tbuckley/cabot-search huggingface dataset:
Home-Delivered Meals and Nursing Home Placement Among People With Self-Reported Dementia
Authors: Kali S. Thomas, Jen Bunker, Emily Gadbois, Michelle Hilgeman, Ellen McCreedy, Whitney Mills, Katherine A. Ornstein, Jennifer Reckrey, Roee Gutman
Journal: JAMA Network Open (2023)

Importance Home-delivered meals promote food security and independence among homebound older adults. However, it is unclear which of the 2 predominant modes of meal delivery, daily-delivered vs mailed (or drop-shipped) frozen meals, promotes community living for homebound older adults with dementia. Objective To assess the risk of nursing home admission within 6 months between homebound individuals receiving daily-delivered vs drop-shipped frozen meals. Design, Setting, and Participants This pilot, multisite, 2-arm, pragmatic clinical trial included older adults with self-reported dementia on waiting lists for meals at 3 Meals on Wheels (MOW) programs in Texas and Florida between April 7 and October 8, 2021, to assess time to nursing home placement. Interventions Participants were randomized to receive either meals delivered by an MOW driver or frozen meals that were mailed to participants’ homes every 2 weeks. Participants received their assigned intervention for up to 6 months. Main Outcomes and Measures The primary study outcome was days from randomization to a Minimum Data Set nursing home admission assessment within 6 months. Feasibility of conducting this type of study was examined by tracking enrollment, examining baseline characteristics, monitoring participants’ intervention fidelity, measuring the proportion of participants linked with Centers for Medicare &amp;amp;amp; Medicaid Services (CMS) data, and analyzing the primary study outcome. Results Among 325 eligible participants who were randomized, 243 enrolled in the study (mean [SD] age, 81 [8.0] years; 152 (62.6%) were female): 128 to the daily-delivered meals group and 115 to the drop-shipped frozen meals group; 119 participants (49.0%) lived alone. Among the total participants enrolled, 227 (93.4%) were linked deterministically to their CMS data; probabilistic methods were used to link the remaining 16 participants (6.6%). At 6 months from randomization, 160 participants (65.8%) were still receiving meals, and 25 (10.1%; 95% CI, 6.3%-14.0%) were admitted to a nursing home. After adjusting for sex, race and ethnicity, age, program, and living arrangement and the use of death as a censoring event, the adjusted log hazard ratio of nursing home placement between daily-delivered and drop-shipped frozen meals was −0.67 (95% CI, −1.52 to 0.19). Conclusions and Relevance This pilot randomized clinical trial demonstrated the feasibility of enrolling participants with self-reported dementia on waiting lists at MOW programs, linking their data, and evaluating outcomes. While this pilot study was not powered to detect meaningful, statistically significant differences in nursing home placement, its feasibility and initial results warrant exploration in a follow-on, adequately powered trial. Trial Registration ClinicalTrials.gov Identifier: NCT04850781
Repeated Measurement for Validity in Data About Surgeon Gender Differences
Authors: Karin Starzmann
Journal: JAMA Surgery (2023)

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 Surgery 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 Surgery journal
Effect of Esketamine Added to Propofol Sedation on Desaturation and Hypotension in Bidirectional Endoscopy
Authors: Nan Song, Yi Yang, Zhong Zheng, Wen-cheng Shi, Ai-ping Tan, Xi-sheng Shan, Hong Liu, Lingzhong Meng, Ke Peng, Fu-hai Ji
Journal: JAMA Network Open (2023)

