tbuckley/cabot-search huggingface dataset:
A phase III study of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric cancer (JCOG0912): Analysis of the safety and short-term clinical outcomes.
Authors: Masakazu Takagi, Hitoshi Katai, Junki Mizusawa, Kenichi Nakamura, Takaki Yoshikawa, Masanori Terashima, Seiji Ito, Shin Teshima, Keisuke Koeda, Takeshi Sano, Norimasa Fukushima, Takeshi Yasuda, Yoshito Asao, Yoshiyuki Fujiwara, Mitsuru Sasako
Journal: Journal of Clinical Oncology (2015)

4017 Background: Although the number of patients undergoing laparoscopy-assisted distal gastrectomy (LADG) has been increasing, there is no confirmatory randomized controlled trial (RCT) to evaluate the efficacy of LADG compared with open distal gastrectomy (ODG). Safety and short term outcome are presented. Methods: We conducted a RCT to confirm the non-inferiority of overall survival (OS) of LADG to ODG in patients with clinical IA (T1N0) or IB (T1N1 or T2 [MP] N0) gastric cancer. D1 or more dissection is applied for clinical stage IA and D2 dissection for clinical stage IB. Only the credentialed surgeons can be responsible for both procedures. The primary endpoint is (OS). The planned sample size was 920. Results: Between March 2010 and November 2013, 921 patients (LADG 462, ODG 459) were enrolled from 33 institutions. Operating time was longer in LADG than ODG (median 278 vs 194 min, p < 0.001). Blood loss was smaller in LADG than ODG (median 38 vs 115 ml, p < 0.001). There were no grade 3 or 4 intraoperative adverse events in either arm. There was no difference in the overall proportion of in-hospital, non-hematological grade 3 or 4 adverse events excluding biochemical data (3.3%: LADG, 3.7%: ODG). The proportion of grade 3 or 4 serum AST/ALT increased was higher in LADG than ODG (16.4% vs 5.3%, p < 0.001). The proportion of the patients who required an analgesic on postoperative days 5–10 was smaller in LADG than ODG (50.3% vs 59.3%, p = 0.006). The median time from surgery until the first episode of flatus was shorter in LADG than ODG (2 days vs 3 days, p < 0.001). There was no difference in both the highest body temperatures during the first 3 days after the surgery and the highest body temperatures during hospitalization. Conclusions: Although the elevation of serum AST/ALT should be taken care, this trial confirmed that LADG performed by the credentialed surgeons was safe as ODG in terms of adverse event and short-term clinical outcomes. LADG will be an alternative procedure in clinical IA/IB gastric cancer if the non-inferiority of LADG in OS is confirmed by the primary analysis planned in 2018. Clinical trial information: UMIN000003319.
The Logic of Climate and Culture: Evolutionary and Psychological Aspects of CLASH
Authors: Paul A. M. Van Lange, Maria I. Rinderu, Brad J. Bushman
Journal: Behavioral and Brain Sciences (2017)

Abstract A total of 80 authors working in a variety of scientific disciplines commented on the theoretical model of CLimate, Aggression, and Self-control in Humans (CLASH). The commentaries cover a wide range of issues, including the logic and assumptions of CLASH, the evidence in support of CLASH, and other possible causes of aggression and violence (e.g., wealth, income inequality, political circumstances, historic circumstances, pathogen stress). Some commentaries also provide data relevant to CLASH. Here we clarify the logic and assumptions of CLASH and discusses its extensions and boundary conditions. We also offer suggestions for future research. Regardless of whether none, some, or all of CLASH is found to be true, we hope it will stimulate future research on the link between climate and human behavior. Climate is one of the most presing issues of our time.
The PNPLA3 variant associated with fatty liver disease (I148M) accumulates on lipid droplets by evading ubiquitylation
Authors: Soumik BasuRay, Eriks Smagris, Jonathan C. Cohen, Helen H. Hobbs
Journal: Hepatology (2017)

