tbuckley/cabot-search huggingface dataset:
Automation Bias and Assistive AI
Authors: Rohan Khera, Melissa A. Simon, Joseph S. Ross
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
Organizational Factors in Clinical Data Sharing for Artificial Intelligence in Health Care
Authors: Alaa Youssef, Madelena Y. Ng, Jin Long, Tina Hernandez-Boussard, Nigam Shah, Adam Miner, David Larson, Curtis P. Langlotz
Journal: JAMA Network Open (2023)

Importance Limited sharing of data sets that accurately represent disease and patient diversity limits the generalizability of artificial intelligence (AI) algorithms in health care. Objective To explore the factors associated with organizational motivation to share health data for AI development. Design, Setting, and Participants This qualitative study investigated organizational readiness for sharing health data across the academic, governmental, nonprofit, and private sectors. Using a multiple case studies approach, 27 semistructured interviews were conducted with leaders in data-sharing roles from August 29, 2022, to January 9, 2023. The interviews were conducted in the English language using a video conferencing platform. Using a purposive and nonprobabilistic sampling strategy, 78 individuals across 52 unique organizations were identified. Of these, 35 participants were enrolled. Participant recruitment concluded after 27 interviews, as theoretical saturation was reached and no additional themes emerged. Main Outcome and Measure Concepts defining organizational readiness for data sharing and the association between data-sharing factors and organizational behavior were mapped through iterative qualitative analysis to establish a framework defining organizational readiness for sharing clinical data for AI development. Results Interviews included 27 leaders from 18 organizations (academia: 10, government: 7, nonprofit: 8, and private: 2). Organizational readiness for data sharing centered around 2 main constructs: motivation and capabilities. Motivation related to the alignment of an organization’s values with data-sharing priorities and was associated with its engagement in data-sharing efforts. However, organizational motivation could be modulated by extrinsic incentives for financial or reputational gains. Organizational capabilities comprised infrastructure, people, expertise, and access to data. Cross-sector collaboration was a key strategy to mitigate barriers to access health data. Conclusions and Relevance This qualitative study identified sector-specific factors that may affect the data-sharing behaviors of health organizations. External incentives may bolster cross-sector collaborations by helping overcome barriers to accessing health data for AI development. The findings suggest that tailored incentives may boost organizational motivation and facilitate sustainable flow of health data for AI development.
Making Sense of Individual Responses to Sodium Reduction
Authors: Jordana B. Cohen, Stephen P. Juraschek
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
Preclinical characterization and clinical trial of CFI-400945, a polo-like kinase 4 inhibitor, in patients with relapsed/refractory acute myeloid leukemia and higher-risk myelodysplastic neoplasms
Authors: Tracy Murphy, Jacqueline M. Mason, Brian Leber, Mark R. Bray, Steven M. Chan, Vikas Gupta, Dina Khalaf, Dawn Maze, Caroline J. McNamara, Aaron D. Schimmer, Andre C. Schuh, Hassan Sibai, Michael Trus, Debbie Valiquette, Kylie Martin, Linh Nguyen, Xuan Li, Tak W. Mak, Mark D. Minden, Karen W. L. Yee
Journal: Leukemia (2023)
Editorial Expression of Concern: Altered neuregulin 1–erbB4 signaling contributes to NMDA&gt; receptor hypofunction in schizophrenia
Authors: Chang-Gyu Hahn, Hoau-Yan Wang, Dan-Sung Cho, Konrad Talbot, Raquel E Gur, Wade H Berrettini, Kalindi Bakshi, Joshua Kamins, Karin E Borgmann-Winter, Steven J Siegel, Robert J Gallop, Steven E Arnold
Journal: Nature Medicine (2023)
Phase 1 trial supports safety and mechanism of action of peptide immunotherapy for peanut allergy
Authors: Astrid L. Voskamp, Sugandhika Khosa, Tracy Phan, Hannah A. DeBerg, Judy Bingham, Mark Hew, William Smith, Jodie Abramovitch, Jennifer M. Rolland, Matthew Moyle, Kari C. Nadeau, Gideon Lack, Mark Larché, Erik Wambre, Robyn E. O'Hehir, Pascal Hickey, Sara R. Prickett
Journal: Allergy (2023)

