tbuckley/cabot-search huggingface dataset:
David Oliver: Mixed sex wards may be inevitable
Authors: David Oliver
Journal: BMJ (2018)

The “humiliation” of “wards of shame” was how a section of the media reported NHS England’s figures on mixed sex wards this spring.12 The figures showed 13 700 “mixed sex breaches” in 2017-18. This was the highest level since 2010, when the collection of monthly mixed section accommodation “breaches” of “unjustified mixing in relation to sleeping accommodation” was introduced.3 Since 2012-13 NHS England has required in its operating framework that “all providers of NHS funded care are expected to eliminate mixed-sex accommodation, except where it is in the overall best interest of the patient.”3

To put that number in context, over 14 million admissions were made to NHS hospitals in England in 2016-17. …
Mapping the Heterogeneous Phenotype of Schizophrenia and Bipolar Disorder Using Normative Models
Authors: Thomas Wolfers, Nhat Trung Doan, Tobias Kaufmann, Dag Alnæs, Torgeir Moberget, Ingrid Agartz, Jan K. Buitelaar, Torill Ueland, Ingrid Melle, Barbara Franke, Ole A. Andreassen, Christian F. Beckmann, Lars T. Westlye, Andre F. Marquand
Journal: JAMA Psychiatry (2018)

Schizophrenia and bipolar disorder are severe and complex brain disorders characterized by substantial clinical and biological heterogeneity. However, case-control studies often ignore such heterogeneity through their focus on the average patient, which may be the core reason for a lack of robust biomarkers indicative of an individual's treatment response and outcome.To investigate the degree to which case-control analyses disguise interindividual differences in brain structure among patients with schizophrenia and bipolar disorder and to map the brain alterations linked to these disorders at the level of individual patients.This study used cross-sectional, T1-weighted magnetic resonance imaging data from participants recruited for the Thematically Organized Psychosis study from October 27, 2004, to October 17, 2012. Data were reanalyzed in 2017 and 2018. Patients were recruited from inpatient and outpatient clinics in the Oslo area of Norway, and healthy individuals from the same catchment area were drawn from the national population registry.Interindividual differences in brain structure among patients with schizophrenia and bipolar disorder. Voxel-based morphometry maps were computed, which were used for normative modeling to map the range of interindividual differences in brain structure.This study included 218 patients with schizophrenia spectrum disorders (mean [SD] age, 30 [9.3] years; 126 [57.8%] male), of whom 163 had schizophrenia (mean [SD] age, 31 [8.7] years; 105 [64.4%] male) and 190 had bipolar disorder (mean [SD] age, 34 [11.3] years; 79 [41.6%] male), and 256 healthy individuals (mean [SD] age, 34 [9.5] years; 140 [54.7%] male). At the level of the individual, deviations from the normative model were frequent in both disorders but highly heterogeneous. Overlap of more than 2% among patients was observed in only a few loci, primarily in frontal, temporal, and cerebellar regions. The proportion of alterations was associated with diagnosis and cognitive and clinical characteristics within clinical groups. Patients with schizophrenia, on average, had significantly reduced gray matter in frontal regions, cerebellum, and temporal cortex. In patients with bipolar disorder, mean deviations were primarily present in cerebellar regions.This study found that group-level differences disguised biological heterogeneity and interindividual differences among patients with the same diagnosis. This finding suggests that the idea of the average patient is a noninformative construct in psychiatry that falls apart when mapping abnormalities at the level of the individual patient. This study presents a workable route toward precision medicine in psychiatry.
The Science of Prognosis in Psychiatry
Authors: Paolo Fusar-Poli, Ziad Hijazi, Daniel Stahl, Ewout W. Steyerberg
Journal: JAMA Psychiatry (2018)

