tbuckley/cabot-search huggingface dataset:
The new concussion in sport guidelines are here. But how do we get them out there?
Authors: Caroline F Finch, Peta White
Journal: British Journal of Sports Medicine (2017)

Ecological (or hierarchical) level of sports safety implementation Implementation rolePlayers and parents of players Target end users and beneficiaries of concussion education, guidelines and prevention; actions would be at both the individual and whole-of-team level ↓Coaches and sports trainers Key community sports personnel to initially recognise a potential concussion has occurred, initiate local actions in response to the suspected/actual concussion, support and monitor the adoption of guidelines and support players diagnosed with concussion return to play ↓ General practitioners (doctors) Key role in diagnosing concussion and providing medical management of concussion.(In most community sport settings, it would not be common for sports physicians or sports physiotherapists to be associated with teams, so access to general medical personnel is necessary.) ↓Sports bodies (regional, national and/or international) and peak sports medicine/health promotion agencies Setting of rule, preparation and dissemination of guideline information and other resources, supporting community sport infrastructure, education ↓International expert opinion Determining, summarising, publishing and disseminating the scientific and medical content of concussion guidelines *This table describes the situation for countries where most sporting participation opportunities are provided through community-based or recreational sporting organisations.It is acknowledged that some countries, like the USA, have sports delivery systems that are more likely to be linked to high schools or university colleges and so some of the opportunities for intervention may be different.In particular, US-based sports have certified athletic trainers who would be a key conduit of concussion knowledge and action.
Arsenic Trioxide Potentiates Extracellular Traps-Formation Cell Death in Acute Promyelocytic Leukemia through mTOR-Regulated Autophagy
Authors: Tao Li, Muhua Cao, Ruishuang Ma, Xiaoming Wu, Lu Zhao, Yan Zhang, Zhipeng Yao, Junjie Kou, Yayan Bi, Jin Zhou, Jialan Shi
Journal: Blood (2016)
Immune Activation in Early-Stage Non–Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab
Authors: John S. Yi, Neal Ready, Patrick Healy, Chelsae Dumbauld, Robyn Osborne, Mark Berry, Debra Shoemaker, Jeffrey Clarke, Jeffrey Crawford, Betty Tong, David Harpole, Thomas A. D'Amico, Frances McSherry, Frank Dunphy, Shannon J. McCall, Jared D. Christensen, Xiaofei Wang, Kent J. Weinhold
Journal: Clinical Cancer Research (2017)

Abstract Purpose: To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early-stage non–small cell lung cancer (NSCLC) patients. Experimental Design: This is a single-arm chemotherapy plus phased ipilimumab phase II study of 24 treatment-naïve patients with stage IB–IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles. Results: Chemotherapy alone had little effect on immune parameters in PBMCs. Profound CD28-dependent activation of both CD4 and CD8 cells was observed following ipilimumab. Significant increases in the frequencies of CD4+ cells expressing activation markers ICOS, HLA-DR, CTLA-4, and PD-1 were apparent. Likewise, increased frequencies of CD8+ cells expressing the same activation markers, with the exception of PD-1, were observed. We also examined 7 resected tumors and found higher frequencies of activated tumor-infiltrating lymphocytes than those observed in PBMCs. Surprisingly, we found 4 cases of preexisting tumor-associated antigens (TAA) responses against survivin, PRAME, or MAGE-A3 present in PBMC at baseline, but neither increased frequencies nor the appearance of newly detectable responses following ipilimumab therapy. Ipilimumab had little effect on the frequencies of circulating regulatory T cells and MDSCs. Conclusions: This study did not meet the primary endpoint of detecting an increase in blood-based TAA T-cell responses after ipilimumab. Collectively, these results highlight the immune activating properties of ipilimumab in early-stage NSCLC. The immune profiling data for ipilimumab alone can contribute to the interpretation of immunologic data from combined immune checkpoint blockade immunotherapies. Clin Cancer Res; 23(24); 7474–82. ©2017 AACR.
Myogenic Progenitor Cells Exhibit Type I Interferon–Driven Proangiogenic Properties and Molecular Signature During Juvenile Dermatomyositis
Authors: Cyril Gitiaux, Claire Latroche, Michèle Weiss‐Gayet, Mathieu P. Rodero, Darragh Duffy, Brigitte Bader‐Meunier, Christophe Glorion, Patrick Nusbaum, Christine Bodemer, Guy Mouchiroud, Jamel Chelly, Stéphane Germain, Isabelle Desguerre, Bénédicte Chazaud
Journal: Arthritis & Rheumatology (2017)