A sequence variation (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is strongly associated with fatty liver disease, but the underlying mechanism remains obscure. In this study, we used knock-in (KI) mice (Pnpla3148M/M ) to examine the mechanism responsible for accumulation of triglyceride (TG) and PNPLA3 in hepatic lipid droplets (LDs). No differences were found between Pnpla3148M/M and Pnpla3+/+ mice in hepatic TG synthesis, utilization, or secretion. These results are consistent with TG accumulation in the Pnpla3148M/M mice being caused by impaired TG mobilization from LDs. Sucrose feeding, which is required to elicit fatty liver in KI mice, led to a much larger and more persistent increase in PNPLA3 protein in the KI mice than in wild-type (WT) mice. Inhibition of the proteasome (bortezomib), but not macroautophagy (3-methyladenine), markedly increased PNPLA3 levels in WT mice, coincident with the appearance of ubiquitylated forms of the protein. Bortezomib did not increase PNPLA3 levels in Pnpla3148M/M mice, and only trace amounts of ubiquitylated PNPLA3 were seen in these animals.These results are consistent with the notion that the 148M variant disrupts ubiquitylation and proteasomal degradation of PNPLA3, resulting in accumulation of PNPLA3-148M and impaired mobilization of TG from LDs. (Hepatology 2017;66:1111-1124).
Catheter Ablation in Patients With Multiple and Unstable Ventricular Tachycardias After Myocardial Infarction
Authors: Kyoko Soejima, Makoto Suzuki, William H. Maisel, Corinna B. Brunckhorst, Etienne Delacretaz, Louis Blier, Stanley Tung, Hafiza Khan, William G. Stevenson
Journal: Circulation (2001)

Background — Extensive lines of radiofrequency (RF) lesions through infarct (MI) can ablate multiple and unstable ventricular tachycardias (VTs). Methods for guiding ablation that minimize unnecessary RF applications are needed. This study assesses the feasibility of guiding RF line placement by mapping to identify a reentry circuit isthmus. Methods and Results — Catheter mapping and ablation were performed in 40 patients (MI location: inferior, 28; anterior, 7; and both, 5) with an electroanatomic mapping system to measure the infarct region and ablation lines. The initial line was placed in the MI region either through a circuit isthmus identified from entrainment mapping or a target identified from pace mapping. A total of 143 VTs (42 stable, 101 unstable) were induced. An isthmus was identified in 25 patients (63%; 5 with only stable VTs, 5 with only unstable VTs, and 15 with both VTs). Inducible VTs were abolished or modified in 100% of patients when the RF line included an isthmus compared with 53% when RF had to be guided by pace mapping ( P =0.0002); those with an isthmus identified received shorter ablation lines (4.9±2.4 versus 7.4±4.3 cm total length, P =0.02). During follow-up, spontaneous VT decreased markedly regardless of whether an isthmus was identified. VT stability and number of morphologies did not influence outcome. Conclusions — A 4- to 5-cm line of RF lesions abolishes all inducible VTs in more than 50% of patients. Less ablation is required if a reentry circuit isthmus is identified even when multiple and unstable VTs are present.
Abstract 227: The Effect of PHLPP2 Removal on Cardiomyocyte Hypertrophy
Authors: Nicole H Purcell, Courtney Moc, Giovanni Birrueta, Amy Taylor, Walter Koch, Cristina Zambrano
Journal: Circulation Research (2015)

Crucial cellular decisions that lead to cell growth, metabolism, proliferation, and survival are all dependent on the precise control of the phosphorylation state of proteins. The serine/threonine phosphatase, PHLPP (PH domain leucine-rich repeat protein phosphatase) has been shown to directly dephosphorylate several members of the AGC family of kinases. Knockdown of PHLPP1 by siRNA in neonatal cardiomyocytes potentiates Akt activity and phosphorylation specifically at Ser473 basally and following agonist stimulation while, the removal of PHLPP2 in cardiomyocytes does not affect Akt phosphorylation as previously reported in other cells. We hypothesize that PHLPP2 may target other AGC kinases in cardiomyocytes to regulate cardiac hypertrophy. Preliminary data suggests that removal of PHLPP2 activates fetal gene re-expression at baseline and potentiates phenylephrine (PE) induced gene expression 2 fold over siControl. Recently, G protein-coupled receptor kinase 5 (GRK5), which is an AGC kinase, has been shown to regulate cardiac hypertrophy through HDAC5 phosphorylation and de-repression of gene transcription. We wanted to determine whether PHLPP2 regulates GRK5 phosphorylation and localization in cardiomyocytes. GRK5 translocates to the nucleus following hypertrophic stimulation and we found that removal of PHLPP2 increased GRK5 translocation to the nucleus at baseline and with PE treatment compared to siControl cells. Also, removal of PHLPP2 increased nuclear export of HDAC5 at baseline and following PE treatment. Conversely, overexpression of PHLPP2 blocked nuclear translocation of GRK5 following PE treatment. Ongoing studies will determine whether PHLPP acts as a scaffold or if its phosphatase activity is necessary for inhibition of GRK5 translocation by directly measuring the phosphorylation of GRK5 in the presence and absence of PHLPP2 following hypertrophic stimulation. Our preliminary data is the first to uncover GRK5 as a novel PHLPP2 target in cardiomyocytes. Since little is known about the non-canonical regulation of GRK5, understanding whether phosphorylation and localization is regulated within the cardiomyocyte by PHLPP has potential for new therapeutic targets in the treatment of cardiac hypertrophy and failure.
Age associated changes in gene expression in the human prostate
Authors: James Lyons-Weiler, Uma Chandran, John Gilbertson, Songhui Li, Michael Becich, Gurkamal Chatta, Rajiv Dhir
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2541 

