c78d6947100003b","question":"Are there ultraconserved regions in the budding yeast (Saccharomyces cerevisiae)?","context":"The systematic analysis of ultraconserved genomic regions in the budding yeast. In the evolution of species, a kind of special sequences, termed ultraconserved sequences (UCSs), have been inherited without any change, which strongly suggests those sequences should be crucial for the species to survive or adapt to the environment. However, the UCSs are still regarded as mysterious genetic sequences so far. Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast.Results: Our results indicate that, in addition to some fundamental biological functions, the UCSs play an important role in the adaptation of Saccharomyces cerevisiae to the acidic environment, which is backed up by the previous observation. Besides that, we also find the highly unchanged genes are enriched in some other pathways, such as the nutrient-sensitive signaling pathway. To facilitate the investigation of unique UCSs, the UCSC Genome Browser was utilized to visualize the chromosomal position and related annotations of UCSs in S.cerevisiae genome. Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast. Motivation In the evolution of species, a kind of special sequences, termed ultraconserved sequences (UCSs), have been inherited without any change, which strongly suggests those sequences should be crucial for the species to survive or adapt to the environment. The systematic analysis of ultraconserved genomic regions in the budding yeast.<AbstractText Label=\"Motivation\">In the evolution of species, a kind of special sequences, termed ultraconserved sequences (UCSs), have been inherited without any change, which strongly suggests those sequences should be crucial for the species to survive or adapt to the environment.  Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast.  Here, we present a systematic study of ultraconserved genomic regions in the budding yeast based on the publicly available genome sequences, in order to reveal their relationship with the adaptability or fitness advantages of the budding yeast.<br><b>Results<\/b>: Our results indicate that, in addition to some fundamental biological functions, the UCSs play an important role in the adaptation of Saccharomyces cerevisiae to the acidic environment, which is backed up by the previous observation.","answer":"yes"}
{"id":"5c640c2ee842deac67000010","question":"Is there any role for HUWE1 in MYC signalling?","context":"HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation. To determine the importance of HUWE1, we chose to examine its function in colorectal cancer, where it is mutated in up to 15 per cent of tumours. Modelling of identified mutations showed that they inactivate the E3 ubiquitin ligase activity of HUWE1. Genetic deletion of Huwe1 rapidly accelerated tumourigenic in mice carrying loss of the intestinal tumour suppressor gene Apc, with a dramatic increase in tumour initiation. Mechanistically, this phenotype was driven by increased MYC and rapid DNA damage accumulation leading to loss of the second copy of Apc The increased levels of DNA damage sensitised Huwe1-deficient tumours to DNA-damaging agents and to deletion of the anti-apoptotic protein MCL1. Taken together, these data identify HUWE1 as a bona fide tumour suppressor gene in the intestinal epithelium and suggest a potential vulnerability of HUWE1-mutated tumours to DNA-damaging agents and inhibitors of anti-apoptotic proteins.","answer":"yes"}
{"id":"5c674aed7c78d69471000019","question":"Do raspberries improve postprandial glucose and acute and chronic inflammation in adults with type 2 Diabetes?","context":"The NLR family pyrin domain containing 3 (NLRP3) inflammasome plays a critical role in insulin resistance and the pathogenesis of type 2 diabetes. Red raspberry (RB) contains high amounts of dietary fibers and polyphenolic compounds, which are known for their anti-oxidative and anti-inflammatory effects.","answer":"yes"}
{"id":"5c7836dad774d04240000002","question":"Are Mesenchymal stem cells (MSC) multipotent cells?","context":"multipotent mesenchymal bone marrow-derived stem cells multipotent hESC-derived mesenchymal cells (MCs)","answer":"yes"}
{"id":"5c6b198f7c78d69471000025","question":"Is there a deep-learning algorithm for protein solubility prediction?","context":"DeepSol: a deep learning framework for sequence-based protein solubility prediction. Protein solubility plays a vital role in pharmaceutical research and production yield. For a given protein, the extent of its solubility can represent the quality of its function, and is ultimately defined by its sequence. Thus, it is imperative to develop novel, highly accurate in silico sequence-based protein solubility predictors. In this work we propose, DeepSol, a novel Deep Learning-based protein solubility predictor. The backbone of our framework is a convolutional neural network that exploits k-mer structure and additional sequence and structural features extracted from the protein sequence. DeepSol: a deep learning framework for sequence-based protein solubility prediction.<AbstractText Label=\"Motivation\" NlmCategory=\"UNASSIGNED\">Protein solubility plays a vital role in pharmaceutical research and production yield.","answer":"yes"}
{"id":"5c5215e67e3cb0e231000004","question":"Have machine learning methods been used to predict the severity of major depressive disorder(MDD)?","context":"Here, we conduct a meta-review to identify predictors of response to antidepressant therapy in order to select robust input features for machine learning models of treatment response.  machine learning framework involving EEG-based functional connectivity to diagnose major depressive disorder (MDD). Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset. persistence and severity of major depressive disorder from baseline self-reports  These results confirm that clinically useful MDD risk-stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure. Notably, while the only information provided for training the classifiers was T(1)-weighted scans plus a categorical label (major depressive disorder versus controls), both relevance vector machine and support vector machine 'weighting factors' (used for making predictions) correlated strongly with subjective ratings of illness severity. BACKGROUND Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. BACKGROUND Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. BACKGROUND Growing evidence documents the potential of machine learning for developing brain based diagnostic methods for major depressive disorder (MDD). OBJECTIVE We aimed to integrate neural data and an advanced machine learning technique to predict individual major depressive disorder (MDD) patient severity. Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure. <b>BACKGROUND<\/b>: Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods.","answer":"yes"}
{"id":"5c6583117c78d69471000002","question":"Can midostaurin inhibit angiogenesis?","context":"Midostaurin was a prototype kinase inhibitor, originally developed as a protein kinase C inhibitor and subsequently as an angiogenesis inhibitor, based on its inhibition of vascular endothelial growth factor receptor.","answer":"yes"}
{"id":"5c629fffe842deac67000009","question":"Does Groucho related gene 5 (GRG5) have a role only in late development?","context":"Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. The malignant characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its pro-oncogenic potential. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state decisions.Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development.","answer":"no"}
{"id":"5c6da11e7c78d69471000042","question":"Are there tools for reviewing variant calls?","context":"VIPER: a web application for rapid expert review of variant calls. With the rapid development in next-generation sequencing, cost and time requirements for genomic sequencing are decreasing, enabling applications in many areas such as cancer research. Many tools have been developed to analyze genomic variation ranging from single nucleotide variants to whole chromosomal aberrations. As sequencing throughput increases, the number of variants called by such tools also grows. Often employed manual inspection of such calls is thus becoming a time-consuming procedure. We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application. Analysts can then quickly iterate through variants, apply filters and make decisions based on the generated images and variant metadata. VIPER was successfully employed in analyses with manual inspection of more than 10 000 calls.Availability and implementation: VIPER is implemented in Java and Javascript and is freely available at https:\/\/github.com\/MarWoes\/viper. Variant Review with the Integrative Genomics Viewer. VIPER: a web application for rapid expert review of variant calls.Supplementary data are available at Bioinformatics online. We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application.","answer":"yes"}
{"id":"5c65495be842deac67000021","question":"Has ivosidenib been FDA approved for use against acute myeloid leukemia?","context":"The FDA approved ivosidenib for patients with IDH1-mutant relapsed\/refractory acute myeloid leukemia.","answer":"yes"}
{"id":"5c51f44c07ef653866000004","question":"Are Copy Number Variants (CNVs) depleted in regions of low mappability?","context":"Human copy number variants are enriched in regions of low mappability. Applying PopSV to 640 human genomes, we find that low-mappability regions are approximately 5\u00a0times more likely to harbor germline CNVs, in stark contrast to the nearly uniform distribution observed for somatic CNVs in 95 cancer genomes. In addition to known enrichments in segmental duplication and near centromeres and telomeres, we also report that CNVs are enriched in specific types of satellite and in some of the most recent families of transposable elements. Finally, using this comprehensive approach, we identify 3455 regions with recurrent CNVs that were missing from existing catalogs. In particular, we identify 347 genes with a novel exonic CNV in low-mappability regions, including 29 genes previously associated with disease. Human copy number variants are enriched in regions of low mappability.Copy number variants (CNVs) are known to affect a large portion of the human genome and have been implicated in many diseases.","answer":"no"}
{"id":"5c5b2f4b1a4c55d80b000001","question":"Is Adar3 involved in learning and memory?","context":"Adar3 Is Involved in Learning and Memory in Mice.  The newest member of the A-I editing family of ADAR proteins, the vertebrate-specific ADAR3, is highly expressed in the brain, but its functional significance is unknown. In vitro studies have suggested that ADAR3 acts as a negative regulator of A-I RNA editing but the scope and underlying mechanisms are also unknown. Meta-analysis of published data indicates that mouse Adar3 expression is highest in the hippocampus, thalamus, amygdala, and olfactory region. Consistent with this, we show that mice lacking exon 3 of Adar3 (which encodes two double stranded RNA binding domains) have increased levels of anxiety and deficits in hippocampus-dependent short- and long-term memory formation. RNA sequencing revealed a dysregulation of genes involved in synaptic function in the hippocampi of Adar3-deficient mice. We also show that ADAR3 transiently translocates from the cytoplasm to the nucleus upon KCl-mediated activation in SH-SY5Y cells. These results indicate that ADAR3 contributes to cognitive processes in mammals. Adar3 Is Involved in Learning and Memory in Mice.-deficient mice.","answer":"yes"}
{"id":"5c5f2cef1a4c55d80b000022","question":"There is no drug available to prevent HIV infection, Pre-exposure prophylaxis (PrEP), yes or no?","context":"pre-exposure prophylaxis with generic tenofovir disoproxil fumarate\/emtrictabine in London - analysis of pharmacokinetics, safety and outcomes. The antiviral agent tenofovir is highly effective for the treatment of HIV and hepatitis B virus infections, and the older prodrug tenofovir disoproxil fumarate (TDF) is also a component of daily preexposure prophylaxis (PrEP) to reduce the risk of HIV infection in high-risk populations.  Following US Food and Drugs Administration approval in July 2012 of daily oral tenofovir and emtricitabine for pre-exposure prophylaxis (PrEP) to prevent HIV infection in high-risk individuals in the USA, there has been much controversy about the implementation of this PrEP regimen in other countries throughout the world, and in Europe in particular. Daily oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative people to prevent HIV infection. HIV pre-exposure prophylaxis (PrEP) is a new approach that involves the ongoing use of antiretroviral medications by HIV-negative individuals to reduce the risk of HIV infection. CONCLUSIONS Combined ART + PrEP is likely to prevent more HIV infections than either strategy alone, but with higher prevalence of drug resistance. INTRODUCTION Use of pre-exposure prophylaxis (PrEP) among people who inject drugs (PWID) has been shown to be effective in preventing HIV transmission. Pre-exposure prophylaxis (PrEP) is an experimental approach to HIV prevention and consists of antiretroviral drugs to be taken before potential HIV exposure in order to reduce the risk of HIV infection and continued during periods of risk. HIV pre-exposure prophylaxis (PrEP) is the use of one or more antiretroviral medications (in combination) to prevent HIV infection. The most commonly used PrEP medication (Truvada<br> The use of antiretrovirals as pre-exposure prophylaxis (PrEP) is highly efficacious in HIV prevention.","answer":"no"}
{"id":"5c52cde87e3cb0e23100000e","question":"Does allele phasing improve the phylogenetic utility of ultraconserved elements?","context":"Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements. Our empirical analyses of Ultraconserved Element (UCE) locus data collected from the South American hummingbird genus Topaza demonstrate that phased allele sequences carry sufficient phylogenetic information to infer the genetic structure, lineage divergence, and biogeographic history of a genus that diversified during the last three million years. The phylogenetic results support the recognition of two species, and suggest a high rate of gene flow across large distances of rainforest habitats but rare admixture across the Amazon River. Our simulations provide evidence that analyzing allele sequences leads to more accurate estimates of tree topology and divergence times than the more common approach of using contig sequences. Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements.Advances in high-throughput sequencing techniques now allow relatively easy and affordable sequencing of large portions of the genome, even for nonmodel organisms.","answer":"yes"}
{"id":"5c5723a007647bbc4b000019","question":"Have yeast prions become important models for the study of the basic mechanisms underlying human amyloid diseases?","context":"Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions Fibrous cross-\u03b2 aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast.  These infectious yeast amyloidoses are outstanding models for the many common human amyloid-based diseases that are increasingly found to have some infectious characteristics. Yeast prions (infectious proteins) were discovered by their outr\u00e9 genetic properties and have become important models for an array of human prion and amyloid diseases. Yeast prions are models for both rare mammalian prion diseases and for several very common amyloidoses such as Alzheimer's disease, type 2 diabetes, and Parkinson's disease.  Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions.  Mechanism of amyloid formation is critical for a complete understanding of the yeast prion phenomenon and human amyloid-related diseases.  Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions. Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions. Mechanism of amyloid formation is critical for a complete understanding of the yeast prion phenomenon and human amyloid-related diseases. Here we summarize the results of studies of prions of the yeast Saccharomyces cerevisiae and of the use of yeast model for investigation of some human amyloidoses, such as prion diseases, Alzheimer's, Parkinson's, and Huntington's diseases. Yeast prions increasingly are serving as models for the understanding and treatment of many mammalian amyloidoses. Yeast prions, based on self-seeded highly ordered fibrous aggregates (amyloids), serve as a model for human amyloid diseases. These infectious yeast amyloidoses are outstanding models for the many common human amyloid-based diseases that are increasingly found to have some infectious characteristics.<br> The yeast system has provided considerable insight into the biology of amyloid and prions. Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions. We also review studies of the roles of chaperones, aggregate-collecting proteins, and other cellular components using yeast that have led the way in improving the understanding of similar processes that must be operating in many human amyloidoses.","answer":"yes"}
