tbuckley/cabot-search huggingface dataset:
Risk of Incident Melanoma Among Individuals With Low-Count Monoclonal B-Cell Lymphocytosis
Authors: Bryan A. Vallejo, Ahmed Ansari, Sameer A. Parikh, Sara J. Achenbach, Kari G. Rabe, Aaron D. Norman, Janet E. Olson, Neil E. Kay, Esteban Braggio, Curtis A. Hanson, Celine M. Vachon, James R. Cerhan, Cristian L. Baum, Tait D. Shanafelt, Susan L. Slager
Journal: Journal of Clinical Oncology (2024)

PURPOSE Chronic lymphocytic leukemia (CLL)-phenotype monoclonal B-cell lymphocytosis (MBL) is a premalignant condition that is roughly 500-fold more common than CLL. It is unknown whether the two-fold increased risk of developing melanoma associated with CLL extends to individuals with MBL. METHODS Using the Mayo Clinic Biobank, we identified participants who were 40 years or older with no previous hematological malignancies, who resided in the 27 counties around Mayo Clinic, and who had available biospecimens for screening. Eight-color flow cytometry was used to screen for MBL. Individuals with MBL were classified as low-count MBL (LC-MBL) or high-count MBL on the basis of clonal B-cell percent. Incident melanomas were identified using International Classification of Diseases codes and confirmed via medical records review. Cox regression models were used to estimate hazard ratios (HRs) and 95% CI. RESULTS Of the 7,334 participants screened, 1,151 were identified with a CD5-positive MBL, of whom 1,098 had LC-MBL. After a median follow-up of 3.2 years (range, 0-13.5), 131 participants developed melanoma, of whom 36 individuals were positive for MBL. The estimated 5-year cumulative incidence of melanoma was 3.4% and 2.0% among those with and without MBL, respectively. After adjusting for age, sex, and history of previous melanoma, individuals with MBL exhibited a 1.86-fold (95% CI, 1.25 to 2.78) risk of melanoma. This elevated risk persisted when analysis was restricted to those without a history of melanoma (HR, 2.05 [95% CI, 1.30 to 3.23]). Individuals with LC-MBL had a 1.92-fold (95% CI, 1.29 to 2.87) increased risk of developing melanoma overall and a 2.74-fold increased risk (95% CI, 1.50 to 5.03) of melanoma in situ compared with those without MBL. CONCLUSION LC-MBL is associated with an approximately two-fold increased risk of melanoma overall and a 2.74-fold increased risk of melanoma in situ.
Gemcitabine, carboplatin, and Epstein Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized Phase 3 trial
Authors: H C Toh, M-H Yang, H-M Wang, C Y Hsieh, I Chitapanarux, K F Ho, R-L Hong, M K Ang, A D Colevas, E Sirachainan, C Lertbutsayanukul, G F Ho, E Nadler, A Algazi, P Lulla, L J Wirth, K Wirasorn, Y C Liu, S F Ang, S H J Low, L M Tho, H H Hasbullah, M K Brenner, W-W Wang, W S Ong, S H Tan, I Horak, C Ding, A Myo, J Samol
Journal: Annals of Oncology (2024)
Functional Status and Quality of Life in Light-Chain Amyloidosis
Authors: Olivier F Clerc, Shilpa Vijayakumar, Sarah A M Cuddy, Giada Bianchi, Jocelyn Canseco Neri, Alexandra Taylor, Dominik C Benz, Yesh Datar, Marie Foley Kijewski, Andrew J Yee, Frederick L Ruberg, Ronglih Liao, Rodney H Falk, Vaishali Sanchorawala, Sharmila Dorbala
Journal: JACC Heart Failure (2024)
Glycolysis in Peritubular Endothelial Cells and Microvascular Rarefaction in CKD
Authors: Yujie Huang, Ansheng Cong, Jinjin Li, Zhanmei Zhou, Hong Zhou, Cailing Su, Zuoyu Hu, Fan Fan Hou, Wei Cao
Journal: Journal of the American Society of Nephrology (2024)

