tbuckley/cabot-search huggingface dataset:
Weight Loss Treatment and Longitudinal Weight Change Among Primary Care Patients With Obesity
Authors: James Henderson, Anne P. Ehlers, Joyce M. Lee, Andrew T. Kraftson, Kenneth Piehl, Caroline R. Richardson, Dina H. Griauzde
Journal: JAMA Network Open (2024)

Importance Among individuals with obesity, 5% or greater weight loss can improve health. Weight management treatments (WMT) include nutrition counseling, very low-calorie meal replacement (MR), antiobesity medications (AOM), and bariatric surgery; however, little is known about how these WMT are associated with weight change among individual patients and populations. Objective To characterize weight status and WMT use among primary care patients and assess associations between WMT and weight trajectories. Design, Setting, and Participants Retrospective, population-based cohort study of primary care patients from 1 academic health system in Michigan between October 2015 and March 2020 using cross-sectional analysis to compare obesity prevalence and WMT utilization. For patients with obesity and WMT exposure or matched controls, a multistate Markov model assessing associations between WMT and longitudinal weight status trajectories was used. Data were analyzed from October 2021 to October 2023. Exposures Cross-sectional exposure was year: 2017 or 2019. Trajectory analysis exposures were WMT: nutrition counseling, MR, AOM, and bariatric surgery. Main Outcomes and Measures Cross-sectional analysis compared mean body mass index (BMI), obesity prevalence, and, among patients with obesity, prospective WMT use. The trajectory analysis examined longitudinal weight status using thresholds of ±5% and 10% of baseline weight with primary outcomes being the 1-year probabilities of 5% or greater weight loss for each WMT. Results Adult patients (146 959 participants) consisted of 83 636 female participants (56.9%); 8940 (6.1%) were Asian, 14 560 (9.9%) were Black, and 116 664 (79.4%) were White. Patients had a mean (SD) age of 49.6 (17.7) years and mean (SD) BMI of 29.2 (7.2). Among 138 682 patients, prevalence of obesity increased from 39.2% in 2017 to 40.7% in 2019; WMT use among patients with obesity increased from 5.3% to 7.1% (difference: 1.7%; 95% CI, 1.3%-2.2%). In a multistate model (10 180 patients; 33 549 patient-years), the 1-year probability of 5% or greater weight loss without WMT exposure was 15.6% (95% CI, 14.3%-16.5%) at reference covariates. In contrast, the probability of 5% or greater weight loss was more likely with year-long exposures to any WMT (nutrition counseling: 23.1%; 95% CI, 21.3%-25.1%; MR: 54.6%; 95% CI, 46.5%-61.2%; AOM: 27.8%; 95% CI, 25.0%-30.5%; bariatric surgery: 93.0%; 95% CI, 89.7%-95.0%). Conclusions and Relevance In this cohort study of primary-care patients with obesity, all WMT increased the patient-level probability of achieving 5% or greater weight loss, but current rates of utilization are low and insufficient to reduce weight at the population level.
Considerations for Prompting Large Language Models
Authors: Brian Schulte
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
A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway
Authors: Bo Huang, Junwu Ren, Qiang Ma, Feifei Yang, Xiaojuan Pan, Yuying Zhang, Yuying Liu, Cong Wang, Dawei Zhang, Ling Wei, Lingyu Ran, Hongwen Zhao, Ce Liang, Xiaolin Wang, Shiming Wang, Haiping Li, Hao Ning, Ai Ran, Wei Li, Yongquan Wang, Bin Xiao
Journal: Molecular Cancer (2024)

