tbuckley/cabot-search huggingface dataset:
Abstract 402: Vitamin C Deficiency Impairs Cardiac Function and Post-infarction Survival in the Mouse
Authors: Adolfo G Mauro, Donatas Kraskauskas, Bassem M Mohammed, Bernard J Fisher, Eleonora Mezzaroma, Alpha A Fowler, Ramesh Natarajan, Stefano Toldo
Journal: Circulation Research (2017)

Introduction: L-gulonolactone oxidase (Gulo) is the rate limiting enzyme for Vitamin C (VitC) biosynthesis. Humans rely on dietary VitC for collagen synthesis, extracellular matrix formation, and tissue regeneration. VitC deficiency is an unrecognized condition and its role in cardiac homeostasis and post-acute myocardial infarction (AMI) remodeling is unknown. Hypothesis: Low levels of VitC impair cardiac function and tissue repair following AMI. Methods: Adult male Gulo -/- knockout mice (C57BL6 background, N=8) and control C57BL (N=8), which are able to synthesize VitC were used. VitC deficiency was maintained supplying low levels of VitC (30mg/l) to Gulo -/- mice in drinking water. Mice underwent M-mode and Doppler echocardiography to measure left ventricular (LV) diameters and wall thicknesses, fractional shortening (FS), E and A waves, E/A ratio, isovolumetric relaxation time (IRT) and myocardial performance index (MPI). Experimental AMI was induced by coronary artery ligation for 7 days. An additional group of Gulo -/- were mice supplemented with physiological levels of VitC (330 mg/l) and underwent AMI. Results: VitC deficient Gulo -/- mice exhibited significantly reduced LV wall thicknesses, reduced FS, and impaired diastolic function, measured as significantly reduced E/A ratio and longer IRT (Panel A, B &amp; C). Following AMI, 100% (8/8) of deficient Gulo -/- mice died within 5 days. Supplementation with physiological levels of VitC significantly improved survival after AMI (Panel D). Conclusion: VitC deficiency impairs systolic and diastolic function. Moreover, VitC is critical for the post-AMI survival.
The Garden at Age 70
Authors: Jerome W. Freeman
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Why replication has more scientific value than original discovery
Authors: John P. A. Ioannidis
Journal: Behavioral and Brain Sciences (2018)

Abstract The presumed dominance of “original discovery” over replication is an anomaly. Original discovery has more value than replication primarily when scientific investigation can immediately generate numerous discoveries most of which are true and accurate. This scenario is uncommon. A model shows how original discovery claims typically have small or even negative value. Science becomes worthy mostly because of replication.
Neural-Tube Defects with Dolutegravir Treatment from the Time of Conception
Authors: Rebecca Zash, Joseph Makhema, Roger L Shapiro
Journal: New England Journal of Medicine (2018)

Dolutegravir and Neural-Tube Defects Preventing mother-to-child transmission of HIV is a priority, but assessing a medication for potential side effects in pregnancy is complicated. In this letter, preliminary data on a possible side effect of dolutegravir are presented.
Pembrolizumab (Pembro) plus enzalutamide (Enz) in metastatic castration resistant prostate cancer (mCRPC): Extended follow up.
