tbuckley/cabot-search huggingface dataset:
Internal workload and non-contact injury: a one-season study of five teams from the UEFA Elite Club Injury Study
Authors: Alan McCall, Gregory Dupont, Jan Ekstrand
Journal: British Journal of Sports Medicine (2018)

Internal workload (ie, from training and matches) is considered one of the most important injury risk factors for elite European football teams, however there is little published evidence to support this belief.We examined the association and predictive power of internal workload and non-contact injuries.Five elite European teams, 171 players (age: 25.1±4.9 years; height: 181.6±6.7 cm; body mass: 77.5±7.2 kg) participated over one full competitive season. Using the session-rating of perceived exertion (s-RPE) method player's internal workloads were calculated for acute week, week-to-week changes, cumulated weeks, chronic weeks and acute:chronic ratios and analysed for association with non-contact injury (using generalised estimating equations (GEE)). Associated variables from GEE analysis were categorised into very low to very high workload zones and checked for increased relative risks (RRs). Associated workload variables were also analysed for predictive power (receiver operating characteristics).Acute:chronic workload ratios at 1:3 and 1:4 weeks were associated with non-contact injury (P<0.05). Specifically, a greater risk of injury was found for players with an acute:chronic workload at 1:4 weeks of 0.97 to 1.38 (RR 1.68; 95% CI 1.02 to 2.78, likely harmful) and >1.38 (RR 2.13; 95% CI 1.21 to 3.77, very likely harmful) compared with players whose acute:chronic workload was 0.60 to 0.97. An acute:chronic workload 1:3 of >1.42 compared with 0.59 to 0.97 displayed a 1.94 times higher risk of injury (RR 1.90; 95% CI 1.08 to 3.36, very likely harmful). Importantly, acute:chronic workload at both 1:4 and 1:3 showed poor predictive power (area under the curve 0.53 to 0.58) despite previous reports and beliefs that it can predict injury.This study provides evidence for the acute:chronic internal workload (measured using s-RPE) as a risk factor for non-contact injury in elite European footballers. However the acute:chronic workload, in isolation, should not be used to predict non-contact injury.
Physician Burnout—Overdiagnosis and Unproven Interventions
Authors: William B. Weeks
Journal: JAMA Internal Medicine (2018)

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Neonatal Abstinence Syndrome
Authors: Elisha M. Wachman, Davida M. Schiff, Michael Silverstein
Journal: JAMA (2018)

<h3>Importance</h3> Neonatal abstinence syndrome, which occurs as a result of in utero opioid exposure, affects between 6.0 and 20 newborns per 1000 live US births. There is substantial variability in how neonatal abstinence syndrome is diagnosed and managed. <h3>Objective</h3> To summarize key studies examining the diagnosis and management (both pharmacologic and nonpharmacologic) of neonatal abstinence syndrome published during the past 10 years. <h3>Evidence Review</h3> PubMed, Web of Science, and CINAHL were searched for articles published between July 1, 2007, and December 31, 2017. Abstracts were screened and included in the review if they pertained to neonatal abstinence syndrome diagnosis or management and were judged by the authors to be clinical trials, cohort studies, or case series. <h3>Findings</h3> A total of 53 articles were included in the review, including 9 randomized clinical trials, 35 cohort studies, 1 cross-sectional study, and 8 case series—representing a total of 11 905 unique opioid-exposed mother-infant dyads. Thirteen studies were identified that evaluated established or novel neonatal abstinence syndrome assessment methods, such as brief neonatal abstinence syndrome assessment scales or novel objective physiologic measures to predict withdrawal. None of the new techniques that measure infant physiologic parameters are routinely used in clinical practice. The most substantial number of studies of neonatal abstinence syndrome management pertain to nonpharmacologic care—specifically, interventions that promote breastfeeding or encourage parents to room-in with their newborns. Although these nonpharmacologic interventions appear to decrease the need for pharmacologic treatment and result in shorter hospitalizations, the interventions are heterogeneous and there are no high-quality clinical trials to support them. Regarding pharmacologic interventions, only 5 randomized clinical trials with prespecified sample size calculations (4 infant, 1 maternal treatment) have been published. Each of these trials was small (from 26 to 131 participants) and tested different therapies, limiting the extent to which results can be aggregated. There is insufficient evidence to support an association between any diagnostic or treatment approach and differential neurodevelopmental outcomes among infants with neonatal abstinence syndrome. <h3>Conclusions and Relevance</h3> Evidence pertaining to the optimal diagnosis and treatment strategies for neonatal abstinence syndrome is based on small or low-quality studies that focus on intermediate outcomes, such as need for pharmacologic treatment or length of hospital stay. Clinical trials are needed to evaluate health and neurodevelopmental outcomes associated with objective diagnostic approaches as well as pharmacologic and nonpharmacologic treatment modalities.
SM-88 therapy in patients with advanced or metastatic pancreatic cancer.
Authors: Steve Hoffman, Jeanetta Stega, Patricia Zawisny, Zachary Gostout, Giuseppe Del Priore, Maria Loushin, Ben R Taylor
Journal: Journal of Clinical Oncology (2018)

