tbuckley/cabot-search huggingface dataset:
The Predictive Value of FDG PET/CT for Determining Progression-Free Survival in Advanced Stage III–IV BRAF-Mutated Melanoma Patients Treated With Targeted Therapy—What Can Be Learned From Progression?
Authors: Bernies van der Hiel, Else A. Aalbersberg, Alfons J.M. van den Eertwegh, Linda J. de Wit-van der Veen, Marcel P.M. Stokkel, Marta Lopez-Yurda, Ronald Boellaard, Ellen W. Kapiteijn, Geke A.P. Hospers, Maureen J.B. Aarts, Filip Y.F.L. de Vos, Marye J. Boers-Sonderen, Astrid A.M. van der Veldt, Jan Willem B. de Groot, John B.A.G Haanen
Journal: Clinical Nuclear Medicine (2023)

Purpose The aims of this study were to investigate whether (early) PERCIST response monitoring with 18 F-FDG PET/CT is predictive for progression-free survival (PFS) in unresectable stage III or IV melanoma patients treated with BRAF/MEK inhibitor (MEKi) and to define dissemination patterns at progression with a lesion-based evaluation in direct comparison to baseline to improve our understanding of 18 F-FDG PET/CT during BRAF/MEKi. Patients and Methods This prospective multicenter single-arm study included 70 patients with unresectable stage III/IV BRAF -mutated melanoma who underwent contrast-enhanced CT and 18 F-FDG PET/CT at baseline and 2 and 7 weeks during treatment with vemurafenib plus cobimetinib and at progression if possible. Tumor response assessment was done with RECIST1.1 and PERCIST. Follow-up PET/CT scans were visually compared with baseline to assess dissemination patterns. Results Using RECIST1.1, PFS was not significantly different between the response groups ( P = 0.26). At 2 weeks, PERCIST median PFS was 15.7 months for patients with complete metabolic response (CMR) versus 8.3 months for non-CMR ( P = 0.035). The hazards ratio (HR) for progression/death in non-CMR versus CMR was 1.99 (95% confidence interval [CI], 1.03–3.84; P = 0.040) and 1.77 (95% CI, 0.91–3.43; P = 0.0935) when adjusting for lactate dehydrogenase (LDH). At 7 weeks, median PFS for PERCIST CMR was 16.7 months versus 8.5 months for non-CMR ( P = 0.0003). The HR for progression/death in the non-CMR group was significantly increased (HR, 2.94; 95% CI, 1.60–5.40; P = 0.0005), even when adjusting for LDH (HR, 2.65; 95% CI, 1.43–4.91; P = 0.0020). At week 7, 18 F-FDG PET/CT was false-positive in all 4 (6%) patients with new FDG-avid lesions but CMR of known metastases. When 18 F-FDG PET/CT was performed at progressive disease, 18/22 (82%) patients had progression of known metastases with or without new 18 F-FDG–avid lesions. Conclusions This study shows that PERCIST response assessment at week 7 is predictive for PFS, regardless of LDH. At 2 weeks, patients with CMR have longer PFS than patients with non-CMR, but different PET parameters should be investigated to further evaluate the added value of early 18 F-FDG PET/CT. Disease progression on PET/CT is predominated by progression of known metastases, and new 18 F-FDG–avid lesions during BRAF/MEKi are not automatically a sign of recurrent disease.
Systematic review and meta-analysis of AI-based conversational agents for promoting mental health and well-being
Authors: Han Li, Renwen Zhang, Yi-Chieh Lee, Robert E. Kraut, David C. Mohr
Journal: npj Digital Medicine (2023)

