tbuckley/cabot-search huggingface dataset:
Reply
Authors: Elisabetta Bacchi, Carlo Negri, Giovanni Targher, Massimo Lanza, Federico Schena, Paolo Moghetti
Journal: Hepatology (2013)

We thank Pesta and Burtscher for their comments on our study. In this article, we have demonstrated, for the first time, that 4 months of resistance (RES) or aerobic (AER) training are equally effective in reducing hepatic fat content among sedentary type 2 diabetes subjects with nonalcoholic fatty liver disease (NAFLD).1 This study was a subproject of the RAED2 Study, a randomized, controlled trial aimed at comparing the metabolic effects of RES and AER training in diabetic patients.2 Pesta and Burtscher hypothesized that in untrained overweight/obese subjects with little experience in exercise, RES training would be unable to induce the specific adaptations characteristic of this exercise modality, and that this, in turn, might explain why the results of AER and RES training were similar. We agree that, in untrained subjects, there may be some overlap between the effects of AER and RES training, and that the full-blown effects of these different exercise modalities can be only appreciated when sustained high-intensity training is performed, as occurs in athletes. Nonetheless, the latter would not be an appropriate model for assessing the effects of these training modalities on hepatic fat accumulation of sedentary subjects with type 2 diabetes, which was the aim of our study. Moreover, as reported previously,2 in our study, peak oxygen uptake improved after training in both groups, but to a greater extent in the AER group, whereas increased strength was found only in the RES group. In addition, lean mass of the limbs significantly increased in the RES group, but not in the AER group. These findings clearly indicate that the stimulus was quite different between the two protocols. These differences were guaranteed through a careful supervision of exercise sessions as well as a progressive increase of workload. In particular, as concerns the RES group, workload was gradually increased to 70%-80% 1-RM, with the weight being adjusted approximately every 2 weeks to match the progress of the subjects. With regard to baseline data, there were not statistically significant differences between groups. Overall, most type 2 diabetes patients are sedentary and have no experience with exercise programs. The clinical message that we were able to give is that exercise alone can provide benefit for NAFLD management in these patients, and that, after 4 months of training, RES exercise is as effective as AER exercise in reducing hepatic fat content in these subjects. Future research should address this important issue in the long term. Elisabetta Bacchi, Ph.D.1 Carlo Negri, M.D.1 Giovanni Targher, M.D.1 Massimo Lanza, M.Sc.2 Federico Schena, M.D., Ph.D.2 Paolo Moghetti, M.D., Ph.D.1 1Unit of Endocrinology, Diabetes and Metabolism Department of Medicine 2Neurological, Neuropsychological, Morphological and Movement Sciences University of Verona Verona, Italy
PREVALENCE OF ACETABULAR LABRAL TEARS IN ASYMPTOMATIC YOUNG ATHLETES
Authors: Karen Briggs, Marc Philippon, Charles Ho, Shannen McNamara
Journal: British Journal of Sports Medicine (2017)

Background Youth sport injuries are on the rise. These injuries at an early age may prevent young people from continuing with sports or eventually limit their ability to participate in physical activity. Objective The purpose of this study was to determine the prevalence of acetabular labral tears in athletes 19 years of age or younger who compete in a club sport. Design Screening Program. Setting Youth sports. Patients (or Participants) 101 (93 males, 8 females) skiers (20) and hockey players (81) with no symptoms around the hip, no history of hip injury or surgery, and parental consent. Average age was 15 (range 11 to 19) years. Interventions (or Assessment of Risk Factors) Participants completed an initial questionnaire and had a clinical exam (hip range of motion, impingement test, hip dial test, FABER distance test). All participants had 3T MRI of dominant hip. Main Outcome Measurements Positive exam findings and labral tear on MRI. Results Labral tears were identified in 70 hips. Average alpha angle was 59 degrees. 89% of the participants 16 years of age or older had labral tears and 56% of the participants 16 years of younger had labral tears. Participants 16 years of older were 7 times more likely to have a labral tear [95% CI: 1.9 to 28] than participants under the age of 16. Participants who had participated in their sport 9 years or greater were 4.9 times more likely to have a labral tear [95% CI: 1.5 to 16.1] compared to participants who had participated less than 9 years. Conclusions This study also showed a high prevalence of labral tears in the asymptomatic young athlete. Patients who were older and participated in their sport longer had increased risk of a labral tear. Limiting certain at risk movements when the young athlete is growing has potential for prevention.
Inducible MyD88/CD40 (iMC) Enhances Proliferation and Survival of Tumor-Specific TCR-Modified T Cells and Improves Anti-Tumor Efficacy in Myeloma
Authors: Tsvetelina Pentcheva-Hoang, David Torres, Tania Rodriguez, Ana Korngold, An Lu, Jeannette Crisostomo, Annemarie Moseley, Lorenz Jahn, Mirjam H.M. Heemskerk, Kevin M Slawin, David M Spencer, Aaron E Foster
Journal: Blood (2016)
Complementary and integrative medicine in the management of headache
Authors: Denise Millstine, Christina Y Chen, Brent Bauer
Journal: BMJ (2017)

