tbuckley/cabot-search huggingface dataset:
Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults
Authors: John F. Trepanowski, Cynthia M. Kroeger, Adrienne Barnosky, Monica C. Klempel, Surabhi Bhutani, Kristin K. Hoddy, Kelsey Gabel, Sally Freels, Joseph Rigdon, Jennifer Rood, Eric Ravussin, Krista A. Varady
Journal: JAMA Internal Medicine (2017)

Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy.To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease.A single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois.Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating "feast days"), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase.The primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease.Among the 100 participants (86 women and 14 men; mean [SD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% CI, -9.1% to -4.6%]) and month 12 (-6.0% [95% CI, -8.5% to -3.6%] vs -5.3% [95% CI, -7.6% to -3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group.Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction.clinicaltrials.gov Identifier: NCT00960505.
Cell Therapy in Kidney Transplantation: Focus on Regulatory T Cells
Authors: Nicholas A. Zwang, Joseph R. Leventhal
Journal: Journal of the American Society of Nephrology (2017)

Renal transplantation is the renal replacement modality of choice for suitable candidates with advanced CKD or ESRD. Prevention of rejection, however, requires treatment with nonspecific pharmacologic immunosuppressants that carry both systemic and nephrologic toxicities. Use of a patient’s own suppressive regulatory T cells (Tregs) is an attractive biologic approach to reduce this burden. Here, we review the immunologic underpinnings of Treg therapy and technical challenges to developing successful cell therapy. These issues include the selection of appropriate Treg subsets, ex vivo Treg expansion approaches, how many Tregs to administer and when, and how to care for patients after Treg administration.
Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation
Authors: Marie Toussaint, David J Jackson, Dawid Swieboda, Anabel Guedán, Theodora-Dorita Tsourouktsoglou, Yee Man Ching, Coraline Radermecker, Heidi Makrinioti, Julia Aniscenko, Nathan W Bartlett, Michael R Edwards, Roberto Solari, Frédéric Farnir, Venizelos Papayannopoulos, Fabrice Bureau, Thomas Marichal, Sebastian L Johnston
Journal: Nature Medicine (2017)
Balancing the Training of Future Cardiologists With the Provision of Team-Based Care
Authors: Susan M. Fernandes, Rhonda L. Larsen, Garrett K. Chan
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Is there enough evidence that low-molecular-weight heparin is superior to unfractionated heparin in pulmonary embolism? [5] (multiple letters)
Authors: G. K. Sharma, R. D. Hull, G. E. Raskob, R. F. Brant, G. F. Pineo, P. D. Stein, A. F. Mah
Journal: JAMA Internal Medicine (2000)
Patient-Derived Induced Pluripotent Stem Cells Identified SLITRK4 As a Causative Gene of Chronic Myelomonocytic Leukemia
Authors: Sho Yamazaki, Kazuki Taoka, Shunya Arai, Masashi Miyauchi, Keisuke Kataoka, Akihide Yoshimi, Mineo Kurokawa
Journal: Blood (2016)
Efficacy and safety of abatacept, a T-cell modulator, in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis
Authors: Philip J Mease, Alice B Gottlieb, Désirée van der Heijde, Oliver FitzGerald, Alyssa Johnsen, Marleen Nys, Subhashis Banerjee, Dafna D Gladman
Journal: Annals of the Rheumatic Diseases (2017)

To assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA).This study randomised patients (1:1) with active PsA (~60% with prior exposure to a tumour necrosis factor inhibitor) to blinded weekly subcutaneous abatacept 125 mg (n=213) or placebo (n=211) for 24 weeks, followed by open-label subcutaneous abatacept. Patients without ≥20% improvement in joint counts at week 16 were switched to open-label abatacept. The primary end point was the proportion of patients with ≥20% improvement in the American College of Rheumatology (ACR20) criteria at week 24.Abatacept significantly increased ACR20 response versus placebo at week 24 (39.4% vs 22.3%; p<0.001). Although abatacept numerically increased Health Assessment Questionnaire-Disability Index response rates (reduction from baseline ≥0.35) at week 24, this was not statistically significant (31.0% vs 23.7%; p=0.097). The benefits of abatacept were seen in ACR20 responses regardless of tumour necrosis factor inhibitor exposure and in other musculoskeletal manifestations, but significance could not be attributed due to ranking below Health Assessment Questionnaire-Disability Index response in hierarchical testing. However, the benefit on psoriasis lesions was modest. Efficacy was maintained or improved up to week 52. Abatacept was well tolerated with no new safety signals.Abatacept treatment of PsA in this phase III study achieved its primary end point, ACR20 response, showed beneficial trends overall in musculoskeletal manifestations and was well tolerated. There was only a modest impact on psoriasis lesions.ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb).
Prognostic quantification of non-small cell lung cancer metastases to the lung
Authors: Y. Oh, G. Srivastava, V. Rana, R. Munden, B. N. Bekele, D. Karp
Journal: Journal of Clinical Oncology (2006)

17080 Background: Lung is the most frequent organ site of metastases from non-small cell lung cancer (NSCLC), yet the impact of these metastases on the natural history of the disease has not been well elucidated. Part of the difficulty of evaluating the prognosis of lung metastases in NSCLC patients is the effect of metastases to other organ sites. Here we have studied the survival of patients with lung as the solitary or dominant site of metastases and correlated it with number and maximal size of tumors. Methods: Data from the M.D. Anderson Cancer Center Tumor Registry during 1998 to 2002 was interrogated. Of 1280 patients registering as new patients, 87 were evaluable as having lung as the only site of metastases on initial staging evaluation. Excluding 13 patients who had bronchioloalveolar carcinoma (BAC) or BAC features on histology, the remaining 74 patients’ baseline CT scans were reviewed and scored for 1) the maximal linear measurement of the largest lung tumor and 2) the number of lung nodules that were growing and consistent with lung metastases. Results: In non-BAC patients with lung only metastases, an inverse correlation is seen between maximal linear measurement of a patient’s largest lung metastasis on baseline staging and their subsequent survival. A similar inverse correlation is seen between the number of lung metastases and survival. When patients with subsequent development of other metastatic sites are excluded from the analysis, these correlations are strengthened. Also, in BAC patients with lung only metastases, a trend toward longer survival with fewer metastases was seen, but only 13 patients were evaluable. Formal statistical analysis of these results is pending. Conclusions: The number and size of lung metastases from NSCLC appear to be independent predictors of survival. This might be explained by lead-time bias where fewer lesions represent an earlier stage of metastatic disease, however, increasing number and size of metastases may also be multiplying the source for further metastatic spread of disease. This interpretation of data may justify the local therapy of individual lung metastases in oligometastatic disease by surgery, stereotactic radiosurgery, or radiofrequency ablation. No significant financial relationships to disclose.
Cell Marker May Help Identify Latent HIV Reservoirs
Authors: Tracy Hampton
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
Tofacitinib for Ulcerative Colitis — A Promising Step Forward
Authors: Sonia Friedman
Journal: New England Journal of Medicine (2017)

Ulcerative colitis is a chronic inflammatory disease of the colon that is often debilitating, commonly occurs at a young age, and has a serious effect on overall health and quality of life. The use of currently available medications for moderate-to-severe ulcerative colitis results in sustained remission less than 30% of the time, and 20 to 30% of patients with ulcerative colitis eventually need to undergo a colectomy, which has its own complications and consequent problems. The worldwide incidence of ulcerative colitis is increasing, with rates as high as 19.2 cases per 100,000 persons in North America, 24.3 per 100,000 in . . .
Multicenter phase II study combining panitumumab with chemoradiation followed by surgery for patients with operable esophageal cancer (PACT-study).
Authors: Sil Kordes, Dirk Richel, Mark I. van Berge Henegouwen, Maarten C. Hulshof, Sybren L. Meijer, Johanna Wilmink
Journal: Journal of Clinical Oncology (2012)