Prognosis is a venerable component of medical knowledge introduced by Hippocrates (460-377 BC). This educational review presents a contemporary evidence-based approach for how to incorporate clinical risk prediction models in modern psychiatry. The article is organized around key methodological themes most relevant for the science of prognosis in psychiatry. Within each theme, the article highlights key challenges and makes pragmatic recommendations to improve scientific understanding of prognosis in psychiatry.The initial step to building clinical risk prediction models that can affect psychiatric care involves designing the model: preparation of the protocol and definition of the outcomes and of the statistical methods (theme 1). Further initial steps involve carefully selecting the predictors, preparing the data, and developing the model in these data. A subsequent step is the validation of the model to accurately test its generalizability (theme 2). The next consideration is that the accuracy of the clinical prediction model is affected by the incidence of the psychiatric condition under investigation (theme 3). Eventually, clinical prediction models need to be implemented in real-world clinical routine, and this is usually the most challenging step (theme 4). Advanced methods such as machine learning approaches can overcome some problems that undermine the previous steps (theme 5). The relevance of each of these themes to current clinical risk prediction modeling in psychiatry is discussed and recommendations are given.Together, these perspectives intend to contribute to an integrative, evidence-based science of prognosis in psychiatry. By focusing on the outcome of the individuals, rather than on the disease, clinical risk prediction modeling can become the cornerstone for a scientific and personalized psychiatry.
Impact of Charlson comorbidity index on survival of octogenarian patients with colorectal cancer
Authors: E.D. Inga Saavedra, J.R. Rodriguez, E. Casaut Lora, A. Gonzalez-Haba, V. Serrano Pecos, M.F. Martinez Barragan, E. Blanco, J. Gomez-Ulla
Journal: Annals of Oncology (2018)
Comprehensive genomic profiling (CGP) of chemotherapy-resistant, primary mediastinal nonseminomatous germ cell tumors (PMNSGCT)
Authors: A. Necchi, G. Bratslavsky, R.J. Corona, J. Chung, S.Z. Millis, L.M. Gay, J.-A. Elvin, J.-A. Vergilio, S. Ramkissoon, E. Severson, S. Daniel, J.K. Killian, S.M. Ali, A.B. Schrock, V.A. Miller, J.S. Ross
Journal: Annals of Oncology (2018)
Characterizing Developmental Trajectories and the Role of Neuropsychiatric Genetic Risk Variants in Early-Onset Depression
Authors: Frances Rice, Lucy Riglin, Ajay K. Thapar, Jon Heron, Richard Anney, Michael C. O’Donovan, Anita Thapar
Journal: JAMA Psychiatry (2018)

Depression often first manifests in adolescence. Thereafter, individual trajectories vary substantially, but it is not known what shapes depression trajectories in youth. Adult studies suggest that genetic risk for schizophrenia, a psychiatric disorder with a neurodevelopmental component, may contribute to an earlier onset of depression.
In utero priming of highly functional effector T cell responses to human malaria
Authors: Pamela M. Odorizzi, Prasanna Jagannathan, Tara I. McIntyre, Rachel Budker, Mary Prahl, Ann Auma, Trevor D. Burt, Felistas Nankya, Mayimuna Nalubega, Esther Sikyomu, Kenneth Musinguzi, Kate Naluwu, Abel Kakuru, Grant Dorsey, Moses R. Kamya, Margaret E. Feeney
Journal: Science Translational Medicine (2018)

Malaria remains a significant cause of morbidity and mortality worldwide, particularly in infants and children. Some studies have reported that exposure to malaria antigens in utero results in the development of tolerance, which could contribute to poor immunity to malaria in early life. However, the effector T cell response to pathogen-derived antigens encountered in utero, including malaria, has not been well characterized. Here, we assessed the frequency, phenotype, and function of cord blood T cells from Ugandan infants born to mothers with and without placental malaria. We found that infants born to mothers with active placental malaria had elevated frequencies of proliferating effector memory fetal CD4+ T cells and higher frequencies of CD4+ and CD8+ T cells that produced inflammatory cytokines. Fetal CD4+ and CD8+ T cells from placental malaria-exposed infants exhibited greater in vitro proliferation to malaria antigens. Malaria-specific CD4+ T cell proliferation correlated with prospective protection from malaria during childhood. These data demonstrate that placental malaria is associated with the generation of proinflammatory malaria-responsive fetal T cells. These findings add to our current understanding of fetal immunity and indicate that a functional and protective pathogen-specific T cell response can be generated in utero.
Study of the pathogenesis of cardiac hypertrophy. Biochemical differences of cultured heart cells from normotensive and spontaneously hypertensive rats.
Authors: Sachiko Yamada, Masaaki Honda, Shigefumi Morioka, Michikuni Ohoka, Yukio Yamori, Katsutoshi Moriyama
Journal: Circulation (1989)

