tbuckley/cabot-search huggingface dataset:
Brexit is bad for health, and doctors should say so
Authors: Neena Modi
Journal: BMJ (2017)

Neena Modi argues that leaving the EU will have wide ranging effects on health in the UK and that the medical and scientific professions should not hold back from saying this

There has been much rueing of the Brexit vote. The result was too close by any stretch of the imagination to be called decisive and was predicated on many so called “alternative facts,” foremost among which must be the shameful battle bus cry of “£350 million more each week for the NHS.”

It could be said that for the large swathe of the populace that voted “remain,” after the initial denial of …
Guidance for Modifying the Definition of Diseases
Authors: Jenny Doust, Per O. Vandvik, Amir Qaseem, Reem A. Mustafa, Andrea R. Horvath, Allen Frances, Lubna Al-Ansary, Patrick Bossuyt, Robyn L. Ward, Ina Kopp, Laragh Gollogly, Holger Schunemann, Paul Glasziou
Journal: JAMA Internal Medicine (2017)

No guidelines exist currently for guideline panels and others considering changes to disease definitions. Panels frequently widen disease definitions, increasing the proportion of the population labeled as unwell and potentially causing harm to patients. We set out to develop a checklist of issues, with guidance, for panels to consider prior to modifying a disease definition.We assembled a multidisciplinary, multicontinent working group of 13 members, including members from the Guidelines International Network, Grading of Recommendations Assessment, Development and Evaluation working group, and the World Health Organisation. We used a 5-step process to develop the checklist: (1) a literature review of issues, (2) a draft outline document, (3) a Delphi process of feedback on the list of issues, (4) a 1-day face-to-face meeting, and (5) further refinement of the checklist. The literature review identified 12 potential issues. From these, the group developed an 8-item checklist that consisted of definition changes, number of people affected, trigger, prognostic ability, disease definition precision and accuracy, potential benefits, potential harms, and the balance between potential harms and benefits. The checklist is accompanied by an explanation of each item and the types of evidence to assess each one. We used a panel's recent consideration of a proposed change in the definition of gestational diabetes mellitus (GDM) to illustrate use of the checklist.We propose that the checklist be piloted and validated by groups developing new guidelines. We anticipate that the use of the checklist will be a first step to guidance and better documentation of definition changes prior to introducing modified disease definitions.
Direct Acting Antivirals in patients with HCV-associated mixed cryoglobulinemia: real life safety and efficacy
Authors: G. Rizzardini, M. Schiavini, F. Niero, C. Magni, S. Landonio, E. Iemoli, M. Bolis, M. Colaneri, G. Gubertini
Journal: Journal of Hepatology (2017)
Biopsy Specimens From Allograft Liver Contain Histologic Features of Hepatitis C Virus Infection After Virus Eradication
Authors: Emma Whitcomb, Won-Tak Choi, Keith R. Jerome, Linda Cook, Charles Landis, Joseph Ahn, Helen S. Te, Jamak Esfeh, Ibrahim A. Hanouneh, Stephen C. Rayhill, William Gibson, Thomas Plesec, Jamie Koo, Hanlin L. Wang, John Hart, Rish K. Pai, Maria Westerhoff
Journal: Clinical Gastroenterology and Hepatology (2017)
Quantifying the mapping precision of genome-wide association studies using whole-genome sequencing data
Authors: Yang Wu, Zhili Zheng, Peter M. Visscher, Jian Yang
Journal: Genome biology (2017)