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer with high aggressive phenotype and poor prognosis. Accumulating evidence suggests that circRNAs have been identified as pivotal mediators in cancers. However, the role of circRNAs in ccRCC progression remains elusive. Methods The differentially expressed circRNAs in 4 paired human ccRCC and adjacent noncancerous tissues ccRCC were screened using circRNA microarrays and the candidate target was selected based on circRNA expression level using weighted gene correlation network analysis (WGCNA) and the gene expression omnibus (GEO) database. CircPDHK1 expression in ccRCC and adjacent noncancerous tissues ( n = 148) were evaluated along with clinically relevant information. RT-qPCR, RNase R digestion, and actinomycin D (ActD) stability test were conducted to identify the characteristics of circPDHK1. The subcellular distribution of circPDHK1 was analyzed by subcellular fractionation assay and fluorescence in situ hybridization (FISH). Immunoprecipitation-mass spectrometry (IP-MS) and immunofluorescence (IF) were employed to evaluate the protein-coding ability of circPDHK1. ccRCC cells were transfected with siRNAs, plasmids or lentivirus approach, and cell proliferation, migration and invasion, as well as tumorigenesis and metastasis in nude mice were assessed to clarify the functional roles of circPDHK1 and its encoded peptide PDHK1-241aa. RNA-sequencing, western blot analysis, immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) assays were further employed to identify the underlying mechanisms regulated by PDHK1-241aa. Results CircPDHK1 was upregulated in ccRCC tissues and closely related to WHO/ISUP stage, T stage, distant metastasis, VHL mutation and Ki-67 levels. CircPDHK1 had a functional internal ribosome entry site (IRES) and encoded a novel peptide PDHK1-241aa. Functionally, we confirmed that PDHK1-241aa and not the circPDHK1 promoted the proliferation, migration and invasion of ccRCC. Mechanistically, circPDHK1 was activated by HIF-2A at the transcriptional level. PDHK1-241aa was upregulated and interacted with PPP1CA, causing the relocation of PPP1CA to the nucleus. This thereby inhibited AKT dephosphorylation and activated the AKT-mTOR signaling pathway. Conclusions Our data indicated that circPDHK1-encoded PDHK1-241aa promotes ccRCC progression by interacting with PPP1CA to inhibit AKT dephosphorylation. This study provides novel insights into the multiplicity of circRNAs and highlights the potential use of circPDHK1 or PDHK1-241aa as a therapeutic target for ccRCC.
Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children’s Oncology Group Report
Authors: N. J. DelRocco, M. L. Loh, M. J. Borowitz, S. Gupta, K. R. Rabin, P. Zweidler-McKay, K. W. Maloney, L. A. Mattano, E. Larsen, A. Angiolillo, R. J. Schore, M. J. Burke, W. L. Salzer, B. L. Wood, A. J. Carroll, N. A. Heerema, S. C. Reshmi, J. M. Gastier-Foster, R. Harvey, I. M. Chen, K. G. Roberts, C. G. Mullighan, C. Willman, N. Winick, W. L. Carroll, R. E. Rau, D. T. Teachey, S. P. Hunger, E. A. Raetz, M. Devidas, J. A. Kairalla
Journal: Leukemia (2024)

Abstract Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PI COG ) that maximized discrimination of the predictive model. Patients with higher PI COG have higher predicted relapse risk. The PI COG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PI COG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PI COG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PI COG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PI COG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.
RANKL blockade for erosive hand osteoarthritis: a randomized placebo-controlled phase 2a trial
Authors: Ruth Wittoek, Gust Verbruggen, Tine Vanhaverbeke, Roos Colman, Dirk Elewaut
Journal: Nature Medicine (2024)