To elucidate the metabolic properties of the heart of spontaneously hypertensive rats (SHR), we examined the uptakes of 3H-uridine (3H)and 14C-leucine (14C) into single cultured heart cells, as well as the total protein content and cell size of heart cells in the presence and absence of stimulation, and compared the findings with those obtained with Wistar Kyoto rat (WKY) cells. As a result, (1) Spontaneous uptakes of 3H and 14C into WKY heart cells increased rapidly from day 2 to days 5-6, and then decreased gradually. In contrast, in SHR heart cells a constant increase in the uptakes of 3H and 14C was observed until the 10th day. The uptakes of both 3H and 14C into 10-day-old SHR heart cells were significantly higher than those into WKY heart cells (p<0.05). (2) The total protein content of SHR heart cells cultured for 4 or 5 days was significantly less than that of WKY heart cells, but there was no significant difference between cells cultured for more than 6 days. As for cell size, no significant difference was observed regardless of how long the cells were cultured. However, the increment in SHR heart cell total protein and cell size during cultivation appeared to be higher than they were in WKY heart cells. (3) Stimulation of heart cells with 10-8-10-5 M L(-)-isoproterenol (ISO) for 1 hour increased the uptake of 3H into heart cells from both kinds of rats, with no significant difference between the two. In contrast, after 3-hour stimulation uptake of 3H into WKY heart cells was lower than it was after a 1-hour stimulation, while that in SHR heart cells increased. Angiotensin II (AngII) also increased the uptake of 3H into both types of heart cells, the responsiveness to various concentrations of AngII showing no significant differences. Our results showed that SHR heart cells in vitro had an increased spontaneous metabolic rate and an increased responsiveness to ISO, confirming previous in vivo results and suggesting that these metabolic properties play a role in cardiac hypertrophy in SHR.
Preoperative hypofractionated radiotherapy (RT) combined with chemotherapy in primary marginally resectable high grade soft tissue sarcomas (STS) of extremities or trunk wall: Interim analysis of prospective phase II clinical trial
Authors: M. Spalek, H.M. Kosela Paterczyk, A. Borkowska, M. Wagrodzki, A. Cieszanowski, P. Castaneda-Wysocka, T. Switaj, M.E. Dudzisz-Sledz, A.M. Czarnecka, E. Dabrowska-Szewczyk, P.L. Rutkowski
Journal: Annals of Oncology (2018)
Remotely Monitored Therapy and Nitric Oxide Suppression Identifies Nonadherence in Severe Asthma
Authors: Liam G. Heaney, John Busby, Peter Bradding, Rekha Chaudhuri, Adel H. Mansur, Robert Niven, Ian D. Pavord, John T. Lindsay, Richard W. Costello
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Poor adherence is common in difficult-to-control asthma. Distinguishing patients with difficult-to-control asthma who respond to inhaled corticosteroids (ICS) from refractory asthma is an important clinical challenge.Objectives: Suppression of fractional exhaled nitric oxide (FeNO) with directly observed ICS therapy over 7 days can identify nonadherence to ICS treatment in difficult-to-control asthma. We examined the feasibility and utility of FeNO suppression testing in routine clinical care within UK severe asthma centers using remote monitoring technologies.Methods: A web-based interface with integrated remote monitoring technology was developed to deliver FeNO suppression testing. We examined the utility of FeNO suppression testing to demonstrate ICS responsiveness and clinical benefit on electronically monitored treatment with standard high-dose ICS and long-acting β2-agonist treatment.Measurements and Main Results: Clinical response was assessed using the Asthma Control Questionnaire-5, spirometry, and biomarker measurements (FeNO and peripheral blood eosinophil count). Of 250 subjects, 201 completed the test with 130 positive suppression tests. Compared with a negative suppression test, a positive test identified a FeNO-low population when adherent with ICS/long-acting β2-agonist (median, 26 ppb [interquartile range, 16–36 ppb] vs. 43 ppb [interquartile range, 38–73 ppb]) with significantly greater FEV1% (mean, 88.2 ± 16.4 vs. 74.1 ± 20.9; P < 0.01). Asthma Control Questionnaire-5 improved significantly in both groups (positive test: mean difference, −1.2; 95% confidence interval, −0.9 to −1.5; negative test: mean difference, −0.9; 95% confidence interval, −0.4 to −1.3).Conclusions: Remote FeNO suppression testing is an effective means of identifying nonadherence to ICS in subjects with difficult-to-control asthma and the substantial population of subjects who derive important clinical benefits from optimized ICS/long-acting β2-agonist treatment.
Deep Learning to Distinguish Recalled but Benign Mammography Images in Breast Cancer Screening
Authors: Sarah S. Aboutalib, Aly A. Mohamed, Wendie A. Berg, Margarita L. Zuley, Jules H. Sumkin, Shandong Wu
Journal: Clinical Cancer Research (2018)