{"id":"5c6b7bee7c78d6947100002a","question":"Is dupilumab effective for treatment of asthma?","context":"The appropriate use of these biologics, and of those in development (e.g., benralizumab and dupilumab), should be aided by further understanding of asthma phenotypes and endotypes, utilizing appropriate biomarkers. Simultaneous targeting of both IL-4 and IL-13 by blocking IL-4 receptor \u03b1 using dupilumab has yielded more consistent results in reducing asthma exacerbations and improving lung function, especially in patients with increased blood eosinophils. In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting \u03b22-agonists. CONCLUSIONS: Dupilumab 300\u00a0mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR. Small molecules (e.g. ligustrazine and SP600125) and large molecule antibodies (e.g. lebrikizumab, benralizumab, dupilumab) are being considered as novel agents for the pharmacotherapy of asthma.  Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. CONCLUSIONS: In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control.  Dupilumab for the treatment of asthma.Dupilumab (REGN668\/SAR231893), produced by a collaboration between Regeneron and Sanofi, is a monoclonal antibody currently in phase III for moderate-to-severe asthma.  Dupilumab inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in asthma. Dupilumab (REGN668\/SAR231893), produced by a collaboration between Regeneron and Sanofi, is a monoclonal antibody currently in phase III for moderate-to-severe asthma. If confirmed, efficacy of dupilumab in both eosinophilic and non-eosinophilic severe asthma phenotype might represent an advantage over approved biologics for asthma, including omalizumab, mepolizumab, and reslizumab. In this review, we focused on IL-4 and IL-13, as these interleukins are considered to play a key role in the pathophysiology of asthma, and on dupilumab, an anti-IL-4 receptor human mAb, as a forthcoming treatment for uncontrolled severe asthma in the near future. Expert opinion: Supported by a strategic mechanism of action, as well as by convincing preliminary clinical results, dupilumab currently appears to be a very promising biological drug for the treatment of severe uncontrolled asthma. All drugs decreased asthma exacerbations but the results were only significant for reslizumab and dupilumab. Anti-IL-4 and IL-13 agents (dupilumab, lebrikizumab, and tralokinumab) which block different Th-2 inflammatory pathways and agents targeting the Th-17 inflammatory pathway in severe refractory asthma are under development. Dupilumab for the treatment of asthma. In addition, dupilumab is currently under phase\u00a0III development across the world for the treatment of asthma and nasal polyposis as well as for atopic dermatitis in paediatric patients. BACKGROUND Dupilumab (an anti-interleukin-4-receptor-\u03b1 monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2\/Th2 cytokines implicated in numerous allergic diseases ranging from asthma to atopic dermatitis. Dupilumab: a novel treatment for asthma. Dupilumab for the treatment of asthma. The efficacy and safety profile of dupilumab in the treatment of allergic diseases has been tested for more than 10 years in a variety of large clinical trials in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. Areas covered: Pathophysiological role of IL-4 and IL-13 in asthma; mechanism of action of dupilumab; pharmacology of IL-4 receptor; phase I and phase II studies with dupilumab; regulatory affairs. Expert opinion: Patients with severe asthma who are not sufficiently controlled with standard-of-care represent the target asthma population for dupilumab. CONCLUSIONS In patients with glucocorticoid-dependent severe asthma, dupilumab treatment reduced oral glucocorticoid use while decreasing the rate of severe exacerbations and increasing the FEV1. CONCLUSIONS In patients with persistent, moderate-to-severe asthma and elevated eosinophil levels who used inhaled glucocorticoids and LABAs, dupilumab therapy, as compared with placebo, was associated with fewer asthma exacerbations when LABAs and inhaled glucocorticoids were withdrawn, with improved lung function and reduced levels of Th2-associated inflammatory markers. Expert opinion: Patients with severe asthma who are not sufficiently controlled with standard-of-care represent the target asthma population for dupilumab. Dupilumab inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in asthma. Expert opinion: Supported by a strategic mechanism of action, as well as by convincing preliminary clinical results, dupilumab currently appears to be a very promising biological drug for the treatment of severe uncontrolled asthma. Dupilumab inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling and was previously found to be effective in asthma. A recent trial showed that in patients with difficult-to-control asthma, dupilumab can markedly decrease asthma exacerbations and improve respiratory symptoms and lung function; these effects were paralleled by significant reductions in T-helper 2-associated inflammatory biomarkers.","answer":"yes"}
{"id":"5c6d441d7c78d69471000037","question":"Does Eucommia ulmoides leaf extract ameliorates steatosis\/fatty liver induced by high-fat diet?","context":"These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.  Together, these results suggest that EUE and its active components enhance lysosomal activity, resulting in decreased ER stress and hepatic dyslipidemi Du-zhong (Eucommia ulmoides Oliver) leaf extract mediates hypolipidemic action in hamsters fed a high-fat diet.This study examined the effect of a Du-zhong (Eucommia ulmoides Oliver) leaf extract (0.175 g\/100 g diet) that was supplemented with a high-fat diet (10% coconut oil, 0.2% cholesterol, wt\/wt) on hyperlipidemic hamsters.  Preventive effect of Eucommia leaf extract on aortic media hypertrophy in Wistar-Kyoto rats fed a high-fat diet.Eucommia ulmoides Oliver leaf extract (ELE) has been shown to have anti-hypertensive and anti-obesity effects in rats that are fed a high-fat diet (HFD).  Eucommia ulmoides Oliver leaf extract (ELE) has been shown to have anti-hypertensive and anti-obesity effects in rats that are fed a high-fat diet (HFD). The hepatic fatty acid synthase and HMG-CoA reductase activities were significantly lowered by a Du-zhong leaf extract supplement in high fat-fed hamsters. These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.<br> Both forms of Eucommia leaves minimised increases in body weight and visceral fat in a dose-dependent fashion. These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters. The hepatic fatty acid synthase and HMG-CoA reductase activities were significantly lowered by a Du-zhong leaf extract supplement in high fat-fed hamsters.","answer":"yes"}
{"id":"5c6b82a17c78d6947100002f","question":"Is verubecestat effective for Alzheimer\u2019s Disease?","context":"The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in AD treatment. This reaction was applied to the preparation of verubecestat, which is currently undergoing clinical evaluation for the treatment of Alzheimer's disease. Verubecestat is an inhibitor of \u03b2-site amyloid precursor protein cleaving enzyme 1 (BACE1) being evaluated in clinical trials for the treatment of Alzheimer's disease.  CONCLUSIONS: Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events.  Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease.Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events.  CONCLUSIONS Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events.","answer":"no"}
{"id":"5c6f15577c78d69471000053","question":"Is galcanezumab effective for treatment of migraine?","context":"Importance: Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention. Conclusions and Relevance: Monthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies.  PURPOSE OF REVIEW: Monoclonal antibodies (mAbs) targeting the calcitonin-gene-related peptide (CGRP) pathway have been developed for episodic and chronic migraine prevention, either through binding the CGRP ligand (eptinezumab, fremanezumab, galcanezumab) or the CGRP receptor (erenumab). Background Safety findings from a Phase 2b study of galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, for prevention of migraine (NCT02163993) are reported here. Safety of galcanezumab in patients with episodic migraine: A randomized placebo-controlled dose-ranging Phase 2b study. Currently, there is considerable excitement regarding monoclonal antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene-related peptide receptor (erenumab). To date, these monoclonal antibodies have shown promising efficacy in clinical trials, with no major safety concerns. If ongoing long-term studies show that their efficacy can be maintained, this may herald a new era for effective antimigraine therapies. CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks.  Four monoclonal antibodies (mAbs) targeting the CGRP pathway are currently under evaluation for the prevention of episodic and chronic migraine: eptinezumab (ALD403), fremanezumab (TEV-48125), galcanezumab (LY2951742), and erenumab (AMG334).  Introduction Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide, used for migraine prevention. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Galcanezumab induced a robust, dose-dependent, and durable inhibition of capsaicin-induced increase in DBF, supporting the continued clinical development of galcanezumab for prophylaxis in migraine patients. The efficacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis.Based on the results of this meta-analysis, CGRP monoclonal antibodies significantly reduced the monthly migraine days and acute migraine-specific medication.  Importance Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention. Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine. BACKGROUND Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine. BACKGROUND Galcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (\u22646-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning. CONCLUSION Twelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days. CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. Conclusions and Relevance Monthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies. Importance Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention. BACKGROUND Galcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (\u22646-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning. BACKGROUND Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine. Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly MHDs compared to placebo (placebo -2.7, galcanezumab 120 mg -4.8, galcanezumab 240 mg -4.6) (<br><b>CONCLUSIONS<\/b>: Both doses of galcanezumab were superior to placebo in reducing the number of monthly MHDs. Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.<br><b>CLINICALTRIALSGOV IDENTIFIER<\/b>: NCT02614261.<br><b>CLASSIFICATION OF EVIDENCE<\/b>: This interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.<br> In September 2018, the US FDA approved galcanezumab as a once-monthly subcutaneous injection for the preventive treatment of migraine in adults. This article summarizes the milestones in the development of galcanezumab leading to its first approval for the preventive treatment of migraine in adults.<br> Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine. This article summarizes the milestones in the development of galcanezumab leading to its first approval for the preventive treatment of migraine in adults. Twelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days.","answer":"yes"}
{"id":"5c52028807ef653866000009","question":"Can mitochondria be inherited by both parents in humans?","context":"Biparental Inheritance of Mitochondrial DNA in Humans. Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring.","answer":"yes"}
{"id":"5c71648b7c78d69471000067","question":"Can Diazepam be beneficial  in the treatment of  traumatic brain injury?","context":"he present experiment examined the effects of diazepam, a positive modulator at the GABA(A) receptor, on survival and cognitive performance in traumatically brain-injured animals. I","answer":"yes"}
{"id":"5c57216e07647bbc4b000018","question":"In clinical trials, the H3 R antagonist CEP-26401 has a positive effect on cognition, yes or no?","context":"CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement hese results demonstrate potent behavioral effects of CEP-26401 in rodent models and suggest that this novel H\u2083R antagonist may have therapeutic utility in the treatment of cognitive and attentional disorders CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement. CEP-26401 (irdabisant), a potent and selective histamine H\u2083 receptor antagonist\/inverse agonist with cognition-enhancing and wake-promoting activities. However, although a number of clinical studies examining the efficacy of H3 receptor antagonists for a variety of cognitive disorders are currently underway, no clinical proof of concept for an H3 receptor antagonist has been reported to date. Further clinical studies are required to establish the potential of low-dose CEP-26401 in cognition enhancement.<br>","answer":"yes"}
{"id":"5c6f6d997c78d69471000055","question":"Is pimavanserin effective for Parkinson's disease psychosis?","context":"Two cases of Parkinson's disease with an unusual delusional misidentification, intermetamorphosis, are presented, along with their improvement with pimavanserin, a novel atypical antipsychotic medication. RATIONALE: Pimavanserin, a selective serotonin 2A receptor inverse agonist, is a promising candidate for treating Parkinson's disease psychosis. OBJECTIVE: Our aim was to describe the efficacy and tolerability of pimavanserin, a highly selective serotonin 5-HT2A receptor inverse agonist\/antagonist indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP), using the metrics of number needed to treat (NNT) and number needed to harm (NNH). Pimavanserin: novel pharmacotherapy for Parkinson's disease psychosis. INTRODUCTION: Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP) A pivotal phase III clinical trial demonstrated significant improvement in PDP symptoms in patients receiving pimavanserin compared to placebo-treated patients.  Pimavanserin's mechanism of action might contribute to its unique psychopharmacological properties in the improved treatment of PDP, and perhaps psychosis in other diseases including schizophrenia and dementia-related psychosis. Pimavanserin (Nuplazid\u2122) for the treatment of Parkinson disease psychosis: A review of the literature.Options for the treatment of Parkinson disease psychosis are limited.  Pimavanserin for the treatment of Parkinson's disease psychosis.Pimavanserin is an antipsychotic with a unique mechanism of action (5-HT2A receptor inverse agonist) and no measurable dopaminergic activity; it has been demonstrated to be efficacious, well tolerated and safe for the treatment of PDP.  A Retrospective Study of Pimavanserin Use in a Movement Disorders Clinic.Pimavanserin, a 5-HT2A inverse agonist, was commercially released in the United States in April 2016 for the treatment of Parkinson disease psychosis.  receptor inverse agonist pimavanserin was recently approved by the US FDA for the treatment of PDP and may prove to be a more targeted therapy without the downsides of atypical antipsychotics. Evidence-Based Review of Pharmacotherapy Used for Parkinson's Disease Psychosis.Despite lack of rigor in study designs, published data to date suggest that clozapine and pimavanserin should be considered drugs of choice to treat PD psychosis. Pimavanserin: A novel therapeutic option for Parkinson disease psychosis.While pimavanserin appears to be a safe, effective, and well-tolerated therapeutic option for PDP, additional clinical trials and open-label extension studies are needed to determine the long-term safety and efficacy of this promising therapy.  Objective: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP). Pimavanserin: A Novel Drug Approved to Treat Parkinson's Disease Psychosis. CONCLUSIONS Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease. OBJECTIVE To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. RESULTS Pimavanserin 34 mg\/d was effective in treating hallucinations and delusions associated with Parkinson's disease. BACKGROUND Pimavanserin is a selective 5-HT2A receptor inverse agonist and antagonist approved in the USA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP). INTERPRETATION Pimavanserin may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist. Pimavanserin (ACP-103) is a selective inverse agonist of the 5-hydroxytryptamine 2A (5-HT2A) receptor intended to treat patients with Parkinson's disease psychosis (PDP). INTERPRETATION Pimavanserin showed efficacy in patients with Alzheimer's disease psychosis at the primary endpoint (week 6) with an acceptable tolerability profile and without negative effect on cognition. [Pimavanserin: a new treatment for the Parkinson's disease psychosis]. Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of parkinson's disease psychosis. Pimavanserin, a selective 5-HT2A inverse agonist\/antagonist, was approved in the U.S. for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Pimavanserin: A Novel Antipsychotic for Parkinson's Disease Psychosis. CONCLUSIONS Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease. OBJECTIVE To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. RESULTS Pimavanserin 34 mg\/d was effective in treating hallucinations and delusions associated with Parkinson's disease. If this is granted, we believe the evidence of Pimavanserin efficacy, safety and tolerability will position this medication as the first choice for treatment of Parkinson's disease psychosis. The development of pimavanserin as an antipsychotic opened a new therapeutic avenue in the treatment of PDP as well as targeting psychosis in other disorders such as Alzheimer's disease. OBJECTIVE To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of pimavanserin for the treatment of hallucinations and delusions of Parkinson's disease psychosis (PDP). INTERPRETATION Pimavanserin may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist. <b>OBJECTIVE<\/b>: To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. Data were available from 616 patients with Parkinson's disease with hallucinations and delusions who received at least 1 dose of pimavanserin, with a total exposure of 825 patient-years in the Parkinson's disease psychosis population.<br><b>RESULTS<\/b>: Pimavanserin 34 mg\/d was effective in treating hallucinations and delusions associated with Parkinson's disease. Pimavanserin did not worsen motor function, an adverse effect commonly observed with other antipsychotics, probably because of a lack of consequential dopamine binding.<br><b>CONCLUSIONS<\/b>: Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease. Pimavanserin (Nuplazid\u2122) is a selective and potent serotonin 2A (5-HT2A) receptor inverse agonist and antagonist developed by ACADIA Pharmaceuticals that has been approved in the US as a treatment for patients with hallucinations and delusions associated with Parkinson's disease psychosis. This article summarizes the milestones in the development of pimavanserin leading to this first approval for the treatment of hallucinations and delusions in patients with Parkinson's disease psychosis. In a Phase 2 study with pimavanserin in Alzheimer's disease psychosis, pimavanserin significantly (p=0.045) improved psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS). To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease. Pimavanserin 34 mg\/d was effective in treating hallucinations and delusions associated with Parkinson's disease.","answer":"yes"}
{"id":"5c5b52731a4c55d80b000003","question":"Is deletion at 6q24.2-26 associated with longer survival of patients with high-grade serous ovarian carcinoma (HGSOCs)?","context":"Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients. We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95%CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95%CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life. OBJECTIVE We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. OBJECTIVE We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life.<br> <b>OBJECTIVE<\/b>: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.<br><b>METHODS<\/b>: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.","answer":"yes"}
{"id":"5c65484ee842deac6700001f","question":"Can mogamulizumab be used for the treatment of cutaneous T-cell lymphoma?","context":"In the large international phase III MAVORIC trial, patients with previously treated cutaneous T-cell lymphoma who received the anti-CCR4 monoclonal antibody mogamulizumab experienced significantly longer progression-free survival and higher response rates, as well as better quality of life, than those who received vorinostat, a standard therapy.","answer":"yes"}
{"id":"5c72ba807c78d69471000076","question":"Is avelumab effective for bladder cancer?","context":"BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma.  The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab.  Five immune CPI have recently been approved for aUC\/mUC by the US Food and Drug Administration (FDA) including atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab.  RECENT FINDINGS: Since May 2016, five different agents targeting the PD-1\/PD-L1 pathway (atezolizumab, pembrolizumab, nivolumab, avelumab, durvalumab) have received FDA approval for the treatment of aUC in the platinum-refractory setting, while pembrolizumab and atezolizumab are FDA-approved for cisplatin-ineligible patients in the first-line setting. Avelumab for the treatment of urothelial cancer. Avelumab, a PD-1 ligand (PD-L1) inhibitor, is currently being investigated for the treatment of UC. Areas covered: This article will review the pharmacological characteristics of avelumab, the efficacy studies which led to its approval, its safety profile, as well as its place within the management of urothelial carcinoma with immunotherapy.  Expert commentary: Avelumab has shown promising antitumor activity and a manageable safety profile in patients with UC.  Atezolizumab is the only member of this class currently approved for the treatment of bladder cancer, but nivolumab, pembrolizumab, durvalumab, and avelumab all have positive results for this indication, and approvals are anticipated in the near future. This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. Atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab are promising PD-1\/PD-L1 blockade drugs under investigation that will redefine the standard of care for bladder cancer. Monoclonal antibodies that target programmed cell death protein 1 (PD-1), including Nivolumab and Pembrolizumab, and its ligand, PD-L1, including Atezolizumab, Durvalumab, Avelumab, have all been investigated and approved in the setting of metastatic refractory urothelial cancer (Gupta et al. Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma. Nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab are among the exciting recent novel therapeutic advances gaining approvals by the FDA for treatment of advanced-stage urothelial carcinoma.","answer":"yes"}
{"id":"5c6b7a9e7c78d69471000029","question":"Is cabozantinib effective for Hepatocellular Carcinoma?","context":"However, clinical trials of nonselective kinase inhibitors with c-Met activity (tivantinib, cabozantinib, foretinib, and golvatinib) in patients with HCC have failed so far to demonstrate significant efficacy.  Rationale for use, clinical trial data, and current recommendations for cabozantinib in renal cell cancer, thyroid cancer, prostate cancer, hepatocellular cancer, and lung cancer are detailed in this article. More recently, promising outcomes have also been reported with new agents, such as nivolumab and cabozantinib. Positive results in recent phase III clinical trials have confirmed the high value of anti-angiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities.  More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab).  The rapidly changing treatment landscape due to the emergence of new treatment options (sorafenib and lenvatinib equally effective in first line; regorafenib, cabozantinib, and ramucirumab showing OS benefit in second line with nivolumab approved by the FDA based on response rate) underscores the importance of re-assessing the role of the first approved systemic agent in HCC, sorafenib.  Positive phase III-study data have been published for lenvatinib as first-line and cabozantinib as second-line therapy.  Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. BACKGROUND: Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease.  CONCLUSIONS: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. Expert opinion: Based on favorable phase III clinical trial data, sorafenib and lenvatinib are considered promising agents for HCC as first-line systemic chemotherapy. Moreover, regorafenib and cabozantinib are useful second-line therapies after the failure of sorafenib. CONCLUSIONS: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo.  Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma.Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo.  CONCLUSIONS Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. More recently, promising outcomes have also been reported with new agents, such as nivolumab and cabozantinib.  Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval [CI], 0.63 to 0.92; P=0.005). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P<0.001), and the objective response rates were 4% and less than 1%, respectively (P=0.009). Positive phase III-study data have been published for lenvatinib as first-line and cabozantinib as second-line therapy.  The most common high-grade events were palmar-plantar erythrodysesthesia (17% with cabozantinib vs. 0% with placebo), hypertension (16% vs. 2%), increased aspartate aminotransferase level (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%).<br><b>CONCLUSIONS<\/b>: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. CONCLUSIONS Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. CONCLUSIONS The tyrosine kinase inhibitors sorafenib (first line) and regorafenib (second line) have been approved for hepatocellular carcinoma, and the immune checkpoint inhibitor nivolumab obtained conditional approval for sorafenib-experienced patients in the United States. The principal advancements in the treatment of hepatocellular carcinoma (HCC) are the use of new systemic treatments such as lenvatinib in first-line treatment and regorafenib, cabozantinib and ramucirumab in second-line treatment due to their benefits in terms of overall survival. Recently, a few systemic chemotherapies proved to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib, cabozantinib, and ramucirumab as second-line therapy. <b>BACKGROUND<\/b>: The approval of the tyrosine kinase inhibitor sorafenib in 2007 marked a milestone in the treatment of hepatocellular carcinoma, as sorafenib was the first systemic therapy to show a survival benefit in patients with advanced hepatocellular carcinoma. We also elaborate the unmet need of biomarkers to guide treatment decisions and discuss the emerging field of immunotherapy in hepatocellular carcinoma.<br><b>CONCLUSIONS<\/b>: The tyrosine kinase inhibitors sorafenib (first line) and regorafenib (second line) have been approved for hepatocellular carcinoma, and the immune checkpoint inhibitor nivolumab obtained conditional approval for sorafenib-experienced patients in the United States. Cabozantinib in the treatment of hepatocellular carcinoma. The approval of the tyrosine kinase inhibitor sorafenib in 2007 marked a milestone in the treatment of hepatocellular carcinoma, as sorafenib was the first systemic therapy to show a survival benefit in patients with advanced hepatocellular carcinoma.","answer":"yes"}
{"id":"5c5839e707647bbc4b00001f","question":"Is there a link between BCL11B haploinsufficiency and syndromic neurodevelopmental delay?","context":"BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells. Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B. Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency. Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo. A further frameshift mutation was transmitted from a similarly affected mother. Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient. Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice. Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice. Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. In addition, we suggest that missense mutations affecting specific sites within zinc-finger domains might result in distinct and more severe clinical outcomes. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay.  Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay.","answer":"no"}
{"id":"5c6f6ae37c78d69471000054","question":"Is Lasmiditan effective for migraine?","context":"Amongst the ditans, lasmiditan: (i) fails to constrict human coronary arteries; and (ii) is effective for the acute treatment of migraine in preliminary Phase III clinical trials. Although ongoing phase III clinical trials are needed to confirm its efficacy and safety, lasmiditan might offer an alternative to treat acute migraine with no associated cardiovascular risk. Lasmiditan is considered to be the first member of a new drug category, the neurally acting anti-migraine agent (NAAMA) Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice. Lasmiditan, a highly selective 5-HT1F agonist, has completed two Phase III randomized, double blind, placebo-controlled clinical trials, with a third - a long-term, open-label safety study - still underway. Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors. Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6, p< 0.001), similar to those dosed with lasmiditan 100 mg (28.2%; OR 2.2, 95% CI 1.6-3.0, p< 0.001). Furthermore, compared with those dosed with placebo, more patients dosed with lasmiditan 200 mg (40.7% vs 29.5%; OR 1.6, 95% CI 1.3-2.1, p< 0.001) and lasmiditan 100 mg (40.9%; OR 1.7, 95% CI, 1.3-2.2, p< 0.001) were free of their MBS at 2 hours after dosing. CONCLUSIONS: Lasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack. For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine.  While lasmiditan most likely is effective in the treatment of migraine attacks it had, unfortunately, a high incidence of CNS related AEs in the oral RCT.  Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan--a randomised proof-of-concept trial.At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine.  Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice.  BACKGROUND Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study. INTERPRETATION Oral lasmiditan seems to be safe and effective in the acute treatment of migraine. The 5-HT1F receptor agonist lasmiditan, a drug acting through non-vasoconstrictive mechanisms, represents a promising safe, effective and tolerated acute migraine therapy also for patients at cardiovascular risk. For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine. The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials. Within the past few years, new and promising drugs such as more specific 5-HT 1F receptor agonists (that is, lasmiditan) and monoclonal calcitonin gene-related peptide (CGRP) receptor antibodies entered advanced development phases while non-invasive neuromodulatory approaches were suggested to be potentially effective as non-pharmaceutical interventions for migraine. CLASSIFICATION OF EVIDENCE This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack. BACKGROUND Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study. INTERPRETATION Oral lasmiditan seems to be safe and effective in the acute treatment of migraine. Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors. The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity. Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6, <br><b>CONCLUSIONS<\/b>: Lasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors.<br><b>CLINICALTRIALSGOV IDENTIFIER<\/b>: NCT02439320.<br><b>CLASSIFICATION OF EVIDENCE<\/b>: This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack.<br> The most common adverse events were CNS related and included dizziness, fatigue, vertigo, paraesthesia, and somnolence.<br><b>INTERPRETATION<\/b>: Oral lasmiditan seems to be safe and effective in the acute treatment of migraine. Dizziness, paresthesia and sensations of heaviness (usually limb) were more common on lasmiditan.<br><b>CONCLUSIONS<\/b>: At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. <b>BACKGROUND<\/b>: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study. For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine. This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack. While lasmiditan most likely is effective in the treatment of migraine attacks it had, unfortunately, a high incidence of CNS related AEs in the oral RCT.","answer":"yes"}
{"id":"5c6d97497c78d69471000040","question":"Are there graph kernel libraries available implemented in JAVA?","context":"graphkernels: R and Python packages for graph comparison. Measuring the similarity of graphs is a fundamental step in the analysis of graph-structured data, which is omnipresent in computational biology. Graph kernels have been proposed as a powerful and efficient approach to this problem of graph comparison. Here we provide graphkernels, the first R and Python graph kernel libraries including baseline kernels such as label histogram based kernels, classic graph kernels such as random walk based kernels, and the state-of-the-art Weisfeiler-Lehman graph kernel. The core of all graph kernels is implemented in C\u2009++ for efficiency. Using the kernel matrices computed by the package, we can easily perform tasks such as classification, regression and clustering on graph-structured samples.","answer":"no"}
