tbuckley/cabot-search huggingface dataset:
Genetic regulatory effects in response to a high-cholesterol, high-fat diet in baboons
Authors: Wenhe Lin, Jeffrey D. Wall, Ge Li, Deborah Newman, Yunqi Yang, Mark Abney, John L. VandeBerg, Michael Olivier, Yoav Gilad, Laura A. Cox
Journal: Cell Genomics (2024)

Steady-state expression quantitative trait loci (eQTLs) explain only a fraction of disease-associated loci identified through genome-wide association studies (GWASs), while eQTLs involved in gene-by-environment (GxE) interactions have rarely been characterized in humans due to experimental challenges. Using a baboon model, we found hundreds of eQTLs that emerge in adipose, liver, and muscle after prolonged exposure to high dietary fat and cholesterol. Diet-responsive eQTLs exhibit genomic localization and genic features that are distinct from steady-state eQTLs. Furthermore, the human orthologs associated with diet-responsive eQTLs are enriched for GWAS genes associated with human metabolic traits, suggesting that context-responsive eQTLs with more complex regulatory effects are likely to explain GWAS hits that do not seem to overlap with standard eQTLs. Our results highlight the complexity of genetic regulatory effects and the potential of eQTLs with disease-relevant GxE interactions in enhancing the understanding of GWAS signals for human complex disease using non-human primate models.
Foot and Ankle Care by Podiatrists and Amputations in Patients With Diabetes and Kidney Failure
Authors: Tze-Woei Tan, Bryan Caldwell, Yi Zhang, Onkar Kshirsagar, Dennis J. Cotter, Thomas W. Brewer
Journal: JAMA Network Open (2024)

Importance Patients with kidney failure have an increased risk of diabetes-related foot complications. The benefit of regular foot and ankle care in this at-risk population is unknown. Objective To investigate foot and ankle care by podiatrists and the outcomes of diabetic foot ulcers (DFUs) in patients with kidney failure. Design, Setting, and Participants This retrospective cohort study included Medicare beneficiaries with type 2 diabetes receiving dialysis who had a new DFU diagnosis. The analysis of the calendar year 2016 to 2019 data from the United States Renal Data System was performed on June 15, 2023, with subsequent updates on December 11, 2023. Exposures Foot and ankle care by podiatrists during 3 months prior to DFU diagnosis. Main Outcomes and Measures The outcomes were a composite of death and/or major amputation, as well as major amputation alone. Kaplan-Meier analysis was used to estimate 2 to 3 years of amputation-free survival. Foot and ankle care by podiatrists and the composite outcome was examined using inverse probability-weighted Cox regression, while competing risk regression models were used for the analysis of amputation alone. Results Among the 14 935 adult patients with kidney failure and a new DFU (mean [SD] age, 59.3 [12.7] years; 35.4% aged ≥65 years; 8284 men [55.4%]; Asian, 2.7%; Black/African American, 35.0%; Hispanic, 17.7%; White, 58.5%), 18.4% (n = 2736) received care by podiatrists in the 3 months before index DFU diagnosis. These patients were older, more likely to be male, and have more comorbidities than those without prior podiatrist visits. Over a mean (SD) 13.5 (12.0)-month follow-up, 70% of those with podiatric care experienced death and/or major amputation, compared with 74% in the nonpodiatric group. Survival probabilities at 36 months were 26.3% vs 22.8% ( P &amp;amp;lt; .001, unadjusted Kaplan-Meier survival analysis). In multivariate regression analysis, foot and ankle care was associated with an 11% lower likelihood of death and/or amputation (hazard ratio [HR], 0.89 95% CI, 0.84-0.93) and a 9% lower likelihood of major amputation (above or below knee) (HR, 0.91; 95% CI, 0.84-0.99) than those who did not. Conclusions and Relevance The findings of this study suggest that patients with kidney failure at risk for DFUs who receive foot and ankle care from podiatrists may be associated with a reduced likelihood of diabetes-related amputations.
Genomic and global gene expression profiling in pediatric and young adult acute leukemia with PICALM::MLLT10 Fusion
Authors: Jingqun Ma, Yen-Chun Liu, Rebecca K. Voss, Jing Ma, Ajay Palagani, Elizabeth Caldwell, Wojciech Rosikiewicz, Maria Cardenas, Scott Foy, Masayuki Umeda, Mark R. Wilkinson, Hiroto Inaba, Jeffery M. Klco, Jeffrey E. Rubnitz, Lu Wang
Journal: Leukemia (2024)
Natural History of Type 2 Diabetes in Indians: Time to Progression
Authors: K.M. Venkat Narayan, Dimple Kondal, Howard H. Chang, Deepa Mohan, Unjali P. Gujral, Ranjit Mohan Anjana, Lisa R. Staimez, Shivani A. Patel, Mohammed K. Ali, Dorairaj Prabhakaran, Nikhil Tandon, Viswanathan Mohan
Journal: Diabetes Care (2024)

