tbuckley/cabot-search huggingface dataset:
Inclusion of the US Preventive Services Task Force Recommendation for Mammography in State Comprehensive Cancer Control Plans in the US
Authors: Mehrnoosh Soori, Elizabeth A. Platz, Otis W. Brawley, Robert S. Lawrence, Norma F. Kanarek
Journal: JAMA Network Open (2022)

The recommendations for the age and frequency that women at average risk for breast cancer should undergo breast cancer mammography screening have been a matter of emotional, political, and scientific debate over the past decades. Multiple national organizations provide recommendations for breast cancer screening age and frequency. US Centers for Disease Control and Prevention (CDC) funding for state comprehensive cancer control (CCC) planning requires compliance with stated objectives for attaining goals. US Preventive Services Task Force (USPSTF) recommendations on cancer prevention and control are currently used to require coverage of prevention services.To evaluate the consistency of state CCC plan objectives compared with the most current (2016) USPSTF recommendations for the age and frequency that individuals should undergo mammography screening and to make recommendations for improvement of state CCC plans.This cross-sectional study used a descriptive, point-in-time evaluation and was conducted from November 1, 2019, to June 30, 2021. In November 2019, the most recent CCC plans from 50 US states and the District of Columbia were downloaded from the CDC website. The recommended ages at which to begin and end mammography examinations and the frequency of mammography examinations were extracted from plan objectives.The recommendations found in CCC plan objectives regarding the ages at which to begin and end mammography examinations and the frequency of mammography examinations for women with average risk for breast cancer were compared with USPSTF recommendations.Of the 51 CCC plans, 16 (31%) were consistent with all USPSTF recommendations for age and frequency that women at average risk should undergo mammography. Twenty-six plans (51%) were partially consistent with recommendations, and 9 plans (18%) were not consistent with any of the 3 guideline components.Compared with the USPSTF recommendation, state CCC plans are not homogenous regarding the age and frequency that women at average risk for breast cancer should undergo mammography. This variation is partially due to differences in state-specific planning considerations and discretion, variations in recommendations among national organizations, and publication of plans prior to the most current USPSTF recommendation (2016). Specifying the concept that high-risk populations need different age and frequency of screening recommendations than the general population may reduce heterogeneity among plans.
Mitochondria-derived peptides in aging and healthspan
Authors: Brendan Miller, Su-Jeong Kim, Hiroshi Kumagai, Kelvin Yen, Pinchas Cohen
Journal: Journal of Clinical Investigation (2022)

The mechanisms that explain mitochondrial dysfunction in aging and healthspan continue to be studied, but one element has been unexplored: microproteins. Small open reading frames in circular mitochondria DNA can encode multiple microproteins, called mitochondria-derived peptides (MDPs). Currently, eight MDPs have been published: humanin, MOTS-c, and SHLPs 1-6. This Review describes recent advances in microprotein discovery with a focus on MDPs. It discusses what is currently known about MDPs in aging and how this new understanding could add to the way we understand age-related diseases including type 2 diabetes, cancer, and neurodegenerative diseases at the genomic, proteomic, and drug-development levels.
Obesity: No European country is on track to halt rising levels by 2025, WHO warns
Authors: Elisabeth Mahase
Journal: BMJ (2022)

Nearly two thirds (60%) of adults and a third of children in the World Health Organization's European region are overweight or obese, and no state is on track to meet the target of halting the increase in the prevalence of obesity by 2025, WHO has said. 1 Consistent increases in the prevalence of overweight and obesity have been seen across the European region of 53 countries, and early studies indicate that the situation has worsened during the covid-19 pandemic.This is despite 60% of countries having a policy, strategy, or action plan for reducing overweight and obesity."Overweight and obesity in adults have reached epidemic proportions," the report said.Estimates indicate that obesity in the region rose by 21% in the 10 years to 2016 and by 138% since 1975.Overweight (including obesity) rose by 8% in the 10 years to 2016 and by 51% since 1975.Being overweight or obese is the fourth most common risk factor for non-communicable disease in Europe and is also the leading risk factor for disability, causing 7% of total years lived with disability.
Regional vs General Anesthesia and Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery
Authors: Zhaohua Zhu, Peihua Cao, Lijun Lin
Journal: JAMA (2022)

