tbuckley/cabot-search huggingface dataset:
Assessing the Ability of Developmentally Precocious Estrogen Signaling to Recapitulate Ovarian Transcriptomes and Follicle Dynamics in Alligators from a Contaminated Lake
Authors: Matthew D. Hale, Benjamin B. Parrott
Journal: Environmental Health Perspectives (2020)

Concern has grown in recent decades over anthropogenic contaminants that interfere with the functioning of endocrine hormones. However, mechanisms connecting developmental processes to pathologies associated with endocrine-disrupting chemical (EDC) exposure are poorly understood in naturally exposed populations.We sought to a) characterize divergence in ovarian transcriptomic and follicular profiles between alligators originating from a historically EDC-contaminated site, Lake Apopka, and a reference site; b) test the ability of developmentally precocious estrogen exposure to recapitulate site-associated patterns of divergence; and c) test whether treatment with exogenous follicle-stimulating hormone (FSH) is capable of rescuing phenotypes associated with contaminant exposure and/or embryonic estrogen treatment.Alligators eggs were collected from a contaminated site and a reference site, and a subset of eggs from the reference site were treated with estradiol (E2) during embryonic development prior to gonadal differentiation. After hatching, alligators were raised under controlled laboratory settings for 5 months. Juveniles from both sites were divided and treated with exogenous FSH. Histological analyses and RNA-sequencing were conducted to characterize divergence in ovarian follicle dynamics and transcriptomes between sites, between reference and E2-treated animals, and between FSH-treated and nontreated animals.We observed broad site-of-origin divergence in ovarian transcriptomes and reductions in ovarian follicle density between juvenile alligators from Lake Apopka and the reference site. Treating embryos from the reference site with E2 overwhelmingly recapitulated transcriptional and histological alterations observed in Lake Apopka juveniles. Ovarian phenotypes observed in Lake Apopka alligators or resulting from estrogen treatment were only partially rescued by treatment with exogenous FSH.Recapitulation of ovarian abnormalities by precocious E2 revealed a relatively simple mechanism underlying contaminant-induced pathologies in a historical example of environmental endocrine disruption. Findings reported here support a model where the developmental timing of estrogen signaling has the potential to permanently alter ovarian organization and function. https://doi.org/10.1289/EHP6627.
Underwater cap-assisted endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy: a pilot study
Authors: Alessandro Fugazza, Andrea Anderloni, Danilo Paduano, Matteo Badalamenti, Roberta Maselli, Silvia Carrara, Roberto Gabbiadini, Matteo Colombo, Marco Spadaccini, Annalisa Cappello, Gregory Haber, Alessandro Repici
Journal: Endoscopy (2020)

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy (SAA) is technically challenging and associated with a significant number of failures. We examined the feasibility and efficacy of a novel technique for the management of bile duct stones (BDSs), called underwater cap-assisted ERCP (u-ERCP). METHODS : Between June 2019 and February 2020 all patients with SAA with jaundice or cholangitis secondary to BDSs who underwent u-ERCP were enrolled. The u-ERCP technique combines the underwater advancement of a pediatric colonoscope with a transparent cap fitted on the tip of the endoscope. We evaluated the technical success, clinical success, and adverse events associated with u-ERCP. RESULTS : We describe the technique itself and our initial experience in six patients. A complete and successful procedure was carried out in all patients, with the occurrence of no adverse events. None of the patients needed additional treatments for recurrence of symptoms during the follow-up period. CONCLUSIONS : u-ERCP can be considered as a promising alternative for successful endoscopic management of biliary disease in patients with SAA.
Abstract 15931: Associated Genetic and Non-Cardiac Anomalies and Outcomes in Prenatally Detected Tetralogy of Fallot
Authors: Rishav Sharma, Lisa K Hornberger, Oana Caluseriu, Karen Y Niederhoffer, Luke Eckersley, Timothy Colen, Lily Lin, Michelle Rushfeldt, Rose He, Angela McBrien
Journal: Circulation (2020)