Abstract Erosive hand osteoarthritis (OA) is a prevalent and disabling disease with limited treatment options. Here we present the results of a monocentric, placebo-controlled, double-blind, randomized phase 2a clinical trial with denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, evaluating the effects on structure modification in erosive hand OA. Patients were randomized to 48 weeks treatment with denosumab 60 mg every 3 months ( n = 51, 41 females) or placebo ( n = 49, 37 females). The primary (radiographic) endpoint was the change in the total Ghent University Scoring System (GUSS) at week 24, where positive changes correspond to remodeling and negative changes to erosive progression. Secondary endpoints were the change in the GUSS at week 48 and the number of new erosive joints at week 48 by the anatomical phase scoring system. Baseline mean GUSS (standard deviation) of target joints was 155.9 (69.3) in the denosumab group and 158.7 (46.8) in the placebo group. The primary endpoint was met with an estimated difference between groups of 8.9 (95% confidence interval (CI) 1.0 to 16.9; P = 0.024) at week 24. This effect was confirmed at week 48 (baseline adjusted GUSS (standard error of the mean) denosumab and placebo were 163.5 (2.9) and 149.2 (3.9), respectively; with an estimated difference between groups of 14.3 (95% CI 4.6 to 24.0; P = 0.003)). At patient level, more new erosive joints were developed in the placebo group compared with denosumab at week 48 (odds ratio 0.24 (95% CI 0.08 to 0.72); P = 0.009). More adverse events occurred in the placebo group (125 events in 44 patients (90%)) compared with the denosumab group (97 events in 41 patients (80%)). These results demonstrate that denosumab has structure modifying effects in erosive hand OA by inducing remodeling and preventing new erosive joints. EU Clinical Trials Register identifier 2015-003223-53 .
Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression
Authors: Junyi Hu, Shao-Gang Wang, Yaxin Hou, Zhaohui Chen, Lilong Liu, Ruizhi Li, Nisha Li, Lijie Zhou, Yu Yang, Liping Wang, Liang Wang, Xiong Yang, Yichen Lei, Changqi Deng, Yang Li, Zhiyao Deng, Yuhong Ding, Yingchun Kuang, Zhipeng Yao, Yang Xun, Fan Li, Heng Li, Jia Hu, Zheng Liu, Tao Wang, Yi Hao, Xuanmao Jiao, Wei Guan, Zhen Tao, Shancheng Ren, Ke Chen
Journal: Nature Genetics (2024)

Abstract Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.
Clonal Hematopoiesis of Indeterminate Potential With Loss of <i>Tet2</i> Enhances Risk for Atrial Fibrillation Through <i>Nlrp3</i> Inflammasome Activation
Authors: Amy Erica Lin, Aneesh C. Bapat, Ling Xiao, Abhishek Niroula, Jiangchuan Ye, Waihay J. Wong, Mridul Agrawal, Christopher J. Farady, Andreas Boettcher, Christopher B. Hergott, Marie McConkey, Patricio Flores-Bringas, Veronica Shkolnik, Alexander G. Bick, David Milan, Pradeep Natarajan, Peter Libby, Patrick T. Ellinor, Benjamin L. Ebert
Journal: Circulation (2024)

Clonal hematopoiesis of indeterminate potential (CHIP), a common age-associated phenomenon, associates with increased risk of both hematological malignancy and cardiovascular disease. Although CHIP is known to increase the risk of myocardial infarction and heart failure, the influence of CHIP in cardiac arrhythmias, such as atrial fibrillation (AF), is less explored.
Macrophages Under the Influence of Tumor Mesothelin Weaken Host Defenses against Pancreatic Cancer Metastasis
Authors: Christine Alewine
Journal: Cancer Research (2024)

Abstract Although pancreatic cancer is a systemic disease that metastasizes early in its course, the signaling systems that promote this behavior remain incompletely understood. In this issue of Cancer Research, Luckett and colleagues identify a paracrine signaling pathway between cancer cells and macrophages that promotes pancreatic cancer metastasis. The authors used immunocompetent murine pancreatic cancer models with high versus low metastatic potential, genetic knockout and complementation strategies, and The Cancer Genome Atlas human data to demonstrate that tumor-secreted mesothelin repolarizes tumor and lung macrophages to a tumor-supportive phenotype. The repolarized macrophages increase secretion of VEGF and S100A9, raising local concentrations. In turn, VEGF enhances colony formation of cancer cells, while S100A9 promotes the recruitment of neutrophils to the lungs and the formation of neutrophil extracellular traps that support tumor metastasis. Together, these findings reveal a systemic signaling pathway that promotes pancreatic cancer metastasis by co-opting macrophages typically protective against cancer to instead promote its spread. See related article by Luckett et al., p. 527
<i>Salmonella enterica</i> serovar Typhimurium remodels mitochondrial dynamics of macrophages via the T3SS effector SipA to promote intracellular proliferation
Authors: Xingmei Liu, Yutao Liu, Xinyu Zhao, Xueping Li, Ting Yao, Ruiying Liu, Qian Wang, Qiushi Wang, Dan Li, Xintong Chen, Bin Liu, Lu Feng
Journal: Gut Microbes (2024)

