tbuckley/cabot-search huggingface dataset:
Implementation of type 1 diabetes genetic risk screening in children in diverse communities: the Virginia PrIMeD project
Authors: Kristin A. Guertin, David R. Repaske, Julia F. Taylor, Eli S. Williams, Suna Onengut-Gumuscu, Wei-Min Chen, Sarah R. Boggs, Liping Yu, Luke Allen, Lacey Botteon, Louis Daniel, Katherine G. Keating, Mika K. Labergerie, Tyler S. Lienhart, Jorge A. Gonzalez-Mejia, Matt J. Starnowski, Stephen S. Rich
Journal: Genome Medicine (2024)

Abstract Background Population screening for risk of type 1 diabetes (T1D) has been proposed to identify those with islet autoimmunity (presence of islet autoantibodies). As islet autoantibodies can be transient, screening with a genetic risk score has been proposed as an entry into autoantibody testing. Methods Children were recruited from eight general pediatric and specialty clinics across Virginia with diverse community settings. Recruiters in each clinic obtained informed consent/assent, a medical history, and a saliva sample for DNA extraction in children with and without a history of T1D. A custom genotyping panel was used to define T1D genetic risk based upon associated SNPs in European- and African-genetic ancestry. Subjects at “high genetic risk” were offered a separate blood collection for screening four islet autoantibodies. A follow-up contact (email, mail, and telephone) in one half of the participants determined interest and occurrence of subsequent T1D. Results A total of 3818 children aged 2–16 years were recruited, with 14.2% ( n = 542) having a “high genetic risk.” Of children with “high genetic risk” and without pre-existing T1D ( n = 494), 7.0% (34/494) consented for autoantibody screening; 82.4% (28/34) who consented also completed the blood collection, and 7.1% (2/28) of them tested positive for multiple autoantibodies. Among children with pre-existing T1D ( n = 91), 52% ( n = 48) had a “high genetic risk.” In the sample of children with existing T1D, there was no relationship between genetic risk and age at T1D onset. A major factor in obtaining islet autoantibody testing was concern over SARS-CoV-2 exposure. Conclusions Minimally invasive saliva sampling implemented using a genetic risk score can identify children at genetic risk of T1D. Consent for autoantibody screening, however, was limited largely due to the SARS-CoV-2 pandemic and need for blood collection.
Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis
Authors: Yuliana Astuti, Meirion Raymant, Valeria Quaranta, Kim Clarke, Maidinaimu Abudula, Olivia Smith, Gaia Bellomo, Vatshala Chandran-Gorner, Craig Nourse, Christopher Halloran, Paula Ghaneh, Daniel Palmer, Robert P. Jones, Fiona Campbell, Jeffrey W. Pollard, Jennifer P. Morton, Ainhoa Mielgo, Michael C. Schmid
Journal: Nature Cancer (2024)

Abstract Pancreatic ductal adenocarcinoma is a highly metastatic disease and macrophages support liver metastases. Efferocytosis, or engulfment of apoptotic cells by macrophages, is an essential process in tissue homeostasis and wound healing, but its role in metastasis is less well understood. Here, we found that the colonization of the hepatic metastatic site is accompanied by low-grade tissue injury and that efferocytosis-mediated clearance of parenchymal dead cells promotes macrophage reprogramming and liver metastasis. Mechanistically, progranulin expression in macrophages is necessary for efficient efferocytosis by controlling lysosomal acidification via cystic fibrosis transmembrane conductance regulator and the degradation of lysosomal cargo, resulting in LXRα/RXRα-mediated macrophage conversion and upregulation of arginase 1. Pharmacological blockade of efferocytosis or macrophage-specific genetic depletion of progranulin impairs macrophage conversion, improves CD8 + T cell functions, and reduces liver metastasis. Our findings reveal how hard-wired functions of macrophages in tissue repair contribute to liver metastasis and identify potential targets for prevention of pancreatic ductal adenocarcinoma liver metastasis.
IL-23 stabilizes an effector Treg cell program in the tumor microenvironment
Authors: Tobias Wertheimer, Pascale Zwicky, Lukas Rindlisbacher, Colin Sparano, Marijne Vermeer, Bruno Marcel Silva de Melo, Claudia Haftmann, Tamina Rückert, Aakriti Sethi, Stefanie Schärli, Anna Huber, Florian Ingelfinger, Caroline Xu, Daehong Kim, Philipp Häne, André Fonseca da Silva, Andreas Muschaweckh, Nicolas Nunez, Sinduya Krishnarajah, Natalie Köhler, Robert Zeiser, Mohamed Oukka, Thomas Korn, Sonia Tugues, Burkhard Becher
Journal: Nature Immunology (2024)