Importance Propofol sedation is widely used for endoscopic procedures, but it poses risks of hemodynamic and respiratory depression. The addition of esketamine as an adjuvant may reduce propofol requirements and associated adverse events. Objective To evaluate the effects of low-dose esketamine added to propofol-based sedation on desaturation and hypotension during same-visit bidirectional endoscopy. Design, Setting, and Participants This multicenter, double-blind, placebo-controlled randomized clinical trial assessed patients from 3 teaching hospitals in China who were scheduled for same-visit bidirectional endoscopy between February 8 and November 30, 2022, and randomly assigned to receive esketamine or normal saline (placebo). Interventions After induction of sedation with 0.1 μg/kg of sufentanil and 0.5 mg/kg of propofol, patients in the esketamine group received 0.15 mg/kg of intravenous esketamine, whereas patients in the placebo group received an equivalent volume of saline. Sedation was achieved through propofol titration. Main Outcomes and Measures The primary outcome was the composite of desaturation and hypotension during the procedures. Secondary outcomes included desaturation, hypotension, propofol requirements, postprocedure pain and fatigue, nausea or vomiting, dizziness or headache, hallucination or nightmare, endoscopist satisfaction, and patient satisfaction. Results Among the 663 initially enrolled patients, 660 completed the study (median [IQR] age, 48 [36-57] years; 355 [53.8%] female), with 331 randomized to the esketamine group and 329 to the placebo group. The administration of esketamine compared with placebo significantly reduced the incidence of the composite outcome of desaturation and hypotension (8.2% vs 21.0%; difference, −12.8 percentage points; odds ratio [OR], 0.34; 95% CI, 0.21-0.54; P &amp;amp;lt; .001). Additionally, esketamine led to significantly lower incidences of desaturation (OR, 0.36; 95% CI, 0.18-0.72; false discovery rate q = .01) and hypotension (OR, 0.33; 95% CI, 0.18-0.60; q &amp;amp;lt; .001) and reduced propofol requirements (difference, −58.9 mg; 95% CI, −65.7 to −52.2 mg; q &amp;amp;lt; .001), without significant effects on other secondary outcomes. Conclusions and Relevance In this randomized clinical trial of patients undergoing same-visit bidirectional endoscopy, the administration of low-dose esketamine resulted in an approximately 61% reduction in the incidence of desaturation and hypotension, accompanied by decreased propofol requirements. These findings support the use of esketamine as an adjuvant to propofol-based sedation in endoscopic procedures. Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2200055938
Endocarditis-Related Deaths Among US Younger Adults Is “Cause for Alarm”
Authors: Emily Harris
Journal: JAMA (2023)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Phospholipase PLCE1 Promotes Transcription and Phosphorylation of MCM7 to Drive Tumor Progression in Esophageal Cancer
Authors: Qi Shi, Guixuan Xu, Yuliang Jiang, Ju Yang, Xueping Han, Qian Wang, Ya Li, Zhiyu Zhang, Kaige Wang, Hao Peng, Fangfang Chen, Yandi Ma, Linyue Zhao, Yunzhao Chen, Zheng Liu, Lan Yang, Xingyuan Jia, Tao Wen, Zhaohui Tong, Xiaobin Cui, Feng Li
Journal: Cancer Research (2023)

Abstract Phospholipase C epsilon 1 (PLCE1) is a well-established susceptibility gene for esophageal squamous cell carcinoma (ESCC). Identification of the underlying mechanism(s) regulated by PLCE1 could lead to a better understanding of ESCC tumorigenesis. In this study, we found that PLCE1 enhances tumor progression by regulating the replicative helicase MCM7 via two pathways. PLCE1 activated PKCα-mediated phosphorylation of E2F1, which led to the transcriptional activation of MCM7 and miR-106b-5p. The increased expression of miR-106b-5p, located in intron 13 of MCM7, suppressed autophagy and apoptosis by targeting Beclin-1 and RBL2, respectively. Moreover, MCM7 cooperated with the miR-106b-25 cluster to promote PLCE1-dependent cell-cycle progression both in vivo and in vitro. In addition, PLCE1 potentiated the phosphorylation of MCM7 at six threonine residues by the atypical kinase RIOK2, which promoted MCM complex assembly, chromatin loading, and cell-cycle progression. Inhibition of PLCE1 or RIOK2 hampered MCM7-mediated DNA replication, resulting in G1–S arrest. Furthermore, MCM7 overexpression in ESCC correlated with poor patient survival. Overall, these findings provide insights into the role of PLCE1 as an oncogenic regulator, a promising prognostic biomarker, and a potential therapeutic target in ESCC. Significance: PLCE1 promotes tumor progression in ESCC by activating PKCα-mediated phosphorylation of E2F1 to upregulate MCM7 and miR-106b-5p expression and by potentiating MCM7 phosphorylation by RIOK2.
Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Retinopathy in Patients With Type 2 Diabetes
Authors: Fu-Shun Yen, James Cheng-Chung Wei, Teng-Shun Yu, Yu-Tung Hung, Chih-Cheng Hsu, Chii-Min Hwu
Journal: JAMA Network Open (2023)