Headaches, including primary headaches such as migraine and tension-type headache, are a common clinical problem. Complementary and integrative medicine (CIM), formerly known as complementary and alternative medicine (CAM), uses evidence informed modalities to assist in the health and healing of patients. CIM commonly includes the use of nutrition, movement practices, manual therapy, traditional Chinese medicine, and mind-body strategies. This review summarizes the literature on the use of CIM for primary headache and is based on five meta-analyses, seven systematic reviews, and 34 randomized controlled trials (RCTs). The overall quality of the evidence for CIM in headache management is generally low and occasionally moderate. Available evidence suggests that traditional Chinese medicine including acupuncture, massage, yoga, biofeedback, and meditation have a positive effect on migraine and tension headaches. Spinal manipulation, chiropractic care, some supplements and botanicals, diet alteration, and hydrotherapy may also be beneficial in migraine headache. CIM has not been studied or it is not effective for cluster headache. Further research is needed to determine the most effective role for CIM in patients with headache.
Danger signals in regulating the immune response to solid organ transplantation
Authors: Jamie L. Todd, Scott M. Palmer
Journal: Journal of Clinical Investigation (2017)

Endogenous danger signals, or damage-associated molecular patterns (DAMPs), are generated in response to cell stress and activate innate immunity to provide a pivotal mechanism by which an organism can respond to damaged self. Accumulating experimental and clinical data have established the importance of DAMPs, which signal through innate pattern recognition receptors (PRRs) or DAMP-specific receptors, in regulating the alloresponse to solid organ transplantation (SOT). Moreover, DAMPs may incite distinct downstream cellular responses that could specifically contribute to the development of allograft fibrosis and chronic graft dysfunction. A growing understanding of the role of DAMPs in directing the immune response to transplantation has suggested novel avenues for the treatment or prevention of allograft rejection that complement contemporary immunosuppression and could lead to improved outcomes for solid organ recipients.
Where the psychological adaptations hit the ecological road
Authors: Peter K. Jonason, David P. Schmitt
Journal: Behavioral and Brain Sciences (2017)

Abstract We argue that the target authors focus too much on adaptive behavioral responses and not enough on actual psychological adaptations . We suggest the Dark Triad traits may represent facultative, psychological adaptations sensitive to seasonal variance and food shortages. We document that shorter distances from the equator are linked to higher national narcissism levels, whereas longer distances are associated with higher national-level machiavellianism. Dark Triad traits may serve as critical survival mechanisms when prioritizing oneself over and/or at the cost of others.
PWE-286 Direct serum markers are more accurate than simple marker panels for the detection of fibrosis in non-alcoholic fatty liver disease (NAFLD): Abstract PWE-286 Table 1
Authors: S Tanwar, P M Trembling, D Thorburn, I N Guha, J Parkes, P Kaye, A Burt, S D Ryder, G Aithal, C Day, W M Rosenberg
Journal: Gut (2012)

