tbuckley/cabot-search huggingface dataset:
Neuronally Derived Extracellular Vesicle α-Synuclein as a Serum Biomarker for Individuals at Risk of Developing Parkinson Disease
Authors: Shijun Yan, Cheng Jiang, Annette Janzen, Thomas R. Barber, Aline Seger, Michael Sommerauer, Jason J. Davis, Kenneth Marek, Michele T. Hu, Wolfgang H. Oertel, George K. Tofaris
Journal: JAMA Neurology (2023)

Nonmotor symptoms of Parkinson disease (PD) often predate the movement disorder by decades. Currently, there is no blood biomarker to define this prodromal phase.
Trends in Before Medically Advised Discharges for Patients With Opioid Use Disorder, 2016-2020
Authors: Ashish P. Thakrar, Margaret Lowenstein, S. Ryan Greysen, M. Kit Delgado
Journal: JAMA (2023)

This study examines discharge trends for opioid-related admissions from 2016-2020 with a focus on admissions with opioid use disorder and an injection-related infection.
Preclerkship Medical Students’ Use of Third-Party Learning Resources
Authors: Emily C. N. Lawrence, C. Jessica Dine, Jennifer R. Kogan
Journal: JAMA Network Open (2023)

Importance Undergraduate medical education increasingly relies on asynchronous, virtual learning; and medical educators have observed students engaging in self-directed learning outside of their institutional curriculum using widely available third-party resources. If medical educators better understand how students are learning, they may uncover novel opportunities to improve preclerkship education. Objective To explore how and why preclerkship medical students use third-party learning resources. Design, Setting, and Participants This qualitative study recruited second-year medical students from 7 public and private allopathic US medical schools and conducted 7 virtual focus groups (1 per institution) from September 2022 to January 2023, exploring how and why students use third-party resources. Data were iteratively analyzed in parallel with focus groups using constructivist grounded theory methodology. Data analysis was performed from October 2022 to February 2023. Results Fifty-eight second-year US medical students who had used a third-party resource at least once participated; 36 (61%) identified as women; 13 (23%) identified as Asian, 6 (11%) as Black, 30 (53%) as White, 6 (11%) as multiracial, and 4 (7%) as other; 6 (10%) identified as Hispanic, Latino, or Spanish origin, and 52 (90%) identified as non–Hispanic, Latino, or Spanish origin; 48 (83%) were aged 23 to 25 years. Participants described engaging in a cyclical process of deciding whether and how to use third-party resources. Four broad themes were identified: (1) hearing about resources, (2) selecting resources, (3) using resources, and (4) tensions and possible solutions. Participants largely heard about third-party resources from peers and turned to resources out of dissatisfaction with some aspect of their medical school curriculum. Students used resources in various ways that were user-dependent and context-dependent. Participants endorsed multiple benefits over their in-house curricula, particularly efficiency, clarity, and concision. Tensions included navigating resource drawbacks and the perception of an antagonistic relationship between medical schools and third-party resources. Participants suggested that medical schools examine the resources, recommend specific ones, integrate them into the curriculum, and subsidize their cost. Conclusions and Relevance In this qualitative study of preclerkship medical student use of third-party resources, participants perceived that the resources had numerous benefits for learning and suggested that medical schools should more formally acknowledge and integrate their use.
Incapacitated and Incarcerated—Double Barriers to Care
Authors: Alison E. Turnbull, Diana C. Bouhassira, Brendan Saloner
Journal: JAMA Internal Medicine (2023)

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 Internal Medicine 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 Internal Medicine journal
Metal Concentrations in E-Cigarette Aerosol Samples: A Comparison by Device Type and Flavor
Authors: Angela Aherrera, Joyce Jy Lin, Rui Chen, Mina Tehrani, Andrew Schultze, Aryan Borole, Stefan Tanda, Walter Goessler, Ana M. Rule
Journal: Environmental Health Perspectives (2023)