{"id":"5c6df86b7c78d69471000045","question":"Is baricitinib effective for rheumatoid arthritis?","context":"CONCLUSION: Baricitinib 2\u2009mg and 4\u2009mg administered once daily, in combination with DMARD, were efficacious interventions for active RA that had no significant risk of TEAE development. CONCLUSIONS: The efficacy and safety profile of baricitinib was maintained during long-term treatment of Japanese patients with RA and background methotrexate therapy. CONCLUSION: In a phase IIb study in RA, the safety and tolerability profile of baricitinib, up to 128 weeks, remained consistent with earlier observations, without unexpected late signals. Clinical improvements seen in the 24-week blinded period were maintained during the OLE. CONCLUSION: Data for baricitinib, with\/without methotrexate, in Japanese subpopulations across all stages of the RA treatment continuum accord with the efficacy\/safety profile in overall study populations. Conclusion: Baricitinib demonstrated a consistent, beneficial treatment effect in bDMARD-refractory patients across subgroups based on baseline characteristics and prior bDMARD use. Baricitinib is effective in treatment of RA, and did not appear to have significant safety concerns during the first 6\u00a0months of treatment. OBJECTIVE Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA). EXPERT OPINION JAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily. OBJECTIVE Baricitinib is an oral, once-daily selective Janus kinase (JAK1\/JAK2) inhibitor for adults with moderately to severely active rheumatoid arthritis (RA). Two different Janus kinase (JAK) inhibitors-baricitinib and tofacitinib-are effective and licensed in active rheumatoid arthritis (RA). Baricitinib for the treatment of rheumatoid arthritis. OBJECTIVES Oral targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), including the Janus kinase inhibitors tofacitinib and baricitinib, are the latest addition to the therapeutic options for rheumatoid arthritis (RA). Baricitinib (Olumiant\u2122) is an orally-administered, small-molecule, janus-associated kinase (JAK) inhibitor developed by Eli Lilly and Incyte Corporation for the treatment of rheumatoid arthritis (RA), atopic dermatitis and systemic lupus erythematosus. EXPERT OPINION JAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily. Tofacitinib 10\u202fmg\u202f+\u2009methotrexate (MTX) and baricitinib 4\u202fmg\u202f+\u2009MTX were among the most effective treatments for active RA with an inadequate DMARD or biologic response, followed by baricitinib 2\u202fmg\u202f+\u2009MTX, tofacitinib 5\u202fmg\u202f+\u2009MTX, and adalimumab\u202f+\u2009MTX. OBJECTIVE Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA). CONCLUSIONS In patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab. Thus, once-daily baricitinib, as monotherapy or in combination with methotrexate, is an effective and generally well tolerated emerging treatment for patients with moderate to severe active RA who have responded inadequately to or are intolerant of \u2265\u00a01 DMARD, and extends the options available for this population. OBJECTIVES Oral targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), including the Janus kinase inhibitors tofacitinib and baricitinib, are the latest addition to the therapeutic options for rheumatoid arthritis (RA). Five phase 3 trials of Baricitinib, a JAK1 and JAK2 inhibitor, have been performed and showed high clinical efficacy in patients with active RA and na\u00efve to sDMARDs or an inadequate response to sDMARDs, MTX or bDMARDs. It is also reported that safety was tolerable within the limited study period.<br><b>AREAS COVERED<\/b>: We here review the recent progress in the development of baricitinib and its potential for the treatment of RA. <b>OBJECTIVE<\/b>: Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA). In February 2017, baricitinib was approved in the EU, as monotherapy or in combination with methotrexate, for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). In patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab. In pivotal multinational trials, once-daily baricitinib 4\u00a0mg, with\/without methotrexate (\u00b1\u00a0another csDMARD), improved the signs and symptoms of RA, disease activity and physical function in DMARD-naive patients and in patients with an inadequate response to methotrexate, csDMARDs or TNF inhibitors; baricitinib treatment also slowed structural joint damage in DMARD-naive patients and in those with an inadequate response to methotrexate and csDMARDs. Five phase 3 trials of Baricitinib, a JAK1 and JAK2 inhibitor, have been performed and showed high clinical efficacy in patients with active RA and na\u00efve to sDMARDs or an inadequate response to sDMARDs, MTX or bDMARDs.","answer":"yes"}
{"id":"5c73acf27c78d6947100008a","question":"Is Semagacestat effective for treatment of Alzheimer's disease?","context":"However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects. BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD). A clinical trial with the wide-spectrum \u03b3-secretase inhibitor semagacestat has, however, demonstrated that global inhibition of all \u03b3-secretases causes serious toxicity.  OBJECTIVE: Semagacestat, a \u03b3-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted.  CONCLUSIONS: As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. Semagacestat was associated with more adverse events, including skin cancers and infections. BACKGROUND In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD). Semagacestat was associated with more adverse events, including skin cancers and infections. CONCLUSIONS As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability. OBJECTIVE Semagacestat, a \u03b3-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted. Recently disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo. The recent failure of semagacestat in two large Phase III studies questions the value of \u03b3-secretase inhibitors in treating Alzheimer's disease. A phase 3 trial of semagacestat for treatment of Alzheimer's disease.As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability.  Preliminary results from Phase III studies showed that semagacestat failed to slow disease progression, and it was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living.  Changes in Neuropsychiatric Inventory Associated with Semagacestat Treatment of\u00a0Alzheimer's Disease.In participants with mild to moderate AD, high dose semagacestat treatment was associated with greater severity and faster worsening of NPS in a pattern resembling an agitated depression.  Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P<0.001 for all comparisons with placebo). <b>OBJECTIVE<\/b>: Semagacestat, a \u03b3-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted. Other relevant safety findings associated with semagacestat treatment included cognitive and functional worsening, skin-related TEAEs, renal and hepatic changes, increased QT interval, and weight loss. Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P&lt;0.001 for all comparisons with placebo). Semagacestat, a \u03b3-secretase inhibitor, demonstrated an unfavorable risk-benefit profile in a Phase 3 study of patients with Alzheimer's disease (IDENTITY trials), and clinical development was halted.","answer":"no"}
{"id":"5c840daf617e120c34000007","question":"Does Rhamnose have any effect on aging?","context":"The monosaccharide analysis showed that rhamnose (Rha) and glucose (Glu) may play vital roles in maintaining the antioxidant and anti-aging activities.  Some of these mechanisms will be reviewed as well as the capacity of fucose- and rhamnose-rich oligo- and polysaccharides (FROP and RROP) to counteract several of the mechanisms involved in skin aging.","answer":"yes"}
{"id":"5c7d6b3e45e140a523000001","question":"Is there any approved treatment for NAFLD?","context":"Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited. Non-alcoholic fatty liver disease (NAFLD) has become one of the most prominent forms of chronic liver disease worldwide, reflecting the epidemic of global obesity. Those with the progressive variant of NAFLD, non-alcoholic steatohepatitis (NASH), are at significantly increased risk of multisystem morbidity and mortality. However, there are currently no approved pharmacologic therapies for NASH. Although much progress has been made in enhancing our understanding of NAFLD pathogenesis, development of pharmacologic treatments has been hindered by challenges in clinical trial enrollment and complexities in clinical trial design.  Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy. Nonalcoholic fatty liver disease (NAFLD) has an increasing prevalence worldwide. At present, no specific pharmacotherapy is approved for NAFLD.","answer":"no"}
{"id":"5c72bd047c78d69471000077","question":"Can pazopanib be used for treatment von Hippel-Lindau disease?","context":"Variable response of CNS hemangioblastomas to Pazopanib in a single patient with von Hippel-Lindau disease: Case report. Treatment of RCCs with tyrosine kinase inhibitors (TKIs) such as Pazopanib is now first line therapy, but their effect on VHL-associated CNS HBs remains unknown. We report the use of Pazopanib in a patient with VHL disease for treatment of RCC who also harbored multiple CNS HBs.  Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single-centre, phase 2 trial. INTERPRETATION: Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials. Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients.  Recurrent multiple CNS hemangioblastomas with VHL disease treated with pazopanib: a case report and literature review.  Here, we report a 37-year-old woman's case with recurrent and rapidly progressive VHL-associated hemangioblastomas, causing severe disability. She was treated 24 months with pazopanib, a multityrosine kinase inhibitor (TKI) targeting VEGF and PDGF-\u03b2 pathways.  Pazopanib therapy for cerebellar hemangioblastomas in von Hippel-Lindau disease: case report. Here we provide the first report demonstrating clinical and radiological anti-tumor response using pazopanib, a small molecule multi-receptor tyrosine kinase inhibitor, in a patient with treatment-refractory VHL-associated CNS hemangioblastoma.  Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients. METHODS In this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician. We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease. INTERPRETATION Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials. FINDINGS Between Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib. Pazopanib therapy for cerebellar hemangioblastomas in von Hippel-Lindau disease: case report.von Hippel-Lindau (VHL) disease is a genetically acquired multisystem tumor syndrome of the viscera and central nervous system (CNS).  Recurrent multiple CNS hemangioblastomas with VHL disease treated with pazopanib: a case report and literature review.Hemangioblastoma is a rare benign neoplasm, accounting for less than 2% of all primitive brain tumors.  We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease.<br><b>METHODS<\/b>: In this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician. This study is registered with ClinicalTrials.gov, number NCT01436227, and is closed to accrual.<br><b>FINDINGS<\/b>: Between Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib. Treatment-related serious adverse events included one case each of appendicitis and gastritis and one patient had a fatal CNS bleed.<br><b>INTERPRETATION<\/b>: Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials. Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients. We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease. In this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician. Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials. Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients. Between Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib.","answer":"yes"}
{"id":"5c89461675a4a5d219000013","question":"Is Netrin-1 a secreted protein?","context":"The axon guidance cues netrin-1 is a secreted protein overexpressed in many different cancer tissues Netrin-1 is a secreted protein that directs long-range axon guidance during early stages of neural circuit formation and continues to be expressed in the mammalian forebrain during the postnatal period of peak synapse formation.   Netrin-1, a laminin-related secreted protein, displays proto-oncogenic activity in cancers. Netrin-1, a multifunctional secreted protein, is up-regulated in cancer and inflammation. etrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. Netrins are a family of secreted protein related to laminin and act as tropic cues directing axon growth and cell migration during neural development.","answer":"yes"}
{"id":"5c62a529e842deac6700000b","question":"Is the yeast (Saccharomyces cerevisiae) genome organized into topologically associated domains (TADs)?","context":"Recent advances in our understanding of the three-dimensional organization of the eukaryotic nucleus have rendered the spatial distribution of genes increasingly relevant. In a recent work (Tsochatzidou et al., Nucleic Acids Res 45:5818-5828, 2017), we proposed the existence of a functional compartmentalization of the yeast genome according to which, genes occupying the chromosomal regions at the nuclear periphery have distinct structural, functional and evolutionary characteristics compared to their centromeric-proximal counterparts. Around the same time, it was also shown that the genome of Saccharomyces cerevisiae is organized in topologically associated domains (TADs), which are largely associated with the replication timing. Form and function of topologically associating genomic domains in budding yeast. Although similar structures appear to be conserved in fission yeast, computational modeling and analysis of high-throughput chromosome conformation capture (Hi-C) data have been used to argue that the small, highly constrained budding yeast chromosomes could not have these structures. In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity. Furthermore, these boundaries separate regions of similarly timed replication origins connecting the long-known effect of genomic context on replication timing to genome architecture. To investigate the molecular basis of TAD formation, we performed Hi-C experiments on cells depleted for the Forkhead transcription factors, Fkh1 and Fkh2, previously associated with replication timing. Forkhead factors do not regulate TAD formation, but do promote longer-range genomic interactions and control interactions between origins near the centromere. Thus, our work defines spatial organization within the budding yeast nucleus, demonstrates the conserved role of genome architecture in regulating DNA replication, and identifies a molecular mechanism specifically regulating interactions between pericentric origins. Around the same time, it was also shown that the genome of Saccharomyces cerevisiae is organized in topologically associated domains (TADs), which are largely associated with the replication timing. Around the same time, it was also shown that the genome of Saccharomyces cerevisiae is organized in topologically associated domains (TADs), which are largely associated with the replication timing.  In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity.","answer":"yes"}
{"id":"5c72a5ca7c78d6947100006d","question":"As of Feb 2019, are major brain gangliosides a target for the treatment of Alzheimer's disease?","context":"An understanding of the mechanism on the interaction of GM1 and A\u03b2s in AD may contribute to the development of new neuroregenerative therapies for this disorder. Abnormal ganglioside metabolism also may occur in AD brains Continuous intraventricular infusion of GM1 has recently been shown to have a significant beneficial effect in Alzheimer disease of early onset (AD Type I). Gangliosides--a new therapeutic agent against stroke and Alzheimer's disease. Gangliosides--a new therapeutic agent against stroke and Alzheimer's disease.Gangliosides are glycosphingolipids localized to the outer leaflet of the plasma membrane of vertebrate cells.  Continuous intraventricular infusion of GM1 has recently been shown to have a significant beneficial effect in Alzheimer disease of early onset (AD Type I).<br>","answer":"yes"}
