tbuckley/cabot-search huggingface dataset:
Abstract 126: Peroxisomal Proliferator Activated Receptor Alpha Overexpression in Hypertrophied Cardiomyocytes Restores Mitochondrial Integrity and Function
Authors: Sagartirtha Sarkar, Santanu Rana
Journal: Circulation Research (2017)

Cardiac tissue engineering is an interdisciplinary field that engineers modulation of viable molecular milieu to restore, maintain or improve heart function. Myocardial workload (energy demand) and energy substrate availability (supply) are in continual flux to maintain specialized cellular processes, yet the heart has a limited capacity for substrate storage and utilization during pathophysiological conditions. Damage to heart muscle, acute or chronic, leads to dysregulation of cardiac metabolic processes associated with gradual but progressive decline in mitochondrial respiratory pathways resulting in diminished ATP production. The Peroxisome Proliferator Activated Receptor Alpha ( PPARα ) is known to regulate fatty acid to glucose metabolic balance as well as mitochondrial structural integrity. In this study, a non-canonical pathway of PPARα was analyzed by cardiomyocyte targeted PPARα overexpression during cardiac hypertrophy that showed significant downregulation in p53 acetylation as well as GSK3β activation levels. Targeted PPARα overexpression during hypertrophy resulted in restoration of mitochondrial structure and function along with significantly improved mitochondrial ROS generation and membrane potential. This is the first report of myocyte targeted PPARα overexpression in hypertrophied myocardium that results in an engineered heart with significantly improved function with increased muscle mitochondrial endurance and reduced mitochondrial apoptotic load, thus conferring a greater resistance to pathological stimuli within cardiac microenvironment.
Validation of the accuracy of pretest and exercise test scores in women with a low prevalence of coronary disease: The National Heart Lung and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE) study Anthony Morise, Marian B. Olson, C. Noel Bairey Merz, Nathaniel Reichek, William J. Rogers, Carl J. Pepine, Steven E. Reis, Barry L. Sharat, George Sopko, Jannet F. Lewis. WVU, Morgantown, WV
Journal: Journal of the American College of Cardiology (2001)
Epigenetic modifications in pancreas development, diabetes, and therapeutics
Authors: Suneesh Kaimala, Challagandla Anil Kumar, Mohammed Z. Allouh, Suraiya Anjum Ansari, Bright Starling Emerald
Journal: Medicinal Research Reviews (2022)

Abstract A recent International Diabetes Federation report suggests that more than 463 million people between 20 and 79 years have diabetes. Of the 20 million women affected by hyperglycemia during pregnancy, 84% have gestational diabetes. In addition, more than 1.1 million children or adolescents are affected by type 1 diabetes. Factors contributing to the increase in diabetes prevalence are complex and include contributions from genetic, environmental, and epigenetic factors. However, molecular regulatory mechanisms influencing the progression of an individual towards increased susceptibility to metabolic diseases such as diabetes are not fully understood. Recent studies suggest that the pathogenesis of diabetes involves epigenetic changes, resulting in a persistently dysregulated metabolic phenotype. This review summarizes the role of epigenetic mechanisms, mainly DNA methylation and histone modifications, in the development of the pancreas, their contribution to the development of diabetes, and the potential employment of epigenetic modulators in diabetes treatment.
Heterogenous Role of IRF4 in Kidney Fibrosis
Authors: Zhenyu Liu, Jingbo Zhang
Journal: Journal of the American Society of Nephrology (2021)

A recent article by Sasaki et al. [1][1] entitled "Deletion of Myeloid Interferon Regulatory Factor 4 (IRF4) in Mouse Model Protects against Kidney Fibrosis after Ischemic Injury by Decreased Macrophage Recruitment and Activation" discussed the role of IRF4 in regulating macrophages during
Customized blood-brain barrier shuttle peptide to increase AAV9 vector crossing the BBB and augment transduction in the brain
Authors: Xintao Zhang, Zheng Chai, Amanda Lee Dobbins, Michelle S. Itano, Charles Askew, Zhe Miao, Hongqian Niu, R. Jude Samulski, Chengwen Li
Journal: Biomaterials (2021)
Incorrect Spelling of a Surname in the Byline
Journal: JAMA Network Open (2022)

