tbuckley/cabot-search huggingface dataset:
Acute sport-related concussion induces transient impairment in dynamic cerebral auto regulation that is related to scat3 performance
Authors: Alexander D Wright, Jonathan D Smirl, Kelsey Bryk, Sarah K Fraser, Harjas S Grewal, Michael Jakovac, Jill Dierijck, Paul van Donkelaar
Journal: British Journal of Sports Medicine (2017)

Objective Examine how the frequency-dependent relationship between blood pressure (BP) and cerebral blood velocity (CBV) is affected by acute sport-related concussion. Design Prospective Cohort. Setting Laboratory. Participants: 136 male contact-sport athletes (19.1±1.4 years) recruited, subset of 14 sustained concussions (19±1.4 years). Intervention Participants completed baseline (T0) and post-injury testing at 72-hours (T1), 2-weeks (T2), and 1-month (T3). BP was monitored via finger photoplethysmography, and transcranial Doppler ultrasound indexed CBV in the middle cerebral artery. Squat-stand manoeuvers were performed at 0.05 and 0.10Hz to enhance BP variation. RM-ANOVA independent variables included time (4) and frequency (2). Outcome measures Transfer function analysis point estimates quantified coherence (correlation), phase (synchronisation) and gain (amplitude buffer) metrics between BP and CBV waveforms. Results Significant frequency-time interactions for phase (p=0.007) and gain (p=0.049). Simple effects analysis revealed time effects for phase at 0.10 Hz, indicating reductions at T1 (95% CI: 0.033 – 0.24 rads, p=0.008) and T2 (95% CI: 0.014–0.196 rads, p=0.02) compared to T0. On average, return-to-play occurred at T2 (median 14 days). Phase reductions at T1 were correlated with Standardised Assessment of Concussion performance (r=0.659, p=0.02). Conclusions These results reveal transient post-concussion impairments in the capacity of the cerebrovasculature to buffer BP oscillations, which exceeded clinical recovery duration. Phase reductions at 0.10Hz suggest the presence of a cerebrovascular autonomic dysregulation, which could leave the brain less protected to BP surges. This key finding may help explain why the brain is more vulnerable to additional trauma during the post-injury recovery period. Competing interests None.
Eye tracking a biomarker for concussion in the paediatricpediatric population
Authors: Uzma Samadani, Abdullah Bin Zahid, Julia Lockyer, Vikalpa Dammavalam, Matthew Grady, Michael Nance, Mitchell Scheiman, Christina L Master
Journal: British Journal of Sports Medicine (2017)

Objective The study aims to validate eye movement tracking performed without a baseline study as a biomarker for concussion in a paediatric population. Design This is a cross-sectional case control study of patients diagnosed with concussion in a referral centre compared to non-concussed controls. Methods Eye movements were recorded with an SR Research Eyelink 1000 eye tracker while a 220-second video was played. Eye tracking metrics were compared to Acute Concussion Evaluation (ACE) scores and clinical assessments of convergence and accommodation. Results 56 children with concussions (mean age of 13 years), as defined by symptom presence following an impulsive injury to the brain were evaluated at a mean of 22 weeks post-injury. Twelve eye tracking metrics were significantly different between concussed children and 83 uninjured controls. A model built on a balanced sub-sample to classify concussion based on eye tracking achieved an AUC of 0.854 (sensitivity 71.9%; specificity 84.4%). Two metrics were significant predictors of abnormal near point convergence (NPC) and accommodation. The model built to classify concussion based on NPC status achieved a specificity of 95.8% and a sensitivity of 57.1%. Reduced binocular amplitude of accommodation had a spearman correlation of 0.752 (p-value&lt;0.001) with NPC. Seven eye tracking metrics were found to have a strong correlation (R=0.781) with binocular amplitude of accommodation. Conclusions Eye tracking reliably detected concussion and convergence and accommodative abnormalities in the paediatric population. We propose that eye tracking without baseline assessment may serve as an objective measure of concussion in paediatric patients. Competing interests Uzma Samadani has submitted intellectual property describing the technology utilised in this paper. These patents are owned by NYU, the VA and HCMC and licensed to Oculogica Inc., a company in which all of the above parties have an equity interest
HIF2α cooperates with RAS to promote lung tumorigenesis in mice
Authors: William Y. Kim, Samanthi Perera, Bing Zhou, Julian Carretero, Jen Jen Yeh, Samuel A. Heathcote, Autumn L. Jackson, Petros Nikolinakos, Beatriz Ospina, George N. Naumov, Kathleyn A. Brandstetter, Victor J. Weigman, Sara Zaghlul, D. Neil Hayes, Robert F. Padera, John V. Heymach, Andrew L. Kung, Norman E. Sharpless, William G. Kaelin, Kwok-Kin Wong
Journal: Journal of Clinical Investigation (2009)
Giant Reverse Transcriptase-Encoding Transposable Elements at Telomeres
Authors: Irina R. Arkhipova, Irina A. Yushenova, Fernando Rodriguez
Journal: Molecular Biology and Evolution (2017)

