tbuckley/cabot-search huggingface dataset:
Child Abuse Awareness Month During the Coronavirus Disease 2019 Pandemic
Authors: Cameron M. Rosenthal, Lindsay A. Thompson
Journal: JAMA Pediatrics (2020)

April is Child Abuse Awareness month, even during the coronavirus disease 2019 (COVID-19) pandemic.Social isolation, the public health measure now in place across the world, is also a proven risk factor for child abuse.Other risks include stress, uncertain access to food and housing, and worries about making ends meet.Owing to the current COVID-19 pandemic, we recognize that parents and caregivers feel overwhelmed with these stresses.They may be experiencing job loss, childcare struggles, and schedule changes.With schools and daycare centers closed for weeks or more, children are no longer in the watchful eyes of their community.Teachers, counselors, extended family, and friends who routinely see children are now physically separated and unable to provide the same social and emotional support.Many school or community programs that prevent child abuse are currently on hold.The vital social distancing that attempts to flatten the curve for COVID-19 hinders these prevention efforts.Research shows that all types of child abuse increase during school holidays and summer breaks and worsen during natural disasters such as hurricanes.We expect that throughout the course of the COVID-19 pandemic, when emotions are running high and children are more socially isolated than ever, child abuse will surge.Much of this abuse will be unreported.While we face these challenges, parents and friends can help reduce the risk of child abuse in several ways.First, call, video chat, or email friends and family.This virtual contact and support can be a good boost for parents and gives children the opportunity to connect with someone outside of their home.Second, establish and stick to a family schedule.This provides structure and routine.Set meal times, bedtimes, schoolwork, and even play time can help with daily tasks.Starting or restarting rest time can help children and caregivers recharge.Third, find out about community resources.Many towns and cities have food banks and free meals for children and families.Some communities are creating fun ways for children to engage socially without physical contact.Chalk messages on sidewalks and teddy bear sightings in windows provide a way to connect.While small, these gestures reduce feelings of isolation.Fourth, financial stress is real.Mortgage lenders, student loan holders, and banks are taking steps to reduce, stop, or postpone penalties.Look into opportunities that may provide financial relief.Last, remember you are not alone.If you need help, you can call the National Par-ent Helpline at 1-855-427-2736 or the Childhelp National Child Abuse Hotline at 1-800-4-A-CHILD.In many states, all citizens serve as mandatory reporters.If someone suspects child abuse or neglect, they are required by law to report these concerns to the police or state welfare agencies.By working together to look out for children, we may be able to help prevent cases of child abuse and neglect.
Abstract 19728: Translesional Time to Determine Complete Bidirectional Block Across the Cavotricuspid Isthmus
Authors: George Thomas
Journal: Circulation (2012)

Introduction: The goal of ablation of typical atrial flutter is to create complete bidirectional block across the cavotricuspid isthmus (CTI). The purpose of this study was to document whether there was a transisthmus time that is associated with complete bidirectional isthmus block (CBIB). Methods: Thirty consecutive patients who had CTI ablation procedures were assessed. A circular right atrial mapping catheter, coronary sinus catheter, and electroanatomical mapping were used in all patients. Before ablation, points were marked medial and lateral to the planned line and bidirectional conduction times were assessed. Post ablation bidirectional conduction times were assessed again at the points medial and lateral to the line. The translesional time (TL) was defined as the difference in bidirectional conduction time recorded lateral to the line from medial to the line. CBIB was verified by reversal of activation of the right atrium on the circular mapping catheter and/or documentation of widely spaced double potentials. Results: CBIB was achieved in 29/30 patients. The average baseline counterclockwise (CCW) conduction time across the CTI was 43 +/- 22 msec The average baseline clockwise (CW) conduction time was 42 +/- 16 msec. The average baseline TL was 10 msec CCW, and 9 msec CW. The longest baseline TL was 52 msec CCW and 28 msec CW . Post ablation, the average CCW conduction time was 149 msec, and CW was 150 msec in patients with CBIB. The average TL in patients with CBIB was 116 msec CCW and 111 msec CW. The shortest TL associated with CBIB was 90 msec CCW and 91 msec CW. The maximum TL associated with incomplete block was 68 msec. Conclusions: A bidirectional TL of greater 90 msec was predictive of CBIB after typical atrial flutter ablation, and could be used simplify assessment of CBIB during CTI ablation.
Deep Learning Predicts Molecular Subtype of Muscle-invasive Bladder Cancer from Conventional Histopathological Slides
Authors: Ann-Christin Woerl, Markus Eckstein, Josephine Geiger, Daniel C. Wagner, Tamas Daher, Philipp Stenzel, Aurélie Fernandez, Arndt Hartmann, Michael Wand, Wilfried Roth, Sebastian Foersch
Journal: European Urology (2020)
REPIC: a database for exploring the N6-methyladenosine methylome
Authors: Shun Liu, Allen Zhu, Chuan He, Mengjie Chen
Journal: Genome biology (2020)

