tbuckley/cabot-search huggingface dataset:
A Novel Locus Predicts Spermatogenic Recovery among Childhood Cancer Survivors Exposed to Alkylating Agents
Authors: Yadav Sapkota, Carmen L. Wilson, Asifa K. Zaidi, Wonjong Moon, Klementina Fon Tacer, Lu Lu, Qi Liu, Jessica Baedke, Rikeenkumar Dhaduk, Zhaoming Wang, Wassim Chemaitilly, Matthew J. Krasin, Fred B. Berry, Jinghui Zhang, Melissa M. Hudson, Leslie L. Robison, Daniel M. Green, Yutaka Yasui
Journal: Cancer Research (2020)

Abstract Exposure to high doses of alkylating agents is associated with increased risk of impaired spermatogenesis among nonirradiated male survivors of childhood cancer, but there is substantial variation in this risk. Here we conducted a genetic study for impaired spermatogenesis utilizing whole-genome sequencing data from 167 nonirradiated male childhood cancer survivors of European ancestry from the St. Jude Lifetime Cohort treated with cyclophosphamide equivalent dose (CED) ≥4,000 mg/m2. Sperm concentration from semen analysis was assessed as the primary outcome. Common variants (MAF &amp;gt; 0.05) were adjusted for age at cancer diagnosis, CED, and top principal components. Rare/low-frequency variants (MAF ≤ 0.05) were evaluated jointly by various functional annotations and 4-kb sliding windows. A novel locus at 7q21.3 containing TAC1/ASNS was associated with decreased sperm concentration (rs7784118: P = 3.5 × 10−8). This association was replicated in two independent samples of SJLIFE survivors of European ancestry, including 34 nonirradiated male survivors treated with 0 &amp;lt; CED &amp;lt; 4,000 mg/m2 (P = 3.1 × 10−4) and 24 male survivors treated with CED ≥4,000 mg/m2 and radiotherapy &amp;lt;40 Gray (P = 0.012). No association was observed among survivors not exposed to alkylating agents included in the CED (P &amp;gt; 0.29). rs7784118 conferred 3.48- and 9.73-fold increases in risk for clinically defined oligospermia and azoospermia and improved prediction of normospermic, oligospermic, and azoospermic states by 13.7%, 5.3%, and 21.7%. rs7784118 was associated with decreased testosterone level, increased levels of follicle stimulating and luteinizing hormones, and 8.52-fold increased risk of Leydig cell failure. Additional research is warranted to determine how this SNP influences spermatogenesis and to assess its clinical utility in characterizing high-risk survivors and guiding intervention strategies. Significance: The identified genetic markers harbor potential clinical utility in characterizing high-risk survivors and guiding intervention strategies including pretreatment patient counseling and use of fertility preservation services.
Upper airways colonisation of Streptococcus pneumoniae in adults aged 60 years and older: A systematic review of prevalence and individual participant data meta-analysis of risk factors
Authors: Emma L. Smith, India Wheeler, Hugh Adler, Daniela M. Ferreira, Raquel Sá-Leão, Osman Abdullahi, Ifedayo Adetifa, Sylvia Becker-Dreps, Susanna Esposito, Helmia Farida, Rama Kandasamy, Grant A. Mackenzie, J. Pekka Nuorti, Susan Nzenze, Shabir A. Madhi, Omar Ortega, Anna Roca, Dodi Safari, Frieder Schaumburg, Effua Usuf, Elisabeth A.M. Sanders, Lindsay R. Grant, Laura L. Hammitt, Katherine L. O'Brien, Prabhu Gounder, Dana J.T. Bruden, Michelle C. Stanton, Jamie Rylance
Journal: Journal of Infection (2020)