David P. Stonko, MD, MS; Chen Dun, MHS; Christi Walsh, MSN, CRNP; Marlin Schul, MD, MBA; John Blebea, MD; Edward M. Boyle, MD; Martin A. Makary, MD, MPH; Caitlin W. Hicks, MD, MS
Prevalence of germline mutations and homologous recombination deficiency (HRD) in a real-world biliary tract cancer (BTC) cohort.
Authors: Robin Kate Kelley, Arya Ashok, Elizabeth Mauer, Reham Abdel-Wahab, Nilofer Saba Azad
Journal: Journal of Clinical Oncology (2022)

476 Background: Biliary tract cancers (BTC) are a heterogeneous family of cancers including intrahepatic and extrahepatic cholangiocarcinomas (ICC, ECC) and gallbladder carcinomas (GBC). Treatment options remain limited and prognosis is poor for advanced BTC, underscoring the need for early detection and new therapeutic targets. Next-generation sequencing (NGS) studies have identified mutations associated with homologous recombination deficiency (HRD) in up to 25% of BTC patients, but the proportion with germline (GMut) versus somatic (SMut) mutations has not been established. This retrospective study was designed to determine the prevalence of GMut and HRD-associated SMut in a large BTC convenience sample and their association with key clinical parameters. Methods: We retrospectively analyzed de-identified records from 804 BTC patients who received tumor/normal (T/N) matched NGS between 2017-2021 via the Tempus|xT assay (DNA-seq of 648 genes at 500x coverage; full transcriptome RNA-seq). This targeted panel detects single nucleotide variants (SNVs), indels, copy number variants (CNVs), and a selection of rearrangements. Analyses focused on pathogenic/likely pathogenic SMut and CNVs, as well as incidental GMut limited to SNVs and small indels in 50 hereditary cancer genes. HRD-associated GMut and SMut were analyzed across 9 and 18 HRR pathway genes, respectively. Results: We identified a cohort of 804 patients with BTC, composed of ICC (n=499), ECC (n=83), and GBC (n=222). The median age was 66 years; 55% were female; and race was White/Black/Asian in 78%/12%/6%. The prevalence of GMut was 4.6% overall. Subgroup analyses showed GMut in 5% of ICC, 4.8% of ECC, and 3.6% of GBC. For patients &lt;50 years of age at diagnosis, pooled prevalence was 6.1% (n=82) vs. 4.5% (n=641) for age ≥50 years (p=0.6). HRD-associated GMut were present in 3.2%. HRD-associated SMut or CNVs were present in 13%, and showed significant variation across subsite (p=0.002) with highest prevalence in GBC (19%, Table). HRD-associated GMut were identified in ATM (n=8), BRCA2 (n=6), and BRCA1 (n=5). Microsatellite instability was present in 1.4% of samples. Conclusions: A significant proportion of BTC patients harbors potentially clinically-relevant GMut and SMut associated with HRD. Future studies are warranted to define the role of germline testing and to examine the activity of HRD-targeted therapies in BTC patients.[Table: see text]
Inflammatory bowel disease
Authors: I Atherton, M Karita, G Gonzalez-Valencia, M Morales, R Peek, G Perez-Perez, Helicobacter Pylori, Q Karim, Rph Logant
Journal: Gut (1996)

