tbuckley/cabot-search huggingface dataset:
Abstract 12631: Peripheral Gamma-aminobutyric Acid(gaba) Signaling in Brown Adipose Tissue Induces Metabolic Dysfunction in Obesity
Authors: Ryutaro Ikegami, Ippei Shimizu, Takeshi Sato, Shuang Jiao, Yohko Yoshida, Masayoshi Suda, Yuka Hayashi, Goro Katsuumi, Hiromi Kayamori, Tohru Minamino
Journal: Circulation (2015)

Accumulating evidence suggests that adult humans possess active brown adipose tissue (BAT) that may contribute significantly to systemic metabolism because of its high energy consumption capacity. Recently, we demonstrated that metabolic stress induced BAT hypoxia and impaired mitochondrial function, leading to the development of BAT “whitening” and systemic metabolic dysfunction in murine obese models. Various neurotransmitters are known to be involved in the maintenance of BAT homeostasis. Among them, the gamma-aminobutyric acid (GABA) signaling in the central nervous system is well accepted to have anti-obesity effects through the activation of the sympathetic nervous system. Here we show the previously unknown role of peripheral GABA signaling in the development of systemic metabolic dysfunction in obesity. We generated an obese model by imposing a high fat/high sucrose (HFHS) diet on C57BL/6NCr mice. Mass spectrometry analysis demonstrated a significant increase in GABA level in BAT of the dietary obese model. Addition of GABA into drinking water induced BAT whitening, reduced the thermogenic response upon cold tolerance test, and promoted systemic metabolic dysfunction in the obese mice. Mitochondrial calcium is important for the maintenance of mitochondrial homeostasis, whereas calcium overload is reported to inhibit mitochondrial function. Treatment of BAT cells with GABA markedly increased mitochondrial calcium level, promoted the production of reactive oxygen species (ROS), and inhibited mitochondrial respiration. These results indicate that peripheral GABA contributes to the development of systemic metabolic dysfunction by inhibiting BAT function in obesity. The inhibition of peripheral GABA signaling would become a new therapeutic target for obesity and diabetes.
Genome-Wide Association Study (GWAS) of High-Risk Minimal Residual Disease and Relapse in B-Cell Acute Lymphoblastic Leukemia on Trial AIEOP-BFM ALL 2000
Authors: Laura Hinze, Stefanie V. Junk, Norman Klein, Anja Moricke, Gunnar Cario, Christian P. Kratz, Richard S Houlston, Claus R Bartam, Rolf Koehler, Martin Zimmermann, Martin Schrappe, Martin Stanulla
Journal: Blood (2017)
Phase 1 Study of TAK-659, an Investigational Reversible Dual SYK/FLT-3 Inhibitor, in Patients (Pts) with Lymphoma: Updated Results from Dose-Escalation and Expansion Cohorts
Authors: Jason Kaplan, Leo I. Gordon, Alessandro Rambaldi, Giuseppe Gritti, Rakesh Popat, Howard A. Burris, Manish R Patel, Sumit Madan, Ian Chau, John A. Radford, Swami P. Iyer, Jaime Perez De Oteyza, Pier Luigi Zinzani, Shining Wang, Emily Sheldon-Waniga, Kate Stumpo, Yaping Shou, Cecilia Carpio, Francesc Bosch
Journal: Blood (2017)
miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a
Authors: Man-Qing Cao, A-Bin You, Xiao-Dong Zhu, Wei Zhang, Yuan-Yuan Zhang, Shi-Zhe Zhang, Ke-wei Zhang, Hao Cai, Wen-Kai Shi, Xiao-Long Li, Kang-Shuai Li, Dong-Mei Gao, De-Ning Ma, Bo-Gen Ye, Cheng-Hao Wang, Cheng-Dong Qin, Hui-Chuan Sun, Ti Zhang, Zhao-You Tang
Journal: Journal of Hematology & Oncology (2018)

High frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown. Real-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression. We showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3′-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a. Consistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.
The E3 ligase tripartite motif 8 targets TAK1 to promote insulin resistance and steatohepatitis
Authors: Feng‐Juan Yan, Xiao‐Jing Zhang, Wen‐Xin Wang, Yan‐Xiao Ji, Pi‐Xiao Wang, Yang Yang, Jun Gong, Li‐Jun Shen, Xue‐Yong Zhu, Zan Huang, Hongliang Li
Journal: Hepatology (2016)

Tripartite motif 8 (TRIM8), an E3 ligase ubiquitously expressed in various cells, is closely involved in innate immunity. However, its role in nonalcoholic steatohepatitis is largely unknown. Here, we report evidence that TRIM8 is a robust enhancer of steatohepatitis and its complications induced by a high‐fat diet or a genetic deficiency ( ob/ob ). Using gain‐of‐function and loss‐of‐function approaches, we observed dramatic exacerbation of insulin resistance, hepatic steatosis, inflammation, and fibrosis by hepatocyte‐specific TRIM8 overexpression, whereas deletion or down‐regulation of TRIM8 in hepatocytes led to a completely opposite phenotype. Furthermore, investigations of the underlying mechanisms revealed that TRIM8 directly binds to and ubiquitinates transforming growth factor‐beta–activated kinase 1, thus promoting its phosphorylation and the activation of downstream c‐Jun N‐terminal kinase/p38 and nuclear factor κB signaling. Importantly, the participation of TRIM8 in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis was verified on the basis of its dramatically increased expression in the livers of these patients, suggesting a promising development of TRIM8 disturbance for the treatment of nonalcoholic steatohepatitis–related metabolic disorders. Conclusion : The E3 ligase TRIM8 is a potent regulator that exacerbates steatohepatitis and metabolic disorders dependent on its binding and ubiquitinating capacity on transforming growth factor‐beta–activated kinase 1. (H epatology 2017;65:1492‐1511)
Household-Contact Investigation for Detection of Tuberculosis in Vietnam
Authors: Greg J. Fox, Nguyen V. Nhung, Dinh N. Sy, Nghiem L.P. Hoa, Le T.N. Anh, Nguyen T. Anh, Nguyen B. Hoa, Nguyen H. Dung, Tran N. Buu, Nguyen T. Loi, Le T. Nhung, Nguyen V. Hung, Phan T. Lieu, Nguyen K. Cuong, Pham D. Cuong, Jessica Bestrashniy, Warwick J. Britton, Guy B. Marks
Journal: New England Journal of Medicine (2018)

Active case finding is a top priority for the global control of tuberculosis, but robust evidence for its effectiveness in high-prevalence settings is lacking. We sought to evaluate the effectiveness of household-contact investigation, as compared with standard, passive measures alone, in Vietnam.
Restricted overexpression of p53 immunohistochemistry (p53IHC RO) as prognostic after colorectal cancer (CRC) resection.
Authors: Marc Van Den Eynde, Ha Molinh Le, Christine Nyiraneza, Alex Kartheuser, Roger Detry, Yves Humblet, Daniel Leonard, Christophe Remue, Karin Dahan, Aline Van Maanen, Anne Jouret-Mourin, Christine Sempoux
Journal: Journal of Clinical Oncology (2014)