Abstract Conversational artificial intelligence (AI), particularly AI-based conversational agents (CAs), is gaining traction in mental health care. Despite their growing usage, there is a scarcity of comprehensive evaluations of their impact on mental health and well-being. This systematic review and meta-analysis aims to fill this gap by synthesizing evidence on the effectiveness of AI-based CAs in improving mental health and factors influencing their effectiveness and user experience. Twelve databases were searched for experimental studies of AI-based CAs’ effects on mental illnesses and psychological well-being published before May 26, 2023. Out of 7834 records, 35 eligible studies were identified for systematic review, out of which 15 randomized controlled trials were included for meta-analysis. The meta-analysis revealed that AI-based CAs significantly reduce symptoms of depression (Hedge’s g 0.64 [95% CI 0.17–1.12]) and distress (Hedge’s g 0.7 [95% CI 0.18–1.22]). These effects were more pronounced in CAs that are multimodal, generative AI-based, integrated with mobile/instant messaging apps, and targeting clinical/subclinical and elderly populations. However, CA-based interventions showed no significant improvement in overall psychological well-being (Hedge’s g 0.32 [95% CI –0.13 to 0.78]). User experience with AI-based CAs was largely shaped by the quality of human-AI therapeutic relationships, content engagement, and effective communication. These findings underscore the potential of AI-based CAs in addressing mental health issues. Future research should investigate the underlying mechanisms of their effectiveness, assess long-term effects across various mental health outcomes, and evaluate the safe integration of large language models (LLMs) in mental health care.
Excess resource use and cost of drug-resistant infections for six key pathogens in Europe: a systematic review and Bayesian meta-analysis
Authors: Rhys Kingston, Venanzio Vella, Koen B. Pouwels, Johannes E. Schmidt, Radwa A. Abdelatif El-Abasiri, Eduardo Reyna-Villasmil, Nasreen Hassoun-Kheir, Stephan Harbarth, Jesús Rodríguez-Baño, Evelina Tacconelli, Fabiana Arieti, Beryl Primrose Gladstone, Marlieke E.A. de Kraker, Nichola R. Naylor, Julie V. Robotham, None Lorenzo Argante, Benedetta Barana, Eva Cappelli, Maria Elena De Rui, Liliana Galia, Jeroen Geurtsen, Mariana Guedes, Jorly Mejia, Andrea Palladino, Maria Diletta Pezzani, Alen Piljic
Journal: Clinical Microbiology and Infection (2023)

<h2>Abstract</h2><h3>Background</h3> Quantifying the resource use and cost of antimicrobial resistance establishes the magnitude of the problem and drives action. <h3>Objectives</h3> Assessment of resource use and cost associated with infections with six key drug-resistant pathogens in Europe. <h3>Methods</h3> A systematic review and Bayesian meta-analysis. <h3>Data sources</h3> MEDLINE (Ovid), Embase (Ovid), Econlit databases, and grey literature for the period 1 January 1990, to 21 June 2022. <h3>Study eligibility criteria</h3> Resource use and cost outcomes (including excess length of stay, overall costs, and other excess in or outpatient costs) were compared between patients with defined antibiotic-resistant infections caused by carbapenem-resistant (CR) <i>Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i>, CR or third-generation cephalosporin <i>Escherichia coli</i> (3GCREC) and <i>Klebsiella pneumoniae</i>, methicillin-resistant <i>Staphylococcus aureus</i>, and vancomycin-resistant <i>Enterococcus faecium</i>, and patients with drug-susceptible or no infection. <h3>Participants</h3> All patients diagnosed with drug-resistant bloodstream infections (BSIs). <h3>Interventions</h3> NA. <h3>Assessment of risk of bias</h3> An adapted version of the Joanna Briggs Institute assessment tool, incorporating case-control, cohort, and economic assessment frameworks. <h3>Methods of data synthesis</h3> Hierarchical Bayesian meta-analyses were used to assess pathogen-specific resource use estimates. <h3>Results</h3> Of 5969 screened publications, 37 were included in the review. Data were sparse and heterogeneous. Most studies estimated the attributable burden by, comparing resistant and susceptible pathogens (32/37). Four studies analysed the excess cost of hospitalization attributable to 3GCREC BSIs, ranging from -€ 2465.50 to € 6402.81. Eight studies presented adjusted excess length of hospital stay estimates for methicillin-resistant <i>S. aureus</i> and 3GCREC BSIs (4 each) allowing for Bayesian hierarchical analysis, estimating means of 1.26 (95% credible interval [CrI], −0.72 to 4.17) and 1.78 (95% CrI, −0.02 to 3.38) days, respectively. <h3>Conclusions</h3> Evidence on most cost and resource use outcomes and across most pathogen-resistance combinations was severely lacking. Given the importance of this evidence for rational policymaking, further research is urgently needed.
Senolytic-facilitated Reversal of End-Organ Dysfunction in a Murine Model of Obstructive Sleep Apnea
Authors: Mohammad Badran, Clementine Puech, Abdelnaby Khalyfa, Rene Cortese, Kylie Cataldo, Zhuanhong Qiao, David Gozal
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Obstructive sleep apnea (OSA) is a highly prevalent condition that is associated with accelerated biological aging and multiple end-organ morbidities. Current treatments, such as continuous positive airway pressure (CPAP), have shown limited cognitive, metabolic, and cardiovascular beneficial outcomes despite adherence. Thus, adjunct therapies aiming to reduce OSA burden, such as senolytics, could improve OSA outcomes.
Comparison of topical 5% permethrin vs. 25% benzyl benzoate in treating scabies — A double-blinded, randomized controlled study
Authors: Damian Meyersburg, Magdalena Hoellwerth, Matthias Brandlmaier, Allesandra Handisurya, Andreas Kaiser, Christine Prodinger, Johann W Bauer
Journal: British Journal of Dermatology (2023)

