tbuckley/cabot-search huggingface dataset:
Judicious Use of Rapid Viral Tests in Emergency Departments
Authors: Lona Mody
Journal: JAMA Internal Medicine (2024)

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 2024 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
Abstract B106: A minimal driver pair for a spontaneous high-grade serous ovarian cancer mouse model: Myc and p53-R270H
Authors: Joe R Delaney
Journal: Cancer Research (2024)

Abstract Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment can be understood. One challenge of the last decade has been to provide evidence for which cells are responsible for the origin of epithelial ovarian cancer. Different promoters, including Pax8, Lgr5, Ogvp1, and others have allowed for expression of transgenes in specific epithelial compartments in mice. Ovgp1 has been shown to be specific for fallopian tube epithelium (FTE), which most HGSOC is now thought to originate from. Pairing Ovgp1 with multiple homozygous deletions of powerful tumor suppressors like Brca1, Trp53, Rb1, and Nf1 yields murine disease after a year of age. However, human tumors do not contain homozygous deletions of these many tumor suppressors. Others have utilized Pax8 to knock out Trp53 and Pten to yield tumors at 3-8 months of age, but human tumors rarely have PTEN knockouts and Pax8 drives kidney and thyroid expression as well. We postulated that it is possible to strictly mimic human HGSOC genetics in a mouse model and nonetheless drive oncogenesis within the lifespan of a mouse. Here, we describe the OvTrpMyc model, Trp53em1Jdel_Tg(Ovgp1-Trp53*R270H-Myc), in which p53-R270H and Myc expression are driven by the Ovgp1 promoter. The transgene was inserted at the endogenous Trp53 locus, predicting that this design would allow for loss of the opposing wild-type chromosome 11 (syntenic to chromosome 17 in humans) to better mimic human HGSOC genetics. This model generated lethal disease at a median of 15.6 months of age. Dissected metastatic tumors were peritoneal and expressed Pax8, consistent with human disease. Immunohistochemical staining of the fallopian tube, ovary, and uterus indicated clear nuclear staining of p53 and Myc on the FTE. Notably, pockets of intraepithelial metastases expressing p53 and Myc were also found on the uterine epithelium. Cells grown ex vivo from uterus or fallopian tube dissections were analyzed for transcriptomes. RNA-seq revealed a clustering of these extracted cancer cells with human HGSOC and p53 mutant serous endometrial cancers. Loss of heterozygosity at the p53 locus was universal in these ex vivo grown cancer cells, as was extensive aneuploidy. The OvTrpMyc model requires only a single transgene for its breeding strategy, better enabling cancer detection, prevention, and treatment experiments. Taken together, the OvTrpMyc model of p53-R270H mutation and Myc expression driven by Ovgp1 is sufficient to recapitulate cancer hallmarks of HGSOC and, surprisingly, p53 mutant serous uterine cancer as well. Citation Format: Joe R Delaney. A minimal driver pair for a spontaneous high-grade serous ovarian cancer mouse model: Myc and p53-R270H [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B106.
Use of SGLT2 Inhibitors vs GLP-1 RAs and Anemia in Patients With Diabetes and CKD
Authors: Jia-Chian Hu, Shih-Chieh Shao, Daniel Hsiang-Te Tsai, Albert Tzu-Ming Chuang, Kuan-Hung Liu, Edward Chia-Cheng Lai
Journal: JAMA Network Open (2024)