Abstract Background Food allergy is a leading cause of anaphylaxis worldwide. Allergen‐specific immunotherapy is the only treatment shown to modify the natural history of allergic disease, but application to food allergy has been hindered by risk of severe allergic reactions and short‐lived efficacy. Allergen‐derived peptides could provide a solution. PVX108 comprises seven short peptides representing immunodominant T‐cell epitopes of major peanut allergens for treatment of peanut allergy. Methods Pre‐clinical safety of PVX108 was assessed using ex vivo basophil activation tests ( n = 185). Clinical safety and tolerability of single and repeat PVX108 doses were evaluated in a first‐in‐human, randomized, double‐blind, placebo‐controlled trial in peanut‐allergic adults (46 active, 21 placebo). The repeat‐dose cohort received six doses over 16 weeks with safety monitored to 21 weeks. Exploratory immunological analyses were performed at pre‐dose, Week 21 and Month 18 after treatment. Results PVX108 induced negligible activation of peanut‐sensitised basophils. PVX108 was safe and well tolerated in peanut‐allergic adults. There were no treatment‐related hypersensitivity events or AEs of clinical concern. The only events occurring more frequently in active than placebo were mild injection site reactions. Exploratory immunological analyses revealed a decrease in the ratio of ST2 + Th2A:CCR6 + Th17‐like cells within the peanut‐reactive Th pool which strengthened following treatment. Conclusion This study supports the concept that PVX108 could provide a safe alternative to whole peanut immunotherapies and provides evidence of durable peanut‐specific T‐cell modulation. Translation of these findings to clinical efficacy in ongoing Phase 2 trials would provide important proof‐of‐concept for using peptides to treat food allergy.
Common Painful Foot and Ankle Conditions
Authors: Minton Truitt Cooper
Journal: JAMA (2023)

Importance Morton neuroma, plantar fasciitis, and Achilles tendinopathy are foot and ankle conditions that are associated with pain and disability, but they can respond to nonoperative treatment. Observations Morton neuroma, consisting of interdigital neuronal thickening and fibrosis, is characterized by burning pain in the ball of the foot and numbness or burning pain that may radiate to the affected toes (commonly the third and fourth toes). First-line nonoperative therapy consists of reducing activities that cause pain, orthotics, and interdigital corticosteroid injection; however, approximately 30% of patients may not respond to conservative treatment. Plantar fasciitis accounts for more than 1 million patient visits per year in the US and typically presents with plantar heel pain. Fifteen years after diagnosis, approximately 44% of patients continue to have pain. First-line nonoperative therapy includes stretching of the plantar fascia and foot orthotics, followed by extracorporeal shockwave therapy, corticosteroid injection, or platelet-rich plasma injection. Midportion Achilles tendinopathy presents with pain approximately 2 to 6 cm proximal to the Achilles insertion on the heel. The primary nonoperative treatment involves eccentric strengthening exercises, but extracorporeal shockwave therapy may be used. Conclusions and Relevance Morton neuroma, plantar fasciitis, and Achilles tendinopathy are painful foot and ankle conditions. First-line therapies are activity restriction, orthotics, and corticosteroid injection for Morton neuroma; stretching and foot orthotics for plantar fasciitis; and eccentric strengthening exercises for Achilles tendinopathy.
NLRP3/IL‐1β induced myeloid‐derived suppressor cells recruitment and PD‐L1 upregulation promotes oxaliplatin resistance of hepatocellular carcinoma
Authors: Wenfeng Liu, Feng Zhang, Bing Quan, Fan Yao, Rongxin Chen, Zhenggang Ren, Xin Yin
Journal: MedComm (2023)

