tbuckley/cabot-search huggingface dataset:
Yield of tuberculosis screening in asylum-seekers by country of origin: analysis of screening data in a German federal state (2002–2015)
Authors: Kayvan Bozorgmehr, Brigitte Joggerst, Ulrich Wagner, Christian Stock
Journal: European Respiratory Journal (2017)

Upon-entry screening for tuberculosis (TB) in immigrants plays a major role in national TB programmes of many low TB incidence countries [1]. The majority of European countries conduct routine screening for active TB in refugees and asylum-seekers using chest radiography alone or combined with other diagnostics [2]. Few countries, however, perform targeted screening among the heterogeneous group of asylum-seekers and refugees by using specific selection criteria [3]. Country of origin may serve as a selection criterion [4] to target and prioritise specific sub-groups and avoid "indiscriminate mass screening" [5]. Targeted screening would support front-line health workers to cope with the challenge of performing screening for TB in times of high immigration [6], e.g. in Germany when about 1 million new asylum-seekers were registered in 2015. Despite being desirable, so far a lack of empirical evidence precludes the (objective) determination of a suitable target group in asylum-seekers and refugees: only a few studies have reported the yield of screening for TB by country of origin [7]. Yield of TB screening varies by country of origin; targeted approaches are needed to increase screening efficiency <http://ow.ly/SuvZ30941Ej> The authors thank Ursula Paschmann (Public Health Services, Section for Disease Control, Landkreis Karlsruhe, Germany) for support in data collection and data management. Authors' contributions: conceived the study: K. Bozorgmehr, B. Joggerst and C. Stock. Data collection: B. Joggerst and U. Wagner. Data analysis: C. Stock. First and last version of manuscript: Kayvan Bozorgmehr. All authors made important contributions to the study design, participated in drafting the article and revising it critically for important intellectual content, and gave final approval of the version to be submitted.
Transfer of mitochondria after stroke: a new hope for cardioprotection coming from the brain?
Authors: Jérémy Fauconnier
Journal: Cardiovascular Research (2017)

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not.The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.Transfer of mitochondria after stroke: a new hope for cardioprotection coming from the brain?
University of Bath: Internationally renowned Master of Science (MSc) programmes in Sport and Exercise Medicine and Sports Physiotherapy for the busy clinician (Continuing Professional Development Series)
Authors: Adam G Culvenor
Journal: British Journal of Sports Medicine (2017)

Department for Health, University of Bath, Bath, UK.

Master of Science (MSc) in Sport and Exercise Medicine (SEM) and MSc in Sports Physiotherapy (both by distance/blended on-line learning).

A Masters qualification in SEM or Sports Physiotherapy provides the foundation for specialisation. The Master’s graduate gains a considerable depth of academic knowledge, clinical skills and experience while also honing his or her understanding of professional practice and service development.1 Such expertise is increasingly demanded of clinicians who work with high-performance athletes, such as those competing in national and Olympic teams.2 

Both MSc programmes (SEM and Sports Physiotherapy) are delivered in an integrated way under the stewardship of the current Director of Studies, Dr Polly McGuigan. She is supported by experienced Clinical Directors for SEM (Dr Julian Widdowson) and Sports Physiotherapy (Beenish Kamal) and approximately 15 other experienced academics and clinicians. The MSc in SEM is only open to medical doctors and the MSc to qualified physiotherapists. A strength of …
Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma
Authors: Robert Chen, Pier Luigi Zinzani, Michelle A. Fanale, Philippe Armand, Nathalie A. Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P. Vassilakopoulos, Akihiro Tomita, Bastian von Tresckow, Margaret A. Shipp, Yinghua Zhang, Alejandro D. Ricart, Arun Balakumaran, Craig H. Moskowitz
Journal: Journal of Clinical Oncology (2017)

Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response ≥ 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.
Humanized monoclonal antibody armanezumab specific to N-terminus of pathological tau: characterization and therapeutic potency
Authors: Michael G. Agadjanyan, Karen Zagorski, Irina Petrushina, Hayk Davtyan, Konstantin Kazarian, Maxim Antonenko, Joy Davis, Charles Bon, Mathew Blurton-Jones, David H. Cribbs, Anahit Ghochikyan
Journal: Molecular Neurodegeneration (2017)