Introduction: Historically, prenatal detection of tetralogy of Fallot (ToF) was poor and around 60% had major extracardiac (ECA) or genetic anomalies. Recently, prenatal detection of ToF has improved, along with a wider range of genetic testing options. Knowledge of outcomes and risk of associated anomalies is crucial for prenatal counselling. We hypothesize that prenatal ToF now has a different risk profile for ECAs and genetic anomalies than previously reported. Methods: A retrospective study of all fetuses with a diagnosis of ToF in our Fetal Cardiology program from 2012-2019. ToF type double outlet right ventricle was excluded. Pre and postnatal charts and imaging reports were reviewed for ToF subtype, additional cardiac and non-cardiac diagnoses and outcomes. Results: Of 83 cases, 49 had standard ToF, 24 pulmonary atresia (14 with major collateral arteries, 10 without), and 10 absent pulmonary valve. There was ≥1 ECA in 41% (34/83), including 6% (5/83) with 2 and 4% (3/83) with 3. ECA sub-types were: 10 gastrointestinal, 8 neurological, 8 pulmonary, 7 renal, 4 musculoskeletal, and 8 others. Of 76 with genetic testing, 37% (28/76) had genetic anomalies (32% (9/28) Trisomy 21, 29% (8/28) 22q11 deletion, 7% (2/28) Trisomy 18, 7% (2/28) Trisomy 13, and 25% (7/28) other). Additional diagnoses: 4% (3/76) VACTERL spectrum, 1% (1/76) possible teratogenic effect. Right aortic arch was associated with 22q11 deletion (28% (7/25) vs 2% (1/51) p&lt;0.001). ToF with atrioventricular septal defect (AVSD) was strongly associated with Trisomy 21 (100%, 3/3 tested). Those with ≥1 ECA were more likely to have a genetic abnormality (52% (17/33) vs 24% (9/37), p&lt;0.05). Outcomes were: 22% (18/83) termination, 5% (4/83) intrauterine fetal deaths and 72% (60/83) livebirths, with 1 lost to follow-up. Of live births, there were 3% (2/60) neonatal and 7% (4/60) late deaths, and 90% (54/60) were alive at last follow-up (mean age 3.5±2.4 years). Conclusion: ECAs are less common in prenatally diagnosed ToF in the modern era, however the rate of genetic diagnoses is similar to previously published data. ToF with right aortic arch and ToF with AVSD in particular have strong genetic associations. Additionally, genetic diagnoses are more common in those with an ECA.
Association Between Health Care Utilization and Immigration Enforcement Events in San Francisco
Authors: Vasil I. Yasenov, Jens Hainmueller, Michael Hotard, Duncan Lawrence, Laura M. Gottlieb, Jacqueline M. Torres
Journal: JAMA Network Open (2020)