Abstract Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (T reg ) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23r in T reg cells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector T reg cells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity.
Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency
Authors: Maddalena Migliavacca, Federica Barzaghi, Claudia Fossati, Paola M. V. Rancoita, Michela Gabaldo, Francesca Dionisio, Stefania Giannelli, Federica Andrea Salerio, Francesca Ferrua, Francesca Tucci, Valeria Calbi, Vera Gallo, Salvatore Recupero, Giulia Consiglieri, Roberta Pajno, Maria Sambuco, Alessio Priolo, Chiara Ferri, Vittoria Garella, Ilaria Monti, Paolo Silvani, Silvia Darin, Miriam Casiraghi, Ambra Corti, Stefano Zancan, Margherita Levi, Daniela Cesana, Filippo Carlucci, Anna Pituch-Noworolska, Dalia AbdElaziz, Ulrich Baumann, Andrea Finocchi, Caterina Cancrini, Saverio Ladogana, Andrea Meinhardt, Isabelle Meyts, Davide Montin, Lucia Dora Notarangelo, Fulvio Porta, Marlène Pasquet, Carsten Speckmann, Polina Stepensky, Alberto Tommasini, Marco Rabusin, Zeynep Karakas, Miguel Galicchio, Lucia Leonardi, Marzia Duse, Sukru Nail Guner, Clelia Di Serio, Fabio Ciceri, Maria Ester Bernardo, Alessandro Aiuti, Maria Pia Cicalese
Journal: Nature Medicine (2024)
Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity
Authors: Xuehui Long, Sulin Zhang, Yuliang Wang, Jingjing Chen, Yanlai Lu, Hui Hou, Bichun Lin, Xutong Li, Chang Shen, Ruirui Yang, Huamin Zhu, Rongrong Cui, Duanhua Cao, Geng Chen, Dan Wang, Yun Chen, Sulan Zhai, Zhiqin Zeng, Shusheng Wu, Mengting Lou, Junhong Chen, Jian Zou, Mingyue Zheng, Jun Qin, Xiaoming Wang
Journal: Nature Immunology (2024)
A research agenda for mental health in sub-Saharan Africa
Authors: Tholene Sodi, Melanie Abas, Mohammed Abdulaziz, Action Amos, Rochelle A. Burgess, Charlotte Hanlon, Adelard Kakunze, Lily Kpobi, Crick Lund, Kibachio J. Mwangi, Victoria Mutiso, Charlene Sunkel, Peter Yaro, Louise Arseneault
Journal: Nature Medicine (2024)
Validation of biomarkers of aging
Authors: Mahdi Moqri, Chiara Herzog, Jesse R. Poganik, Kejun Ying, Jamie N. Justice, Daniel W. Belsky, Albert T. Higgins-Chen, Brian H. Chen, Alan A. Cohen, Georg Fuellen, Sara Hägg, Riccardo E. Marioni, Martin Widschwendter, Kristen Fortney, Peter O. Fedichev, Alex Zhavoronkov, Nir Barzilai, Jessica Lasky-Su, Douglas P. Kiel, Brian K. Kennedy, Steven Cummings, P. Eline Slagboom, Eric Verdin, Andrea B. Maier, Vittorio Sebastiano, Michael P. Snyder, Vadim N. Gladyshev, Steve Horvath, Luigi Ferrucci
Journal: Nature Medicine (2024)
Wearable Microneedle Patch for Colorimetric Detection of Multiple Signature Biomarkers in vivo Toward Diabetic Diagnosis
Authors: Ziting Bao, Sheng Lu, Duo Zhang, Guanyu Wang, Xiaolin Cui, Guozhen Liu
Journal: Advanced Healthcare Materials (2024)