Colonisation with Streptococcus pneumoniae can lead to invasive pneumococcal disease and pneumonia. Pneumococcal acquisition and prevalence of colonisation are high in children. In older adults, a population susceptible to pneumococcal disease, colonisation prevalence is reported to be lower, but studies are heterogeneous.This is a systematic review and meta-analysis of prevalence of, and risk factors for, pneumococcal colonisation in adults ≥ 60 years of age (PROSPERO #42016036891). We identified peer-reviewed studies reporting the prevalence of S. pneumoniae colonisation using MEDLINE and EMBASE (until April 2016), excluding studies of acute disease. Participant-level data on risk factors were sought from each study.Of 2202 studies screened, 29 were analysable: 18 provided participant-level data (representing 6290 participants). Prevalence of detected pneumococcal colonisation was 0-39% by conventional culture methods and 3-23% by molecular methods. In a multivariate analysis, colonisation was higher in persons from nursing facilities compared with the community (odds ratio (OR) 2•30, 95% CI 1•26-4•21 and OR 7•72, 95% CI 1•15-51•85, respectively), in those who were currently smoking (OR 1•69, 95% CI 1•12-2•53) or those who had regular contact with children (OR 1•93, 95%CI 1•27-2•93). Persons living in urban areas had significantly lower carriage prevalence (OR 0•43, 95%CI 0•27-0•70).Overall prevalence of pneumococcal colonisation in older adults was higher than expected but varied by risk factors. Future studies should further explore risk factors for colonisation, to highlight targets for focussed intervention such as pneumococcal vaccination of high-risk groups.No funding was required.
Growth from adversity in trans and gender diverse people of color
Authors: Lee N. Taube, Alexander J. Mussap
Journal: International Journal of Transgender Health (2020)

Trans-negativity and gender-based discrimination negatively impact on the wellbeing and mental health in transgender (trans) and gender diverse people (TGD). There is limited research on TGD people thriving under adversity, and no research to date has considered TGD people of color in this context.We used the Post-Traumatic Growth Inventory (PTGI-X) to survey 125 TGD people of color and 625 white TGD adults (18 to 68 years old, M = 26.0, SD = 9.2) about their experiences of growth from adversity. Confirmatory factor analysis (CFA), using sub-sampling to compensate for our unequal sample sizes, supported a five-factor structure of the PTGI-X consisting of growth in relating to others, finding new possibilities, personal strength, greater appreciation of life, and spiritual/existential change. Measurement invariance tests confirmed configural, metric, and scalar invariance of this structure across the two TGD subgroups.A MANOVA revealed that growth from adversity in TGD participants was generally greater than that reported by people who have recently been exposed to a traumatic event. T-tests revealed that TGD people of color experienced more growth in terms of relating to others and more personal strength than white TGD participants. Subsequent hierarchical regressions revealed that race moderated associations between PTGI-X scores and personal well-being, with TGD people of color reporting more benefits (more well-being) at high levels of growth but also more deficits (less well-being) at low levels of growth than the white TGD subgroup.The results support the use of the PTGI-X with TGD populations and across racial TGD subgroups and indicate that growth from adversity is not only prevalent in TGD people but also relevant to positive outcomes, particularly in TGD people of color.
Enhancing postnatal care of women with gestational diabetes
Authors: Brian McMillan, Jennifer Boyd, Caroline Mitchell
Journal: BMJ (2020)