Understanding the mapping precision of genome-wide association studies (GWAS), that is the physical distances between the top associated single-nucleotide polymorphisms (SNPs) and the causal variants, is essential to design fine-mapping experiments for complex traits and diseases.Using simulations based on whole-genome sequencing (WGS) data from 3642 unrelated individuals of European descent, we show that the association signals at rare causal variants (minor allele frequency ≤ 0.01) are very unlikely to be mapped to common variants in GWAS using either WGS data or imputed data and vice versa. We predict that at least 80% of the common variants identified from published GWAS using imputed data are within 33.5 Kbp of the causal variants, a resolution that is comparable with that using WGS data. Mapping precision at these loci will improve with increasing sample sizes of GWAS in the future. For rare variants, the mapping precision of GWAS using WGS data is extremely high, suggesting WGS is an efficient strategy to detect and fine-map rare variants simultaneously. We further assess the mapping precision by linkage disequilibrium between GWAS hits and causal variants and develop an online tool (gwasMP) to query our results with different thresholds of physical distance and/or linkage disequilibrium ( http://cnsgenomics.com/shiny/gwasMP ).Our findings provide a benchmark to inform future design and development of fine-mapping experiments and technologies to pinpoint the causal variants at GWAS loci.
Intra-tumour heterogeneity in the regulation of immune-tolerogenic pathways in primary and metastatic hepatocellular carcinoma
Authors: D.J. Pinato, S. Victor, P. Spina, P. Trivedi, M. Pirisi, M.E. Burlone, J.R. Black, R. Minisini, M. Leutner, R.L. Boldorini, F.A. Mauri, R. Sharma
Journal: Journal of Hepatology (2017)
State HCV Incidence and Policies Related to HCV Preventive and Treatment Services for Persons Who Inject Drugs — United States, 2015–2016
Authors: Cecily A. Campbell, Lauren Canary, Nicole Smith, Eyasu Teshale, A. Blythe Ryerson, John W. Ward
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Hepatitis C is associated with more deaths in the United States than 60 other infectious diseases reported to CDC combined. Despite curative hepatitis C virus (HCV) therapies and known preventive measures to interrupt transmission, new HCV infections have increased in recent years (1,2). Injection drug use is the primary risk factor for new HCV infections (2). One potential strategy to decrease the prevalence of HCV is to create and strengthen public health laws and policies aimed specifically at reducing transmission risks among persons who inject drugs. To evaluate factors affecting access to HCV preventive and treatment services, CDC assessed state laws governing access to safe injection equipment and Medicaid policies related to sobriety requirements for approval of HCV treatment for persons who inject drugs. Acute HCV incidence rates were obtained from CDC's National Notifiable Disease Surveillance System (NNDSS). States were categorized based on analysis of laws related to access to clean needles and syringes and Medicaid HCV treatment policies associated with sobriety requirements. In 2015, HCV incidence remained high in the United States, with rates in 17 states exceeding the national average. Three states were determined to have state laws and Medicaid policies capable of comprehensively preventing and treating HCV among persons who inject drugs. Opportunities exist for states to adopt laws and policies that could help increase access to HCV preventive and treatment services reducing the number of persons at risk for HCV transmission and disease.
EpiTEome: Simultaneous detection of transposable element insertion sites and their DNA methylation levels
Authors: Josquin Daron, R. Keith Slotkin
Journal: Genome biology (2017)

The genome-wide investigation of DNA methylation levels has been limited to reference transposable element positions. The methylation analysis of non-reference and mobile transposable elements has only recently been performed, but required both genome resequencing and MethylC-seq datasets. We have created epiTEome, a program that detects both new transposable element insertion sites and their methylation states from a single MethylC-seq dataset. EpiTEome outperforms other split-read insertion site detection programs, even while functioning on bisulfite-converted reads. EpiTEome characterizes the previously discarded fraction of DNA methylation at sites of new insertions, enabling future investigation into the epigenetic regulation of non-reference and transposed elements.
Comparison of efficacy of cefotaxime, ceftriaxone, and ciprofloxacin for the treatment of spontaneous bacterial peritonitis in patients with liver cirrhosis: a randomized controlled trial
Authors: H.J. Yim, S.J. Suh, Y.K. Jung, M.Y. Kim, S.K. Baik, H.S. Kim, Y.S. Kim, S.Y. Park, B.I. Kim, J.Y. Park, H. Jung, K.-H. Han, Y.S. Seo, S.H. Um
Journal: Journal of Hepatology (2017)
100% efficacy to ombitasvir/paritaprevir/ritonavir ( ± dasabuvir) with or without ribavirin in hepatitis C virus genotypes 1 and 4-infected hemodialysis patients
Authors: F.M. Sanai, A.S. Alghamdi, A. Afghani, K.A. Alswat, A. Aseeri, M.A. Babatin
Journal: Journal of Hepatology (2017)
Cancer-related cognitive dysfunction (CRCD) and psychosocial development in young adult cancer survivors.
Authors: Kim Edelstein, Norma Mammone D'Agostino, Gregory Russell Pond, Sylvie Aubin, Andrew Matthew, Kate Wahl, Abha A. Gupta, Petr Kavan, Michael Crump, Philippe L. Bedard, Andre C. Schuh, David C. Hodgson, Te Vuong, Thierry Muanza, Gerald Batist, Lori J Bernstein
Journal: Journal of Clinical Oncology (2015)