Abstract Type 2 diabetes is rapidly emerging as a global public health problem. While blood glucose monitoring has been the primary method of managing diabetes for decades, the increasing global prevalence of the disease suggests that there might be a need to identify additional biomarkers for a more precise early diagnosis. Herein, a microneedle patch based wearable sensor is developed for the purpose of diabetic diagnosis. Utilizing methacrylic acid modified gelatin and polyvinyl alcohol in the fabrication of microneedles has improved their mechanical properties for skin penetration and increased swelling capacity for interstitial fluid extraction, thanks to the double crosslinking mechanism. The fabricated microneedles are further integrated with test paper functionalized with enzyme and dye molecules to detect multiple signature biomarkers of diabetes in vivo through a colorimetric reaction. Such a wearable microneedle patch holds significant promise for the real‐time monitoring of various biomarkers related to chronic diseases and aging.
ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner
Authors: Chuanpeng Zhang, Ziyi Yu, Susu Yang, Yitao Liu, Jiangni Song, Juan Mao, Minghui Li, Yi Zhao
Journal: Molecular Cancer (2024)

Abstract Background Circular RNAs are highly stable regulatory RNAs that have been increasingly associated with tumorigenesis and progression. However, the role of many circRNAs in triple-negative breast cancer (TNBC) and the related mechanisms have not been elucidated. Methods In this study, we screened circRNAs with significant expression differences in the RNA sequencing datasets of TNBC and normal breast tissues and then detected the expression level of circRPPH1 by qRT‒PCR. The biological role of circRPPH1 in TNBC was then verified by in vivo and in vitro experiments. Mechanistically, we verified the regulatory effects between circRPPH1 and ZNF460 and between circRPPH1 and miR-326 by chromatin immunoprecipitation (ChIP), fluorescence in situ hybridization assay, dual luciferase reporter gene assay and RNA pull-down assay. In addition, to determine the expression of associated proteins, we performed immunohistochemistry, immunofluorescence, and western blotting. Results The upregulation of circRPPH1 in TNBC was positively linked with a poor prognosis. Additionally, both in vivo and in vitro, circRPPH1 promoted the biologically malignant behavior of TNBC cells. Additionally, circRPPH1 may function as a molecular sponge for miR-326 to control integrin subunit alpha 5 (ITGA5) expression and activate the focal adhesion kinase (FAK)/PI3K/AKT pathway. Conclusion Our research showed that ZNF460 could promote circRPPH1 expression and that the circRPPH1/miR-326/ITGA5 axis could activate the FAK/PI3K/AKT pathway to promote the progression of TNBC. Therefore, circRPPH1 can be used as a therapeutic or diagnostic target for TNBC.
Effect of aggressive vs conservative screening and confirmatory test on time to extubation among patients at low or intermediate risk: a randomized clinical trial
Authors: Gonzalo Hernández Martínez, Patricia Rodriguez, Jesus Soto, Oriol Caritg, Andrea Castellví-Font, Borja Mariblanca, Antonio Maria García, Laura Colinas, Jose Manuel Añon, Francisco Jose Parrilla-Gomez, Jose Alberto Silva-Obregón, Joan Ramon Masclans, Alicia Propin, Alicia Cuadra, Mario Guillermo Dalorzo, Gemma Rialp, Fernando Suarez-Sipmann, Oriol Roca
Journal: Intensive Care Medicine (2024)
Ion channel TRPV2 is critical in enhancing B cell activation and function
Authors: Cuifeng Li, Meng Zhao, Xiaohang Liu, Yuxin Li, Bihua Xu, Lina Zhou, Xiaolin Sun, Wenbo Sun, Na Kang, Zhenglin Ji, Tong Li, Haoran An, Fei Wang, Chuan Wu, Jing-Ying Ye, Jing-Ren Zhang, Qingwen Wang, Xiaodong Zhao, Zhanguo Li, Wanli Liu
Journal: The Journal of Experimental Medicine (2024)