<h3>Introduction</h3> The identification of fibrosis in patients with NAFLD is important for ascertaining prognosis and stratifying patients for emerging therapeutic interventions. Use of both direct marker panels (liver matrix components) and indirect marker panels (simple biochemical tests) have been described for the detection of fibrosis in NAFLD. The aim of this study was to compare the performance of direct and indirect serum marker panels in the detection of fibrosis in NAFLD as compared with liver biopsy. <h3>Methods</h3> From two centres, 177 patients were recruited and underwent percutaneous liver biopsy. Fibrosis staging was assessed using Kleiner criteria by two senior liver-histopathologists. Serum at the time of biopsy was used to calculate six indirect marker panels of fibrosis (APRI, BAAT, BARD, Cirrhosis discriminate score, NAFLD fibrosis index and Fib4). These panels were compared with the ELF Test (HA, TIMP1, PIIINP) and HA alone. Diagnostic accuracy was assessed using receiver operating characteristic curves which were compared using the method of DeLong. <h3>Results</h3> The distribution of fibrosis stages in the cohort were as follows: F0 39.5% (n=70), F1 19.2% (n=34), F2 17.5% (n=31), F3 13.6% (n=24), F4 10.2% (n=18). While ELF and HA alone had the best performance overall, the ELF test was better than HA in its ability to discriminate minimal fibrosis (p=0.02) and cirrhosis (p=0.06). All indirect serum markers tested had significantly worse performance than ELF in the detection of cirrhosis (p&lt;0.05). <h3>Conclusion</h3> In patients with NAFLD, direct serum marker panels have superior performance compared to indirect marker panels allowing superior stratification and prognostication. The performance of HA alone is enhanced by the addition of PIIINP and TIMP1. <h3>Competing interests</h3> None declared.
Secondary Adrenal Insufficiency Is Associated with Poor Survival Outcomes in Multiple Myeloma
Authors: Seo-Yeon Ahn, Sung-Hoon Jung, Hee Kyung Kim, Ho-Cheol Kang, Deok-Hwan Yang, Seung-Shin Lee, Jae-Sook Ahn, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Je-Jung Lee
Journal: Blood (2016)
Lessons to be Learned From 22q2.11 Syndromes—Reply
Authors: Louise K. Hoeffding, Carsten B. Pedersen, Thomas Werge
Journal: JAMA Psychiatry (2017)

In Reply We are grateful to Vann Jones for his interest and most relevant commentary to our populationwide study on the risk of psychiatric disorders among individuals with the 22q11.2 deletion and duplication.1
Expansion of Tumor-Infiltrating CD8+ T cells Expressing PD-1 Improves the Efficacy of Adoptive T-cell Therapy
Authors: Sarita M. Fernandez-Poma, Diego Salas-Benito, Teresa Lozano, Noelia Casares, Jose-Ignacio Riezu-Boj, Uxua Mancheño, Edurne Elizalde, Diego Alignani, Natalia Zubeldia, Itziar Otano, Enrique Conde, Pablo Sarobe, Juan Jose Lasarte, Sandra Hervas-Stubbs
Journal: Cancer Research (2017)

Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1+ TILs can be used in adoptive T-cell therapy (ACT). However, no study thus far has evaluated the antitumor activity of PD-1-selected TILs in vivo In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TILs without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TILs before expansion, only T-cell products derived from sorted PD-1+, but not from PD-1- or bulk CD8 TILs, specifically recognized tumor cells. The fold expansion of PD-1+ CD8 TILs was 10 times lower than that of PD-1- cells, suggesting that outgrowth of PD-1- cells was the limiting factor in the tumor specificity of cells derived from bulk CD8 TILs. The highly differentiated state of PD-1+ cells was likely the main cause hampering ex vivo expansion of this subset. Moreover, PD-1 precisely identified marrow-infiltrating, myeloma-specific T cells in a mouse model of multiple myeloma. In vivo, only cells expanded from PD-1+ CD8 TILs contained tumor progression, and their efficacy was enhanced by PDL-1 blockade. Overall, our data provide a rationale for the use of PD-1-selected TILs in ACT. Cancer Res; 77(13); 3672-84. ©2017 AACR.
Authors’ reply to Colquhoun and Buchinsky
Authors: Jason M R Gill, Carlos A Celis-Morales, Naveed Sattar, Jill P Pell
Journal: BMJ (2017)