Importance Sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with lower anemia risk, based on findings from post hoc analyses of the CREDENCE and DAPA-CKD trials; however, the effectiveness of SGLT2 inhibitors in a more generalizable type 2 diabetes (T2D) and chronic kidney disease (CKD) population, with active comparisons pertinent to current practice, is unknown. Objective To evaluate and compare anemia incidence between SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among patients with T2D and CKD stages 1 to 3. Design, Setting, and Participants This retrospective cohort study used target trial emulation of an expanded CREDENCE and DAPA-CKD study framework. The study was conducted among adults with T2D and CKD initiating SGLT2 inhibitors or GLP-1 RAs between January 1, 2016, and December 31, 2021, with follow-up until December 31, 2022. The study was conducted at the Chang Gung Medical Foundation, the largest multi-institutional hospital system in Taiwan. Exposures Initiation of SGLT2 inhibitors or GLP-1 RAs. Main Outcomes and Measures The primary outcome was a composite of anemia outcomes, including anemia event occurrence (hemoglobin level &amp;amp;lt;12-13 g/dL or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes) or anemia treatment initiation. Changes in hematological parameters, including hemoglobin level, hematocrit level, and red blood cell count, were evaluated during the follow-up period for as long as 3 years. Results The cohort included a total of 13 799 patients with T2D and CKD, initiating SGLT2 inhibitors (12 331 patients; mean [SD] age, 62.4 [12.3] years; 7548 [61.2%] male) or GLP-1 RAs (1468 patients; mean [SD] age, 61.5 [13.3] years; 900 [61.3%] male). After the median follow-up period of 2.5 years, patients receiving SGLT2 inhibitors had lower incidence of composite anemia outcomes (hazard ratio [HR], 0.81; 95% CI, 0.73-0.90) compared with those receiving GLP-1 RAs. SGLT2 inhibitors were associated with a lower incidence of anemia events (HR, 0.79; 95% CI, 0.71-0.87) but not with a lower rate of anemia treatment initiation (HR, 0.99; 95% CI, 0.83-1.19). Changes in hematological parameters for SGLT2 inhibitors and GLP-1 RAs throughout the 3-year follow-up period supported the primary analyses. Conclusions and Relevance In this multi-institutional cohort study with target trial emulation, SGLT2 inhibitors were associated with a decreased risk of composite anemia outcomes, especially anemia event occurrences. SGLT2 inhibitors may be considered as an adjunct therapy to reduce anemia incidence in patients with T2D and CKD.
Abstract IA017: A liquid biopsy fingerprint of disease via nanoengineering
Authors: Daniel A. Heller, Mijin Kim, Lakshmi Ramanathan, Kara Long Roche
Journal: Cancer Research (2024)

Abstract Serum biomarkers are often insufficiently sensitive or specific to facilitate cancer screening or diagnostic testing. In many cancers, including high-grade serous carcinoma (HGSC), biomarkers fail to detect early-stage cancer detection or to substantially impact mortality rates. We developed a perception-based sensing method that captures a biomarker-agnostic ‘disease fingerprint’ of HGSC using serum. Instead of measuring individual biomarkers, the method collects large data sets of molecular binding interactions to a diverse array of moderately-selective sensors, which were used to train machine learning algorithms. In an initial study using serum from 264 patients, we built a prediction model of nanosensor responses that reliably identified HGSC substantially better than CA125. We believe that the improvement of such a method, using larger nanosensor arrays, more sophisticated AI algorithms, and larger patient cohorts, could improve the detection of HGSC and facilitate biomarker discovery efforts. Citation Format: Daniel A. Heller, Mijin Kim, Lakshmi Ramanathan, Kara Long Roche. A liquid biopsy fingerprint of disease via nanoengineering [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr IA017.
Spinal Muscular Atrophy Hypotonia Detection Using Computer Vision and Artificial Intelligence
Authors: Adel Taleb, Philippe Rambaud, Samuel Diop, Raphaël Fauches, Joanna Tomasik, François Jouen, Jean Bergounioux
Journal: JAMA Pediatrics (2024)

This case-control study uses computer vision and artificial intelligence to develop a screening tool for detecting spinal muscular atrophy in infants.
MACE and Hyperthyroidism Treated With Medication, Radioactive Iodine, or Thyroidectomy
Authors: Carol Chiung-Hui Peng, Yu-Jie Lin, Sun Y. Lee, Shu-Man Lin, Cheng Han, Ching-Hui Loh, Huei-Kai Huang, Elizabeth N. Pearce
Journal: JAMA Network Open (2024)