Authors: Julie Nicole Graff, Joshi J. Alumkal, Reid F. Thompson, Amy Moran, George V. Thomas, Mary A Wood, Charles G. Drake, Rachel Slottke, Tomasz M. Beer
Journal: Journal of Clinical Oncology (2018)

5047 Background: Anti-PD1 treatment with Pembro is a promising treatment strategy in many solid tumors. Here, we report clinical outcomes of adding Pembro to men with mCRPC progressing on Enz. Methods: We enrolled 28 patients with mCRPC who had not previously had chemotherapy for mCRPC or checkpoint inhibitors. Pembro was given 200 mg IV every 3 weeks for 4 doses, which could be repeated for the patients who had stable or responsive disease. The primary endpoint was prostate specific antigen (PSA) response (PSA decline of ≥ 50%). Secondary endpoints were radiographic objective response (RECIST 1.1), PSA progression free survival, time to subsequent treatment, and time to death from any cause. Baseline tumor biopsies were done if there was a metastatic deposit amenable to biopsy. We are presenting updated clinical outcomes and evaluation of samples for presence of Program Death-Ligand 1 (PD-L1), microsatellite instability (MSI) and DNA repair defects. Results: Five of 28 patients (18%) had a PSA decline of ≥ 50%. Three of 12 patients (25%) with measurable disease at baseline achieved an objective response on radiographs. Of the responders (R), one passed away from an unrelated cause without PSA recurrence after 14.2 mos, and one relapsed after 10 mos and did not respond to a second course of Pembro. The other 3 continue to be in response (range 21.9-33.8 mos). For the entire cohort, the median follow up was 22.7 mos, and the median PSA-PFS time was 3.8 mos (95% CI: 2.8 – 9.9 mos). Time to subsequent treatment was 8.2 mos (95% CI: 5.1 – 12.8 mos). Median overall survival was 22.2 mos (95% CI: 14.7 – 28 .4 mos). Median radiographic PFS was 10.8 mos (5-22 mos). There were 8 immune related adverse events in 7 unique patients (hypothyroid 3, hyperthyroid 1, myositis 2, colitis 2). Seventeen patients had baseline biopsies of a metastatic deposit: 3 R, 14 non-responders (NR). Of the 3 R who had baseline biopsies, one had MSI and DNA repair defects. The other 2 had neither. Of the NR who had sequencing, 4 had a DNA repair defects, and none had MSI. None of the biopsies showed tumoral PD-L1 expression (Qualtek, 22C3). Conclusions: Pembro has activity in mCRPC when added to Enz. Responses were deep and durable in a subset of patients. Clinical trial information: NCT02312557.
18F-FDG PET/CT in a Patient With Pregnancy and Lactation-Associated Osteoporosis
Authors: Jinchuan Chen, Qian Wang, Liheng Qiu
Journal: Clinical Nuclear Medicine (2018)

A 33-year-old woman in the 6th month postpartum and breast-feeding period suffered from acute thoracolumbar pain for 1 month. She presented with slightly decreased serum calcium level. Other laboratory assessments were unremarkable. Considering the worsening symptom and her strong demand to exclude potential malignancy, F-FDG PET/CT was performed. Multiple FDG-avid foci in the thoracic and lumbar vertebra were detected on FDG PET, corresponding to vertebral compression fractures on CT, and diffuse FDG uptake was seen within bilateral breast, and dual-X ray absorptiometry showed markedly decreased bone mineral density, all of which supported the diagnosis of pregnancy and lactation-associated osteoporosis.
Rectal Cancer, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology
Authors: Al B. Benson, Alan P. Venook, Mahmoud M. Al-Hawary, Lynette Cederquist, Yi-Jen Chen, Kristen K. Ciombor, Stacey Cohen, Harry S. Cooper, Dustin Deming, Paul F. Engstrom, Jean L. Grem, Axel Grothey, Howard S. Hochster, Sarah Hoffe, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Jeffrey Meyerhardt, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Evan Wuthrick, Kristina M. Gregory, Lisa Gurski, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2018)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer. This portion of the guidelines focuses on the management of localized disease, which involves careful patient selection for curative-intent treatment options that sequence multimodality therapy usually comprised of chemotherapy, radiation, and surgical resection.