To the Editor We have a concern about the article by Dr Li and colleagues,1 which found that regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia in elderly patients undergoing hip fracture surgery.
PET-Based Radiogenomics Supports mTOR Pathway Targeting for Hepatocellular Carcinoma
Authors: Jihyun An, Minyoung Oh, Seog-Young Kim, Yoo-Jin Oh, Bora Oh, Ji-Hye Oh, Wonkyung Kim, Jin Hwa Jung, Ha Il Kim, Jae-Seung Kim, Chang Ohk Sung, Ju Hyun Shim
Journal: Clinical Cancer Research (2022)

This work aimed to explore in-depth the genomic and molecular underpinnings of hepatocellular carcinoma (HCC) with increased fluorine-18 fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) and to identify therapeutic targets based on this imaging-genomic surrogate.We used RNA sequencing and whole exome sequencing data obtained from 117 HCC patients who underwent hepatic resection with preoperative FDG-PET/CT imaging as a discovery cohort. The primary radiogenomic results were validated with transcriptomes from a second cohort of 81 patients with more advanced tumors. All patients were allocated to an FDG-avid or FDG-non-avid group according to the PET findings. We also screened potential drug candidates targeting FDG-avid HCCs in vitro and in vivo Results: High FDG avidity conferred worse recurrence-free survival after HCC resection. Whole transcriptome analysis revealed upregulation of mTOR pathway signals in the FDG-avid tumors, together with higher abundance of associated mutations. These clinical and genomic findings were replicated in the validation set. A molecular signature of FDG-avid HCCs identified in the discovery set consistently predicted poor prognoses in the public-access datasets of two cohorts. Treatment with an mTOR inhibitor resulted in decreased FDG uptake followed by effective tumor control in both the hyperglycolytic HCC cell lines and xenograft mouse models.Our PET-based radiogenomic analysis indicates that mTOR pathway genes are markedly activated and altered in HCCs with high FDG retention. This nuclear imaging biomarker may stimulate umbrella trials and tailored treatments in precision care of HCC patients.
Self-monitoring of Blood Pressure During Pregnancy
Authors: Malavika Prabhu, Line Malha, Laura E. Riley
Journal: JAMA (2022)

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 Publications 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 2023 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
Single-cell proteomics defines the cellular heterogeneity of localized prostate cancer
Authors: Laura De Vargas Roditi, Andrea Jacobs, Jan H. Rueschoff, Pete Bankhead, Stéphane Chevrier, Hartland W. Jackson, Thomas Hermanns, Christian D. Fankhauser, Cedric Poyet, Felix Chun, Niels J. Rupp, Alexandra Tschaebunin, Bernd Bodenmiller, Peter J. Wild
Journal: Cell Reports Medicine (2022)