{"id":"5c72f8557c78d69471000080","question":"Is Miller-Dieker syndrome associated with abnormalities of chromosome 1?","context":"A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion).  Chromosome microdeletions within 17p13.3 can result in either isolated lissencephaly sequence (ILS) or Miller-Dieker syndrome (MDS).  We report a fetus with lissencephaly diagnosed as Miller-Dieker Syndrome postnatally. G banded chromosome analysis revealed 45,X,psu dic(17;Y)(p13;p11.32).ish dic (17;Y)(LIS1-,RARA+, SRY+, DYZ3+) by G-banding analysis using high resolution banding technique. Fetal delayed cortical development will be the findings to perform further investigations including fluorescence in situ hybridization analysis for MDS, a 17p13.3 microdeletion syndrome, pre\/postnatally. This will be the first case of MDS with unbalanced translocation between deleted short arm of chromosome 17 and Y chromosome.  We report the finding of a 2.5-Mb gene region quadruplication of Chromosome 17p13.3. This region is well characterized for the deletion leading to Miller-Dieker syndrome but has an unclear replication phenotype.  Both deletions have overlapped with the critical region of Miller-Dieker syndrome (MDS) and involved candidate genes such as PAFAH1B1, YWHAE and CRK. In addition, SNP array and FISH analyses on the parental peripheral blood samples demonstrated that both 17p13.3 and 17p13.3p13.2 deletions were of de novo origin. Miller-Dieker syndrome (MDS) is caused by a heterozygous deletion of chromosome 17p13.3 involving the genes LIS1 and YWHAE (coding for 14.3.3\u03b5) and leads to malformations during cortical development. We studied after death a 3-month-old girl whose karyotype was 45,XX,-15,-17,+der(17),t(15;17)(q13;p13.3) and thus combines abnormalities of chromosome 15 associated with the Prader-Willi syndrome and of chromosome 17 associated with the Miller-Dieker syndrome. The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13. The Miller-Dieker syndrome (type I lissencephaly) is a neuronal migration disorder which is associated with microdeletions in the short arm of chromosome 17. Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome. A 15-month-old girl with Miller-Dieker syndrome, a contiguous gene deletion syndrome involving chromosome 17p13.3 and resulting in lissencephaly, was diagnosed with precursor B-cell acute lymphoblastic leukemia. A computed tomography scan revealed evidence of lissencephaly, and chromosomal analysis showed a microdeletion on the short arm of chromosome 17 (17p13.3), confirming the diagnosis as Miller-Dieker syndrome. Familial Miller-Dieker syndrome associated with pericentric inversion of chromosome 17. The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region. Miller-Dieker syndrome (MDS), a disorder manifesting the severe brain malformation lissencephaly (\"smooth brain\"), is caused, in the majority of cases, by a chromosomal microdeletion of the distal short arm of chromosome 17. The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment. Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome. HIC1 is a candidate tumor suppressor gene which is frequently hypermethylated in human tumors, and its location within the Miller-Dieker syndrome's critical deletion region at chromosome 17p13.3 makes it a candidate gene for involvement in this gene deletion syndrome. A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion). About 15% of patients with isolated lissencephaly and more than 90% of patients with Miller-Dieker syndrome have microdeletions in a critical 350-kilobase region in chromosome 17p13.3 (ref. Chromosome aberrations in which epilepsy is a major and consistent finding include Angelman syndrome due to loss of the maternal 15q11.2-q12 segment, tetrasomy of the maternal segment 15pter-q13 due to an additional inv dup chromosome, Miller-Dieker syndrome due to deletion of the 17p13.3 segment including the lissencephaly1 gene, ring chromosome 20, and Wolf-Hirschhorn syndrome due to deletion of at least the 4p16.3 segment. Miller-Dieker syndrome and trisomy 5p in a child carrying a derivative chromosome with a microdeletion in 17p13.3 telomeric to the LIS1 and the D17S379 loci. The Miller-Dieker syndrome, a disorder of neuronal migration, is caused by deletions of chromosome 17p13.3. The girl was diagnosed by subtelomeric FISH and array-CGH, showing a 4.43-Mb heterozygous deletion on chromosome 10p that involved 14 genes and a 3.22-Mb single-copy gain on chromosome 17p, which includes the critical region of the Miller-Dieker syndrome and 61 genes. Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome.The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13.  Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment.Microdeletions of chromosome 17p13.3 involving YWHAE present with growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment.  Unbalanced translocation (15;17)(q13;13.3) with apparent Prader-Willi syndrome but without Miller-Dieker syndrome.We studied after death a 3-month-old girl whose karyotype was 45,XX,-15,-17,+der(17),t(15;17)(q13;p13.3) and thus combines abnormalities of chromosome 15 associated with the Prader-Willi syndrome and of chromosome 17 associated with the Miller-Dieker syndrome.  The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region.  A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3.Miller-Dieker syndrome (MDS) is a multiple malformation syndrome characterized by classical lissencephaly and a characteristic facies.  Case Report of Proliferative Peripheral Retinopathy in Two Familial Lissencephaly Infants with Miller-Dieker Syndrome.A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion).  Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome.Profilin is a conserved actin-monomer-binding protein which is found in all eukaryotes, including yeast.  We propose that essentially no loss of 17p material has occurred and confirm previous reports that the critical region for the production of the Miller-Dieker phenotype is located subterminally in the 17p13.3 region.<br> A review of the literature revealed five additional patients in three families, who had Miller-Dieker syndrome and an abnormality of 17p. We propose that essentially no loss of 17p material has occurred and confirm previous reports that the critical region for the production of the Miller-Dieker phenotype is located subterminally in the 17p13.3 region. Miller-Dieker syndrome: lissencephaly and monosomy 17p. Thus, we propose that monosomy of distal 17p may be the cause of Miller-Dieker syndrome in some patients. Miller-Dieker syndrome with der(17)t(12;17)(q24.33;p13.3)pat presenting with a potential risk of mis-identification as a de novo submicroscopic deletion of 17p13.3. Most cases of Miller-Dieker syndrome have a de novo deletion involving 17p13.3.","answer":"no"}
{"id":"5c93e6a1ecadf2e73f00001b","question":"Does the interaction of MOV10 and RNASEH2 promote L1 retrotransposition?","context":"Interplay between RNASEH2 and MOV10 controls LINE-1 retrotransposition. We show that MOV10 interacts with RNASEH2, and their interplay is crucial for restricting L1 retrotransposition.  Furthermore, we show that RNASEH2-MOV10-mediated L1 restriction downregulates expression of the rheumatoid arthritis-associated inflammatory cytokines and matrix-degrading proteinases in synovial cells, implicating a potential causal relationship between them and disease development in terms of disease predisposition.","answer":"no"}
{"id":"5c8cfca70101eac870000005","question":"Has the protein SIRT2 been associated to cervical cancer?","context":"A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal\u2009<\u2009preneoplasia\u2009<\u2009cancer.  We demonstrate that treatment of cervical cancer cells with a RhoGDI\u03b1-derived K52-trifluoroacetylated, substrate-derived peptidic sirtuin inhibitor severely impairs cell proliferation.","answer":"yes"}
{"id":"5c6438a5e842deac67000016","question":"Are recessive coding variants responsible for the majority of undiagnosed nonconsanguineous individuals?","context":"Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.","answer":"no"}
{"id":"5c6445f0e842deac67000017","question":"Is the NLM medical text indexer (MTI) still useful and relevant?","context":"12 years on - Is the NLM medical text indexer still useful and relevant? Facing a growing workload and dwindling resources, the US National Library of Medicine (NLM) created the Indexing Initiative project in 1996. This cross-library team's mission is to explore indexing methodologies for ensuring quality and currency of NLM document collections. The NLM Medical Text Indexer (MTI) is the main product of this project and has been providing automated indexing recommendations since 2002. After all of this time, the questions arise whether MTI is still useful and relevant.METHODS: To answer the question about MTI usefulness, we track a wide variety of statistics related to how frequently MEDLINE indexers refer to MTI recommendations, how well MTI performs against human indexing, and how often MTI is used. To answer the question of MTI relevancy compared to other available tools, we have participated in the 2013 and 2014 BioASQ Challenges. The BioASQ Challenges have provided us with an unbiased comparison between the MTI system and other systems performing the same task.RESULTS: Indexers have continually increased their use of MTI recommendations over the years from 15.75% of the articles they index in 2002 to 62.44% in 2014 showing that the indexers find MTI to be increasingly useful. The MTI performance statistics show significant improvement in Precision (+0.2992) and F1 (+0.1997) with modest gains in Recall (+0.0454) over the years. MTI consistency is comparable to the available indexer consistency studies. MTI performed well in both of the BioASQ Challenges ranking within the top tier teams.CONCLUSIONS: Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded. The BioASQ Challenge results have shown that we need to incorporate more machine learning into MTI while still retaining the indexing rules that have earned MTI the indexers' trust over the years. We also need to expand MTI through the use of full text, when and where it is available, to provide coverage of indexing terms that are typically only found in the full text. The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant. The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant. CONCLUSIONS Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded. 12 years on - Is the NLM medical text indexer still useful and relevant?Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded.  The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant. After all of this time, the questions arise whether MTI is still useful and relevant.<br><b>METHODS<\/b>: To answer the question about MTI usefulness, we track a wide variety of statistics related to how frequently MEDLINE indexers refer to MTI recommendations, how well MTI performs against human indexing, and how often MTI is used. The MTI performance statistics show significant improvement in Precision (+0.2992) and F<br><b>CONCLUSIONS<\/b>: Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded. The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant.<br> After all of this time, the questions arise whether MTI is still useful and relevant. The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant. Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded.","answer":"yes"}
{"id":"5c8972d4d558e5f232000006","question":"Has strimvelis been approved by the European Medicines Agency?","context":"Strimvelis (autologous CD34+ cells transduced to express adenosine deaminase [ADA]) is the first ex vivo stem cell gene therapy approved by the European Medicines Agency (EMA), indicated as a single treatment for patients with ADA-severe combined immunodeficiency (ADA-SCID) who lack a suitable matched related bone marrow donor.","answer":"yes"}
{"id":"5c83f858617e120c34000003","question":"Is treatment with Bacillus Calmette Guerin used for bladder cancer?","context":"Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer.  this result indicates that they may be used as putative biomarkers for monitoring changes in bladder carcinogenesis in response to BCG immunotherapy. response of urothelial precancerous lesions to intravesical BCG treatment bladder cancer (BC) is a major clinical issue.METHODS: We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT\u2009+\u2009intravesical instillations of bacillus Calmette-Guerin (BCG). To evaluate the efficacy and safety of a tailored endovesical immunotherapy protocol with biweekly BCG for elderly Patients with high risk non muscle invasive bladder cancer  Bacillus of Calmette-Guerin (BCG) therapy for high risk non muscle invasive bladder cancer treatment in older patients. BCG (Bacillus of Calmette Guerin) has been used for more than 20 years and is currently the most active agent for superficial bladder cancer therapy. BCG (Bacillus of Calmette Guerin) therapy of high-risk superficial bladder cancer. Production of IL-5, a classical T(H)2 cytokine, following bacillus Calmette guerin immunotherapy of bladder cancer. Intravesical Bacillus Calmette-Guerin is used to treat patients with superficial bladder cancer. There is some evidence that BCG therapy improves survival and progression rates of patients with high-risk superficial bladder cancer decreasing the proportion who require radical cystectomy. Local immunotherapy with bacillus Calmette-Guerin (BCG) is an effective and frequently used treatment for superficial bladder cancer. CONCLUSIONS Intravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids. PURPOSE Bacillus Calmette-Guerin is the most effective therapy for nonmuscle invasive bladder cancer. INTRODUCTION Bacillus Calmette-Guerin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used to treat urothelial carcinoma since 1976, and has been reported to eradicate disease in more than 70% of patients with in situ and stage I disease. Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer. Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results. We describe a 53 year- old man with a disseminated bacillus Calmette-Guerin (BCG) infection after intravescical instillation for bladder carcinoma. We tested the hypothesis that tumor expression of natural cytotoxicity receptor ligands can serve as a predictive factor for the response to intravesical bacillus Calmette-Guerin in patients with nonmuscle invasive, high grade bladder cancer. Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer. Pancreatic and psoas abscesses as a late complication of intravesical administration of bacillus Calmette-Guerin for bladder cancer: a case report and review of the literature.This case illustrates the fact that although intravesical administration of bacillus Calmette-Guerin is generally considered to be safe, it is not exempt from complications and these could appear immediately after treatment or as a delayed complication many years later. Effects of local bacillus Calmette-Guerin therapy in patients with bladder carcinoma on immunocompetent cells of the bladder wall.The antitumoral effects of intravesical bacillus Calmette-Guerin against recurrent superficial urothelial bladder cancer seem to be linked to immunological effector mechanisms.  Fatal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer.Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer.  Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results.We treated 40 patients with superficial bladder cancer via intravesical bacillus Calmette-Guerin for 1) prophylaxis against tumor recurrence, 2) residual carcinoma or 3) flat carcinoma in situ.  Bacillus Calmette-Guerin immunotherapy for bladder cancer.Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer.  Safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients.Intravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids.  Our results suggest that intralesional bacillus Calmette-Guerin immunotherapy can afford long term protection from transplanted bladder cancer, and that live bacillus Calmette-Guerin is superior to levamisole and P3 + Re-glycolipid + bacillus Calmette-Guerin cell walls in the treatment of bladder cancer. A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder. Up to 90% of patients with high grade superficial bladder tumors experience tumor recurrence and up to 50% have progression despite bacillus Calmette-Guerin treatment. We review how the bacillus Calmette-Guerin vaccine evolved to become standard therapy for superficial bladder cancer. We reviewed the historical literature describing the origin of the bacillus Calmette-Guerin vaccine as an anticancer agent and its singular success as the most effective immunotherapy used against a human neoplasm.","answer":"yes"}