To describe the natural history of diabetes in Indians.
Expert consensus on difficulty assessment of endodontic therapy
Authors: Dingming Huang, Xiaoyan Wang, Jingping Liang, Junqi Ling, Zhuan Bian, Qing Yu, Benxiang Hou, Xinmei Chen, Jiyao Li, Ling Ye, Lei Cheng, Xin Xu, Tao Hu, Hongkun Wu, Bin Guo, Qin Su, Zhi Chen, Lihong Qiu, Wenxia Chen, Xi Wei, Zhengwei Huang, Jinhua Yu, Zhengmei Lin, Qi Zhang, Deqin Yang, Jin Zhao, Shuang Pan, Jian Yang, Jiayuan Wu, Yihuai Pan, Xiaoli Xie, Shuli Deng, Xiaojing Huang, Lan Zhang, Lin Yue, Xuedong Zhou
Journal: International Journal of Oral Science (2024)

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.
Educational Mobility, Pace of Aging, and Lifespan Among Participants in the Framingham Heart Study
Authors: Gloria H. J. Graf, Allison E. Aiello, Avshalom Caspi, Meeraj Kothari, Hexuan Liu, Terrie E. Moffitt, Peter A. Muennig, Calen P. Ryan, Karen Sugden, Daniel W. Belsky
Journal: JAMA Network Open (2024)

Importance People who complete more education live longer lives with better health. New evidence suggests that these benefits operate through a slowed pace of biological aging. If so, measurements of the pace of biological aging could offer intermediate end points for studies of how interventions to promote education will affect healthy longevity. Objective To test the hypothesis that upward educational mobility is associated with a slower pace of biological aging and increased longevity. Design, Setting, and Participants This prospective cohort study analyzed data from 3 generations of participants in the Framingham Heart Study: (1) the original cohort, enrolled beginning in 1948; (2) the Offspring cohort, enrolled beginning in 1971; and (3) the Gen3 cohort, enrolled beginning in 2002. A 3-generation database was constructed to quantify intergenerational educational mobility. Mobility data were linked with blood DNA-methylation data collected from the Offspring cohort in 2005 to 2008 (n = 1652) and the Gen3 cohort in 2009 to 2011 (n = 1449). Follow-up is ongoing. Data analysis was conducted from June 2022 to November 2023 using data obtained from the National Institutes of Health database of Genotypes and Phenotypes (dbGaP). Exposure Educational mobility was measured by comparing participants’ educational outcomes with those of their parents. Main Outcomes and Measures The pace of biological aging was measured from whole-blood DNA-methylation data using the DunedinPACE epigenetic clock. For comparison purposes, the analysis was repeated using 4 other epigenetic clocks. Survival follow-up was conducted through 2019. Results This study analyzed data from 3101 participants from the Framingham Heart Study; 1652 were in the Offspring cohort (mean [SD] age, 65.57 [9.22] years; 764 [46.2%] male) and 1449 were in the Gen3 cohort (mean [SD] age, 45.38 [7.83] years; 691 [47.7%] male). Participants who were upwardly mobile in educational terms tended to have slower pace of aging in later life ( r = −0.18 [95% CI, −0.23 to −0.13]; P &amp;amp;lt; .001). This pattern of association was similar across generations and held in within-family sibling comparisons. There were 402 Offspring cohort participants who died over the follow-up period. Upward educational mobility was associated with lower mortality risk (hazard ratio, 0.89 [95% CI, 0.81 to 0.98]; P = .01). Slower pace of aging accounted for approximately half of this association. Conclusions and Relevance This cohort study’s findings support the hypothesis that interventions to promote educational attainment may slow the pace of biological aging and promote longevity. Epigenetic clocks have potential as near-term outcome measures of intervention effects on healthy aging. Experimental evidence is needed to confirm findings.
The transcription factor NF-κB orchestrates nucleosome remodeling during the primary response to Toll-like receptor 4 signaling
Authors: An-Chieh Feng, Brandon J. Thomas, Prabhat K. Purbey, Filipe Menegatti de Melo, Xin Liu, Allison E. Daly, Fei Sun, Jerry Hung-Hao Lo, Lijing Cheng, Michael F. Carey, Philip O. Scumpia, Stephen T. Smale
Journal: Immunity (2024)

Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters shapes the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. We aimed to define the identities of the transcription factors that promote TLR-induced remodeling. An analysis strategy based on ATAC-seq and single-cell ATAC-seq that enriched for genomic regions most likely to undergo remodeling revealed that the transcription factor nuclear factor κB (NF-κB) bound to all high-confidence peaks marking remodeling during the primary response to the TLR4 ligand, lipid A. Deletion of NF-κB subunits RelA and c-Rel resulted in the loss of remodeling at high-confidence ATAC-seq peaks, and CRISPR-Cas9 mutagenesis of NF-κB-binding motifs impaired remodeling. Remodeling selectivity at defined regions was conferred by collaboration with other inducible factors, including IRF3- and MAP-kinase-induced factors. Thus, NF-κB is unique among TLR4-activated transcription factors in its broad contribution to inducible nucleosome remodeling, alongside its ability to activate poised enhancers and promoters assembled into open chromatin.
HIV Preexposure Prophylaxis With Emtricitabine and Tenofovir Disoproxil Fumarate Among Cisgender Women
Authors: Jeanne Marrazzo, Li Tao, Marissa Becker, Ashley A. Leech, Allan W. Taylor, Faith Ussery, Michael Kiragu, Sushena Reza-Paul, Janet Myers, Linda-Gail Bekker, Juan Yang, Christoph Carter, Melanie de Boer, Moupali Das, Jared M. Baeten, Connie Celum
Journal: JAMA (2024)

Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when adherence is high (>4 doses/week). Real-world effectiveness and adherence with F/TDF for PrEP in cisgender women is less well characterized.
Using illness trajectories to inform person centred, advance care planning
Authors: Scott A Murray, Kirsty Boyd, Sebastien Moine, Marilyn Kendall, Stella Macpherson, Geoffrey Mitchell, Jordi Amblàs-Novellas
Journal: BMJ (2024)

The authors are general practitioners from France and Australia, a geriatrician from Catalonia, a social scientist, a patient representative, a palliative medicine specialist and medical educator, and a professor of primary palliative care from the UK.We drew on extensive qualitative research with patients and families and extended the concepts of physical, social, psychological and spiritual dimensions described in 2005 and 2017 as well as proposing a distinctive multimorbidity trajectory.We also reviewed broader patient experience research internationally, and interventions in many countries that provides guidance on palliative care throughout Europe, Australia, and America to inform this educational resource. Information and resources for patients, carers and the general publicUK public information websites about care planning, serious illness, death, dying and bereavement: NHS Inform -thinking and planning ahead (NHS Scotland) Dying Matters (England) Good Life, Good Death, Good Grief (Scotland) Marie Curie -care and support through terminal illness (UK) Macmillan Cancer Support -cancer information and support (UK) Age UK -information and advice (UK) How to live and die well: understand what might happen and plan.This short video is for everyone, explaining illness trajectories.It's for people who are well just now to think ahead.It is also for people who currently live with progressive illness.It's also for family members and carers of those who are ill, and who want to learn what can happen in the future so they can plan ahead
Exposure to Neighborhood Greenness and Hypertension Incidence in Adults: A Longitudinal Cohort Study in Taiwan
Authors: Yi Qian Zeng, Ka Chun Chong, Ly-yun Chang, Xue Liang, Li-Hao Guo, Guanghui Dong, Tony Tam, Xiang Qian Lao
Journal: Environmental Health Perspectives (2024)