The rapid evolution of electronic cigarette (e-cigarette) products warrants surveillance of the differences in exposure across device types-modifiable devices (MODs), cartridge ("pod")-containing devices (PODs), disposable PODs (d-PODs)-and flavors of the products available on the market.
Maternal Prenatal Depressive Symptoms and Fetal Growth During the Critical Rapid Growth Stage
Authors: Lu Zhang, Ping Li, Qiaoyue Ge, Zeyuan Sun, Jiarui Cai, Chenghan Xiao, Chuan Yu, Chiara Nosarti, Jiaqiang Liao, Zhenmi Liu
Journal: JAMA Network Open (2023)

Importance Fetal growth in the critical rapid growth stage (CRGS) before delivery, approximately between 30 to 37 gestational weeks, carries significant implications for subsequent overweight, obesity, and arterial health. Previous evidence has demonstrated the association between maternal depressive symptoms and fetal growth trajectories from early to late pregnancy, but there remains limited understanding of the association of these symptoms with the longitudinal fetal growth change within the CRGS. Objective To investigate the association between maternal depressive symptoms and fetal growth during the CRGS before delivery. Design, Setting, and Participants This prospective birth cohort study was conducted from January 2018 to December 2020. Volunteer pregnant women were enrolled in their first trimester of prenatal visits. Women with severe disease before pregnancy and multiple births, fetuses with congenital anomalies, and preterm or postterm births were excluded. This multicenter study was based in 13 hospitals covering 81 counties across 12 cities in Sichuan Province, China. Follow-up visits were performed at the second trimester, the third trimester, and 24 hours after delivery. The analysis was conducted from January to May 2023. Exposures Maternal depressive symptoms, as a continuous variable, measured by the Edinburgh Postpartum Depression Scale (EPDS) at a median gestational week of 24 (range, 14 to 27) weeks of gestation. A higher score on the EPDS indicates worse depressive symptoms. Main Outcomes and Measures The main outcomes included ultrasonography-measured biparietal diameter (BPD), femur length (FL), and abdominal circumference (AC), along with calculated estimated fetal weight (EFW). These parameters were evaluated longitudinally at a median gestational week of 30 (range, 28 to 32) and 37 (range, 35 to 39) weeks. Linear mixed models were used to estimate the associations between maternal depressive symptoms and fetal growth parameters. Results A total of 2676 mother-offspring dyads were included, in which the mean (SD) age of mothers was 28.0 (4.4) years, and 1294 (48.4%) of the offspring were female. The median (IQR) maternal EPDS score was 5.0 (4.0 to 9.0). After adjustment for confounders, a significant correlation was found between a higher score of depressive symptoms in mothers and a slower rate of fetal growth across FL (β = −0.40; 95% CI, −0.58 to −0.22), AC (β = −1.97; 95% CI, −2.90 to −1.03), and EFW (β = −50.11; 95% CI, −68.46 to −31.75). These associations were stronger in female fetuses or those with better family socioeconomic conditions. Conclusions and Relevance In this prospective cohort study, maternal depressive symptoms were associated with slower fetal growth rate in the CRGS before delivery. Early screening for depressive disorders in pregnant women appears to be essential for fetal growth and later health.
Consequences of a Health System Not Knowing Which Patients Are Deceased
Authors: Neil S. Wenger, Fernando Javier Sanz Vidorreta, Michael T. Dudley, Anne M. Walling, Michael Hogarth
Journal: JAMA Internal Medicine (2024)

This quality improvement study in a California health system investigates the proportion of active patients who were deceased but not noted as such in the electronic health record (EHR), as well as encounters after death.
Decision-Making for Hospitalized Incarcerated Patients Lacking Decisional Capacity
Authors: Sarah Batbold, Jennifer D. Duke, Kirsten A. Riggan, Erin S. DeMartino
Journal: JAMA Internal Medicine (2023)