Abstract The REPIC ( R NA E PI transcriptome C ollection) database records about 10 million peaks called from publicly available m 6 A-seq and MeRIP-seq data using our unified pipeline. These data were collected from 672 samples of 49 studies, covering 61 cell lines or tissues in 11 organisms. REPIC allows users to query N 6 -methyladenosine (m 6 A) modification sites by specific cell lines or tissue types. In addition, it integrates m 6 A/MeRIP-seq data with 1418 histone ChIP-seq and 118 DNase-seq data tracks from the ENCODE project in a modern genome browser to present a comprehensive atlas of m 6 A methylation sites, histone modification sites, and chromatin accessibility regions. REPIC is accessible at https://repicmod.uchicago.edu/repic .
Abstract 11934: Cardiovascular Outcomes in Adults With Systolic Blood Pressure Between 130 and 139 mmHg at Screening in the Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Gabriel Contreras, Lingyi Lu, Leonardo Tamariz, Michael Rocco, Vasilios Papademetriou, John B Kostis, Roberto Pisoni, Stephen P Glasser, Mary Ellen Sweeney, Jan Basile, Lisa H. Gren, Sara Zamanian, William C Cushman
Journal: Circulation (2018)

Introduction: Approximately 17.3 million adults have systolic blood pressure (SBP) between 130 and 139 mmHg in the USA, and they have increased risk of cardiovascular disease (CVD). Hypothesis: In ...
Early Metabolic Features of Genetic Liability to Type 2 Diabetes: Cohort Study With Repeated Metabolomics Across Early Life
Authors: Joshua A. Bell, Caroline J. Bull, Marc J. Gunter, David Carslake, Anubha Mahajan, George Davey Smith, Nicholas J. Timpson, Emma E. Vincent
Journal: Diabetes Care (2020)

OBJECTIVE Type 2 diabetes develops for many years before diagnosis. We aimed to reveal early metabolic features characterizing liability to adult disease by examining genetic liability to adult type 2 diabetes in relation to metabolomic traits across early life. RESEARCH DESIGN AND METHODS Up to 4,761 offspring from the Avon Longitudinal Study of Parents and Children were studied. Linear models were used to examine effects of a genetic risk score (162 variants) for adult type 2 diabetes on 229 metabolomic traits (lipoprotein subclass–specific cholesterol and triglycerides, amino acids, glycoprotein acetyls, and others) measured at age 8 years, 16 years, 18 years, and 25 years. Two-sample Mendelian randomization (MR) was also conducted using genome-wide association study data on metabolomic traits in an independent sample of 24,925 adults. RESULTS At age 8 years, associations were most evident for type 2 diabetes liability (per SD higher) with lower lipids in HDL subtypes (e.g., −0.03 SD [95% CI −0.06, −0.003] for total lipids in very large HDL). At 16 years, associations were stronger with preglycemic traits, including citrate and with glycoprotein acetyls (0.05 SD; 95% CI 0.01, 0.08), and at 18 years, associations were stronger with branched-chain amino acids. At 25 years, associations had strengthened with VLDL lipids and remained consistent with previously altered traits, including HDL lipids. Two-sample MR estimates among adults indicated persistent patterns of effect of disease liability. CONCLUSIONS Our results support perturbed HDL lipid metabolism as one of the earliest features of type 2 diabetes liability, alongside higher branched-chain amino acid and inflammatory levels. Several features are apparent in childhood as early as age 8 years, decades before the clinical onset of disease.
Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children’s Oncology Group
Authors: Rajen Mody, Alice L. Yu, Arlene Naranjo, Fan F. Zhang, Wendy B. London, Barry L. Shulkin, Marguerite T. Parisi, Sabah-E-Noor Servaes, Mitchell B. Diccianni, Jacquelyn A. Hank, Mildred Felder, Jennifer Birstler, Paul M. Sondel, Shahab Asgharzadeh, Julia Glade-Bender, Howard Katzenstein, John M. Maris, Julie R. Park, Rochelle Bagatell
Journal: Journal of Clinical Oncology (2020)