There are few studies on the health effects of long-term exposure to neighborhood greenness in a longitudinal setting, especially in Asian countries with high population densities.
Updated Treatment Recommendation on Use of Cabotegravir and Rilpivirine for People With HIV From the IAS-USA Guidelines Panel
Authors: Paul E. Sax, Melanie A. Thompson, Michael S. Saag
Journal: JAMA (2024)

Rajesh T. Gandhi, MD; Roger Bedimo, MD; Jennifer F. Hoy, MBBS; Raphael J. Landovitz, MD; Davey M. Smith, MD; Ellen F. Eaton, MD; Clara Lehmann, MD; Sandra A. Springer, MD; Paul E. Sax, MD; Melanie A. Thompson, MD; Constance A. Benson, MD; Susan P. Buchbinder, MD; Carlos del Rio, MD; Joseph J. Eron Jr, MD; Huldrych F. Günthard, MD; Jean-Michel Molina, MD; Donna M. Jacobsen, BS; Michael S. Saag, MD
Air Pollution and Health—New Advances for an Old Public Health Problem
Authors: Jesse D. Berman
Journal: JAMA Network Open (2024)

Yiqun Ma, MPhil; Federica Nobile, MSc; Anne Marb, MSc; Robert Dubrow, MD, PhD; Massimo Stafoggia, PhD; Susanne Breitner, ScD; Patrick L. Kinney, ScD; Kai Chen, PhD
Short-Term Exposure to Fine Particulate Matter and Nitrogen Dioxide and Mortality in 4 Countries
Authors: Yiqun Ma, Federica Nobile, Anne Marb, Robert Dubrow, Massimo Stafoggia, Susanne Breitner, Patrick L. Kinney, Kai Chen
Journal: JAMA Network Open (2024)

Importance The association between short-term exposure to air pollution and mortality has been widely documented worldwide; however, few studies have applied causal modeling approaches to account for unmeasured confounders that vary across time and space. Objective To estimate the association between short-term changes in fine particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) concentrations and changes in daily all-cause mortality rates using a causal modeling approach. Design, Setting, and Participants This cross-sectional study used air pollution and mortality data from Jiangsu, China; California; central-southern Italy; and Germany with interactive fixed-effects models to control for both measured and unmeasured spatiotemporal confounders. A total of 8 963 352 deaths in these 4 regions from January 1, 2015, to December 31, 2019, were included in the study. Data were analyzed from June 1, 2021, to October 30, 2023. Exposure Day-to-day changes in county- or municipality-level mean PM 2.5 and NO 2 concentrations. Main Outcomes and Measures Day-to-day changes in county- or municipality-level all-cause mortality rates. Results Among the 8 963 352 deaths in the 4 study regions, a 10-μg/m 3 increase in daily PM 2.5 concentration was associated with an increase in daily all-cause deaths per 100 000 people of 0.01 (95% CI, 0.001-0.01) in Jiangsu, 0.03 (95% CI, 0.004-0.05) in California, 0.10 (95% CI, 0.07-0.14) in central-southern Italy, and 0.04 (95% CI, 0.02- 0.05) in Germany. The corresponding increases in mortality rates for a 10-μg/m 3 increase in NO 2 concentration were 0.04 (95% CI, 0.03-0.05) in Jiangsu, 0.03 (95% CI, 0.01-0.04) in California, 0.10 (95% CI, 0.05-0.15) in central-southern Italy, and 0.05 (95% CI, 0.04-0.06) in Germany. Significant effect modifications by age were observed in all regions, by sex in Germany (eg, 0.05 [95% CI, 0.03-0.06] for females in the single-pollutant model of PM 2.5 ), and by urbanicity in Jiangsu (0.07 [95% CI, 0.04-0.10] for rural counties in the 2-pollutant model of NO 2 ). Conclusions and Relevance The findings of this cross-sectional study contribute to the growing body of evidence that increases in short-term exposures to PM 2.5 and NO 2 may be associated with increases in all-cause mortality rates. The interactive fixed-effects model, which controls for unmeasured spatial and temporal confounders, including unmeasured time-varying confounders in different spatial units, can be used to estimate associations between changes in short-term exposure to air pollution and changes in health outcomes.
Shifting the Narrative of Preexposure Prophylaxis Adherence Counseling for Cisgender Women
Authors: Anandi N. Sheth, Florence Momplaisir, Julie B. Dumond
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
Authors' Reply: Prioritizing Skills for Optimal Peritoneal Dialysis Care: A Focus Beyond Specialty
Authors: Elaine Ku, Charles E. McCulloch, Timothy P. Copeland, Kirsten L. Johansen
Journal: Journal of the American Society of Nephrology (2024)