e14602 Background: p53IHC RO was previously described as a distinct pattern from the negative or diffuse p53 IHC expression. p53IHC RO is characterized by a limited number of homogenously scattered strongly positive CRC cells and is associated with some clinico-pathologic CRC feature. The prognostic impact of p53IHC RO remains unknown. Methods: p53 and MMR (MLH1, MSH2, MSH6 and PMS2) proteins IHC expression were performed on CRC primary tumors from an unselected cohort of patients who underwent surgery at the Cliniques St-Luc between 1995 and 2000. p53 IHC results were defined as negative, diffuse or restricted expression. Clinico-pathologic CRC characteristics and patients follow-up were available for this analysis. Comparisons of numerical and categorical clinico-pathological data were evaluated respectively by ANOVA and Fisher exact tests between p53 expression groups. Progression-Free Survival (PFS) and Overall Survival (OS) analyses were performed using Kaplan-Meier method and compared with the log-rank test (Bonferroni correction applied for multiplicity). Uni and multivariate PFS and OS regression were performed using a Cox Proportional Hazard model. Results: Among 100 CRCs (99 patients), p53 IHC expression was categorized as restricted (n=36), diffuse (n= 46) or negative (n=18). p53IHC RO (total n=36, defective MMR n=20, proficient MMR n=16) was associated with age (≥60y), proximal location, poor differentiated CRC, and a lowest lymph node ratio (LNR) (p<0.05). Among the analysed defective MMR CRCs, 20/24 was p53IHC RO (p<0.001). After a mean follow-up of 13 years after CRC resection, median PFS and OS were significantly higher in the p53IHC RO group as compared with the diffuse and negative p53 IHC expression (median PFS respectively not reached vs 40.9 vs 22.8 months, p<0.001 and median OS respectively not reached vs 70.7 vs 48.0 months, p=0.009). LNR, synchronous metastases and p53IHC RO were significantly associated with a better PFS in multivariate analysis (p<0.05). Conclusions: p53IHC RO is a prognostic factor after CRC resection. These results must be confirmed on a larger cohort but could be clinically relevant for prognosis.
Umbilical cord blood transplantation without in vivo T-cell depletion for children with MHC class II deficiency
Authors: Reem Elfeky, Juliana M. Furtado-Silva, Robert Chiesa, Kanchan Rao, Giovanna Lucchini, Persis Amrolia, Austen Worth, Bobby Gaspar, Waseem Qasim, Paul Veys
Journal: Journal of Allergy and Clinical Immunology (2018)
PT and OT Helper Golf Elbow: a mobile app user guide for getting a grip on medial epicondylalgia
Authors: Caitlin George, Crystal O Kean, Robert Stanton, Luke J Heales
Journal: British Journal of Sports Medicine (2018)

PT and OT Helper: Golf Elbow.

Health and fitness.

iOS V.8.0 or later; Android V.2.3 and up.

Apple iTunes $A12.99; Google Play $A10.99.

PT and OT Helper offers a number of injury-specific apps, including one targeted at golfer’s elbow (GE), a musculoskeletal condition associated with pain over the medial epicondyle.1 Consistent with other apps in the PT and OT Helper range, this user-friendly app (iOS version: 121 MB; and Android version: 95.1 MB) provides a bank of exercises designed to assist clinicians and patients in the treatment of GE. Although lacking evidence from randomised controlled trials,2 the app includes 17 different exercises, consisting of specific wrist/forearm strengthening and stretching, as well as general upper limb strengthening exercises. Some exercises require additional equipment (eg, dumbbells, TheraBand Flexbar). In addition, the number of sets and repetitions, tempo (ie, repetitions/minute), duration, and level of resistance can be customised for each exercise for either the right and/or left arm. The clinician, in collaboration with the patient, can select appropriate exercises, based on clinical examination, to create an individualised exercise programme, which can be saved within the app as a ‘routine’. Each patient is first added as a ‘user’, and various routines can be …
Throw Like a Pro V.2.0 mobile app review
Authors: Anuruddh Kumar Misra, Rafael Escamilla, Narendra Nath Trivedi
Journal: British Journal of Sports Medicine (2018)

Throw Like a Pro V.2.0.

Abracadabra Health.

Health and fitness (injury prevention).

iPhone/iPad: requires iOS V.7.0 or later, tested on iOS V.10.3.2; Android: requires 4.0 or later, tested on Android V.7.0.

iPhone/iPad: $9.99.

In-App purchases:

All Star Bundle $4.99.

Throwers Ten $0.99.

Cool Down Stretches $0.99.

Dynamic Warmup $1.99.

Advanced Throwers Ten $1.99.

The primary clinical focus of the app is injury prevention, closely followed by enhancing pitching performance via best rehabilitation practices (ie, stretches, warm-up, cool-down, improving core strength). It is an easy-to-use app for all involved in baseball, from players to parents, to coaches, to medical professionals. The app interface is user-friendly and has four main categories: Overview, Pre Season, In Season and About. The videos are instructive and consistent with the type of care a pitcher would receive in a sports medicine clinic and in real-time games as with a physical therapist and/or athletic trainer. While ‘Tommy John’ (ulnar collateral ligament) injuries are unlikely to ever totally be eliminated, the goal is its absolute minimization.