Vounzoulaki and colleagues’ finding that women with a history of gestational diabetes are almost 10 times more likely to develop type 2 diabetes starkly underscores the importance of providing ongoing postnatal support to this high risk group.1 Postnatal and annual HbA1c screening alone, however, is unlikely to achieve reduction in the risk of incident type 2 diabetes without access to interventions that support sustained lifestyle change in …
Association Between Medication Use and Bullous Pemphigoid
Authors: Sian-De Liu, Wei-Ti Chen, Ching-Chi Chi
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> The association between the use of medications and the development of bullous pemphigoid (BP) is unclear. <h3>Objective</h3> To assess the associations between previous exposure to certain medications and BP. <h3>Data Sources</h3> For this systematic review and meta-analysis, PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched for relevant studies from inception to February 20, 2020. <h3>Study Selection</h3> Case-control or cohort studies and randomized clinical trials that examined the odds or risk of BP in patients with previous medication use were included. No geographic or language limitations were imposed. <h3>Data Extraction and Synthesis</h3> The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included observational studies; Cochrane Collaboration’s tool was used for randomized clinical trials. Aggregate data were used to conduct a random-effects model meta-analysis if the included studies were sufficiently homogenous. Subgroup analyses were performed for use of various medications of the same category. <h3>Main Outcomes and Measures</h3> Odds ratio (OR), hazard ratio, and risk ratio of bullous pemphigoid in association with medication use. <h3>Results</h3> This meta-analysis included 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with a total of 285 884 participants. The meta-analysis of case-control studies showed a significant association of BP with previous use of aldosterone antagonists (pooled OR, 1.75; 95% CI, 1.28-2.40), dipeptidyl peptidase 4 inhibitors (pooled OR, 1.92; 95% CI, 1.55-2.38), anticholinergics (pooled OR, 3.12; 95% CI, 1.54-6.33), and dopaminergic medications (pooled OR, 2.03; 95% CI, 1.34-3.05). One cohort study found an increased risk of BP among patients receiving dipeptidyl peptidase 4 inhibitors (hazard ratio, 2.38; 95% CI, 1.16-4.88;<i>P</i> = .02). One trial found a higher occurrence of BP in patients with diabetes receiving linagliptin (0.2% in diabetes group vs 0% in the placebo group). <h3>Conclusions and Relevance</h3> The findings of this systematic review and meta-analysis suggest that aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications are associated with BP. These medications should be judiciously prescribed, particularly in high-risk patients who are elderly and have disabling neurologic disorders.
Dose-Response and Normal Tissue Complication Probabilities after Proton Therapy for Choroidal Melanoma
Authors: Charlotte A. Espensen, Jens F. Kiilgaard, Ane L. Appelt, Lotte S. Fog, Joel Herault, Celia Maschi, Jean-Pierre Caujolle, Juliette Thariat
Journal: Ophthalmology (2020)
The Impact of a Pass/Fail Step 1 — A Residency Program Director’s View
Authors: Lisa L. Willett
Journal: New England Journal of Medicine (2020)

Interview with Dr. Debra Weinstein on the announcement that scores for Step 1 of the U.S. Medical Licensing Examination will be reported as pass or fail. (11:38)Download The change to pass/fail scores on the USMLE Step 1 exam means, among other things, that residency programs will lose the ability to compare students' performance across schools, leaving Step 2 CK scores as the only objective measure for comparative data.
Characteristics Associated with Hospitalization Among Patients with COVID-19 — Metropolitan Atlanta, Georgia, March–April 2020
Authors: Marie E. Killerby, Ruth Link-Gelles, Sarah C. Haight, Caroline A. Schrodt, Lucinda England, Danica J. Gomes, Mays Shamout, Kristen Pettrone, Kevin O'Laughlin, Anne Kimball, Erin F. Blau, Eleanor Burnett, Chandresh N. Ladva, Christine M. Szablewski, Melissa Tobin-D’Angelo, Nadine Oosmanally, Cherie Drenzek, David J. Murphy, James M. Blum, Julie Hollberg, Benjamin Lefkove, Frank W. Brown, Tom Shimabukuro, Claire M. Midgley, Jacqueline E. Tate, Sean D. Browning, Beau B. Bruce, Juliana da Silva, Jeremy A.W. Gold, Brendan R. Jackson, Sapna Bamrah Morris, Pavithra Natarajan, Robyn Neblett Fanfair, Priti R. Patel, Jessica Rogers-Brown, John Rossow, Karen K. Wong
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1).As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have been reported in the United States.*Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4).Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4).For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged ≥18 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia.Multivariable analyses were performed to identify patient characteristics associated with hospitalization.The following characteristics were independently associated with hospitalization: age ≥65 years (adjusted odds ratio [aOR] = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9).Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19.Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk.Potential barriers to the ability to adhere to these measures need to be addressed.Patients were selected from six acute care hospitals and associated outpatient clinics affiliated with a single academic health care system in metropolitan Atlanta.Hospitalized patients were selected sequentially from hospital-provided lists of * https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html.
A Randomized Open-Label Phase III Trial Evaluating the Addition of Denosumab to Standard First-Line Treatment in Advanced NSCLC: The European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR Trial
Authors: Solange Peters, Sarah Danson, Baktiar Hasan, Urania Dafni, Niels Reinmuth, Margarita Majem, Kurt G. Tournoy, Michael T. Mark, Miklos Pless, Manuel Cobo, Delvys Rodriguez-Abreu, Lionel Falchero, Teresa Moran, Ana Laura Ortega Granados, Isabelle Monnet, Katja Mohorcic, Bartomeu Massutí Sureda, Daniel Betticher, Ingel Demedts, Jose Antionio Macias, Sinead Cuffe, Andrea Luciani, Jose Garcia Sanchez, Alessandra Curioni-Fontecedro, Oliver Gautschi, Gillian Price, Linda Coate, Roger von Moos, Christoph Zielinski, Mariano Provencio, Jessica Menis, Barbara Ruepp, Alessia Pochesci, Heidi Roschitzki-Voser, Benjamin Besse, Manuela Rabaglio, Mary E.R. O’Brien, Rolf A. Stahel
Journal: Journal of Thoracic Oncology (2020)
Quality of care and maternal mortality in a tertiary-level hospital in Mozambique: a retrospective study of clinicopathological discrepancies
Authors: Clara Menéndez, Llorenç Quintó, Paola Castillo, Fabiola Fernandes, Carla Carrilho, Mamudo R Ismail, Cesaltina Lorenzoni, Juan Carlos Hurtado, Natalia Rakislova, Khátia Munguambe, Cinta Moraleda, Maria Maixenchs, Eusebio Macete, Inacio Mandomando, Miguel J Martínez, Pedro L Alonso, Quique Bassat, Jaume Ordi
Journal: The Lancet Global Health (2020)

BackgroundAlthough an increasing number of pregnant women in resource-limited areas deliver in health-care facilities, maternal mortality remains high in these settings. Inadequate diagnosis and management of common life-threatening conditions is an important determinant of maternal mortality. We analysed the clinicopathological discrepancies in a series of maternal deaths from Mozambique and assessed changes over 10 years in the diagnostic process. We aimed to provide data on clinical diagnostic accuracy to be used for improving quality of care and reducing maternal mortality.MethodsWe did a retrospective analysis of clinicopathological discrepancies in 91 maternal deaths occurring from Nov 1, 2013, to March 31, 2015 (17 month-long period), at a tertiary-level hospital in Mozambique, using complete diagnostic autopsies as the gold standard to ascertain cause of death. We estimated the performance of the clinical diagnosis and classified clinicopathological discrepancies as major and minor errors. We compared the findings of this analysis with those of a similar study done in the same setting 10 years earlier.FindingsWe identified a clinicopathological discrepancy in 35 (38%) of 91 women. All diagnostic errors observed were classified as major discrepancies. The sensitivity of the clinical diagnosis for puerperal infections was 17% and the positive predictive value was 50%. The sensitivity for non-obstetric infections was 48%. The sensitivity for eclampsia was 100% but the positive predictive value was 33%. Over the 10-year period, the performance of clinical diagnosis did not improve, and worsened for some diagnoses, such as puerperal infection.InterpretationDecreasing maternal mortality requires improvement of the pre-mortem diagnostic process and avoidance of clinical errors by refining clinical skills and increasing the availability and quality of diagnostic tests. Comparison of post-mortem information with clinical diagnosis will help monitor the reduction of clinical errors and thus improve the quality of care.FundingBill & Melinda Gates Foundation and Instituto de Salud Carlos III.
The Effect of Vitamin D Supplementation on Insulin Sensitivity: A Systematic Review and Meta-analysis
Authors: Adriyan Pramono, Johan W.E. Jocken, Ellen E. Blaak, Marleen A. van Baak
Journal: Diabetes Care (2020)

BACKGROUND Vitamin D has been suggested to affect peripheral insulin sensitivity. Evidence regarding the effect of vitamin D supplementation on insulin sensitivity is still conflicting. PURPOSE This meta-analysis aimed to assess the effect of vitamin D supplementation on insulin sensitivity in humans with or at risk for insulin resistance. DATA SOURCES AND STUDY SELECTION PubMed, Web of Science, Embase, CINAHL, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) from 1980 until 31 December 2018 reporting treatment effects of vitamin D supplementation on insulin sensitivity. DATA EXTRACTION The main outcome of interest was the change in insulin sensitivity, derived from the gold standard hyperinsulinemic-euglycemic clamp or the Matsuda index derived from the oral glucose tolerance test and insulin sensitivity index from intravenous glucose tolerance test. We extracted data on the standardized mean difference between the vitamin D treatment and placebo groups in change from baseline insulin sensitivity. DATA SYNTHESIS Eighteen RCTs were included in this meta-analysis comparing vitamin D supplementation (n = 612) with placebo (n = 608). Vitamin D supplementation had no effect on insulin sensitivity (standardized mean difference −0.01, 95% CI −0.12, 0.10; P = 0.87, I2 = 0%). Visual inspection of funnel plot symmetry did not suggest potential publication bias. LIMITATIONS The number of individuals who participated in the included studies was relatively small, possibly due to the invasive character of the measurement (e.g., clamp). CONCLUSIONS This meta-analysis provides no evidence that vitamin D supplementation has a beneficial effect on peripheral insulin sensitivity in people with or at risk for insulin resistance.
Targeted deep sequencing reveals clonal and subclonal mutational signatures in Adult T-cell leukemia/lymphoma and defines an unfavorable indolent subtype
Authors: Ambroise Marçais, Ludovic Lhermitte, Maria Artesi, Cécile Laurent, Keith Durkin, Vincent Hahaut, Nicolas Rosewick, Felipe Suarez, David Sibon, Morgane Cheminant, Veronique Avettand-Fenoel, Julie Bruneau, Michel Georges, Claudine Pique, Anne Van den Broeke, Vahid Asnafi, Olivier Hermine
Journal: Leukemia (2020)
Standardizing translational microbiome studies and metagenomic analyses
Authors: Jessica Gambardella, Vanessa Castellanos, Gaetano Santulli
Journal: Cardiovascular Research (2020)

Emerging evidence has demonstrated the functional contribution of gut microbiota alterations in the pathogenesis of cardiovascular and metabolic disorders.2][3][4] However, the mechanisms underlying such association have been only partially elucidated.
KIR- Ligand Mismatching Is Associated with Inferior Survival in Patients with Acute Leukemia Following T-Cell Replete Peripheral-Blood Stem Cell Haplo-Identical Transplantation with Post-Transplant Cyclophosphamide. a Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Avichai Shimoni, Myriam Labopin, Francesca Lorentino, Maria Teresa Van Lint, Koc Yener, Zafer Gülbas, Johanna Tischer, Benedetto Bruno, Didier Blaise, Pietro Pioltelli, Boris Afanasiev, Fabio Ciceri, Mohamad Mohty, Arnon Nagler
Journal: Blood (2017)
On the relationship between androgen-deprivation therapy for prostate cancer and risk of infection by SARS-CoV-2
Authors: O. Caffo, V. Zagonel, C. Baldessari, A. Berruti, R. Bortolus, S. Buti, G.L. Ceresoli, M. Donini, P. Ermacora, G. Fornarini, L. Fratino, C. Masini, F. Massari, A. Mosca, C. Mucciarini, G. Procopio, M. Tucci, E. Verri, P. Zucali, C. Buttigliero
Journal: Annals of Oncology (2020)
Radiotherapy targeting cancer stem cells “awakens” them to induce tumour relapse and metastasis in oral cancer
Authors: Yangfan Liu, Miao Yang, Jingjing Luo, Hongmei Zhou
Journal: International Journal of Oral Science (2020)

Radiotherapy is one of the most common treatments for oral cancer. However, in the clinic, recurrence and metastasis of oral cancer occur after radiotherapy, and the underlying mechanism remains unclear. Cancer stem cells (CSCs), considered the "seeds" of cancer, have been confirmed to be in a quiescent state in most established tumours, with their innate radioresistance helping them survive more easily when exposed to radiation than differentiated cancer cells. There is increasing evidence that CSCs play an important role in recurrence and metastasis post-radiotherapy in many cancers. However, little is known about how oral CSCs cause tumour recurrence and metastasis post-radiotherapy. In this review article, we will first summarise methods for the identification of oral CSCs and then focus on the characteristics of a CSC subpopulation induced by radiation, hereafter referred to as "awakened" CSCs, to highlight their response to radiotherapy and potential role in tumour recurrence and metastasis post-radiotherapy as well as potential therapeutics targeting CSCs. In addition, we explore potential therapeutic strategies targeting these "awakened" CSCs to solve the serious clinical challenges of recurrence and metastasis in oral cancer after radiotherapy.