tbuckley/cabot-search huggingface dataset:
Patients with Inflammatory Bowel Disease are at Increased Risk for Complications of Herpes Zoster
Authors: Freddy Caldera, Siddharth Singh, Emily E Zona, Oscar Ramirez Ramirez, Jonathan Inselman, Herbert Heien, Andrew P Keaveny, Mary S Hayney, Francis A Farraye
Journal: Clinical Gastroenterology and Hepatology (2024)
PCDH7-antibodies and PCDH7 immune deposits are mostly found in patients with PLA2R1- or NELL1-associated membranous nephropathy
Authors: Maya Machalitza, Hanna Debiec, Benedikt Krümpelmann, Nicoletta Ferru, Muhammed Elyesa Kilictas, Tobias B Huber, Linda Reinhard, Thorsten Wiech, Pierre Ronco, Elion Hoxha
Journal: Kidney International (2024)
GALNT3 in Ischemia-Reperfusion Injury of the Kidney
Authors: Wenwen Wu, Ying Fu, Honglin Li, Yu Xiang, Yuqing Zeng, Juan Cai, Zheng Dong
Journal: Journal of the American Society of Nephrology (2024)

Background: Damages to subcellular organelles, such as mitochondria and endoplasmic reticulum, are well-recognized in tubular cell injury and death in acute kidney injury (AKI). However, the changes and involvement of Golgi apparatus are much less known. Here, we report the regulation and role of N-acetylgalactosaminyltransferase-3 (GALNT3), a key enzyme for protein glycosylation in Golgi apparatus, in AKI. Methods: AKI was induced in mice by renal ischemia-reperfusion or cisplatin. In vitro, rat kidney proximal tubular cells were subjected to hypoxia/reoxygenation (H/R) injury. To determine the role of GALNT3, its specific inhibitor T3inh-1 was tested in mice, and the effects of GALNT3 overexpression as well as knockdown were examined in the rat renal proximal tubular cells. EGFR activation was induced by recombinant EGF or by overexpressing EGFR. Results: GALNT3 was significantly decreased in both in vivo and in vitro models of AKI induced by renal ischemia-reperfusion and cisplatin. T3Inh-1, a specific GALNT3 inhibitor, exacerbated ischemic AKI and suppressed tubular cell proliferation in mice. Moreover, knockdown of GALNT3 increased apoptosis during H/R treatment in rat renal proximal tubular cells, while overexpression of GALNT3 attenuated H/R-induced apoptosis, further supporting a protective role of GALNT3. Mechanistically, GALNT3 contributed to O-glycosylation of epidermal growth factor receptor (EGFR) and associated EGFR signalling. Activation or overexpression of EGFR suppressed the pro-apoptotic effect of GALNT3 knockdown in H/R-treated rat renal proximal tubular cells. Conclusions: GALNT3 protected kidney tubular cells in AKI at least partially through O-glycosylation of EGFR.
Firearm Experiences, Behaviors, and Norms Among Rural Adolescents
Authors: Elizabeth H. Weybright, Heather F. Terral, Ashley Hall, Gary Varrella, Alice M. Ellyson, Julia P. Schleimer, Margaret R. Kuklinski, Kimberly Dalve, Emma L. Gause, Sabrina Oesterle, Ali Rowhani-Rahbar
Journal: JAMA Network Open (2024)