The experience from clinical trials indicates that anti-Aβ immunotherapy could be effective in early/pre-clinical stages of AD, whereas at the late stages promoting the clearing of Aβ alone may be insufficient to halt the disease progression. At the same time, pathological tau correlates much better with the degree of dementia than Aβ deposition. Therefore, targeting pathological tau may provide a more promising approach for the treatment of advanced stages of AD. Recent data demonstrates that the N-terminal region of tau spanning aa 2-18 termed "phosphatase activation domain" that is normally hidden in the native protein in 'paperclip'-like conformation, becomes exposed in pathological tau and plays an essential role in the inhibition of fast axonal transport and in aggregation of tau. Hence, we hypothesized that anti-Tau2-18 monoclonal antibodies (mAb) may recognize pathological, but not normal tau at very early stages of tauopathy and prevent or decrease the aggregation of this molecule.Mouse mAbs were generated using standard hybridoma methodology. CDR grafting was used for humanization of mouse mAb. Humanized mAb (Armanezumab) was characterized and tested in vitro/ex vivo/in vivo using biochemical and immunological methods (HPLC, Biacore, ELISA, IHC, FRET, etc.). Stable DG44 cell line expressing Armanezumab was generated by clone selection with increased concentrations of methotrexate (MTX).A panel of mouse mAbs was generated, clone 1C9 was selected based on binding to pathological human tau with high affinity and humanized. Fine epitope mapping revealed conservation of the epitope of human tau recognized by the parent murine mAb and Armanezumab. Importantly, Armanezumab (i) bound to tau with high affinity as determined by Biacore; (ii) bound pathological tau in brains from AD, FTD and Pick's disease cases; (iii) inhibited seeding effect of aggregated tau from brain lysate of P301S Tg mice; (iv) inhibited cytotoxic effect of tau oligomers; (v) reduced total tau (HT7) and AT100, PHF1, AT8, AT180, p212, p214-positive tau species in brains of tau transgenic mice after intracranial injection. A stable CHO cell line producing >1.5 g/l humanized mAb, Armanezumab was generated.These findings suggest that Armanezumab could be therapeutic in clinical studies for treatment of AD.
Oral contraceptive use is a provoking factor for venous thromboembolism
Authors: Saskia Middeldorp, Alfonso Iorio
Journal: BMJ (2017)

Decisions on whether to stop anticoagulation in patients with venous thromboembolism (VTE) are a daily challenge for doctors and patients. We read with interest the validation study of the HERDOO2 rule, in which women considered to be at low risk of VTE discontinued oral anticoagulants.1 We congratulate the authors for their persistence in …
Sepsis quality standards are laudable but have low specificity
Authors: Ed Moran, Melinda Munang, Cathleen Chan, Saleem Chaudhri, Methini Himayakanthan, Steven Laird, Amy Moltu, Natasha Naworynsky, Christopher Pollard, Tahir Saeed, Paul Scott, Maya Sussman, Shaun Thein, George Trafford, Ariyur Balaji, Neil Jenkins
Journal: BMJ (2017)

The proposed quality standards for sepsis from the National Institute for Health and Care Excellence (NICE) are laudable in principle.1 But the practical reality of applying them to the 2016 NICE sepsis definition2 is unclear.

To establish the proportion of patients classified as septic by NICE guidance compared with previous criteria based on systemic inflammatory response syndrome (SIRS), we retrospectively reviewed the initial …
P06.03 Optical barcoding reveals immunoediting of the clonal tumor architecture in a syngeneic glioma model
Authors: M. Mohme
Journal: Neuro-Oncology (2017)