Abstract Purpose: False positives in digital mammography screening lead to high recall rates, resulting in unnecessary medical procedures to patients and health care costs. This study aimed to investigate the revolutionary deep learning methods to distinguish recalled but benign mammography images from negative exams and those with malignancy. Experimental Design: Deep learning convolutional neural network (CNN) models were constructed to classify mammography images into malignant (breast cancer), negative (breast cancer free), and recalled-benign categories. A total of 14,860 images of 3,715 patients from two independent mammography datasets: Full-Field Digital Mammography Dataset (FFDM) and a digitized film dataset, Digital Dataset of Screening Mammography (DDSM), were used in various settings for training and testing the CNN models. The ROC curve was generated and the AUC was calculated as a metric of the classification accuracy. Results: Training and testing using only the FFDM dataset resulted in AUC ranging from 0.70 to 0.81. When the DDSM dataset was used, AUC ranged from 0.77 to 0.96. When datasets were combined for training and testing, AUC ranged from 0.76 to 0.91. When pretrained on a large nonmedical dataset and DDSM, the models showed consistent improvements in AUC ranging from 0.02 to 0.05 (all P &amp;gt; 0.05), compared with pretraining only on the nonmedical dataset. Conclusions: This study demonstrates that automatic deep learning CNN methods can identify nuanced mammographic imaging features to distinguish recalled-benign images from malignant and negative cases, which may lead to a computerized clinical toolkit to help reduce false recalls.
Increased Myocardial Stiffness Detected by Intrinsic Cardiac Elastography in Patients With Amyloidosis
Authors: Cristina Pislaru, Mahmoud M. Alashry, Filip Ionescu, Ioana Petrescu, Patricia A. Pellikka, Martha Grogan, Angela Dispenzieri, Sorin V. Pislaru
Journal: JACC. Cardiovascular imaging (2018)
Using Big Data to Determine Reference Values for Laboratory Tests
Authors: Amrom E. Obstfeld, Stephen R. Master, W. Greg Miller
Journal: JAMA (2018)

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Data-Driven Scheduling for Improving Patient Efficiency in Ophthalmology Clinics
Authors: Michelle R. Hribar, Abigail E. Huang, Isaac H. Goldstein, Leah G. Reznick, Annie Kuo, Allison R. Loh, Daniel J. Karr, Lorri Wilson, Michael F. Chiang
Journal: Ophthalmology (2018)
GW29-e0611 Acacetin inhibits doxorubicin–induced cardiotoxicity by activating Sirt1/AMPK/Nrf2 pathway
Authors: Weiyin Wu, Yukai Cui, Yunda Li, Yixiang Hong, Yao Wu, Lingjun Jie, Gang Li, Guirong Li, Yan Wang
Journal: Journal of the American College of Cardiology (2018)
Haemodynamic mechanisms and long-term prognostic impact of pulmonary hypertension in patients with severe aortic stenosis undergoing valve replacement
Authors: Lukas Weber, Hans Rickli, Philipp K. Haager, Lucas Joerg, Daniel Weilenmann, Roman Brenner, Maurizio Taramasso, Philipp Baier, Francesco Maisano, Micha T. Maeder
Journal: European Journal of Heart Failure (2018)
Subgroup analyses of efficacy from a phase III study comparing SB3 (trastuzumab biosimilar) with reference trastuzumab in early breast cancer patients
Authors: J. Cortes Castan, M. Pegram, X. Pivot, G. Curigliano, J.Y. Lim, S. Song, Y.C. Yoon
Journal: Annals of Oncology (2018)
Topical antimicrobial resistance in <i>S. aureus</i> from patients with AD
Authors: C.P. Harkins, M.A. McAleer, D. Bennett, M. McHugh, O.M. Fleury, K.A. Pettigrew, K. Oravcová, J. Parkhill, C.M. Proby, R.S. Dawe, J.A. Geoghegan, A.D. Irvine, M.T.G. Holden
Journal: British Journal of Dermatology (2018)
Software Tools to Facilitate Systematic Review Used for Cancer Hazard Identification
Authors: Andrew J. Shapiro, Sébastien Antoni, Kathryn Z. Guyton, Ruth M. Lunn, Dana Loomis, Ivan Rusyn, Gloria D. Jahnke, Pamela J. Schwingl, Suril S. Mehta, Josh Addington, Neela Guha
Journal: Environmental Health Perspectives (2018)