Importance Rural adolescents are at high risk for firearm-related injury, yet most existing prevention efforts are informed by research conducted in urban areas. Despite the need to account for rural perspectives, few studies have investigated the unique social ecological context of firearms for rural adolescents or have directly engaged with rural adolescents to understand their views on firearm use. Objective To describe rural adolescents’ firearm behaviors and perceptions of firearm-related social norms within their communities, peer groups, and families. Design, Setting, and Participants This cross-sectional study used a convergent mixed-methods design and involved a community-based participatory research approach. Participants comprised 93 adolescents residing in rural Washington state and enrolled in a county or tribal reservation 4-H youth development program as an intermediate or senior age-level grouping (ie, aged 12-19 years). Adolescents completed a survey and participated in a semistructured focus group or interview between September 1, 2021, and September 30, 2022. Data were analyzed using descriptive and thematic analysis. Main Outcomes and Measures Individual handgun behavior and peer, family, and community perceptions of firearm-related social norms. Results The sample included 93 adolescents (mean [SD] age, 15.7 [1.7] years; 49 female participants [52.7%]). Approximately half of participants (52 [55.9%]) had carried a handgun at some point in their lives, with a mean (SD) age at first carry of 10.9 (3.1) years. Primary themes across quantitative and qualitative data focused on social norms (specifically, acceptable and unacceptable ways to engage with firearms, reasons for carrying firearms, and places to carry a firearm). Conclusions and Relevance In this cross-sectional study, rural adolescents in 4-H programs generally understood acceptable and unacceptable firearm carrying behaviors, which aligned with state laws. Findings provide context for rural adolescent behaviors such as carrying a firearm predominantly for prosocial reasons (hunting, recreation, and sport) and adult behavior such as carrying for protection of person and personal property. Understanding firearm-related social norms in rural communities holds implications for firearm injury prevention efforts, especially related to enhancing training, developing norms-based prevention approaches, and tailoring efforts to rural settings.
Cancer Incidence among Marines and Navy Personnel and Civilian Workers Exposed to Industrial Solvents in Drinking Water at US Marine Corps Base Camp Lejeune: A Cohort Study
Authors: Frank J. Bove, April Greek, Ruth Gatiba, Betsy Kohler, Recinda Sherman, Gene T. Shin, Aaron Bernstein
Journal: Environmental Health Perspectives (2024)

Drinking water at US Marine Corps Base Camp Lejeune, North Carolina, was contaminated with trichloroethylene and other industrial solvents from 1953 to 1985.
Safety of Simultaneous Vaccination With Adjuvanted Zoster Vaccine and Adjuvanted Influenza Vaccine
Authors: Kenneth E. Schmader, Emmanuel B. Walter, Kawsar R. Talaat, Wes Rountree, Marek Poniewierski, Emily Randolph, Sean X. Leng, Bettina Wunderlich, Michael M. McNeil, Oidda Museru, Karen R. Broder
Journal: JAMA Network Open (2024)

Importance Quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) and adjuvanted recombinant zoster vaccine (RZV) contain novel adjuvants. Data are limited on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of the simultaneous administration of these vaccines. Objective To compare the safety and reactogenicity after simultaneous doses of RZV and aIIV4 administration (opposite arms) with simultaneous doses of RZV with quadrivalent high-dose inactivated influenza vaccine [HD-IIV4]). Design, Setting, and Participants This randomized blinded clinical trial was conducted during the 2021-2022 and 2022-2023 influenza seasons at 2 centers in the US among community-dwelling adults aged 65 years or older. Analysis was performed on an intention-to-treat basis. Intervention Simultaneous intramuscular administration of RZV dose 1 and aIIV4 or HD-IIV4 in opposite arms after age stratification (65-69 and ≥70 years) and randomization. Main Outcomes and Measures The primary outcome was the proportions of participants with 1 or more severe solicited reactions during days 1 to 8, using a noninferiority test (10% noninferiority margin). Additional measures included serious adverse events and adverse events of clinical interest during days 1 to 43 of the study period. Results A total of 267 adults (median age, 71 years [range, 65-92 years]; 137 men [51.3%]) were randomized; 130 received simultaneous RZV and aIIV4, and 137 received simultaneous RZV and HD-IIV4. The proportion of patients reporting 1 or more severe reactions after simultaneous administration of RZV and aIIV4 (15 of 115 [11.5%]) was noninferior compared with simultaneous RZV and HD-IIV4 (17 of 119 [12.5%]) (absolute difference, −1.0% [95% CI, −8.9% to 7.1%]). There were no significant differences in the number of serious adverse events or adverse events of clinical interest between the groups. Conclusions and Relevance In this clinical trial of simultaneous doses of RZV and aIIV4 compared with simultaneous doses of RZV and HD-IIV4, overall safety findings were similar between groups. From a safety standpoint, this study supports the simultaneous administration of RZV and aIIV4 among older adults. Trial Registration ClinicalTrials.gov Identifier: NCT05007041
Pharmacologic Treatments for Dementia and the Risk of Developing Age-Related Macular Degeneration
Authors: Jingya Wang, Christina Antza, Wen Hwa Lee, Jesse Coker, Pearse A. Keane, Alastair K. Denniston, Krishnarajah Nirantharakumar, Nicola J. Adderley
Journal: JAMA Network Open (2024)