Incarcerated patients admitted to the hospital face threats to their rights to privacy and self-determination in medical decision-making. Little is known about medical decision-making processes for hospitalized incarcerated persons who lack decisional capacity.
Tumor-immune microenvironment and NRF2 associate with clinical efficacy of PD-1 blockade combined with chemotherapy in lung squamous cell carcinoma
Authors: Jianchun Duan, Yun Zhang, Ran Chen, Liang Liang, Yi Huo, Shun Lu, Jun Zhao, Chunhong Hu, Yuping Sun, Kunyu Yang, Mingwei Chen, Yan Yu, Jianming Ying, Ruiqi Huang, Xiaopeng Ma, Shiangjiin Leaw, Fan Bai, Zhirong Shen, Shangli Cai, Daming Gao, Jie Wang, Zhijie Wang
Journal: Cell Reports Medicine (2023)

The RATIONALE-307 study (ClinicalTrials.gov: NCT03594747) demonstrates prolonged progression-free survival (PFS) with first-line tislelizumab plus chemotherapy versus chemotherapy in advanced lung squamous cell carcinoma (LUSC; N = 360). Here we describe an immune-related gene expression signature (GES), composed of genes involved in both innate and adaptive immunity, that appears to differentiate tislelizumab plus chemotherapy PFS benefit versus chemotherapy. In contrast, a tislelizumab plus chemotherapy PFS benefit is observed regardless of programmed death ligand 1 (PD-L1) expression or tumor mutational burden (TMB). Genetic analysis reveals that NRF2 pathway activation is enriched in PD-L1positive and TMBhigh patients. NRF2 pathway activation is negatively associated with PFS, which affects efficacy outcomes associated with PD-L1 and TMB status, impairing their predictive potential. Mechanistic studies demonstrate that NRF2 directly mediates PD-L1 constitutive expression independent of adaptive PD-L1 regulation in LUSC. In summary, the GES is an immune signature that might identify LUSC patients likely to benefit from first-line tislelizumab plus chemotherapy.
Non-additive genetic components contribute significantly to population-wide gene expression variation
Authors: Andreas Tsouris, Gauthier Brach, Joseph Schacherer, Jing Hou
Journal: Cell Genomics (2023)

Gene expression variation, an essential step between genotype and phenotype, is collectively controlled by local (cis) and distant (trans) regulatory changes. Nevertheless, how these regulatory elements differentially influence gene expression variation remains unclear. Here, we bridge this gap by analyzing the transcriptomes of a large diallel panel consisting of 323 unique hybrids originating from genetically divergent Saccharomyces cerevisiae isolates. Our analysis across 5,087 transcript abundance traits showed that non-additive components account for 36% of the gene expression variance on average. By comparing allele-specific read counts in parent-hybrid trios, we found that trans-regulatory changes underlie the majority of gene expression variation in the population. Remarkably, most cis-regulatory variations are also exaggerated or attenuated by additional trans effects. Overall, we showed that the transcriptome is globally buffered at the genetic level mainly due to trans-regulatory variation in the population.
Dietary environmental factors shape the immune defense against Cryptosporidium infection
Authors: Muralidhara Rao Maradana, N. Bishara Marzook, Oscar E. Diaz, Tapoka Mkandawire, Nicola Laura Diny, Ying Li, Anke Liebert, Kathleen Shah, Mauro Tolaini, Martin Kváč, Brigitta Stockinger, Adam Sateriale
Journal: Cell Host & Microbe (2023)

