tbuckley/cabot-search huggingface dataset:
The Harms of Postoperative Antibiotic Prophylaxis
Authors: Sheliza Halani, Mark McIntyre, Alon Vaisman
Journal: JAMA Internal Medicine (2022)

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 Journals 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
The hematopoietic saga of clonality in sickle cell disease
Authors: Aaron J. Stonestrom, Ross L. Levine
Journal: Journal of Clinical Investigation (2022)

Sickle cell disease (SCD) is associated with an increased risk of vascular-occlusive events and of leukemia. Clonal hematopoiesis (CH) may increase both risks. In turn, physiologic abnormalities in SCD may modify the incidence and/or distribution of genetic alterations in CH. In a recent issue of the JCI, Liggett et al. found no difference in CH rate between individuals with versus without SCD. Here we contextualize this report and discuss the complex interplay between CH and SCD with particular attention to consequences for emerging gene therapies. We further consider the limitations in our current understanding of these topics that must be addressed in order to optimize therapeutic strategies for SCD.
MULTIFACTORIAL RV DYSFUNCTION: SCLERODERMA MYOCARDITIS COMPLICATING PARTIAL ANOMALOUS PULMONARY VENOUS RETURN
Authors: Michael Basir, Ro-Kaye A. Simmonds, Zachary A. Banbury, Enrique Baez, Matthew V. Tavares, Aalap Dilip Chokshi
Journal: Journal of the American College of Cardiology (2022)
Where Is the Culprit Lesion in the New Electrocardiogram Pattern?
Authors: Chuan-Hai Zhang, Zhaolong Xu
Journal: JAMA Internal Medicine (2022)

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
Pirfenidone exacerbates Th2-driven vasculopathy in a mouse model of systemic sclerosis-associated interstitial lung disease
Authors: Anna Birnhuber, Katharina Jandl, Valentina Biasin, Elisabeth Fließer, Francesco Valzano, Leigh M. Marsh, Christina Krolczik, Andrea Olschewski, Jochen Wilhelm, Wolfgang Toller, Akos Heinemann, Horst Olschewski, Malgorzata Wygrecka, Grazyna Kwapiszewska
Journal: European Respiratory Journal (2022)

Systemic sclerosis (SSc) is an autoimmune disease characterised by severe vasculopathy and fibrosis of various organs including the lung. Targeted treatment options for SSc-associated interstitial lung disease (SSc-ILD) are scarce. We assessed the effects of pirfenidone in a mouse model of SSc-ILD.Pulmonary function, inflammation and collagen deposition in response to pirfenidone were assessed in Fra-2-overexpressing transgenic (Fra-2 TG) and bleomycin-treated mice. In Fra-2 TG mice, lung transcriptome was analysed after pirfenidone treatment. In vitro, pirfenidone effects on human eosinophil and endothelial cell function were analysed using flow cytometry-based assays and electric cell-substrate impedance measurements, respectively.Pirfenidone treatment attenuated pulmonary remodelling in the bleomycin model, but aggravated pulmonary inflammation, fibrosis and vascular remodelling in Fra-2 TG mice. Pirfenidone increased interleukin (IL)-4 levels and eosinophil numbers in lung tissue of Fra-2 TG mice without directly affecting eosinophil activation and migration in vitro. A pronounced immune response with high levels of cytokines/chemokines and disturbed endothelial integrity with low vascular endothelial (VE)-cadherin levels was observed in pirfenidone-treated Fra-2 TG mice. In contrast, eosinophil and VE-cadherin levels were unchanged in bleomycin-treated mice and not influenced by pirfenidone. In vitro, pirfenidone exacerbated the IL-4 induced reduction of endothelial barrier resistance, leading to higher leukocyte transmigration.This study shows that antifibrotic properties of pirfenidone may be overruled by unwanted interactions with pre-injured endothelium in a setting of high T-helper type 2 inflammation in a model of SSc-ILD. Careful ILD patient phenotyping may be required to exploit benefits of pirfenidone while avoiding therapy failure and additional lung damage in some patients.
Intermittent glucocorticoid treatment enhances skeletal muscle performance through sexually dimorphic mechanisms
Authors: Isabella M. Salamone, Mattia Quattrocelli, David Y. Barefield, Patrick G. Page, Ibrahim Tahtah, Michele Hadhazy, Garima Tomar, Elizabeth M. McNally
Journal: Journal of Clinical Investigation (2022)

