tbuckley/cabot-search huggingface dataset:
Author Correction: Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: the phase 2 CORE-001 trial
Authors: Roger Li, Paras H. Shah, Tyler F. Stewart, Jong Kil Nam, Trinity J. Bivalacqua, Donald L. Lamm, Edward M. Uchio, Daniel M. Geynisman, Joseph M. Jacob, Joshua J. Meeks, Rian Dickstein, Shane M. Pearce, Seok Ho Kang, Seung Il Jung, Ashish M. Kamat, James M. Burke, Kirk A. Keegan, Gary D. Steinberg
Journal: Nature Medicine (2024)

of the article.
Dysfunction of infiltrating cytotoxic CD8+ T cells within the graft promotes murine kidney allotransplant tolerance
Authors: Takahiro Yokose, Edward S. Szuter, Ivy Rosales, Michael T. Guinn, Andrew S. Liss, Taisuke Baba, David A. Ruddy, Michelle Piquet, Jamil Azzi, A. Benedict Cosimi, Paul S. Russell, Joren C. Madsen, Robert B. Colvin, Alessandro Alessandrini
Journal: Journal of Clinical Investigation (2024)

Tolerance of mouse kidney allografts arises in grafts that develop regulatory Tertiary Lymphoid Organs (rTLOs). scRNAseq data and adoptive transfer of alloreactive T cells post-transplant showed that cytotoxic CD8+ T cells are reprogrammed within the accepted graft to an exhausted/regulatory-like phenotype mediated by IFN-γ. Establishment of rTLOs was required since adoptive transfer of alloreactive T cells prior to transplantation results in kidney allograft rejection. Despite intragraft CD8+ cells with a regulatory phenotype, they were not essential for the induction and maintenance of kidney allograft tolerance since renal allotransplantation into CD8 KO recipients resulted in acceptance and not rejection. Analysis of scRNAseq data from allograft kidneys and malignant tumors identified similar regulatory-like cell types within the T cell clusters and trajectory analysis showed that cytotoxic CD8+ T cells are reprogrammed into an exhausted/regulatory-like phenotype intratumorally. Induction of cytotoxic CD8+ T cell dysfunction of infiltrating cells appears to be a beneficial mechanistic pathway that protects the kidney allotransplant from rejection through a process we call "defensive tolerance." This pathway has implications for our understanding of allotransplant tolerance and tumor resistance to host immunity.
Effects of microplastics on the kidneys: a narrative review
Authors: Rodrigo Bueno de Oliveira, Lauter E. Pelepenko, Daniela A. Masaro, Glauco M.M.M. Lustosa, Mariana C. de Oliveira, Noemí A.V. Roza, Marina A. Marciano, Luciene M. dos Reis, Saïd Kamel, Loïc Louvet, Talita Mazon
Journal: Kidney International (2024)
Branched‐Tail Lipid Nanoparticles for Intravenous mRNA Delivery to Lung Immune, Endothelial, and Alveolar Cells in Mice
Authors: Daria M. Strelkova Petersen, Ryan M. Weiss, Khalid A. Hajj, Saigopalakrishna S. Yerneni, Namit Chaudhary, Alexandra N. Newby, Mariah L. Arral, Kathryn A. Whitehead
Journal: Advanced Healthcare Materials (2024)

Lipid nanoparticles (LNPs) are proven safe and effective delivery systems on a global scale. However, their efficacy has been limited primarily to liver and immune cell targets. To extend the applicability of mRNA drugs, 580 ionizable lipidoids are synthesized and tested for delivery to extrahepatocellular targets. Of these, over 40 enabled protein expression in mice, with the majority transfecting the liver. Beyond the liver, several LNPs containing new, branched-tail ionizable lipidoids potently delivered mRNA to the lungs, with cell-level specificity depending on helper lipid chemistry. Incorporation of the neutral helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) at 16 mol% enabled highly specific delivery to natural killer and dendritic cells within the lung. Although inclusion of the cationic lipid 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) improved lung tropism, it decreased cell specificity, resulting in equal transfection of endothelial and lymphoid cells. DOTAP formulations are also less favorable than DOPE formulations because they elevated liver enzyme and cytokine levels. Together, these data identify a new branched-tailed LNP with a unique ability to selectively transfect lung immune cell populations without the use of toxicity-prone cationic helper lipids. This novel vehicle may unlock RNA therapies for lung diseases associated with immune cell dysregulation, including cancer, viral infections, and autoimmune disorders.
The Alzheimer’s disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling
Authors: Andree Schmidt, Brian Hrupka, Frauke van Bebber, Sanjay Sunil Kumar, Xiao Feng, Sarah K. Tschirner, Marlene Aßfalg, Stephan A. Müller, Laura Sophie Hilger, Laura I. Hofmann, Martina Pigoni, Georg Jocher, Iryna Voytyuk, Emily L. Self, Mana Ito, Kana Hyakkoku, Akimasa Yoshimura, Naotaka Horiguchi, Regina Feederle, Bart De Strooper, Stefan Schulte-Merker, Eckhard Lammert, Dieder Moechars, Bettina Schmid, Stefan F. Lichtenthaler
Journal: Journal of Clinical Investigation (2024)