457 Background: SM-88 (tyrosine derivative, mTOR inhibitor, CYP3a4 inducer and oxidative stress catalyst) is a relatively non-toxic, targeted therapy that utilizes the Warburg Effect in combination with oxidative stress to cause tumor cell death. Previously reported results (Phase I and preliminary Phase II) showed safety and efficacy for SM-88 in metastatic and recurrent cancers. Pancreatic cancer continues to have a poor prognosis with toxic standard of care (SOC) therapies, associated serious adverse events (SAEs), and QOL degradation. SM-88 is being evaluated as a minimally toxic alternative treatment. Methods: Retrospective chart review between 2012-17 of 12 patients with advanced or metastatic pancreatic cancer treated with SM-88 through a Phase 1 study (3/12) or compassionate use (9/12) with 10/12 evaluable. Although treatment regimens specifics varied, all were provided SM-88 therapy five days a week, administered by clinicians, orally or through subcutaneous injection; 7/10 patients received SM-88 mono therapy; and 3/10 received combination therapy (5FU-based). Results: 40% (4/10) of patients achieved survival benefit of greater than one year (mean 12.2 mo) (see table). Monotherapy patients maintained or improved ECOG PS and did not experience drug-related SAEs during treatment. 2/10 patients achieved partial responses. One patient maintained rPFS for 13 months despite positive margins post-surgery and elevated CA19.9 levels. Conclusions: SM-88 appears well tolerated and demonstrated notable survival times in comparison to expected SOC therapies. In addition, several of the patients demonstrating benefit had baseline ECOG PSs of 2, for which current SOC is palliative care only. For further evaluation, a North American Phase II trial in recurrent pancreatic cancer has been initiated. [Table: see text]
Implantable sandwich PHBHHx film for burst-free controlled delivery of thymopentin peptide
Authors: Ke Peng, Chengyu Wu, Guoxu Wei, Jinghui Jiang, Zhirong Zhang, Xun Sun
Journal: Acta Pharmaceutica Sinica B (2018)

Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small peptides such as thymopentin (TP5). To this end, implantable sandwich poly (hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) films were designed to prolong release time and to inhibit burst release phenomenon of TP5 by a simple volatilization method. In vitro release studies revealed that sandwich films had nearly no burst release. In vivo release time of sandwich films was prolonged to 42 days. Pharmacodynamic evaluation demonstrated that TP5 sandwich films significantly increased survival rates in a rat immunosuppressive model and normalized CD4+/CD8+ values. These results suggest that TP5 released from sandwich films can attenuate cyclophosphamide's immunosuppressive activity, and possibly achieve results comparable to daily TP5 injection therapy. Thus, sandwich PHBHHx films show excellent potential as a sustained, burst-free release system for small molecular weight, hydrophilic peptide drugs.
Association of differential mucosal microbiome composition with clinicopathologic characteristics of rectal adenocarcinoma.
Authors: Michael Sangmin Lee, Cheryl Ann Carlson, Benjamin F. Calvo, Bert H. O'Neil, Nicole Amber McCoy, Temitope O Keku
Journal: Journal of Clinical Oncology (2018)