Localized prostate cancer exhibits multiple genomic alterations and heterogeneity at the proteomic level. Single-cell technologies capture important cell-to-cell variability responsible for heterogeneity in biomarker expression that may be overlooked when molecular alterations are based on bulk tissue samples. This study aims to identify prognostic biomarkers and describe the heterogeneity of prostate cancer and the associated microenvironment by simultaneously quantifying 36 proteins using single-cell mass cytometry analysis of over 1.6 million cells from 58 men with localized prostate cancer. We perform this task, using a high-dimensional clustering pipeline named Franken to describe subpopulations of immune, stromal, and prostate cells, including changes occurring in tumor tissues and high-grade disease that provide insights into the coordinated progression of prostate cancer. Our results further indicate that men with localized disease already harbor rare subpopulations that typically occur in castration-resistant and metastatic disease.
Global progress toward the elimination of active trachoma: an analysis of 38 countries
Authors: Kristen K Renneker, Mariamo Abdala, James Addy, Tawfik Al-Khatib, Khaled Amer, Mouctar Dieng Badiane, Wilfrid Batcho, Lucienne Bella, Clarisse Bougouma, Victor Bucumi, Tina Chisenga, Tran Minh Dat, Djore Dézoumbé, Balgesa Elshafie, Mackline Garae, André Goepogui, Jaouad Hammou, George Kabona, Boubacar Kadri, Khumbo Kalua, Sarjo Kanyi, Asad Aslam Khan, Benjamin Marfo, Sultani Matendechero, Aboulaye Meite, Abdellahi Minnih, Francis Mugume, Nicholas Olobio, Fatma Juma Omar, Isaac Phiri, Salimato Sanha, Shekhar Sharma, Fikre Seife, Oliver Sokana, Raebwebwe Taoaba, Andeberhan Tesfazion, Lamine Traoré, Naomi Uvon, Georges Yaya, Makoy Yibi Logora, P J Hooper, Paul M Emerson, Jeremiah M Ngondi
Journal: The Lancet Global Health (2022)

Global elimination of trachoma as a public health problem was targeted for 2020. We reviewed progress towards the elimination of active trachoma by country and geographical group.In this retrospective analysis of national survey and implementation data, all countries ever known to be endemic for trachoma that had either implemented at least one trachoma impact survey shown in the publicly available Trachoma Atlas, or are in Africa were invited to participate in this study. Scale-up was described according to the number of known endemic implementation units and mass drug administration implementation over time. The prevalence of active trachoma-follicular among children aged 1-9 years (TF1-9) from baseline, impact, and surveillance surveys was categorised and used to show programme progress towards reaching the elimination threshold (TF1-9 <5%) using dot maps, spaghetti plots, and boxplots.We included data until Nov 10, 2021, for 38 countries, representing 2097 ever-endemic implementation units. Of these, 1923 (91·7%) have had mass drug administration. Of 1731 implementation units with a trachoma impact survey, the prevalence of TF1-9 had reduced by at least 50% in 1465 (84·6%) implementation units and 1182 (56·4%) of 2097 ever-endemic implementation units had reached the elimination threshold. 2 years after reaching a TF1-9 prevalence below 5%, most implementation units sustained this target; however, 58 (56·3%) of 103 implementation units in Ethiopia showed recrudescence.Global elimination of trachoma as a public health problem by 2020 was not possible, but this finding masks the great progress achieved. Implementation units in high baseline categories and recrudescent TF1-9 might prolong the attainment of elimination of active trachoma. Elimination is delayed but, with an understanding of the patterns and timelines to reaching elimination targets and a commitment toward meeting future targets, global elimination can still be achieved by 2030.None.
Antidepressant Combinations Compared With Monotherapy
Authors: Anita Slomski
Journal: JAMA (2022)

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 Publications 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 2023 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
SvAnna: efficient and accurate pathogenicity prediction of coding and regulatory structural variants in long-read genome sequencing
Authors: Daniel Danis, Julius O. B. Jacobsen, Parithi Balachandran, Qihui Zhu, Feyza Yilmaz, Justin Reese, Matthias Haimel, Gholson J. Lyon, Ingo Helbig, Christopher J. Mungall, Christine R. Beck, Charles Lee, Damian Smedley, Peter N. Robinson
Journal: Genome Medicine (2022)