In the US, H. pylori vacA shows allelic variation in the signal sequence (which may be type sla, slb or s2) and the mid-region (type ml or m2).Previous PCR-based vacA mid-region typing classified most, but not all, Asian and South American strains tested as ml or m2.We now sought to investigate vacA mid-region diversity further.MotlmodL We studied 13 Japanese, 6 Chinese, 9 Thai, and 8 Peruvian H. pylori isolates.cagA was identified by colony hybridisation (CH), vacA signal sequence was typed by PCR, and vacA mid-region was typed proximally by CH and distally by PCR.Sections of the vacA mid-region from 8 strains were PCR-amplified, sequenced, and compared with known sequences from 8 other strains.Rcuts Of the 36 Asian and South American strains studied, 35 were cagA+ (the cagAwas Peruvian) and 35 were vacA sla (1 cagA + Peruvian was slb).vacA mid-regions from the 13 Japanese strains were not PCR-amplified by ml or m2-specific primers, but hybridised weakly with an ml probe.Sequence analysis of vacA from 1 Japanese strain revealed 91% nucleotide identity with the ml probe but only 71% identity with the m2 probe.The previously equivocal Thai and Peruvian strains also had ml-like mid-region sequences.A Chinese strain was ml in the proximal mid-region and m2 distally, showing a clear crossover site.Final mid-region types were: Japanese, all 13 ml; Chinese, 1 ml, 1 ml/m2, 4 m2; Thai, 3 ml, 6 m2; Peruvian 4 ml, 4 m2.Distal mid-region sequences of 16 strains, compared over 294 bp, clustered into 2 groups, ml and m2.Nucleotide identity between ml and m2 strains ranged from 73-78%.Within groups, m2 strains were less diverse than ml strains (m2 range 94-99.7%,ml 88-99.3%,p<0.001).Sequence analysis of 7 ml and 3 m2 strains over 1.1kb proximally showed maintenance of clustering outside the 294bp region C duions These Asian and South American strains are similar in terms of cagA status and vacA sla genotype, but fall into 2 vacA mid- region groups.ml sequences are more diverse than m2, and thus may be phylogenetically older.The vacA sequence of 1 Chinese strain suggests recombination in vivo between ml and m2 alleles.W58
Books Received
Journal: JAMA (1986)

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
In Brief
Journal: JAMA (1977)

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
Wives' ischemic heart disease linked with husbands' smoking
Authors: P. Gunby
Journal: JAMA (1985)

Nonsmoking women whose husbands do smoke appear to be at greater risk of dying from ischemic heart disease than wives of nonsmokers, according to University of California, San Diego, School of Medicine scientists (<i>Am J Epidemiol</i>1985;121:645-650). The authors, however, call for caution in interpreting their results, terming them "provocative rather than definitive." Cedric Garland, DPH, assistant professor of community and family medicine and principal author, emphasizes: "This should be considered an exploratory study. I hope other researchers are stimulated to see if the risk is present in larger population groups over a longer period." The prospective study was conducted in Rancho Bernardo, a suburb of San Diego that the investigators describe as "a community of older adults." A total of 695 married women, aged 50 to 79 years, who never had smoked, were entered in the study between 1972 and 1974, categorized by whether their husbands were nonsmokers (never
Updated Interim Surveillance Case Definition for Severe Acute Respiratory Syndrome (SARS)--United States, April 29, 2003
Journal: JAMA (2003)

CDC's interim surveillance case definition for severe acute respiratory syndrome (SARS) has been updated to include laboratory criteria for evidence of infection with the SARS-associated coronavirus (SARS-CoV) (Figure, Box). In addition, clinical criteria have been revised to reflect the possible spectrum of respiratory illness associated with SARS-CoV. Epidemiologic criteria have been retained. The majority of U.S. cases of SARS continue to be associated with travel, with only limited secondary spread to household members or health-care providers.
Preferences and attitudes of cardiologists in the management of cancer patients.
Authors: Ibrahim Azar, Stephani Wang, Jacqueline Kenitz, Dawn Lombardo, Roderick Deaño, Anthony Frank Shields, Syed S. Mahmood, Philip Agop Philip, Mohammed Najeeb Al Hallak, Joshua Schulman-Marcus
Journal: Journal of Clinical Oncology (2022)