Juvenile dermatomyositis (JDM) is an inflammatory pediatric myopathy characterized by focal capillary loss in muscle, followed by progressive recovery upon adequate treatment with immunomodulating drugs, although some patients remain refractory to treatment. While the underlying mechanism of capillary depletion remains uncertain, recent studies have identified an up-regulation of type I interferon (IFN) expression specific to JDM. Given that myogenic precursor cells (MPCs) exert proangiogenic activity during normal skeletal muscle regeneration, we hypothesized that they may also modulate vascular remodeling/angiogenesis during JDM. The aim of this study was to investigate that hypothesis.Human cell cocultures were used to analyze angiogenic properties in patients with JDM, patients with Duchenne's muscular dystrophy (DMD) (control patients for vascular remodeling), and healthy control subjects. Transcriptome analysis was used to examine muscle-derived MPCs. Histologic analysis of type I IFN in muscle biopsy samples was also performed.Using human cell cocultures, we showed highly angiogenic properties of MPCs from JDM patients in association with the expression of an angiogenic molecular signature. Transcriptome analysis of MPCs freshly isolated from muscle samples revealed type I IFN as the master regulator of the most up-regulated genes in JDM-derived MPCs. Functionally, treatment of normal MPCs with type I IFN recapitulated the molecular pattern and the proangiogenic functions of JDM-derived MPCs. In vivo histologic investigation showed that MPCs synthesized type I IFN and major proangiogenic molecules in JDM muscle. Moreover, MPCs derived from JDM muscles that were characterized by strong vasculopathy produced higher levels of type I IFN, confirming MPCs as a cellular source of type I IFN during JDM, and this correlated with the severity of the disease.These results demonstrate a new type I IFN pathway in JDM that activates the production of angiogenic effectors by MPCs, triggering their proangiogenic function to promote vessel recovery and muscle reconstruction.
Insecticide Use and Breast Cancer Risk among Farmers’ Wives in the Agricultural Health Study
Authors: Lawrence S. Engel, Emily Werder, Jaya Satagopan, Aaron Blair, Jane A. Hoppin, Stella Koutros, Catherine C. Lerro, Dale P. Sandler, Michael C. Alavanja, Laura E. Beane Freeman
Journal: Environmental Health Perspectives (2017)

Some epidemiologic and laboratory studies suggest that insecticides are related to increased breast cancer risk, but the evidence is inconsistent. Women engaged in agricultural work or who reside in agricultural areas may experience appreciable exposures to a wide range of insecticides.We examined associations between insecticide use and breast cancer incidence among wives of pesticide applicators (farmers) in the prospective Agricultural Health Study.Farmers and their wives provided information on insecticide use, demographics, and reproductive history at enrollment in 1993-1997 and in 5-y follow-up interviews. Cancer incidence was determined via cancer registries. Among 30,594 wives with no history of breast cancer before enrollment, we examined breast cancer risk in relation to the women's and their husbands' insecticide use using Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).During an average 14.7-y follow-up, 39% of the women reported ever using insecticides, and 1,081 were diagnosed with breast cancer. Although ever use of insecticides overall was not associated with breast cancer risk, risk was elevated among women who had ever used the organophosphates chlorpyrifos [HR=1.4 (95% CI: 1.0, 2.0)] or terbufos [HR=1.5 (95% CI: 1.0, 2.1)], with nonsignificantly increased risks for coumaphos [HR=1.5 (95% CI: 0.9, 2.5)] and heptachlor [HR=1.5 (95% CI: 0.7, 2.9)]. Risk in relation to the wives' use was associated primarily with premenopausal breast cancer. We found little evidence of differential risk by tumor estrogen receptor status. Among women who did not apply pesticides, the husband's use of fonofos was associated with elevated risk, although no exposure-response trend was observed.Use of several organophosphate insecticides was associated with elevated breast cancer risk. However, associations for the women's and husbands' use of these insecticides showed limited concordance. Ongoing cohort follow-up may help clarify the relationship, if any, between individual insecticide exposures and breast cancer risk. https://doi.org/10.1289/EHP1295.
Redesign of EAF Peg Hb As an Oxygen Transfer Catalyst for Improved Tissue Oxygenation of Hypoxic Areas: A Therapeutic for Anemia and Sickle Cell Disease
Authors: Savita Bhutoria, Amy Tsai, Marcos Intaglietta, Sandra M. Suzuka, Sangeetha Thangaswamy, Prabhakaran Muthuchidambaram, Caterina Minniti, Henny Heisler H Billett, Craig A Branch, Seetharama A Acharya
Journal: Blood (2016)
The Effect of Treatment on Mortality in Mild Hypertension
Journal: New England Journal of Medicine (1982)