Scabies is a pruritic parasitic infestation of the skin. High-income countries have reported an increasing incidence over the last few years. Studies have indicated a reduction in the sensitivity of scabies mites to the standard treatment of choice, topical permethrin 5%.
Attenuation of allergen-specific immunotherapy for atopic dermatitis by ectopic colonization of Brevundimonas vesicularis in the intestine
Authors: Xiaochun Liu, Beilei Xu, Xiaoqiang Xu, Zhifeng Wang, Yang Luo, Yingxia Gao, Shiqi Ling, Ao Wang, Yuan Zhou, Xiaokai Wang, Sean Xiao Leng, Wei Li, Xu Yao
Journal: Cell Reports Medicine (2023)

Allergen-specific immunotherapy (AIT) has shown beneficial effects against atopic dermatitis (AD); however, the mechanisms and parameters underlying the efficacy of AIT remain unclear. Here, we report that the community structure and function of the oral and gut microbiota are changed in patients with AD undergoing AIT. Transplantation of fecal microbiota from patients who respond well to AIT improves AD-like dermatitis in mice. The abundance of Brevundimonas vesicularis in the gut of AD patients has been found to be positively correlated with disease severity and is decreased following AIT. Furthermore, we find that B. vesicularis from the oral cavity might ectopically colonize the gut of AD patients. In AD model mice, meanwhile, B. vesicularis promotes the skewing of the Treg/Th17 balance toward Th17 polarization and attenuates the efficacy of ovalbumin-specific immunotherapy. Our findings provide potential strategies for the optimization of AIT for AD via the modulation of the gut microbiota.
Use of Donanemab in Early Symptomatic Alzheimer Disease
Authors: Nunzio Pomara, Bruno Pietro Imbimbo
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
Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity
Authors: Sergio Quesada-Vázquez, Anna Castells-Nobau, Jèssica Latorre, Núria Oliveras-Cañellas, Irene Puig-Parnau, Noemi Tejera, Yaiza Tobajas, Julio Baudin, Falk Hildebrand, Naiara Beraza, Rémy Burcelin, Laura Martinez-Gili, Julien Chilloux, Marc-Emmanuel Dumas, Massimo Federici, Lesley Hoyles, Antoni Caimari, Josep M. del Bas, Xavier Escoté, José-Manuel Fernández-Real, Jordi Mayneris-Perxachs
Journal: Cell Reports Medicine (2023)

The gut microbiota contributes to the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Histidine is a key energy source for the microbiota, scavenging it from the host. Its role in NAFLD is poorly known. Plasma metabolomics, liver transcriptomics, and fecal metagenomics were performed in three human cohorts coupled with hepatocyte, rodent, and Drosophila models. Machine learning analyses identified plasma histidine as being strongly inversely associated with steatosis and linked to a hepatic transcriptomic signature involved in insulin signaling, inflammation, and trace amine-associated receptor 1. Circulating histidine was inversely associated with Proteobacteria and positively with bacteria lacking the histidine utilization (Hut) system. Histidine supplementation improved NAFLD in different animal models (diet-induced NAFLD in mouse and flies, ob/ob mouse, and ovariectomized rats) and reduced de novo lipogenesis. Fecal microbiota transplantation (FMT) from low-histidine donors and mono-colonization of germ-free flies with Enterobacter cloacae increased triglyceride accumulation and reduced histidine content. The interplay among microbiota, histidine catabolism, and NAFLD opens therapeutic opportunities.
Screening for Social Determinants of Health During Primary Care and Emergency Department Encounters
Authors: Stacie Vilendrer, Samuel C. Thomas, Tom Belnap, Kim Burnisholz, Nancy Song, Raj Srivastava, Sara Singer
Journal: JAMA Network Open (2023)