This cohort study explores whether an inclusive, local health care system could serve as a buffer against adverse effects on access to health care due to actions related to immigration status in patients who are likely undocumented.
Validating clinical practice guidelines for the management of children with non-blanching rashes in the UK (PiC): a prospective, multicentre cohort study
Authors: Thomas Waterfield, Juli-Ann Maney, Derek Fairley, Mark D Lyttle, James P McKenna, Damian Roland, Michael Corr, Lisa McFetridge, Hannah Mitchell, Kerry Woolfall, Fiona Lynn, Bethany Patenall, Michael D Shields, Amy Kitching, Matthew Rotheram, Gisela Robinson, Paula Brassey, Stuart Hartshorn, Rachel Wane, Mark Lyttle, Jo Dangerfield, Michael Hayes, Rebecca McFarlane, Helen Armstrong, Damian Roland, Sally Smith, Carl VanHeyningen, Sally Smith, Esther Wilson, Lisa Kehler, Christopher Gough, Fraser Scott, Claire Backhouse, Sylvester Gomes, Darryl Wood, Julie-Ann Maney, Graham Johnson, Steven Foster, Ben Bloom, Andrew Lancaster, Sebastian Gray, Shammi Ramlakhan, Sharryn Gardner, Sharon Floyd, Chris Cleaver, Susan MacFarlane, Claire Bell, Maggie Nyirenda, Jane Bayreuther, Asim Ijaz, Natalie Rogers, Sarah Wilson, Sarah Diment, Caroline Boulind, Kathryn Allison, Thomas Waterfield, Derek Fairley, James McKenna, Michael Corr, Lisa McFetridge, Hannah Mitchell, Kerry Woolfall, Fiona Lynn, Bethany Petenall, Michael Shields
Journal: The Lancet Infectious Diseases (2020)
Progress Toward Regional Measles Elimination — Worldwide, 2000–2019
Authors: Minal K. Patel, James L. Goodson, James P. Alexander, Katrina Kretsinger, Samir V. Sodha, Claudia Steulet, Marta Gacic-Dobo, Paul A. Rota, Jeffrey McFarland, Lisa Menning, Mick N. Mulders, Natasha S. Crowcroft
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In 2010, the World Health Assembly (WHA) set the following three milestones for measles control to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district, 2) reduce global annual measles incidence to <5 cases per 1 million population, and 3) reduce global measles mortality by 95% from the 2000 estimate* (1). In 2012, WHA endorsed the Global Vaccine Action Plan,† with the objective of eliminating measles§ in five of the six World Health Organization (WHO) regions by 2020. This report describes progress toward WHA milestones and regional measles elimination during 2000-2019 and updates a previous report (2). During 2000-2010, estimated MCV1 coverage increased globally from 72% to 84% but has since plateaued at 84%-85%. All countries conducted measles surveillance; however, approximately half did not achieve the sensitivity indicator target of two or more discarded measles and rubella cases per 100,000 population. Annual reported measles incidence decreased 88%, from 145 to 18 cases per 1 million population during 2000-2016; the lowest incidence occurred in 2016, but by 2019 incidence had risen to 120 cases per 1 million population. During 2000-2019, the annual number of estimated measles deaths decreased 62%, from 539,000 to 207,500; an estimated 25.5 million measles deaths were averted. To drive progress toward the regional measles elimination targets, additional strategies are needed to help countries reach all children with 2 doses of measles-containing vaccine, identify and close immunity gaps, and improve surveillance.
Efficacy and immune-related adverse event associations in avelumab-treated patients
Authors: Karen Kelly, Juliane Manitz, Manish R Patel, Sandra P D’Angelo, Andrea B Apolo, Arun Rajan, Vijay Kasturi, Isabell Speit, Marcis Bajars, John Warth, James L Gulley
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Adverse events (AEs) of special interest that arise during treatment with immune checkpoint inhibitors, including immune-related AEs (irAEs), have been reported to be associated with improved clinical outcomes. We analyzed patients treated with avelumab from the JAVELIN Solid Tumor and Merkel 200 trials, examining the association between AEs and efficacy while adjusting for confounding factors such as treatment duration and event order. Methods We analyzed efficacy and safety data from 1783 patients treated with the programmed death ligand 1 inhibitor avelumab who were enrolled in expansion cohorts of the JAVELIN Solid Tumor and Merkel 200 trials. To analyze the association between irAEs and efficacy with regard to survival, we used a time-dependent Cox model with time-varying indicators for irAEs, as well as multistate models that accounted for competing risks and time inhomogeneity. Results 295 patients (16.5%) experienced irAEs and 454 patients (25.5%) experienced infusion-related reactions. There was a reduced risk of death in patients who experienced irAEs compared with those who did not (HR 0.71, 95% CI 0.59 to 0.85) using the time-dependent Cox model. The multistate model did not suggest that the occurrence of irAEs could predict response; however, it predicted a higher chance of irAEs occurring after a response. No association was observed between response and infusion-related reactions. Conclusions Patients who experience irAEs showed improved survival. Although irAEs are not predictors for response to immune checkpoint inhibitors, increased vigilance for irAEs is needed after treatment with avelumab. Trial registration numbers NCT01772004 and NCT02155647 .
Randomized, Controlled Trial to Evaluate the Effect of Dapagliflozin on Left Ventricular Diastolic Function in Patients With Type 2 Diabetes Mellitus
Authors: Chi Young Shim, Jiwon Seo, Iksung Cho, Chan Joo Lee, In-Jeong Cho, Purevjargal Lhagvasuren, Seok-Min Kang, Jong-Won Ha, Gyoonhee Han, Yangsoo Jang, Geu-Ru Hong
Journal: Circulation (2020)
Immunophenotyping in pemphigus reveals a TH17/TFH17 cell–dominated immune response promoting desmoglein1/3-specific autoantibody production
Authors: Julia Holstein, Farzan Solimani, Carolin Baum, Katharina Meier, Robert Pollmann, Dario Didona, Tobias Tekath, Martin Dugas, Nicolas Casadei, Christoph Hudemann, Alexandra Polakova, Jakob Matthes, Iris Schäfer, Amir S. Yazdi, Rüdiger Eming, Michael Hertl, Wolfgang Pfützner, Kamran Ghoreschi, Christian Möbs
Journal: Journal of Allergy and Clinical Immunology (2020)
Gallstone impaction at the orifice of the duct of Wirsung successfully treated via needle-knife papillotomy
Authors: Takashi Abe, Takayuki Nagai, Takehiko Nariyasu, Marina Hamamoto, Masato Hanzawa, Yasuhisa Hiroshima, Kazunari Murakami
Journal: Endoscopy (2020)