Halobetasol 0.01%/tazarotene 0.045% lotion in the treatment of moderate-to-severe plaque psoriasis: Maintenance of therapeutic effect after cessation of therapy
Authors: David M Pariser, Lawrence J Green, Linda Stein Gold, Jeffrey L Sugarman, Tina Lin, Radhakrishnan Pillai
Journal: Journal of the American Academy of Dermatology (2019)
Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes
Authors: Michela Miani, Julie Le Naour, Emmanuelle Waeckel-Enée, Subash chand Verma, Marjolène Straube, Patrick Emond, Bernhard Ryffel, Peter van Endert, Harry Sokol, Julien Diana
Journal: Cell Metabolism (2018)
The Making of a PreCancer Atlas: Promises, Challenges, and Opportunities
Authors: Sudhir Srivastava, Sharmistha Ghosh, Jacob Kagan, Richard Mazurchuk, Emily Boja, Rodrigo Chuaqui, Eric Chavarria-Johnson, Tanja Davidsen, Janet Eary, Todd Haim, Sean Hanlon, Stephen Hewitt, Shannon Hughes, Paula Jacobs, Jerry Li, Tracy Lively, Stephen Lockett, Tom Misteli, Stefanie Nelson, Hana Odeh, Miguel Ossandon, Sonia Rosenfield, Goli Samimi, Jack Shern, Rob Star, Naoko Takebe, Norbert Tavares, James Tricoli, Ted Trimble, Asad Umar, Jose Velazquez, Chiayeng Wang, JC Zenklusen, Philipp Oberdoerffer, Jerry Lee, Nicholas Kenney
Journal: Trends in cancer (2018)
AB0839 Radiologic parameters of ankylosing spondylitis patients treated with anti-tnf-Α versus non-steroidal anti-inflammatory drugs and sulfasalazine
Authors: S.M. Son, J.S. Lee, T.S. Goh, W. Park
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The introduction of anti-tumour necrosis factor-α (anti-TNF-α) has significantly altered the treatment landscape of inflammatory arthritis. It has proven to be an excellent treatment option for reducing Ankylosing spondylitis(AS) symptoms. The impact of anti-TNF-α on the radiographic progression of AS has been difficult to characterise, in part because of the relatively slow rate of radiographic change in AS and the hurdles it imposes on longer-term placebo-controlled trials. Despite symptomatic improvement, conclusions concerning effect of anti-TNF-α treatment on radiographic progression in patients with AS remain inconsistent. Furthermore, while many studies have reported the impact of anti-TNF-α on radiographic progression, limited data are available on the relationship between treatment agents and sagittal balance in AS. <h3>Objectives</h3> Limited data are available on the relationship between treatment agents and sagittal balance in AS. We investigated radiological features related to treatment agents and compared sagittal balance between patients treated with anti-tumour necrosis factor-α (anti-TNF- α) or non-steroidal anti-inflammatory drugs (NSAIDs) and sulfasalazine. <h3>Methods</h3> We prospectively enrolled 133 consecutive AS patients. Patients were eligible for the trial if they were under medical treatment with the same treatment agents for at least 1 year. All patients were treated initially with NSAIDs and sulfasalazine. Sixty-nine patients were achieved an excellent pain control outcome with these agents (Group A). Sixty-four patients who complained of intractable low back pain were switched to anti-TNF-α treatment (Group B). Twelve radiographic parameters were measured. Clinical outcome was assessed with the Bath AS Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). All parameters were measured at enrolment, upon changing treatment agents, and every 6 months during follow-up. <h3>Results</h3> Mean ESR, CRP, BASDAI, and thoracic kyphosis at baseline were significantly higher in group B. After treatment, group B had significantly higher lumbar lordosis and significantly better clinical outcomes. Correlation analysis revealed significant relationships between radiologic parameters and BASDAI. On multiple regression analysis, lumbar lordosis was a significant predictor of BASDAI. <h3>Conclusions</h3> This study demonstrated a clear association between treatment agents and radiologic parameters in AS. Anti-TNF-α treatment improved lumbar lordosis and slowed thoracic kyphotic progression with improvement of clinical outcomes. Lumbar lordosis was a significant predictor of clinical outcome in AS patients treated with anti-TNF-α <h3>Disclosure of Interest</h3> None declared
Temporal Associations of Alcohol and Tobacco Consumption With Cancer Mortality
Authors: Heng Jiang, Michael Livingston, Robin Room, Richard Chenhall, Dallas R. English