Since tumors are subject to constant selective pressure by tumor-specific immune cells, cancer immunoediting plays a critical role throughout all stages of tumor evolution. Therefore, investigating the actual impact of the immune system on tumor heterogeneity is crucial to understand the mechanisms of immune escape and tumor recurrence during chemo- and immunotherapy. We compared the in-vivo clonality, as well as cellular and molecular phenotypes of syngeneic mouse gliomas grown in an immunocompetent versus immunodeficient environment.To quantify the impact of the immune system on tumor cell clonality we developed a new clonal labeling strategy, termed optical barcoding. This lentiviral multicolor labeling strategy allows to track individual clones and, in combination with ex-vivo flow cytometry, to quantify the clonal architecture of individual tumors. Optically barcoded mouse GL261 glioma cells were administered through stereotactic intracranial injection in wild-type and immunodeficient pfp-/- rag2-/- C57BL/6 mice. Clonal composition, survival, tumor growth pattern, vascularization and phenotype of tumor-infiltrating immune cells were analyzed by immunohistochemistry. Gene expression profiling of ex-vivo isolated tumors was performed using RNA sequencing. Phenotype and cytokine production of infiltrating lymphocytes were assessed using multicolor flow cytometry and correlated to PD-L1 expression over a time-course during tumor development.Ex-vivo flow-cytometric analysis of individually labelled tumor clones demonstrated that brain tumors established in immunocompetent C57BL/6 showed a different clonal architecture compared to those in pfp-/- rag2-/- C57BL/6 mice. Whereas pfp-/- rag2-/- C57BL/6 mice displayed a homogeneous clonal distribution in all tumors, wildtype mice showed a more heterogeneous clonal mixture with greater variation in clonal composition. As expected, survival of immunodeficient mice was significantly shorter compared to wildtype mice. Interestingly, significant differences in macroscopic growth patterns, defined by tumor expansion morphology, vascularity and invasion were evident. Immunohistochemical stainings and phenotyping of tumor-infiltrating immune cells highlighted a role for PD-L1 in response to interferon-ɣ expression of infiltrating T lymphocytes. Furthermore, RNASeq of GL261 tumors grown in wt vs pfp-/- rag2-/- mice allowed the identification of new pathways potentially involved in the process of cancer-immune cell interaction and immune escape.Taken together, optical barcoding demonstrates that the continuous process of cancer immunoediting during tumor evolution not only shapes the expression profile and growth pattern, but also has a profound impact on the intratumoral heterogeneity of glioma in the syngeneic GL261 model.
Improved Safety with the Use of Subcutaneous Bortezomib in Combination with Panobinostat and Dexamethasone: Preliminary Data from a Panobinostat Global Expanded Treatment Protocol
Authors: Andreas Guenther, Lars-Olof Mügge, Mathias Haenel, Fredrik H. Schjesvold, Daniel Lechner, Sameer Yaser, Holger Hebart, Heinz Gisslinger, Richard Greil, Eberhard Gunsilius, Martin Goerner, Katja Weisel, Jan Dürig, Mohamed Elemary, Denise Wolleschak, Stefan A. Klein, Markus Munder, Alexander Kiani, Hareth Nahi, Christian Junghanss, Valerie Campello-Iddison, Ythier Deniau, Xiaoshu Feng, Hermann Einsele
Journal: Blood (2016)
Psychiatric Genomics: An Update and an Agenda
Authors: Patrick F. Sullivan, Arpana Agrawal, Cynthia M. Bulik, Ole A. Andreassen, Anders D. Børglum, Gerome Breen, Sven Cichon, Howard J. Edenberg, Stephen V. Faraone, Joel Gelernter, Carol A. Mathews, Caroline M. Nievergelt, Jordan W. Smoller, Michael C. O’Donovan
Journal: American Journal of Psychiatry (2017)

The Psychiatric Genomics Consortium (PGC) is the largest consortium in the history of psychiatry. This global effort is dedicated to rapid progress and open science, and in the past decade it has delivered an increasing flow of new knowledge about the fundamental basis of common psychiatric disorders. The PGC has recently commenced a program of research designed to deliver "actionable" findings-genomic results that 1) reveal fundamental biology, 2) inform clinical practice, and 3) deliver new therapeutic targets. The central idea of the PGC is to convert the family history risk factor into biologically, clinically, and therapeutically meaningful insights. The emerging findings suggest that we are entering a phase of accelerated genetic discovery for multiple psychiatric disorders. These findings are likely to elucidate the genetic portions of these truly complex traits, and this knowledge can then be mined for its relevance for improved therapeutics and its impact on psychiatric practice within a precision medicine framework. [AJP at 175: Remembering Our Past As We Envision Our Future November 1946: The Genetic Theory of Schizophrenia Franz Kallmann's influential twin study of schizophrenia in 691 twin pairs was the largest in the field for nearly four decades. (Am J Psychiatry 1946; 103:309-322 )].
P16.31 Posttraumatic progressive vertebral hemangioma
Authors: K. Kilic, T. Hasanov
Journal: Neuro-Oncology (2017)

Introduction: The authors present an extremely rare case, an aggressive and progressive vertebral capillary hemangioma of the lumbar spine secondary to a trauma. CASE DESCIPTION: A 40 year old man with back and leg pain due to a hemangioma of L1, that appeared one year after the fracture of the same vertebra, was operated on after a suboptimal embolization. Profuse bleeding had allowed only a subtotal removal and laminectomy. Histopathologic diagnosis of the lesion was capillary hemangioma. After the surgery, the patient’s pain disappeared; motor and sensory impairment had recovered. Postoperative control MRI at eight months showed that the lesion and destruction of the L1 vertebra was progressive. A second embolisation was performed and the hemangioma was totally removed via an anterior approach and corpectomy. Fusion was achieved by Th12-L2 graft and plaque. Results: On the fourteenth year of follow-up he was symptom free and radiologically clear of lesion. CONCLUSION: This case is the second extradural capillary hemangioma secondary to spinal trauma presented. The progression in hemangiomas is extremely rare nevertheless cure is possible without radiotherapy if the surgical removal is total.
P16.33 Postoperative ischemia and neurological deficits after glioma resection: incidence and risk factors
Authors: A. T. J. van der Boog, M. Rados, A. Akkermans, J. W. Dankbaar, U. Kizilates, J. Hendrikse, R. G. Hoff, P. A. J. Robe
Journal: Neuro-Oncology (2017)