651 Background: With recent improvements in survival of cancer patients and emphasis on high-value care at end-of-life, the management of cardiovascular disease in patients with cancer is increasingly important. To our knowledge, there is no current US data examining how the presence and extent of cancer influence cardiologists’ decision-making for common cardiovascular conditions. Methods: An anonymous online vignette-based survey of cardiologists was conducted at five US institutions investigating how the extent of gastrointestinal and thoracic malignancies (prior/localized, metastatic) would influence treatment recommendation for atrial fibrillation (AF), aortic stenosis (AS), unstable angina (UA) and obstructive coronary artery disease (CAD). Results: Thirty-three percent (86/259) of cardiologists completed the survey between September and November 2019. Participants were 67% male, 51% below age 40, and 58% had five or more years of clinical experience. Majority of cardiologists practiced at teaching hospitals (72%) and were non-interventional (63%). Cardiologists were more likely to recommend procedural interventions in patients with localized cancer than with metastatic disease: AF (LAAO: 20% vs 8%), AS (AVR: 83% vs 11%), UA (LHC: 70% vs 27%) and obstructive CAD (PCI: 81% vs 38%) (Table). In patients with metastatic cancer, most cardiologists sought an oncology (82%) or a palliative care (69%) consult. Conclusions: Cardiologists were less likely to recommend invasive cardiovascular therapies to patients with metastatic cancer. This preference pattern likely reflects the influence of comorbidities and quality of life expectation on cardiologists’ treatment recommendations but may also be related to the stigma of advanced cancer. Better communication between cardiologists and oncologists is necessary to a personalized care of patients with cancer and cardiovascular disease that would maximize treatment benefit with least morbidity.[Table: see text]
Benign Parathyroid Hyperplasia With Incidental Pulmonary Seeding on 99mTc-MIBI Scintigraphy and FDG PET/CT
Authors: Yao-Kuang Tsai, Chi-Jung Tsai, Chuang-Hsin Chiu, Kai-Hsiung Ko, Yao-Feng Li
Journal: Clinical Nuclear Medicine (2022)

Abstract A 50-year-old woman with end-stage renal disease presented with recurrent hyperparathyroidism after parathyroidectomy. 99m Tc-MIBI scintigraphy did not show MIBI-avid lesion in the neck or mediastinum but in bilateral lung fields instead. On suspicion of malignancy, 18 F-FDG PET/CT was performed and depicted no significant FDG uptake throughout the whole body. After resection of the pulmonary nodules, the final histopathology revealed benign parathyroid hyperplasia with pulmonary seeding, which is exceptionally a rare entity.
Retrospective study of survival outcomes in patients with hereditary pathogenic and variants of unknown significance mutations in pancreatic adenocarcinoma.
Authors: Ching Ying Lin, Natalie Moshayedi, Shant Thomassian, Jun Gong, Arsen Osipov, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2022)