Abstract Oxaliplatin is commonly used as the first‐line chemotherapeutic agent for advanced hepatocellular carcinoma (HCC). Unfortunately, the acquired resistance, limits the effectiveness of oxaliplatin and the underlying mechanisms remain unknown. Therefore, we explored the role of NOD‐like receptor protein 3 (NLRP3)/IL‐1β in mediating oxaliplatin resistance in HCC. We observed that NLRP3/IL‐1β expression was much higher in oxaliplatin‐resistant HCC cells. To further understand its impact on drug resistance, we knocked down NLRP3 and observed that it sensitized HCC cells to the growth‐inhibitory effects of oxaliplatin and induced cell apoptosis. NLRP3/IL‐1β overexpressing tumor cells also attracted polymorphonuclear myeloid‐derived suppressor cells. Using mouse models, we demonstrated that NLRP3/IL‐1β inhibition by short hairpin RNA or MCC950 effectively overcame oxaliplatin resistance. Furthermore, NLRP3/IL‐1β inhibition resulted in reduced expression of PD‐L1. We also found that PD‐L1 antibody combined with NLRP3/IL‐1β blockade displayed significant antitumor effect in HCC. Overall, our study provides compelling evidence supporting the essential role of NLRP3/IL‐1β in conferring resistance to oxaliplatin and reshaping the immunosuppressive microenvironment in HCC. Targeting NLRP3/IL‐1β presents a potential therapeutic target for overcoming oxaliplatin resistance and reshaping microenvironment of HCC.
Urolithin A protects severe acute pancreatitis‐associated acute cardiac injury by regulating mitochondrial fatty acid oxidative metabolism in cardiomyocytes
Authors: Yue Yang, Qian Hu, Hongxin Kang, Juan Li, Xianlin Zhao, Lv Zhu, Wenfu Tang, Meihua Wan
Journal: MedComm (2023)

Severe acute pancreatitis (SAP) often develops into acute cardiac injury (ACI), contributing to the high mortality of SAP. Urolithin A (UA; 3,8-dihydroxy-6H-dibenzopyran-6-one), a natural polyphenolic compound, has been extensively studied and shown to possess significant anti-inflammatory effects. Nevertheless, the specific effects of UA in SAP-associated acute cardiac injury (SACI) have not been definitively elucidated. Here, we investigated the therapeutic role and mechanisms of UA in SACI using transcriptomics and untargeted metabolomics analyses in a mouse model of SACI and in vitro studies. SACI resulted in severely damaged pancreatic and cardiac tissues with myocardial mitochondrial dysfunction and mitochondrial metabolism disorders. UA significantly reduced the levels of lipase, amylase and inflammatory factors, attenuated pathological damage to pancreatic and cardiac tissues, and reduced myocardial cell apoptosis and oxidative stress in SACI. Moreover, UA increased mitochondrial membrane potential and adenosine triphosphate production and restored mitochondrial metabolism, but the efficacy of UA was weakened by the inhibition of CPT1. Therefore, UA can attenuate cardiac mitochondrial dysfunction and reduce myocardial apoptosis by restoring the balance of mitochondrial fatty acid oxidation metabolism. CPT1 may be a potential target. This study has substantial implications for advancing our understanding of the pathogenesis and drug development of SACI.
Analysis of off-tumour toxicities of T-cell-engaging bispecific antibodies via donor-matched intestinal organoids and tumouroids
Authors: Marius F. Harter, Timothy Recaldin, Regine Gerard, Blandine Avignon, Yannik Bollen, Cinzia Esposito, Karolina Guja-Jarosz, Kristina Kromer, Adrian Filip, Julien Aubert, Anneliese Schneider, Marina Bacac, Michael Bscheider, Nadine Stokar-Regenscheit, Salvatore Piscuoglio, Joep Beumer, Nikolche Gjorevski
Journal: Nature Biomedical Engineering (2023)

