tbuckley/cabot-search huggingface dataset:
Abstract 17003: Effect of Angiographic Collaterals on Long-Term Clinical Outcomes in Patients With Chest Pain
Authors: Robert C Schutt, Shiu M Young, Ling Liu, Lewis C Lipson, Ellen C Keeley
Journal: Circulation (2013)

Background: Coronary collaterals are an innate protective mechanism that preserves myocardial perfusion in the presence of severe stenoses. The effect of collaterals on long-term clinical outcomes remains controversial. Methods: The study design was a prospective cohort study of 984 patients with chest pain referred for angiography. Patients were followed for one year after angiography. The primary outcome was the composite endpoint of major adverse cardiac events (MACE) including death, myocardial infarction (MI), and the need for coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). Secondary outcomes were the individual endpoints of death, MI, recurrent angina, and need for CABG or PCI following angiography. Results: 984 patients were followed for 1 year and 233 (24%) had spontaneously visible coronary collaterals at the time of angiography. Patients with collaterals were older (62 ± 11 vs. 60 ± 11 years, p=0.042), men (77% vs. 62%, p<0.001), with higher rates of smok...
HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G-Quadruplex DNA
Authors: Wenwen Wu, Nana Rokutanda, Jun Takeuchi, Yongqiang Lai, Reo Maruyama, Yukiko Togashi, Hiroyuki Nishikawa, Naoko Arai, Yasuo Miyoshi, Nao Suzuki, Yasushi Saeki, Keiji Tanaka, Tomohiko Ohta
Journal: Cancer Research (2018)

BLM and WRN are RecQ DNA helicasesessential for genomic stability. Here, we demonstrate that HERC2, a HECT E3 ligase, is critical for their functions to suppress G-quadruplex (G4) DNA. HERC2 interacted with BLM, WRN, and replication protein A (RPA) complexes during the S-phase of the cell cycle. Depletion of HERC2 dissociated RPA from BLM and WRN complexes and significantly increased G4 formation. Triple depletion revealed that HERC2 has an epistatic relationship with BLM and WRN in their G4-suppressing function. In vitro, HERC2 released RPA onto single-stranded DNA (ssDNA) rather than anchoring onto RPA-coated ssDNA. CRISPR/Cas9-mediated deletion of the catalytic ubiquitin-binding site of HERC2 inhibited ubiquitination of RPA2, caused RPA accumulation in the helicase complexes, and increased G4, indicating an essential role for E3 activity in the suppression of G4. Both depletion of HERC2 and inactivation of E3 sensitized cells to the G4-interacting compounds telomestatin and pyridostatin. Overall, these results indicate that HERC2 is a master regulator of G4 suppression that affects the sensitivity of cells to G4 stabilizers. Given that HERC2 expression is frequently reduced in many types of cancers, G4 accumulation as a result of HERC2 deficiency may provide a therapeutic target for G4 stabilizers.Significance: HERC2 is revealed as a master regulator of G-quadruplex, a DNA secondary structure that triggers genomic instability and may serve as a potential molecular target in cancer therapy.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/22/6371/F1.large.jpg Cancer Res; 78(22); 6371-85. ©2018 AACR.
Distinctive Mechanisms of Impaired Cxcr4/Sdf Chemotaxis in Acute Leukemia
Authors: 林亮音, 林東燦, 唐季祿, 田蕙芬, Liang-In Lin, Lin Dong-Tsamn, Tang Jih-Luh, Tien Hwei-Fang
Journal: Blood (2003)
Lactic Acidosis, Metformin Use, and Dose-Response Association
Authors: Giovanni Gulli
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
PEPT1-mediated prodrug strategy for oral delivery of peramivir
Authors: Yongbing Sun, Wei Gan, Mingdao Lei, Wei Jiang, Meng Cheng, Junwei He, Qi Sun, Wan Liu, Lvjiang Hu, Yi Jin
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Peramivir was a novel and highly potent neuraminidase (NA) inhibitor for the treatment of influenza A and B. However, it exhibited a very low oral bioavailability (only 3%) due to the high polarity (log P of −1.4) and the low membrane permeability across the intestine. To utilize the PEPT1-mediated prodrug strategy to improve the oral absorption and develop the oral alternative, seven amino acid ester prodrugs and seven amino acid amide prodrugs have been synthesized. The permeability of these prodrugs across Caco-2 cells were screened. Peramivr-(CH2)2-l-Val and Peramivir-l-Ile were of the highest permeability in ester prodrugs and amide prodrugs, respectively, and then they were selected for further studies. Glycylsarcosine (gly-sar) uptake by Caco-2 could be inbihited by Peramivir-(CH2)2-l-Val and Peramivir-l-Ile in a concentration-dependent manner, and the IC50 was 1.34 ± 0.31 mM and 1.78 ± 0.48 mM, respectively. The direct uptake of Peramivir-(CH2)2-l-Val and Peramivir-l-Ile in MDCK-PEPT1 cells were significantly higher than in MDCK mock cells, and could be markedly inhibited by gly-sar. The uptake of Peramivir-(CH2)2-l-Val and Peramivir-l-Ile (0.01 to 50 mM) in MDCK-hPEPT1 cells conformed to Michaelis–Menten Equation. The oral bioavailability of peramivir was 65.3% and 37.3% after the oral administration of Peramivir-(CH2)2-l-Val and Peramivir-l-Ile to rats, respectively. The oral absorption and bioactivation of Peramivir-(CH2)2-l-Val was rapid and extensive, and no Peramivir-(CH2)2-l-Val was found in plasma. Because the amide bond was relatively stable, Peramivir-l-Ile could not be totally converted to the parent drug in vivo. Peramivir-(CH2)2-l-Val with good oral profiles and rapid bioactivation might be a promising prodrug for the further clinic development. The present study also corroborated the idea that the PEPT1-mediated prodrug approach has enormous promise for improving the oral absorption of poorly absorbed drug.
Shipping Out MEK Inhibitor Resistance with SHP2 Inhibitors
Authors: Pedro Torres-Ayuso, John Brognard
Journal: Cancer Discovery (2018)