Cryptosporidium is a leading cause of diarrheal-related deaths in children, especially in resource-poor settings. It also targets the immunocompromised, chronically infecting people living with HIV and primary immunodeficiencies. There is no vaccine or effective treatment. Although it is known from human cases and animal models that CD4+ T cells play a role in curbing Cryptosporidium, the role of CD8+ T cells remains to be defined. Using a Cryptosporidium tyzzeri mouse model, we show that gut-resident CD8+ intraepithelial lymphocytes (IELs) confer resistance to parasite growth. CD8+ IELs express and depend on the ligand-dependent transcription factor aryl hydrocarbon receptor (AHR). AHR deficiency reduces CD8+ IELs, decreases their cytotoxicity, and worsens infection. Transfer of CD8+ IELs rescues severely immunodeficient mice from death following Cryptosporidium challenge. Finally, dietary supplementation of the AHR pro-ligand indole-3-carbinol in newborn mice promotes resistance to infection. Therefore, common dietary metabolites augment the host immune response to cryptosporidiosis, protecting against disease.
A novel memory-like Tfh cell subset is precursor to effector Tfh cells in recall immune responses
Authors: Han Feng, Zixuan Zhao, Xiaohong Zhao, Xue Bai, Weiwei Fu, Liangtao Zheng, Boxi Kang, Xiaohu Wang, Zemin Zhang, Chen Dong
Journal: The Journal of Experimental Medicine (2023)

T follicular helper (Tfh) cells, essential for germinal center reactions, are not identical, with different phenotypes reported. Whether, when, and how they generate memory cells is still poorly understood. Here, through single-cell RNA-sequencing analysis of CXCR5+Bcl6+ Tfh cells generated under different conditions, we discovered, in addition to PD-1hi effector Tfh cells, a CD62L+PD1low subpopulation. CD62L-expressing Tfh cells developed independently from PD-1+ cells and not in direct contact with B cells. More importantly, CD62L+ Tfh cells expressed memory- and stemness-associated genes, and with better superior long-term survival, they readily generated PD-1hi cells in the recall response. Finally, KLF2 and IL7R, also highly expressed by CD62L+ Tfh cells, were required to regulate their development. Our work thus demonstrates a novel Tfh memory-like cell subpopulation, which may benefit our understanding of immune responses and diseases.
Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma
Authors: Santosh Kesari, Naveed Wagle, Jose A. Carrillo, Akanksha Sharma, Minhdan Nguyen, Judy Truong, Jaya M. Gill, Raffi Nersesian, Natsuko Nomura, Elnaz Rahbarlayegh, Garni Barkhoudarian, Walavan Sivakumar, Daniel F. Kelly, Howard Krauss, Matias A. Bustos, Dave S.B. Hoon, Lars Anker, Arun S. Singh, Kamalesh K. Sankhala, Tiffany M. Juarez
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma. Patients and Methods: Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers. Results: Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4–31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months–undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms. Conclusions: High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.
Oral Sodium Bicarbonate and Bone Turnover in CKD: A Secondary Analysis of the BASE Pilot Trial
Authors: Kalani L. Raphael, Ronit Katz, Brett Larive, Cynthia Kendrick, Tamara Isakova, Stuart Sprague, Myles Wolf, Dominic S. Raj, Linda F. Fried, Jennifer Gassman, Andy Hoofnagle, Alfred K. Cheung, Joachim H. Ix
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement In CKD, metabolic acidosis is commonly treated with alkali in the hope that it will improve bone health. In a post hoc analysis of the Bicarbonate Administration to Stabilize eGFR Pilot Trial, we investigated whether sodium bicarbonate affects serum levels of bone turnover markers and other hormones related to bone health in individuals with CKD who have normal to slightly reduced total CO 2 (20–28 mEq/L). Sodium bicarbonate increased serum levels of α -klotho but had no significant effect on other bone health markers, including intact fibroblast growth factor-23 (iFGF-23), intact parathyroid hormone (iPTH), and bone-specific alkaline phosphatase (B-SAP). Further study is needed to determine the effect of bicarbonate administration on clinical aspects of bone health. Background Treatment with alkali has been hypothesized to improve bone health in CKD by mitigating adverse effects of acid on bone mineral. We investigated the effect of treatment with sodium bicarbonate on bone turnover markers and other factors related to bone metabolism in CKD. Methods This is a post hoc analysis of the Bicarbonate Administration to Stabilize eGFR Pilot Trial in which 194 individuals with CKD and serum total CO 2 20–28 mEq/L were randomly assigned to placebo or one of two doses of sodium bicarbonate (0.5 or 0.8 mEq/kg lean body weight per day) for 28 weeks. The following serum measurements were performed at baseline, week 12, and week 28: B-SAP, c-telopeptide, procollagen type I intact N -terminal propeptide, iPTH, iFGF-23, soluble klotho, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and tartrate-resistant acid phosphatase 5b. The difference (sodium bicarbonate versus placebo) in mean change of each bone biomarker from baseline was determined using linear mixed models. Results One hundred sixty-eight participants submitted samples for post hoc investigations. Mean eGFR was 37±10 ml/min per 1.73 m 2 and mean total CO 2 was 24±3 mEq/L at baseline. Sodium bicarbonate induced a dose-dependent increase in soluble klotho levels compared with placebo. There was no significant effect of treatment with either dose of sodium bicarbonate on any of the other bone biomarkers, including iFGF-23, iPTH, and B-SAP. Effects on bone biomarkers were similar in those with baseline serum total CO 2 &lt;24 mEq/L compared with those with total CO 2 ≥24 mEq/L. Conclusions In this pilot trial of individuals with CKD and total CO 2 20–28 mEq/L, sodium bicarbonate treatment increased serum klotho levels but did not affect other bone health markers over 28 weeks. Clinical Trial registry name and registration number ClinicalTrials.gov, NCT02521181.
Longitudinal Sleep Patterns and Cognitive Impairment in Older Adults
Authors: Samantha A. Keil, Abigail G. Schindler, Marie X. Wang, Juan Piantino, Lisa C. Silbert, Jonathan E. Elliott, Madeleine L. Werhane, Ronald G. Thomas, Sherry Willis, Miranda M. Lim, Jeffrey J. Iliff
Journal: JAMA Network Open (2023)