The app tracks pitch …
Abstract 14239: Wall Stress-Mediated Rgs5 Expression in Vascular Smooth Muscle Cells Controls Arterial Remodeling During Hypertension
Authors: Caroline Arnold, Eda Demirel, Guillem Genové, Hangjun Zhang, Thomas Wieland, Markus Hecker, Scott Heximer, Thomas Korff
Journal: Circulation (2016)

The onset of hypertension is characterized by an increase in arterial wall stress which results in a compensatory remodeling of the vascular wall which ultimately leads to arterial stiffening. While G-protein signaling has been reported to control contraction and differentiation of vascular smooth muscle cells (VSMCs) in this context, the role of the regulators of G-protein signaling (RGS) has not been elucidated in detail. While earlier reports demonstrate that RGS5 regulates biomechanically induced arterial growth (arteriogenesis), we aimed at investigating the relevance of RGS5 for hypertension-induced VSMC responses. In vitro, exposing VSMCs to biomechanical stretch increased RGS5 protein abundance (3.2-fold, p<0.05, n=3). Likewise, RGS5 mRNA expression was augmented in isolated arteries in response to increased wall stress (1.7-fold, p<0.05, n=13). As evidenced by a whole genome microarray, overexpression of RGS5 under these conditions shifted the transcriptome towards expression of RhoA pathway-asso...
Effects of interferon on pancreatic cancer
Authors: Reza F. Saidi, Michael J. Jacobs
Journal: Cancer Research (2006)

4934  Introduction: Our previous study showed that expression of interferon receptors in patients with pancreatic cancer had prognostic value. Interferons (IFNs) have been known to possess an antiproliferative effect on tumor cells besides their well characterized antiviral effect in cell cultures. The mechanism of action of the different IFNs is not fully understood. The aims of the present study are to explore the antitumor effects of interferons (IFN) in pancreatic cancer in term of: (1) apoptosis, (b) sensitivity to current chemotherapeutic agents such as gemcitabine or 5-Fluorouracil (5-FU). Material and Methods: In the present study we examined the antiproliferative effect of IFN-alpha, -beta and -gamma on human pancreatic cancer cells (PANC-1, Capan-1, MIA-PaCa-2, BxPC-3) alone or combined with gemcitabine or 5-FU using (i) the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium tetrazolium bromide] cell survival assay and (ii) single strand DNA apoptosis assay. Cells were treated with different doses of above IFNs (500, 1000, 5000, 10000 IU/ml) for different period (24, 48, 72, and 96h) with or without gemcitabine or 5-FU to find the optimal effective dose and schedule. Expression of IFN receptor was determined using immunohistochemistry. Caspase-8 inhibitor (100-100,000 U/ml) was used to block the caspase cascade. Results: The pancreatic cancer cell lines differed markedly in their sensitivity to the IFNs tested based on the expression of IFN receptor. Both IFN-beta and IFN-gamma were found to have an antiproliferative and apoptotic effect on the growth of the cells which express the corresponding IFN receptor. IFN alpha had minimal effect on the cells. Overall, IFN beta was markedly more effective in antiproliferative effects than others. Capan-1 and BxPC-3 (not PANC-1 and MIA-PaCa-2) express the IFN receptor and underwent apoptosis. This effect was successfully block by adding caspase-8 inhibitor. In a cell survival assay, IFN gamma and beta at concentration that produced less than 1 log cell killing significantly increased the cytotoxic effects of 5-FU and gemcitabine in the cell lines which express the IFN alpha/beta or gamma receptor. Median effect analysis demonstrated that IFN beta and gamma exhibited synergy with the above agents only if the cell did express the corresponding IFN receptors. Conclusion: IFN’s cause apoptosis in pancreatic cancer cells through IFN receptor and caspase cascade. IFNs are capable of increasing the cytotoxic actions of 5-FU and gemcitiabine. This phenomenon depends on expression of IFN receptor in the cells. IFNs are potential candidate for biologic treatment of IFN receptor positive-pancreatic cancer.
Early Chemotherapy Intensification With Escalated BEACOPP in Patients With Advanced-Stage Hodgkin Lymphoma With a Positive Interim Positron Emission Tomography/Computed Tomography Scan After Two ABVD Cycles: Long-Term Results of the GITIL/FIL HD 0607 Trial
Authors: Andrea Gallamini, Corrado Tarella, Simonetta Viviani, Andrea Rossi, Caterina Patti, Antonino Mulé, Marco Picardi, Alessandra Romano, Maria Cantonetti, Giorgio La Nasa, Livio Trentin, Silvia Bolis, Davide Rapezzi, Roberta Battistini, Daniela Gottardi, Paolo Gavarotti, Paolo Corradini, Michele Cimminiello, Corrado Schiavotto, Guido Parvis, Roberta Zanotti, Guido Gini, Andrés J.M. Ferreri, Piera Viero, Maurizio Miglino, Atto Billio, Abraham Avigdor, Alberto Biggi, Federico Fallanca, Umberto Ficola, Michele Gregianin, Agostino Chiaravalloti, Giuseppe Prosperini, Fabrizio Bergesio, Stephane Chauvie, Chiara Pavoni, Alessandro Massimo Gianni, Alessandro Rambaldi
Journal: Journal of Clinical Oncology (2018)