The adult human prostate is a complex, hormone sensitive organ that undergoes significant transformations over a person’s lifetime. First, there is initiation of function and enlargement of the gland that begins at puberty and plateaus around age 25 yrs. Subsequently, beginning in the mid-forties, a poorly understood second transformation occurs, resulting either in benign prostatic hyperplasia (BPH) or cancer in most men over the age of 80. Gene expression shifts associated with normal, disease-free aging have not been previously characterized. Whole genome expression data were obtained for 19 donors using Affymetrix GeneChip® arrays. Samples were grouped by age into pubertal (13-19 yrs; n= 5) vs. post-pubertal (20-39 yrs; n=7) vs adult (> 40 yrs; n=7), and global gene expression differences were measured using the pooled variance t-test. Seven genes exhibited significant difference in expression levels using the pooled variance t-test, p   60 yrs of age.
Optimal vs Feasible Volume Thresholds in Vascular Surgery
Authors: Sarah E. Deery, Marc L. Schermerhorn
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Letter by Tunçez et al Regarding Article, “Identifying Patients at Risk for Prehospital Sudden Cardiac Arrest at the Early Phase of Myocardial Infarction: The e-MUST Study (Evaluation en Médecine d’Urgence des Stratégies Thérapeutiques des infarctus du myocarde)”
Authors: Abdullah Tunçez, Muhammed Salih Ateş, Hüseyin Tezcan
Journal: Circulation (2017)

We read
Abstract 13881: Determining Factors and Prognostic Value of Plasma γ- Atrial Natriuretic Peptide Ratio in Patients With Heart Failure
Authors: Seiji Takashio, Hiroyuki Takahama, Tomohiro Hayashi, Chiaki Nagai-Okatani,, Toshio Nishikimi, Yasuaki Nakagawa, Makoto Amaki, Takahiro Ohara, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Kenji Kangawa, Naoto Minamino, Toshihisa Anzai
Journal: Circulation (2016)