Key Points Peritubular endothelial cells have a hypoglycolytic metabolism in CKD. Restoration of glycolysis in CKD peritubular endothelial cells by overexpressing 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase attenuates microvascular rarefaction and kidney fibrosis. Strategies targeting the metabolic defect in glycolysis in peritubular endothelial cells may be effective in the treatment of CKD. Background Peritubular endothelial cell dropout leading to microvascular rarefaction is a common manifestation of CKD. The role of metabolism reprogramming in peritubular endothelial cell loss in CKD is undetermined. Methods Single-cell sequencing and metabolic analysis were used to characterize the metabolic profile of peritubular endothelial cells from patients with CKD and from CKD mouse models. In vivo and in vitro models demonstrated metabolic reprogramming in peritubular endothelial cells in conditions of CKD and its contribution to microvascular rarefaction. Results In this study, we identified glycolysis as a top dysregulated metabolic pathway in peritubular endothelial cells from patients with CKD. Specifically, CKD peritubular endothelial cells were hypoglycolytic while displaying an antiangiogenic response with decreased proliferation and increased apoptosis. The hypoglycolytic phenotype of peritubular endothelial cells was recapitulated in CKD mouse models and in peritubular endothelial cells stimulated by hydrogen peroxide. Mechanically, oxidative stress, through activating a redox sensor kruppel-like transcription factor 9, downregulated the glycolytic activator 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase expression, thereby reprogramming peritubular endothelial cells toward a hypoglycolytic phenotype. 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase overexpression in peritubular endothelial cells restored hydrogen peroxide–induced reduction in glycolysis and cellular ATP levels and enhanced the G1/S cell cycle transition, enabling peritubular endothelial cells to improve proliferation and reduce apoptosis. Consistently, restoration of peritubular endothelial cell glycolysis in CKD mice, by overexpressing endothelial Pfkfb3, reversed the antiangiogenic response in peritubular endothelial cells and protected the kidney from microvascular rarefaction and fibrosis. By contrast, suppression of glycolysis by endothelial Pfkfb3 deletion exacerbated microvascular rarefaction and fibrosis in CKD mice. Conclusions Our study revealed a disrupted regulation of glycolysis in peritubular endothelial cells as an initiator of microvascular rarefaction in CKD. Restoration of peritubular endothelial cell glycolysis in CKD kidney improved microvascular rarefaction and ameliorated fibrotic lesions.
Mutational mechanisms in multiply relapsed pediatric acute lymphoblastic leukemia
Authors: Cédric G van der Ham, Lianne C Suurenbroek, Michelle M Kleisman, Željko Antić, Stefan H Lelieveld, Marley Yeong, Liset Westera, Edwin Sonneveld, Peter M Hoogerbrugge, Vincent H J van der Velden, Frank N van Leeuwen, Roland P Kuiper
Journal: Leukemia (2024)
Simultaneous enhancement of cellular and humoral immunity by the lymph node-targeted cholesterolized TLR7 agonist liposomes
Authors: Dandan Wan, Ziyi Bai, Yu Zhang, Li Chen, Haiying Que, Tianxia Lan, Weiqi Hong, Jiayu Huang, Cai He, Yuquan Wei, Qiang Pu, Xiawei Wei
Journal: Acta Pharmaceutica Sinica B (2024)

Toll-like receptor (TLR) agonists, as promising adjuvants and immunotherapeutic agents, have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct signaling pathways. However, their clinical application is hindered by uncontrolled systemic inflammatory reactions. Therefore, it is imperative to create a vaccine adjuvant for TLR receptors that ensures both safety and efficacy. In this study, we designed lymph node-targeted cholesterolized TLR7 agonist cationic liposomes (1V209-Cho-Lip
Revertant Mosaic Skin Punch Grafting in Recessive Dystrophic Epidermolysis Bullosa
Authors: Ahreum Song, Gue-Ho Hwang, Song-Ee Kim, Mi Ryung Roh, Sung-Ah Hong, Sangsu Bae, Sang Eun Lee
Journal: JAMA Dermatology (2024)