An 80-year-old woman presented with epigastralgia. Laboratory investigations demonstrated markedly elevated cholestatic parameters and slightly elevated pancreatic enzymes, including total bilirubin 3.6 mg/dL (normal range 0.4 – 1.5 mg/dL), aspartate aminotransferase 725 U/L (13 – 30 U/L), alanine aminotransferase 637 U/L (10 – 42 U/L), alkaline phosphatase 353 U/L (38 – 113 U/L), γ-glutamyl transpeptidase 486 U/L (9 – 32 U/L), amylase 144 U/L (44 – 132 U/L), pancreatic amylase 47.2 % (13.0 – 47.0 %), and lipase 70 U/L (11 – 59 U/L). Her white blood cell count and C-reactive protein level were within normal limits. Abdominal computed tomography (CT) revealed a gallstone (approximately 8 mm in size) impacted at the ampulla of Vater ([Fig. 1]), but the gallstone was not shown on magnetic resonance cholangiopancreatography (MRCP). Additionally, CT and MRCP showed mild common bile duct (CBD) dilatation and cholecystolithiasis, with no evidence of pancreatitis or dilatation of the pancreatic duct ([Fig. 2]).
Abstract 12360: Utilization of Cholesterol-lowering Therapies in Patients With Chronic Kidney Disease and Atherosclerotic Cardiovascular Disease (ASCVD). Results From a National Survey in the Getting to an Improved Understanding of Low-density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) Registry
Authors: Robert S Rosenson, Katie Mues, Yuyin Liu, Christie M Ballantyne, James A De Lemos, Shushama Alam, Mary Elliott-Davey, Deepak L Bhatt, Mikhail N Kosiborod, Christopher P Cannon
Journal: Circulation (2019)

Introduction: Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), and statin therapy (along with ezetimibe) has been proven to redu...
Youth sports in the wake of COVID-19: a call for change
Authors: Andrew Watson, Jennifer Scott Koontz
Journal: British Journal of Sports Medicine (2020)

The COVID-19 pandemic has had a significant impact on virtually every facet of life throughout the world. Among youth athletes, the cancellation of school and sports was accompanied by decreases in physical activity and significant mental health consequences. The reintroduction of sports has varied considerably, with the full return of sports in some regions and continued restriction in others. Given that youth sports faced serious problems prior to the pandemic including high costs, professionalisation, decreased participation and barriers to access,1 we should consider more than just returning to ‘normal’. This unexpected pause provides an opportunity to not only guide the return to youth sport participation but invest in programmes and organisations that increase physical activity and increase access to sports for all children.

Physical activity and sports participation have a wide range of physical and mental health benefits in children.2 Unfortunately, the restrictions during the COVID-19 pandemic have resulted in significant reductions in physical activity and worrisome increases in anxiety and depression in young athletes. For example, in a survey of over 13 000 adolescent athletes throughout the …
Impact of heart failure on the clinical course and outcomes of patients hospitalized for <scp>COVID</scp>‐19. Results of the <scp>Cardio‐COVID‐Italy</scp> multicentre study
Authors: Daniela Tomasoni, Riccardo M. Inciardi, Carlo M. Lombardi, Chiara Tedino, Piergiuseppe Agostoni, Pietro Ameri, Lucia Barbieri, Antonio Bellasi, Rita Camporotondo, Claudia Canale, Valentina Carubelli, Stefano Carugo, Francesco Catagnano, Laura A. Dalla Vecchia, Gian Battista Danzi, Mattia Di Pasquale, Margherita Gaudenzi, Stefano Giovinazzo, Massimiliano Gnecchi, Annamaria Iorio, Maria Teresa La Rovere, Sergio Leonardi, Gloria Maccagni, Massimo Mapelli, Davide Margonato, Marco Merlo, Luca Monzo, Andrea Mortara, Vincenzo Nuzzi, Massimo Piepoli, Italo Porto, Andrea Pozzi, Filippo Sarullo, Gianfranco Sinagra, Maurizio Volterrani, Gregorio Zaccone, Marco Guazzi, Michele Senni, Marco Metra
Journal: European Journal of Heart Failure (2020)
Abstract 14403: Troponin as a Powerful Predictor of Mortality in Critically Ill Covid-19 Patientsmulticenter Analysis in 159 Patients
Authors: Zulfiqar Qutrio Baloch, Abbas Ali, Abdullah Alabcha, manel boumegouas, Steven Do, Randy Ip, Matt Wilcox, John Ip
Journal: Circulation (2020)