In the Hypertension Detection and Follow-up Program, 7825 (71.5 per cent) of the 10,940 participants had diastolic blood pressures averaging between 90 and 104 mm Hg on entry into the study and were designated Stratum 1. Half were referred to their usual source of care in the community (the referred-care group), and half were treated intensively in special clinics (the stepped-care group). Five-year mortality in the Stratum 1 patients given stepped care was 20.3 per cent lower than in those given referred care (P<0.01). Particularly noteworthy was the beneficial effect of stepped-care treatment on persons with diastolic pressures of 90 to 104 mm Hg who had no evidence of end-organ damage and were not receiving antihypertensive medication when they entered the study. This subgroup had 28.6 per cent fewer deaths at five years among those treated with stepped care than among those treated with referred care (P<0.01). These findings support a recommendation that in patients with mild hypertension, treatment should be considered early, before damage to end organs occurs. (N Engl J Med. 1982; 307:976–80.)
Discovering gene expression signatures for breast cancer subtype stratification using DNA methylation profiles
Authors: Vinay Varadan, Nilanjana Banerjee, Sitharthan Kamalakaran, Nevenka Dimitrova, Yasser alSafadi, Angel Janevski
Journal: Clinical Cancer Research (2008)

B37  Predicting the clinical course of breast cancer is often difficult because it is a diverse disease comprising many biological subtypes. Gene expression profiling has identified a number of breast cancer signatures that are useful for prognostic and therapeutic strategies. The dimension and complexity of genomic data demand advanced predictive models that can distinguish subtle phenotypes. We have developed tools that can generate thousands of potential gene expression signatures that have very good performance in retrospective subtyping of breast cancer samples, many of which are likely to suffer from misclassifications in independent validation data. We therefore attempted to use additional modalities to further characterize these signatures in order to filter out the spurious ones. Previously, we were successful in using clinical prognostic indices (Nottingham Prognostic Index, St. Gallen, and NCI) to improve gene expression signature discovery. In this work, we investigated the use of DNA methylation information with gene expression to improve gene expression signature discovery and refine breast cancer subtyping.  Immuno-histological-based subtypes of luminal or basal were assigned to 104 breast cancer samples for which gene expression data was publicly available. Additionally, we obtained DNA methylation profiles for 60 of the samples using an advanced DNA methylation (MOMA) technology. These samples were clustered into the two subtypes based on their methylation profiles.  We use a Genetic Algorithm-based feature selection method for Support Vector Machine classification (GA-SVM) to identify gene expression signatures. To assess the reproducibility of the signatures, we repeat our analysis over 100 independent trials, randomly selecting samples for signature discovery and validation. In the first leg of our study, we identified gene expression signatures using only the gene expression data to guide the discovery process. This was then compared with the second leg of our study, where the discovery of gene expression signatures was aided by the methylation subtyping. Here the subtyping performance of a gene expression signature was evaluated both with respect to the immuno-histological subtypes and the methylation-based subtyping.  In both legs of the study, the GA-SVM identified a large number of statistically significant gene expression signatures, nearly all with very low average misclassification rate (
Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity
Authors: Carmelo Quarta, Christoffer Clemmensen, Zhimeng Zhu, Bin Yang, Sini S. Joseph, Dominik Lutter, Chun-Xia Yi, Elisabeth Graf, Cristina García-Cáceres, Beata Legutko, Katrin Fischer, Robert Brommage, Philippe Zizzari, Bernardo S. Franklin, Martin Krueger, Marco Koch, Sabine Vettorazzi, Pengyun Li, Susanna M. Hofmann, Mostafa Bakhti, Aimée Bastidas-Ponce, Heiko Lickert, Tim M. Strom, Valerie Gailus-Durner, Ingo Bechmann, Diego Perez-Tilve, Jan Tuckermann, Martin Hrabě de Angelis, Darleen Sandoval, Daniela Cota, Eicke Latz, Randy J. Seeley, Timo D. Müller, Richard D. DiMarchi, Brian Finan, Matthias H. Tschöp
Journal: Cell Metabolism (2017)
Risk prediction tools for keratinocyte carcinoma after solid organ transplantation: a review of the literature
Authors: S.E. Lowenstein, G. Garrett, A.E. Toland, A. Jambusaria‐Pahlajani, M.M. Asgari, A. Green, E.A. Engels, S.T. Arron
Journal: British Journal of Dermatology (2017)