656 Background: Alterations in gut microbial composition are associated with development and progression of colorectal cancer (CRC), and may contribute to interpatient biologic and clinical heterogeneity. While recent studies have emphasized primary CRC tumor site as explaining much of these differences, there is still marked heterogeneity in clinical outcomes among the more homogeneous subgroup of rectal cancers. As such, we hypothesized that differential mucosal microbial populations are associated with distinct clinicopathologic characteristics among patients with locally advanced rectal cancer. Methods: Patients with T3-4 or N+ rectal adenocarcinoma were prospectively identified and underwent endoscopic tumor biopsy before starting neoadjuvant chemoradiation. Tumor samples were fresh frozen, bacterial DNA was extracted, and the V1-V2 region of the 16S bacterial ribosomal RNA was sequenced (IonTorrent). Sequences were processed through QIIME and an average of 16,189 reads per sample was obtained after quality filtering. Multivariate analyses were conducted using PRIMER VII and SPSS v24 software. P-values were determined using Mann-Whitney tests, and Benjamini-Hochberg procedure for false discovery rate was used and only results with false discovery rate &lt; 0.25 are presented. Results: Among the 37 patients, mean age at diagnosis was 54 (range 30-77) and pre-treatment clinical stage was II (30%) vs. III-IV (70%). Younger patients (age &lt; 50) had samples underrepresented for Streptococcus (0.9% vs 7.1%, p = 0.016, FDR 0.224) genus. Higher clinical stage was associated with enrichment of Fusobacterium (16.2% vs 5.6%, p = 0.019) and Parvimonas (4.6% vs 1.4%, p = 0.033) genera. Conclusions: Differential composition of tumor mucosal microbiota is associated with key clinical features among rectal adenocarcinomas, including age of diagnosis and tumor stage. Further investigation to determine associations between gut dysbiosis and transcriptomic subtypes may shed light on etiology of interpatient heterogeneity of rectal cancers.
No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma
Authors: Issei Saeki, Takahiro Yamasaki, Masaki Maeda, Reo Kawano, Takuro Hisanaga, Takuya Iwamoto, Toshihiko Matsumoto, Isao Hidaka, Tsuyoshi Ishikawa, Taro Takami, Isao Sakaida
Journal: Liver Cancer (2018)

Sorafenib is a standard therapy for patients with advanced hepatocellular carcinoma (HCC). However, no predictive biomarkers of sorafenib efficacy have been discovered. Herein, we investigated the impact of body composition, such as skeletal muscle and visceral fat, on the prognosis of advanced HCC patients treated with sorafenib.We enrolled 100 patients with advanced HCC treated with sorafenib. Prior to receiving sorafenib therapy, skeletal muscle index (SMI) and visceral fat area (VFA) were measured using computed tomography at the third lumbar vertebra and umbilical level, respectively. Muscle depletion was defined as an SMI value < 42 cm2/m2 in men and < 38 cm2/m2 in women. High VFA (H-VFA) was defined as a value ≥100 cm2. In addition to SMI and VFA, we also analyzed various clinical parameters as potential prognostic factors.Multivariate analysis showed that having a tumor number < 7 (hazard ratio [HR] = 0.409, p < 0.001), absence of extrahepatic spread (EHS) (HR = 0.562, p < 0.001), absence of muscle depletion (HR = 0.498, p = 0.006), and H-VFA (HR = 0.556, p = 0.031) were significant factors for long-term survival. Therefore, we evaluated the prognosis of those with no muscle depletion with H-VFA. The no muscle depletion with H-VFA group showed significantly longer survival than the other group (median survival time 15.6 vs. 11.0 months, p = 0.003). Multivariate analysis showed that having a tumor number < 7 (HR = 0.454, p = 0.001), absence of EHS (HR = 0.511, p = 0.008), and no muscle depletion with H-VFA (HR = 0.454, p = 0.002) were significant predictors of survival.We identified no muscle depletion with H-VFA as a novel biomarker for advanced HCC patients treated with sorafenib.
Self-reported health outcomes of veterans with prostate cancer: The impact of PTSD or PTSD-like symptoms.
Authors: Wen-Wei Tchou, Lisa A Bevilacqua, Jamie L Romeiser, Elizabeth A Vanner, Nikita Agrawal, Xiaoann Ni, Jennifer A Lyon, A. Laurie W Shroyer
Journal: Journal of Clinical Oncology (2017)