The β-secretase β-site APP cleaving enzyme (BACE1) is a central drug target for Alzheimer's disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet little is known about physiological BACE2 substrates and functions in vivo. Here, we identify BACE2 as the protease shedding the lymphangiogenic vascular endothelial growth factor receptor 3 (VEGFR3). Inactivation of BACE2, but not BACE1, inhibited shedding of VEGFR3 from primary human lymphatic endothelial cells (LECs) and reduced release of the shed, soluble VEGFR3 (sVEGFR3) ectodomain into the blood of mice, nonhuman primates, and humans. Functionally, BACE2 inactivation increased full-length VEGFR3 and enhanced VEGFR3 signaling in LECs and also in vivo in zebrafish, where enhanced migration of LECs was observed. Thus, this study identifies BACE2 as a modulator of lymphangiogenic VEGFR3 signaling and demonstrates the utility of sVEGFR3 as a pharmacodynamic plasma marker for BACE2 activity in vivo, a prerequisite for developing BACE1-selective inhibitors for safer prevention of Alzheimer's disease.
Peripheral gating of mechanosensation by glial diazepam binding inhibitor
Authors: Xinmeng Li, Arthur Silveira Prudente, Vincenzo Prato, Xianchuan Guo, Han Hao, Frederick Jones, Sofia Figoli, Pierce Mullen, Yujin Wang, Raquel Tonello, Sang Hoon Lee, Shihab Shah, Benito Maffei, Temugin Berta, Xiaona Du, Nikita Gamper
Journal: Journal of Clinical Investigation (2024)

We report that diazepam binding inhibitor (DBI) is a glial messenger mediating satellite glia-sensory neuron crosstalk in the dorsal root ganglion (DRG). DBI is highly expressed in satellite glia cells (SGCs) of mice, rat and human, but not in sensory neurons or most other DRG-resident cells. Knockdown of DBI results in a robust mechanical hypersensitivity without major effects on other sensory modalities. In vivo overexpression of DBI in SGCs reduces sensitivity to mechanical stimulation and alleviates mechanical allodynia in neuropathic and inflammatory pain models. We further show that DBI acts as an unconventional agonist and positive allosteric modulator at the neuronal GABAA receptors, particularly strongly effecting those with a high-affinity benzodiazepine binding site. Such receptors are selectively expressed by a subpopulation of mechanosensitive DRG neurons and these are also more enwrapped with DBI-expressing glia, as compared to other DRG neurons, suggesting a mechanism for specific effect of DBI on mechanosensation. These findings identified a new, peripheral neuron-glia communication mechanism modulating pain signalling, which can be targeted therapeutically.
Dermoscopic Features of Melanocytic Nevi in Cardiofaciocutaneous and Costello Syndromes
Authors: Alexandra R. Vaughn, Summer N. Meyer, Zaeem H. Nazir, Jennifer Tavernetti, Elanee Simmons, Hong Li, Irina Rybak, Katherine A. Rauen, Ashfaq A. Marghoob, Maija Kiuru
Journal: JAMA Dermatology (2024)

Somatic variants in the RAS/MAPK pathway genes are commonly associated with melanocytic nevi and melanoma, whereas germline variants in these genes are associated with RASopathies, syndromes involving multiple organs, including the skin. Nevi counts may be higher in some RASopathies, but studies on features observed through dermoscopy are limited.
State Cannabis Legalization and Trends in Cannabis-Related Disorders in US Older Adults, 2017 to 2022
Authors: Silvia Perez-Vilar, Pablo Freyria Duenas, Rose Radin, Sandia Akhtar, Michael Wernecke, Jeffrey A. Kelman, David J. Graham
Journal: JAMA Network Open (2024)