Importance Diabetic nephropathy and diabetic retinopathy share many similarities in pathophysiological processes. Preclinical studies have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2is) have a protective role in the risk of diabetic retinopathy. Objective To compare the risk of sight-threatening retinopathy associated with SGLT2is and other second-line glucose-lowering medications (including pioglitazone, sulfonylureas, and dipeptidyl peptidase-4 inhibitors [DPP-4is]) in patients with type 2 diabetes (T2D). Design, Setting, and Participants This cohort study in Taiwan applied a new-user and active-comparator design. Patient demographic and clinical data were obtained from the National Health Insurance Research Database. Adult patients with newly diagnosed T2D from January 1, 2009, to December 31, 2019, were recruited and followed up until December 31, 2020. Propensity score matching was used to identify pairs of patients treated with SGLT2i vs DPP-4i, SGLT2i vs pioglitazone, and SGLT2i vs sulfonylurea from January 1, 2016, to December 31, 2019. Data were analyzed between August 18, 2022, and May 5, 2023. Exposures Treatment with SGLT2i, DPP-4i, pioglitazone, and sulfonylureas starting on January 1, 2016. Main Outcomes and Measures The main outcome was sight-threatening retinopathy in participants. Cox proportional hazards regression models were used to assess relative hazards of sight-threatening retinopathy between the matched case and control groups. Results A total of 3 544 383 patients with newly diagnosed T2D were identified. After 1:1 propensity score matching, 65 930 pairs of patients treated with SGLT2i vs DPP-4i, 93 760 pairs treated with SGLT2i vs pioglitazone, and 42 121 pairs treated with SGLT2i vs sulfonylurea were identified. These matched patients included 236 574 males (58.6%), with a mean (SD) age of 56.9 (11.8) years. In the matched cohorts, SGLT2i had a significantly lower risk of sight-threatening retinopathy than DPP-4i (adjusted hazard ratio [AHR], 0.57; 95% CI, 0.51-0.63), pioglitazone (AHR, 0.75; 95% CI, 0.69-0.81), and sulfonylureas (AHR, 0.62; 95% CI, 0.53-0.71). The Kaplan-Meier curves showed that SGLT2i was associated with a significantly lower cumulative incidence of sight-threatening retinopathy than DPP-4i (3.52 vs 6.13; P &amp;amp;lt; .001), pioglitazone (4.32 vs 5.76; P &amp;amp;lt; .001), and sulfonylureas (2.94 vs 4.67; P &amp;amp;lt; .001). Conclusions and Relevance This cohort study found that SGLT2i was associated with a lower risk of sight-threatening retinopathy compared with DPP-4i, pioglitazone, and sulfonylureas. This finding suggests that SGLT2i may play a role not only in reduced risk of diabetic nephropathy but also in the slow progression of diabetic retinopathy in patients with T2D.
Newborn Brain Function and Early Emerging Callous-Unemotional Traits
Authors: Rebecca G. Brady, Megan Rose Donohue, Rebecca Waller, Aidan Latham, Mia Ayala, Tara A. Smyser, Barbara B. Warner, Deanna M. Barch, Joan L. Luby, Cynthia E. Rogers, Christopher D. Smyser
Journal: JAMA Psychiatry (2023)