Structural variants (SVs) are implicated in the etiology of Mendelian diseases but have been systematically underascertained owing to sequencing technology limitations. Long-read sequencing enables comprehensive detection of SVs, but approaches for prioritization of candidate SVs are needed. Structural variant Annotation and analysis (SvAnna) assesses all classes of SVs and their intersection with transcripts and regulatory sequences, relating predicted effects on gene function with clinical phenotype data. SvAnna places 87% of deleterious SVs in the top ten ranks. The interpretable prioritizations offered by SvAnna will facilitate the widespread adoption of long-read sequencing in diagnostic genomics. SvAnna is available at https://github.com/TheJacksonLaboratory/SvAnn a .
Trauma Surgeon Ars Poetica
Authors: Maya J. Sorini
Journal: JAMA (2022)

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 Publications 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 2023 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
Patient-derived models of brain metastases recapitulate human disseminated disease
Authors: Claudia C. Faria, Rita Cascão, Carlos Custódia, Eunice Paisana, Tânia Carvalho, Pedro Pereira, Rafael Roque, José Pimentel, José Miguéns, Isidro Cortes-Ciriano, João T. Barata
Journal: Cell Reports Medicine (2022)

Dissemination of cancer cells from primary tumors to the brain occurs in many cancer patients, increasing morbidity and death. There is an unmet medical need to develop translational platforms to evaluate therapeutic responses. Toward this goal, we established a library of 23 patient-derived xenografts (PDXs) of brain metastases (BMs) from eight distinct primary tumors. In vivo tumor formation correlates with patients' poor survival. Mouse subcutaneous xenografts develop spontaneous metastases and intracardiac PDXs increase dissemination to the CNS, both models mimicking the dissemination pattern of the donor patient. We test the FDA-approved drugs buparlisib (pan-PI3K inhibitor) and everolimus (mTOR inhibitor) and show their efficacy in treating our models. Finally, we show by RNA sequencing that human BMs and their matched PDXs have similar transcriptional profiles. Overall, these models of BMs recapitulate the biology of human metastatic disease and can be valuable translational platforms for precision medicine.
In CKD, the Kidney Failure Risk Equation predicted 2-y risk for ESKD better than eGFR alone
Authors: Diego Aguilar-Ramirez, William G. Herrington
Journal: Annals of Internal Medicine (2022)

Bundy JD, Mills KT, Anderson AH, et al. Prediction of end-stage kidney disease using estimated glomerular filtration rate with and without race: a prospective cohort study. Ann Intern Med. 2022;175:305-13. 35007146.
Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance
Authors: Yanrui Huang, Jenny H. Zhou, Haifeng Zhang, Alberto Canfran-Duque, Abhishek K. Singh, Rachel J. Perry, Gerald I. Shulman, Carlos Fernandez-Hernando, Wang Min
Journal: Journal of Clinical Investigation (2022)

Brown adipose tissue (BAT), a crucial heat-generating organ, regulates whole-body energy metabolism by mediating thermogenesis. BAT inflammation is implicated in the pathogenesis of mitochondrial dysfunction and impaired thermogenesis. However, the link between BAT inflammation and systematic metabolism remains unclear. Herein, we use mice with BAT deficiency of thioredoxin-2 (TRX2), a protein that scavenges mitochondrial reactive oxygen species (ROS), to evaluate the impact of BAT inflammation on metabolism and thermogenesis and its underlying mechanism. Our results show that BAT-specific TRX2 ablation improves systematic metabolic performance via enhancing lipid uptake, which protects mice from diet-induced obesity, hypertriglyceridemia, and insulin resistance. TRX2 deficiency impairs adaptive thermogenesis by suppressing fatty acid oxidation. Mechanistically, loss of TRX2 induces excessive mitochondrial ROS, mitochondrial integrity disruption, and cytosolic release of mitochondrial DNA, which in turn activate aberrant innate immune responses in BAT, including the cGAS/STING and the NLRP3 inflammasome pathways. We identify NLRP3 as a key converging point, as its inhibition reverses both the thermogenesis defect and the metabolic benefits seen under nutrient overload in BAT-specific Trx2-deficient mice. In conclusion, we identify TRX2 as a critical hub integrating oxidative stress, inflammation, and lipid metabolism in BAT, uncovering an adaptive mechanism underlying the link between BAT inflammation and systematic metabolism.
The Ca2+-gated channel TMEM16A amplifies capillary pericyte contraction and reduces cerebral blood flow after ischemia
Authors: Nils Korte, Zeki Ilkan, Claire L. Pearson, Thomas Pfeiffer, Prabhav Singhal, Jason R. Rock, Huma Sethi, Dipender Gill, David Attwell, Paolo Tammaro
Journal: Journal of Clinical Investigation (2022)