Importance Excessive thyroid hormones from hyperthyroidism increase cardiovascular risks. Among 3 available treatments for hyperthyroidism, comparisons of long-term outcomes associated with antithyroid drugs (ATDs), radioactive iodine (RAI), and surgery to treat newly diagnosed hyperthyroidism are lacking. Objective To compare risks of major adverse cardiovascular events (MACE) and all-cause mortality among patients with hyperthyroidism treated with ATDs, RAI, or surgery. Design, Setting, and Participants This nationwide cohort study used the Taiwan National Health Insurance Research Database. Patients aged 20 years or older with newly diagnosed hyperthyroidism between 2011 and 2020 were enrolled. Treatment groups were determined within 18 months from diagnosis, with follow-up until the development of MACE, death, or the end date of the database, whichever came first. Data were analyzed from October 2022 through December 2023. Exposures The ATD group received ATDs only. RAI and surgery groups could receive ATDs before treatment. Anyone who underwent thyroid surgery without RAI was classified into the surgery group and vice versa. Main Outcomes and Measures The primary outcomes included MACE (a composite outcome of acute myocardial infarction, stroke, heart failure, and cardiovascular mortality) and all-cause mortality. Results Among 114 062 patients with newly diagnosed hyperthyroidism (mean [SD] age, 44.1 [13.6] years; 83 505 female [73.2%]), 107 052 patients (93.9%) received ATDs alone, 1238 patients (1.1%) received RAI, and 5772 patients (5.1%) underwent surgery during a mean (SD) follow-up of 4.4 (2.5) years. Patients undergoing surgery had a significantly lower risk of MACE (hazard ratio [HR] = 0.76; 95% CI, 0.59-0.98; P = .04), all-cause mortality (HR = 0.53; 95% CI, 0.41-0.68; P &amp;amp;lt; .001), heart failure (HR = 0.33; 95% CI, 0.18-0.59; P &amp;amp;lt; .001), and cardiovascular mortality (HR = 0.45; 95% CI, 0.26-0.79; P = .005) compared with patients receiving ATDs. Compared with ATDs, RAI was associated with lower MACE risk (HR = 0.45; 95% CI, 0.22-0.93; P = .03). Risks for acute myocardial infarction and stroke did not significantly differ between treatment groups. Conclusions and Relevance In this study, surgery was associated with lower long-term risks of MACE and all-cause mortality, while RAI was associated with a lower MACE risk compared with ATDs.
Medical Debt—An Iatrogenic Epidemic With Mortal Consequences
Authors: Christopher T. Su, Scott D. Ramsey
Journal: JAMA Network Open (2024)

If medical debt were a chronic illness, it would be more common than coronary artery disease, diabetes, or cancer.But is it deadly?This is the central question posed by Han et al, 1 who used countylevel records to explore the associations between medical debt, premature death, and overall mortality.Linking consumer credit, self-reported health status, and mortality records for 93% of counties in the US, the authors examined the associations between levels of medical debt and selfreported physical and mental unhealthy days, disease-specific mortality rates (including cancer and cardiovascular disease), and overall mortality.Adjusting for race, education level, health insurance status, employment status, and metropolitan status, the authors found a significant dose-response association between levels of medical debt and these outcomes.The associations are both statistically and clinically significant.For example, Hans et al 1 found that an extra 1 percentage point increase in population with medical debt was associated with 18.3 (95% CI, 16.3-20.2) more physically unhealthy days in the past month, 17.9 (95% CI, 16.1-19.8)more mentally unhealthy days in the past month, and 1.12 (95% CI, 1.03-1.21)more years of life lost per 1000 people.Adding this information to a voluminous prior literature associating medical debt and poor health outcomes, they then pose the question: what can we do about it?Previous large retrospective analyses on medical debt have not included patient-reported health outcomes. 2Through novel linkage of 3 data sources, the authors argue that medical debt is not simply an economic issue, but a public health crisis with morbid and mortal consequences.Not surprisingly, the highest levels of medical debt (and negative health consequences of debt) are concentrated among those who are least able to resolve it: those who are living in poverty,
Five-Year Follow-Up of Surgery vs Functional Bracing for Closed Displaced Humeral Shaft Fractures
Authors: Lasse Rämö, Thomas Ibounig, Bakir O. Sumrein, Vesa Lepola, Mika Paavola, Simo Taimela, Teppo L. N. Järvinen
Journal: JAMA (2024)