Glucocorticoid steroids are commonly prescribed for many inflammatory conditions, but chronic daily use produces adverse effects, including muscle wasting and weakness. In contrast, shorter glucocorticoid pulses may improve athletic performance, although the mechanisms remain unclear. Muscle is sexually dimorphic and comparatively little is known about how male and female muscles respond to glucocorticoids. We investigated the impact of once-weekly glucocorticoid exposure on skeletal muscle performance comparing male and female mice. One month of once-weekly glucocorticoid dosing improved muscle specific force in both males and females. Transcriptomic profiling of isolated myofibers identified a striking sexually dimorphic response to weekly glucocorticoids. Male myofibers had increased expression of genes in the IGF1/PI3K pathway and calcium handling, while female myofibers had profound upregulation of lipid metabolism genes. Muscles from weekly prednisone–treated males had improved calcium handling, while comparably treated female muscles had reduced intramuscular triglycerides. Consistent with altered lipid metabolism, weekly prednisone–treated female mice had greater endurance relative to controls. Using chromatin immunoprecipitation, we defined a sexually dimorphic chromatin landscape after weekly prednisone. These results demonstrate that weekly glucocorticoid exposure elicits distinct pathways in males versus females, resulting in enhanced performance.
RACIAL AND ECHOCARDIOGRAPHIC PREDICTORS OF ALL-CAUSE MORTALITY IN PATIENTS WITH MODERATE TRICUSPID REGURGITATION: A SINGLE CENTER STUDY
Authors: Harish Ravipati, Maria Gabriela Gastanadui, Miguel Sotelo, Loren Wagner, Chris Rogers, Efstathia Andrikopoulou
Journal: Journal of the American College of Cardiology (2022)
Harnessing associative learning paradigms to optimize drug treatment
Authors: Martin Hadamitzky, Manfred Schedlowski
Journal: Trends in Pharmacological Sciences (2022)

Continuous treatment with drugs is an inevitable prerequisite for many clinical conditions, such as chronic inflammatory diseases, pain, or depression. However, the amount of adverse side effects induced by opioids, antidepressants, or immunosuppressive drugs urges the need for developing alternative or supportive treatment strategies. In this context, conditioned pharmacological effects, obtained by means of associative learning, have been successfully implemented as controlled drug-dose reduction strategies to maintain and strengthen the efficacy of medical treatments. Such approaches have been proven effective in experimental animals, healthy subjects, and patient populations. Thus, a systematic use of conditioned pharmacological effects should be seriously considered as a supportive treatment option to optimize pharmacological treatment effects for the patients benefit.
Abstract P4-01-13: Low tumor TLR9 expression results in resistance to growth inhibitory and autophagy responses to common breast cancer treatments
Authors: Katri Selander, Juha Klaper, Nataliia Petruk, Mauricio Ramm, Arja Jukkola, Eeva-Liisa Eskelinen
Journal: Cancer Research (2022)