Children with high callous-unemotional traits are more likely to develop severe and persistent conduct problems; however, the newborn neurobiology underlying early callous-unemotional traits remains unknown. Understanding the neural mechanisms that precede the development of callous-unemotional traits could help identify at-risk children and encourage development of novel treatments.
Serine-129 phosphorylation of α-synuclein is an activity-dependent trigger for physiologic protein-protein interactions and synaptic function
Authors: Leonardo A. Parra-Rivas, Kayalvizhi Madhivanan, Brent D. Aulston, Lina Wang, Dube Dheeraj Prakashchand, Nicholas P. Boyer, Veronica M. Saia-Cereda, Kristen Branes-Guerrero, Donald P. Pizzo, Pritha Bagchi, V.S. Sundar, Yong Tang, Utpal Das, David A. Scott, Padmini Rangamani, Yuki Ogawa, None Subhojit Roy
Journal: Neuron (2023)

Phosphorylation of α-synuclein at the serine-129 site (α-syn Ser129P) is an established pathologic hallmark of synucleinopathies and a therapeutic target. In physiologic states, only a fraction of α-syn is phosphorylated at this site, and most studies have focused on the pathologic roles of this post-translational modification. We found that unlike wild-type (WT) α-syn, which is widely expressed throughout the brain, the overall pattern of α-syn Ser129P is restricted, suggesting intrinsic regulation. Surprisingly, preventing Ser129P blocked activity-dependent synaptic attenuation by α-syn—thought to reflect its normal function. Exploring mechanisms, we found that neuronal activity augments Ser129P, which is a trigger for protein-protein interactions that are necessary for mediating α-syn function at the synapse. AlphaFold2-driven modeling and membrane-binding simulations suggest a scenario where Ser129P induces conformational changes that facilitate interactions with binding partners. Our experiments offer a new conceptual platform for investigating the role of Ser129 in synucleinopathies, with implications for drug development.
CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility
Authors: Mulong Du, Junyi Xin, Rui Zheng, Qianyu Yuan, Zhihui Wang, Hongliang Liu, Hanting Liu, Guoshuai Cai, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Stig E. Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, Gad Rennert, Susanne Arnold, Paul Brennan, John K. Field, Sanjay S. Shete, Loïc Le Marchand, Geoffrey Liu, Angeline S. Andrew, Lambertus A. Kiemeney, Shan Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E. Caporaso, Angela Cox, Yun-Chul Hong, Jian-Min Yuan, Matthew B. Schabath, Melinda C. Aldrich, Meilin Wang, Hongbing Shen, Feng Chen, Zhengdong Zhang, Rayjean J. Hung, Christopher I. Amos, Qingyi Wei, Philip Lazarus, David C. Christiani
Journal: Cancer Research (2023)

Abstract Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen–metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke–exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C&amp;gt;T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers (OR = 0.88, 95% confidence interval = 0.85–0.91, P = 2.18 × 10−16), which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor helicase-like transcription factor. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis. Significance: The causal pathway connecting CYP2A6 genetic variability and activity, cigarette consumption, and lung cancer susceptibility in smokers highlights the need for behavior modification interventions based on host susceptibility for cancer prevention.
Glycosylation-modified antigens as a tolerance-inducing vaccine platform prevent anaphylaxis in a pre-clinical model of food allergy
Authors: Shijie Cao, Chitavi D. Maulloo, Michal M. Raczy, Matthew Sabados, Anna J. Slezak, Mindy Nguyen, Ani Solanki, Rachel P. Wallace, Ha-Na Shim, D. Scott Wilson, Jeffrey A. Hubbell
Journal: Cell Reports Medicine (2023)

