tbuckley/cabot-search huggingface dataset:
Glucagon-Like Peptide 1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors and Risk of Nonalcoholic Fatty Liver Disease Among Patients With Type 2 Diabetes
Authors: Richeek Pradhan, Hui Yin, Oriana Yu, Laurent Azoulay
Journal: Diabetes Care (2022)

To determine whether glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, separately, are associated with a decreased risk of nonalcoholic fatty liver disease (NAFLD) compared with dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes.We assembled two new-user, active comparator cohorts using the U.K. Clinical Practice Research Datalink. The first included 30,291 and 225,320 new users of GLP-1 RA and DPP-4 inhibitors, respectively. The second included 41,184 and 148,421 new users of SGLT-2 inhibitors and DPP-4 inhibitors, respectively. Cox proportional hazards models weighted using propensity score fine stratification were fit to estimate hazard ratios (HRs) with 95% CIs of NAFLD. We also determined whether the study drugs were associated with a decreased risk of hepatic transaminase elevation within restricted subcohorts.GLP-1 RA were associated with a lower incidence of NAFLD with a wide CI compared with DPP-4 inhibitors (3.9 vs. 4.6 per 1,000 person-years, respectively; HR 0.86, 95% CI 0.73-1.01). SGLT-2 inhibitors were associated with a decreased risk of NAFLD (5.4 vs. 7.0 per 1,000 person-years, respectively; HR 0.78, 95% CI 0.68-0.89). In the restricted subcohorts, both GLP-1 RA and SGLT-2 inhibitors were associated with a decreased risk of hepatic transaminase elevation (HR 0.89, 95% CI 0.83-0.95, and HR 0.66, 95% CI 0.61-0.71).SGLT-2 inhibitors, and possibly GLP-1 RA, may be associated with a decreased incidence of NAFLD and hepatic transaminase elevation among patients with type 2 diabetes.
Influence of Sex Hormones on Cancer Progression
Authors: Elizabeth J. Folkerd, Mitch Dowsett
Journal: Journal of Clinical Oncology (2010)

To review the influence of sex hormones on the progression of breast, prostate, gynecologic, and colorectal cancer. The literature was reviewed in an informal manner utilizing the authors' prior knowledge to collate the current evidence for the involvement of sex hormones, particularly estrogens and androgens in the progression of a range of hormonally responsive cancers. In particular, the effect of treatment involving hormone withdrawal treatment was considered strong evidence for involvement. The impact of basal levels of endogenous steroids was considered. Data from clinical trials indicate the efficacy of therapeutic interventions that result in ablation or antagonism of host steroids for a range of cancers. Demonstration of the correlation of the completeness of withdrawal with clinical outcome together with direct evidence of progression from studies looking at the influence of tissue and circulating levels of sex hormones more recently in conjunction with gene expression profiles all provide compelling evidence for the involvement of steroids in the progression of disease. The involvement of steroids in the progression of cancer in hormone-sensitive tissues is well established and an important target for therapy.
Oncology Research Program
Journal: Journal of the National Comprehensive Cancer Network (2011)

The goal of the Highlights of the NCCN Oncology Research Program (ORP) is to provide readers with more information on the ORP, including studies currently accruing patients.For more information on specific trials, including patient selection criteria, please use the contact information listed with each study.For more information on the NCCN ORP, including a complete detailing of the clinical studies currently underway at NCCN Member Institutions, please access the NCCN ORP pages at http://www.nccn.org/clinical_trials/clinicians.
Effective engagement of survivors of harassment and abuse in sport in athlete safeguarding initiatives: a review and a conceptual framework
Authors: Margo Mountjoy, Tine Vertommen, Rachael Denhollander, Sheldon Kennedy, Renald Majoor
Journal: British Journal of Sports Medicine (2022)

Sport, as a microcosm of society, is not immune to the abuse of its stakeholders. Attention to abuse in sport has recently become a priority for sport organisations following several high-profile cases of athlete abuse from different sports around the world. Resulting from this increased awareness, many sport organisations have commenced work in the field of athlete safeguarding including the development of policy, educational programmes, reporting pathways, investigation mechanisms and research initiatives. One mechanism adopted by many sport organisations to support their safeguarding efforts is the engagement of survivors of abuse in sport: typically, as guest speakers at conferences or educational events. Unfortunately, many sport organisations do not have the knowledge or trauma-informed expertise to engage survivors safely and effectively; and in doing so, may unintentionally retraumatise the survivor if erroneous methods of engagement are employed. For some survivors, this experience may compound the original harms, and thus it also represents an area of vulnerability for the organising entity. The purpose of this paper is to explore the rationale for partnering with survivors of abuse in sport in safeguarding initiatives and to propose a living conceptual framework to support effective and safe survivor engagement in safeguarding initiatives. We will explore the underpinning scientific background, as well as the ‘why’, and ‘how’ of survivor engagement to inform sport organisations, research scientists, policy-makers, conference organisers, safeguarding officers, sport medicine clinicians and survivors themselves.
Repeated dose budesonide/formoterol compared to salbutamol in adult asthma: a randomised crossover trial
Authors: Nethmi Kearns, Pepa Bruce, Mathew Williams, Marjan Doppen, Melissa Black, Mark Weatherall, Richard Beasley
Journal: European Respiratory Journal (2022)