TPS9636 Background: Chemotherapy is associated with long-lasting neurocognitive sequelae and structural and functional brain imaging changes in about 25% of older adults who do not receive central nervous system (CNS) directed treatment. This suggests that cancer or its treatment affects the brain regardless of primary tumor site. Because the brain continues to develop into the 3rd decade of life, younger adults (YA; age 18-39 yrs) may be vulnerable to CRCD. Cancer also disrupts acquisition of developmental milestones in YA. CRCD may exacerbate those disruptions, but this has never been studied. Study aims are to characterize CRCD in YA, explore its relation to psychosocial development, and identify subgroups at risk of adverse outcomes. Methods: In this prospective, inception-cohort study, we are recruiting YA who do not require CNS-directed therapy from ambulatory clinics at the Princess Margaret Cancer Centre (leukemia, lymphoma, breast, gynecology, gastrointestinal, genitourinary, sarcoma) and the YA Oncology clinic at the Jewish General Hospital: 200 YA with cancer who require chemotherapy, 100 YA with cancer who do not require it, and 100 healthy YA with no cancer history. As of Jan 30 2015, 113 participants were enrolled. Chemotherapy patients are assessed prior to treatment, and then 6 and 12 months later. The other groups are assessed at similar time intervals. The 2-hr test battery consists of standardized neurocognitive tests sensitive to CRCD and validated self-report psychosocial measures. Repeated measures mixed effects models will be used to examine longitudinal changes in each of the neurocognitive domains and each of the psychosocial development scores, using the predicted residual sum of squares method to avoid interpretation problems associated with repeated testing. Relationships between CRCD, psychosocial development, treatment, cancer type, and individual characteristics will be examined using regression. Exploratory analyses will investigate whether demographic, disease, or treatment factors contribute to longitudinal changes. Results will provide the basis for interventions that alleviate the psychosocial and cognitive sequelae in this underserved population.
Alternate scheduling of Gemcitabine (GEM) - Oxaliplatin (OXA) association in metastatic (MTS) or locally advanced (LA) pancreatic adenocarcinoma: a clinical and pharmacokinetic (pk) evaluation
Authors: M Airoldi, L Cattel, F Pedani, C Micari, A Nigro, L Branciforte, C Zanon, P Milla
Journal: Annals of Oncology (2004)
Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010
Authors: Nicholas S. Downing, Nilay D. Shah, Jenerius A. Aminawung, Alison M. Pease, Jean-David Zeitoun, Harlan M. Krumholz, Joseph S. Ross
Journal: JAMA (2017)

<h3>Importance</h3> Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. <h3>Objectives</h3> To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. <h3>Design and Setting</h3> Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. <h3>Exposures</h3> Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near–regulatory deadline approval, and regulatory review time. <h3>Main Outcomes and Measures</h3> A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. <h3>Results</h3> From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52;<i>P</i> = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06;<i>P</i> &lt; .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21;<i>P</i> = .02), and those with near–regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05;<i>P</i> = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87;<i>P</i> = .02). <h3>Conclusions and Relevance</h3> Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event. Biologics, psychiatric therapeutics, and accelerated and near–regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle.
FibroScan-based score to identify patients with non-alcoholic steatohepatitis: development in a multi-centric British cohort and validation in a large American cohort
Authors: M. Sasso, S.A. Harrison, P.J. Eddowes, Q.M. Anstee, I.N. Guha, D. Sherridan, E. Tsochatzis, J.F. Cobbold, M. Allison, C. Fournier, V. Miette, K.K. Roberts, A.H. Paredes, K.M. Cebe, V. Paradis, P. Bedossa, V. de Ledinghen, P.N. Newsome
Journal: Journal of Hepatology (2017)
Etiology in psychiatry: embracing the reality of poly‐gene‐environmental causation of mental illness
Authors: Rudolf Uher, Alyson Zwicker
Journal: World Psychiatry (2017)

Intriguing findings on genetic and environmental causation suggest a need to reframe the etiology of mental disorders. Molecular genetics shows that thousands of common and rare genetic variants contribute to mental illness. Epidemiological studies have identified dozens of environmental exposures that are associated with psychopathology. The effect of environment is likely conditional on genetic factors, resulting in gene‐environment interactions. The impact of environmental factors also depends on previous exposures, resulting in environment‐environment interactions. Most known genetic and environmental factors are shared across multiple mental disorders. Schizophrenia, bipolar disorder and major depressive disorder, in particular, are closely causally linked. Synthesis of findings from twin studies, molecular genetics and epidemiological research suggests that joint consideration of multiple genetic and environmental factors has much greater explanatory power than separate studies of genetic or environmental causation. Multi‐factorial gene‐environment interactions are likely to be a generic mechanism involved in the majority of cases of mental illness, which is only partially tapped by existing gene‐environment studies. Future research may cut across psychiatric disorders and address poly‐causation by considering multiple genetic and environmental measures across the life course with a specific focus on the first two decades of life. Integrative analyses of poly‐causation including gene‐environment and environment‐environment interactions can realize the potential for discovering causal types and mechanisms that are likely to generate new preventive and therapeutic tools.
How to Look for Thyroid Cancer
Authors: Anne R. Cappola
Journal: JAMA (2017)