Abstract Summary: RAS is one of the most frequently altered oncogenes, yet RAS-driven tumors are largely refractory to anticancer therapies. Fedele and colleagues demonstrate that SHP2 inhibitors prevent adaptive MEK inhibitor resistance; therefore, combining MEK and SHP2 inhibitors represents an exciting new therapeutic approach for the treatment of RAS-driven cancers. Cancer Discov; 8(10); 1210–2. ©2018 AACR. See related article by Fedele et al., p. 1237.
A tale of two vaccines
Authors: Fiona Godlee
Journal: BMJ (2018)

Public trust in vaccination programmes is crucial to their success. History tells us that trust is easily undermined by misinformation, but this should not prevent an open and informed debate on the evidence for the effectiveness and safety of vaccines.

Peter Doshi tells a tale of two vaccines rapidly deployed by GSK in 2009 amid fears of a flu pandemic (doi:10.1136/bmj.k3948). There were early internal safety reports showing a higher rate of serious adverse events logged in relation to one of the vaccines, Pandemrix, but these reports were not actively shared with the public, …
Abstract 20657: Influence of Gender on Pulmonary Hypertension Phenotype in Chronic Kidney Disease
Authors: Jared O’Leary, Tufik Assad, Anna Hemnes, Meng Xu, Quinn Wells, Eric Farber-Eger, Kelly Birdwell, Evan Brittain
Journal: Circulation (2016)