Importance Age-related macular degeneration (AMD) is the leading cause of blindness among people aged 50 years or older worldwide. There is a need for new strategies for the prevention and treatment of AMD. There is some limited evidence to suggest the possibility of a protective association of dementia medications with the development of some types of AMD, but the evidence is weak. Objective To investigate whether the dementia medications memantine and donepezil are associated with the risk of developing AMD. Design, Setting, and Participants Three population-based cohort studies were performed using data from the Clinical Practice Research Datalink GOLD and Aurum databases from May 15, 2002, to June 21, 2022. Participants included individuals with dementia (vascular dementia, nonvascular dementia, or Alzheimer disease) aged 40 years or older. Statistical analysis was carried out between February and November 2023. Exposures Exposures were dementia medications. Cohort 1 compared patients prescribed donepezil with those prescribed rivastigmine or galantamine using the new-user design. Cohort 2 compared memantine with donepezil, rivastigmine, or galantamine using the prevalent new-user design. In a sensitivity analysis, cohort 3 compared memantine with rivastigmine or galantamine only. Main Outcomes and Measures New diagnosis of AMD. Results There were 132 846 individuals (mean [SD] age, 80.4 [7.6] years; 61.8% women; mean [SD] body mass index [BMI], 25.5 [4.6]) with a diagnosis of dementia included in cohort 1, 159 419 individuals (mean [SD] age, 81.2 [7.6] years; 59.7% women; mean [SD] body mass index [BMI], 25.6 [4.7]) with a diagnosis of dementia included in cohort 2, and 92 328 individuals with a diagnosis of dementia included in cohort 3 (mean [SD] age, 80.9 [7.7] years; 58.5% women; mean [SD] body mass index [BMI], 25.5 [4.7]). The adjusted hazard ratio (HR) for donepezil compared with rivastigmine or galantamine (cohort 1) was 0.95 (95% CI, 0.67-1.35). The adjusted HR for memantine compared with donepezil, rivastigmine, or galantamine (cohort 2) was 1.03 (95% CI, 0.83-1.27). The adjusted HR for memantine vs rivastigmine or galantamine only (cohort 3) was 1.24 (95% CI, 0.83-1.86). Conclusions and Relevance This cohort study of patients with dementia found no significant associations between memantine or donepezil compared with other dementia medications and the risk of development of AMD. Further research is recommended to examine any possible pathophysiological protective action of memantine and other dementia medications against the development of AMD.
Hairy Kidneys and Sclerotic Bone Lesions
Authors: Juan Esteban Velez-Hernandez, Julia T. Geyer, Mateo Mejia Saldarriaga
Journal: JAMA Oncology (2024)

A 72-year-old man with a history of polycythemia vera (positive for JAK2 V617F) presented with several months of functional decline and weight loss. An 18 F-fluorodeoxyglucose positron emission tomography/computed tomography showed soft tissue infiltrates and sclerosis of the perirenal spaces with fluorodeoxyglucose uptake. What is your diagnosis?
Decision Support for Clinician Referral of Patients With Potential <i>BRCA1/2</i> Mutations for Genetic Counseling
Authors: Rita Kukafka, Samuel Pan, Thomas Silverman, Wendy K. Chung, Mary Beth Terry, Elaine Fleck, Richard G. Younge, Jill Dimond, Katherine D. Crew
Journal: JAMA Network Open (2024)

This secondary analysis of a randomized clinical trial reports primary care clinician outcomes of decision support tools for referral of patients with potential BRCA1/2 mutations for genetic counseling.
Collaboration for Firearm Injury Prevention—Asking Questions to Save Lives
Authors: Marian E. Betz, Megan L. Ranney
Journal: JAMA Network Open (2024)

Elizabeth H. Weybright, PhD; Heather F. Terral, PhD; Ashley Hall, PhD; Gary Varrella, PhD; Alice M. Ellyson, MS, PhD; Julia P. Schleimer, MPH; Margaret R. Kuklinski, PhD; Kimberly Dalve, PhD; Emma L. Gause, MS, MA; Sabrina Oesterle, PhD; Ali Rowhani-Rahbar, MD, MPH, PhD
Impacts of Immunotherapy on Patients With Aggressive Thyroid Carcinomas
Authors: Alfred King-yin Lam
Journal: JAMA Oncology (2024)

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Normothermic Regional Perfusion for Organ Donation in the US—The Dangers of Unregulated Adoption
Authors: Dale Gardiner, Andrew McGee
Journal: JAMA Network Open (2024)