Importance Sleep disturbances and clinical sleep disorders are associated with all-cause dementia and neurodegenerative conditions, but it remains unclear how longitudinal changes in sleep impact the incidence of cognitive impairment. Objective To evaluate the association of longitudinal sleep patterns with age-related changes in cognitive function in healthy older adults. Design, Setting, and Participants This cross-sectional study is a retrospective longitudinal analyses of the Seattle Longitudinal Study (SLS), which evaluated self-reported sleep duration (1993-2012) and cognitive performance (1997-2020) in older adults. Participants within the SLS were enrolled as part of a community-based cohort from the Group Health Cooperative of Puget Sound and Health Maintenance Organization of Washington between 1956 and 2020. Data analysis was performed from September 2020 to May 2023. Main Outcomes and Measures The main outcome for this study was cognitive impairment, as defined by subthreshold performance on both the Mini-Mental State Examination and the Mattis Dementia Rating Scale. Sleep duration was defined by self-report of median nightly sleep duration over the last week and was assessed longitudinally over multiple time points. Median sleep duration, sleep phenotype (short sleep, median ≤7 hours; medium sleep, median = 7 hour; long sleep, median ≥7 hours), change in sleep duration (slope), and variability in sleep duration (SD of median sleep duration, or sleep variability) were evaluated. Results Of the participants enrolled in SLS, only 1104 participants who were administered both the Health Behavior Questionnaire and the neuropsychologic battery were included for analysis in this study. A total of 826 individuals (mean [SD] age, 76.3 [11.8] years; 468 women [56.7%]; 217 apolipoprotein E ε4 allele carriers [26.3%]) had complete demographic information and were included in the study. Analysis using a Cox proportional hazard regression model (concordance, 0.76) showed that status as a short sleeper (hazard ratio, 3.67; 95% CI, 1.59-8.50) and higher sleep variability (hazard ratio, 3.06; 95% CI, 1.14-5.49) were significantly associated with the incidence of cognitive impairment. Conclusions and Relevance In this community-based longitudinal study of the association between sleep patterns and cognitive performance, the short sleep phenotype was significantly associated with impaired cognitive performance. Furthermore, high sleep variability in longitudinal sleep duration was significantly associated with the incidence of cognitive impairment, highlighting the possibility that instability in sleep duration over long periods of time may impact cognitive decline in older adults.