Mitochondrial dynamics are critical in cellular energy production, metabolism, apoptosis, and immune responses. Pathogenic bacteria have evolved sophisticated mechanisms to manipulate host cells' mitochondrial functions, facilitating their proliferation and dissemination. Salmonella enterica serovar Typhimurium (S. Tm), an intracellular foodborne pathogen, causes diarrhea and exploits host macrophages for survival and replication. However, S. Tm-associated mitochondrial dynamics during macrophage infection remain poorly understood. In this study, we showed that within macrophages, S. Tm remodeled mitochondrial fragmentation to facilitate intracellular proliferation mediated by Salmonella invasion protein A (SipA), a type III secretion system effector encoded by Salmonella pathogenicity island 1. SipA directly targeted mitochondria via its N-terminal mitochondrial targeting sequence, preventing excessive fragmentation and the associated increase in mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and release of mitochondrial DNA and cytochrome c into the cytosol. Macrophage replication assays and animal experiments showed that mitochondria and SipA interact to facilitate intracellular replication and pathogenicity of S. Tm. Furthermore, we showed that SipA delayed mitochondrial fragmentation by indirectly inhibiting the recruitment of cytosolic dynamin-related protein 1, which mediates mitochondrial fragmentation. This study revealed a novel mechanism through which S. Tm manipulates host mitochondrial dynamics, providing insights into the molecular interplay that facilitates S. Tm adaptation within host macrophages.
Mesothelin Secretion by Pancreatic Cancer Cells Co-opts Macrophages and Promotes Metastasis
Authors: Teifion Luckett, Maidinaimu Abudula, Lucy Ireland, Mark Glenn, Gaia Bellomo, Ruth Stafferton, Chris Halloran, Paula Ghaneh, Rob Jones, Michael C. Schmid, Ainhoa Mielgo
Journal: Cancer Research (2024)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease, yet effective treatments to inhibit PDAC metastasis are lacking. The rich PDAC tumor microenvironment plays a major role in disease progression. Macrophages are the most abundant immune cell population in PDAC tumors and can acquire a range of functions that either hinder or promote tumor growth and metastasis. Here, we identified that mesothelin secretion by pancreatic cancer cells co-opts macrophages to support tumor growth and metastasis of cancer cells to the lungs, liver, and lymph nodes. Mechanistically, secretion of high levels of mesothelin by metastatic cancer cells induced the expression of VEGF alpha (VEGFA) and S100A9 in macrophages. Macrophage-derived VEGFA fed back to cancer cells to support tumor growth, and S100A9 increased neutrophil lung infiltration and formation of neutrophil extracellular traps. These results reveal a role for mesothelin in regulating macrophage functions and interaction with neutrophils to support PDAC metastasis. Significance: Mesothelin secretion by cancer cells supports pancreatic cancer metastasis by inducing macrophage secretion of VEGFA and S100A9 to support cancer cell proliferation and survival, recruit neutrophils, and stimulate neutrophil extracellular trap formation. See related commentary by Alewine, p. 513
An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH)
Authors: Zewu Zhu, Bryan Bo-Ran Ho, Alyssa Chen, James Amrhein, Andreea Apetrei, Thomas Oliver Carpenter, Marise Lazaretti-Castro, Juan Manuel Colazo, Kathryn McCrystal Dahir, Michaela Geßner, Evgenia Gurevich, Cathrine Alsaker Heier, Jill Hickman Simmons, Tracy Earl Hunley, Bernd Hoppe, Christina Jacobsen, Anne Kouri, Nina Ma, Sachin Majumdar, Arnaud Molin, Natalie Nokoff, Susan M. Ott, Helena Gil Peña, Fernando Santos, Peter Tebben, Lisa Swartz Topor, Yanhong Deng, Clemens Bergwitz
Journal: Kidney International (2024)
Editor's Note: <i>In Vivo</i> Persistence, Tumor Localization, and Antitumor Activity of CAR-Engineered T Cells Is Enhanced by Costimulatory Signaling through CD137 (4-1BB)
Authors: De-Gang Song, Qunrui Ye, Carmine Carpenito, Mathilde Poussin, Li-Ping Wang, Chunyan Ji, Mariangela Figini, Carl H. June, George Coukos, Daniel J. Powell
Journal: Cancer Research (2024)
Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells
Authors: Ziwen Cai, Miaomiao Zhu, Li Xu, Yue Wang, Yin Xu, Wai Yen Yim, Hong Cao, Ruikang Guo, Xiang Qiu, Ximiao He, Jiawei Shi, Weihua Qiao, Nianguo Dong
Journal: Circulation (2024)