Postoperative ischemia can lead to neurological deficits and is a known complication of glioma resection. There is an inconsistency in documented incidence of ischemia after glioma resection and the precise cause of ischemia is yet to be explored. The aim of this study was to assess the incidence of postoperative ischemia and neurological deficits and to evaluate their correlation and risk factors in patients who underwent glioma resection. 144 WHO grade II-IV glioma patients, of whom 34 had recurrent tumours, with postoperative MRI within 72 hours were retrospectively included in this IRB approved study. Patient characteristics, cardiovascular comorbidities, tumour characteristics, potential risk factors, anaesthetic parameters, intraoperative blood pressures and the presence of any new postoperative neurological deficit were extracted from the Electronic Patient Record. Two experienced neuroradiologists evaluated the presence of ischemia on diffusion-weighted MRI. Postoperative ischemia was found in 65,3% of the cases and any new or enhanced neurological deficit at discharge from the hospital and at first check-up in 27,8% and 35,6% of the cases respectively. There was a significant correlation between ischemia and any new or enhanced neurological deficit at both discharge from hospital (p=0,007) and at first check-up (p=0,031). Previously described risk factors for postoperative ischemia (insular, opercular and temporal tumour location, proximity to perforating arteries, re-resection, prior radiotherapy and MGMT promoter non-methylation) were not found to have a significant correlation with either ischemia or neurological deficit in our population. Intraoperative hypo- or hypertension and perioperative administration of vasoactive drugs were not significantly correlated with postoperative ischemia. Postoperative ischemia and neurological deficit were significantly correlated with each other. Risk factors described in the literature were not significantly correlated with either ischemia or neurological deficit, neither was intraoperative hypo- or hypertension.
P08.61 N cadherin upregulation mediates adaptive radioresistance in glioma stem cells
Authors: E. G. Van Meir
Journal: Neuro-Oncology (2017)

N cadherin upregulation mediates adaptive radioresistance in glioma stem cells Satoru Osuka,1 Oltea Sampetrean,2 Nobuyuki Onishi,2 Hideyuki Saya,2 Erwin G Van Meir,1, Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery and Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia, USA. 2, Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan Glioblastoma (GBM) is composed of heterogeneous tumor cell populations including those with stem cell properties and slow growth, termed glioma stem cells (GSCs). GSCs display reduced sensitivity to chemo- and radiotherapy and play an important role in tumor recurrence, the main cause of patient demise. However, the molecular mechanisms underlying GSC’s therapeutic resistance are still unknown. To identify important mediators of radioresistance in GBM, we generated radioresistant GSCs by exposing mice GSCs derived from a mouse model of glioblastoma (Ink4A/Arf-/- neural stem cells with H-RasV12 overexpression) to repeated cycles of irradiation (5Gy x 12). The surviving subpopulation acquired strong radioresistance in vivo, accompanied by a reduction in cell proliferation and an increase in cell-cell adhesion. Because cell-cell adhesion is important for the maintenance of a quiescent stem-like state in normal stem cells, we analyzed the expression of related adhesion molecules, and found gradual increase in N-cadherin (N-cad) expression during repeated irradiation. To unravel the role of N-cad in radioresistance we modulated its expression in GSCs through overexpression vectors and CRISPR/Cas9-mediated knockout. Increased N-cad expression was associated with radio- and chemoresistance to temozolomide, reduced GSC proliferation and increased stemness properties, including suppression of neural differentiation. Conversely, radioresistant GSCs lost their acquired phenotypes (in vivo radioresistance, slow proliferation, cell-cell adhesion and stemness) upon CRISPR/Cas9-mediated knockout of N-cad. Mechanistically, we found that elevated N-cad expression led to the accumulation of β-catenin on the cell surface, resulting in the suppression of Wnt/ β-catenin signaling. To further validate our mice GSC findings in patients, we analyzed single cell RNA-seq data of human glioblastoma samples (GSE57872) and found that cells with high N-cad expression had low expression of cell cycle genes and high expression of stemness-related genes. In conclusion, our data indicate that increased N-cad expression induces a state of slow growth in GSCs through a reduction in Wnt/β-catenin signaling, which underlies their therapeutic resistance. Therefore, N-cadherin represents a new important target to antagonize tumor recurrence in glioblastoma.