616 Background: Since 2019, all patients with pancreatic adenocarcinoma (PDAC) are recommended to undergo germline testing per the National Comprehensive Cancer Network guidelines. Outside of PARP inhibitors in germline BRCA mutated PDAC, the predictive and prognostic implications of these genetic alterations are unclear. Many hereditable mutations are continually discovered, but the majority are considered Variants of Unknown Significance (VUS). The purpose of this retrospective study is to characterize the clinical characteristics of multiple pathogenic and VUS germline mutations in PDAC. Methods: An IRB approved institutional database of PDAC patients (n=442) was queried for patients diagnosed between 2007 and 2021. Only patients who tested positive for hereditary mutations (n=35) or VUS (n=41) were included. Patients with both pathogenic mutation and VUS were considered in the pathogenic mutation group. Results: 76 patients (35 pathogenic, 41 VUS) were included in the analysis. Pathogenic mutations were divided into subcategories including DNA repair (n=21), polyposis (n=2), pancreatitis-associated (n=11), and other (n=2). With a mean follow-up period of 636 days, the overall survival (OS) for pathogenic mutations at 90 days, 180 days, 1 year, and 2 years was 100%, 97.1%, 88.6%, and 74.3% respectively. The cumulative recurrence was 2.9%, 11.4%, 22.9%, and 37.1%. For VUS, the OS was 97.6%, 95.1%, 75.6%, and 56.1% and cumulative recurrence was 0%, 14.6%, 31.7%, and 43.9% in the same time intervals. Conclusions: This data suggests that patients with germline mutations may have favorable outcomes when compared to the general population. Overall germline alterations in our intuitional cohort had a 2-year survival of nearly 75%. Notably, pancreatitis-associated hereditable mutations consisted a sizeable portion of our overall cohort. Although current therapy is most focused on DNA repair mechanisms, these results show that other novel germline genetic alterations may be prognostic and warrant further investigation.[Table: see text]
COVID-19 and UK family carers: policy implications
Authors: Juliana Onwumere, Cathy Creswell, Gill Livingston, David Shiers, Kate Tchanturia, Tony Charman, Alisa Russell, Janet Treasure, Marta Di Forti, Emilie Wildman, Helen Minnis, Allan Young, Annette Davis, Elizabeth Kuipers
Journal: The Lancet Psychiatry (2021)

Informal (unpaid) carers are an integral part of all societies and the health and social care systems in the UK depend on them. Despite the valuable contributions and key worker status of informal carers, their lived experiences, wellbeing, and needs have been neglected during the COVID-19 pandemic. In this Health Policy, we bring together a broad range of clinicians, researchers, and people with lived experience as informal carers to share their thoughts on the impact of the COVID-19 pandemic on UK carers, many of whom have felt abandoned as services closed. We focus on the carers of children and young people and adults and older adults with mental health diagnoses, and carers of people with intellectual disability or neurodevelopmental conditions across different care settings over the lifespan. We provide policy recommendations with the aim of improving outcomes for all carers.
The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: a systematic review and meta-analysis
Authors: Dimitrios A Koutoukidis, Susan A Jebb, Matthew Zimmerman, Afolarin Otunla, J. Aaron Henry, Anne Ferrey, Ella Schofield, Jade Kinton, Paul Aveyard, Julian R. Marchesi
Journal: Gut Microbes (2022)

The gut microbiome may be a mediator between obesity and health outcomes. However, it is unclear how intentional weight loss changes the gut microbiota and intestinal permeability. We aimed to systematically review and quantify this association. We searched Medline, Embase, CINAHL, Cochrane databases, and trial registries until June 2020 (PROSPERO: CRD42020205292). We included trials of weight loss interventions (energy-restricted diets, pharmacotherapy, bariatric surgery) reporting on the microbiome. Two reviewers independently completed screening, extraction, and risk assessment with the ROBINS-I tool. Pooled standardized mean differences (SMDs) were obtained from random-effects meta-analyses. Forty-seven trials with 1,916 participants (81% female) and a median follow-up of 6 months (range: 2–24) were included. Based on imprecise evidence but with fairly consistent direction of effect, weight loss was associated with a statistically significant increase in α-diversity [SMD: 0.4 (95% CI: 0.2, 0.6], p < .0001, I2 = 70%, n = 30 studies) and a statistically significant reduction in intestinal permeability [SMD: −0.7 (95% CI: −0.9, −0.4), p < .0001, I2 = 83%, n = 17 studies]. Each kg of weight loss was associated with a 0.012 (95% CI: 0.0003, 0.024, p = .045) increase in α-diversity and a −0.017 (95% CI: −0.034, −0.001, p = .038) reduction in intestinal permeability. There was clear evidence of increases in the relative abundance of Akkermansia, but no clear evidence of changes in individual phyla, species, or fecal short-chain fatty acids. Restricting the analyses to the studies with lower risk of bias did not materially alter the estimates. Increasing weight loss is positively associated with increases in gut microbiota α-diversity and reductions in intestinal permeability.