4094 Background: A consistent finding in many studies in patients with operable esophageal and gastro-esophageal junction cancer is that response to preoperative therapy, particularly the absence of residual disease in the surgical specimen, is an indicator of better disease-free and overall survival. One of the potential strategies to improve these local effects of preoperative chemoradiation (CRT) is the concurrent inhibition of the epidermal growth factor receptor (EGFR). Therefore in our trial we evaluated the pathologic response of panitumumab in combination with neoadjuvant CRT as first line treatment of operable adenocarcinomas or squamous cell carcinomas of the esophagus. Methods: Patients with resectable cT1N1M0 or cT2-3N0-2M0 tumors received preoperative CRT consisting of 3 administrations of panitumumab (6mg/kg) in weeks 1-3-5, weekly administrations of carboplatin (AUC = 2) and paclitaxel (50 mg·m 2 ) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery. The primary endpoint was the percentage of pathologic complete responses (pCR). Results: From January 2010 till December 2011, 91 patients were enrolled. 3 patients were not resected due to the development of metastatic disease during CRT. Results of all patients will be presented at ASCO. The majority of the 74 patients operated thus far had T3 (85%) and node positive (77%) tumors. 21.6% reached pCR and 13.5% had less than 10% viable tumor cells in the resected specimen. R0-resection was achieved in 98.6%. There were 58 patients with adenocarcinoma and 11 patients with squamous cell carcinoma. The pCR of these patients were 15.5% and 45.5%, respectively. Main grade 3 toxicities were esophagitis, fatigue, rash and anorexia. 1 postoperative death occurred due to ischemia of the esophageal reconstruction. Conclusions: The addition of panitumumab to chemoradiotherapy with carboplatin and paclitaxel was feasible without increasing postoperative mortality, but did not improve the rate of pathologic complete responses compared to historical data.
Abstract 17947: Regulator of G-Protein Signaling 5 Prevents Smooth Muscle Cell Proliferation and Attenuates Neointima Formation
Authors: Jan-Marcuss Daniel, Andre Prock, Jochen Dutzmann, Johann Bauersachs, Daniel Sedding
Journal: Circulation (2015)

Introduction: Regulator of G-protein signaling 5 (RGS5) is abundantly and specifically expressed in vascular smooth muscle cells (SMCs) and inhibits G-protein signaling by enhancing the GTP-hydrolyzing activity of Gα-subunits. Hypothesis: In the present study, we aimed to investigate the effects of RGS5 on vascular SMC function in vitro and neointima formation in vivo and to determine the underlying molecular mechanisms. Methods: Expression of RGS5 was assessed in vitro and in vivo by qPCR, immunoblotting and immunohistochemistry. Proliferation and migration of human coronary artery SMC were assessed in vitro following the adenoviral-mediated over expression of wild type (WT) RGS5, of a non-degradable mutant (C2A-RGS5) or siRNA-mediated knock down. In vivo, the proliferation and neointima formation were assessed in a wire-mediated injury model of the femoral artery in C57BL/6J mice. Results: We found a robust expression of RGS5 in native arteries of C57BL/6 mice and a significant down-regulation within neointimal lesions 10 and 21 days after vascular injury as assessed by qPCR, immunohistochemistry and immunoblotting. In vitro, RGS5 was found significantly down-regulated after mitogenic stimulation of SMCs. Overexpression of RGS5 or, even more prominently, the C2A-RGS5 mutant prevented SMC proliferation and migration. In contrast, the siRNA-mediated knockdown of RGS5 significantly augmented SMC proliferation. Following overexpression of RGS5, FACS analysis of propidium iodide-stained cells indicated cell cycle arrest in G0/G1 phase. Mechanistically, inhibition of ERK1/2 phosphorylation and MAPK downstream signaling was found to be responsible for the anti-proliferative effect since over expression of a constitutive active form of MEK reversed the growth-inhibitory effect of of RGS5. Following wire-induced injury, adenoviral-mediated overexpression of RGS5 or C2A-RGS5 significantly decreased ERK phosphorylation, SMC proliferation and neointima formation in vivo (n=8; p&lt;0.001). Conclusions: Down-regulation of RGS5 is an important prerequisite for SMC proliferation and neointima Formation. Therefore, reconstitution of RGS5 levels might represent a promising therapeutic option to prevent vascular remodeling processes.
Enhanced orotate phosphoribosyltransferase activity in renal cell carcinoma and its prognostic significance
Authors: Y. Mizutani, D. Toiyama, T. Shiraishi, T. Nakamura, K. Mikami, N. Takaha, K. Okihara, O. Ukimura, A. Kawauchi, T. Miki
Journal: Journal of Clinical Oncology (2007)

