tbuckley/cabot-search huggingface dataset:
US crackdown on cash for referrals brings more arrests
Authors: O. Dyer
Journal: BMJ (2015)

A California radiologist is among eight people charged with paying and accepting illegal kickbacks for patient referrals in what prosecutors called the “first wave” of arrests arising from investigations into schemes to defraud insurers associated with the California workers’ compensation system.

A chiropractor, a medical equipment provider, a medical clinic administrator, and a self employed medical marketer were also arrested in raids last week. They were charged with conspiracy and mail fraud, alongside six corporations and three other people in three federal grand jury indictments. One of the men charged is still at large.

Laura Duffy, US attorney, noted connections between the three cases but said that these cannot be disclosed while the investigation continues. “Today’s indictments are only the first wave of charges in what we believe is rampant corruption …
Results of a Nationwide Capacity Survey of Hospitals Providing Trauma Care in War-Affected Syria
Authors: Hani Mowafi, Mahmoud Hariri, Houssam Alnahhas, Elizabeth Ludwig, Tammam Allodami, Bahaa Mahameed, Jamal Kaby Koly, Ahmed Aldbis, Maher Saqqur, Baobao Zhang, Anas Al-Kassem
Journal: JAMA Surgery (2016)

The Syrian civil war has resulted in large-scale devastation of Syria's health infrastructure along with widespread injuries and death from trauma. The capacity of Syrian trauma hospitals is not well characterized. Data are needed to allocate resources for trauma care to the population remaining in Syria.To identify the number of trauma hospitals operating in Syria and to delineate their capacities.From February 1 to March 31, 2015, a nationwide survey of 94 trauma hospitals was conducted inside Syria, representing a coverage rate of 69% to 93% of reported hospitals in nongovernment controlled areas.Identification and geocoding of trauma and essential surgical services in Syria.Although 86 hospitals (91%) reported capacity to perform emergency surgery, 1 in 6 hospitals (16%) reported having no inpatient ward for patients after surgery. Sixty-three hospitals (70%) could transfuse whole blood but only 7 (7.4%) could separate and bank blood products. Seventy-one hospitals (76%) had any pharmacy services. Only 10 (11%) could provide renal replacement therapy, and only 18 (20%) provided any form of rehabilitative services. Syrian hospitals are isolated, with 24 (26%) relying on smuggling routes to refer patients to other hospitals and 47 hospitals (50%) reporting domestic supply lines that were never open or open less than daily. There were 538 surgeons, 378 physicians, and 1444 nurses identified in this survey, yielding a nurse to physician ratio of 1.8:1. Only 74 hospitals (79%) reported any salary support for staff, and 84 (89%) reported material support. There is an unmet need for biomedical engineering support in Syrian trauma hospitals, with 12 fixed x-ray machines (23%), 11 portable x-ray machines (13%), 13 computed tomographic scanners (22%), 21 adult (21%) and 5 pediatric (19%) ventilators, 14 anesthesia machines (10%), and 116 oxygen cylinders (15%) not functional. No functioning computed tomographic scanners remain in Aleppo, and 95 oxygen cylinders (42%) in rural Damascus are not functioning despite the high density of hospitals and patients in both provinces.Syrian trauma hospitals operate in the Syrian civil war under severe material and human resource constraints. Attention must be paid to providing biomedical engineering support and to directing resources to currently unsupported and geographically isolated critical access surgical hospitals.
Interleukin-1α drives the dysfunctional cross-talk of the airway epithelium and lung fibroblasts in COPD
Authors: Emmanuel T. Osei, Jacobien A. Noordhoek, Tillie L. Hackett, Anita I.R. Spanjer, Dirkje S. Postma, Wim Timens, Corry-Anke Brandsma, Irene H. Heijink
Journal: European Respiratory Journal (2016)