Pericyte-mediated capillary constriction decreases cerebral blood flow in stroke after an occluded artery is unblocked. The determinants of pericyte tone are poorly understood. We show that a small rise in cytoplasmic Ca2+ concentration ([Ca2+]i) in pericytes activated chloride efflux through the Ca2+-gated anion channel TMEM16A, thus depolarizing the cell and opening voltage-gated calcium channels. This mechanism strongly amplified the pericyte [Ca2+]i rise and capillary constriction evoked by contractile agonists and ischemia. In a rodent stroke model, TMEM16A inhibition slowed the ischemia-evoked pericyte [Ca2+]i rise, capillary constriction, and pericyte death; reduced neutrophil stalling; and improved cerebrovascular reperfusion. Genetic analysis implicated altered TMEM16A expression in poor patient recovery from ischemic stroke. Thus, pericyte TMEM16A is a crucial regulator of cerebral capillary function and a potential therapeutic target for stroke and possibly other disorders of impaired microvascular flow, such as Alzheimer's disease and vascular dementia.
RUNX1 mutations contribute to the progression of MDS due to disruption of antitumor cellular defense: a study on patients with lower-risk MDS
Authors: Monika Kaisrlikova, Jitka Vesela, David Kundrat, Hana Votavova, Michaela Dostalova Merkerova, Zdenek Krejcik, Vladimir Divoky, Marek Jedlicka, Jan Fric, Jiri Klema, Dana Mikulenkova, Marketa Stastna Markova, Marie Lauermannova, Jolana Mertova, Jacqueline Soukupova Maaloufova, Anna Jonasova, Jaroslav Cermak, Monika Belickova
Journal: Leukemia (2022)

Abstract Patients with lower-risk myelodysplastic syndromes (LR-MDS) have a generally favorable prognosis; however, a small proportion of cases progress rapidly. This study aimed to define molecular biomarkers predictive of LR-MDS progression and to uncover cellular pathways contributing to malignant transformation. The mutational landscape was analyzed in 214 LR-MDS patients, and at least one mutation was detected in 137 patients (64%). Mutated RUNX1 was identified as the main molecular predictor of rapid progression by statistics and machine learning. To study the effect of mutated RUNX1 on pathway regulation, the expression profiles of CD34 + cells from LR-MDS patients with RUNX1 mutations were compared to those from patients without RUNX1 mutations. The data suggest that RUNX1 -unmutated LR-MDS cells are protected by DNA damage response (DDR) mechanisms and cellular senescence as an antitumor cellular barrier, while RUNX1 mutations may be one of the triggers of malignant transformation. Dysregulated DDR and cellular senescence were also observed at the functional level by detecting γH2AX expression and β-galactosidase activity. Notably, the expression profiles of RUNX1 -mutated LR-MDS resembled those of higher-risk MDS at diagnosis. This study demonstrates that incorporating molecular data improves LR-MDS risk stratification and that mutated RUNX1 is associated with a suppressed defense against LR-MDS progression.
COVID-19 Pandemic Effects on Neurodevelopment?
Authors: Ken Springer
Journal: JAMA Pediatrics (2022)

To the Editor The cohort study by Shuffrey et al1 showed that birth during the COVID-19 pandemic was associated with lower neurodevelopmental functioning at 6 months, even in the absence of maternal SARS-CoV-2 infection. However, methodological limitations prevent the data from being interpretable.