Abstract Predicting the toxicity of cancer immunotherapies preclinically is challenging because models of tumours and healthy organs do not typically fully recapitulate the expression of relevant human antigens. Here we show that patient-derived intestinal organoids and tumouroids supplemented with immune cells can be used to study the on-target off-tumour toxicities of T-cell-engaging bispecific antibodies (TCBs), and to capture clinical toxicities not predicted by conventional tissue-based models as well as inter-patient variabilities in TCB responses. We analysed the mechanisms of T-cell-mediated damage of neoplastic and donor-matched healthy epithelia at a single-cell resolution using multiplexed immunofluorescence. We found that TCBs that target the epithelial cell-adhesion molecule led to apoptosis in healthy organoids in accordance with clinical observations, and that apoptosis is associated with T-cell activation, cytokine release and intra-epithelial T-cell infiltration. Conversely, tumour organoids were more resistant to damage, probably owing to a reduced efficiency of T-cell infiltration within the epithelium. Patient-derived intestinal organoids can aid the study of immune–epithelial interactions as well as the preclinical and clinical development of cancer immunotherapies.
Abstract 393: Distribution and Elimination Kinetics of Midazolam and Metabolites in Patients With Post-Cardiac Arrest Care
Authors: Changshin Kang, Wonjoon Jeong, Jung Sunwoo, Jung Soo Park, Yeonho You, Jin Hong Min, Yong Nam In, So Young Jeon
Journal: Circulation (2023)

Background: Administration of midazolam (MDZ) can make neuroprognostication more complex, especially in determining the safe timing for avoiding inappropriately pessimistic prognostications. This study aims to investigate the distribution and elimination kinetics of MDZ and metabolites in patients with post-resuscitation care. Methods: This was a prospectively observational study between May 2020 and April 2022. Samples for analyzing plasma concentration of MDZ and seven metabolites were obtained immediately, at 4, 8, 12, and 24 h from discontinuation of MDZ infusion. Briefly, absolute and relative concentrations of MDZ and metabolites were determined by LC-MS/MS and LC-QTOF. The area under the plasma concentration-time curve from time 0 to last measurable time point (AUC last ) and estimated half-life ( t 1/2 ) were calculated according to pharmacokinetic rules. Results: Of the 13 enrolled patients, 8 (61.5%) awakened after discontinuation of MDZ administration. MDZ, 1-hydroxylmidazolam (1-OH-MDZ), 1-hydroxylmidazolam-glucuronide (1-OH-MDZ-Glu), and midazolam-glucuronide (MDZ-Glu) were identified as the major compounds, comprising approximately 96% of the total proportion. All compounds had individual mean t 1/2 (MDZ, 1-OH-MDZ, 1-OH-MDZ-Glc, and MDZ-Glc: 6.4, 7.6, 14.3, and 10.5 h, respectively). In the subgroup analysis for the awakened patients, the significant correlation between AUC last and awakening time measured from discontinuation of MDZ infusion was demonstrated in MDZ (r 2 = 0.66) and 1-OH-MDZ (r 2 = 0.55). Conclusions: Even in the normothermia state of the patients, t 1/2 of MDZ and metabolites was prolonged compared with that reported in healthy individuals. Among all compounds, MDZ and 1-OH-MDZ concentrations may be mainly active compounds related to the sedation effect. Hence, to prevent inappropriate WLST for patients with potential for recovery, we recommend clinicians consider the prolonged t 1/2 of the main active compounds.
Abstract 381: Simultaneous Use of VA-ECMO and Impella (ECPELLA) Improves Mid-Term Mortality in Patients With Refractory Cardiac Arrest or Cardiac Shock Who Required VA-ECMO
Authors: Taiji Inamori, Takashi Unoki, Tomoko Nakayama, Toshiki Fukuda, Takaaki Toyofuku, Junya Matsura, Yutaka Konami, Hiroto Suzuyama, Masayuki Inoue, Eiji Horio, Kazuhisa Kodama, Eiji Taguchi, Tadashi Sawamura, Tomohiro Sakamoto, Koichi Nakao, Jyunjiro Koyama
Journal: Circulation (2023)