Marty T. Sellers, MD, MPH; Jennifer L. Philip, MD; Aleah L. Brubaker, MD, PhD; Roxane L. Cauwels, MBA; Kristopher P. Croome, MD, MS; Jordan R. Hoffman, MD; Nikole A. Neidlinger, MD, MBA; Andrea M. Reynolds, BFA; Anji E. Wall, MD, PhD; John M. Edwards, RN
Racial Disparities in Receipt of Guideline-Concordant Care in Older Adults With Early Breast Cancer
Authors: Brenda S. Castillo, Taussia Boadi, Xiaoyan Han, Lawrence N. Shulman, Yehoda M. Martei
Journal: JAMA Network Open (2024)

Importance Racial disparities in receipt of guideline-concordant care (GCC) among older patients with potentially curable breast cancer are understudied. Objective To determine whether rates of GCC, time to treatment initiation, and all-cause mortality in stage I to III breast cancer differ by race among older adults. Design, Setting, and Participants This cohort study used data from the National Cancer Database and included patients aged 65 years and older with stage I to III breast cancer, diagnosed between 2010 and 2019. Data analysis was conducted between July 2022 to July 2023. Exposures Race, defined as non-Hispanic Black or non-Hispanic White. Main Outcomes and Measures The primary outcome was nonreceipt of GCC, defined using the National Comprehensive Cancer Network guidelines, and all-cause mortality. The secondary outcome was time to treatment initiation. Univariate and multivariate regression analysis were used to determine association between exposure and outcomes. Models for GCC and all-cause mortality included age, stage, receptor status, year of diagnosis, Charlson-Deyo comorbidity index, insurance, health care setting, and neighborhood-level educational attainment and median income. Results The analytic cohort included 258 531 participants (mean [SD] age, 72.5 [6.0] years), with 25 174 participants who identified as non-Hispanic Black (9.7%) and 233 357 participants who identified as non-Hispanic White (90.3%), diagnosed between 2010 and 2017. A total of 4563 non-Hispanic Black participants (18.1%) and 35 374 non-Hispanic White participants (15.2%) did not receive GCC. Non-Hispanic Black race, compared with non-Hispanic White race, was associated with increased odds of not receiving GCC in the multivariate analysis (adjusted odds ratio [aOR], 1.13; 95% CI, 1.08-1.17; P &amp;amp;lt; .001). Non-Hispanic Black race was associated with 26.1% increased risk of all-cause mortality in the univariate analysis, which decreased to 4.7%, after adjusting for GCC and clinical and sociodemographic factors (adjusted hazard ratio, 1.05; 95% CI, 1.01-1.08; P = .006). Non-Hispanic White race, compared with non-Hispanic Black race, was associated with increased odds of initiating treatment within 30 (OR, 1.65; 95% CI, 1.6-1.69), 60 (OR, 2.11; 95% CI, 2.04-2.18), and 90 (OR, 2.39; 95% CI, 2.27-2.51) days of diagnosis. Conclusions and Relevance In this cohort study, non-Hispanic Black race was associated with increased odds of not receiving GCC and less timely treatment initiation. Non-Hispanic Black race was associated with increased all-cause mortality, which was reduced after adjusting for GCC and clinical and sociodemographic factors. These findings suggest that optimizing timely receipt of GCC may represent a modifiable pathway to improving inferior survival outcomes among older non-Hispanic Black patients with breast cancer.
GDH1-catalytic glutaminolysis feedback activate EGFR/PI3K/AKT pathway and reprogram glioblastoma metabolism
Authors: Rui Yang, Guanghui Zhang, Zhen Meng, Li Wang, Yanping Li, Haibin Li, Siyuan Yan, Xiaonan Wei, Shanshan Wang, Hongjuan Cui
Journal: Neuro-Oncology (2024)