This cross-sectional study examines trends in health care encounters with cannabis-related disorders among Medicare beneficiaries from 2017 to 2022.
Enhanced Recovery After Surgery Guidelines and Hospital Length of Stay, Readmission, Complications, and Mortality
Authors: Khara M. Sauro, Christine Smith, Seremi Ibadin, Abigail Thomas, Heather Ganshorn, Linda Bakunda, Bishnu Bajgain, Steven P. Bisch, Gregg Nelson
Journal: JAMA Network Open (2024)

Importance A comprehensive review of the evidence exploring the outcomes of enhanced recovery after surgery (ERAS) guidelines has not been completed. Objective To evaluate if ERAS guidelines are associated with improved hospital length of stay, hospital readmission, complications, and mortality compared with usual surgical care, and to understand differences in estimates based on study and patient factors. Data Sources MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central were searched from inception until June 2021. Study Selection Titles, abstracts, and full-text articles were screened by 2 independent reviewers. Eligible studies were randomized clinical trials that examined ERAS-guided surgery compared with a control group and reported on at least 1 of the outcomes. Data Extraction and Synthesis Data were abstracted in duplicate using a standardized data abstraction form. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Risk of bias was assessed in duplicate using the Cochrane Risk of Bias tool. Random-effects meta-analysis was used to pool estimates for each outcome, and meta-regression identified sources of heterogeneity within each outcome. Main Outcome and Measures The primary outcomes were hospital length of stay, hospital readmission within 30 days of index discharge, 30-day postoperative complications, and 30-day postoperative mortality. Results Of the 12 047 references identified, 1493 full texts were screened for eligibility, 495 were included in the systematic review, and 74 RCTs with 9076 participants were included in the meta-analysis. Included studies presented data from 21 countries and 9 ERAS-guided surgical procedures with 15 (20.3%) having a low risk of bias. The mean (SD) Reporting on ERAS Compliance, Outcomes, and Elements Research checklist score was 13.5 (2.3). Hospital length of stay decreased by 1.88 days (95% CI, 0.95-2.81 days; I 2 = 86.5%; P &amp;amp;lt; .001) and the risk of complications decreased (risk ratio, 0.71; 95% CI, 0.59-0.87; I 2 = 78.6%; P &amp;amp;lt; .001) in the ERAS group. Risk of readmission and mortality were not significant. Conclusions and Relevance In this meta-analysis, ERAS guidelines were associated with decreased hospital length of stay and complications. Future studies should aim to improve implementation of ERAS and increase the reach of the guidelines.
Availability of Medications for Opioid Use Disorder in Community Mental Health Facilities
Authors: Jonathan Cantor, Beth Ann Griffin, Barbara Levitan, Sapna J. Mendon-Plasek, Bradley D. Stein, Sarah B. Hunter, Allison J. Ober
Journal: JAMA Network Open (2024)

Importance Medications for opioid use disorder (MOUD) are an effective but underutilized treatment. Opioid use disorder prevalence is high among people receiving treatment in community outpatient mental health treatment facilities (MHTFs), but MHTFs are understudied as an MOUD access point. Objective To quantify availability of MOUD at community outpatient MHTFs in high-burden states as well as characteristics associated with offering MOUD. Design, Setting, and Participants This cross-sectional study performed a phone survey between April and July 2023 among a representative sample of community outpatient MHTFs within 20 states most affected by the opioid crisis, including all Certified Community Behavioral Health Centers (CCBHCs). Participants were staff at 450 surveyed community outpatient MHTFs in 20 states in the US. Main Outcomes and Measures MOUD availability. A multivariable logistic regression was fit to assess associations of facility, county, and state-level characteristics with offering MOUD. Results Surveys with staff from 450 community outpatient MHTFs (152 CCBHCs and 298 non-CCBHCs) in 20 states were analyzed. Weighted estimates found that 34% (95% CI, 29%-39%) of MHTFs offered MOUD in these states. Facility-level factors associated with increased odds of offering MOUD were: self-reporting being a CCBHC (odds ratio [OR], 2.11 [95% CI, 1.08-4.11]), providing integrated mental and substance use disorder treatment (OR, 5.21 [95% CI, 2.44-11.14), having a specialized treatment program for clients with co-occurring mental and substance use disorders (OR, 2.25 [95% CI, 1.14-4.43), offering housing services (OR, 2.54 [95% CI, 1.43-4.51]), and laboratory testing (OR, 2.15 [95% CI, 1.12-4.12]). Facilities that accepted state-financed health insurance plans other than Medicaid as a form of payment had increased odds of offering MOUD (OR, 1.95 [95% CI, 1.01-3.76]) and facilities that accepted state mental health agency funds had reduced odds (OR, 0.43 [95% CI, 0.19-0.99]). Conclusions and Relevance In this study of 450 community outpatient MHTFs in 20 high-burden states, approximately one-third offered MOUD. These results suggest that further study is needed to report MOUD uptake, either through increased prescribing at all clinics or through effective referral models.
Variation in Postoperative Outcomes Across Federally Designated Hospital Star Ratings
Authors: Adrian Diaz, Calista Harbaugh, Justin B. Dimick, Nicholas Kunnath, Andrew M. Ibrahim
Journal: JAMA Surgery (2024)