The function of transient receptor potential vanilloid (TRPV) cation channels governing B cell activation remains to be explored. We present evidence that TRPV2 is highly expressed in B cells and plays a crucial role in the formation of the B cell immunological synapse and B cell activation. Physiologically, TRPV2 expression level is positively correlated to influenza-specific antibody production and is low in newborns and seniors. Pathologically, a positive correlation is established between TRPV2 expression and the clinical manifestations of systemic lupus erythematosus (SLE) in adult and child SLE patients. Correspondingly, mice with deficient TRPV2 in B cells display impaired antibody responses following immunization. Mechanistically, the pore and N-terminal domains of TRPV2 are crucial for gating cation permeation and executing mechanosensation in B cells upon antigen stimulation. These processes synergistically contribute to membrane potential depolarization and cytoskeleton remodeling within the B cell immunological synapse, fostering efficient B cell activation. Thus, TRPV2 is critical in augmenting B cell activation and function.
Cognitive Symptoms of Post–COVID-19 Condition and Daily Functioning
Authors: Abhishek Jaywant, Faith M. Gunning, Lauren E. Oberlin, Mauricio Santillana, Katherine Ognyanova, James N. Druckman, Matthew A. Baum, David Lazer, Roy H. Perlis
Journal: JAMA Network Open (2024)

Importance The frequent occurrence of cognitive symptoms in post–COVID-19 condition has been described, but the nature of these symptoms and their demographic and functional factors are not well characterized in generalizable populations. Objective To investigate the prevalence of self-reported cognitive symptoms in post–COVID-19 condition, in comparison with individuals with prior acute SARS-CoV-2 infection who did not develop post–COVID-19 condition, and their association with other individual features, including depressive symptoms and functional status. Design, Setting, and Participants Two waves of a 50-state nonprobability population-based internet survey conducted between December 22, 2022, and May 5, 2023. Participants included survey respondents aged 18 years and older. Exposure Post–COVID-19 condition, defined as self-report of symptoms attributed to COVID-19 beyond 2 months after the initial month of illness. Main Outcomes and Measures Seven items from the Neuro-QoL cognition battery assessing the frequency of cognitive symptoms in the past week and patient Health Questionnaire-9. Results The 14 767 individuals reporting test-confirmed COVID-19 illness at least 2 months before the survey had a mean (SD) age of 44.6 (16.3) years; 568 (3.8%) were Asian, 1484 (10.0%) were Black, 1408 (9.5%) were Hispanic, and 10 811 (73.2%) were White. A total of 10 037 respondents (68.0%) were women and 4730 (32.0%) were men. Of the 1683 individuals reporting post–COVID-19 condition, 955 (56.7%) reported at least 1 cognitive symptom experienced daily, compared with 3552 of 13 084 (27.1%) of those who did not report post–COVID-19 condition. More daily cognitive symptoms were associated with a greater likelihood of reporting at least moderate interference with functioning (unadjusted odds ratio [OR], 1.31 [95% CI, 1.25-1.36]; adjusted [AOR], 1.30 [95% CI, 1.25-1.36]), lesser likelihood of full-time employment (unadjusted OR, 0.95 [95% CI, 0.91-0.99]; AOR, 0.92 [95% CI, 0.88-0.96]) and greater severity of depressive symptoms (unadjusted coefficient, 1.40 [95% CI, 1.29-1.51]; adjusted coefficient 1.27 [95% CI, 1.17-1.38). After including depressive symptoms in regression models, associations were also found between cognitive symptoms and at least moderate interference with everyday functioning (AOR, 1.27 [95% CI, 1.21-1.33]) and between cognitive symptoms and lower odds of full-time employment (AOR, 0.92 [95% CI, 0.88-0.97]). Conclusions and Relevance The findings of this survey study of US adults suggest that cognitive symptoms are common among individuals with post–COVID-19 condition and associated with greater self-reported functional impairment, lesser likelihood of full-time employment, and greater depressive symptom severity. Screening for and addressing cognitive symptoms is an important component of the public health response to post–COVID-19 condition.
Academic Surgery in the Era of Large Language Models
Authors: Timothy A. Rengers, Cornelius A. Thiels, Hojjat Salehinejad
Journal: JAMA Surgery (2024)