This cross-sectional study explores characteristics of patients who are screened and who screen positive for social determinants of health (SDOH) needs in different clinical settings within a large integrated health system.
Pan-viral serology uncovers distinct virome patterns as risk predictors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma
Authors: Whitney L Do, Limin Wang, Marshonna Forgues, Jinping Liu, Siritida Rabibhadana, Benjarath Pupacdi, Yongmei Zhao, Heelah Gholian, Vajarabhongsa Bhudhisawasdi, Chawalit Pairojkul, Wattana Sukeepaisarnjaroen, Ake Pugkhem, Vor Luvira, Nirush Lertprasertsuke, Anon Chotirosniramit, Chirayu U Auewarakul, Teerapat Ungtrakul, Thaniya Sricharunrat, Suleeporn Sangrajrang, Kannika Phornphutkul, Anuradha Budhu, Curtis C Harris, Chulabhorn Mahidol, Mathuros Ruchirawat, Xin Wei Wang
Journal: Cell Reports Medicine (2023)

Highlights•Pan-viral serological profiling can distinguish liver cancer from healthy individuals•Exposure to hepatitis and non-hepatitis viruses associated with liver cancer•HCC viral score can determine clinical risk and mortality in at-risk populationSummaryThis study evaluates the pan-serological profiles of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) compared to several diseased and non-diseased control populations to identify risk factors and biomarkers of liver cancer. We used phage immunoprecipitation sequencing, an anti-viral antibody screening method using a synthetic-phage-displayed human virome epitope library, to screen patient serum samples for exposure to over 1,280 strains of pathogenic and non-pathogenic viruses. Using machine learning methods to develop an HCC or iCCA viral score, we discovered that both viral scores were positively associated with several liver function markers in two separate at-risk populations independent of viral hepatitis status. The HCC score predicted all-cause mortality over 8 years in patients with chronic liver disease at risk of HCC, while the viral hepatitis status was not predictive of survival. These results suggest that non-hepatitis viral infections may contribute to HCC and iCCA development and could be biomarkers in at-risk populations.Graphical abstract
Single-cell RNA-sequencing of PBMCs from SAVI patients reveals disease-associated monocytes with elevated integrated stress response
Authors: Camille de Cevins, Laure Delage, Maxime Batignes, Quentin Riller, Marine Luka, Anne Remaury, Boris Sorin, Tinhinane Fali, Cécile Masson, Bénédicte Hoareau, Catherine Meunier, Mélanie Parisot, Mohammed Zarhrate, Brieuc P. Pérot, Víctor García-Paredes, Francesco Carbone, Lou Galliot, Béatrice Nal, Philippe Pierre, Luc Canard, Charlotte Boussard, Etienne Crickx, Jean-Claude Guillemot, Brigitte Bader-Meunier, Alexandre Bélot, Pierre Quartier, Marie-Louise Frémond, Bénédicte Neven, Galina Boldina, Franck Augé, Fischer Alain, Michel Didier, Frédéric Rieux-Laucat, Mickaël M. Ménager
Journal: Cell Reports Medicine (2023)

Gain-of-function mutations in stimulator of interferon gene 1 (STING1) result in STING-associated vasculopathy with onset in infancy (SAVI), a severe autoinflammatory disease. Although elevated type I interferon (IFN) production is thought to be the leading cause of the symptoms observed in patients, STING can induce a set of pathways, which have roles in the onset and severity of SAVI and remain to be elucidated. To this end, we performed a multi-omics comparative analysis of peripheral blood mononuclear cells (PBMCs) and plasma from SAVI patients and healthy controls, combined with a dataset of healthy PBMCs treated with IFN-β. Our data reveal a subset of disease-associated monocyte, expressing elevated CCL3, CCL4, and IL-6, as well as a strong integrated stress response, which we suggest is the result of direct PERK activation by STING. Cell-to-cell communication inference indicates that these monocytes lead to T cell early activation, resulting in their senescence and apoptosis. Last, we propose a transcriptomic signature of STING activation, independent of type I IFN response.
Strategies for mitigating adverse events related to selective RET inhibitors in patients with RET-altered cancers
Authors: Mirella Nardo, Mohamed A. Gouda, Blessie E. Nelson, Carmelia M.N. Barreto, J. Hoyt Slade, Anna Poullard, Mark Zafereo, Mimi I. Hu, Maria E. Cabanillas, Vivek Subbiah
Journal: Cell Reports Medicine (2023)