Colquhoun makes an important comment about reverse causality in our study of active commuting.12 We excluded people with reported prevalent disease at baseline but cannot exclude the possibility that including those with subclinical or undiagnosed disease at baseline could have influenced the findings. In the manuscript we originally submitted we simply considered two groups of commuters—active and non-active. We tried to minimise the potential contribution of reverse causality by undertaking a sensitivity …
Sex and drugs and rock and roll
Authors: Martin McKee
Journal: BMJ (1999)

Papers p 1321 

In this week's BMJ Nicoll et al describe how, on a wide range of indicators, the sexual health of adolescents in England and Wales worsened between 1995 and 1996 (p 1321).1 Even before this deterioration there were considerable grounds for concern as the United Kingdom had the highest teenage pregnancy rate in western Europe, with birth rates among 15-19 year olds seven times those in the Netherlands,2 where, although rates of adolescent sexual activity are comparable, contraceptive use is much more common.3 What is especially worrying is that it is not only in sexual health that British teenagers to do rather worse than their continental counterparts.

Before Christmas the European Drugs Monitoring Centre reported that British teenagers were more likely to have used all categories of illicit drugs than were their counterparts in any other European Union country.4 Cross-European surveys show that 15 year old boys living in Wales and …
Abstract 379: Inhibition of Bcl-x Phosphorylation Prevents Cardiomyocyte Death, Cardiac Remodeling and Heart Failure After Myocardial Infarction
Authors: Michinari Nakamura, Peiyong Zhai, Dominic D Re, Junichi Sadoshima
Journal: Circulation Research (2015)

Cardiac remodeling promotes heart failure (HF). Cardiomyocyte (CM) death is one of the mechanisms to develop cardiac remodeling. We recently reported that Mst1 phosphorylates Bcl-xL at Ser14, which promotes apoptosis by inducing dissociation of Bcl-xL from Bax and consequent activation of Bax in CMs. Its phosphorylation is increased in response to ischemia-reperfusion (IR) in an Mst1-dependent manner. However, the functional significance of endogenous Bcl-xL phosphorylation remains unclear in vivo. To address this question, knock-in (KI) mice with alanine mutation at Ser14 in Bcl-x were generated. At baseline, cardiac function was similar between wild-type (WT) and heterozygous KI (HKI) mice (EF 76% and 79%, respectively). HKI mice exhibited smaller % infarct area (30%) than WT (43%) (p=0.016) upon IR, suggesting that phosphorylation of endogenous Bcl-xL at Ser14 plays an essential role in mediating IR injury. In order to test the role of Bcl-xL phosphorylation in the development of HF, HKI and WT mice were subjected to permanent ligation of LAD for 4 weeks. During progression of cardiac remodeling, Mst1 was activated in both WT and HKI mice. Phosphorylation of Bcl-xL and Bcl-xS, an alternative transcriptional variant of Bcl-x, both at Ser14, were increased in WT mice, which were abrogated in HKI mice. The infarct area evaluated with TTC staining at Day 1 was similar in WT and HKI mice (59.1% and 61.2%, p=0.65). Four weeks after myocardial infarction (MI), WT mice exhibited lower cardiac contraction (EF 46.5%) and higher LVEDP (10.8mmHg) than those in HKI mice (EF 68.9% and LVEDP 7.0mmHg) (both p&lt;0.05). Scar area and TUNEL-positive CMs were greater in WT (49.0% and 1.6%, respectively) than in HKI mice (29.2% and 0.4%, respectively) (both p&lt;0.05). Cleaved caspase 3 and 9 were significantly increased (3.2- and 5.7-fold, respectively) in WT but not in HKI mice. In vitro experiments with overexpression of phospho-mimicking mutant (Bcl-xS-S14D) showed 13% reduction in cell viability compared with that of phospho-resistant mutant (Bcl-xS-S14A) (p=0.01%). Our results suggest that phosphorylation of Bcl-xL and Bcl-xS at Ser14 contributes to CM death in response to IR and chronic MI in vivo, thereby promoting cardiac remodeling and HF.
Ki67 labelling index and performance status are predictive factors of response to concomitant radiochemotherapy (RCT) in esophageal cancer
Authors: J. F. Seitz, L. Dahan, E. Ressiot, A. Liprandi, R. Giorgi, X. B. D’journo, L. Padovani, S. Alibert, P. Ries, P. A. Thomas
Journal: Journal of Clinical Oncology (2007)