{"id":"5c73acf17c78d69471000089","question":"Is eculizumab used for treatment of myasthenia gravis?","context":"Eculizumab treatment improved symptoms compared with placebo in a phase II study in patients with refractory gMG. D Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis.  The humanized monoclonal antibody eculizumab (Soliris\u00ae) is a complement inhibitor indicated for use in anti-acetylcholine receptor (AChR) antibody-positive adults with generalized myasthenia gravis (gMG) in the USA, refractory gMG in the EU, or gMG with symptoms that are difficult to control with high-dose IVIg therapy or PLEX in Japan.  Although several questions remain, such as duration of treatment, cost effectiveness and long-term efficacy and tolerability, current evidence indicates that eculizumab is a valuable emerging therapy for patients with refractory gMG. The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis. INTRODUCTION A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response. QMG and MG-ADL correlations: Study of eculizumab treatment of myasthenia gravis. Rituximab seems to be particularly effective in MuSK myasthenia gravis, and eculizumab arises as an option in refractory AChR myasthenia gravis. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. The humanized monoclonal antibody eculizumab (Soliris\u00ae) is a complement inhibitor indicated for use in anti-acetylcholine receptor (AChR) antibody-positive adults with generalized myasthenia gravis (gMG) in the USA, refractory gMG in the EU, or gMG with symptoms that are difficult to control with high-dose IVIg therapy or PLEX in Japan. Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis. Eculizumab: A Review in Generalized Myasthenia Gravis. A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Eculizumab: A Review in Generalized Myasthenia Gravis.)  <b>INTRODUCTION<\/b>: A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response. Correlations were then analyzed between these assessments.<br><b>METHODS<\/b>: Patients were given eculizumab or placebo during the first 16-week treatment period of the crossover study, with treatment assignments reversed for the second treatment period following a 5-week washout. A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response. The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis.","answer":"yes"}
{"id":"5c928afeecadf2e73f000018","question":"Can cardiospheres be produced from skin fibroblasts?","context":"Therefore, there is an emerging interest in generating cardiosphere-like stem cells from somatic cells via somatic reprogramming.  Here we provide the detailed protocol for generating induced cardiospheres (iCS) for cardiac regeneration by somatic reprogramming of mouse fibroblasts using a panel of pluripotent transcription factors and cardiotrophic growth factors.","answer":"yes"}
{"id":"5c73ad347c78d69471000098","question":"Does Axitinib prolong survival of Pancreatic Cancer patients?","context":"CONCLUSIONS: Axitinib\/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions. RESULTS: Among Japanese patients, median overall survival was not estimable (95% confidence interval, 7.4 months-not estimable) with axitinib\/gemcitabine (n = 58) and 9.9 months (95% confidence interval, 7.4-10.5) with placebo\/gemcitabine (n = 56) (hazard ratio 1.093 [95% confidence interval, 0.525-2.274]). Median survival follow-up (range) was 5.1 months (0.02-12.3) with axitinib\/gemcitabine vs. 5.4 months (1.8-10.5) with placebo\/gemcitabine. Similarly, no difference was detected in overall survival between axitinib\/gemcitabine and placebo\/gemcitabine in patients from North America or the European Union.  At an interim analysis in January, 2009, the independent data monitoring committee concluded that the futility boundary had been crossed. Median overall survival was 8\u00b75 months (95% CI 6\u00b79-9\u00b75) for gemcitabine plus axitinib (n=314, data missing for two patients) and 8\u00b73 months (6\u00b79-10\u00b73) for gemcitabine plus placebo (n=316; hazard ratio 1\u00b7014, 95% CI 0\u00b7786-1\u00b7309; one-sided p=0\u00b75436).  INTERPRETATION: The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer.  INTERPRETATION The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer. However, as with other tyrosine kinase inhibitors of the same class, axitinib does not prolong overall survival; therefore, selection of second-line tyrosine kinase inhibitor therapy, including axitinib, must be carefully considered to maximize outcomes for each patient. CONCLUSIONS Axitinib\/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions. Similarly, no difference was detected in overall survival between axitinib\/gemcitabine and placebo\/gemcitabine in patients from North America or the European Union. Axitinib\/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions. The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer.","answer":"no"}
{"id":"5c5217fd7e3cb0e231000005","question":"Is there any association between suicide and autism in adolescents, yes or no?","context":": In all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined.  Suicide attempts are accompanied by a willingness for death and can lead to suicide. They are more common in high-functioning autism and Asperger subjects.  A total sample of 10 adolescents and young adults diagnosed with AS was obtained. The high proportion of respondents with scores above the cutoff point on the overt victimization and relational victimization scales suggests that these adolescents and young adults experienced high levels of victimization. Of the sample, 20 percent met criteria for a diagnosis of Major Depressive Disorder, 30 percent met criteria for Generalized Anxiety Disorder and 50 percent had clinically significant level of suicidal ideation. Previous studies reported a high prevalence of depression among patients with autism spectrum disorder (ASD) and suggested a relationship between ASD and suicidality Patients with ASD had an increased risk of suicide attempts compared with those without ASD. The suicidal behaviors are frequently observed in the adolescents and adults with an ASD without intellectual deficience.  Suicide is a major problem in Western society. However we have very little understanding of suicidal behaviour among individuals with autism spectrum disorders.  The available research provides little empirical evidence for the processes underlying suicidal behaviour in adolescents and young adults with autism  The present study aims to assess the rate of suicidality (suicidal ideation, behaviors and attempts) and associated risk factors for suicidality in high functioning ASD here is a lack of clinical awareness on suicidal behaviors of children and adolescents with autism spectrum disorder (ASD) suicidality in children and adolescents with diagnosis of high functioning autism spectrum disorder  Consistent with the previous findings, rate of suicidality is higher in individuals with ASD Detection of Suicidality in Adolescents with Autism Spectrum Disorders Over 15% of young people with autism spectrum disorders (ASD) will contemplate or attempt suicide during adolescence. Yet, Until recently, suicidality in autism spectrum disorder (ASD) was rarely discussed.  Suicidality in Autism Spectrum Disorder. highlighted not only that suicidal thoughts and suicide attempts can occur in adolescents and young adults with ASD, but also that suicidality is likely more common in ASD than in the general population.  The emerging studies indicate that the increased risk of self-injurious behavior in younger and less cognitively able children with ASD3,4 is matched by an increased risk of suicidality in those at a more advanced developmental level. RESULTS In all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined. Risk of Suicide Attempts Among Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Follow-Up Study. Although the suicide risk of autism spectrum disorder (ASD) has been suggested to be higher than previously recognized, there are few case reports focusing on the process for preventing suicide reattempts.","answer":"yes"}
{"id":"5c8c05c70101eac870000001","question":"Is lactotransferrin a tumour suppressor?","context":"LTF (lactotransferrin, or lactoferrin) plays important role in innate immunity, and its anti-tumor function has also been reported in multiple cancers. We previously reported that LTF is significantly down-regulated in nasopharyngeal carcinoma (NPC) and acts as a tumor suppressor by suppressing AKT signaling. The tumor suppressor function of lactotransferrin (LTF) has been reported in a variety of tumors, including GC, nasopharyngeal carcinoma (NPC) and prostate cancer. Lactotransferrin (LTF) has been confirmed to act as a tumor suppressor in multiple cancers Lactotransferrin acts as a tumor suppressor in nasopharyngeal carcinoma by repressing AKT through multiple mechanisms. LTF is likely to be a candidate tumor suppressor and downregulates the development of NPC by inhibiting NPC proliferation through induction of cell cycle arrest and modulation of the MAPK signaling pathway.","answer":"yes"}
{"id":"5c6ad3be7c78d69471000021","question":"Are there tools for visualizing and processing long-read sequencing data?","context":"NanoPack: visualizing and processing long-read sequencing data. Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences.Availability and implementation: The NanoPack tools are written in Python3 and released under the GNU GPL3.0 License. The source code can be found at https:\/\/github.com\/wdecoster\/nanopack, together with links to separate scripts and their documentation. The scripts are compatible with Linux, Mac OS and the MS Windows 10 subsystem for Linux and are available as a graphical user interface, a web service at http:\/\/nanoplot.bioinf.be and command line tools. Summary Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences. NanoPack: visualizing and processing long-read sequencing data.Supplementary data are available at Bioinformatics online. <b>Summary<\/b>: Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences.<br><b>Availability and implementation<\/b>: The NanoPack tools are written in Python3 and released under the GNU GPL3.0 License. Here we describe NanoPack, a set of tools developed for visualization and processing of long-read sequencing data from Oxford Nanopore Technologies and Pacific Biosciences.","answer":"yes"}
{"id":"5c674eac7c78d6947100001b","question":"Has Hesperidin any role as a Neuroprotective Agent?","context":"Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer's disease Hesperidin attenuates depression-related symptoms in mice with mild traumatic brain injury Neuroprotective Effects of Hesperidin on Cerebral Vasospasm The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation. This study suggests a potential neuroprotective role of hesperidin against 3-NP-induced Huntington's disease-like manifestations. Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations. Hesperidin, a flavanoglycone abundantly present in citrus fruits, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties. PURPOSE Hesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types. Hesperidin is a flavonone glycoside, belonging to the flavonoid family, which is widely found in Citrus species and acts as a potent antioxidant and anticancer agent. BACKGROUND Hesperidin, a flavanone present in citrus fruits, has been identified as a potent anticancer agent because of its proapoptotic and antiproliferative characteristics in some tumor cells. Oxidative stress and cancer; the role of hesperidin, a citrus natural bioflavonoid, as a cancer chemoprotective agent. Our data suggests that hesperidin exerts its neuroprotective effect against rotenone due to its antioxidant, maintenance of mitochondrial function, and antiapoptotic properties in a neuroblastoma cell line. Taken together, these results demonstrate potent antioxidant and neuroprotective effects of hesperetin, implying its potential role in protecting neurons against various types of insults associated with many neurodegenerative diseases. The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation.We found that hesperidin, a plant-derived bioflavonoid, may be a candidate agent for neuroprotective treatment in the retina, after screening 41 materials for anti-oxidative properties in a primary retinal cell culture under oxidative stress.  Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson's disease.Rotenone a widely used pesticide that inhibits mitochondrial complex I has been used to investigate the pathobiology of PD both in vitro and in vivo.  Cytoprotective effects of hesperetin and hesperidin against amyloid \u03b2-induced impairment of glucose transport through downregulation of neuronal autophagy. Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations.Hesp possesses potent anticonvulsant activity which might be mediated through modulation of gamma-amino butyric acid\/benzodiazepine receptor action. Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin.The present study evaluated antioxidant and neuroprotective activities of hesperidin, a flavanone mainly isolated from citrus fruits, and its aglycone hesperetin using cell-free bioassay system and primary cultured rat cortical cells.  Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats. Hesperidin inhibits glutamate release and exerts neuroprotection against excitotoxicity induced by kainic acid in the hippocampus of rats. Emerging evidences indicate hesperidin, a citrus flavanone, attenuates neurodegenerative processes and related complications. Potential anti-inflammatory effects of hesperidin from the genus Citrus. Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin. Hesperidin is a flavonoid present in high concentration in citrus species and has numerous biological properties, principally antioxidant and anti-inflammatory.","answer":"yes"}
{"id":"5c8857e975a4a5d219000009","question":"Are apoE mimetics being considered as a treatment against Alzheimer's disease?","context":"The apolipoprotein-E-mimetic COG112 protects amyloid precursor protein intracellular domain-overexpressing animals from Alzheimer's disease-like pathological features. Studies show that administration of apolipoprotein E (apoE) and apoE-derived small peptide mimetics protect AD mouse models against these AD-like features.","answer":"yes"}
{"id":"5c6d9a157c78d69471000041","question":"Can you computationally predict Molecular Recognition Features (MoRFs) regions in Intrinsically Disordered Proteins (IDPs)?","context":"Predicting Functions of Disordered Proteins with MoRFpred. Intrinsically disordered proteins and regions are involved in a wide range of cellular functions, and they often facilitate protein-protein interactions. Molecular recognition features (MoRFs) are segments of intrinsically disordered regions that bind to partner proteins, where binding is concomitant with a transition to a structured conformation. MoRFs facilitate translation, transport, signaling, and regulatory processes and are found across all domains of life. A popular computational tool, MoRFpred, accurately predicts MoRFs in protein sequences. MoRFpred is implemented as a user-friendly web server that is freely available at http:\/\/biomine.cs.vcu.edu\/servers\/MoRFpred\/ . We describe this predictor, explain how to run the web server, and show how to interpret the results it generates. We also demonstrate the utility of this web server based on two case studies, focusing on the relevance of evolutionary conservation of MoRF regions. MoRFPred-plus: Computational Identification of MoRFs in Protein Sequences using Physicochemical Properties and HMM profiles. Intrinsically Disordered Proteins (IDPs) lack stable tertiary structure and they actively participate in performing various biological functions. These IDPs expose short binding regions called Molecular Recognition Features (MoRFs) that permit interaction with structured protein regions. Upon interaction they undergo a disorder-to-order transition as a result of which their functionality arises. Predicting these MoRFs in disordered protein sequences is a challenging task.METHOD: In this study, we present MoRFpred-plus, an improved predictor over our previous proposed predictor to identify MoRFs in disordered protein sequences. Two separate independent propensity scores are computed via incorporating physicochemical properties and HMM profiles, these scores are combined to predict final MoRF propensity score for a given residue. The first score reflects the characteristics of a query residue to be part of MoRF region based on the composition and similarity of assumed MoRF and flank regions. The second score reflects the characteristics of a query residue to be part of MoRF region based on the properties of flanks associated around the given residue in the query protein sequence. The propensity scores are processed and common averaging is applied to generate the final prediction score of MoRFpred-plus.RESULTS: Performance of the proposed predictor is compared with available MoRF predictors, MoRFchibi, MoRFpred, and ANCHOR. Using previously collected training and test sets used to evaluate the mentioned predictors, the proposed predictor outperforms these predictors and generates lower false positive rate. In addition, MoRFpred-plus is a downloadable predictor, which makes it useful as it can be used as input to other computational tools. OPAL: prediction of MoRF regions in intrinsically disordered protein sequences. Intrinsically disordered proteins lack stable 3-dimensional structure