Introduction: Pulmonary hypertension (PH) is common among CKD patients and associated with a worse prognosis. Risk factors for PH among CKD patients are poorly understood, particularly among the Pre-Capillary PH (Pre-PH) phenotype. We examined the risk factors and clinical correlates of Pre-PH in CKD. Methods: We extracted clinical, hemodynamic and echocardiographic data from Vanderbilt’s de-identified electronic medical record in patients referred for right heart catheterization (RHC) between 1998-2014. CKD stage was defined by GFR thresholds. Results: Among 4,635 patients referred for RHC, 1,267 (46%) had PH and CKD (stage 3 or greater). After adjustment for 24 relevant covariates, the recognized risk factors COPD, CHF, BMI, and scleroderma were associated with PH (all p<0.001) in addition to CKD (OR 1.40 95%CI 1.18-1.65, p<0.001) and black race (OR 1.56 95%CI 1.23-1.99; p<0.001). Established risk factors for pulmonary vascular disease (ILD, SLE, Scleroderma) were more prevalent in Pre-PH patients with ...
Abstract 18867: High Density Electrical Mapping With Conformal Electrode Arrays
Authors: Leon Ptaszek, Roozbeh Ghaffari, Cliff Liu, Fernando Quivira, E Kevin Heist, Lauren Klinker, John Work, Yung-Yu Hsu, Stephen Lee, Garren Su, Kevin Cordaro, Jeremy N Ruskin, Moussa Mansour
Journal: Circulation (2013)

Introduction: High-resolution mapping catheters could facilitate detailed mapping of complex arrhythmias, such as persistent atrial fibrillation (AF). Detailed map information acquired with a high-resolution catheter could potentially improve the efficacy of ablation. The goal of this study was to test the feasibility of cardiac mapping using a catheter-based conformal high-density (HD) electrode array (16 electrodes/cm2) that significantly enhances spatial mapping resolution relative to existing devices. Methods: In vivo studies of the catheter-based HD electrode arrays were performed in 4 swine. The HD array was embedded in the balloon and was used to measure atrial electrical activity during both sinus rhythm (SR) and pacing-induced AF. Signal fidelity was evaluated during maneuvers of the catheter in the atria. Results: Activation patterns were identified and propagation speeds were characterized during sinus rhythm and pacing-induced AF. These HD recordings were then used to generate iso-potential conduction maps (Figure). Conclusions: Electrogram measurement with the HD conformal electrode array was feasible, and enabled fine spatio-temporal mapping of the atria during SR and AF, and has the potential to help better define the arrhythmogenic substrate(s) of complex arrhythmias.
Glyburide vs Insulin for Gestational Diabetes—Reply
Authors: Marie-Victoire Sénat, Helene Affres, Jean Bouyer
Journal: JAMA (2018)

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
Glyburide vs Insulin for Gestational Diabetes
Authors: Shiqiao Peng, Chenyan Li, Xuren Sun
Journal: JAMA (2018)

To the Editor Dr Sénat1 and colleagues conducted a randomized clinical trial investigating the effect of glyburide or insulin on perinatal complications among women with gestational diabetes. We wonder whether the study design can be applied to most women with gestational diabetes.
Systolic and Diastolic Blood Pressure Variability as Risk Factors for Adverse Events After Coronary Artery Bypass Grafting
Authors: Cornelius M. Dyke, Cecilia L. Benz, Chani M. Taggart, Marilyn G. Klug, Marc D. Basson
Journal: JAMA Surgery (2018)

This study assesses whether blood pressure variability is associated with adverse outcomes after coronary artery bypass grafting surgery.
Abstract 19838: REmission From Stage D Heart Failure (RESTAGE-HF): Interim Results and Insights From a Prospective Multi-Center Non-Randomized Study of Myocardial Recovery Using LVADs
Authors: Emma J Birks, Eduardo Rame, Snehal R Patel, Craig Selzman, Chris Cunningham, Randall Starling, John Um, Daniel Goldstein, Mark Slaughter, Pavan Alturi, Daniel Spevack, David Farrar, Brian D Lowes, Stavros G Drakos
Journal: Circulation (2016)

Introduction: Myocardial recovery from advanced heart failure (HF) can occur following LVAD support. However the rate sufficient to allow device explantation is generally considered low. Hypothesis...
The combination of 5-flurouracil (5-FU) and 2-methoxyestradiol enhance the antitumor activity of radiation in vivo in a murine colon cancer model
Authors: Eiko Nakata, Theresa Lavallee, Yoshihiro Takai, Kenji Nemoto, Yoshihiro Ogawa, Shogo Yamada
Journal: Cancer Research (2005)