e16589 Background: The impact of PTSD on the health of veterans with prostate cancer is unknown. Methods: From September 2015 to October 2016, patients with prostate cancer at a Veterans Administration Hospital completed self-report surveys assessing their overall health status. Survey findings for patients with PTSD were compared to those without PTSD. Patients were considered PTSD+ if they had a diagnosis of PTSD in their Electronic Medical Record (EMR) or scored ≥50 on the PTSD Checklist—Civilian Version (PCL-C). Health outcomes included scores on the following measures: VR-36 (Physical Component Score [PCS] and Mental Component Score [MCS]), Beck Depression Index (BDI), Beck Anxiety Index (BAI), and Pain Visual Analogue Scale (VAS). Results: A total of 104 veterans (18 PTSD+) completed all surveys. The average age was 74.6 ±7.8. 82.7% of patients were Caucasian. PTSD+ Veterans were significantly younger (p&lt;0.001). No PTSD-related differences were found for race/ethnicity, BMI, or VR-36 PCS scores. PTSD+ patients had lower overall VR-36 MCS scores (36.9±12.8 vs. 52.7±10.5; p&lt;0.001), and higher Pain VAS scores (3.9±2.6 vs. 2.1±2.2; p&lt;0.01). PTSD+ patients were more likely to meet criteria for depression (61.1% vs. 8.1%; p&lt;0.01) and anxiety (55.6% vs. 4.7%; p&lt;0.01), and to have a history of suicidality (18.75% vs. 0.00%; p&lt;0.01). Conclusions: Compared to PTSD- veterans with prostate cancer, PTSD+ patients were more likely to self-report increased symptoms of depression, anxiety, and pain as well as overall poorer mental health status. Further research is warranted to identify opportunities to improve mental health care for PTSD+ veterans with prostate cancer. [Table: see text]
Clinical outcomes of FOLFIRINOX and gemcitabine/nab-paclitaxel in the real world setting.
Authors: Fernando Franco Franco, Camara Juan C, Jose Ignacio Martin Valades, David Marrupe, David Gutierrez Abad, Ana Leon, Ignacio Juez, Maria Victoria De Torres, Antonio Carlos Sánchez-Ruiz, Elsa Bernal, Silvia Garcia Adrian, Diana Moreno, Ana Cardena, Roberto Hernández, Ana Ruiz-Casado
Journal: Journal of Clinical Oncology (2018)

440 Background: The incidence of pancreatic cancer is increasing in developed countries. Though FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GNP) are associated with increased toxicity and are addressed to a well selected population, there seems to have been a rapid incorporation of these regimens in the real world. Overall survival (OS) was 11.1 months for FFX and 8.5 months for GNP. Survival rate at 18 m with FFX was 18.6%; at 24 m with GNP was 9%. Questions have arisen about external validity of original trials and how could these regimens impact overall survival since they are available nowadays for second line settings. Methods: This is a retrospective study. The Departments of Pharmacy of 5 Spanish hospitals generated the listings of patients (pts) treated in first line with the new regimens, namely FFX or GNP. To avoid bias related to non-prospective data collection, we restricted the analysis to survival data, serious toxicity and 2nd line options. Results: From Jan 2012 to Dec 2016, a total of 136 pts (M/F 52/48 %) were treated. Med age 63 y (38-83 y), 95% adenocarcinoma. 48% head of pancreas. ECOG 88% 0-1. 36 % locally advanced and 64% metastatic. 88% had liver mets. In the 1st line 64% were treated with FFX and 36% with GNP. 5 (3,7%) pts died in the first 3 months of treatment, because of infectious complications. 16 pts were operated after chemotherapy. 60% of the pts could receive a 2nd line (43% GNP, 25% FFX, 32% other). 27 pts (19.8%) were treated with a 3rd line. More pts treated with FFX required G-CSF (85% vs 15%). The median OS was 13 months with no differences between regimens. Survival rate at 30 months was 25% for both regimens. Elevated Ca 19.9 levels and Neutrophil-Lymphocyte ratio (NLR) increased the risk of death during the first-line. Conclusions: Originally reported OS is not only reproduced but improved in the real world despite a less strict inclusion of pts. 25% of patients remain alive 30 months after diagnosis. Superiority could not be demonstrated for any of the schemes. The availability of both regimens seems to dilute the potential differences and it is not so important the election of the 1st line. Both NLR and Ca 19.9 level predicted risk of death during the 1st line impairing the possibility of being treated in 2nd line.
Bedside Computer Vision — Moving Artificial Intelligence from Driver Assistance to Patient Safety
Authors: Serena Yeung, N. Lance Downing, Li Fei-Fei, Arnold Milstein
Journal: New England Journal of Medicine (2018)