Ku, Elaine; McCulloch, Charles E.; Copeland, Timothy P.; Johansen, Kirsten L. Author Information
Eculizumab Seems to be a Life Saver Even in Shiga Toxin–Related Hemolytic–Uremic Syndrome
Authors: Jaicy Pottokaran
Journal: Journal of the American Society of Nephrology (2024)

Division of Pediatric Nephrology, Shands Hospital, University of Florida, Gainesville, Florida Correspondence: Dr. Jaicy Pottokaran, Division of Pediatric Nephrology, Shands Hospital, University of Florida, 1600 Southwest Archer Road, Second Floor, Room #214, Gainesville, FL 32608. Email: [email protected] See related reply, "Authors' Reply: Eculizumab Seems to be a Life Saver Even in Shiga Toxin–Related Hemolytic–Uremic Syndrome," on page 385, and original article, "Efficacy and Safety of Eculizumab in Pediatric Patients Affected by Shiga Toxin–Related Hemolytic and Uremic Syndrome: A Randomized, Placebo-Controlled Trial," in Vol. 34, Iss. 9, 1561–1573.
Prioritizing Skills for Optimal Peritoneal Dialysis Care: A Focus Beyond Specialty
Authors: Tuncay Sahutoglu
Journal: Journal of the American Society of Nephrology (2024)

Nephrology, Mehmet Akif Inan Training and Research Hospital, Sanliurfa, Turkey Correspondence: Dr. Tuncay Sahutoglu, Nephrology, Mehmet Akif Inan Education and Research Hospital, EsentepeMah. Ertuğrul Cad, Sanliurfa, Turkey. Email: [email protected] See related reply, "Authors' Reply: Authors' Reply: Prioritizing Skills for Optimal Peritoneal Dialysis Care: A Focus Beyond Specialty," on pages 382–383, and original article, "Peritoneal Dialysis Catheter Complications after Insertion by Surgeons, Radiologists, or Nephrologists," in Vol. 35, Iss. 1, 85–93. Published online ahead of print. Publication date available at www.jasn.org.
Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19
Authors: Aimee L. Hanson, Matthew P. Mulè, Hélène Ruffieux, Federica Mescia, Laura Bergamaschi, Victoria S. Pelly, Lorinda Turner, Prasanti Kotagiri, Berthold Göttgens, Christoph Hess, Nicholas Gleadall, John R. Bradley, James A. Nathan, Paul A. Lyons, Hal Drakesmith, Kenneth G. C. Smith
Journal: Nature Immunology (2024)

Abstract Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC. A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity. A whole-blood heme-metabolism signature, enriched in hospitalized patients at month 1–3 post onset, coincided with pronounced iron-deficient reticulocytosis. Lymphopenia and low numbers of dendritic cells persisted in those with PASC, and single-cell analysis reported iron maldistribution, suggesting monocyte iron loading and increased iron demand in proliferating lymphocytes. Thus, defects in iron homeostasis, dysregulated erythropoiesis and immune dysfunction due to COVID-19 possibly contribute to inefficient oxygen transport, inflammatory disequilibrium and persisting symptomatology, and may be therapeutically tractable.
Addressing fertility in gender-affirming care and its mental health implications: a cross-sectional study from Turkey
Authors: Deha Onar, Burçin Çolak, Betül Yıldırım, Bedriye Öncü
Journal: International Journal of Transgender Health (2024)

Background: Transgender and non-binary (TNB) people may seek gender-affirming treatments and these treatments have well-known effects on fertility.