PURPOSE The combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neuroblastoma in the randomized Children’s Oncology Group ANBL1221 trial. To more accurately assess response rate and toxicity, an expanded cohort was nonrandomly assigned to I/T/DIN/GM-CSF. PATIENTS AND METHODS Patients were eligible at first relapse or first designation of refractory disease. Oral T and intravenous (IV) irinotecan were administered on days 1 to 5 of 21-day cycles. DIN was administered IV (days 2-5), and GM-CSF was administered subcutaneously (days 6-12). The primary end point was objective response, analyzed on an intent-to-treat basis per the International Neuroblastoma Response Criteria. RESULTS Seventeen eligible patients were randomly assigned to I/T/DIN/GM-CSF (February 2013 to March 2015); 36 additional patients were nonrandomly assigned to I/T/DIN/GM-CSF (August 2016 to May 2017). Objective (complete or partial) responses were observed in nine (52.9%) of 17 randomly assigned patients (95% CI, 29.2% to 76.7%) and 13 (36.1%) of 36 expansion patients (95% CI, 20.4% to 51.8%). Objective responses were seen in 22 (41.5%) of 53 patients overall (95% CI, 28.2% to 54.8%); stable disease was also observed in 22 of 53. One-year progression-free and overall survival for all patients receiving I/T/DIN/GM-CSF were 67.9% ± 6.4% (95% CI, 55.4% to 80.5%) and 84.9% ± 4.9% (95% CI, 75.3% to 94.6%), respectively. Two patients did not receive protocol therapy and were evaluable for response but not toxicity. Common grade ≥ 3 toxicities were fever/infection (18 [35.3%] of 51), neutropenia (17 [33.3%] of 51), pain (15 [29.4%] of 51), and diarrhea (10 [19.6%] of 51). One patient met protocol-defined criteria for unacceptable toxicity (grade 4 hypoxia). Higher DIN trough levels were associated with response. CONCLUSION I/T/DIN/GM-CSF has significant antitumor activity in patients with relapsed/refractory neuroblastoma. Study of chemoimmunotherapy in the frontline setting is indicated, as is further evaluation of predictive biomarkers.
Offline: Why President Trump is wrong about WHO
Authors: Richard Horton
Journal: The Lancet (2020)

April 14, 2020: President Trump, speaking at The White House—"Today, I am instructing my administration to halt funding of the World Health Organization while a review is conducted to assess the World Health Organization's role in severely mismanaging and covering up the spread of the coronavirus…The WHO's reliance on China's disclosures likely caused a 20-fold increase in cases worldwide, and it may be much more than that. The WHO has not addressed a single one of these concerns nor provided a serious explanation that acknowledges its own mistakes, of which there were many…so much death has been caused by their mistakes." Here are the facts.
Abstract 4014: Connexin43 Remodeling in Septal Biopsies as a Sensitive Marker for Diagnosing Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Maartje Noorman, Sara Hakim, Moniek G Cox, Harold van Rijen, Marcel A van der Heyden, Nicolaas de Jonge, Jasper J van der Smagt, Aryan Vink, Roel A de Weger, Andras Varro, Jacques M de Bakker, Richard N Hauer, Toon A van Veen
Journal: Circulation (2009)
Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia
Authors: Howard A. Fink, Eric J. Linskens, Roderick MacDonald, Pombie C. Silverman, J. Riley McCarten, Kristine M.C. Talley, Mary L. Forte, Priyanka J. Desai, Victoria A. Nelson, Margaret A. Miller, Laura S. Hemmy, Michelle Brasure, Brent C. Taylor, Weiwen Ng, Jeannine M. Ouellette, Kerry M. Sheets, Timothy J. Wilt, Mary Butler
Journal: Annals of Internal Medicine (2020)

Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain.To summarize evidence on the effects of prescription drugs and supplements for CATD treatment.Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies.English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD).Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy.Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes.Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials.Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes.Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).
Vitamin K<sub>1</sub> Treatment Duration in Patients with Brodifacoum Poisoning
Authors: Luke Yip, Noel V Stanton, Robert A Middleberg
Journal: New England Journal of Medicine (2020)

Vitamin K1 Treatment Duration in Brodifacoum Poisoning The rodenticide brodifacoum, a long-acting vitamin K epoxide cycle antagonist, can produce life-threatening hemorrhage in exposed humans. Its ...
Human Plasmodium vivax mosquito experimental transmission
Authors: David J. Sullivan, Peter Agre
Journal: Journal of Clinical Investigation (2020)

Plasmodium vivax bench research greatly lags behind Plasmodium falciparum because of an inability to culture in vitro. A century ago, intentionally inducing a malaria infection was a strategy commonly used to cure late-stage syphilis. These controlled human malaria infections were used with expertise and persisted to the end of World War II. While controlled malaria liver-stage infection has been achieved for both P. vivax and P. falciparum, controlled human transmission to mosquitoes falls short for both species. In this issue of the JCI, Collins et al. present groundbreaking work that establishes a system to transmit P. vivax gametocytes from humans to mosquitoes. The authors injected a unique human isolate of P. vivax that reached high gametocyte density within weeks. This study provides a technical advance that will facilitate the study and eradication of the human parasite P. vivax.
Systematic review and critical appraisal of prediction models for diagnosis and prognosis of COVID-19 infection
Authors: L Wynants, B Van Calster, Bonten Mmj., G Collins, Debray Tpa., M De Vos, M Haller, G Heinze, Moons Kgm., R Riley, E Schuit, L Smits, Snell Kie., E Steyerberg, C Wallisch, M van Smeden
Journal: BMJ (2020)
Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopaenic purpura
Authors: Wenhui Xie, Zhuoli Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopaenic purpuraWe read the published article by Zhu et al 1 with great interest.In this population-based retrospective cohort study, the authors demonstrated that the patients with idiopathic thrombocytopaenic purpura (ITP) had a 26 times higher risk of new-onset systemic lupus erythematosus (SLE) compared with the control population.However, some concerns do exist and should be addressed.First, thrombocytopaenia is known as a common clinical manifestation of SLE and can be the initial presentation in 5% of patients with SLE. 2 3 The diagnosis of ITP is based principally on the exclusion of any known causes of thrombocytopaenia by history, clinical manifestations, physical examination, laboratory tests, bone marrow examination and so on. 4In the study, the search of patients with ITP was according to International Classification of Diseases, Ninth Revision, Clinical Modification code 287.3.In the setting of nationwide population, obviously, most patients with thrombocytopaenia initially see haematologists, rather than rheumatologists.Under the circumstances, some early stage of SLE patients with thrombocytopaenia as the only initial manifestation may be wrongly diagnosed as ITP and were included in ITP group in the study.Therefore, serious selection bias exists, which is, at least in part, attributable to the incredibly high HR.The authors should have checked the diagnosis of ITP before these patients were included in the ITP group.A potential solution is to exclusively include the patients with negative autoantibodies at the time of ITP diagnosis.Second, only 0.19% of patients in the non-ITP group developed SLE during follow-up.In the context of extremely low incidence rates, a cohort design is deeply challenging and problematic and usually lead to poor robustness of estimates, embodied in the particularly wide 95% CI in the study (eg, 95% CI 13.7 to 46.0).Meanwhile, although the authors had controlled a range of baseline characteristics, several considerable risk factors strongly related to developing SLE still failed to be adjusted, for example, family history of SLE (or rheumatic diseases) in first-degree relatives and smoking. 