Long‐term iatrogenic immunosuppression increases the risk of cutaneous malignancies in organ transplant recipients (OTRs), particularly the keratinocyte cancers basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC). cSCC is the most common malignancy in OTRs, with the risk increased to over 65‐fold in transplanted patients relative to the general population. There have been very few risk prediction tools developed for accurate determination of the risk of developing keratinocyte cancers in the OTR population. This review summarizes the prediction tools developed to date, and outlines future directions for developing more accurate prediction models that are clinically useful for the transplant physician and dermatologist.
Concomitant suppression of TH2 and TH17 cell responses in allergic asthma by targeting retinoic acid receptor–related orphan receptor γt
Authors: Hyeongjin Na, Hoyong Lim, Garam Choi, Byung-Keun Kim, Sae-Hoon Kim, Yoon-Seok Chang, Roza Nurieva, Chen Dong, Seon Hee Chang, Yeonseok Chung
Journal: Journal of Allergy and Clinical Immunology (2017)
Efficacy and safety of the Janus kinase 1 inhibitor PF-04965842 in patients with moderate-to-severe psoriasis: phase II, randomized, double-blind, placebo-controlled study
Authors: G.J. Schmieder, Z.D. Draelos, D.M. Pariser, C. Banfield, L. Cox, M. Hodge, E. Kieras, D. Parsons-Rich, S. Menon, M. Salganik, K. Page, E. Peeva
Journal: British Journal of Dermatology (2017)

PF‐04965842 is an oral Janus kinase 1 inhibitor being investigated for the treatment of plaque psoriasis. To evaluate the efficacy, safety and tolerability of PF‐04965842 in patients with moderate‐to‐severe plaque psoriasis. Patients in this phase II, placebo‐controlled study (NCT02201524) were randomized to receive placebo, 200 mg once daily (OD), 400 mg OD or 200 mg twice daily (TD) PF‐04965842 for 4 weeks. The primary endpoint was change from baseline in Psoriasis Area Severity Index (PASI) at week 4. Study enrolment was discontinued on 25 June 2015 due to changes in the sponsor's development priorities. Fifty‐nine patients were randomized and received at least one dose of PF‐04965842 or placebo. The estimated treatment effect (active –placebo PASI change from baseline) and 90% confidence interval at week 4 was −5·1 (−9·2 to −1·0), −5·6 (−9·6 to −1·6) and −10·0 (−14·2 to −5·8) for the 200 mg OD, 400 mg OD and 200 mg TD groups, respectively. At week 4, the proportion of patients achieving PASI 75 was 17% for the placebo and 200 mg OD groups, 50% for the 400 mg OD group and 60% for the 200 mg TD group. There were more abnormal laboratory test results of clinical interest (low neutrophil, reticulocyte and platelet counts) in the 200 mg TD group compared with the OD treatment groups. No serious infections or bleeding events related to neutropenia or thrombocytopenia, respectively, were reported. These results suggest that treatment with PF‐04965842 improves symptoms and is well tolerated in patients with moderate‐to‐severe psoriasis.
Reply to Backes et al.
Authors: Qing-Wei Zhang, La-Mei Teng, Xin-Tian Zhang, Xia-Lin Yan, Chen-Yue Tang, Xiao-Bo Li
Journal: Endoscopy (2017)