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Understanding whether the population-level consumption of alcohol and tobacco is associated with cancer mortality is a crucial question for public health policy that has not been answered by previous studies. <h3>Objective</h3> To examine temporal associations of alcohol and tobacco consumption with overall cancer mortality in the Australian population, looking across different sex and age groups. <h3>Design, Setting, and Participants</h3> This population-based cohort study conducted a time series analysis (autoregressive integrated moving average models) using aggregate-level annual time series data from multiple sources. Data on alcohol consumption and tobacco consumption per capita between 1935 and 2014 among the Australian population aged 15 years and older were collected from the Australian Bureau of Statistics and Cancer Council Victoria. Analysis was conducted from June 1, 2017, to October 30, 2017. <h3>Exposures</h3> Sex- and age-specific cancer mortality rates from 1968 to 2014 were collected from the Australian Institute Health and Welfare. <h3>Main Outcomes and Measures</h3> Population-level cancer mortality in different sex and age groups in Australia, controlling for the effects of health expenditure. <h3>Results</h3> Among the Australian total population aged 15 years and older in this study, 50.5% were women. Cancer death rates per 100 000 persons increased from 199 in 1968 to 214 in 1989 and then decreased steadily to 162 in 2014. Taking into account lagged effects, 1-L decreases in alcohol consumption per capita were associated with a decline of 3.9% in overall cancer mortality over a 20-year period, and 1-kg decreases in tobacco consumption per capita were associated with a 16% reduction. Alcohol consumption per capita was significantly associated with overall cancer mortality among men aged 50 to 69 years and women aged 50 years and older. Tobacco consumption per capita was found to be significantly associated with overall cancer mortality only among men aged 50 years and older. <h3>Conclusions and Relevance</h3> In this study, alcohol consumption per capita was positively associated with overall cancer mortality among older men and women, and tobacco consumption per capita was positively associated with overall cancer mortality among older men over a 20-year period. This study provides evidence that a decrease in population-level drinking and tobacco smoking could lead to a reduction in cancer mortality.
Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma
Authors: Zhigang Ren, Ang Li, Jianwen Jiang, Lin Zhou, Zujiang Yu, Haifeng Lu, Haiyang Xie, Xiaolong Chen, Li Shao, Ruiqing Zhang, Shaoyan Xu, Hua Zhang, Guangying Cui, Xinhua Chen, Ranran Sun, Hao Wen, Jan P Lerut, Quancheng Kan, Lanjuan Li, Shusen Zheng
Journal: Gut (2018)

Objective To characterise gut microbiome in patients with hepatocellular carcinoma (HCC) and evaluate the potential of microbiome as non-invasive biomarkers for HCC. Design We collected 486 faecal samples from East China, Central China and Northwest China prospectively and finally 419 samples completed Miseq sequencing. We characterised gut microbiome, identified microbial markers and constructed HCC classifier in 75 early HCC, 40 cirrhosis and 75 healthy controls. We validated the results in 56 controls, 30 early HCC and 45 advanced HCC. We further verified diagnosis potential in 18 HCC from Xinjiang and 80 HCC from Zhengzhou. Results Faecal microbial diversity was increased from cirrhosis to early HCC with cirrhosis. Phylum Actinobacteria was increased in early HCC versus cirrhosis. Correspondingly, 13 genera including Gemmiger and Parabacteroides were enriched in early HCC versus cirrhosis. Butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early HCC versus controls. The optimal 30 microbial markers were identified through a fivefold cross-validation on a random forest model and achieved an area under the curve of 80.64% between 75 early HCC and 105 non-HCC samples. Notably, gut microbial markers validated strong diagnosis potential for early HCC and even advanced HCC. Importantly, microbial markers successfully achieved a cross-region validation of HCC from Northwest China and Central China. Conclusions This study is the first to characterise gut microbiome in patients with HCC and to report the successful diagnosis model establishment and cross-region validation of microbial markers for HCC. Gut microbiota-targeted biomarkers represent potential non-invasive tools for early diagnosis of HCC.