Abstract Background: Toll like receptor-9 (TLR9) is an intracellular, innate immune system DNA-receptor, which is widely expressed in cancers. We previously demonstrated that low tumor TLR9 protein expression is associated with poor prognosis among triple negative breast cancer (TNBC) patients. A similar result is now detected also in larger, mRNA expression based datasets (Kmplot.com), which extend our initial observation to basal and luminal B clinical subtypes. The reason for TLR9 association with poor prognosis is not known.Aim: Since poor outcomes in early breast cancer are due to adjuvant treatment failures, we studied the role of TLR9 in breast cancer chemotherapy responses, growth inhibition and autophagy. Materials and Methods: Chemotherapy effects on the growth of control shRNA and TLR9 shRNA TNBC MDA-MB-231 and estrogen receptor expressing (ER+) T47-D cells were studied with cell confluency assays in vitro and in orthotopic mouse models in vivo. Autophagy was assessed with LC3I and II Western blots. Association of tumor TLR9 status with autophagy will be further studied in a cohort of neo-adjuvant treated patients, by comparing pre-treatment TLR9 expression with post-treatment LC3 vesicular expression, with immunohistochemistry. Autophagy gene expression will also be studied with RNAseq. Results: TLR9 shRNA cells were significantly less sensitive to the growth inhibitory effects of standard breast cancer chemotherapies than the corresponding control shRNA cells in vitro. The TLR9 shRNA T47-D cells were also significantly less sensitive to tamoxifen, than corresponding control shRNA cells. Docetaxel inhibited the growth of tumors formed by control shRNA cells, but not by TLR9 shRNA MDA-MB-231 cells in an orthotopic mouse model in vivo. Further chemotherapies and autophagy responses are being tested in this model as well. Standard chemotherapies induced accumulation of LC3IIB in control shRNA cells, but not in TLR9 cells, as demonstrated with Western blots. Conclusions: Decreased expression of tumor TLR9 is associated with 1) poor prognosis among basal and luminal B subtype patient samples, and in 2) decreased growth inhibitory and 3) decreased autophagy responses to common breast cancer chemotherapies and tamoxifen. Our results suggest that treatment responses, and thereby survival of patients with low-TLR9 tumors, may be improved by enhancing TLR9-associated autophagy. Citation Format: Katri Selander, Juha Klaper, Nataliia Petruk, Mauricio Ramm, Arja Jukkola, Eeva-Liisa Eskelinen. Low tumor TLR9 expression results in resistance to growth inhibitory and autophagy responses to common breast cancer treatments [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-01-13.
ACUTE CORONARY SYNDROME IN PATIENTS WITH PRIOR CORONARY BYPASS SURGERY: IMPACT OF NATIVE VS GRAFT VS ABSENT CULPRIT LESIONS ON CLINICAL OUTCOMES AND TREATMENT STRATEGY
Authors: Frederik T.W. Groenland, Jay Yee, Karim D. Mahmoud, Jeroen M. Wilschut, Roberto Diletti, Felix Zijlstra, Joost Daemen, Nicolas M. Van Mieghem, Wijnand K. den Dekker
Journal: Journal of the American College of Cardiology (2022)
Dermatologist awareness of scalp cooling for chemotherapy-induced alopecia
Authors: Lu Yin, Elizabeth J. Klein, Katerina Svigos, Taylor Novice, Daniel Gutierrez, Ruth Oratz, Mario E. Lacouture, Molly Powers, Maryanne Senna, Jerry Shapiro, Kristen Lo Sicco
Journal: Journal of the American Academy of Dermatology (2022)
An Extremely Streamlined Macronuclear Genome in the Free-Living Protozoan <i>Fabrea salina</i>
Authors: Bing Zhang, Lina Hou, Hongli Qi, Lingling Hou, Tiancheng Zhang, Fangqing Zhao, Miao Miao
Journal: Molecular Biology and Evolution (2022)

Ciliated protists are among the oldest unicellular organisms with a heterotrophic lifestyle and share a common ancestor with Plantae. Unlike any other eukaryotes, there are two distinct nuclei in ciliates with separate germline and somatic cell functions. Here, we assembled a near-complete macronuclear genome of Fabrea salina, which belongs to one of the oldest clades of ciliates. Its extremely minimized genome (18.35 Mb) is the smallest among all free-living heterotrophic eukaryotes and exhibits typical streamlined genomic features, including high gene density, tiny introns, and shrinkage of gene paralogs. Gene families involved in hypersaline stress resistance, DNA replication proteins, and mitochondrial biogenesis are expanded, and the accumulation of phosphatidic acid may play an important role in resistance to high osmotic pressure. We further investigated the morphological and transcriptomic changes in the macronucleus during sexual reproduction and highlighted the potential contribution of macronuclear residuals to this process. We believe that the minimized genome generated in this study provides novel insights into the genome streamlining theory and will be an ideal model to study the evolution of eukaryotic heterotrophs.
Abstract P3-12-33: Breast cancer incidence rates in Japan showed unimodal age distribution
Authors: Ken Uchida, Hitoshi Ohashi, Hiroko Nogi
Journal: Cancer Research (2022)

