tbuckley/cabot-search huggingface dataset:
Geriatric Medicine as a Profession—Reply
Authors: Jerry H. Gurwitz
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
Endothelium-specific SIRT7 targeting ameliorates pulmonary hypertension through Krüpple-like factor 4 deacetylation
Authors: Jin Zhang, Chenzhong Xu, Xiaolong Tang, Shimin Sun, Siqi Liu, Langmei Yang, Yuqin Chen, Qifeng Yang, Tong-You Wade Wei, Xiaojing Wu, Jian Wang, Chen Wang, Xiaosong Yan, Lei Yang, Yanqin Niu, Deming Gou, John Y J Shyy, Baohua Liu
Journal: Cardiovascular Research (2024)

Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by a high mortality rate. Pulmonary arterial endothelium cells (PAECs) serve as a primary sensor of various environmental cues, such as shear stress and hypoxia, but PAEC dysfunction may trigger vascular remodelling during the onset of PH. This study aimed to illustrate the role of Sirtuin 7 (SIRT7) in endothelial dysfunction during PH and explore the potential therapeutic strategy for PH. SIRT7 levels were measured in human and murine experimental PH samples. Bioinformatic analysis, immunoprecipitation, and deacetylation assay were used to identify the association between SIRT7 and Krüpple-like factor 4 (KLF4), a key transcription factor essential for endothelial cell (EC) homeostasis. Sugen5416 + hypoxia (SuHx)-induced PH mouse models and cell cultures were used for the study of the therapeutic effect of SIRT7 for PH. SIRT7 level was significantly reduced in lung tissues and PAECs from PH patients and the SuHx-induced PH mouse model as compared with healthy controls. Pulmonary endothelium-specific depletion of Sirt7 increased right ventricular systolic pressure and exacerbated right ventricular hypertrophy in the SuHx-induced PH model. At the molecular level, we identified KLF4 as a downstream target of SIRT7, which deacetylated KLF4 at K228 and inhibited the ubiquitination-proteasome degradation. Thus, the SIRT7/KLF4 axis maintained PAEC homeostasis by regulating proliferation, migration, and tube formation. PAEC dysfunction was reversed by adeno-associated virus type 1 vector-mediated endothelial overexpression of Sirt7 or supplementation with nicotinamide adenine dinucleotide (NAD)+ intermediate nicotinamide riboside which activated Sirt7; both approaches successfully reversed PH phenotypes. The SIRT7/KLF4 axis ensures PAEC homeostasis, and pulmonary endothelium-specific SIRT7 targeting might constitute a PH therapeutic strategy.
Publisher Correction: A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC
Authors: Laurel B. Darragh, Michael M. Knitz, Junxiao Hu, Eric T. Clambey, Jennifer Backus, Andrew Dumit, Von Samedi, Andrew Bubak, Casey Greene, Timothy Waxweiler, Sanjana Mehrotra, Shilpa Bhatia, Jacob Gadwa, Thomas Bickett, Miles Piper, Kareem Fakhoury, Arthur Liu, Joshua Petit, Daniel Bowles, Ashesh Thaker, Kimberly Atiyeh, Julie Goddard, Robert Hoyer, Adrie Van Bokhoven, Kimberly Jordan, Antonio Jimeno, Angelo D’Alessandro, David Raben, Jessica D. McDermott, Sana D. Karam
Journal: Nature Cancer (2024)
Geriatric Medicine as a Profession
Authors: Venu Gopal Jonnalagadda
Journal: JAMA (2024)

To the Editor I would like to make few comments about a recent Viewpoint1 on geriatric medicine. First, according to the World Health Organization, the proportion of older adults will nearly double from 12% to 22%, and 80% of older people will be living in low- and middle-income countries.2
Activation of basophils in children with food allergies by blood from donors ingesting the corresponding food
Authors: Ryu Yanagisawa, Yumi Koike, Yoko Usami, Ayako Kanai, Mai Tokunaga, Minoru Tozuka, Yasunori Ito
Journal: Allergy (2024)

Research data are not shared. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Miscalculation of Incidence Rates
Journal: JAMA Network Open (2024)