Background: Atrial natriuretic peptide (ANP) is a peptide hormone that maintain sodium homeostasis and inhibit activation of the renin-angiotensin-aldosterone system. Three endogenous molecular forms of human ANP, including fully bioactive α-ANP, β-ANP; an antiparallel dimer of α-ANP, and γ-ANP; α-ANP precursor, are present in heart and plasma of patients with heart failure (HF). However, the clinical importance of molecular ratio of ANP has not been evaluated. This study was designed to evaluate plasma γ-ANP and total amount of ANP levels (total ANP) in patients HF, and identify the determining factor and prognostic value of %γ-ANP (γ-ANP /total ANP ratio). Method and Results: We prospectively evaluated plasma γ-ANP and total ANP levels in 148 patients with acute decompensated HF before discharge using by chemiluminescence enzyme immunoassay. Median plasma total ANP and γ-ANP levels were 142.5 [63.2-231.3] and 10.9 [4.4-25.6] pmol/ml, respectively. %γ-ANP was 8.9 [5.5-15.2]% and significantly correlated with age (ρ=0.205; p=0.01), body mass index (BMI) (ρ=-0.316; p&lt;0.001), left ventricular ejection fraction (LVEF) (ρ=-0.250; p=0.002), hemoglobin (ρ=-0.182; p=0.03), and B-type natriuretic peptide (BNP) levels (ρ=0.393; p&lt;0.002). Patients with high %γ-ANP (≥ median value) were more likely to have ischemic etiology and prior HF hospitalization history. High %γ-ANP tended to increase all cause death (p=0.06) and was significantly associated with repeat HF-related hospitalization (p=0.01; Figure ). Conclusion: Increase of %γ-ANP was associated with older age, lower BMI, LVEF hemoglobin, and higher BNP levels. High %γ-ANP was a predictor of future HF-related rehospitalization. These results suggested that %γ-ANP was affected by presence of known poor prognostic factors of HF.
Flexible IgE epitope-containing domains of Phl p 5 cause high allergenic activity
Authors: Christoph Göbl, Margarete Focke-Tejkl, Nazanin Najafi, Evelyne Schrank, Tobias Madl, Simone Kosol, Christoph Madritsch, Yulia Dorofeeva, Sabine Flicker, Josef Thalhamer, Rudolf Valenta, Klaus Zangger, Nico Tjandra
Journal: Journal of Allergy and Clinical Immunology (2017)
Hepatobiliary Cancers
Authors: Al B. Benson, Thomas A. Abrams, Edgar Ben-Josef, P. Mark Bloomston, Jean F. Botha, Bryan M. Clary, Anne Covey, Steven A. Curley, Michael I. D'Angelica, Rene Davila, William D. Ensminger, John F. Gibbs, Daniel Laheru, Mokenge P. Malafa, Jorge Marrero, Steven G. Meranze, Sean J. Mulvihill, James O. Park, James A. Posey, Jasgit Sachdev, Riad Salem, Elin R. Sigurdson, Constantinos Sofocleous, Jean-Nicolas Vauthey, Alan P. Venook, Laura Williams Goff, Yun Yen, Andrew X. Zhu
Journal: Journal of the National Comprehensive Cancer Network (2009)
Systemic Management of Colorectal Cancer
Authors: Wells A. Messersmith
Journal: Journal of the National Comprehensive Cancer Network (2017)

Advances have been made in the systemic treatment of colorectal cancer, with approximately 12 chemotherapy or biologic agents approved for use as a single agent or in a combination. However, numerous gaps in our understanding of the disease remain, such as the lack of benefit with biologics in the adjuvant setting, the absence of biomarkers for most systemic therapies, and the reason why left-sided and right-sided tumors behave differently. At the 22nd NCCN Annual Conference, Dr. Wells A. Messersmith presented several impactful updates to the 2017 NCCN Clinical Practice Guidelines in Oncology for Colon Cancer and reviewed the outcomes with a host of therapies used for both early-stage and metastatic disease.
A randomized, double-blind, placebo (Pbo)-controlled phase III study of ombrabulin plus cisplatin in patients (pts) with advanced-stage soft-tissue sarcoma after failure of anthracycline and ifosfamide chemotherapies.
Authors: Zsuzsanna Papai, Anthony W. Tolcher, Antoine Italiano, Didier Cupissol, Antonio Lopez-Pousa, Sant P. Chawla, Emmanuelle Bompas, Nicolas Penel, Nicolas Isambert, Arthur P. Staddon, Antoine Thyss, Armando Santoro, Fabio A. Franke, Patrick Cohen, Solenn Le-Guennec, George D. Demetri, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2013)