Abstract Purpose: Breast cancer incidence rates in Japan have been increasing recently. The incidence rates show bimodal age distribution in the developed countries. The latest studies have thrown new light on a close association between etiologic subtypes and the bimodal age distribution. To determine whether bimodal age distributions are also present in Japanese breast cancer, we investigated Japanese breast cancer incidence rates by age and biological features involved in incidence rates.Methods: Using Japanese breast Cancer Registry data, we examined age-at-diagnosis frequency distributions of breast cancer for 2017 and their hormone receptors (estrogen and progesterone) and HER2 status. Japanese female population data were referred to the registry of Statistics Bureau of Japan. Results: We included 94,612 breast cancer cases for 2017 in Japan. The number of breast cancer cases showed bimodal age distributions at 45-49 years and 65-69 years. However, the age distributions altered to unimodal age distribution with slight peaked at 45-49 years by adjusting with Japanese female population. Estrogen and progesterone receptor rates showed higher level at 45-49 years than other age groups (92.3% and 86.8%, respectively). HER2 expression rates showed lower rates (12.2%) at 45-49 years than other age groups.Conclusions: Japanese breast cancer incidence rates showed unimodal age distribution with slight peaks at 45-49 years. Luminal type breast cancer accounted for younger ages at 45-49 than elderly. Etiology of Japanese female breast cancer was different from the developed countries represented as bimodal age distribution. Citation Format: Ken Uchida, Hitoshi Ohashi, Hiroko Nogi. Breast cancer incidence rates in Japan showed unimodal age distribution [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-33.
Non-apoptotic cell death-based cancer therapy: Molecular mechanism, pharmacological modulators, and nanomedicine
Authors: Xuan Wang, Peng Hua, Chengwei He, Meiwan Chen
Journal: Acta Pharmaceutica Sinica B (2022)

As an emerging cancer therapeutic target, non-apoptotic cell death such as ferroptosis, necroptosis and pyroptosis, etc., has revealed significant potential in cancer treatment for bypassing apoptosis to enhance the undermined therapeutic efficacy triggered by apoptosis resistance. A variety of anticancer drugs, synthesized compounds and natural products have been proven recently to induce non-apoptotic cell death and exhibit excellent anti-tumor effects. Moreover, the convergence of nanotechnology with functional materials and biomedicine science has provided tremendous opportunities to construct non-apoptotic cell death-based nanomedicine for innovative cancer therapy. Nanocarriers are not only employed in targeted delivery of non-apoptotic inducers, but also used as therapeutic components to induce non-apoptotic cell death to achieve efficient tumor treatment. This review first introduces the main characteristics, the mechanism and various pharmacological modulators of different non-apoptotic cell death forms, including ferroptosis, necroptosis, pyroptosis, autophagy, paraptosis, lysosomal-dependent cell death, and oncosis. Second, we comprehensively review the latest progresses of nanomedicine that induces various forms of non-apoptotic cell death and focus on the nanomedicine targeting different pathways and components. Furthermore, the combination therapies of non-apoptotic cell death with photothermal therapy, photodynamic therapy, immunotherapy and other modalities are summarized. Finally, the challenges and future perspectives in this regard are also discussed.
Soluble uric acid inhibits β2 integrin–mediated neutrophil recruitment in innate immunity
Authors: Qiuyue Ma, Roland Immler, Monika Pruenster, Markus Sellmayr, Chenyu Li, Albrecht von Brunn, Brigitte von Brunn, Rosina Ehmann, Roman Wölfel, Matteo Napoli, Qiubo Li, Paola Romagnani, Ralph Thomas Böttcher, Markus Sperandio, Hans-Joachim Anders, Stefanie Steiger
Journal: Blood (2022)

Neutrophils are key players during host defense and sterile inflammation. Neutrophil dysfunction is a characteristic feature of the acquired immunodeficiency during kidney disease. We speculated that the impaired renal clearance of the intrinsic purine metabolite soluble uric acid (sUA) may account for neutrophil dysfunction. Indeed, hyperuricemia (HU, serum UA of 9-12 mg/dL) related or unrelated to kidney dysfunction significantly diminished neutrophil adhesion and extravasation in mice with crystal- and coronavirus-related sterile inflammation using intravital microscopy and an air pouch model. This impaired neutrophil recruitment was partially reversible by depleting UA with rasburicase. We validated these findings in vitro using either neutrophils or serum from patients with kidney dysfunction-related HU with or without UA depletion, which partially normalized the defective migration of neutrophils. Mechanistically, sUA impaired β2 integrin activity and internalization/recycling by regulating intracellular pH and cytoskeletal dynamics, physiological processes that are known to alter the migratory and phagocytic capability of neutrophils. This effect was fully reversible by blocking intracellular uptake of sUA via urate transporters. In contrast, sUA had no effect on neutrophil extracellular trap formation in neutrophils from healthy subjects or patients with kidney dysfunction. Our results identify an unexpected immunoregulatory role of the intrinsic purine metabolite sUA, which contrasts the well-known immunostimulatory effects of crystalline UA. Specifically targeting UA may help to overcome certain forms of immunodeficiency, for example in kidney dysfunction, but may enhance sterile forms of inflammation.
LEFT POSTERIOR FASCICULAR PACING: A NOVEL AND SUPERIOR PACING STRATEGY
Authors: Vikas Yellapu, Sudip Nanda, Matthew Krinock, Hardik Mangrolia, Steven M. Stevens, Darren M. Traub, Steven Tessier, Purujit Thacker, Vivek Amit Modi, Debabrata Bera, Tanujit Dey
Journal: Journal of the American College of Cardiology (2022)
Prepare the Way for Hemophilia A Gene Therapy
Authors: Courtney D Thornburg
Journal: New England Journal of Medicine (2022)