This study compares outcomes of surgery and functional bracing for closed humeral shaft fractures after 5 years of follow-up.
Clinical Outcomes of Rapid Respiratory Virus Testing in Emergency Departments
Authors: Tilmann Schober, Kimberly Wong, Gaëlle DeLisle, Chelsea Caya, Nathan J. Brendish, Tristan W. Clark, Nandini Dendukuri, Quynh Doan, Patricia S. Fontela, Genevieve C. Gore, Patricia Li, Allison J. McGeer, Kim Chloe Noël, Joan L. Robinson, Eva Suarthana, Jesse Papenburg
Journal: JAMA Internal Medicine (2024)

Rapid tests for respiratory viruses, including multiplex panels, are increasingly available in emergency departments (EDs). Their association with patient outcomes remains unclear.
Abstract PR-011: Role of cancer associated fibroblasts in ovarian cancer relapse
Authors: Yiming Fang, Argha Ghosh, Ji Wang, Subramanyam Dasari, Dimitriy Zamarin, Anirban Kumar Mitra
Journal: Cancer Research (2024)

Abstract Frequent relapse and development of chemoresistance leads to poor prognosis in ovarian cancer (OC). Cancer stem cells (CSCs) consist of a small subpopulation in the tumor that are typically resistant to cytotoxic chemotherapy and are a potential cause of relapse and chemoresistance. Using patient specimens as well as in vitro models, we determined that CSCs are enriched in a niche adjacent to cancer associated fibroblasts (CAFs) after chemotherapy. Cancer associated fibroblasts (CAFs) are a major constituent of the ovarian cancer tumor microenvironment and are highly enriched in the residual tumors following chemotherapy. Therefore, we studied the role of CAFs in promoting ovarian cancer chemoresistance and disease relapse by providing an optimal microenvironment for CSCs. CAFs isolated from ovarian cancer patient tumors were used in heterotypic 2D or 3D coculture systems with high-grade serous ovarian cancer cell lines or with patient-derived ovarian cancer cells to study their effect on CSCs and chemoresistance. Matched pre-and post-chemotherapy patient tumors were used to confirm our findings. CAFs significantly increased resistance to carboplatin and enriched CSCs by increasing their symmetric division as well as dedifferentiation of bulk ovarian cancer cells. Pre-coculture with CAFs increased in vivo tumor initiation capacity of the ovarian cancer cells by 10-fold. The CSC-CAF crosstalk responsible for CSC induction was found to be mediated by Wnt5a signaling. CRISPR knockdown of Wnt5a in CAFs or treatment with a specific Wnt5a inhibitor abrogated the induction of CSCs by CAFs. Only cancer cells with ROR2 Wnt coreceptor respond to Wnt5a signaling triggered by CAFs and developed into CSCs. Responders were found to signal through a non-canonical Wnt pathway involving the coreceptor ROR2, protein kinase C (PKC), and CAMP Responsive Element Binding Protein 1 (CREB1). Inhibition of each of them prevented CSC induction and functional rescue experiments confirmed the sequence of the Wnt5a-ROR2-PKC-CREB1 axis. Treatment of mouse xenografts was established by co-injection of CAFs and ovarian cancer cells, with the Wnt5a inhibitor sensitized them to carboplatin, and eliminated the CSCs in the residual tumors. Our results indicate that CAF-derived Wnt5a is instrumental in ovarian cancer CSC growth and maintenance. In the long term, our studies will broaden the understanding of the mechanism of CSC maintenance by the tumor microenvironment and contribute towards the development of novel therapeutic approaches to prevent ovarian cancer chemoresistance and relapse. Citation Format: Yiming Fang, Argha Ghosh, Ji Wang, Subramanyam Dasari, Dimitriy Zamarin, Anirban Kumar Mitra. Role of cancer associated fibroblasts in ovarian cancer relapse [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr PR-011.
Complication Rates of Central Venous Catheters
Authors: Bijan Teja, Nicholas A. Bosch, Calvin Diep, Tiago V. Pereira, Paolo Mauricio, Michael C. Sklar, Ashwin Sankar, Harindra C. Wijeysundera, Refik Saskin, Allan Walkey, Duminda N. Wijeysundera, Hannah Wunsch
Journal: JAMA Internal Medicine (2024)