5he presence of residual factors was acceptable in some situation, but the confounding bias caused by confounding factors could be amplified in the presence of extremely low incidence rates and largely weakened the reliability of findings.In addition, we consider the time to the SLE for the two groups should be provided in the study.
Longitudinal Monitoring of ctDNA in Patients with Melanoma and Brain Metastases Treated with Immune Checkpoint Inhibitors
Authors: Jenny H. Lee, Alexander M. Menzies, Matteo S. Carlino, Ashleigh C. McEvoy, Shahneen Sandhu, Alison M. Weppler, Russell J. Diefenbach, Sarah-Jane Dawson, Richard F. Kefford, Michael J. Millward, Zeyad Al-Ogaili, Thien Tra, Elin S. Gray, Stephen Q. Wong, Richard A. Scolyer, Georgina V. Long, Helen Rizos
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Brain involvement occurs in the majority of patients with metastatic melanoma. The potential of circulating tumor DNA (ctDNA) for surveillance and monitoring systemic therapy response in patients with melanoma brain metastases merits investigation. Experimental Design: This study examined circulating BRAF, NRAS, and c-KIT mutations in patients with melanoma with active brain metastases receiving PD-1 inhibitor–based therapy. Intracranial and extracranial disease volumes were measured using the sum of product of diameters, and response assessment performed using RECIST. Longitudinal plasma samples were analyzed for ctDNA over the first 12 weeks of treatment (threshold 2.5 copies/mL plasma). Results: Of a total of 72 patients, 13 patients had intracranial metastases only and 59 patients had concurrent intracranial and extracranial metastases. ctDNA detectability was 0% and 64%, respectively, and detectability was associated with extracranial disease volume (P &amp;lt; 0.01). Undetectable ctDNA on-therapy was associated with extracranial response (P &amp;lt; 0.01) but not intracranial response. The median overall survival in patients with undetectable (n = 34) versus detectable (n = 38) ctDNA at baseline was 39.2 versus 10.6 months [HR, 0.51; 95% confidence interval (CI), 0.28–0.94; P = 0.03] and on-therapy was 39.2 versus 9.2 months (HR, 0.32; 95% CI, 0.16–0.63; P &amp;lt; 0.01). Conclusions: ctDNA remains a strong prognostic biomarker in patients with melanoma with brain metastases, especially in patients with concurrent extracranial disease. However, ctDNA was not able to detect or monitor intracranial disease activity, and we recommend against using ctDNA as a sole test during surveillance and therapeutic monitoring in patients with melanoma.
Exposure to air pollutants and the gut microbiota: a potential link between exposure, obesity, and type 2 diabetes
Authors: Maximillian J. Bailey, Noopur N. Naik, Laura E. Wild, William B. Patterson, Tanya L. Alderete
Journal: Gut Microbes (2020)

Work has shown that increased exposure to air pollutants independently contributes to obesity and type 2 diabetes risk, yet the exact mechanisms underlying these associations have not been fully characterized. The current review summarizes recent findings regarding the impact of inhaled and ingested air pollutants on the gut microbiota. Animal and human studies provide evidence that air pollutants, such as particulate matter, nitrogen oxides, and ozone, have the potential to alter the gut microbiota. Further, studies suggest that such exposure-induced alterations to the gut microbiota may contribute to increased risk for obesity and type 2 diabetes through inflammatory pathways. Future work is needed to fully understand the complex interactions between air pollution, the gut microbiome, and human health. Additionally, advanced sequencing methods for gut microbiome research present unique opportunities to study the underlying pathways that link increased air pollution exposure with obesity and type 2 diabetes risk.