Summary: Objective and systematic methods to search, review, and synthesize published studies are a fundamental aspect of carcinogen hazard classification. Systematic review is a historical strength of the International Agency for Research on Cancer (IARC) Monographs Program and the United States National Toxicology Program (NTP) Office of the Report on Carcinogens (RoC). Both organizations are tasked with evaluating peer-reviewed, published evidence to determine whether specific substances, exposure scenarios, or mixtures pose a cancer hazard to humans. This evidence synthesis is based on objective, transparent, published methods that call for extracting and interpreting data in a systematic manner from multiple domains, including a) human exposure, b) epidemiological evidence, c) evidence from experimental animals, and d) mechanistic evidence. The process involves multiple collaborators and requires an extensive literature search, review, and synthesis of the evidence. Several online tools have been implemented to facilitate these collaborative systematic review processes. Specifically, Health Assessment Workplace Collaborative (HAWC) and Table Builder are custom solutions designed to record and share the results of the systematic literature search, data extraction, and analyses. In addition, a content management system for web-based project management and document submission has been adopted to enable access to submitted drafts simultaneously by multiple co-authors and to facilitate their peer review and revision. These advancements in cancer hazard classification have applicability in multiple systematic review efforts. https://doi.org/10.1289/EHP4224
THU0310 Biologic disease-modifying antirheumatic drugs in psoriatic arthritis: a real-world cohort of 439 patients
Authors: J.-G. Letarouilly, J.-H. Salmon, P. Coquerelle, V. Goeb, M.-H. Guyot, E. Houvenagel, F. Maury, L. Marguerie, G. Morel, G. Baudens, E. Solau-Gervais, N. Ramdane, R.-M. Flipo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> For more than 15 years, severe psoriatic arthritis (PsA) has been treated only by TNF inhibitors. Two new Biologic Disease-modifying Antirheumatic Drugs (bDMARDs) have recently arrived on the market with different targets: IL12–23 for ustekinumab and IL 17 for secukinumab. Few studies exist with a large number of patients and with required hindsight. <h3>Objectives</h3> The objective was to assess drug survival in an observational cohort of 630 PsA depending on the line of treatment and to analyse the reasons of discontinuation. <h3>Methods</h3> This is a retrospective, multicentric observational study based on the data of the registry RIC Nord de France, from patients suffering from PsA (CASPAR criteria) and treated by bDMARDs from january 2000 to august 2017. Drug survival is defined as the time from initiation to discontinuation (stop/switch) of biologic therapy on the registry. The number of patients who discontinued each treatment and the duration of therapy were recorded. Using Kaplan-Meier survival curves and Cox-regression analyses [hazard ratios (HR) and 95% confidence intervals (CIs)], time to discontinuation was compared across cohorts undergoing first-, second- or third-line treatment. <h3>Results</h3> Out of 630 PsA, 439 were included with a mean follow up greater than or equal to 6 months. The sex ratio was balanced with 47% of women. The mean age was 54.5 years old and the body mass index (BMI) was 28.7 kg/m². The disease duration was 14.25 years. 51.6% of patients did not smoke. The DAS-28 CRP was 3.99 at the initiation of the biotherapy. The drug survival of the TNF inhibitors was similar at first-line treatment (n=439 patients) (figure 1) and at second-line treatment (n=238 patients). The drug survival of infliximab was statistically longer at third-line treatment (n=209) (p&lt;0.0001), as the drug survival of TNF inhibitors compared to non TNF inhibitor biotherapies (ustekinumab and secukinumab) (p0.011). There was no impact of the age, the sex or the BMI on the drug survival. The discontinuation was mainly due to primary and secondary failure at first-line (respectively 33.33% and 33.71%) and to adverse events at second- and third-line (respectively 30.22% and 44.55%). <h3>Conclusions</h3> The results of the large observational study confirm those of the clinical trials, especially for the patients with failing initial TNF inhibitor therapy. <h3>Disclosure of Interest</h3> None declared
ATOM trial: a randomized phase II study of mFOLFOX6+Bmab vs. mFOLFOX6+Cmab for not-optimary resectable KRAS wt mCRC
Authors: Kei Muro, Yasunori Emi, Takeharu Yamanaka, Hiroyuki Uetake, Eiji Oki, Takao Takahashi, Yoshiharu Sakai, Toshiyoshi Fujiwara, Yuh Katayose, Kazuhiro Yoshida, Michiaki Unno, Ichinosuke Hyodo, Naohiro Tomita, Kenichi Sugihara, Yoshihiko Maehara
Journal: Annals of Oncology (2018)