Introduction: Certain cardiac biomarkers have been shown to predict survival in patients infected with COVID-19. However. The use of Troponins, CPK and LDH in predicting the outcome in patients who are critically ill and require advanced respiratory support is less clear. Methods: We performed a multicenter analysis of 159 consecutive patients with confirmed COVID-19 who were admitted to Intensive Care Unit (ICU) between March 01, 2020 and April 30, 2020. Patients were then followed until May 23, 2020. Demographic data (age, sex, race, BMI) were recorded. Cardiac biomarkers (CPK, Troponins, BNP, LDH) were analyzed. Patient status was classified either alive or deceased at the end of follow up period. Results: Mean patient age was 66+/-15 and 53% were male. Mean BMI was 31+/- 9. Mean hospital ICU stay was 11+/-8 days. Mortality rate of this ICU cohort at the end of follow-up was 63%. Fifty-five (34%) patients were discharged from the hospital. A multivariate logistic regression analysis identified 2 factors (Age &gt;62 HR 2.4, 95% CI 1.21-4.676, p&lt;0.01 and elevated Troponin &gt;0.5 HR 3.45, 95% CI 1.01-11.8, p 0.048) has significant and independent contributions to the likelihood of survival (Fig 1 and Fig 2). Fig 1 KM curve of different strata of Troponin levels Fig 2 KM curve of 2 strata of Age Conclusion: Elevated Troponins level are common in critically ill COVID-19 patients. The highly predictive value of Troponins in survival may indicate possible cardiac involvement of COVID-19 infection as a determinant of mortality. Early and serial determination of Troponin values can provide risk stratification for these patients and timely aggressive intervention may decrease mortality.
Correspondence to ‘Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour necrosis factor inhibitor biologics and targeted synthetic agents in patients with rheumatoid arthritis: results from a large US registry study’
Authors: Wenjie Zheng, Pui-Ying Leong, James Cheng-Chung Wei
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article by Pappas et al 1 who evaluated the comparative effectiveness of a tumour necrosis factor inhibitor (TNFi) such as adalimumab, etanercept, certolizumab pegol, golimumab or infliximab versus a non-TNFi (abatacept, tocilizumab, rituximab, anakinra or tofacitinib) as the first-line treatment in patients with rheumatoid arthritis (RA). The authors concluded that there were no statistically significant differences observed between the TNFi and non-TNFi treatment groups for the outcomes assessed, including the Clinical Disease Activity Index (CDAI), the 28-Joint Modified Disease Activity Score, the Health Assessment Questionnaire Disability Index, EuroQol-5 Dimension score, morning stiffness and fatigue. In this observational study, data collected from 1 October 2001 to 31 January 2018 within a large US healthcare registry were evaluated, and 4816 patients who had a non-remission CDAI score …
Machine-learning, MRI bone shape and important clinical outcomes in osteoarthritis: data from the Osteoarthritis Initiative
Authors: Michael A. Bowes, Katherine Kacena, Oras A. Alabas, Alan D. Brett, Bright Dube, Neil Bodick, Philip G Conaghan
Journal: Annals of the Rheumatic Diseases (2020)

Objectives Osteoarthritis (OA) structural status is imperfectly classified using radiographic assessment. Statistical shape modelling (SSM), a form of machine-learning, provides precise quantification of a characteristic 3D OA bone shape. We aimed to determine the benefits of this novel measure of OA status for assessing risks of clinically important outcomes. Methods The study used 4796 individuals from the Osteoarthritis Initiative cohort. SSM-derived femur bone shape (B-score) was measured from all 9433 baseline knee MRIs. We examined the relationship between B-score, radiographic Kellgren-Lawrence grade (KLG) and current and future pain and function as well as total knee replacement (TKR) up to 8 years. Results B-score repeatability supported 40 discrete grades. KLG and B-score were both associated with risk of current and future pain, functional limitation and TKR; logistic regression curves were similar. However, each KLG included a wide range of B-scores. For example, for KLG3, risk of pain was 34.4 (95% CI 31.7 to 37.0)%, but B-scores within KLG3 knees ranged from 0 to 6; for B-score 0, risk was 17.0 (16.1 to 17.9)% while for B-score 6, it was 52.1 (48.8 to 55.4)%. For TKR, KLG3 risk was 15.3 (13.3 to 17.3)%; while B-score 0 had negligible risk, B-score 6 risk was 35.6 (31.8 to 39.6)%. Age, sex and body mass index had negligible effects on association between B-score and symptoms. Conclusions B-score provides reader-independent quantification using a single time-point, providing unambiguous OA status with defined clinical risks across the whole range of disease including pre-radiographic OA. B-score heralds a step-change in OA stratification for interventions and improved personalised assessment, analogous to the T-score in osteoporosis.