This case report describes a patient with severe generalized recessive dystrophic epidermolysis bullosa who presented with an unhealed ulcer that had persisted for the past 3 years.
Low-Dose Metformin and Profibrotic Signature in Central Centrifugal Cicatricial Alopecia
Authors: Aaron Bao, Aasheen Qadri, Aditi Gadre, Elizabeth Will, Dina Collins, Rexford Ahima, Lindsey A. Bordone, Crystal Aguh
Journal: JAMA Dermatology (2024)

Importance Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia predominantly affecting Black female individuals. Current conventional treatments target inflammation but not the underlying fibrotic processes, often leading to permanent hair loss. Objective To investigate the associations of low-dose oral metformin, an antidiabetic medication with antifibrotic properties, with clinical symptoms and scalp gene expression patterns in patients with CCCA. Design, Setting, and Participants This retrospective clinical case series and transcriptomic analysis included patients treated at a single tertiary academic medical center between January 2023 and March 2024. All patients had biopsy-confirmed CCCA refractory to standard treatments. Transcriptomic analysis was performed on patients with previously banked, paired scalp biopsies before and after treatment with adjuvant metformin for at least 6 weeks. Exposure Extended-release metformin, 500 mg, once daily was added to participants’ baseline CCCA treatment regimens. Main Outcomes and Measures Clinical assessments included pruritus, inflammation, scalp resistance, and hair regrowth. Gene expression profiling via bulk RNA sequencing analysis evaluated differential gene expression and pathway enrichment. Results A total of 12 Black female participants were included in the study, and transcriptomic analysis was performed in 4 participants. After at least 6 months of metformin treatment, 9 participants experienced improvement in disease, including scalp pain, inflammation, and/or pruritus, and 6 demonstrated clinical evidence of hair regrowth. The addition of metformin led to reversal of many prominent gene pathways previously identified in CCCA. Transcriptomic analysis revealed upregulation of pathways and genes (keratin-associated proteins [KRTAPs]) involved in keratinization, epidermis development, and the hair cycle (absolute log 2 -fold change &amp;amp;gt; 4), with concomitant downregulation of fibrosis-related pathways and genes (eg, MMP7 , COL6A1 ) (fold change &amp;amp;gt;1.5; all false discovery rate &amp;amp;lt;.05). Gene set analysis showed reduced expression of helper T cell 17 and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and KRTAPs after metformin treatment. Conclusions and Relevance In this case series of patients with treatment-refractory CCCA, low-dose oral metformin was associated with symptomatic improvement and dual modulation of gene expression, stimulating hair growth pathways while suppressing fibrosis and inflammation markers. These findings provide a rationale for future clinical trials studying metformin as a targeted therapy for CCCA and other cicatricial alopecias.
Sudden Hemodynamic Deterioration of a 75-Year-Old Woman With Progressive Jaw Pain
Authors: Sven L. Van Laer, Pieterjan Van Rijckeghem, Vincent F. M. Segers
Journal: JAMA Cardiology (2024)

This case report describes a diagnosis of left ventricular anterior free-wall rupture in a patient given anticoagulant treatment for subacute myocardial infarction.
Low-molecular-weight estrogenic phytoprotein suppresses osteoporosis development through positive modulation of skeletal estrogen receptors
Authors: John Akrofi Kubi, Augustine Suurinobah Brah, Kenneth Man Chee Cheung, Andy Chun Hang Chen, Yin Lau Lee, Kai-Fai Lee, Wei Qiao, Yibin Feng, Kelvin Wai Kwok Yeung
Journal: Bioactive Materials (2024)
Growth Rate and Outcomes in Locally Recurrent Extremity and Truncal Soft Tissue Sarcoma
Authors: George Z. Li, Kenneth Seier, Li-Xuan Qin, Murray Brennan, Carol D. Morris, Aimee M. Crago, Samuel Singer
Journal: JAMA Network Open (2024)