and play a crucial role in performing various biological functions. Key to their biological function are the molecular recognition features (MoRFs) located within long disordered regions. Computationally identifying these MoRFs from disordered protein sequences is a challenging task. In this study, we present a new MoRF predictor, OPAL, to identify MoRFs in disordered protein sequences. OPAL utilizes two independent sources of information computed using different component predictors. The scores are processed and combined using common averaging method. The first score is computed using a component MoRF predictor which utilizes composition and sequence similarity of MoRF and non-MoRF regions to detect MoRFs. The second score is calculated using half-sphere exposure (HSE), solvent accessible surface area (ASA) and backbone angle information of the disordered protein sequence, using information from the amino acid properties of flanks surrounding the MoRFs to distinguish MoRF and non-MoRF residues.Results: OPAL is evaluated using test sets that were previously used to evaluate MoRF predictors, MoRFpred, MoRFchibi and MoRFchibi-web. The results demonstrate that OPAL outperforms all the available MoRF predictors and is the most accurate predictor available for MoRF prediction. It is available at http:\/\/www.alok-ai-lab.com\/tools\/opal\/. OPAL+: Length-Specific MoRF Prediction in Intrinsically Disordered Protein Sequences. Intrinsically disordered proteins (IDPs) contain long unstructured regions, which play an important role in their function. These intrinsically disordered regions (IDRs) participate in binding events through regions called molecular recognition features (MoRFs). Computational prediction of MoRFs helps identify the potentially functional regions in IDRs. In this study, OPAL+, a novel MoRF predictor, is presented. OPAL+ uses separate models to predict MoRFs of varying lengths along with incorporating the hidden Markov model (HMM) profiles and physicochemical properties of MoRFs and their flanking regions. Together, these features help OPAL+ achieve a marginal performance improvement of 0.4-0.7% over its predecessor for diverse MoRF test sets. This performance improvement comes at the expense of increased run time as a result of the requirement of HMM profiles. OPAL+ is available for download at https:\/\/github.com\/roneshsharma\/OPAL-plus\/wiki\/OPAL-plus-Download. Computational Identification of MoRFs in Protein Sequences Using Hierarchical Application of Bayes Rule. Key to their regulatory function is often the binding to globular protein domains via sequence elements known as molecular recognition features (MoRFs). Development of computational tools for the identification of candidate MoRF locations in amino acid sequences is an important task and an area of growing interest. Given the relative sparseness of MoRFs in protein sequences, the accuracy of the available MoRF predictors is often inadequate for practical usage, which leaves a significant need and room for improvement. In this work, we introduce MoRFCHiBi_Web, which predicts MoRF locations in protein sequences with higher accuracy compared to current MoRF predictors.METHODS: Three distinct and largely independent property scores are computed with component predictors and then combined to generate the final MoRF propensity scores. The first score reflects the likelihood of sequence windows to harbour MoRFs and is based on amino acid composition and sequence similarity information. It is generated by MoRFCHiBi using small windows of up to 40 residues in size. The second score identifies long stretches of protein disorder and is generated by ESpritz with the DisProt option. Lastly, the third score reflects residue conservation and is assembled from PSSM files generated by PSI-BLAST. These propensity scores are processed and then hierarchically combined using Bayes rule to generate the final MoRFCHiBi_Web predictions.RESULTS: MoRFCHiBi_Web was tested on three datasets. Results show that MoRFCHiBi_Web outperforms previously developed predictors by generating less than half the false positive rate for the same true positive rate at practical threshold values. Computational identification of MoRFs in protein sequences. In this study, we introduce MoRFCHiBi, a new computational approach for fast and accurate prediction of MoRFs in protein sequences. MoRFCHiBi combines the outcomes of two support vector machine (SVM) models that take advantage of two different kernels with high noise tolerance. The first, SVMS, is designed to extract maximal information from the general contrast in amino acid compositions between MoRFs, their surrounding regions (Flanks), and the remainders of the sequences. The second, SVMT, is used to identify similarities between regions in a query sequence and MoRFs of the training set.RESULTS: We evaluated the performance of our predictor by comparing its results with those of two currently available MoRF predictors, MoRFpred and ANCHOR. Using three test sets that have previously been collected and used to evaluate MoRFpred and ANCHOR, we demonstrate that MoRFCHiBi outperforms the other predictors with respect to different evaluation metrics. In addition, MoRFCHiBi is downloadable and fast, which makes it useful as a component in other computational prediction tools.AVAILABILITY AND IMPLEMENTATION: http:\/\/www.chibi.ubc.ca\/morf\/. OPAL: prediction of MoRF regions in intrinsically disordered protein sequences.Supplementary data are available at Bioinformatics online. Computational prediction of MoRFs helps identify the potentially functional regions in IDRs.","answer":"yes"}
{"id":"5c97a08becadf2e73f000029","question":"Velocardial facial syndrome, otherwise known as Di George syndrome  is caused by a deletion in chromosome 21, yes or no?","context":"The deletion of chromosome 22q11.2 is involved in the majority of DiGeorge or velo-cardiofacial syndrome. deletions of chromosome 7q11.23 (Williams syndrome), 15q11-q13 (Angelman syndrome, Prader-Willi syndrome) and 22q11 (Di George syndrome) Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome The 22q11.2 deletion syndrome (di George syndrome) is one of the most prevalent genetic disorders. UNLABELLED Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11. Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome. 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1\/4000 births, de novo: 90%). Di George syndrome due to mutation on 22q or 10q) and can also result from microdeletion or point mutation (in the Shprintzen syndrome 70% represent microdeletion and 30% point mutation at 22q11, in Rubinstein-Taybi syndrome 10% cases result from microdeletions and 90% from point mutations); 7) Population incidence of microdeletions is high (1:4000 to 1:30,000) because their etiologic mechanism is related to the common unequal crossing over; 8) Imprinting plays a role in some cases, e.g. [Microdeletion of the chromosome 22q11 in children: apropos of a series of 49 patients].<AbstractText Label=\"UNLABELLED\">Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11.  22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1\/4000 births, de novo: 90%).  <b>UNLABELLED<\/b>: Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11. Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11.","answer":"no"}
{"id":"5c8ab614d558e5f23200000d","question":"Is the protein Asporin related to disease?","context":"Accumulating evidence demonstrates the involvement of asporin in OA pathogenesis. Asporin has been reported as a tumor suppressor in breast cancer, while asporin-activated invasion has been described in gastric cancer. Asporin has been implicated as an oncogene in various types of human cancers;   These results suggested that asporin promoted the tumor growth and metastasis of CRC, and it could be a potential therapeutic target for CRC patients in future. Our results suggest that ASPN is a stromally expressed biomarker that correlates with disease progression, and is observed in reactive stroma.","answer":"yes"}
{"id":"5ca61176ecadf2e73f00004e","question":"Can TAD disruption lead to disease?","context":"its perturbation will lead to human disease, highlighting the accumulating evidence that links the diverse 3D genome architecture components to a multitude of human diseases and the emerging mechanisms by which 3D genome derangement causes disease phenotypes. TAD boundaries are insulators of genomic neighborhoods. In this issue, Sun et\u00a0al. show that disease-associated tandem repeats are located to TAD boundaries and affect their insulation.  Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers. the disruption of these structures by genomic rearrangements can result in gene misexpression and disease. TAD disruption as oncogenic driver. Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms. Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements. However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression. Disruption of this organization by structural variations can lead to ectopic interactions between enhancers and promoters, and to alteration of genes expression patterns. Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. Deletion in 2q35 excluding the IHH gene leads to fetal severe limb anomalies and suggests a disruption of chromatin architecture. We demonstrate that disruption of TADs can rewire long-range regulatory architecture and result in pathogenic phenotypes.  Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements.  Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers.  Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation.  Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs.  Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms.  Disruption of this organization by structural variations can lead to ectopic interactions between enhancers and promoters, and to alteration of genes expression patterns.  Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers.  However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression.","answer":"yes"}
{"id":"5c8908a475a4a5d21900000c","question":"Is L-4F an apoE mimetic peptide?","context":"Apolipoprotein A-I mimetic peptide 4F suppresses tumor-associated macrophages and pancreatic cancer progression. L-4F, an Apolipoprotein A-I (ApoA-I) mimetic peptide, is engineered to mimic the anti-inflammatory and anti-oxidative functionalities of ApoA-I.","answer":"no"}
{"id":"5c890c3375a4a5d21900000e","question":"Can oleuropein aglycone interfere with amyloid aggregation?","context":"Oleuropein, a phenolic secoiroid glycoside, is the main polyphenol in the olive oil. It has been reported that the aglycone form of Oleuropein (OleA) interferes in vitro and in vivo with amyloid aggregation of a number of proteins\/peptides involved in amyloid, particularly neurodegenerative, diseases avoiding the growth of toxic oligomers and displaying protection against cognitive deterioration.","answer":"yes"}
{"id":"5caa0806ecadf2e73f000057","question":"Is Apelin usually decreased in diabetes?","context":"Apelin has been shown to act on glucose and lipid metabolism but also to modulate insulin secretion. Moreover, different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes. Upregulated expression of resistin, vaspin, apelin and TNF-\u03b1 plays a significant role in induction of insulin resistance linked with obesity and type 2 diabetes. Moreover, different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes. Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus. In men at risk for diabetes (HbA1c 5.7-6.4%, FPG 100-125mg\/dl, or OGTT-2h-PG 140-199mg\/dl), the risk for developing diabetes was higher in those with higher plasma apelin concentration than in those with lower plasma apelin concentrations (10.6%\/year vs. 5.1%\/year, p<0.001).<br><b>CONCLUSIONS<\/b>: Plasma apelin is a novel biomarker for predicting type 2 diabetes in men.<br>","answer":"no"}
{"id":"5ca0fdb0ecadf2e73f000049","question":"Is actin present in the nucleus?","context":"Moreover, inhibition of ATM kinase or deficiency in nuclear actin polymerization causes carcinogenic RET\/PTC chromosome rearrangements after DSBs induction in human cells.  Our findings establish that nuclear actin-based mobility shapes chromatin organization by generating repair domains that are essential for homology-directed repair in eukaryotic cells. The discovery of nuclear actin opened new perspective on the field, suggesting that the nuclear activities of actin reflect the functions of primordial actin-like proteins.  The revitalization of research into nuclear actin occurred after it was found that cellular stresses induce the nuclear localization and alter the structure of actin.  While it is long known that actin is part of the nuclear proteome, its properties and functions as regulated, functional and dynamically assembled actin filaments are only recently emerging.","answer":"yes"}
{"id":"5c8fea130101eac87000000d","question":"Can miR-122 target RUNX2?","context":"MiR-122 functions as a tumor suppressor by inhibiting proliferation and inducing apoptosis, which is achieved by directly targeting RUNX2.","answer":"yes"}
{"id":"5c960d88ecadf2e73f00001f","question":"Tocilizumab is an anti-TNF antibody, yes or no?","context":"was treated with tocilizumab, an anti-interleukin-6 receptor monoclonal antibody  Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6\u00a0receptor licensed in 2009 that has demonstrated clinical efficacy in various adult RA populations. RA management guidelines and recommendations consider TCZ as one of the bDMARDS indicated after methotrexate or other conventional synthetic DMARDs and\/or TNF inhibitors failure in adult RA Tocilizumab (RoActemra or Actemra) is a recombinant humanized monoclonal antibody that acts as an interleukin (IL)-6 receptor antagonist. METHODS Patients (n = 93) were treated with an anti-IL-6 receptor antibody (tocilizumab) or TNF-\u03b1 inhibitors for 16 weeks. The recent development of biological agents, namely, anti-tumour necrosis factor alpha (TNF-\u03b1) agents (infliximab, adalimumab and etanercept), anti- CD20 monoclonal antibody (rituximab) and anti-interleukin 6 receptor (IL-6R) monoclonal antibody (tocilizumab), represents a major breakthrough for the treatment of immune-mediated disorders. Recently, an anti-IL-6 receptor monoclonal antibody, tocilizumab, has been licensed for the treatment as monotherapy or in combination with methotrexate of moderate to severe RA, when disease modifying anti-rheumatic drugs or anti-tumour necrosis factors (TNF) have failed. Tocilizumab is a monoclonal humanized anti-IL-6-receptor antibody used for the treatment of rheumatoid arthritis. Indeed, worldwide clinical trials of TNF inhibiting biologic disease modifying antirheumatic drugs (bDMARDs) including infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept as well as the humanized anti-human IL-6 receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy and tolerable safety profiles, resulting in worldwide approval for using these bDMARDs to treat moderate to severe active RA in patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs). Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody, which binds to circulating soluble IL-6 receptor and membrane-expressed IL-6 receptor, inhibiting IL-6 binding to both forms of IL-6 receptor. Subsequent options include a TNF-alpha antagonist, followed by rituximab or possibly abatacept; (2) Tocilizumab, a monoclonal antibody, inhibits interleukin-6 receptors. Tocilizumab (TCZ) is a monoclonal antibody which inhibits the interleukin-6 receptor.","answer":"no"}
{"id":"5c9e6ab9ecadf2e73f000035","question":"Is it possible to analyze exosomes with FACS?","context":"whose presence was validated by a bead-exosome FACS assay. We analyzed exosomes from mouse (C57Bl\/6) and breast, lung, and ovarian cancer patient samples and cultured cancer cells with different approaches, including nanoparticle tracking analysis, biolayer interferometry, FACS, and electron microscopy. we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis we used a novel strategy for generating metabolically-labeled fluorescent exosomes that can be counted by flow cytometry assay (FACS) and characterized.","answer":"yes"}
{"id":"5c915e51ecadf2e73f00000c","question":"Can prevnar 13 be used in children?","context":"PCV13 is approved for routine vaccination of all infants as a 4-dose series at age 2, 4, 6, and 12-15 months for children who previously received 1 or more doses of the 7-valent pneumococcal conjugate vaccine (PCV7), and for children with underlying medical conditions that increase their risk for pneumococcal disease or its complications.  Based on published immunogenicity and safety data, as well as the recent recommendations by the ACIP for routine use in infants and indications for high-risk pediatric patients, PCV13 is a revised formulation of pneumococcal vaccine that should be included on pharmacy formularies. To review the immunogenicity, efficacy, and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in pediatric patients.","answer":"yes"}