Congenital hemophilia A (factor VIII deficiency) is a bleeding disorder that results from pathologic variants in the gene F8 on the X chromosome. Among persons with hemophilia, those with severe disease (i.e., a factor VIII activity level of <1%) have the highest risk of spontaneous and traumatic life- and limb-threatening bleeding.1 Poorly controlled hemophilia manifests with chronic arthropathy associated with pain, decreased mobility, and a restricted lifestyle. To correct the coagulation defect and ameliorate bleeding, the factor VIII protein or function must be restored. The standard of care for severe hemophilia A is the prevention of bleeding with regular prophylactic . . .
A DEADLY EMOTIONAL ARGUMENT: PREVENTION OF SUDDEN CARDIAC DEATH IN CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA (CPVT)
Authors: Michele Violano, Wolfgang C. Poller, Maria R. Abraham, Martin Huemer, Melvin M. Scheinman, Ulf Landmesser, Bettina Heidecker
Journal: Journal of the American College of Cardiology (2022)
A NOVEL INTERVENTIONAL THERAPY FOR FIBROSING MEDIASTINITIS-INDUCED PULMONARY ARTERY STENOSIS:PUL-STENT(A NEW PULMONARY ARTEY STENT)
Authors: Jie-Ling Ma, Yun-Peng Wei, Yu-Ping Zhou, Xin Jiang, Xi-Qi Xu, Tao Wu, Fan Guo, Yi-Ning Wang, Meng-Tao Li, Qi Miao, Zhi-Cheng Jing
Journal: Journal of the American College of Cardiology (2022)
EFFICACY AND SAFETY OF AFICAMTEN AND DISOPYRAMIDE COADMINISTRATION IN OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY: RESULTS FROM REDWOOD-HCM COHORT 3
Authors: Anjali Tiku Owens, Ahmad Masri, Theodore P. Abraham, Lubna Choudhury, Florian Rader, John D. Symanski, Aslan Teyfik Turer, Timothy C. Wong, Albree Tower-Rader, Caroline Coats, Michael A. Fifer, Iacopo Olivotto, Scott D. Solomon, Hugh Watkins, Laura Robertson, Lisa Meng, Sharon Paige, Amy Wohltman, Stuart Kupfer, Fady I. Malik, Stephen B. Heitner, Martin S. Maron
Journal: Journal of the American College of Cardiology (2022)
Inhaled Ciclesonide for Patients With Asthma or Chronic Obstructive Pulmonary Disease and COVID-19
Authors: Chao-Hsien Chen, Cheng-Yi Wang, Chih-Cheng Lai
Journal: JAMA Internal Medicine (2022)

Evaluation System for Health Technology) could help achieve these aims.We hope that this dialogue is not limited to a comparative exercise, but rather, that it marks a renewed effort toward global harmonization of regulatory standards for medical devices.For instance, the EU is finalizing updates to its medical device regulations, including key considerations for postmarket surveillance that could help inform similar policy reforms in the US.Consistency in regulatory expectations would avoid duplicative study designs by manufacturers.Likewise, the FDA Medical Device Epidemiology Network could help facilitate the coordination of the new Japanese registries for neuroendovascular devices, referred to by Dr Yamamoto and colleagues, with other global efforts-something the agency has previously done for orthopedic and vascular devices. 5Taken together, these perspectives reaffirm the need for medical device reform and the opportunities for shared regulatory learnings and global collaboration.