A main obstacle in current valvular heart disease research is the lack of high-quality homogeneous functional heart valve cells. Human induced pluripotent stem cells (hiPSCs)-derived heart valve cells may help with this dilemma. However, there are no well-established protocols to induce hiPSCs to differentiate into functional heart valve cells, and the networks that mediate the differentiation have not been fully elucidated.
S-Nitrosylation of Septin2 Exacerbates Aortic Aneurysm and Dissection by Coupling the TIAM1-RAC1 Axis in Macrophages
Authors: Yan Zhang, Hao Zhang, Shuang Zhao, Zhenhua Qi, Yiwei He, Xuhong Zhang, Wencheng Wu, Ke Yan, Lulu Hu, Shixiu Sun, Xinlong Tang, Qing Zhou, Feng Chen, Aihua Gu, Liansheng Wang, Zhiren Zhang, Bo Yu, Dongjin Wang, Yi Han, Liping Xie, Yong Ji
Journal: Circulation (2024)

S-Nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in cardiovascular disease. Aortic aneurysm and dissection are high-risk cardiovascular diseases without an effective cure. The aim of this study was to determine the role of SNO of Septin2 in macrophages in aortic aneurysm and dissection.
Genome-wide ATAC-see screening identifies TFDP1 as a modulator of global chromatin accessibility
Authors: Satoko Ishii, Taishi Kakizuka, Sung-Joon Park, Ayako Tagawa, Chiaki Sanbo, Hideyuki Tanabe, Yasuyuki Ohkawa, Mahito Nakanishi, Kenta Nakai, Yusuke Miyanari
Journal: Nature Genetics (2024)
A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis
Authors: Paula R. Haynes, Elana S. Pyfrom, Yongjun Li, Carly Stein, Vishnu Anand Cuddapah, Jack A. Jacobs, Zhifeng Yue, Amita Sehgal
Journal: Nature Neuroscience (2024)

Abstract Sleep is thought to be restorative to brain energy homeostasis, but it is not clear how this is achieved. We show here that Drosophila glia exhibit a daily cycle of glial mitochondrial oxidation and lipid accumulation that is dependent on prior wake and requires the Drosophila APOE orthologs NLaz and GLaz, which mediate neuron–glia lipid transfer. In turn, a full night of sleep is required for glial lipid clearance, mitochondrial oxidative recovery and maximal neuronal mitophagy. Knockdown of neuronal NLaz causes oxidative stress to accumulate in neurons, and the neuronal mitochondrial integrity protein, Drp1, is required for daily glial lipid accumulation. These data suggest that neurons avoid accumulation of oxidative mitochondrial damage during wake by using mitophagy and passing damage to glia in the form of lipids. We propose that a mitochondrial lipid metabolic cycle between neurons and glia reflects a fundamental function of sleep relevant for brain energy homeostasis.