See also: Magnifying chromoendoscopy does not seem helpful in avoiding unnecessary surgery once deep submucosal invasion is suspectedEndoscopy 2017; 49(10): 1017-1017DOI: 10.1055/s-0043-117408
Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events
Authors: Johan Sundström, Jakob Hedberg, Marcus Thuresson, Pernilla Aarskog, Kasper Munk Johannesen, Jonas Oldgren
Journal: Circulation (2017)

There are increasing concerns about risks associated with aspirin discontinuation in the absence of major surgery or bleeding. We investigated whether long-term low-dose aspirin discontinuation and treatment gaps increase the risk of cardiovascular events.We performed a cohort study of 601 527 users of low-dose aspirin for primary or secondary prevention in the Swedish prescription register between 2005 and 2009 who were >40 years of age, were free from previous cancer, and had ≥80% adherence during the first observed year of treatment. Cardiovascular events were identified with the Swedish inpatient and cause-of-death registers. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk.During a median of 3.0 years of follow-up, 62 690 cardiovascular events occurred. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37; 95% confidence interval, 1.34-1.41), corresponding to an additional cardiovascular event observed per year in 1 of every 74 patients who discontinue aspirin. The risk increased shortly after discontinuation and did not appear to diminish over time.In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding was associated with a >30% increased risk of cardiovascular events. Adherence to low-dose aspirin treatment in the absence of major surgery or bleeding is likely an important treatment goal.
Mechano-Signal Transduction in Mesenchymal Stem Cells Induces Prosaposin Secretion to Drive the Proliferation of Breast Cancer Cells
Authors: Seiichiro Ishihara, David R. Inman, Wan-Ju Li, Suzanne M. Ponik, Patricia J. Keely
Journal: Cancer Research (2017)

Abstract In response to chemical stimuli from cancer cells, mesenchymal stem cells (MSC) can differentiate into cancer-associated fibroblasts (CAF) and promote tumor progression. How mechanical stimuli such as stiffness of the extracellular matrix (ECM) contribute to MSC phenotype in cancer remains poorly understood. Here, we show that ECM stiffness leads to mechano-signal transduction in MSC, which promotes mammary tumor growth in part through secretion of the signaling protein prosaposin. On a stiff matrix, MSC cultured with conditioned media from mammary cancer cells expressed increased levels of α-smooth muscle actin, a marker of CAF, compared with MSC cultured on a soft matrix. By contrast, MSC cultured on a stiff matrix secreted prosaposin that promoted proliferation and survival of mammary carcinoma cells but inhibited metastasis. Our findings suggest that in addition to chemical stimuli, increased stiffness of the ECM in the tumor microenvironment induces differentiation of MSC to CAF, triggering enhanced proliferation and survival of mammary cancer cells. Cancer Res; 77(22); 6179–89. ©2017 AACR.
An updated overview on the development of new photosensitizers for anticancer photodynamic therapy
Authors: Juan Zhang, Chengshi Jiang, João Paulo Figueiró Longo, Ricardo Bentes Azevedo, Hua Zhang, Luis Alexandre Muehlmann
Journal: Acta Pharmaceutica Sinica B (2017)

Photodynamic therapy (PDT), based on the photoactivation of photosensitizers (PSs), has become a well-studied therapy for cancer. Photofrin®, belonging to the first generation of PS, is still widely used for the treatment of different kinds of cancers; however, it has several drawbacks that significantly limit its general clinical use. Consequently, there has been extensive research on the design of PS molecules with optimized pharmaceutical properties, with aiming of overcoming the disadvantages of traditional PS, such as poor chemical purity, long half-life, excessive accumulation into the skin, and low attenuation coefficients. The rational design of novel PS with desirable properties has attracted considerable research in the pharmaceutical field. This review presents an overview on the classical photosensitizers and the most significant recent advances in the development of PS with regard to their potential application in oncology.