Opportunities and priorities for breast surgical research
Authors: Ramsey I Cutress, Stuart A McIntosh, Shelley Potter, Amit Goyal, Cliona C Kirwan, James Harvey, Adele Francis, Amtul R Carmichael, Raghavan Vidya, Jayant S Vaidya, Patricia Fairbrother, John R Benson, Malcolm W R Reed, Narendra N Basu, John R Benson, Nigel J Bundred, Amtul R Carmichael, Nathan Coombs, Ramsey I Cutress, John Dickson, J Michael Dixon, Michael Douek, Patricia Fairbrother, Adele Francis, Amit Goyal, Diana Harcourt, James Harvey, Chris Holcombe, Jonathan Horsnell, Fahad M Iqbal, Lucy R Khan, Cliona C Kirwan, Daniel R Leff, Anthony J Maxwell, Stuart A McIntosh, Nicole Paraskeva, Shelley Potter, Tim Rattay, Malcolm WR Reed, Amtul S Sami, Julian Singer, Edward R St John, Ash Subramanian, Jeffrey S Tobias, Nader Touqan, Jayant S Vaidya, Raghavan Vidya, Zoe E Winters
Journal: The Lancet Oncology (2018)
Abstract 10862: Safety and Effectiveness of Innovative Tissue Therapy for Porcine Myocardial Infarction Using Autologous Skeletal-myobkast-sheets
Authors: Yutaka Terajima, Tatsuya Shimizu, Shinpei Tsuruyama, Hidekazu Sekine, Hikaru Ishii, Kenji Yamazaki, Nobuhisa Hagiwara, Teruo Okano
Journal: Circulation (2012)

Background:  Autologous skeletal myoblast (SkM) injection has been used for repairing infracted myocardium. However, safety concerns of ventricular tachyarrhythmia have arisen from some clinical trials of SkM-injection therapy. This study examined the effect and safety of SkM sheet therapy in a pig model of chronic myocardial infarction.   Methods:  Mini-pigs underwent LAD occlusion by a balloon catheter for 2 hours, followed by reperfusion. After 28 days, 12 SkM sheets were transplanted onto infarcted myocardium (Sheet-group n = 8), the same amount of cells were injected into the myocardium (Injection-group n = 7) and sham operations were performed as control (Sham-group n = 7). Implantable ECG loop recorder (ILR) was implanted subcutaneous on the left thorax. At 28 days after the transplantation, we assessed cardiac function with MDCT, interrogated ILR, and performed programmed ventricular stimulation (PVS); after which organs were harvested for histopathology. For assessing the inflammatory and injury response, inflammation factors, and high-sensitive CRP and Troponin-I were measured at 1, 3, 7, and 28 days after the transplantation by cytokine array method and ELISA, respectively.   Results:  Sheet-group improved their cardiac function compared with the Injection-group and the Sham-group (LVEF change: 5.8 ± 2.7, -1.0 ± 2.6 and -3.8 ± 1.8 % in the Sheet, Injection and Sham-groups, respectively, P    Conclusions:  SkM sheets transplanted onto infarcted myocardium improved cardiac function over SkM injection without increasing arrhythmogenicity. Myocardium inflammation may increase the arrhythmia risk.
International Initiative for Outcomes ( <scp>INFO</scp> ) for vitiligo: workshops with patients with vitiligo on repigmentation
Authors: V. Eleftheriadou, I. Hamzavi, A.G. Pandya, P. Grimes, J.E. Harris, R.H. Huggins, H.W. Lim, N. Elbuluk, B. Bhatia, A. Tovar‐Garza, A.F. Nahhas, T. Braunberger, K. Ezzedine
Journal: British Journal of Dermatology (2018)

There is no cure or firm clinical recommendations for the treatment of vitiligo. One of the main issues is the heterogeneity of outcome measures used in randomized controlled trials for vitiligo. To define successful repigmentation from the patients' point of view and to propose how and when repigmentation should be evaluated in clinical trials in vitiligo. We conducted three workshops with patients with vitiligo and their parents or caregivers. Workshop 1 was held at World Vitiligo Day (Detroit, MI), workshop 2 at the University of Texas Southwestern Medical Center and workshop 3 at the Vitiligo and Pigmentation Institute of Southern California, University of California. Seventy‐three participants were recruited. Consensus on the following questions was achieved unanimously: (i) the definition of 'successful repigmentation' was 80–100% of repigmentation of a target lesion and (ii) both an objective and a subjective scale to measure repigmentation should be used. This was the largest patients' outcomes workshop. We followed the guidance from the CSG‐COUSIN and the Vitiligo Global Issues Consensus Group. Our recommendations to use percentage of repigmentation quartiles (0–25%, 26–50%, 51–79%, 80–100%) and the Vitiligo Noticeability Scale are based on the best available current evidence. A limitation of the research is that the workshops were conducted only in the U.S.A., due to pre‐existing organisational support and the availability of funding.