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P &lt; .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD–negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.
Abstract 19276: Skeletal Muscle Index and Malnutrition in Children With End-Stage Heart Failure Awaiting Heart Transplant
Authors: Lisa M Schultz, David Larson, Jared Isaacson, Katelin Dennis, David N Rosenthal, John C Dykes, Esther Liu, Yulin Zhang, Doff B McElhinney, Christopher S Almond
Journal: Circulation (2017)

Introduction:  Malnutrition is an important complication of end-stage heart failure (HF) but is difficult to assess reliably in children because of fluid overload. In adults, CT has been used to measure muscle mass to assess muscle loss (sarcopenia), a method that is independent of fluid status.   Hypothesis:  Skeletal muscle index as defined by CT is lower for children with end-stage HF compared to age, gender and race-matched healthy controls.   Methods:  All children undergoing formal evaluation for heart transplant (HT) at Stanford University between 2013 and 2016 were identified using a hospital database. Skeletal Muscle Index (SMI) was calculated using a single CT plane at L-3 where the cross sectional area of the psoas muscle is measured. Malnutrition severity was defined using criteria adapted from the American Society for Parenteral and Enteral Nutrition (ASPEN). The Wilcoxon signed rank test was used to compare SMI between paired subjects and healthy controls matched for age, gender and race.   Results:  A total of 36 children who met the study eligibility criteria were included for analysis. Patients had a median age of 9 years (IQR, 4.7-13.4), a median weight of 21.6 kg (IQR, 13.9-34.4); and 86% had congenital heart disease (CHD). Overall, 17% met criteria for mild malnutrition, 33% for moderate malnutrition, 25% for severe malnutrition, while 25% were categorized as non-malnourished. Among those who were malnourished, SMI was significantly lower for children with HF than their matched non-malnourished normal controls (27 pairs, p   Conclusions:  Malnourished children with end-stage heart failure appear to have significantly lower skeletal muscle mass than healthy controls. Evaluation of sarcopenia using the skeletal muscle index appears to be a promising method to evaluate nutritional status objectively in children with end-stage heart failure that is independent of volume status.
Limited value of end-expiratory inferior vena cava diameter to predict fluid responsiveness impact of intra-abdominal pressure
Authors: Antoine Vieillard-Baron, Bruno Evrard, Xavier Repessé, Julien Maizel, Christophe Jacob, Marine Goudelin, Cyril Charron, Gwenaël Prat, Michel Slama, Guillaume Geri, Philippe Vignon
Journal: Intensive Care Medicine (2018)
Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (RIX-FP) in Previously Treated Children < 12 Years of Age with Hemophilia B: Long-Term Efficacy and Safety from an Ongoing Phase 3b Extension Clinical Trial
Authors: Gili Kenet, Andres Brainsky, Jerry S. Powell, Yanyan Li, Wilfried Seifert
Journal: Blood (2017)