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Prediction of hepatitis B virus reactivation in lymphoma patients with resolved hepatitis B virus infection who received rituximab-containing chemotherapy: the roles of antiHBc/antiHBs quantification
Authors: H.-C. Yang, H.-H. Tsou, S.-N. Pei, C.-S. Chang, J.-H. Chen, M. Yao, S.-J. Lin, J. Lin, T.-W. Liu, P.-J. Chen, A.-L. Cheng, C. Hsu
Journal: Journal of Hepatology (2017)
Ustekinumab inhibits Th1 and Th17 polarisation in a patient with giant cell arteritis
Authors: Maxime Samson, Thibault Ghesquière, Sabine Berthier, Bernard Bonnotte
Journal: Annals of the Rheumatic Diseases (2017)

Although glucocorticoids (GC) remain the corner stone of giant cell arteritis (GCA) treatment, GC-sparing strategies are needed because GC are responsible for side effects.1 Recent advances in the pathophysiology of GCA showed that CD4+ T cells are recruited in the arterial wall and polarised into Th1 and Th17 cells,2 3 the latter being sensitive to GC-mediated suppression, whereas Th1 response persists in GC-treated patients,2 which triggers the recruitment of macrophages4 and could be implicated in the occurrence of relapses when GC are tapered. Interleukin (IL)-12 and IL-23 are two cytokines involved in Th1 and Th17 polarisations, respectively.5 These two cytokines share a common subunit (p40), which allows ustekinumab, a humanised anti-p40 monoclonal antibody, to target both IL-12 and IL-23 pathways, thus disrupting in theory Th1 and Th17 immune responses.6 Recently, an open-label study reported on the efficacy and safety of …
A pilot study detailing cancer-specific biomarkers in giant macrophages mimicking circulating tumor cells in the circulation of cancer patients.
Authors: Daniel Adams, Raymond C. Bergan, Irene M. Ogden, R. Katherine Alpaugh, Massimo Cristofanilli, Olga V. Makarova, Peixuan Zhu, Shuhong Li, Platte T. Amstutz, Cha-Mei Tang
Journal: Journal of Clinical Oncology (2014)

e22015 Background: Recently, circulating cancer associated macrophage-like cells (CAMLs) have been identified in cancer patient peripheral blood and distinguished from circulating tumor cells (CTCs). CTCs contain filamentous cytoplasmic cytokeratin and are negative for CD45. By contrast, CAMLS are defined by a large atypical nucleus, diffuse cytokeratin-positive cytoplasmic signal and vacuoles containing cancer biomarkers. CAMLs are of myeloid lineage (CD14+/CD11c+), presenting with enlarged nuclei, CD45+ and exhibit cytoplasmic staining characteristics of epithelial cells. Our pilot study shows that vacuoles within CAMLs provide access to relevant clinical biomarkers that indicate tumor of origin, such as PSMA for prostate cancer, and other valuable information on the primary tumor. Methods: Peripheral blood samples were provided by Northwestern University and Fox Chase Cancer Center for 22 prostate cancer patients, stage I-IV. CellSieve microfilters were used to isolate CTCs and CAMLs from 7.5 mL of whole blood, and stained with DAPI, antibody cocktail against cytokeratin 8, 18, 19, EpCAM, PSMA and CD45. CTCs, defined as filamentous cytokeratin cells not positive for CD45, and CAMLs, defined as enlarged, multinuclear cells with diffuse cytoplasmic cytokeratin, were counted on the filters using a fluorescent microscope. Both cell types were then imaged for PSMA positivity. Results: Although CTCs were commonly found and were positive for PSMA, they were only found in 41% of patients, limiting the utility of CTCs to measure biomarkers across a broad group of patients. By contrast, 86% of patients had CAMLs with detectable tumor biomarkers, including PSMA, EpCAM, and cytokeratin. These biomarkers were readily visualized in CAMLs, appearing as vacuoles of concentrated material within the cytoplasmic borders. Conclusions: The low prevalence of CTCs in prostate cancer patients limits their utility in evaluating tumor specific biomarkers. CAMLs, the more common cell type, also found by microfiltration, may provide the same clinical information on a more consistent basis. Together they present an important, non-invasive strategy for accessing clinically relevant biomarkers.