Background Our objective was to determine the comparative bronchodilator, systemic β 2 -agonist, cardiovascular and adverse effects of salbutamol 200 µg and budesonide/formoterol 200/6 µg when taken repeatedly in stable asthma. Methods This open-label, crossover, single-centre, controlled trial randomised adults with asthma to different orders of two treatment regimens: salbutamol 200 µg via metered-dose inhaler at 0, 30, 60 and 90 min, then salbutamol 2.5 mg via nebuliser at 120, 140, 160 and 420 min; or budesonide/formoterol 200/6 µg one actuation via Turbuhaler at 0, 30, 60 and 90 min, then two actuations at 120, 140, 160 and 420 min. The primary outcome measure was forced expiratory volume in 1 s (FEV 1 ) after 180 min. Secondary outcomes included repeat measures of FEV 1 , serum potassium, heart rate and adverse events Results Of 39 patients randomised, two withdrew due to adverse events (QT CF prolongation and T-wave abnormalities) after the first intervention with salbutamol. The mean± sd change from baseline FEV 1 180 min after randomisation for salbutamol and budesonide/formoterol regimens was 0.71±0.46 L (n=38) and 0.58±0.45 L (n=37), respectively, with a mean± sd paired difference of −0.10±0.40 L (n=37) and a model-based estimated difference of −0.12 (95% CI −0.25–0.02) L (p=0.088). In the main secondary analysis, salbutamol resulted in significantly greater FEV 1 from 30 to 240 min, but lesser FEV 1 at 360 and 420 min. Salbutamol resulted in a significantly lower serum potassium, and a higher heart rate and number of adverse events. Conclusions The comparative bronchodilator responses of repeated administration of salbutamol 200 µg and budesonide/formoterol 200/6 µg differed depending on the time of measurement. Salbutamol caused greater systemic β 2 -agonist and cardiovascular effects and more adverse events.
NMNAT2 is downregulated in glaucomatous RGCs, and RGC-specific gene therapy rescues neurodegeneration and visual function
Authors: Fang Fang, Pei Zhuang, Xue Feng, Pingting Liu, Dong Liu, Haoliang Huang, Liang Li, Wei Chen, Liang Liu, Yang Sun, Haowen Jiang, Jiangbin Ye, Yang Hu
Journal: Molecular Therapy (2022)