Chronic obstructive pulmonary disease (COPD) has been associated with aberrant epithelial–mesenchymal interactions resulting in inflammatory and remodelling processes. We developed a co-culture model using COPD and control-derived airway epithelial cells (AECs) and lung fibroblasts to understand the mediators that are involved in remodelling and inflammation in COPD. AECs and fibroblasts obtained from COPD and control lung tissue were grown in co-culture with fetal lung fibroblast or human bronchial epithelial cell lines. mRNA and protein expression of inflammatory mediators, pro-fibrotic molecules and extracellular matrix (ECM) proteins were assessed. Co-culture resulted in the release of pro-inflammatory mediators interleukin (IL)-8/CXCL8 and heat shock protein (Hsp70) from lung fibroblasts, and decreased expression of ECM molecules ( e.g. collagen, decorin) that was not different between control and COPD-derived primary cells. This pro-inflammatory effect was mediated by epithelial-derived IL-1α and increased upon epithelial exposure to cigarette smoke extract (CSE). When exposed to CSE, COPD-derived AECs elicited a stronger IL-1α response compared with control-derived airway epithelium and this corresponded with a significantly enhanced IL-8 release from lung fibroblasts. We demonstrate that, through IL-1α production, AECs induce a pro-inflammatory lung fibroblast phenotype that is further enhanced with CSE exposure in COPD, suggesting an aberrant epithelial–fibroblast interaction in COPD.
Inhibitors and Antibody Fragments as Potential Anti-Inflammatory Therapeutics Targeting Neutrophil Proteinase 3 in Human Disease
Authors: Brice Korkmaz, Adam Lesner, Carla Guarino, Magdalena Wysocka, Christine Kellenberger, Hervé Watier, Ulrich Specks, Francis Gauthier, Dieter E. Jenne
Journal: Pharmacological Reviews (2016)

Proteinase 3 (PR3) has received great scientific attention after its identification as the essential antigenic target of antineutrophil cytoplasm antibodies in Wegener's granulomatosis (now called granulomatosis with polyangiitis). Despite many structural and functional similarities between neutrophil elastase (NE) and PR3 during biosynthesis, storage, and extracellular release, unique properties and pathobiological functions have emerged from detailed studies in recent years. The development of highly sensitive substrates and inhibitors of human PR3 and the creation of PR3-selective single knockout mice led to the identification of nonredundant roles of PR3 in cell death induction via procaspase-3 activation in cell cultures and in mouse models. According to a study in knockout mice, PR3 shortens the lifespan of infiltrating neutrophils in tissues and accelerates the clearance of aged neutrophils in mice. Membrane exposure of active human PR3 on apoptotic neutrophils reprograms the response of macrophages to phagocytosed neutrophils, triggers secretion of proinflammatory cytokines, and undermines immune silencing and tissue regeneration. PR3-induced disruption of the anti-inflammatory effect of efferocytosis may be relevant for not only granulomatosis with polyangiitis but also for other autoimmune diseases with high neutrophil turnover. Inhibition of membrane-bound PR3 by endogenous inhibitors such as the <i>α</i>-1-protease inhibitor is comparatively weaker than that of NE, suggesting that the adverse effects of unopposed PR3 activity resurface earlier than those of NE in individuals with <i>α</i>-1-protease inhibitor deficiency. Effective coverage of PR3 by anti-inflammatory tools and simultaneous inhibition of both PR3 and NE should be most promising in the future.
Can intermediate monocytes predict response to infliximab therapy in sarcoidosis?
Authors: Daniëlle Hijdra, Adriane D.M. Vorselaars, Heleen A. Crommelin, Coline H.M. van Moorsel, Bob Meek, Anke M.E. Claessen, Ger T. Rijkers, Jan C. Grutters
Journal: European Respiratory Journal (2016)

Sarcoidosis is a systemic granulomatous disease of unknown origin that can cause a variety of symptoms, but most often affects the lungs [1]. Because sarcoidosis is self-limiting in the majority of patients, not all patients require therapy [2]. In case of severe sarcoidosis, first-line therapy consists of prednisone, with methotrexate or azathioprine being the most commonly used second-line options [3]. Infliximab, a monoclonal anti-tumour necrosis factor (TNF) drug, is an effective third-line therapeutic for severe sarcoidosis [4, 5]. Responders to infliximab therapy have more intermediate monocytes at baseline compared with non-responders <http://ow.ly/fMLp300oVrO>
Accuracy of FE<sub>NO</sub>for diagnosing asthma: a systematic review
Authors: Stefan Karrasch, Klaus Linde, Gerta Rücker, Harriet Sommer, Marlies Karsch-Völk, Jos Kleijnen, Rudolf A Jörres, Antonius Schneider
Journal: Thorax (2016)