15590 Background: 5-Fluorouracil ( 5-FU ) is an anticancer agent clinically used against various cancers including renal cell carcinoma ( RCC ). 5-FU is a prodrug and orotate phosphoribosyltransferase ( OPRT ) is the principal enzyme which directly converts 5-FU to an active anticancer metabolite, 5-fluoro-2’-deoxyuridine 5’-monophosphate. Furthermore, OPRT is the key enzyme in the de novo DNA and RNA synthetic process, which converts orotic acid to orotidine 5’-phosphate. Little is known about the significance of OPRT in a variety of cancers including RCC. We investigated OPRT activity in 83 RCC and evaluated the association between OPRT activity and the stage/grade of RCC. The relationship between OPRT activity in RCC cells and their sensitivity to 5-FU was also examined. Methods: OPRT activity in non-fixed fresh frozen RCC and normal kidney were determined enzymatically by the 5-FU phosphorylation assay. The sensitivity of RCC cells to 5-FU was assessed by the microculture tetrazolium dye assay. Results: OPRT activity was approximately 8.5-fold higher in RCC compared to normal kidney. OPRT activity in T3/4 RCC was 3-fold higher than that in T1/2 RCC. OPRT activity in M1 RCC was 2.5-fold higher than that in M0 RCC. In addition, OPRT activity in Stage III/IV RCC was 3-fold higher than that in Stage I/II RCC. The level of OPRT activity in Grade 3 RCC was 3-fold higher than that in Grade 1/2 cancer. Patients with RCC with low OPRT activity had a longer postoperative disease-specific survival than those with high activity in the 5-year follow-up. OPRT activity in RCC cells positively correlated with their sensitivity to 5-FU. Conclusions: The present study has demonstrated that OPRT activity in RCC was higher than that in normal kidney, and that OPRT activity positively correlated with the stage/grade of RCC. Moreover, higher OPRT activity in RCC predicted worse prognosis and higher sensitivity to 5-FU. These results suggest that OPRT activity may be used as both a prognostic parameter and a predictive indicator for 5-FU efficacy in RCC. No significant financial relationships to disclose.
Excess Treatment-Related Mortality in Obese Children and Adolescents with Acute Myeloid Leukemia on AAML0531: A Report from the Children's Oncology Group
Authors: Lillian Sung, Robert Gerbing, Todd A. Alonzo, Yi-Cheng Wang, Etan Orgel, Alan S. Gamis, Richard Aplenc
Journal: Blood (2016)
The BMJ Awards 2018: Outstanding Contribution to Health
Authors: Nigel Hawkes
Journal: BMJ (2018)

Wendy Savage always has a new campaign up her sleeve. “If I get a call at 8 30 am on a Saturday morning, it’ll be Wendy saying, ‘I’ve got this fantastic idea,’” says Melanie Davies, consultant obstetrician and gynaecologist at University College London Hospitals. “She’s an inveterate campaigner—it’s her raison d’etre.”

It’s this campaigning spirit, particularly on the NHS and women’s rights, that make Wendy Savage a worthy winner of this year’s The BMJ Award for Outstanding Contribution to Health.

Jacky Davis, the consultant radiologist who, with Savage, started the campaign Keep our NHS Public in 2005, knows her well but admits she has no idea of half of what she does. Her quality, she says, is absolute fearlessness. “She’s been involved in lots of organisations, including the GMC and the BMA, and she’s achieved what she has by challenging the medical establishment. She will speak truth to power.”

Her unflinching nature was forged in 1985 when she was the victim of an attempt to unseat her from her position as senior lecturer in obstetrics at the (then) London Hospital. What started as a difference over style and attitude quickly turned into allegations of incompetence, and two trials …