Despite widespread use to guide patients to hospitals providing the best care, it remains unknown whether Centers for Medicare & Medicaid Services (CMS) hospital star ratings are a reliable measure of hospital surgical quality.
Comments on a Randomized Clinical Trial of Intraoperative Wound Irrigation—Reply
Authors: Tara Catharina Mueller, Victoria Kehl, Daniel Reim
Journal: JAMA Surgery (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 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
Performance of Large Language Models on Medical Oncology Examination Questions
Authors: Jack B. Longwell, Ian Hirsch, Fernando Binder, Galileo Arturo Gonzalez Conchas, Daniel Mau, Raymond Jang, Rahul G. Krishnan, Robert C. Grant
Journal: JAMA Network Open (2024)

Importance Large language models (LLMs) recently developed an unprecedented ability to answer questions. Studies of LLMs from other fields may not generalize to medical oncology, a high-stakes clinical setting requiring rapid integration of new information. Objective To evaluate the accuracy and safety of LLM answers on medical oncology examination questions. Design, Setting, and Participants This cross-sectional study was conducted between May 28 and October 11, 2023. The American Society of Clinical Oncology (ASCO) Oncology Self-Assessment Series on ASCO Connection, the European Society of Medical Oncology (ESMO) Examination Trial questions, and an original set of board-style medical oncology multiple-choice questions were presented to 8 LLMs. Main Outcomes and Measures The primary outcome was the percentage of correct answers. Medical oncologists evaluated the explanations provided by the best LLM for accuracy, classified the types of errors, and estimated the likelihood and extent of potential clinical harm. Results Proprietary LLM 2 correctly answered 125 of 147 questions (85.0%; 95% CI, 78.2%-90.4%; P &amp;amp;lt; .001 vs random answering). Proprietary LLM 2 outperformed an earlier version, proprietary LLM 1, which correctly answered 89 of 147 questions (60.5%; 95% CI, 52.2%-68.5%; P &amp;amp;lt; .001), and the best open-source LLM, Mixtral-8x7B-v0.1, which correctly answered 87 of 147 questions (59.2%; 95% CI, 50.0%-66.4%; P &amp;amp;lt; .001). The explanations provided by proprietary LLM 2 contained no or minor errors for 138 of 147 questions (93.9%; 95% CI, 88.7%-97.2%). Incorrect responses were most commonly associated with errors in information retrieval, particularly with recent publications, followed by erroneous reasoning and reading comprehension. If acted upon in clinical practice, 18 of 22 incorrect answers (81.8%; 95% CI, 59.7%-94.8%) would have a medium or high likelihood of moderate to severe harm. Conclusions and Relevance In this cross-sectional study of the performance of LLMs on medical oncology examination questions, the best LLM answered questions with remarkable performance, although errors raised safety concerns. These results demonstrated an opportunity to develop and evaluate LLMs to improve health care clinician experiences and patient care, considering the potential impact on capabilities and safety.
Thermoelectric‐Feedback Nanocomposite Hydrogel for Temperature‐Synchronized Monitoring and Regulation in Accurate Photothermal Therapy
Authors: Hongtao Xu, Gang Huang, Han Cheng, Fangjie Li, Zhiyuan Zhang, Xiaojuan Huang, Hailong Huang, Chongyang Zheng
Journal: Advanced Healthcare Materials (2024)