Central venous catheters (CVCs) are commonly used but are associated with complications. Quantifying complication rates is essential for guiding CVC utilization decisions.
Author Correction: The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial
Authors: Deepak L. Bhatt, Harold E. Bays, Michael Miller, James E. Cain, Katarzyna Wasilewska, Nabil S. Andrawis, Teresa Parli, Shibao Feng, Lulu Sterling, Leo Tseng, Cynthia L. Hartsfield, Germaine D. Agollah, Hank Mansbach, John J. P. Kastelein
Journal: Nature Medicine (2024)
Weights, resistance bands, and rest days are best for tendinopathy
Authors: Helen Saul, Samantha Cassidy, Laura Swaithes, Anastasia Pavlova
Journal: BMJ (2024)

The study Pavlova AV, Shim JSC, Moss R, et al. Effect of resistance exercise dose components for tendinopathy management: a systematic review with meta-analysis. Br J Sports Med 2023;57:1327-34. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/weights-resistance-bands-rest-days-best-tendinopathy/
Access to Reproductive Services and Catholic Hospitals
Authors: Giselle Corbie, Mitchell H. Katz
Journal: JAMA Internal Medicine (2024)

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 2024 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
Dementia Prevention and Treatment
Authors: David B. Reuben, Sarah Kremen, Donovan T. Maust
Journal: JAMA Internal Medicine (2024)

Importance Dementia affects 10% of those 65 years or older and 35% of those 90 years or older, often with profound cognitive, behavioral, and functional consequences. As the baby boomers and subsequent generations age, effective preventive and treatment strategies will assume increasing importance. Observations Preventive measures are aimed at modifiable risk factors, many of which have been identified. To date, no randomized clinical trial data conclusively confirm that interventions of any kind can prevent dementia. Nevertheless, addressing risk factors may have other health benefits and should be considered. Alzheimer disease can be treated with cholinesterase inhibitors, memantine, and antiamyloid immunomodulators, with the last modestly slowing cognitive and functional decline in people with mild cognitive impairment or mild dementia due to Alzheimer disease. Cholinesterase inhibitors and memantine may benefit persons with other types of dementia, including dementia with Lewy bodies, Parkinson disease dementia, vascular dementia, and dementia due to traumatic brain injury. Behavioral and psychological symptoms of dementia are best treated with nonpharmacologic management, including identifying and mitigating the underlying causes and individually tailored behavioral approaches. Psychotropic medications have minimal evidence of efficacy for treating these symptoms and are associated with increased mortality and clinically meaningful risks of falls and cognitive decline. Several emerging prevention and treatment strategies hold promise to improve dementia care in the future. Conclusions and Relevance Although current prevention and treatment approaches to dementia have been less than optimally successful, substantial investments in dementia research will undoubtedly provide new answers to reducing the burden of dementia worldwide.
A Novel Polymer Nanoparticle Polydimethyl Diallyl Ammonium Chloride as An Adjuvant Enhances the Immune Response of SARS‐CoV‐2 Subunit Vaccine
Authors: Lili Ren, Chengcheng Ouyang, Shuqing Zhao, Qiqi Zheng, Weilu Guo, Baochao Fan, Jinzhu Zhou, Wei Zhang, Mi Hu, Jizong Li, Bin Li
Journal: Advanced Healthcare Materials (2024)

The Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has a significant impact on global health and the economy. It has underscored the urgent need for a stable, easily produced and effective vaccine. This study presents a novel approach using SARS-CoV-2 spike (S) protein-conjugated nanoparticles (NPs) in combination with cyclic GMP-AMP (cGAMP) (S-NPs-cGAMP) as a subunit vaccine. When mice are immunized, the antiserum of S-NPs-cGAMP group exhibits a 16-fold increase in neutralizing activity against a pseudovirus, compared to S protein group. Additionally, S-NPs-cGAMP induces even higher levels of neutralizing antibodies. Remarkably, the vaccine also triggers a robust humoral immune response, as evidenced by a notable elevation in virus-specific IgG and IgM antibodies. Furthermore, after 42 days of immunization, there is an observed increase in specific immune cell populations in the spleen. CD3