{"id":"5c9160bcecadf2e73f00000d","question":"Was stelara developed by Amgen?","context":"NICE does not specifically recommend switching from one biologic to another, and only ustekinumab (UST; STELARA\u00ae, Janssen Pharmaceuticals, Inc., Horsham, PA, USA) is recommended after anti-tumour necrosis factor failure.","answer":"no"}
{"id":"5c9e766becadf2e73f000038","question":"Can mitochondria pass through membrane nanotubes?","context":"Membrane nanotubes (MNTs) act as \"highways\" between cells to facilitate the transfer of multiple signals and play an important role in many diseases. Our previous work reported on the transfer of mitochondria via MNTs between cardiomyocytes (CMs) and cardiac myofibroblasts (MFs) Membrane nanotubes play important functional roles in numerous cell activities such as cellular transport and communication.","answer":"yes"}
{"id":"5c9f1b0cecadf2e73f00003c","question":"Are protamines ubiquitously expressed?","context":"Protamines are nuclear proteins which are specifically expressed in haploid male germ cells.","answer":"no"}
{"id":"5c891d5075a4a5d219000011","question":"Are Crocus sativus compounds being considered against Alzheimer's disease?","context":"Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer's disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD.  Collectively, findings from this study support the positive effect of Crocus sativus against AD by reducing A\u03b2 pathological manifestations.","answer":"yes"}
{"id":"5ca0848aecadf2e73f000044","question":"Are there any anti-amyloid antibody approved as drug for Alzheimer's disease treatment?","context":"Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer's disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer's disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats.  anti-Amyloid agents (13.30%) no new drugs have been approved during the past 15\u00a0years; and the available medications are not cost-effective.","answer":"no"}
{"id":"5c891e5575a4a5d219000012","question":"Do Crocus sativus extracts loosen the blood-brain barrier?","context":"Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid \u03b2 Load and Related Toxicity in 5XFAD Mice. In vitro results showed that Crocus sativus extract increases the tightness of a cell-based blood-brain barrier (BBB) model and enhances transport of A\u03b2. Further in vivo studies confirmed the effect of Crocus sativus extract (50 mg\/kg\/day, added to mice diet) on the BBB tightness and function that was associated with reduced A\u03b2 load and related pathological changes in 5XFAD mice used as an AD model. Reduced A\u03b2 load could be explained, at least in part, by Crocus sativus extract effect to enhance A\u03b2 clearance pathways including BBB clearance, enzymatic degradation and ApoE clearance pathway.","answer":"no"}
{"id":"5ca0fa96ecadf2e73f000048","question":"Are artificial blood cells available?","context":"The critical point for the break through for artificial blood products did not come yet but could be ahead- We suggest a novel method that uses artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment (at 595-nm wavelength) for port-wine stains (i.e., capillary malformations presenting as red birthmarks) based on the results of animal experiments.","answer":"no"}
{"id":"5c895cf0f9c2ba6b28000001","question":"Have apolipoprotein mimetics been used in clinical trials?","context":"One of these (AEM-28) has recently been given orphan drug status and is undergoing clinical trials.","answer":"yes"}
{"id":"5ca10fefecadf2e73f00004a","question":"Is the Philadelphia chromosome a fusion between parts of chromosomes 1 and 9?","context":"The Philadelphia chromosome, t(9;22)(q34;q11), is present in 95% of CML patients, resulting in constitutive tyrosine kinase activity; however, ~5% of CML patients possess a Philadelphia variant.  Chronic Myeloid Leukemia (CML) is myeloproliferative neoplasm characterized by Philadelphia chromosome which is a balanced translocation between chromosome 9 and 22 in 90% of cases. Chronic myeloid leukemia is a stem cell disease with the presence of Philadelphia chromosome generated through reciprocal translocation of chromosome 9 and 22.","answer":"no"}
{"id":"5c9f7bb6ecadf2e73f00003e","question":"Can therapeutic levels of  Vedolizumab be found in the breast milk of nursing mothers following treatment for Inflammatory bowel disease?","context":"Vedolizumab can be detected in the breast milk of nursing mothers. Although more data are imperative, the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant. Although more data are imperative, the concentrations of vedolizumab in breast milk are minute and are therefore unlikely to result in systemic or gastro-intestinal immune-suppression of the infant. Results Vedolizumab was undetectable in breast milk in IBD patients before the first infusion of vedolizumab [n = 3] and in all of the healthy controls [n = 5]. However, on serial measurements in breast milk after an infusion, drug levels did not surpass 480 ng\/ml, which was roughly 1\/100 of the comparable serum levels. However, on serial measurements in breast milk after an infusion, drug levels did not surpass 480 ng\/ml, which was roughly 1\/100 of the comparable serum levels.<br><b>Conclusions<\/b>: Vedolizumab can be detected in the breast milk of nursing mothers. However, on serial measurements in breast milk after an infusion, drug levels did not surpass 480 ng\/ml, which was roughly 1\/100 of the comparable serum levels.","answer":"no"}
{"id":"5c8fe71b0101eac87000000b","question":"Does RUNX2 inhibit astrocyte differentiation?","context":"The method was able to recapitulate experimentally validated cell-fate determinants, and validation of two predicted cell-fate determinants confirmed that overexpression of ESR1 and RUNX2 in mouse neural stem cells induces neuronal and astrocyte differentiation, respectively.","answer":"no"}
{"id":"5c9906dcecadf2e73f00002f","question":"Are cardenolides inhibitors of Na+\/K+ ATPase?","context":". Previously, we reported that a variety of cardenolides impart anti-transmissible gastroenteritis coronavirus (TGEV) activity in swine testicular (ST) cells, through targeting of the cell membrane sodium\/potassium pump, Na+\/K+-ATPase.  : We found evidence for low cardenolides by HPLC, but substantial toxicity when extracts were assayed on Na+ \/K+ -ATPases. Cardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells.","answer":"yes"}
{"id":"5c900779ecadf2e73f000001","question":"Can antisense threapy be used for Huntington's disease?","context":"In this issue of Neuron, Kordasiewicz et\u00a0al. (2012) show the benefit of transient antisense oligonucleotide (ASO) therapy to degrade Huntingtin mRNA and elicit sustained therapeutic benefit in HD mice. \"Huntingtin holiday\": progress toward an antisense therapy for Huntington's disease.","answer":"yes"}
{"id":"5ca5127eecadf2e73f00004c","question":"Is collagen matrix of human articular cartilage changing with disease?","context":"The collagen matrix of human articular cartilage is an essentially permanent structure that has no significant turnover in adults, even with the occurrence of disease. the chondrocytes in ageing articular cartilage have limited capacity to turnover the interterritorial matrix. Type II collagen is a major component of articular cartilage and its breakdown is a key feature of osteoarthritis.","answer":"no"}
{"id":"5c9162b5ecadf2e73f00000e","question":"Is ustekinumab a polyclonal antibody?","context":"Ustekinumab, a human monoclonal IgG1 antibody targeting the p40-subunit shared by interleukin (IL)12 and IL-23, represents a potential treatment for atopic dermatitis (AD).","answer":"no"}
{"id":"5cb37f76ecadf2e73f00005c","question":"Is Pim-1 a protein phosphatase?","context":"Pim-1 proto-oncogene, serine\/threonine kinase (PIM-1) phosphorylates a series of substrates to exert its oncogenic function in numerous malignancies. The Pim1 serine\/threonine kinase is associated with multiple cellular functions including proliferation, survival, differentiation, apoptosis, tumorigenesis, immune regulation and inflammation in vertebrates.","answer":"no"}
{"id":"5cb38a56ecadf2e73f00005e","question":"Is myc a tumour suppressor gene?","context":"oncogenic Myc, a master transcription factor that turns on anabolic metabolism to promote cell growth in many cancers.  he MYC oncogene  the proto-oncogene protein c-MYC however, other genes such as the proto-oncogene c-Myc are promising targets for anticancer therapy","answer":"no"}
{"id":"5cb3a2dd99d1e53537000001","question":"Is CD63 an exosomal marker?","context":"f exosome marker proteins (e.g., CD63, Alix)   CD63 levels and acetylcholinesterase (AChE) activity were used as markers of exosome,  The results demonstrated these exosomes all expressed CD9, CD63, CD81, Alix","answer":"yes"}
{"id":"5ca0c81eecadf2e73f000047","question":"Is subdural empyema a complication of sinusitis?","context":"Acute and chronic sinusitis can give rise to a wide array of intracranial and orbital complications. These complications include brain abscess, subdural empyema,  A computed tomography scan showed bilateral paranasal sinus disease, and magnetic resonance imaging showed a right frontal abscess and subdural empyema. Frontal sinusitis complicated by a brain abscess and subdural empyema. In older children, sinusitis and otitis media are usually the source for subdural empyem Subdural empyema as a complication of sinusitis in the pediatric population. Second, subdural empyema appears to arise in the setting of subacute rather than acute frontal sinusitis. Subdural empyema is a rare but potentially life-threatening complication following paranasal sinusitis and should be considered as a neurological emergency. [Subdural empyema as a complication of sinusitis. INTRODUCTION Subdural empyema is an uncommon but serious complication of sinusitis. Intracranial subdural empyema is most frequently a complication of sinusitis or, less frequently, otitis or neurosurgical procedures. Subdural empyema is a rare complication of sinusitis although very severe. Subdural empyema is a rare complication of sinusitis in children. Subdural empyema is a rare but serious complication of paranasal sinusitis which may result in death or permanent disability in a significant proportion of cases. We report a case of subdural empyema secondary to frontal sinusitis in an otherwise healthy immunocompetent adolescent boy. Subdural empyema is a rare but life-threatening complication of paranasal sinusitis, otitis media, or mastoid disease. Wolf in Sheep's Clothing Subdural Empyema: A Rare Complication of Acute Sinusitis. Interhemispheric and Infratentorial Subdural Empyema with Preseptal Cellulitis as Complications of Sinusitis: A Case Report. Subdural empyema as a complication of sinusitis in the pediatric population.<AbstractText Label=\"OBJECTIVE\" NlmCategory=\"OBJECTIVE\">Sinusitis is a rare cause of intracranial infection in children.  [Subdural empyema as a complication of sinusitis.  Intracranial subdural empyema is most frequently a complication of sinusitis or, less frequently, otitis or neurosurgical procedures.  Streptococcus pluranimalium: A novel human pathogen?<AbstractText Label=\"INTRODUCTION\" NlmCategory=\"BACKGROUND\">We present the first case of a subdural empyema caused by Streptococcus pluranimalium, in a healthy adolescent male as a possible complication of subclinical frontal sinusitis.  <AbstractText Label=\"DISCUSSION\" NlmCategory=\"CONCLUSIONS\">The diagnosis of subdural empyema as a complication of asymptomatic sinusitis in an immunocompetent patient with no history of fever or upper respiratory symptoms was unanticipated.  Second, subdural empyema appears to arise in the setting of subacute rather than acute frontal sinusitis.  Bifrontal decompressive craniectomy for acute subdural empyema.<AbstractText Label=\"INTRODUCTION\" NlmCategory=\"BACKGROUND\">Subdural empyema is an uncommon but serious complication of sinusitis.  Subdural empyema is a rare but potentially life-threatening complication following paranasal sinusitis and should be considered as a neurological emergency.  We present a patient with subdural empyema in whom the diagnosis was delayed, followed by a discussion of suppurative complications of sinusitis.  <AbstractText Label=\"CASE REPORT\" NlmCategory=\"METHODS\">We report an unusual case of sinusitis-associated acute subdural empyema in a 13-year-old patient, presenting in a catastrophic manner with acutely raised intracranial pressure.  The symptoms of subdural empyema may be mild and may be the same as those associated with sinusitis, or the infection may result in alteration of the level of consciousness and focal neurologic deficits. We report the clinical and radiological course of an adolescent with a subdural empyema secondary to sinusitis. We report two cases of subdural empyema secondary to sinusitis in persons without impaired immunity. Subdural empyema as a complication of sinusitis. Furthermore, subdural empyema usually is related to sinus infections, particularly those caused by Streptococcus milleri, an anaerobic organism. Subdural empyema is an uncommon but serious complication of sinusitis.","answer":"yes"}
{"id":"5c98ac7fecadf2e73f00002b","question":"Anaplasma phagocytophilum is an obligate gram-negative, intracellular bacterium, yes  or no","context":"The genus Anaplasma belonging to the Anaplasmataceae family (order Rickettsiales) comprises obligate intracellular Gram-negative bacteria of veterinary and public health importance. Six species and five types of strains genetically related are currently assigned to the genus Anaplasma including Anaplasma marginale, A. centrale, A. bovis, A. phagocytophilum, A. ovis and A. platys as classified species, and \"A. capra\", A. odocolei sp. nov. Human granulocytic anaplasmosis (HGA), an increasingly recognized febrile tick-borne illness, is caused by a gram-negative obligate intracellular bacterium Anaplasma phagocytophilum","answer":"yes"}
{"id":"5cb380b8ecadf2e73f00005d","question":"Is the crystal structure of Pim-1 available?","context":"Recent crystallographic studies of Pim-1 have identified unique structural features but have not provided insight into how the kinase recognizes its target substrates.  a co-crystal structure of lead molecule (HS38) in complex with DAPK3, a dual Pim\/DAPK3 inhibitor (HS56) The crystal structure of this compound with PIM1 confirmed the predicted binding mode and protein-ligand interactions except those in the acidic ribose pocket.  Using the determined X-ray crystal structure of PIM1 complexed to the compound 1-R as a control, we discuss the importance of including the protein flexibility inherent in the ensemble docking protocol, for the accuracy of the structure prediction of the bound state.  Here, we describe the crystal structure of Pim1 in complex with a newly developed pyrido[4,3-d]pyrimidine-derivative inhibitor (SKI-O-068). Crystallographic and docking data analyses have been undertaken using inhibitor complexes  The crystal structures of Pim1 in apo form and bound with AMPPNP have been solved","answer":"yes"}
{"id":"5c92159becadf2e73f000012","question":"Do tumour-associated macrophages have a prognostic role in gliomas?","context":"Increasing evidence suggests that tumour-associated macrophages\/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using automated quantitative double immunofluorescence. This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold an unfavourable prognostic value in high-grade gliomas and may contribute to a pro-tumourigenic microenvironment. Our data revealed that the amount of especially CD204+ TAMs increases with malignancy grade. In grade III-IV, high CD204 expression was associated with shorter survival, while high IBA-1 intensity correlated with a longer survival. In grade IV, CD204 showed independent prognostic value when adjusting for clinical data and the methylation status of O6-methylguanine-DNA methyltransferase.","answer":"yes"}
{"id":"5c9f0dabecadf2e73f00003b","question":"Is TNF-\u03b1 an activator of pancreatic stellate cells?","context":"TNF-\u03b1 is the prime factor responsible for the activation of pancreatic stellate cells Activated PSCs expressed IL-33 in the nucleus, and the expression was increased by IL-1\u03b2, TNF-\u03b1, PDGF-BB, and IFN-\u03b3, but not TGF-\u03b21.","answer":"yes"}
{"id":"5c9e738decadf2e73f000037","question":"Can mitochondria transfer from cell to cell?","context":"Interest in the recently discovered phenomenon of mitochondrial transfer between mammalian cells has gained momentum since it was first described in cell culture systems more than a decade ago. We show evidence that mitochondria transfer from Jurkat cells to MSCs, which is mediated by cell adhesion This process of mitochondria transfer is mediated by tunneling nanotubes, which are protrusions that extend from the cell membrane .","answer":"yes"}