Importance This review aims to assess the benefits and risks of implementing large language model (LLM) solutions in an academic surgical setting. Observations The integration of LLMs and artificial intelligence (AI) into surgical practice has generated international attention with the emergence of OpenAI’s ChatGPT and Google’s Bard. From an administrative standpoint, LLMs have the potential to revolutionize academic practices by reducing administrative burdens and improving efficiency. LLMs have the potential to facilitate surgical research by increasing writing efficiency, building predictive models, and aiding in large dataset analysis. From a clinical standpoint, LLMs can enhance efficiency by triaging patient concerns and generating automated responses. However, challenges exist, such as the need for improved LLM generalization performance, validating content, and addressing ethical concerns. In addition, patient privacy, potential bias in training, and legal responsibility are important considerations that require attention. Research and precautionary measures are necessary to ensure safe and unbiased use of LLMs in surgery. Conclusions and Relevance Although limitations exist, LLMs hold promise for enhancing surgical efficiency while still prioritizing patient care. The authors recommend that the academic surgical community further investigate the potential applications of LLMs while being cautious about potential harms.
Primary Care Physicians Are Key to Improving Dementia Care and Access
Authors: Emily Harris
Journal: JAMA (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 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
ENIGMA Brain Morphometry in CHR-P—Risk Enrichment and Antipsychotics
Authors: Andrea Raballo, Michele Poletti, Antonio Preti
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Addressing the urgency: Advocating for the inclusion of meningococcal vaccine in Pakistan’s immunization program
Authors: Hafsa Ghouri, Ashna Habib, Tooba Ali, Zainab Nazir, Md Ariful Haque
Journal: International Journal of Surgery (2024)

Ghouri, Hafsa MBBS; Habib, Ashna MBBS; Ali, Tooba MBBS; Nazir, Zainab MBBS; Haque, Md Ariful MBBS, MD, MPH Author Information
Deep Vein Thrombosis and Healing Outcomes in Patients With Pyoderma Gangrenosum
Authors: Hannah Zhao, Sidharth K. Sengupta, Jonathan M. Sisley, Olivia Haddadin, Hailey Pfeifer, Alex G. Ortega-Loayza
Journal: JAMA Dermatology (2024)

This single-center prospective case-control study assessed the association between deep vein thrombosis and healing outcomes in patients with pyoderma gangrenosum.
Efficacy and Durability of Intravenous Ertapenem Therapy for Recalcitrant Hidradenitis Suppurativa
Authors: Avigdor Nosrati, Peter Y. Ch’en, McCall E. Torpey, Neda Shokrian, Gretchen Ball, Gabrielle Benesh, Tyler M. Andriano, Tian Ran Zhu, Haley D. Heibel, H. Dean Hosgood, Kristina L. Campton, Steven R. Cohen
Journal: JAMA Dermatology (2024)

Hidradenitis suppurativa (HS) is a debilitating follicular skin disorder in which bacterial colonization is typical. Oral antibiotic efficacy can be unreliable; however, selective intravenous antibiotics, specifically ertapenem, may provide favorable clinical outcomes.
From past to present to future: Terlipressin and hepatorenal syndrome-acute kidney injury
Authors: Andrew S. Allegretti, Kavish R. Patidar, Ann T. Ma, Giuseppe Cullaro
Journal: Hepatology (2024)

Hepatorenal syndrome (HRS) is a rare and highly morbid form of kidney injury unique to patients with decompensated cirrhosis. HRS is a physiologic consequence of portal hypertension, leading to a functional kidney injury that can be reversed by restoring effective circulating volume and renal perfusion. While liver transplantation is the only definitive “cure” for HRS, medical management with vasoconstrictors and i.v. albumin is a cornerstone of supportive care. Terlipressin, a V1a receptor agonist that acts on the splanchnic circulation, has been used for many years outside the United States for the treatment of HRS. However, its recent Food and Drug Administration approval has generated new interest in this population, as a new base of prescribers now work to incorporate the drug into clinical practice. In this article, we review HRS pathophysiology and diagnostic criteria, the clinical use of terlipressin and alternative therapies, and identify areas of future research in the space of HRS and kidney injury in cirrhosis.