Eva Havers-Borgersen, MD; Jawad H. Butt, MD; Marianne Johansen, MD, PhD; Olav Bjørn Petersen, MD, PhD; Charlotte Kvist Ekelund, MD, PhD; Line Rode, MD, PhD; Jonas Bjerring Olesen, MD, PhD; Lars Køber, MD, DMSc; Emil L. Fosbøl, MD, PhD
Geriatric Medicine as a Profession
Authors: Robert S. Crupi, Melissa Patterson, Cynthia X. Pan
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
Imaging of Pheochromocytomas and Paragangliomas
Authors: Henri J L M Timmers, David Taïeb, Karel Pacak, Jacques W M Lenders
Journal: Endocrine Reviews (2024)

Abstract Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations translate into different clusters with distinct tumor locations, biochemical/metabolomic features, tumor cell characteristics (eg, receptors, transporters), and disease course. Such tumor heterogeneity calls for different imaging strategies in order to provide proper diagnosis and follow-up. This also warrants selection of the most appropriate and locally available imaging modalities tailored to an individual patient based on consideration of many relevant factors including age, (anticipated) tumor location(s), size, and multifocality, underlying genotype, biochemical phenotype, chance of metastases, as well as the patient's personal preference and treatment goals. Anatomical imaging using computed tomography and magnetic resonance imaging and functional imaging using positron emission tomography and single photon emission computed tomography are currently a cornerstone in the evaluation of patients with pheochromocytomas/paragangliomas. In modern nuclear medicine practice, a multitude of radionuclides with relevance to diagnostic work-up and treatment planning (theranostics) is available, including radiolabeled metaiodobenzylguanidine, fluorodeoxyglucose, fluorodihydroxyphenylalanine, and somatostatin analogues. This review amalgamates up-to-date imaging guidelines, expert opinions, and recent discoveries. Based on the rich toolbox for anatomical and functional imaging that is currently available, we aim to define a customized approach in patients with (suspected) pheochromocytomas/paragangliomas from a practical clinical perspective. We provide imaging algorithms for different starting points for initial diagnostic work-up and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, postsurgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics, and response monitoring.
‘Our Roots Run Deep’: Historical Myths as Culturally Evolved Technologies for Coalitional Recruitment
Authors: Amine Sijilmassi, Lou Safra, Nicolas Baumard
Journal: Behavioral and Brain Sciences (2024)

Abstract One of the most remarkable manifestations of social cohesion in large-scale entities is the belief in a shared, distinct and ancestral past. Human communities around the world take pride in their ancestral roots, commemorate their long history of shared experiences, and celebrate the distinctiveness of their historical trajectory. Why do humans put so much effort into celebrating a long-gone past? Integrating insights from evolutionary psychology, social psychology, evolutionary anthropology, political science, cultural history and political economy, we show that the cultural success of historical myths is driven by a specific adaptive challenge for humans: the need to recruit coalitional support to engage in large scale collective action and prevail in conflicts. By showcasing a long history of cooperation and shared experiences, these myths serve as super-stimuli, activating specific features of social cognition and drawing attention to cues of fitness interdependence. In this account, historical myths can spread within a population without requiring group-level selection, as long as individuals have a vested interest in their propagation and strong psychological motivations to create them. Finally, this framework explains, not only the design-features of historical myths, but also important patterns in their cross-cultural prevalence, inter-individual distribution, and particular content.
Corrigendum to “Lipid nanoparticles for targeted delivery of anticancer therapeutics: Recent advances in development of siRNA and lipoprotein-mimicking nanocarriers” [Adv. Drug Delivery Rev. 203 (2023) 115136]
Authors: Anan Yaghmur, Jesper Østergaard, Huiling Mu
Journal: Advanced Drug Delivery Reviews (2024)
HIMALAYA Overall Survival Prominence and Other Routes to the Peak—Reply
Authors: Josep M. Llovet, Sarah Cappuyns, Richard S. Finn
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Renal Mitochondrial ATP Transporter Ablation Ameliorates Obesity-Induced CKD
Authors: Anna Permyakova, Sharleen Hamad, Liad Hinden, Saja Baraghithy, Aviram Kogot-Levin, Omri Yosef, Ori Shalev, Manish Kumar Tripathi, Haitham Amal, Abhishek Basu, Muhammad Arif, Resat Cinar, George Kunos, Michael Berger, Gil Leibowitz, Joseph Tam
Journal: Journal of the American Society of Nephrology (2024)