Transposable elements are omnipresent in eukaryotic genomes and have a profound impact on chromosome structure, function and evolution. Their structural and functional diversity is thought to be reasonably well-understood, especially in retroelements, which transpose via an RNA intermediate copied into cDNA by the element-encoded reverse transcriptase, and are characterized by a compact structure. Here, we report a novel type of expandable eukaryotic retroelements, which we call Terminons. These elements can attach to G-rich telomeric repeat overhangs at the chromosome ends, in a process apparently facilitated by complementary C-rich repeats at the 3'-end of the RNA template immediately adjacent to a hammerhead ribozyme motif. Terminon units, which can exceed 40 kb in length, display an unusually complex and diverse structure, and can form very long chains, with host genes often captured between units. As the principal polymerizing component, Terminons contain Athena reverse transcriptases previously described in bdelloid rotifers and belonging to the enigmatic group of Penelope-like elements, but can additionally accumulate multiple cooriented ORFs, including DEDDy 3'-exonucleases, GDSL esterases/lipases, GIY-YIG-like endonucleases, rolling-circle replication initiator (Rep) proteins, and putatively structural ORFs with coiled-coil motifs and transmembrane domains. The extraordinary length and complexity of Terminons and the high degree of interfamily variability in their ORF content challenge the current views on the structural organization of eukaryotic retroelements, and highlight their possible connections with the viral world and the implications for the elevated frequency of gene transfer.
Brief Report: Anti–RNPC‐3 Antibodies As a Marker of Cancer‐Associated Scleroderma
Authors: Ami A. Shah, George Xu, Antony Rosen, Laura K. Hummers, Fredrick M. Wigley, Stephen J. Elledge, Livia Casciola‐Rosen
Journal: Arthritis & Rheumatology (2017)

Prior studies have demonstrated an increased risk of cancer-associated scleroderma in patients with anti-RNA polymerase III (anti-RNAP III) autoantibodies as well as in patients who are triple-negative for anticentromere (anti-CENP), anti-topoisomerase I (anti-topo I), and anti-RNAP III (also known as anti-POL) autoantibodies (referred to as CTP negative). In a recent study of 16 CTP-negative scleroderma patients with coincident cancer, 25% of the patients were found to have autoantibodies to RNPC-3, a member of the minor spliceosome complex. This investigation was undertaken to validate the relationship between anti-RNPC-3 antibodies and cancer and examine the associated clinical phenotype in a large sample of scleroderma patients.Scleroderma patients with cancer were assayed for anti-CENP, anti-topo I, anti-RNAP III, and anti-RNPC-3 autoantibodies. Disease characteristics and the cancer-scleroderma interval were compared across autoantibody groups. The relationship between autoantibody status and cancer-associated scleroderma was assessed by logistic regression.Of 318 patients with scleroderma and cancer, 70 (22.0%) were positive for anti-RNAP III, 54 (17.0%) were positive for anti-topo I, and 96 (30.2%) were positive for anti-CENP. Twelve patients (3.8% of the overall group or 12.2% of CTP-negative patients) were positive for anti-RNPC-3. Patients with anti-RNPC-3 had a short cancer-scleroderma interval (median 0.9 years). Relative to patients with anti-CENP, patients with anti-RNPC-3 and those with anti-RNAP III had a >4-fold increased risk of cancer within 2 years of scleroderma onset (for anti-RNPC-3-positive patients, odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.10-16.9 [P = 0.037]; for anti-RNAP III-positive patients, OR 4.49, 95% CI 1.98-10.2 [P < 0.001]). Patients with anti-RNPC-3 had severe restrictive lung disease, gastrointestinal disease, Raynaud's phenomenon, and myopathy.Anti-RNPC-3 autoantibodies, similar to anti-RNAP III autoantibodies, are associated with an increased risk of cancer at the onset of scleroderma. These data suggest the possibility of cancer-induced autoimmunity in this subset of patients with scleroderma.
Use of first-line chemotherapy for advanced pancreatic cancer: FOLFIRINOX versus gemcitabine-based therapy.
Authors: Thomas H. Cartwright, Aimee Ginsburg, Lalan S. Wilfong, Robyn K. Harrell, J. Russell Hoverman
Journal: Journal of Clinical Oncology (2014)

4132 Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 46,420 patients will be diagnosed in 2014 and 35,590 will die (Siegel, CA Cancer J Clin 2014). Gemcitabine has long been the standard of care chemotherapy. Recent advances in treatment created the combination regimens (oxaliplatin, irinotecan, leucovorin, fluorouracil [FOLFIRINOX]) and gemcitabine, nab-paclitaxel (GN) for patients with good Karnofsky performance status (PS) (Conroy, NEJM 2011; Von Hoff, NEJM 2013). This retrospective analysis was conducted as an update to results reported at ASCO 2013 (Cartwright, JCO 2013) to evaluate characteristics and overall survival (OS) of patients receiving FOLFIRINOX and gemcitabine-based treatments in a large outpatient community setting. This is the largest study describing FOLFIRINOX patients to date. Methods: Patients with advanced PC treated at practices in The US Oncology Network entered into the iKnowMed (iKM) database between June 2010 and November 2013 were included. Patterns of treatment were characterized by the median age at diagnosis, sex, PS, and first-line metastatic chemotherapy prescribed. The primary endpoints of the analysis were OS and uptake of FOLFIRINOX within The Network. Results: Compared to ASCO 2013 results, 700 additional patients were identified. Of the 2,422 total patients, 27% received FOLFIRINOX (24% in 2013) and 73% received gemcitabine-based therapy (76% in 2013). Increased utilization of FOLFIRINOX for good PS patients began in June 2010 and GN April 2013. For all patients (55% male), the median age at diagnosis was 67 and 95% had a PS of 70% or greater. When controlled for age and PS, the OS was significantly longer for FOLFIRINOX (11.2 mos) versus gemcitabine (7.2 mos) (p<0.0001). Median OS for GN (n=189) was 10.2 mos, despite shorter follow up time. Conclusions: Utilization of FOLFIRINOX and GN has continued to increase after the publication of phase III trials. Our data in a community setting continues to support a survival advantage for FOLFIRINOX as well as GN. The magnitude of benefit appears slightly better in the community; therefore, we agree that FOLFIRINOX should become a standard of care for good PS patients.
Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade
Authors: Simon J. Dovedi, Eleanor J. Cheadle, Amy L. Popple, Edmund Poon, Michelle Morrow, Ross Stewart, Erik C. Yusko, Catherine M. Sanders, Marissa Vignali, Ryan O. Emerson, Harlan S. Robins, Robert W. Wilkinson, Jamie Honeychurch, Timothy M. Illidge
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Radiotherapy is a highly effective anticancer treatment forming part of the standard of care for the majority of patients, but local and distal disease recurrence remains a major cause of mortality. Radiotherapy is known to enhance tumor immunogenicity; however, the contribution and mechanisms of radiotherapy-induced immune responses are unknown. Experimental Design: The impact of low-dose fractionated radiotherapy (5 × 2 Gy) alone and in combination with αPD-1 mAb on the tumor microenvironment was evaluated by flow cytometry and next-generation sequencing of the T-cell receptor (TCR) repertoire. A dual-tumor model was used, with fractionated radiotherapy delivered to a single tumor site to enable evaluation of the local and systemic response to treatment and ability to induce abscopal responses outside the radiation field. Results: We show that fractionated radiotherapy leads to T-cell infiltration at the irradiated site; however, the TCR landscape remains dominated by polyclonal expansion of preexisting T-cell clones. Adaptive resistance via the PD-1/PD-L1 pathway restricts the generation of systemic anticancer immunity following radiotherapy, which can be overcome through combination with αPD-1 mAb leading to improved local and distal tumor control. Moreover, we show that effective clearance of tumor following combination therapy is dependent on both T cells resident in the tumor at the time of radiotherapy and infiltrating T cells. Conclusions: These data provide evidence that radiotherapy can enhance T-cell trafficking to locally treated tumor sites and augment preexisting anticancer T-cell responses with the capacity to mediate regression of out-of-field tumor lesions when delivered in combination with αPD-1 mAb therapy. Clin Cancer Res; 23(18); 5514–26. ©2017 AACR.
Race vs Burden in Understanding Health Equity
Authors: Rachel R. Hardeman, Eduardo M. Medina, Katy B. Kozhimannil
Journal: JAMA (2017)

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Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression
Authors: Eunsun Kim, Ying Cheng, Elisabeth Bolton-Gillespie, Xiongwei Cai, Connie Ma, Amy Tarangelo, Linh Le, Madhumita Jambhekar, Pichai Raman, Katharina E. Hayer, Gerald Wertheim, Nancy A. Speck, Wei Tong, Patrick Viatour
Journal: The Journal of Experimental Medicine (2017)

Prolonged exit from quiescence by hematopoietic stem cells (HSCs) progressively impairs their homeostasis in the bone marrow through an unidentified mechanism. We show that Rb proteins, which are major enforcers of quiescence, maintain HSC homeostasis by positively regulating thrombopoietin (Tpo)-mediated Jak2 signaling. Rb family protein inactivation triggers the progressive E2f-mediated transactivation of Socs3, a potent inhibitor of Jak2 signaling, in cycling HSCs. Aberrant activation of Socs3 impairs Tpo signaling and leads to impaired HSC homeostasis. Therefore, Rb proteins act as a central hub of quiescence and homeostasis by coordinating the regulation of both cell cycle and Jak2 signaling in HSCs.
Adolescent athletes’ social perspectives following a sport-related concussion
Authors: Tamara Valovich McLeod, Alyssa J Wagner, John T Parsons, Cailee E Welch Bacon
Journal: British Journal of Sports Medicine (2017)

Objective To explore adolescent athletes’ social perspectives regarding sport and concussion. Design Qualitative inquiry. Setting Individual in-person interviews. Participants 12 interscholastic athletes (4 females, 8 males; age=15.7±1.7 years; grade level=10.2±1.4; sports=football, soccer, volleyball, basketball, and wrestling) were interviewed. Outcome measures A semi-structured interview protocol was used. Interviews focused on injury details, and explored the physical, psychosocial, emotional, and spiritual components of sport and health. Themes and categories were identified based on the consensus process by a three-person research team. A comprehensive codebook that captured the main themes and categories resulted. Results Following concussion, participants discussed two primary themes: perceptions regarding the social aspects of sport and social perspectives regarding their concussion. Specific categories related to the social aspects of sport included friendships and family and decision to participate based on peers. Specific categories regarding the social perspectives of the concussion included: uncertainty of the diagnosis, perceptions of others regarding their injury, being ashamed of the concussion, parent and peer roles, and communication and expectation about their concussion. Conclusions Participation in sport and removal from sport following a concussion have significant social implications for adolescent athletes. Specifically, the perceptions of peers, parents, and others regarding the injury can influence reporting of symptoms and recovery following concussion. Limited communication regarding recovery and expectations post-concussion may cause undue social pressures to return to activity prematurely. Anticipatory guidance, with education regarding the possible signs and symptoms, risk factors pre- and post-injury, and recovery expectations following a concussion are important to include in post-injury management. Competing interests Funded from a grant from the National Operating Committee on Standards for Athletic Equipment.
L’endoscopie “Dual Focus” versus la magnification conventionnelle dans le diagnostic des lésions épidermoïdes superficielles du pharynx et de l’œsophage: un essai randomisé
Journal: Endoscopy (2016)

Des cancers épidermoïdes multiples peuvent se développer dans les voies aéro-digestives supérieures des malades alcoolo-tabagiques. La détection de ces lésions par voie endoscopique à un stade précoce peut être difficile du fait de la présentation fréquente sous la forme de lésions planes ou discrètement dyschromiques (rougeâtres ou blanchâtres), souvent peu visibles en lumière blanche (white light endoscopy). La coloration vitale au lugol est recommandée pour ces malades, les lésions suspectes se caractérisant par une absence de coloration brune au lugol, due à l'absence de réserves en glycogène des cellules à renouvellement rapide. Le lugol n'est pas toujours utilisable du fait de réactions allergiques ou encore d'une exploration proche du larynx pouvant exposer à une inhalation.
Prospective observational cohort of paediatricpediatric sport-related concussion
Authors: Neil Dilworth, Siobhan Karam, Ryan Eardley, Sari Kraft, Hemen Shukla, Mark Leung, Ira Smith
Journal: British Journal of Sports Medicine (2017)

Objective To determine the symptom duration, and time to return to school and sport after sport-related concussion in paediatric population aged 12–18 years. Symptom duration was hypothesised to be &gt;7–10 days. Design Prospective observational cohort study. Setting Large urban community primary care sports medicine clinic. Paticipants 30 participants age 12–18 years (Male: n=27;Female: n=3) presenting to clinic ≤14 days with sport-related concussion. 100% completed study. Exclusion criteria: age &lt;12 and &gt;18 years, presentation ≥15 days, non-sport related concussion. Independent variable(s)/modifiers Sport, SCAT3 score, past medical and concussion history, objective assessment variables (oculomotor, near-point convergence, vestibular, cognitive, cervical dysfunction). Outcome measures Symptom duration, return to sport, return to school (days) Main results Most concussions occurred playing ice-hockey (53%), followed by Canadian football and basketball. Mean intake SCAT3 symptom number was 10 and symptom score was 22. Patient characteristics included prior concussion (50%), prior neurological conditions (40%), and pre-existing psychological diagnosis (20%). The mean initial exam findings included near point convergence=6.5 cm and Balance Error Scoring System=26.1/30. Vestibular dysfunction (46.7%), cervical pain (53.3%), and abnormal coordination in (43.3%) were present. Mean duration of symptoms was 30.6 days; return to school was 23.9 days. 73.3% of patients would return to sport within 3 months (mean=34.6 days). Conclusions Sport-related concussion symptoms resolved ≥30 days after injury confirming prolonged symptoms in an adolescent population, affecting return to school and sport. Future larger similar prospective studies may identify associations between past medical history or clinical exam findings and symptom duration, return to school and sport. Competing interests None.