4755  Capecitabine (N4-pentyloxycarbonyl-5’-deoxy-5-fluorocytidine, Xeloda®) and 2-ME2 (2-Methoxyestradiol, Panzem®) are being evaluated for the treatment of many cancers. Capecitabine is a new fluolopyrimidine carvamate, which is converted to 5-fluorouracil (5-FU) selectively in tumors through the intermediate metabolite and shows potent antitumor effects on a variety of malignant tumors such as breast and colon cancers. The drug is currently under intensive clinical investigation. 2-ME2 is an endogenous estradiol metabolite that disrupts microtuble function, suppresses murine tumors, and inhibits angiogenesis. The purpose of the present study is to investigate whether the combination of Capecitabine and 2-ME2 is effective in the treatment of human colon cancer and whether this combination enhances the effect of ionizing radiation. The study was performed using a human colon cancer cell line, DLD-1. The cells were implanted into the leg of nude mice to generate tumor xenografts. When tumor volume reached 80-100 mm3, the mice were divided into 8 treatment groups: vehicle control treated, treated with a single dose of 5 Gy local tumor irradiation, 100 mg/kg Capecitabine or 50 mg/kg 2-ME2 orally once daily for 21 consecutive days, and combination treatments: Capcitabine and radiation, 2-ME2 and radiation, Capcitabine and 2-ME2 or Capcitabine, 2-ME2 and radiation . When radiation treatment- was combined, administration of Capecitabine and/or 2-ME2 began 1 hour before tumor irradiation. Tumor growth was measured every 2 to 3 days, and the effects of the treatments were expressed by tumor growth delay. The results showed that the combined treatment with Capecitabine and 2-ME2 plus tumor irradiation 5Gy was highly effective in delaying tumor growth compared to the drug only, or drug plus irradiation. Thus, the combined Capecitabine, 2-ME2 plus radiation treatment showed activity on the DLD-1 colon cancer xenografts. Current experiments explore cellular and molecular mechanisms underlying the interaction between Capecitabine, 2-ME2 and radiation.
Huntingtin suppression restores cognitive function in a mouse model of Huntington’s disease
Authors: Amber L. Southwell, Holly B. Kordasiewicz, Douglas Langbehn, Niels H. Skotte, Matthew P. Parsons, Erika B. Villanueva, Nicholas S. Caron, Michael E. Østergaard, Lisa M. Anderson, Yuanyun Xie, Louisa Dal Cengio, Hailey Findlay-Black, Crystal N. Doty, Bethany Fitsimmons, Eric E. Swayze, Punit P. Seth, Lynn A. Raymond, C. Frank Bennett, Michael R. Hayden
Journal: Science Translational Medicine (2018)

Mutant huntingtin suppression with antisense oligonucleotides reverses cognitive impairments in a mouse model of Huntington’s disease.
Fusion Kinases Identified by Genomic Analyses of Sporadic Microsatellite Instability–High Colorectal Cancers
Authors: Kazuhito Sato, Masahito Kawazu, Yoko Yamamoto, Toshihide Ueno, Shinya Kojima, Genta Nagae, Hiroyuki Abe, Manabu Soda, Takafumi Oga, Shinji Kohsaka, Eirin Sai, Yoshihiro Yamashita, Hisae Iinuma, Masashi Fukayama, Hiroyuki Aburatani, Toshiaki Watanabe, Hiroyuki Mano
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Colorectal cancers with microsatellite instability–high (MSI-H) status, due to mismatch repair deficiency, are associated with poor patient outcomes after relapse. We aimed to identify novel therapeutic targets for them. Experimental Design: We performed MSI analyses of over 2,800 surgically resected colorectal tumors obtained from consecutive patients treated in Japan from 1998 through June 2016. Whole-exome sequencing, transcriptome sequencing, and methylation analyses were performed on 149 of 162 tumors showing MSI in BAT25 and BAT26 loci. We analyzed patient survival times using Bonferroni-adjusted log-rank tests. Results: Sporadic MSI-H colorectal cancers with promoter methylation of MLH1 (called MM) had a clinicopathological profile that was distinct from that of colorectal cancers of patients with germline mutations (Lynch syndrome, LS-associated) or somatic, Lynch-like mutations in mismatch repair genes. MM tumors had more insertions and deletions and more recurrent mutations in BRAF and RNF43 than LS-associated or Lynch-like MSI-H tumors. Eleven fusion kinases were exclusively detected in MM MSI-H colorectal cancers lacking oncogenic KRAS/BRAF missense mutations and were associated with worse post-relapse prognosis. We developed a simple method to identify MM tumors and applied it to a validation cohort of 28 MSI-H colorectal cancers, identifying 16 MM tumors and 2 fusion kinases. Conclusions: We discovered that fusion kinases are frequently observed among sporadic MM MSI-H colorectal cancers. The new method to identify MM tumors enables us to straightforwardly group MSI-H patients into candidates of LS or fusion kinase carriers.
Effects of psychosocial interventions on patient‐reported outcomes in patients with psoriasis: a systematic review and meta‐analysis
Authors: J.M. Zill, E. Christalle, N. Tillenburg, U. Mrowietz, M. Augustin, M. Härter, J. Dirmaier
Journal: British Journal of Dermatology (2018)