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an effective therapy to rescue patients with refractory cardiogenic shock, including cardiac arrest. VA-ECMO increase damaged left ventricular (LV) afterload. The intra-aortic balloon pump (IABP) has been often used as the additional circulatory support for LV unloading. However, the effectiveness of combining VA-ECMO with IABP has not been definitively established. The Impella , a percutaneous micro-axial pump, can reduce damaged LV preload with circulatory support, which may have significant effect on clinical outcome by concomitant use of VA-ECMO and Impella (ECPELLA). Objective: This single-site cohort study aimed to assess the impact of ECPELLA compared to VA-ECMO with or without IABP in patients with refractory cardiogenic shock who received VA-ECMO treatment. Methods: We retrospectively reviewed 275 consecutive patients who received VA-ECMO from January 2012 through December 2022 in our institute. The patients were divided into two groups, ECEPLLA (n = 81) and VA-ECMO with or without IABP (n = 194). The primary outcome of this study was the 180-day all-cause mortality rate. Results: There were no significant differences in age, gender ratio, prevalence of coronary risk factors, serum lactate levels at the emergency room (ER), the rate of extracorporeal cardiopulmonary resuscitation (E-CPR), and instances of out-of-hospital cardiac arrest between the groups. The ECPELLA groups had a significantly higher rate of acute coronary syndrome and a lower prevalence of chronic kidney disease. Kaplan-Meier analysis demonstrated that the 180-day all-cause mortality was significantly lower in the ECPELLA group compared to the VA-ECMO group (p &lt; 0.001). Multivariate cox proportional hazard analysis revealed that age (hazard ratio [HR], 1.27 [10 years increase]; 95% confidence interval [CI], 1.13-1.42, p &lt; 0.001), E-CPR (HR 1.43; 95% CI 1.02-2.00, p = 0.04), lactate level at ER (HR 1.07; 95% CI 1.04-1.10, p &lt; 0.001), and ECPELLA (HR, 0.55, 95% CI, 0.40-0.76, p &lt; 0.001) were significantly associated with the 180-day all-cause mortality. Conclusion: ECPELLA was associated with improvement of mid-term mortality in patients with refractory cardiogenic shock who received VA-ECMO.
Abstract 392: TAT-PHLPP9c and TAT-PIF Administration During CPR Synergistically Improves Cardiac Arrest Survival
Authors: Jing Li, Xiangdong Zhu, Shaoxia Lin, Terry L Vanden
Journal: Circulation (2023)

Introduction: We have demonstrated that a novel fast-acting peptide TAT-PHLPP9c improves survival in both mouse and swine models of cardiac arrest. The protective effect is mediately by activation of Akt via inhibiting phosphatase PHLPP. We have designed another peptide TAT-PIF to activate Akt by promoting the active conformation of PDK1 via binding to PDK1 Interacting Fragment (PIF). Hypothesis: We hypothesize that TAT-PHLPP9c and TAT-PIF synergistically enhance Akt activation and improve cardiac arrest survival when administered intravenously during CPR. Methods: Cardiomyocytes were treated with TAT-PHLPP9c (10uM), or TAT-PIF (10uM) or in combination. Akt phosphorylation (p-Akt) at both Thr308 and Ser473 sites were assessed by Western blot. In C57BL/6 retired female mice (n=24), a 12-min asystolic cardiac arrest was induced with KCl followed by CPR and blinded randomized administration of the peptides or saline control. Four experimental groups were included: 1) saline, 2) TAT-PHLPP9c (7.5 mg/kg), 3) TAT-PIF (7.5 mg/kg), 4) TAT-PHLPP9c and TAT-PIF. Survival was evaluated at 4 hour post-ROSC. Results: In cardiomyocytes, compared to saline, both TAT-PHLPP9c and TAT-PIF independently increased AktSer473 phosphorylation, and the combined treatment of both peptides synergistically enhanced p-AktSer473. For AktThr308 site, TAT-PIF increased its phosphorylation while TAT-PHLPP9c induced a slight increase of its phosphorylation. Enhanced phosphorylation was also seen with the combined treatment. In mice, compared to saline control, both peptides improved 4-h survival when given alone, but the combined treatment improved 4-h survival synergistically over 30%. Conclusions: The cocktail of TAT-PHLPP9c and TAT-PIF may be a novel treatment regimen for improving outcome following cardiac arrest.