Computer vision, a rapidly progressing domain of artificial intelligence, may ultimately permit further improvement in patient safety. Researchers have been testing an AI-based system for detecting deviations from such essential behavior as maintaining hand hygiene.
Abstract 15472: Midkine Contributes the Development of Pulmonary Arterial Hypertension via Cell Surface Nucleolin
Authors: Daisuke Kinoshita, Tetsuro Shishido, Tetsuya Takahashi, Miyuki Yokoyama, Satoshi Nishiyama, Hiroki Takahashi, Takanori Arimoto, Takuya Miyamoto, Tetsu Watanabe, Tsuneo Konta, Kenji Kadomatsu, Yasuchika Takeishi, Isao Kubota
Journal: Circulation (2016)

Background:  Pulmonary arterial hypertension (PAH) is a progressive and fatal disease caused by pulmonary arterial remodeling. Midkine is a multifunctional growth factor which regulates cell growth and migration. Hypoxia induces midkine expression in the lung; however the role of midkine on the pathogenesis of pulmonary arterial remodeling remains to be elucidated.   Methods and Results:  Chronic hypoxia upregulated midkine expressions in the lung, and induced pulmonary arterial remodeling in wild type (WT) mice. Pulmonary arterial remodeling and right heart hypertrophy were significantly ameliorated in midkine knockout (Mdk -/- ) mice comparted with WT mice. In vitro, midkine exposure strongly enhanced the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) induced by hypoxia. Importantly, hypoxia caused translocation of nucleolin, which functioned as a receptor of midkine, from cytosol to membrane. Silencing of low density lipoprotein receptor-related protein 1 (LRP1) or the use of nucleolin inhibitor, AS1411, attenuated the surface translocation of nucleolin, resulting in the suppression of the midkine-induced phosphorylation of extracellular signal-regulated kinase 1/2, migration and proliferation of PASMCs. To confirm the association between midkine and nucleolin in vivo, Sugen5416-hypoxia induced PAH rats were treated with AS1411. AS1411 significantly decreased right ventricular systolic pressure, pulmonary arterial remodeling, and right heart hypertrophy.   Conclusions:  These results indicate that midkine play a crucial role of development of PAH through the surface nucleolin.
Commitment enforcement also explains shamanism's culturally shared features
Authors: Stefan Linquist
Journal: Behavioral and Brain Sciences (2018)

Abstract The proposed explanation for the evolution of shamanism is not the only viable option. I sketch an alternative commitment hypothesis that views shamanism as an adaptation at the level of biological individuals or cultural groups. To the extent that these hypotheses make overlapping predictions about the culturally shared features of shamanism, we lack adequate evidence to discriminate among them.
Impaired Recovery of Left Ventricular Function in Patients With Cardiomyopathy and Left Bundle Branch Block (vol 71, pg 306, 2018)
Authors: BD Atwater, KB Campbell, K Chiswell, JP Daubert, A Dunning, Joseph Andrew Kisslo, Z Loring, Zainab Samad, E Sze, Eric J Velazquez
Journal: Journal of the American College of Cardiology (2018)
The receptor repertoire and functional profile of follicular T cells in HIV-infected lymph nodes
Authors: Ben S. Wendel, Daniel del Alcazar, Chenfeng He, Perla M. Del Río-Estrada, Benjamas Aiamkitsumrit, Yuria Ablanedo-Terrazas, Stefany M. Hernandez, Ke-Yue Ma, Michael R. Betts, Laura Pulido, Jun Huang, Phyllis A. Gimotty, Gustavo Reyes-Terán, Ning Jiang, Laura F. Su
Journal: Science Immunology (2018)

Follicular helper CD4+ T cells (TFH) play an integral role in promoting B cell differentiation and affinity maturation. Whereas TFH cell frequencies are increased in lymph nodes (LNs) from individuals infected with HIV, humoral immunity remains impaired during chronic HIV infection. Whether HIV inhibits TFH responses in LNs remains unclear. Advances in this area have been limited by the difficulty of accessing human lymphoid tissues. Here, we combined high-dimensional mass cytometry with T cell receptor repertoire sequencing to interrogate the composition of TFH cells in primary human LNs. We found evidence for intact antigen-driven clonal expansion of TFH cells and selective utilization of specific complementarity-determining region 3 (CDR3) motifs during chronic HIV infection, but the resulting TFH cells acquired an activation-related TFH cell signature characterized by interleukin-21 (IL-21) dominance. These IL-21+ TFH cells contained an oligoclonal HIV-reactive population that preferentially accumulated in patients with severe HIV infection and was associated with aberrant B cell distribution in the same LN. These data indicate that TFH cells remain capable of responding to HIV antigens during chronic HIV infection but become functionally skewed and oligoclonally restricted under persistent antigen stimulation.