Photothermal therapy (PTT) is a promising approach for tumor ablation and cancer treatment. However, controlling the therapeutic temperature during treatment remains challenging, and imprecise thermal regulation can harm adjacent healthy tissues, reduce therapeutic accuracy, and promote the thermotolerance of cellular phenotypes, potentially leading to tumor invasion and recurrence. Although existing methods provide basic temperature control by adjusting irradiation power and photothermal agent dosing, they lack real-time temperature monitoring and feedback control capabilities, underscoring the urgent need for more integrated and precise PTT systems. In this context, an innovative photothermoelectric (PTE) cobalt-infused chitosan (CS) nanocomposite hydrogel (PTE-Co@CS) is developed for precise temperature-regulated PTT, exhibiting desirable mechanical properties and exceptional biocompatibility. Enhanced by embedded nanoparticles, PTE-Co@CS demonstrates superior photothermal conversion efficiency compared with existing methods, while also featuring thermoelectric responsiveness and increased sensitivity to photostimuli. Its advantageous PTE response characteristics ensure a linear correlation between temperature shifts and resistance changes (e.g., R
<i>RNF213</i> Variants, Vasospastic Angina, and Risk of Fatal Myocardial Infarction
Authors: Keiko Hikino, Satoshi Koyama, Kaoru Ito, Yoshinao Koike, Masaru Koido, Takayoshi Matsumura, Ryo Kurosawa, Kohei Tomizuka, Shuji Ito, Xiaoxi Liu, Yuki Ishikawa, Yukihide Momozawa, Takayuki Morisaki, Yoichiro Kamatani, Taisei Mushiroda, Chikashi Terao, Yuji Yamanashi, Yoichi Furukawa, Yoshinori Murakami, Kaori Muto, Akiko Nagai, Wataru Obara, Ken Yamaji, Kazuhisa Takahashi, Satoshi Asai, Yasuo Takahashi, Takao Suzuki, Nobuaki Sinozaki, Hiroki Yamaguchi, Shiro Minami, Shigeo Murayama, Kozo Yoshimori, Satoshi Nagayama, Daisuke Obata, Masahiko Higashiyama, Akihide Matsumoto, Yukihiro Koretsune
Journal: JAMA Cardiology (2024)

Vasospastic angina (VSA) is vasospasm of the coronary artery and is particularly prevalent in East Asian populations. However, the specific genetic architecture for VSA at genome-wide levels is not fully understood.
Online interpretable dynamic prediction models for clinically significant posthepatectomy liver failure based on machine learning algorithms: A retrospective cohort study
Authors: Yuzhan Jin, Wanxia Li, Yachen Wu, Qian Wang, Zhiqiang Xiang, Zhangtao Long, Hao Liang, Jianjun Zou, Zhu Zhu, Xiaoming Dai
Journal: International Journal of Surgery (2024)

Background: Posthepatectomy liver failure (PHLF) is the leading cause of mortality in patients undergoing hepatectomy. However, practical models for accurately predicting the risk of PHLF are lacking. This study aimed to develop precise prediction models for clinically significant PHLF. Methods: A total of 226 patients undergoing hepatectomy at a single center were recruited. The study outcome was clinically significant PHLF. Five pre- and postoperative machine learning (ML) models were developed and compared with four clinical scores, namely, the MELD, FIB-4, ALBI, and APRI scores. The robustness of the developed ML models was internally validated using 5-fold cross-validation by calculating the average of the evaluation metrics and was externally validated on an independent temporal dataset, including the area under the curve (AUC) and the area under the precision‒recall curve (AUPRC). SHapley Additive exPlanations analysis was performed to interpret the best performance model. Results: Clinically significant PHLF was observed in 23 of 226 patients (10.2%). The variables in the preoperative model included creatinine, total bilirubin, and Child‒Pugh grade. In addition to the above factors, the extent of resection was also a key variable for the postoperative model. The pre- and postoperative artificial neural network (ANN) models exhibited excellent performance, with mean AUCs of 0.766 and 0.851, respectively, and mean AUPRC values of 0.441 and 0.645, whereas the MELD, FIB-4, ALBI, and APRI scores reached AUCs of 0.714, 0.498, 0.536 and 0.551, respectively, and AUPRC values of 0.204, 0.111, 0.128 and 0.163, respectively. In addition, the AUCs of the pre- and postoperative ANN models were 0.720 and 0.731, respectively, and the AUPRC values were 0.380 and 0.408, respectively, on the temporal dataset. Conclusion: Our online interpretable dynamic ML models outperformed common clinical scores and could function as a clinical decision support tool to identify patients at high risk of PHLF pre- and postoperatively.