The US Food and Drug Administration (FDA) approval of the selective RET inhibitors selpercatinib and pralsetinib has led to a paradigm change in the treatment of RET-altered lung and thyroid cancers through a higher response rate and a more tolerable safety and toxicity profile than multi-kinase inhibitors. Recently, selpercatinib has received a tissue-agnostic FDA approval for all RET-fusion-positive cancers, and pralsetinib has shown pan-cancer activity as well. Given the anticipated increase in the use of both drugs across multiple tumor types, it is crucial to recognize the possible side effects and approaches for their optimal management in order to maximize the clinical benefit for treated patients. In this review, we underscore potential toxicities associated with selective RET inhibitors and discuss strategies to mitigate them.
Entrectinib inhibits NLRP3 inflammasome and inflammatory diseases by directly targeting NEK7
Authors: Xiangyu Jin, Didi Liu, Xinru Zhou, Xianyu Luo, Qian Huang, Yi Huang
Journal: Cell Reports Medicine (2023)

Excessive inflammation caused by abnormal activation of the NLRP3 inflammasome contributes to the pathogenesis of multiple human diseases, but clinical drugs targeting the NLRP3 inflammasome are still not available. In this study, we identify entrectinib (ENB), a US Food and Drug Administration (FDA)-approved anti-cancer agent, as a target inhibitor of the NLRP3 inflammasome to treat related diseases. ENB specifically blocks NLRP3 without affecting activation of other inflammasomes. Furthermore, we demonstrate that ENB directly binds to arginine 121 (R121) of NEK7 and blocks the interaction between NEK7 and NLRP3, thereby inhibiting inflammasome assembly and activation. In vivo studies show that ENB has a significant ameliorative effect on mouse models of NLRP3 inflammasome-related diseases, including lipopolysaccharide (LPS)-induced systemic inflammation, monosodium urate (MSU)-induced peritonitis, and high-fat diet (HFD)-induced type 2 diabetes (T2D). These data show that ENB is a targeted inhibitor of NEK7 with strong anti-NLRP3 inflammasome activity, making it a potential candidate drug for the treatment of inflammasome-related diseases.
Therapeutic Hope on the Surface of Ewing Sarcoma
Authors: Kelly M. Bailey
Journal: Clinical Cancer Research (2023)

A detailed analysis of the Ewing sarcoma surfacesome has arrived. Robust expression of surface CDH11 and ENPP1 was identified. This "comprehensive catalog" of the Ewing surfacesome serves as a fresh roadmap to development of new therapeutic approaches, including immunotherapies and multi-modality therapeutic combinations, to target aggressive Ewing tumor subpopulations. See related article by Mooney et al., p. 1022.
Challenges to Door-In-Door-Out Time Thresholds for Patients With Stroke
Authors: Nin-Chieh Hsu, Hsin-Lu Yang, Chia-Hao Hsu
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
Prenatal Intravenous Magnesium and Neurodevelopmental Outcomes in Offspring—Reply
Authors: Caroline A. Crowther, Jane E. Harding
Journal: JAMA (2023)

In Reply We appreciate the comments by Dr Marret and colleagues about our recently published MAGENTA trial1 that evaluated magnesium sulfate compared with placebo administered to pregnant individuals at risk of imminent preterm birth between 30 and 34 weeks’ gestation.
The manosphere and men’s wellbeing: How healthcare can help young men find alternatives to toxic online spaces
Authors: Brandon Sparks, Chloe Papandreou
Journal: BMJ (2023)

Online forums are exploiting the insecurity and vulnerability of young men. Healthcare can improve their mental and social wellbeing by providing healthy, alternative support systems and challenging harmful ideologies, write Brandon Sparks and Chloe Papandreou