<h3>Background</h3> Measurement of FE<sub>NO</sub> might substitute bronchial provocation for diagnosing asthma. We aimed to investigate the diagnostic accuracy of FE<sub>NO</sub> measurement compared with established reference standard. <h3>Methods</h3> Systematic review and diagnostic meta-analysis. Data sources were Medline, Embase and Scopus up to 29 November 2015. Sensitivity and specificity were estimated using a bivariate model. Additionally, summary receiver-operating characteristic curves were estimated. <h3>Results</h3> 26 studies with 4518 participants (median 113) were included. Risk of bias was considered low for six of seven items in five studies and for five items in seven studies. The overall sensitivity in the meta-analysis was 0.65 (95% CI 0.58 to 0.72), the overall specificity 0.82 (0.76 to 0.86), the diagnostic OR 9.23 (6.55 to 13.01) and the area under the curve 0.80 (0.77 to 0.85). In meta-regression analyses, higher cut-off values were associated with increasing specificity (OR 1.46 per 10 ppb increase in cut-off) while there was no association with sensitivity. Sensitivities varied significantly within the different FE<sub>NO</sub> devices, but not specificities. Neither prevalence, age, use of bronchoprovocation in &gt;90% of participants or as exclusive reference standard test, nor risk of bias were significantly associated with diagnostic accuracy. <h3>Conclusions</h3> There appears to be a fair accuracy of FE<sub>NO</sub> for making the diagnosis of asthma. The overall specificity was higher than sensitivity, which indicates a higher diagnostic potential for ruling in than for ruling out the diagnosis of asthma.
GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines
Authors: Pablo Alonso-Coello, Andrew D Oxman, Jenny Moberg, Romina Brignardello-Petersen, Elie A Akl, Marina Davoli, Shaun Treweek, Reem A Mustafa, Per O Vandvik, Joerg Meerpohl, Gordon H Guyatt, Holger J Schünemann
Journal: BMJ (2016)

Formulating the questionWhen formulating the relevant questions, panels should specify the patients, intervention, comparison, and outcomes (PICO), 9 their perspective, subgroups for which the evidence and their judgments and recommendation might differ from an overall recommendation, and the settings for which the recommendation is intended. Summary poIntS• Clinicians do not have the time or resources to consider the underlying evidence for the myriad decisions they must make each day and, as a consequence, rely on recommendations from clinical practice guidelines• Guideline panels should consider all the relevant factors (criteria) that influence a decision or recommendation in a structured, explicit, and transparent way and provide clinicians with clear and actionable recommendations• The GRADE working group has developed Evidence to Decision (EtD) frameworks for different types of decisions and recommendations.
MCR-1 in multidrug-resistant and copper-tolerant clinically relevant Salmonella 1,4,[5],12:i:- and S. Rissen clones in Portugal, 2011 to 2015
Authors: Joana Campos, Luís Cristino, Luísa Peixe, Patrícia Antunes
Journal: Eurosurveillance (2016)

The mcr-1 gene was found in 11 isolates from a Portuguese Salmonella collection (n = 1,010; 58 serotypes; 2002–15) of clinical samples, foodstuff, food-animals and water. Mcr-1 has been located on different plasmids (IncX4/IncHI2) in pig-associated multidrug-resistant, copper-tolerant S. 1,4,[5],12:i:-/ST34 and S . Rissen/ST469 clones from human and pork products since at least 2011. Our data highlight dissemination of mcr-1 by successful resistant clones in Europe and raise questions about the efficacy of copper-based interventions to reduce colistin use.
Clinical utility of a custom next-generation sequencing panel in the diagnosis of needle biopsies from renal masses.
Authors: Banumathy Gowrishankar, Manickam Janakiraman, Raghavendra Padmanabhan, Venkata Jaganmohan Thodima, Massimiliano Spaliviero, Kelly Lynn Stratton, Rekha Soni, Jeremy C. Durack, Raju S.K. Chaganti, Stephen Barnett Solomon, Jonathan A. Coleman, Sitharthan Kamalakaran, Jane Houldsworth
Journal: Journal of Clinical Oncology (2016)