Significance Statement This study sheds light on the central role of adenine nucleotide translocase 2 (ANT2) in the pathogenesis of obesity-induced CKD. Our data demonstrate that ANT2 depletion in renal proximal tubule cells (RPTCs) leads to a shift in their primary metabolic program from fatty acid oxidation to aerobic glycolysis, resulting in mitochondrial protection, cellular survival, and preservation of renal function. These findings provide new insights into the underlying mechanisms of obesity-induced CKD and have the potential to be translated toward the development of targeted therapeutic strategies for this debilitating condition. Background The impairment in ATP production and transport in RPTCs has been linked to the pathogenesis of obesity-induced CKD. This condition is characterized by kidney dysfunction, inflammation, lipotoxicity, and fibrosis. In this study, we investigated the role of ANT2, which serves as the primary regulator of cellular ATP content in RPTCs, in the development of obesity-induced CKD. Methods We generated RPTC-specific ANT2 knockout ( RPTC-ANT2 −/− ) mice, which were then subjected to a 24-week high-fat diet–feeding regimen. We conducted comprehensive assessment of renal morphology, function, and metabolic alterations of these mice. In addition, we used large-scale transcriptomics, proteomics, and metabolomics analyses to gain insights into the role of ANT2 in regulating mitochondrial function, RPTC physiology, and overall renal health. Results Our findings revealed that obese RPTC-ANT2 −/− mice displayed preserved renal morphology and function, along with a notable absence of kidney lipotoxicity and fibrosis. The depletion of Ant2 in RPTCs led to a fundamental rewiring of their primary metabolic program. Specifically, these cells shifted from oxidizing fatty acids as their primary energy source to favoring aerobic glycolysis, a phenomenon mediated by the testis-selective Ant4. Conclusions We propose a significant role for RPTC-Ant2 in the development of obesity-induced CKD. The nullification of RPTC-Ant2 triggers a cascade of cellular mechanisms, including mitochondrial protection, enhanced RPTC survival, and ultimately the preservation of kidney function. These findings shed new light on the complex metabolic pathways contributing to CKD development and suggest potential therapeutic targets for this condition.
HIMALAYA Overall Survival Prominence and Other Routes to the Peak
Authors: Ghassan K. Abou-Alfa, Bruno Sangro
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Combining venetoclax and azacytidine with T-cell bispecific antibodies for treatment of acute myeloid leukemia: a preclinical assessment
Authors: Gerulf Hänel, Anne Schönle, Anne-Sophie Neumann, Daniel Nixdorf, Nora Philipp, Monika Sponheimer, Alexandra Leutbecher, Alica-Joana Emhardt, Giulia Magno, Veit Bücklein, Jan Eckmann, Diana Dunshee, Vesna Kramar, Koorosh Korfi, Sara Colombetti, Pablo Umaña, Christian Klein, Marion Subklewe
Journal: Leukemia (2024)

The development of Venetoclax (Ven) and Azacytidine (Aza) as treatment option in Acute Myeloid Leukemia (AML) has been a breakthrough especially for patients unfit for intensive chemotherapy (IC).Ven/Aza induced complete remission (CR) in 36.7% of newly diagnosed elderly AML patients [1].However, long term response rates remain poor with a median event-free survival of 9.8 months and a median overall survival of 14.1 months [1], due to persistence of measurable residual disease (MRD) that drives relapse.Novel therapeutic strategies are therefore urgently needed.Data from B-cell malignancies have demonstrated that T-cell based immunotherapy platforms, e.g.T-cell bispecific antibodies (TCBs) or chimeric antigen receptor (CAR) engineered T cells, are able to induce long-term remission and even cure in this patient cohort.Treatment with Blinatumomab in B-cell precursor acute lymphoblastic leukemia resulted in significant elimination of MRD in low-burden disease [2].Therefore, utility of immunotherapies such as TCBs post Ven/Aza could be envisaged to eradicate the MRD pool in AML and to improve survival rates in this patient population.This concept is further supported by preclinical data that demonstrated a Venetoclax induced increase in reactive oxygen-species (ROS) production in T cells, which resulted in enhanced T-cell effector function [3].In addition, Azacytidine increased the susceptibility of AML cells for T-cell mediated lysis [3].Multiple early phase clinical trials with TCBs targeting CD123 (Flotetuzumab and Vibecotamab) or the intracellular tumor antigen Wilms tumor 1 (WT1) presented on HLA-A*02 are currently underway in AML [4-6].In the current report, we investigate the immune modulating impact of Ven/Aza on the efficacy of a WT1-targeted TCB in AML in vitro and in vivo.To this end, we analyzed the PBMC composition of three healthy donors (HD) in vitro by flow cytometry after three days of treatment with 25 nM Ven and 1 µM Aza, reflecting patient serum concentrations [7, 8], and compared to an untreated control.High
SMARTdb: An Integrated Database for Exploring Single-cell Multi-omics Data of Reproductive Medicine
Authors: Zekai Liu, Zhen Yuan, Yunlei Guo, Ruilin Wang, Yusheng Guan, Zhanglian Wang, Yunan Chen, Tianlu Wang, Meining Jiang, Shuhui Bian
Journal: Genomics Proteomics & Bioinformatics (2024)