BackgroundPsoriasis can lead to high psychosocial burden, and the occurrence of psoriasis is related to psychological distress.
Rates of Carpal Tunnel Syndrome in a State Workers’ Compensation Information System, by Industry and Occupation — California, 2007–2014
Authors: Rebecca Jackson, John Beckman, Matt Frederick, Kristin Musolin, Robert Harrison
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Carpal tunnel syndrome (CTS) occurs when the median nerve becomes compressed as it passes through the wrist within the carpal tunnel, resulting in pain, tingling, weakness, or numbness in the hand or the wrist. Occupational risk factors for CTS include engaging in work activities that require forceful, repetitive tasks, prolonged use of the hands or wrists in an awkward posture, or vibration (1). To assess trends and identify high-risk industries and occupations for CTS, the California Department of Public Health (CDPH) analyzed California workers' compensation claims for CTS by industry (2007-2014) and occupation (2014) and calculated rates per full-time equivalent (FTE) worker. During 2007-2014, a total of 139,336 CTS cases were reported (incidence = 6.3 cases per 10,000 FTE) in California workers; the rate among women (8.2) was 3.3 times higher than that among men (2.5). Industries with the highest rates of CTS were textile, fabric finishing, and coating mills (44.9), apparel accessories and other apparel manufacturing (43.1), and animal slaughtering and processing (39.8). Industries with high rates of CTS should consider implementing intervention measures, including ergonomic evaluations and development of tools and instruments that require less repetition and force and that correct awkward postures.
Abstract 003: Growth Trajectories of Body Mass Index During Childhood and Adult Hypertension
Authors: Shengxu Li, Tao Zhang, Paul K Wheltong, Marie Krousel-Wood, Lydia Bazzano, Jiang He
Journal: Circulation (2018)

Background: Childhood body mass index (BMI) predicts adult hypertension. However, information is lacking regarding the relationship between BMI growth trajectories during childhood and adult hypertension risk. We aimed to test the hypothesis that BMI growth rates at different childhood ages have differential influences on adult hypertension risk, independent of BMI levels. Methods: The study included 1,772 Whites and 960 Blacks with repeated BMI and blood pressure measurements from childhood (4-19 years) to adulthood (20-51 years). A random-effects mixed model was used to construct BMI growth curves by race and sex. Model-estimated linear growth rates of BMI at different childhood ages were linked to adult hypertension (defined by measured blood pressure or antihypertensive medication) in multivariable logistic regression models. Results: Hypertensive adults had higher BMI across childhood than normotensive adults. Overall, linear slope and cubic parameters of BMI were higher in hypertensive adults than in normotensive adults in all four race-sex groups (p ≤ 0.023). Odds ratio of adult hypertension for each kg/m 2 /year increase in BMI linear slope was 1.22 (95% CI =1.11-1.34) at age 4, was non-significant between ages 5-9, and gradually increased thereafter and plateaued beginning at age 15 (odds ratio = 1.41 and 95% CI = 1.28-1.56) (Figure). Conclusions: Rapid increase in BMI during and after puberty is associated with elevated risk of hypertension in adult life, which has implications for early prevention.