tbuckley/cabot-search huggingface dataset:
Association of Childhood Infection With IQ and Adult Nonaffective Psychosis in Swedish Men
Authors: Golam M. Khandaker, Christina Dalman, Nils Kappelmann, Jan Stochl, Henrik Dal, Kyriaki Kosidou, Peter B. Jones, Håkan Karlsson
Journal: JAMA Psychiatry (2018)

<h3>Importance</h3> Associations between childhood infection, IQ, and adult nonaffective psychosis (NAP) are well established. However, examination of sensitive periods for exposure, effect of familial confounding, and whether IQ provides a link between childhood infection and adult NAP may elucidate pathogenesis of psychosis further. <h3>Objectives</h3> To test the association of childhood infection with IQ and adult NAP, to find whether shared familial confounding explains the infection-NAP and IQ-NAP associations, and to examine whether IQ mediates and/or moderates the childhood infection-NAP association. <h3>Design, Setting, and Participants</h3> Population-based longitudinal cohort study using linkage of Swedish national registers. The risk set included all Swedish men born between 1973 and 1992 and conscripted into the military until the end of 2010 (n = 771 698). We included 647 515 participants in the analysis. <h3>Measurement of Exposures</h3> Hospitalization with any infection from birth to age 13 years. <h3>Main Outcomes and Measures</h3> Hospitalization with an<i>International Classification of Diseases </i>diagnosis of NAP until the end of 2011. At conscription around age 18 years, IQ was assessed for all participants. <h3>Results</h3> At the end of follow-up, the mean (SD) age of participants was 30.73 (5.3) years. Exposure to infections, particularly in early childhood, was associated with lower IQ (adjusted mean difference for infection at birth to age 1 year: –1.61; 95% CI, −1.74 to −1.47) and with increased risk of adult NAP (adjusted hazard ratio for infection at birth to age 1 year: 1.19; 95% CI, 1.06 to 1.33). There was a linear association between lower premorbid IQ and adult NAP, which persisted after excluding prodromal cases (adjusted hazard ratio per 1-point increase in IQ: 0.976; 95% CI, 0.974 to 0.978). The infection-NAP and IQ-NAP associations were similar in the general population and in full-sibling pairs discordant for exposure. The association between infection and NAP was both moderated (multiplicative, β = .006; SE = 0.002;<i>P</i> = .02 and additive, β = .008; SE = 0.002;<i>P</i> = .001) and mediated (β = .028; SE = 0.002;<i>P</i> &lt; .001) by IQ. Childhood infection had a greater association with NAP risk in the lower, compared with higher, IQ range. <h3>Conclusions and Relevance</h3> Early childhood is a sensitive period for the effects of infection on IQ and NAP. The associations of adult NAP with early-childhood infection and adolescent IQ are not fully explained by shared familial factors and may be causal. Lower premorbid IQ in individuals with psychosis arises from unique environmental factors, such as early-childhood infection. Early-childhood infections may increase the risk of NAP by affecting neurodevelopment and by exaggerating the association of cognitive vulnerability with psychosis.
Atopic Comorbidities and Biomarkers of Type 2 Inflammation in Patients With Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP) Who Failed Intranasal Corticosteroids
Authors: Claus Bachert, Peter W. Hellings, Joaquim Mullol, Robert M. Naclerio, Daniel L. Hamilos, Philippe Gevaert, Dongui Zhang, Asif Khan, Chunpeng Fan, Nikhil Amin, Jennifer D. Hamilton, Brian N. Swanson, Gianluca Pirozzi, Neil M.H. Graham, Leda Mannent
Journal: Journal of Allergy and Clinical Immunology (2018)
Jarid1b protects from metformin-induced chemosensitization to cisplatin through p53 downregulation in NSCLC
Authors: Tharcisio Citrangulo Tortelli Jr., Rodrigo Esaki Tamura, Michele Tatiana Pereira Tomitao, Silvina Odete Bustos, Renata de Freitas Saito, Sarah Milani de Moraes Leandrini, Mayara D'Aurea Jacomassi, Ulysses Ribeiro Jr., Bryan Erik Strauss, Roger Chammas
Journal: Clinical Cancer Research (2018)
Mise en place de fiduciels intrapancréatiques sous échoendoscopie en vue d'une radiothérapie. Expérience préliminaire
Authors: JM Samson, A Guemnie-Tafo, P Gustin, F Le Roy, R Bou-Farah, D Malka, V Boige, M Ducreux, P Burtin
Journal: Endoscopy (2018)

La radiothérapie stéréotaxique a été peu évaluée pour traiter les tumeurs pancréatiques. Elle nécessite cependant la mise en place de repères radio-opaques («fiduciels») pour cibler la tumeur, soit par voie transcutanée soit sous guidage échoendoscopique (EE).
Abstract 18446: Treatment With Tetrahydrobiopterin Decreases White Matter Injury in a Mouse Model for In Utero Hypoxia in Congenital Heart Disease
Authors: Jennifer Romanowicz, Ludmila Korotcova, Paul Morton, Amrita Cheema, Vittorio Gallo, Richard A Jonas, Nobuyuki Ishibashi
Journal: Circulation (2015)

Introduction: Reduced oxygen delivery in complex congenital heart disease (CHD) can lead to brain white matter (WM) injury in utero. Currently, no treatment exists. Tetrahydrobiopterin (BH4) is a cofactor for neuronal nitric oxide synthase, and in its absence, toxic peroxynitrite production is favored. Hypoxia activates nitric oxide synthase, which reduces BH4 availability. Hypothesis: Decreased BH4 levels underlie WM injury in the fetus with CHD, and treatment with BH4 will reduce this injury. Methods: Mice were divided into three groups: normoxic controls (Nx), hypoxic (Hx), and hypoxic with BH4 treatment (Hx-BH4). Hx and Hx-BH4 mice were kept at 10.5% FiO2 from postnatal day 3 to 11--a period of WM development equivalent to the 3rd trimester in humans. Brain BH4 levels were quantified and compared between Nx (n=11) and Hx (n=12). Densities of cells expressing CNP (marker of oligodendrocytes--cells responsible for myelination) and Caspase3 (apoptosis marker) were quantified in three WM regions and compared between groups (n=3-6 each). Western blot detected myelin basic protein (myelin marker). Results: Brain BH4 levels were depleted in Hx compared to Nx (-38.4%, p=0.02). CNP+ oligodendrocytes increased after Hx compared to Nx (Fig.1a), consistent with hypoxia-induced proliferation seen previously. BH4 treatment did not limit this proliferation (Fig.1a). Hx had increased WM apoptosis (Fig.1b), which decreased with BH4 treatment (Fig.1b). Remarkably, there was no difference in WM caspase3+ cells between Nx and Hx-BH4 (Fig.1b). There was no difference in effect across WM region. Finally, loss of myelin with hypoxia was mitigated by BH4 treatment (Fig.1c). Conclusions: Our results show that suboptimal BH4 levels influence hypoxic WM injury. BH4 treatment of phenylketonuria is safe during pregnancy, thus maternal BH4 therapy is feasible. Our data demonstrate that repurposing BH4 for use during fetal brain development has potential to limit WM injury in CHD.
Comparison of European ICU patients in 2012 (ICON) versus 2002 (SOAP)
Authors: Jean-Louis Vincent, Jean-Yves Lefrant, Katarzyna Kotfis, Rahul Nanchal, Ignacio Martin-Loeches, Xavier Wittebole, Samir G. Sakka, Peter Pickkers, Rui Moreno, Yasser Sakr
Journal: Intensive Care Medicine (2018)

To evaluate differences in the characteristics and outcomes of intensive care unit (ICU) patients over time.We reviewed all epidemiological data, including comorbidities, types and severity of organ failure, interventions, lengths of stay and outcome, for patients from the Sepsis Occurrence in Acutely ill Patients (SOAP) study, an observational study conducted in European intensive care units in 2002, and the Intensive Care Over Nations (ICON) audit, a survey of intensive care unit patients conducted in 2012.We compared the 3147 patients from the SOAP study with the 4852 patients from the ICON audit admitted to intensive care units in the same countries as those in the SOAP study. The ICON patients were older (62.5 ± 17.0 vs. 60.6 ± 17.4 years) and had higher severity scores than the SOAP patients. The proportion of patients with sepsis at any time during the intensive care unit stay was slightly higher in the ICON study (31.9 vs. 29.6%, p = 0.03). In multilevel analysis, the adjusted odds of ICU mortality were significantly lower for ICON patients than for SOAP patients, particularly in patients with sepsis [OR 0.45 (0.35-0.59), p < 0.001].Over the 10-year period between 2002 and 2012, the proportion of patients with sepsis admitted to European ICUs remained relatively stable, but the severity of disease increased. In multilevel analysis, the odds of ICU mortality were lower in our 2012 cohort compared to our 2002 cohort, particularly in patients with sepsis.
Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial
Authors: Bernhard Ludvik, Juan P Frías, Francisco J Tinahones, Julio Wainstein, Honghua Jiang, Kenneth E Robertson, Luis-Emilio García-Pérez, D Bradley Woodward, Zvonko Milicevic
Journal: The Lancet Diabetes & Endocrinology (2018)
Migration and risk of HIV acquisition in Rakai, Uganda: a population-based cohort study
Authors: Oluwasolape Olawore, Aaron A R Tobian, Joseph Kagaayi, Jeremiah M Bazaale, Betty Nantume, Grace Kigozi, Justine Nankinga, Fred Nalugoda, Gertrude Nakigozi, Godfrey Kigozi, Ronald H Gray, Maria J Wawer, Robert Ssekubugu, John S Santelli, Steven J Reynolds, Larry W Chang, David Serwadda, Mary K Grabowski
Journal: The Lancet HIV (2018)
E-cigarettes are beneficial in short term but longer forecast is uncertain, landmark US report finds
Authors: Owen Dyer
Journal: BMJ (2018)

A US report that examined over 800 published studies has concluded that electronic cigarettes can help older smokers avoid the worst health consequences of cigarette smoking but can also lead younger non-smokers to try the deadly habit.

Public Health Consequences of E-Cigarettes ,1 a consensus study published by the National Academies of Sciences, describes a scenario in which the overall health impact of e-cigarettes could initially be broadly positive, as millions of smokers shift from tobacco cigarettes to vaping. But these gains could fade over time as more of the new users are adolescent never-smokers rather than older adults seeking an alternative to tobacco.

On the key question of how harmful e-cigarettes are the evidence is still lacking, the report says. It assigns one of six evidence levels to each finding: conclusive, substantial, moderate, limited, insufficient, or no …
Polarised epithelial monolayers of the gastric mucosa reveal insights into mucosal homeostasis and defence against infection
Authors: Francesco Boccellato, Sarah Woelffling, Aki Imai-Matsushima, Gabriela Sanchez, Christian Goosmann, Monika Schmid, Hilmar Berger, Pau Morey, Christian Denecke, Juergen Ordemann, Thomas F Meyer
Journal: Gut (2018)

Objective Helicobacter pylori causes life-long colonisation of the gastric mucosa, leading to chronic inflammation with increased risk of gastric cancer. Research on the pathogenesis of this infection would strongly benefit from an authentic human in vitro model. Design Antrum-derived gastric glands from surgery specimens served to establish polarised epithelial monolayers via a transient air–liquid interface culture stage to study cross-talk with H. pylori and the adjacent stroma. Results The resulting ‘mucosoid cultures’, so named because they recapitulate key characteristics of the gastric mucosa, represent normal stem cell-driven cultures that can be passaged for months. These highly polarised columnar epithelial layers encompass the various gastric antral cell types and secrete mucus at the apical surface. By default, they differentiate towards a foveolar, MUC5AC-producing phenotype, whereas Wnt signalling stimulates proliferation of MUC6-producing cells and preserves stemness—reminiscent of the gland base. Stromal cells from the lamina propria secrete Wnt inhibitors, antagonising stem-cell niche signalling and inducing differentiation. On infection with H. pylori , a strong inflammatory response is induced preferentially in the undifferentiated basal cell phenotype. Infection of cultures for several weeks produces foci of viable bacteria and a persistent inflammatory condition, while the secreted mucus establishes a barrier that only few bacteria manage to overcome. Conclusion Gastric mucosoid cultures faithfully reproduce the features of normal human gastric epithelium, enabling new approaches for investigating the interaction of H. pylori with the epithelial surface and the cross-talk with the basolateral stromal compartment. Our observations provide striking insights in the regulatory circuits of inflammation and defence.
Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol
Authors: M.R. Sydes, M.R. Spears, M.D. Mason, N.W. Clarke, D.P. Dearnaley, J.S. de Bono, G. Attard, S. Chowdhury, W. Cross, S. Gillessen, Z.I. Malik, R. Jones, C.C. Parker, A.W.S. Ritchie, J.M. Russell, R. Millman, D. Matheson, C. Amos, C. Gilson, A. Birtle, S. Brock, L. Capaldi, P. Chakraborti, A. Choudhury, L. Evans, D. Ford, J. Gale, S. Gibbs, D.C. Gilbert, R. Hughes, D. McLaren, J.F. Lester, A. Nikapota, J. O’Sullivan, O. Parikh, C. Peedell, A. Protheroe, S.M. Rudman, R. Shaffer, D. Sheehan, M. Simms, N. Srihari, R. Strebel, S. Sundar, S. Tolan, D. Tsang, M. Varughese, J. Wagstaff, M.K.B. Parmar, N.D. James
Journal: Annals of Oncology (2018)

Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP.
La Dilatation Endoscopique des Sténoses Bénignes Pyloro-Bulbaires
Authors: A Sarhani, M Acharki, M Salihoun, N Kabbaj
Journal: Endoscopy (2018)

La sténose pyloro-bulbaire est une complication classique de la maladie ulcéreuse gastroduodénale qui nécessitait le recours à la chirurgie. Actuellement la dilatation endoscopique est une alternative au traitement chirurgical. L'objectif de cette étude est d'évaluer l'efficacité de la dilatation endoscopique dans la prise en charge thérapeutique des sténoses pyloro-bulbaires bénignes.
Low uptake of palliative care for COPD patients within primary care in the UK
Authors: Chloe I. Bloom, Bhavan Slaich, Daniel R. Morales, Liam Smeeth, Patrick Stone, Jennifer K. Quint
Journal: European Respiratory Journal (2018)

Mortality and symptom burden from chronic obstructive pulmonary disease (COPD) and lung cancer are similar but there is thought to be an inequality in palliative care support (PCS) between diseases. This nationally representative study assessed PCS for COPD patients within primary care in the UK.This was a cohort study using electronic healthcare records (2004-2015). Factors associated with receiving PCS were assessed using logistic regression for the whole cohort and deceased patients.There were 92 365 eligible COPD patients, of which 26 135 died. Only 7.8% of the whole cohort and 21.4% of deceased patients received PCS. Lung cancer had a strong association with PCS compared with other patient characteristics, including Global Initiative for Chronic Obstructive Lung Disease stage and Medical Research Council Dyspnoea score (whole cohort, lung cancer: OR 14.1, 95% CI 13.1-15; deceased patients, lung cancer: OR 6.5, 95% CI 6-7). Only 16.7% of deceased COPD patients without lung cancer received PCS compared with 56.5% of deceased patients with lung cancer. In patients that received PCS, lung cancer co-diagnosis significantly increased the chances of receiving PCS before the last month of life (1-6 versus ≤1 month pre-death: risk ratio 1.4, 95% CI 1.3-1.7).Provision of PCS for COPD patients in the UK is inadequate. Lung cancer, not COPD, was the dominant driver for COPD patients to receive PCS.
Contextualizing Pediatric Decision Making Within an Ethics of Families
Authors: Sabrina F. Derrington, Erin D. Paquette
Journal: The American Journal of Bioethics (2018)

Olszewski and Goldkind assert that children should be routinely involved in medical decision making, to the extent of their ability and interest in doing so (Olszewski and Goldkind 2018). They prop...
Ethical Dilemmas in Protecting Susceptible Subpopulations From Environmental Health Risks: Liberty, Utility, Fairness, and Accountability for Reasonableness
Authors: David B. Resnik, D. Robert MacDougall, Elise M. Smith
Journal: The American Journal of Bioethics (2018)

Various U.S. laws, such as the Clean Air Act and the Food Quality Protection Act, require additional protections for susceptible subpopulations who face greater environmental health risks. The main ethical rationale for providing these protections is to ensure that environmental health risks are distributed fairly. In this article, we (1) consider how several influential theories of justice deal with issues related to the distribution of environmental health risks; (2) show that these theories often fail to provide specific guidance concerning policy choices; and (3) argue that an approach to public decision making known as accountability for reasonableness can complement theories of justice in establishing acceptable environmental health risks for the general population and susceptible subpopulations. Since accountability for reasonableness focuses on the fairness of the decision-making process, not the outcome, it does not guarantee that susceptible subpopulations will receive a maximum level of protection, regardless of costs or other morally relevant considerations.
Trends in Survival After In-Hospital Cardiac Arrest During Nights and Weekends
Authors: Uchenna R. Ofoma, Suresh Basnet, Andrea Berger, H. Lester Kirchner, Saket Girotra, Benjamin Abella, Monique L. Anderson, Steven M. Bradley, Paul S. Chan, Dana P. Edelson, Matthew M. Churpek, Romergryko Geocadin, Zachary D. Goldberger, Patricia K. Howard, Michael C. Kurz, Vincent N. Mosesso, Boulos Nassar, Joseph P. Ornato, Mary Ann Peberdy, Sarah M. Perman
Journal: Journal of the American College of Cardiology (2018)
Risk of Cardiovascular Disease and Death in Individuals With Prediabetes Defined by Different Criteria: The Whitehall II Study
Authors: Dorte Vistisen, Daniel R. Witte, Eric J. Brunner, Mika Kivimäki, Adam Tabák, Marit E. Jørgensen, Kristine Færch
Journal: Diabetes Care (2018)

OBJECTIVE We compared the risk of cardiovascular disease (CVD) and all-cause mortality in subgroups of prediabetes defined by fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), or HbA1c. RESEARCH DESIGN AND METHODS In the Whitehall II cohort, 5,427 participants aged 50–79 years and without diabetes were followed for a median of 11.5 years. A total of 628 (11.6%) had prediabetes by the World Health Organization (WHO)/International Expert Committee (IEC) criteria (FPG 6.1–6.9 mmol/L and/or HbA1c 6.0–6.4%), and 1,996 (36.8%) by the American Diabetes Association (ADA) criteria (FPG 5.6–6.9 mmol/L and/or HbA1c 5.7–6.4%). In a subset of 4,730 individuals with additional measures of 2hPG, 663 (14.0%) had prediabetes by 2hPG. Incidence rates of a major event (nonfatal/fatal CVD or all-cause mortality) were compared for different definitions of prediabetes, with adjustment for relevant confounders. RESULTS Compared with that for normoglycemia, incidence rate in the context of prediabetes was 54% higher with the WHO/IEC definition and 37% higher with the ADA definition (P &amp;lt; 0.001) but declining to 17% and 12% after confounder adjustment (P ≥ 0.111). Prediabetes by HbA1c was associated with a doubling in incidence rate for both the IEC and ADA criteria. However, upon adjustment, excess risk was reduced to 13% and 17% (P ≥ 0.055), respectively. Prediabetes by FPG or 2hPG was not associated with an excess risk in the adjusted analysis. CONCLUSIONS Prediabetes defined by HbA1c was associated with a worse prognosis than prediabetes defined by FPG or 2hPG. However, the excess risk among individuals with prediabetes is mainly explained by the clustering of other cardiometabolic risk factors associated with hyperglycemia.
Biologics Delay Progression of Crohn’s Disease, but Not Early Surgery, in Children
Authors: Basavaraj Kerur, Jason T. Machan, Jason M. Shapiro, Carolina S. Cerezo, James Markowitz, David R. Mack, Anne M. Griffiths, Anthony R. Otley, Marian D. Pfefferkorn, Joel R. Rosh, David J. Keljo, Brendan Boyle, Maria Oliva-Hemker, Marsha H. Kay, Shehzad A. Saeed, Andrew B. Grossman, Boris Sudel, Michael D. Kappelman, Marc Schaefer, Gitit Tomer, Athos Bousvaros, Trudy Lerer, Jeffrey S. Hyams, Neal S. LeLeiko
Journal: Clinical Gastroenterology and Hepatology (2018)
Improving Evidence for Implementation of Guideline-Based Care in Low- and Middle-Income Countries
Authors: Christopher B. Granger, Denis Xavier
Journal: JAMA (2018)

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Animal models of monoclonal immunoglobulin-related renal diseases
Authors: Christophe Sirac, Guillermo A. Herrera, Paul W. Sanders, Vecihi Batuman, Sebastien Bender, Maria V. Ayala, Vincent Javaugue, Jiamin Teng, Elba A. Turbat-Herrera, Michel Cogné, Guy Touchard, Nelson Leung, Frank Bridoux
Journal: Nature Reviews Nephrology (2018)
Les complications de la pancréatite chronique calcifiante: place du traitement endoscopique
Authors: N Bellil, N Bibani, D Trad, M Sabbah, H Elloumi, D Gargouri, A Ouakaa-Kchaou, J Kharrat
Journal: Endoscopy (2018)

La Pancréatite chronique calcifiante (PCC) est une affection inflammatoire chronique caractérisée par une fibrose responsable de la destruction progressive du parenchyme pancréatique. Nombreuses complications peuvent survenir chez les sujets porteurs d'une PCC. C'est d'ailleurs souvent à l'occasion de la survenue d'une complication que le diagnostic de la maladie est posé.