The lack of neuroprotective treatments for retinal ganglion cells (RGCs) and optic nerve (ON) is a central challenge for glaucoma management. Emerging evidence suggests that redox factor NAD+ decline is a hallmark of aging and neurodegenerative diseases. Supplementation with NAD+ precursors and overexpression of NMNAT1, the key enzyme in the NAD+ biosynthetic process, have significant neuroprotective effects. We first profile the translatomes of RGCs in naive mice and mice with silicone oil-induced ocular hypertension (SOHU)/glaucoma by RiboTag mRNA sequencing. Intriguingly, only NMNAT2, but not NMNAT1 or NMNAT3, is significantly decreased in SOHU glaucomatous RGCs, which we confirm by in situ hybridization. We next demonstrate that AAV2 intravitreal injection-mediated overexpression of long half-life NMNAT2 mutant driven by RGC-specific mouse γ-synuclein (mSncg) promoter restores decreased NAD+ levels in glaucomatous RGCs and ONs. Moreover, this RGC-specific gene therapy strategy delivers significant neuroprotection of both RGC soma and axon and preservation of visual function in the traumatic ON crush model and the SOHU glaucoma model. Collectively, our studies suggest that the weakening of NMNAT2 expression in glaucomatous RGCs contributes to a deleterious NAD+ decline, and that modulating RGC-intrinsic NMNAT2 levels by AAV2-mSncg vector is a promising gene therapy for glaucomatous neurodegeneration. The lack of neuroprotective treatments for retinal ganglion cells (RGCs) and optic nerve (ON) is a central challenge for glaucoma management. Emerging evidence suggests that redox factor NAD+ decline is a hallmark of aging and neurodegenerative diseases. Supplementation with NAD+ precursors and overexpression of NMNAT1, the key enzyme in the NAD+ biosynthetic process, have significant neuroprotective effects. We first profile the translatomes of RGCs in naive mice and mice with silicone oil-induced ocular hypertension (SOHU)/glaucoma by RiboTag mRNA sequencing. Intriguingly, only NMNAT2, but not NMNAT1 or NMNAT3, is significantly decreased in SOHU glaucomatous RGCs, which we confirm by in situ hybridization. We next demonstrate that AAV2 intravitreal injection-mediated overexpression of long half-life NMNAT2 mutant driven by RGC-specific mouse γ-synuclein (mSncg) promoter restores decreased NAD+ levels in glaucomatous RGCs and ONs. Moreover, this RGC-specific gene therapy strategy delivers significant neuroprotection of both RGC soma and axon and preservation of visual function in the traumatic ON crush model and the SOHU glaucoma model. Collectively, our studies suggest that the weakening of NMNAT2 expression in glaucomatous RGCs contributes to a deleterious NAD+ decline, and that modulating RGC-intrinsic NMNAT2 levels by AAV2-mSncg vector is a promising gene therapy for glaucomatous neurodegeneration.
The Oncology Care Model and Adherence to Oral Cancer Drugs: A Difference-in-Differences Analysis
Authors: Nancy L Keating, Gabriel A Brooks, Mary Beth Landrum, Pang-Hsiang Liu, Robert Wolf, Lauren E Riedel, Nirav S Kapadia, Shalini Jhatakia, Amanda Tripp, Carol Simon, Van Doren Hsu, Colleen M Kummet, Andrea Hassol
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Adherence to oral cancer drugs is suboptimal. The Oncology Care Model (OCM) offers oncology practices financial incentives to improve the value of cancer care. We assessed the impact of OCM on adherence to oral cancer therapy for chronic myelogenous leukemia (CML), prostate cancer, and breast cancer. Methods Using 2014-2019 Medicare data, we studied chemotherapy episodes for Medicare fee-for-service beneficiaries prescribed tyrosine kinase inhibitors (TKIs) for CML, antiandrogens (ie, enzalutamide, abiraterone) for prostate cancer, or hormonal therapies for breast cancer in OCM-participating and propensity-matched comparison practices. We measured adherence as the proportion of days covered and used difference-in-difference (DID) models to detect changes in adherence over time, adjusting for patient, practice, and market-level characteristics. Results There was no overall impact of OCM on improved adherence to TKIs for CML (DID = −0.3%, 90% confidence interval [CI] = −1.2% to 0.6%), antiandrogens for prostate cancer (DID = 0.4%, 90% CI = −0.3% to 1.2%), or hormonal therapy for breast cancer (DID = 0.0%, 90% CI = −0.2% to 0.2%). Among episodes for Black beneficiaries in OCM practices, for whom adherence was lower than for White beneficiaries at baseline, we observed small improvements in adherence to high cost TKIs (DID = 3.0%, 90% CI = 0.2% to 5.8%) and antiandrogens (DID = 2.2%, 90% CI = 0.2% to 4.3%). Conclusions OCM did not impact adherence to oral cancer therapies for Medicare beneficiaries with CML, prostate cancer, or breast cancer overall but modestly improved adherence to high-cost TKIs and antiandrogens for Black beneficiaries, who had somewhat lower adherence than White beneficiaries at baseline. Patient navigation and financial counseling are potential mechanisms for improvement among Black beneficiaries.
Hepatitis Awareness Month and Testing Day — May 2019
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

May is designated as Hepatitis Awareness Month, and May 19 is Hepatitis Testing Day. Hepatitis B and hepatitis C, the most common types of viral hepatitis in the United States, can cause chronic infections, and many persons remain unaware of their infection until serious complications occur. In 2016, an estimated 862,000 and 2.4 million persons were living with hepatitis B and hepatitis C, respectively, despite availability of a vaccine and effective treatment for hepatitis B and a cure for hepatitis C (1,2).
Tracking Cancer Evolution through the Disease Course
Authors: Chris Bailey, James R.M. Black, James L. Reading, Kevin Litchfield, Samra Turajlic, Nicholas McGranahan, Mariam Jamal-Hanjani, Charles Swanton
Journal: Cancer Discovery (2021)

During cancer evolution, constituent tumor cells compete under dynamic selection pressures. Phenotypic variation can be observed as intratumor heterogeneity, which is propagated by genome instability leading to mutations, somatic copy-number alterations, and epigenomic changes. TRACERx was set up in 2014 to observe the relationship between intratumor heterogeneity and patient outcome. By integrating multiregion sequencing of primary tumors with longitudinal sampling of a prospectively recruited patient cohort, cancer evolution can be tracked from early- to late-stage disease and through therapy. Here we review some of the key features of the studies and look to the future of the field. SIGNIFICANCE: Cancers evolve and adapt to environmental challenges such as immune surveillance and treatment pressures. The TRACERx studies track cancer evolution in a clinical setting, through primary disease to recurrence. Through multiregion and longitudinal sampling, evolutionary processes have been detailed in the tumor and the immune microenvironment in non-small cell lung cancer and clear-cell renal cell carcinoma. TRACERx has revealed the potential therapeutic utility of targeting clonal neoantigens and ctDNA detection in the adjuvant setting as a minimal residual disease detection tool primed for translation into clinical trials.
Clonal Expansion of Stem/Progenitor Cells in Cancer, Fibrotic Diseases, and Atherosclerosis, and CD47 Protection of Pathogenic Cells
Authors: R. Majeti, C. Jamieson, W.W. Pang, S. Jaiswal, N.J. Leeper, G. Wernig, I.L. Weissman
Journal: Annual Review of Medicine (2022)

We proposed and demonstrated that myelogenous leukemia has a preleukemic phase. In the premalignant phase, normal hematopoietic stem cells (HSCs) gradually accumulate mutations leading to HSC clonal expansion, resulting in the emergence of leukemic stem cells (LSCs). Here, we show that preleukemic HSCs are the basis of clonal hematopoiesis, as well as late-onset blood diseases (chronic-phase chronic myeloid leukemia, myeloproliferative neoplasms, and myelodysplastic disease). The clones at some point each trigger surface expression of “eat me” signals for macrophages, and in the clones and their LSC progeny, this is countered by upregulation of “don't eat me” signals for macrophages such as CD47,opening the possibility of CD47-based therapies. We include evidence that similar processes result in fibroblast expansion in a variety of fibrotic diseases, and arterial smooth muscle clonal expansion is a basis of atherosclerosis, including upregulation of both “eat me” and “don't eat me” molecules on the pathogenic cells.
A Death in the Family
Authors: Asif Khan
Journal: JAMA (2020)

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
Abstract 277: MicroRNA-125a-5p Protects the Mouse Heart From Ischemic Injury by Repressing Pro-apoptotic Bak1 and Klf13 in Cardiomyocytes
Authors: Bruno Moukette, Tatsuya Aonuma, Il-man Kim
Journal: Circulation Research (2020)

Background: Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), which are small noncoding RNAs to downregulate target genes. MiR-125a-5p (miR-125a) is downregulated in patients with myocardial infarction (MI). We reported that miR-125a is upregulated by the β-blocker carvedilol (Carv) acting through β-arrestin1-biased β1-adrenergic receptor (β1AR; receptor found mainly in cardiomyocytes [CMs]) cardioprotective signaling (Figure A). We also showed that pro-apoptotic genes bak1 and klf13 are downregulated by Carv and are upregulated after MI. Here, we hypothesize that miR-125a in CMs favorably regulates cardiac functional and structural remodeling after MI by repressing bak1 and klf13. Methods and Results: Fractionation of cardiac cell types from heart tissues reveals that the expression of miR-125a is higher in CMs than other myocardial cells. Using cultured CM and in vivo approaches, we show that miR-125a is an ischemic stress-responsive protector against CM apoptosis. CMs lacking miR-125a exhibit an increased sensitivity to apoptosis, while CMs overexpressing miR-125a have increased phospho-AKT pro-survival signaling. Moreover, we show that miR-125a is downregulated in post-MI mouse hearts and miR-125a overexpression protects mouse hearts against MI. We also show that global genetic deletion of miR-125a in mice worsens maladaptive post-MI remodeling. Mechanistically, the cardioprotective role of miR-125a during MI is in part attributed to direct repression of the pro-apoptotic genes bak1 and klf13 in CMs (Figure B). Conclusions: These findings reveal a pivotal role for miR-125a in regulating CM survival during MI.
The Care of the Consumptive. A Consideration of the Scientific Use of Natural Therapeutic Agencies in the Prevention and Cure of Consumption; Together with a Chapter on Colorado as a Resort for Invalids.
Journal: JAMA (1901)

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