528 Background: Image-guided core-needle biopsies are increasingly being utilized to assist in the management of patients with renal masses, where only limited material is available for analysis. In this study, the performance of a custom next-generation sequencing (NGS) panel was evaluated for diagnostic and prognostic utility in this setting. Methods: DNA was available for NGS from 41 of 48 core-needle biopsies from renal masses previously submitted to array-CGH (aCGH) in this IRB-approved study. The targeted NGS panel comprised genes mutated in renal cancer, prognostic SNPs, and a 3Mbp SNP backbone. After library preparation from as little as 25ng DNA, sequencing was performed (MiSeq, Illumina), variants identified using CLCbio, and genomic gain/loss estimated by CNVKit (Talevich E, et al, manuscript in preparation). A classification algorithm based on 15 copy number alterations (CNAs) was applied to aCGH and NGS CNA profiles (PMID: 25498568). Histology of the biopsy or resected specimen (if available) served as the gold standard. Results: By histology, the 41 profiled biopsies comprised: 13 clear cell RCC (ccRCC), 9 papillary RCC (pRCC), 2 chromophobe RCC (chrRCC), 12 benign neoplasms, 2 unclassified, 2 high grade/poorly differentiated RCC, and 1 non-diagnostic. Among ccRCC, aCGH correctly subtyped 8/13. No CNAs were detected in the remaining 5, but for which NGS detected CNAs in 3/5 and TET2 mutations in 1. Mutations in PBRM1 and BAP1 with reported prognostic significance in ccRCC were found in 3 and 1 specimens respectively. Apart from 1 without any detectable mutations or CNAs, aCGH and NGS correctly subtyped 8/9 pRCCs based on CNAs. Also, activating MET mutations were seen in 2 pRCC specimens. aCGH and NGS accurately diagnosed the 2 chrRCC and detected pRCC-related CNAs in 2/13 benign neoplasms. In the two unclassified specimens, both methods identified ccRCC-related CNAs. Notably, NGS identified CNAs and mutations in the biopsy non-diagnostic by histology. Conclusions: Overall, targeted NGS can robustly detect genomic alterations requiring only limited DNA, that together with histology, contributes important diagnostic and prognostic information in the management of renal mass patients.
Influence of Pre-Transplant Cytomegalovirus (CMV) Serostatus on Post-Transplant Viral Reactivation after Allogeneic Stem Cell Transplantation in Patients Receiving Post-Transplant Cyclophosphamide for Gvhd Prophylaxis
Authors: Ravi K. Paluri, Racquel Shelton, Melissa Gazi, Lawrence S. Lamb, Ayman Saad, Donna Salzman, Antonio Di Stasi, Shin Mineishi
Journal: Blood (2014)
Junior doctors rise up in Poland
Authors: Katherine Bettany
Journal: BMJ (2016)

Pawel Supernak/Polish Press Agency

Around 5000 junior doctors from across Poland took part in a demonstration in Warsaw last weekend in protest at poor wages and quality of training, and a lack of regulation of working hours.

Organised by the Porozumienie Rezydentow (Residents Association), which represents junior doctors, the protest drew attention to the working conditions faced …
Tumors and Hyperplastic Nodules in Transplanted Mammary Glands
Authors: Bichmond T. Prehn
Journal: JNCI Journal of the National Cancer Institute (1953)