Abstract Background Glutamine is an important nutriment for cancer cell growth that provides biological sources for nucleic acid and fatty acid synthesis, but the role of glutaminolysis in signal transduction and glioblastoma (GBM) progression remains little known. Methods Knockdown and overexpression cells were obtained to explore the functional roles of GDH1 in cell proliferation, tumor formation and aerobic glycolysis. RNA-seq, Chromatin immunoprecipitation, luciferase assay and western blot were performed to verify the regulation of EGFR-AKT pathway by the glutamate dehydrogenase 1 (GDH1, also known as GLUD1) and KDM6A. Metabolite-level measurements and Seahorse Assay were performed to assess the functional role of GHD1 in reprogramming glycolysis. Results Here, we report that GDH1 catalytic glutaminolysis is essential for GBM cell line proliferation and brain tumorigenesis even in high-glucose conditions. Glutamine is metabolized through glutaminolysis to produce α-ketoglutarate (α-KG). We demonstrate that glutamine in combination with leucine activates mammalian TORC1 by enhancing glutaminolysis and α-KG production. α-KG increases the transcription of PDPK1 by reducing the suppressive histone modification H3K27me3, and then promotes the activation of PI3K/AKT/mTOR pathway. This transcriptional activation induced by α-KG requires histone demethylase KDM6A, which is a 2-oxoglutarate oxygenase that plays important roles in converting α-KG to succinate. Furthermore, we show that GDH1-catalytic glutaminolysis also increases the expression of HK2 and promotes glycolysis in high-glucose condition dependent on KDM6A-mediated demethylation of H3K27. Conclusion These findings suggest a novel function of glutaminolysis in regulation of signal transduction and metabolism reprograming, provide further evidence for unique role of glutaminolysis in GBM progression.
Fecal Immunochemical Test Positivity Threshold vs Multitarget Genetic Stool Testing for Colorectal Cancer Screening—Reply
Authors: Hermann Brenner, Teresa Seum, Michael Hoffmeister
Journal: JAMA (2024)

In Reply Our study1 adjusted the FIT cutoff to yield the same overall positivity rate as reported for the mt-sRNA test (17%) to enhance comparability of diagnostic performance of both tests. Below we address each of the 3 points made by Drs Yang and Ma.
Fentanyl, Heroin, Methamphetamine, and Cocaine Analyte Concentrations in Urine Drug Testing Specimens
Authors: Andrew S. Huhn, Penn Whitley, B. Levi Bolin, Kelly E. Dunn
Journal: JAMA Network Open (2024)

Importance The US is experiencing a protracted drug overdose crisis primarily associated with exposure to illicitly manufactured fentanyl (IMF), methamphetamine, and cocaine. Overdose risk and treatment responses may be directly affected by absolute drug exposure concentrations and drug use prevalence. Objective To quantify changes in absolute drug exposure concentrations from 2013 to 2023. Design, Setting, and Participants This cross-sectional study analyzed urine drug testing (UDT) results from urine specimens collected between January 1, 2013, and August 22, 2023, in 49 states and the District of Columbia. Urine specimens were obtained from patients aged 18 years or older who presented to substance use disorder treatment clinics. The UDT was ordered by clinicians based on medical necessity. Exposures Urine specimens were analyzed for the following drugs or metabolites (analytes tested in parentheses): fentanyl (fentanyl), heroin (6-monoacetylmorphine), cocaine (benzoylecgonine), and methamphetamine (methamphetamine) using liquid chromatography with tandem mass spectrometry. Main Outcomes and Measures Relative concentrations of fentanyl, heroin, cocaine, and methamphetamine. Creatinine-normalized drug concentration values were log-transformed prior to visualization and statistical analyses. The Mann-Kendall trend test was performed to examine trends over time. To estimate the geospatial and temporal patterns of drug concentration, a second series of models (1 for each drug) with an interaction effect for clinic location and collection year were fit. Results A total of 921 931 unique UDT samples were collected from patients (549 042 males [59.6%]; median [IQR] age, 34 [27-44] years). The adjusted fentanyl concentration in urine specimens was 38.23 (95% CI, 35.93-40.67) ng/mg creatinine in 2023 and 4.61 (95% CI, 3.59-5.91) ng/mg creatinine in 2013. The adjusted methamphetamine concentration was 3461.59 (95% CI, 3271.88-3662.30) ng/mg creatinine in 2023 and 665.27 (95% CI, 608.51-727.32) ng/mg creatinine in 2013. The adjusted cocaine concentration was 1122.23 (95% CI, 1032.41-1219.87) ng/mg creatinine in 2023 and 559.71 (95% CI, 524.69-597.06) ng/mg creatinine in 2013. The adjusted heroin concentration was 58.36 (95% CI, 48.26-70.58) ng/mg creatinine in 2023 and 146.59 (95% CI, 136.06-157.92) ng/mg creatinine in 2013. Drug concentrations varied across US Census divisions. Conclusions and Relevance This cross-sectional study found that absolute concentrations of fentanyl, methamphetamine, and cocaine in urine specimens increased from 2013 to 2023, with a decrease in heroin concentration during that period. The findings suggest that exposure to these substances, as well as the illicit drug supply, has fundamentally changed in many parts of the US, highlighting the need to reinforce surveillance initiatives and accelerate efforts to treat individuals with IMF and/or stimulant exposure.