The only FDA-approved oral immunotherapy for a food allergy provides protection against accidental exposure to peanuts. However, this therapy often causes discomfort or side effects and requires long-term commitment. Better preventive and therapeutic solutions are urgently needed. We develop a tolerance-inducing vaccine technology that utilizes glycosylation-modified antigens to induce antigen-specific non-responsiveness. The glycosylation-modified antigens are administered intravenously (i.v.) or subcutaneously (s.c.) and traffic to the liver or lymph nodes, respectively, leading to preferential internalization by antigen-presenting cells, educating the immune system to respond in an innocuous way. In a mouse model of cow's milk allergy, treatment with glycosylation-modified β-lactoglobulin (BLG) is effective in preventing the onset of allergy. In addition, s.c. administration of glycosylation-modified BLG shows superior safety and potential in treating existing allergies in combination with anti-CD20 co-therapy. This platform provides an antigen-specific immunomodulatory strategy to prevent and treat food allergies.
Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes
Authors: Udi Ehud Knebel, Shani Peleg, Chunhua Dai, Roni Cohen-Fultheim, Sara Jonsson, Karin Poznyak, Maya Israeli, Liza Zamashanski, Benjamin Glaser, Erez Y. Levanon, Alvin C. Powers, Agnes Klochendler, Yuval Dor
Journal: Cell Metabolism (2023)

A major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon response and inflammation; however, a causal virus has not been identified. Here, we use a mouse model, corroborated with human islet data, to demonstrate that endogenous dsRNA in beta cells can lead to a diabetogenic immune response, thus identifying a virus-independent mechanism for T1D initiation. We found that disruption of the RNA editing enzyme adenosine deaminases acting on RNA (ADAR) in beta cells triggers a massive interferon response, islet inflammation, and beta cell failure and destruction, with features bearing striking similarity to early-stage human T1D. Glycolysis via calcium enhances the interferon response, suggesting an actionable vicious cycle of inflammation and increased beta cell workload.
Decoupling NAD+ metabolic dependency in chondrosarcoma by targeting the SIRT1-HIF-2α axis
Authors: Jooyeon Suh, Hyeonkyeong Kim, Jiyun Min, Hyun Ju Yeon, Martin Hemberg, Luca Scimeca, Ming-Ru Wu, Hyun Guy Kang, Yi-Jun Kim, Jin-Hong Kim
Journal: Cell Reports Medicine (2023)

Chondrosarcomas represent the second most common primary bone malignancy. Despite the vulnerability of chondrosarcoma cells to nicotinamide adenine dinucleotide (NAD
A Biodegradable “One‐For‐All” Nanoparticle for Multimodality Imaging and Enhanced Photothermal Treatment of Breast Cancer
Authors: Jessica C. Hsu, Diego Barragan, Alexander E. Tward, Maryam Hajfathalian, Ahmad Amirshaghaghi, Katherine J. Mossburg, Derick N. Rosario‐Berríos, Mathilde Bouché, Alexander K. Andrianov, Edward J. Delikatny, David P. Cormode
Journal: Advanced Healthcare Materials (2023)

Silver sulfide nanoparticles (Ag
Synthetically mannosylated antigens induce antigen-specific humoral tolerance and reduce anti-drug antibody responses to immunogenic biologics
Authors: Rachel P. Wallace, Kirsten C. Refvik, Jennifer T. Antane, Kym Brünggel, Andrew C. Tremain, Michal R. Raczy, Aaron T. Alpar, Mindy Nguyen, Ani Solanki, Anna J. Slezak, Elyse A. Watkins, Abigail L. Lauterbach, Shijie Cao, D. Scott Wilson, Jeffrey A. Hubbell
Journal: Cell Reports Medicine (2023)

Immunogenic biologics trigger an anti-drug antibody (ADA) response in patients that reduces efficacy and increases adverse reactions. Our laboratory has shown that targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy to increase delivery of otherwise immunogenic biologics to the liver via conjugation to a synthetic mannose polymer, p(Man). This delivery leads to reduced antigen-specific T follicular helper cell and B cell responses resulting in diminished ADA production, which is maintained throughout subsequent administrations of the native biologic. We find that p(Man)-antigen treatment impairs the ADA response against recombinant uricase, a highly immunogenic biologic, without a dependence on hapten immunodominance or control by T regulatory cells. We identify increased T cell receptor signaling and increased apoptosis and exhaustion in T cells as effects of p(Man)-antigen treatment via transcriptomic analyses. This modular platform may enhance tolerance to biologics, enabling long-term solutions for an ever-increasing healthcare problem.