Tumors and Hyperplastic Nodules in Transplanted Mammary Glands Get access Bichmond T. Prehn Bichmond T. Prehn National Cancer Institute3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 13, Issue 4, February 1953, Pages 859–871, https://doi.org/10.1093/jnci/13.4.859 Published: 01 February 1953 Article history Received: 23 September 1952 Published: 01 February 1953
Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials
Authors: Benjamin Kasenda, Erik von Elm, John J. You, Anette Blümle, Yuki Tomonaga, Ramon Saccilotto, Alain Amstutz, Theresa Bengough, Joerg J. Meerpohl, Mihaela Stegert, Kelechi K. Olu, Kari A. O. Tikkinen, Ignacio Neumann, Alonso Carrasco-Labra, Markus Faulhaber, Sohail M. Mulla, Dominik Mertz, Elie A. Akl, Dirk Bassler, Jason W. Busse, Ignacio Ferreira-González, Francois Lamontagne, Alain Nordmann, Viktoria Gloy, Heike Raatz, Lorenzo Moja, Shanil Ebrahim, Stefan Schandelmaier, Xin Sun, Per O. Vandvik, Bradley C. Johnston, Martin A. Walter, Bernard Burnand, Matthias Schwenkglenks, Lars G. Hemkens, Heiner C. Bucher, Gordon H. Guyatt, Matthias Briel
Journal: PLoS Medicine (2016)

Background Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. Methods and Findings We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. Conclusions Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol.
The clinical research ward as a therapeutic community: incompatibilities
Authors: L H Reich, B L Weiss
Journal: American Journal of Psychiatry (1975)

The authors discuss the numerous incompatibilities between the clinical research ward, with its emphasis on the collection of baseline and treatment data, and the therapeutic milieu environment, with its emphasis on an open door, team orientation, and nonauthoritarianism. They posit that the two orientations may be mutually destructive and that the therapeutic milieu may not be the best treatment setting for patients with schizophrenic or certain affective disorders. Two case histories illustrating these ideas are included.
Loss of<i>Ezh2</i>synergizes with<i>JAK2</i>-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis
Authors: Takafumi Shimizu, Lucia Kubovcakova, Ronny Nienhold, Jakub Zmajkovic, Sara C. Meyer, Hui Hao-Shen, Florian Geier, Stephan Dirnhofer, Paola Guglielmelli, Alessandro M. Vannucchi, Jelena D. Milosevic Feenstra, Robert Kralovics, Stuart H. Orkin, Radek C. Skoda
Journal: The Journal of Experimental Medicine (2016)

Myeloproliferative neoplasm (MPN) patients frequently show co-occurrence of JAK2-V617F and mutations in epigenetic regulator genes, including EZH2. In this study, we show that JAK2-V617F and loss of Ezh2 in hematopoietic cells contribute synergistically to the development of MPN. The MPN phenotype induced by JAK2-V617F was accentuated in JAK2-V617F;Ezh2−/− mice, resulting in very high platelet and neutrophil counts, more advanced myelofibrosis, and reduced survival. These mice also displayed expansion of the stem cell and progenitor cell compartments and a shift of differentiation toward megakaryopoiesis at the expense of erythropoiesis. Single cell limiting dilution transplantation with bone marrow from JAK2-V617F;Ezh2+/− mice showed increased reconstitution and MPN disease initiation potential compared with JAK2-V617F alone. RNA sequencing in Ezh2-deficient hematopoietic stem cells (HSCs) and megakaryocytic erythroid progenitors identified highly up-regulated genes, including Lin28b and Hmga2, and chromatin immunoprecipitation (ChIP)–quantitative PCR (qPCR) analysis of their promoters revealed decreased H3K27me3 deposition. Forced expression of Hmga2 resulted in increased chimerism and platelet counts in recipients of retrovirally transduced HSCs. JAK2-V617F–expressing mice treated with an Ezh2 inhibitor showed higher platelet counts than vehicle controls. Our data support the proposed tumor suppressor function of EZH2 in patients with MPN and call for caution when considering using Ezh2 inhibitors in MPN.
Global disparities in HPV vaccination
Authors: Ophira Ginsburg
Journal: The Lancet Global Health (2016)

Cervical cancer is the fourth most common cancer in women globally, but remains the second most common cancer (after breast cancer) in many low-income and middle-income countries, and is still more common than breast cancer in sub-Saharan Africa.1 Most new cervical cancer cases (85%) and deaths (88%) occur in low-income and middle-income countries, where health systems are often fragmented or fragile, and where most have not yet implemented effective national cervical cancer screening programmes.