Single-cell multi-omics sequencing has greatly accelerated reproductive research in recent years, and the data are continually growing. However, utilizing these data resources is challenging for wet-lab researchers. A comprehensive platform for exploring single-cell multi-omics data related to reproduction is urgently needed. Here, we introduce the single-cell multi-omics atlas of reproduction (SMARTdb), an integrative and user-friendly platform for exploring molecular dynamics of reproductive development, aging, and disease, which covers multi-omics, multi-species, and multi-stage data. We curated and analyzed single-cell transcriptomic and epigenomic data of over 2.0 million cells from 6 species across the entire lifespan. A series of powerful functionalities are provided, such as "Query gene expression", "DIY expression plot", "DNA methylation plot", and "Epigenome browser". With SMARTdb, we found that the male germ cell-specific expression pattern of RPL39L and RPL10L is conserved between human and other model animals. Moreover, DNA hypomethylation and open chromatin may collectively regulate the specific expression pattern of RPL39L in both male and female germ cells. In summary, SMARTdb is a powerful platform for convenient data mining and gaining novel insights into reproductive development, aging, and disease. SMARTdb is publicly available at https://smart-db.cn.
Integrated Single-cell Multiomic Analysis of HIV Latency Reversal Reveals Novel Regulators of Viral Reactivation
Authors: Manickam Ashokkumar, Wenwen Mei, Jackson J Peterson, Yuriko Harigaya, David M Murdoch, David M Margolis, Caleb Kornfein, Alex Oesterling, Zhicheng Guo, Cynthia D Rudin, Yuchao Jiang, Edward P Browne
Journal: Genomics Proteomics & Bioinformatics (2024)

Despite the success of antiretroviral therapy, human immunodeficiency virus (HIV) cannot be cured because of a reservoir of latently infected cells that evades therapy. To understand the mechanisms of HIV latency, we employed an integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq) approach to simultaneously profile the transcriptomic and epigenomic characteristics of ∼ 125,000 latently infected primary CD4+ T cells after reactivation using three different latency reversing agents. Differentially expressed genes and differentially accessible motifs were used to examine transcriptional pathways and transcription factor (TF) activities across the cell population. We identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and demonstrated that a machine learning model trained on these data was 75%-79% accurate at predicting viral reactivation. Finally, we validated the role of two candidate HIV-regulating factors, FOXP1 and GATA3, in viral transcription. These data demonstrate the power of integrated multimodal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.
MSIsensor-RNA: Microsatellite Instability Detection for Bulk and Single-cell Gene Expression Data
Authors: Peng Jia, Xuanhao Yang, Xiaofei Yang, Tingjie Wang, Yu Xu, Kai Ye
Journal: Genomics Proteomics & Bioinformatics (2024)

Microsatellite instability (MSI) is an indispensable biomarker in cancer immunotherapy. Currently, MSI scoring methods by high-throughput omics methods have gained popularity and demonstrated better performance than the gold standard method for MSI detection. However, the MSI detection method on expression data, especially single-cell expression data, is still lacking, limiting the scope of clinical application and prohibiting the investigation of MSI at a single-cell level. Herein, we developed MSIsensor-RNA, an accurate, robust, adaptable, and standalone software to detect MSI status based on expression values of MSI-associated genes. We demonstrated the favorable performance and promise of MSIsensor-RNA in both bulk and single-cell gene expression data in multiplatform technologies including RNA sequencing (RNA-seq), microarray, and single-cell RNA-seq. MSIsensor-RNA is a versatile, efficient, and robust method for MSI status detection from both bulk and single-cell gene expression data in clinical studies and applications. MSIsensor-RNA is available at https://github.com/xjtu-omics/msisensor-rna.