10506 Background: Ombrabulin (AVE8062) is a vascular disrupting agent that damages established tumor vasculature and has demonstrated synergistic antitumor activity with cisplatin in vivo. In a phase I study, ombrabulin 25 mg/m² plus cisplatin 75 mg/m² was identified as the recommended dose in pts with solid tumors (AACR 2008; Abs 08-AB-4925). This phase III study evaluated the efficacy and safety of ombrabulin plus cisplatin in pts with advanced soft-tissue sarcoma (NCT00699517). Methods: Pts (aged ≥18 yrs, ECOG PS ≤2) with metastatic soft-tissue sarcoma who had received prior anthracycline and ifosfamide, with ≤2 prior chemotherapies for advanced disease, were randomized (1:1) to receive either ombrabulin 25 mg/m² or Pbo plus cisplatin 75 mg/m² every 3 weeks. The primary objective was to compare progression-free survival (PFS) between arms; secondary objectives included overall survival (OS) and safety. Results: Overall, 355 pts (median age 52 yrs; 51.5% male) were randomized (176 ombrabulin, 179 Pbo) in 44 centers worldwide. Median duration of follow-up was 27.9 and 30.5 months in Pbo and ombrabulin arms, respectively. PFS analysis showed a statistically significant improvement with ombrabulin (median 1.54 vs 1.41 months Pbo; HR=0.76, 95% CI 0.59–0.98; p=0.0302), with 3- and 6-month rates in favor of ombrabulin vs Pbo: 35.4% vs 24.9% and 19.3% vs 10.6%, respectively. A trend for an improvement with ombrabulin was observed in 3 of the 4 prespecified histology strata: liposarcoma, leiomyosarcoma, and “other”, but not for pleomorphic. Analysis of OS did not show statistically significant improvement with ombrabulin (median 11.43 vs 9.33 months Pbo, HR=0.85, 95% CI 0.67–1.09). OS rates at 1 year were in favor of ombrabulin (48.6% vs 42.4% Pbo). Grade 3/4 TEAEs more frequently seen with ombrabulin included neutropenia (19.2% vs 7.9% Pbo) and thrombocytopenia (8.5% vs 3.4% Pbo). Conclusions: Although this trial met its primary efficacy endpoint, the combination of ombrabulin and cisplatin did not demonstrate sufficient clinical benefit in pts with advanced soft-tissue sarcoma to warrant further study. Clinical trial information: NCT00699517.
Abstract 323: Growth Differentiation Factor-15 Is Upregulated in Profibrotic States of Dilated Cardiomyopathy and Not Hypertrophic Cardiomyopathy
Authors: Stephen Chang, Danos Christodoulou, Joshua Gorham, Hiroko Wakimoto, Seda Eminaga, Dave Conner, Steve Depalma, Libby Sparks, Jonathan Seidman, Christine Seidman
Journal: Circulation Research (2012)

Introduction: Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are leading causes of morbidity and mortality in the adult population. Both DCM and HCM arise from structural perturbations and remodeling of the heart, and many cases have been found to result from underlying familial mutations. The signaling pathways by which these mutations lead to pathological ventricular remodeling, fibrosis, and heart failure remain unknown. Methods: In this study we attempt to identify molecular pathways in a DCM mouse model and compare and contrast the results with those previously observed in HCM mouse models. We use a transgenic mouse expressing an arginine-to-cysteine (R9C) mutation in phospholamban (PLN), previously identified in DCM patients. To define molecules involved in disease progression, we generated expression profiles using high-throughput sequencing and assessed genes of interest by immunostaining. Results: PLN R9C/+ hearts exhibit increasing fibrosis, with proliferation of non-myocyte cells occurring throughout the disease spectrum. Losartan treatment, which effectively blocks the HCM phenotype, does not block the emergence of DCM and neither reduces fibrosis nor increases lifespan in PLN R9C/+ mice. Growth differentiation factor-15 (GDF15) RNA and protein levels are significantly upregulated in the left ventricles of PLN R9C/+ mice during DCM and heart failure. GDF15 is predominantly expressed in non-myocytes in WT mice, but in PLN R9C/+ mice, is upregulated almost 25-fold in myocytes and less than 1.5-fold in non-myocytes. Conclusion: Both fibrosis and the proliferation of non-myocytes in PLN R9C/+ mouse hearts increase as the DCM phenotype worsens, similar to that observed in HCM mouse models. However, losartan has no effect on the DCM phenotype suggesting that the molecular pathways of DCM and HCM may be different. This study identifies GDF15 as a signaling molecule that may play a unique role in DCM. GDF15 is upregulated in myocytes during DCM, but remains relatively unchanged in HCM. Understanding the genetic mechanisms underlying the progression of disease and fibrosis in both DCM and HCM will help us to characterize the distinct pathways of both diseases, as well as identify new, more specific targets for therapy.
Home Noninvasive Ventilation to Reduce Readmissions for Chronic Obstructive Pulmonary Disease
Authors: Nicholas S. Hill, Aylin Ozsancak Ugurlu
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal