tbuckley/cabot-search huggingface dataset:
Hypertension Management in Older and Frail Older Patients
Authors: Athanase Benetos, Mirko Petrovic, Timo Strandberg
Journal: Circulation Research (2019)

The prevalence of arterial hypertension, particularly systolic hypertension, is constantly rising worldwide. This is mainly the clinical expression of arterial stiffening as a result of the population's aging. Chronic elevation in blood pressure represents a major risk factor not only for cardiovascular morbidity and mortality but also for cognitive decline and loss of autonomy later in life. Clinical evidence obtained in community-dwelling older people with few comorbidities and preserved autonomy supports the beneficial effects of lowering blood pressure in older hypertensive subjects even after the age of 80 years. However, observational studies in frail older individuals treated for hypertension have shown higher morbidity and mortality rates compared with those with lower blood pressure levels. Clearly, in very old subjects, the therapeutic strategy of one size fits all cannot be applied because of the enormous functional heterogeneity in these individuals. Geriatric medicine proposes taking into account the function/frailty/autonomy status of older people. In the present review, we propose to adapt the antihypertensive treatment using an easy-to-apply visual numeric scale allowing the identification of 3 different patient profiles according to the functional status and autonomy for activities of daily living. For the preserved function profile, strategies should be those proposed for younger old adults. For the loss of function/preserved activities of daily living' profile, a more detailed geriatric assessment is needed to define the benefit/risk balance as well as requirements for the tailoring of the various therapeutic strategies. Lastly, for the loss of function and altered activities of daily living' profile, therapeutic strategies should be thoroughly reassessed, including deprescribing (when considered appropriate). In the near future, controlled trials are necessary for the most frail older subjects (ie, in those systematically excluded from previous clinical trials) to gain stronger evidence regarding the benefits of the various therapeutic strategies.
miR-147b-mediated TCA cycle dysfunction and pseudohypoxia initiate drug tolerance to EGFR inhibitors in lung adenocarcinoma
Authors: Wen Cai Zhang, Julie M. Wells, Kin-Hoe Chow, He Huang, Min Yuan, Tanvi Saxena, Mary Ann Melnick, Katerina Politi, John M. Asara, Daniel B. Costa, Carol J. Bult, Frank J. Slack
Journal: Nature Metabolism (2019)
Recent Advances in Scaffold Design and Material for Vascularized Tissue‐Engineered Bone Regeneration
Authors: Shi Yin, Wenjie Zhang, Zhiyuan Zhang, Xinquan Jiang
Journal: Advanced Healthcare Materials (2019)

Bone tissue is a highly vascularized tissue and concomitant development of the vascular system and mineralized matrix requires a synergistic interaction between osteogenesis and angioblasts. Several strategies have been applied to achieve vascularized tissue-engineered bone, including the addition of cytokines as well as pre-vascularization strategies and co-culture systems. However, the scaffold is another extremely important component to consider, and development of vascularized bone scaffolds remains one of the greatest challenges for engineering clinically relevant bone substitutes. Here, this review highlights the biomaterial selection, preparation of pre-vascularized scaffolds, composition modification of the scaffold, structural design, and the comprehensive use of the above synergistic modifications of scaffold materials for vascular scaffolds in bone tissue engineering. Moreover, a strategy is proposed for the design of future scaffold structures, in which promoting the regeneration of vascularized bone by regulating the microenvironment should be the main focus. This overview can help illuminate progress in this field and identify the most recently developed scaffolds that show the greatest potential for achieving clinically vascularized bone.
Smaller-Diameter Covered Transjugular Intrahepatic Portosystemic Shunt Stents Are Associated With Increased Survival
Authors: Jonel Trebicka, Diana Bastgen, Jonathan Byrtus, Michael Praktiknjo, Sophia Terstiegen, Carsten Meyer, Daniel Thomas, Rolf Fimmers, Markus Treitl, Wulf Euringer, Tilman Sauerbruch, Martin Rössle
Journal: Clinical Gastroenterology and Hepatology (2019)

We studied the effects of diameter of covered, self-expandable, nitinol stents on survival times of patients with a transjugular intrahepatic portosystemic shunt (TIPS).We collected data from 185 patients (median age, 55 y; 30% female) who received a covered nitinol stent, from February 2006 through September 2010, using the online multicenter German TIPS registry. TIPS were given to 107 patients for refractory ascites and to 78 patients for variceal bleeding. Patients at risk of hepatic encephalopathy (owing to advanced age, prior episodes) or liver failure (bilirubin level, >3 mg/dL), and bleeding patients receiving variceal embolization at TIPS, received 8-mm stents (n = 53). The remaining patients received 10-mm stents (n = 132). Eighty-one of the 10-mm stents were underdilated using 8-mm dilation balloons. Clinical and biochemical data were collected after TIPS placement at 1 month, 3 months, 6 months, 9 months, 1 year, and thereafter every 3 to 6 months. Groups were compared using propensity score analysis.Patients who received 8-mm stents survived significantly longer (34 ± 26 mo) than patients who received 10-mm stents (18 ± 19 mo), regardless of whether they were fully dilated or underdilated. When we compared 10-mm stents with or without underdilation, we found that a significantly higher proportion of patients who received underdilated stents survived for 1 month after TIPS placement (95% vs 84%; P = .03), but not for 3 months (P = .10). In multivariate analysis, 1-year mortality correlated with full dilation of the stent to 10 mm (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5) and with serum creatinine concentration at baseline (HR, 1.5; 95% CI, 1.0-1.7). Five-year mortality was associated with use of the 10-mm stents (HR, 1.8; 95% CI, 1.4-2.7) and baseline concentration of creatinine (HR, 1.3; 95% CI, 1.1-1.6).A smaller stent (nominal diameter of 8 mm, but not underdilation of a 10-mm stent) is associated with a prolonged survival compared with 10-mm stents, independent of liver-specific prognostic criteria.
Retroperitoneal Pelvic Solitary Fibrous Tumor With High Tracer Uptake in 68Ga-DOTATOC PET/CT
Authors: Philippe Thuillier, Jean-Romain Risson, Yves Eusen, Arnaud Uguen, Ronan Abgral
Journal: Clinical Nuclear Medicine (2019)

We report the case of a 27-year-old woman referred to our department for the characterization of a 7 × 6-cm left ischio-anal fossa mass by Ga-DOTATOC PET/CT. Several diagnoses were previously mentioned, in particular, myxoid sarcoma but also pelvic paraganglioma. Urinary methoxylated derivates and blood chromogranin A tests were negative. PET/CT showed a high Ga-DOTATOC uptake of the mass that was strongly consistent with paraganglioma diagnosis. Histopathological analysis surprisingly revealed a solitary fibrous tumor without aggressive criteria.
Hemodynamic Response in Low-Flow Low-Gradient Aortic Stenosis With Preserved Ejection Fraction After TAVR
Authors: Mackram F. Eleid, Ratnasari Padang, Mohammed Al-Hijji, Sorin V. Pislaru, Kevin L. Greason, Simon Maltais, Philippe Pibarot, Patricia A. Pellikka, Gurpreet S. Sandhu, Charanjit S. Rihal, Rick A. Nishimura, Barry A. Borlaug
Journal: Journal of the American College of Cardiology (2019)
Abstract 14928: Burden and Consequences of Medical Debt From Healthcare Bills Among Non-Elderly Adults With Atherosclerotic Cardiovascular Disease in the United States
Authors: Javier Valero-Elizondo, Rohan Khera, Anshul Saxena, Gowtham Grandhi, Salim S Virani, Javed Butler, Zainab Samad, Nihar Desai, Harlan M Krumholz, Khurram Nasir
Journal: Circulation (2018)

Introduction: Financial hardship caused by healthcare expenses is a growing problem for those with chronic conditions in US. In this study we examine the burden, financial consequences and cost-red...
Hair Reduction for Transgender Persons
Authors: Dustin H. Marks, J. Klint Peebles, Erica Dommasch
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
General Predictors and Moderators of Depression Remission: A VAST-D Report
Authors: Sidney Zisook, Gary R. Johnson, Ilanit Tal, Paul Hicks, Peijun Chen, Lori Davis, Michael Thase, Yinjun Zhao, Julia Vertrees, Somaia Mohamed
Journal: American Journal of Psychiatry (2019)

Objective: Almost two-thirds of patients with major depressive disorder do not achieve remission with initial treatments. Thus, identifying and providing effective, feasible, and safe “next-step” treatments are clinical imperatives. This study explores patient baseline features that might help clinicians select between commonly used next-step treatments. Methods: The authors used data from the U.S. Department of Veterans Affairs (VA) Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, a multisite, randomized, single-blind trial of 1,522 Veterans Health Administration patients who did not have an adequate response to at least one course of antidepressant treatment meeting minimal standards for dosage and duration. For 12 weeks, participants received one of three possible next-step treatments: switch to another antidepressant—sustained-release bupropion; combination with another antidepressant—sustained-release bupropion; or augmentation with an antipsychotic—aripiprazole. Life table regression models were used to identify baseline characteristics associated with remission overall (general predictors) and their interaction with remission among the three treatment groups (moderators). Results: Remission was more likely for individuals who were employed, less severely and chronically depressed, less anxious, not experiencing complicated grief symptoms, did not experience childhood adversity, and had better quality of life and positive mental health. Two features suggested specific next-step treatment selections: age ≥65 years (for whom augmentation with aripiprazole was more effective than switch to bupropion) and severe mixed hypomanic symptoms (for which augmentation with aripiprazole and combination with bupropion were more effective than switch to bupropion). Conclusions: If replicated, these preliminary findings could help clinicians determine which patients with depression requiring next-step treatment will benefit most from a specific augmentation, combination, or switching strategy.
Adjuvant Treatment of Hepatocellular Carcinoma: Prospect of Immunotherapy
Authors: Zachary J. Brown, Tim F. Greten, Bernd Heinrich
Journal: Hepatology (2019)

Although patients undergo procedures with curative intent for early‐stage hepatocellular carcinoma (HCC), up to 70% of patients may have disease recurrence in the liver at 5 years. Thus far, no therapy has proven to be effective in the adjuvant setting. Here, we discuss the application of immune‐based therapies in the adjuvant setting for HCC, focusing on the underlying rationale for immunotherapies, which patients may benefit from an immune‐based therapy, and what type of immune therapy should be implemented.
Medication Effects on Fecal Occult Blood Testing—Reply
Authors: Saroja Bangaru, Deepak Agrawal
Journal: JAMA Internal Medicine (2019)

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
Induction of cytotoxic T lymphocytes that recognize a tumor antigen, Mac-2 binding protein (M2BP) with an HLA-A24 restriction: The possibility of its clinical use as a target antigen in cancer immunotherapy
Authors: Keiichi Kontani, Yoshitomo Ozaki, Koji Teramoto, Takuya Fujita, Noriaki Tezuka, Satoru Sawai, Shozo Fujino
Journal: Cancer Research (2004)

5478  Mac-2 Binding Protein (M2BP) is highly expressed in various types of cancer cells and involved in cancer progression and regulation of the immune response in cancer patients. In the present study, we studied the possibility of its clinical use in cancer immunotherapy as a target antigen. CD8-positive T lymphocytes obtained from peripheral blood of HLA-24-positive normal volunteers were stimulated in vitro with 8 synthetic peptides derived from M2BP with HLA-24 binding motif and cultured in the presence of IL-2 for 3 weeks. The cytotoxic T lymphocytes (CTL) induced using the M2BP peptide (241-250) were shown to produce interferon-gamma in response to HLA-A24-positive leukemia cells pulsed with the same peptide. Also, the CTLs responded to cancer cells with both M2BP and HLA-A24 expressions, not to cancer cells lacking either M2BP or HLA-A24 expressions. These data suggest that M2BP is sufficiently immunogenic to elicit M2BP-specific cellular immune responses and that the M2BP peptide (241-250) is a CTL epitope. This molecule is expected to be useful as a target antigen in cancer immunotherapy.
Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial
Authors: Kazuhiro Yoshida, Yasuhiro Kodera, Mitsugu Kochi, Wataru Ichikawa, Yoshihiro Kakeji, Takeshi Sano, Narutoshi Nagao, Masazumi Takahashi, Akinori Takagane, Takuya Watanabe, Masahide Kaji, Hiroshi Okitsu, Takashi Nomura, Takanori Matsui, Takaki Yoshikawa, Jin Matsuyama, Makoto Yamada, Seiji Ito, Masahiro Takeuchi, Masashi Fujii
Journal: Journal of Clinical Oncology (2019)

S-1 is a standard postoperative adjuvant chemotherapy for patients with stage II or III gastric cancer in Asia. Neoadjuvant or perioperative strategies dominate in Western countries, and docetaxel has recently shown significant survival benefits when combined with other standard regimens in advanced cancer and perioperative settings.This randomized phase III study was designed to prove the superiority of postoperative S-1 plus docetaxel over S-1 alone for R0 resection of pathologic stage III gastric cancer. The sample size of 1,100 patients was necessary to detect a 7% increase in 3-year relapse-free survival as the primary end point (hazard ratio, 0.78; 2-sided α = .05; β = .2).The second interim analysis was conducted when the number of events reached 216 among 915 enrolled patients (median follow-up, 12.5 months). Analysis demonstrated the superiority of S-1 plus docetaxel (66%) to S-1 (50%) for 3-year relapse-free survival (hazard ratio, 0.632; 99.99% CI, 0.400 to 0.998; stratified log-rank test, P < .001), and enrollment was terminated as recommended by the independent data and safety monitoring committee. Incidences of grade 3 or greater adverse events, particularly neutropenia and leukopenia, were higher in the S-1 plus docetaxel group, but all events were manageable.Addition of docetaxel to S-1 is effective with few safety concerns in patients with stage III gastric cancer. The present findings may also be applicable in countries in which perioperative adjuvant chemotherapy or chemoradiation is not standard.
RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer
Authors: Violeta Serra, Pieter J.A. Eichhorn, Celina García-García, Yasir H. Ibrahim, Ludmila Prudkin, Gertrudis Sánchez, Olga Rodríguez, Pilar Antón, Josep-Lluís Parra, Sara Marlow, Maurizio Scaltriti, José Pérez-Garcia, Aleix Prat, Joaquín Arribas, William C. Hahn, So Young Kim, José Baselga
Journal: Journal of Clinical Investigation (2014)
Understanding the riboflavin biosynthesis pathway for the development of antimicrobial agents
Authors: Biswajit Kundu, Dipayan Sarkar, Namrata Ray, Arindam Talukdar
Journal: Medicinal Research Reviews (2019)

Abstract Life on earth depends on the biosynthesis of riboflavin, which plays a vital role in biological electron transport processes. Higher mammals obtain riboflavin from dietary sources; however, various microorganisms, including Gram‐negative pathogenic bacteria and yeast, lack an efficient riboflavin‐uptake system and are dependent on endogenous riboflavin biosynthesis. Consequently, the inhibition of enzymes in the riboflavin biosynthesis pathway would allow selective toxicity to a pathogen and not the host. Thus, the riboflavin biosynthesis pathway is an attractive target for designing novel antimicrobial drugs, which are urgently needed to address the issue of multidrug resistance seen in various pathogens. The enzymes involved in riboflavin biosynthesis are lumazine synthase (LS) and riboflavin synthase (RS). Understanding the details of the mechanisms of the enzyme‐catalyzed reactions and the structural changes that occur in the enzyme active sites during catalysis can facilitate the design and synthesis of suitable analogs that can specifically inhibit the relevant enzymes and stop the generation of riboflavin in pathogenic bacteria. The present review is the first compilation of the work that has been carried out over the last 25 years focusing on the design of inhibitors of the biosynthesis of riboflavin based on an understanding of the mechanisms of LS and RS. This review aimed to address the fundamental advances in our understanding of riboflavin biosynthesis as applied to the rational design of a novel class of inhibitors. These advances have been aided by X‐ray structures of ligand‐enzyme complexes, rotational‐echo, double‐resonance nuclear magnetic resonance spectroscopy, high‐throughput screening, virtual screenings, and various mechanistic probes.
“Is It Safe?” — The Many Unanswered Questions about Medications and Breast-Feeding
Authors: John J. Byrne, Catherine Y. Spong
Journal: New England Journal of Medicine (2019)

More than half of new mothers take one or more medications in the months after delivery. But health care providers often lack the evidence they need to counsel breast-feeding women on medications' potential effects on lactation, on mothers, or on their babies.
Elastic 3D‐Printed Hybrid Polymeric Scaffold Improves Cardiac Remodeling after Myocardial Infarction
Authors: Yang Yang, Dong Lei, Shixing Huang, Qi Yang, Benyan Song, Yifan Guo, Ao Shen, Zhize Yuan, Sen Li, Feng‐Ling Qing, Xiaofeng Ye, Zhengwei You, Qiang Zhao
Journal: Advanced Healthcare Materials (2019)

Myocardial remodeling, including ventricular dilation and wall thinning, is an important pathological process caused by myocardial infarction (MI). To intervene in this pathological process, a new type of cardiac scaffold composed of a thermoset (poly-[glycerol sebacate], PGS) and a thermoplastic (poly-[ε-caprolactone], PCL) is directly printed by employing fused deposition modeling 3D-printing technology. The PGS-PCL scaffold possesses stacked construction with regular crisscrossed filaments and interconnected micropores and exhibits superior mechanical properties. In vitro studies demonstrate favorable biodegradability and biocompatibility of the PGS-PCL scaffold. When implanted onto the infarcted myocardium, this scaffold improves and preserves heart function. Furthermore, the scaffold improves several vital aspects of myocardial remodeling. On the morphological level, the scaffold reduces ventricular wall thinning and attenuated infarct size, and on the cellular level, it enhances vascular density and increases M2 macrophage infiltration, which might further contribute to the mitigated myocardial apoptosis rate. Moreover, the flexible PGS-PCL scaffold can be tailored to any desired shape, showing promise for annular-shaped restraint device application and meeting the demands for minimal invasive operation. Overall, this study demonstrates the therapeutic effects and versatile applications of a novel 3D-printed, biodegradable and biocompatible cardiac scaffold, which represents a promising strategy for improving myocardial remodeling after MI.
Role of vitamin D receptor in the regulation of CYP3A gene expression
Authors: Xuan Qin, Xin Wang
Journal: Acta Pharmaceutica Sinica B (2019)

Vitamin D3 (VD3) is a multifunctional nutrient which can be either synthesized or absorbed from the diet. It plays a pivotal role in systemic calcium and phosphate homeostasis, as well as in various physiological and pathological processes. VD3 is converted to the active form, 1α,25-dihydroxyvitamin D3 (1,25-D3), by cytochrome P450 2R1 (CYP2R1)/CYP27A1 and CYP27B1 sequentially, and deactivated by multiple enzymes including CYP3A4. On the other hand, 1,25-D3 is capable of activating the transcription of CYP3A genes in humans, mice and rats. The vitamin D receptor (VDR)-mediated transactivation of human CYP3A4 and CYP3A5 resembles that known for pregnane X receptor (PXR). Activated VDR forms a heterodimer with retinoid X receptor α (RXRα), recruits co-activators, translocates to the cell nucleus, binds to the specific vitamin D responsive elements (VDRE), and activates the gene transcription. In mice, intestinal Cyp3a11 mRNA levels, but not those of hepatic CYP3As, were induced by in vivo administration of VDR and PXR agonists. In rats, intestinal Cyp3a1 and Cyp3a2 mRNAs were induced by 1,25-D3 or lithocholic acid (LCA), whereas hepatic Cyp3a2, but not Cyp3a1 and Cyp3a9, was modulated to 1,25-D3 treatment. In general, the VDR-mediated regulation of CYP3A presents species and organ specificity.