15119 Background: In oesophageal cancer, preoperative RCT allows a prolonged survival for patients achieving a complete pathological response at time of surgery. However, predictive factors for complete response to RCT are not well known. The aim of this retrospective study was to identify clinical and histopathological factors predictive of complete endoscopic response (CER) in patients treated by RCT before surgery or as exclusive treatment for esophagus cancer. Methods: from 2000 september to 2006 march, 56 patients with esophagus cancer (35 squamous cell carcinoma (SCC), 20 adenocarcinoma (ADK), 1 undifferentiated) were treated by RCT (45–50 grays /25 fractions / 5 weeks and 2 courses of 5FU-CDDP at weeks 1 and 5). 16 patients subsequently underwent oesophageal resection. Endoscopy with biopsies was performed 3 weeks after the end of RCT. Clinical, biological, radiological and pathological (including EGFR, p53 and Ki67 immunostaining) parameters were included in univariate and multivariate analysis to determine predictive factors for CER. Results: CER was observed in 31 out of 54 appraisable patients (57.4%). In both univariate and multivariate analysis, 2 factors were predictive of complete endoscopic response: good performance status (PS 0 vs 1–2: OR = 15.75 - p=0.01) and higher expression of Ki67 (&gt;=18 vs &lt;18: OR = 4.46 - p=0.04).A pCR was seen in 7 (44%) of the 16 operated patients. Positive predictive value of endoscopy for pCR was 87.5% (IC95%: 47.4–99.7%), and negative predictive value was 100% (IC95%: 68.7–100%). Predictive factors of pCR were: a complete endoscopic response (p&lt;0.01), a complete CT-scan response (p=0.03) and a good performance status (p=0.04). Median survival in all 56 patients was 40 months. Pejorative prognostic variables for survival in multivariate analysis were adenocarcinoma histology (RR=3.11; p=0.03), and performance status (RR=4.79; p=0.04). Conclusions: In our study, a good performance status and surexpression of Ki67 were independent predictive factors for complete endoscopic response after RCT. The 2 prognostic factors for survival are histologic type and performance status. No significant financial relationships to disclose.
Androgen Receptor Supports an Anchorage-Independent, Cancer Stem Cell-like Population in Triple-Negative Breast Cancer
Authors: Valerie N. Barton, Jessica L. Christenson, Michael A. Gordon, Lisa I. Greene, Thomas J. Rogers, Kiel Butterfield, Beatrice Babbs, Nicole S. Spoelstra, Nicholas C. D'Amato, Anthony Elias, Jennifer K. Richer
Journal: Cancer Research (2017)

Abstract Preclinical and early clinical trials indicate that up to 50% of triple-negative breast cancers (TNBC) express androgen receptor (AR) and are potentially responsive to antiandrogens. However, the function of AR in TNBC and the mechanisms by which AR-targeted therapy reduces tumor burden are largely unknown. We hypothesized that AR maintains a cancer stem cell (CSC)-like tumor-initiating population and serves as an antiapoptotic factor, facilitating anchorage independence and metastasis. AR levels increased in TNBC cells grown in forced suspension culture compared with those in attached conditions, and cells that expressed AR resisted detachment-induced apoptosis. Culturing TNBC cells in suspension increased the CSC-like population, an effect reversed by AR inhibition. Pretreatment with enzalutamide (Enza) decreased the tumor-initiating capacity of TNBC cells and reduced tumor volume and viability when administered simultaneously or subsequent to the chemotherapeutic paclitaxel; simultaneous treatment more effectively suppressed tumor recurrence. Overall, our findings suggest that AR-targeted therapies may enhance the efficacy of chemotherapy even in TNBCs with low AR expression by targeting a CSC-like cell population with anchorage independence and invasive potential. Cancer Res; 77(13); 3455–66. ©2017 AACR.