Importance Improved prognostic tools are needed for patients with locally recurrent extremity or truncal soft tissue sarcoma (STS). Objective To examine the association between average local recurrence (LR) growth rate and outcomes following resection of locally recurrent extremity or truncal STS. Design, Setting, and Participants This retrospective cohort study used a prospectively maintained database from a single high-volume tertiary sarcoma referral center in the US to identify patients 16 years of age or older who underwent repeat resection of a locally recurrent extremity or truncal STS between July 1, 1982, and December 31, 2021. Patients with atypical lipomatous tumors, desmoid tumors, dermatofibrosarcoma protuberans, angiosarcomas, and prior or synchronous distant recurrence were excluded. Data were analyzed from November 1, 2022, to June 17, 2024. Exposure Average LR growth rate, defined as the sum of recurrent tumor maximal diameters divided by the disease-free interval after index operation. Main Outcomes and Measures The primary outcomes were cumulative incidences of disease-specific death (DSD), with death from other causes as a competing risk, and second LR, with death from any cause as a competing risk. Results The study cohort included 253 patients (median [IQR] age, 64 [51-73] years; 140 [55.3%] male). The 5-year cumulative incidence of DSD after repeat resection was 29%. Multivariable analysis indicated that LR growth rate (hazard ratio [HR], 1.12 [95% CI, 1.08-1.18]; P &amp;amp;lt; .001), younger age (HR, 0.98 [95% CI, 0.97-0.99]; P = .002), R1 or R2 margins (HR, 1.71 [95% CI, 1.03-2.84]; P = .04), high LR grade (HR, 2.90 [95% CI, 1.17-7.20]; P = .02), and multifocality (HR, 2.92 [95% CI, 1.70-5.00]; P &amp;amp;lt; .001) were independently associated with higher incidence of DSD. Using the minimum P value method, the optimal cutoff for growth rate was found to be 0.68 cm/mo. Patients with values above this cutoff had higher 5-year incidences of DSD following repeat resection (63% vs 19%; permutation test P &amp;amp;lt; .001) and higher amputation rates (19% vs 7%; P = .008). Only R1 margins were independently associated with higher incidence of second LR (HR, 1.81 [95% CI, 1.19-2.78]; P = .006). Conclusions and Relevance In this cohort study of patients undergoing resection of a locally recurrent extremity or truncal STS, LR growth rate was independently associated with DSD. These findings suggest that patients with growth rates higher than 0.68 cm/mo who undergo LR resection may have high disease-specific mortality and amputation rates and should be considered for perioperative systemic therapy.
Trends in Body Mass Index Among Individuals With Neurodevelopmental Disorders
Authors: Miguel Garcia-Argibay, Sebastian Lundström, Samuele Cortese, Henrik Larsson
Journal: JAMA Network Open (2024)

Importance Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are increasingly common. Individuals with NDDs have heightened obesity risks, but long-term data on body mass index (BMI) trends over time in this population are lacking. Objective To assess secular BMI changes from 2004 to 2020 among children with NDDs compared with those without NDDs. Design, Setting, and Participants This repeated cross-sectional study used data from the Child and Adolescent Twin Study in Sweden. Children born between January 1, 1992, and December 31, 2010, were screened for neurodevelopmental symptoms using the Autism-Tics, ADHD, and Other Comorbidities inventory between July 2004 and April 2020 when they were 9 or 12 years of age. Data analysis was conducted between September 27, 2023, and January 30, 2024. Main Outcomes and Measures BMI percentiles (15th, 50th, and 85th) were modeled using quantile regression and compared between youths with and without NDDs. Secular changes in BMI percentiles over time spanning 2004 to 2020 were evaluated and stratified by NDD subtype. Results The cohort included 24 969 Swedish twins (12 681 [51%] boys) born between 1992 and 2010, with mean (SD) age of 9 (0.6) years. Of these, 1103 (4%) screened positive for 1 or more NDDs, including ADHD, ASD, and/or learning disability. Results indicated that at the 85th BMI percentile, there was a greater increase in BMI from 2004 to 2020 among youths with NDDs compared with those without NDDs (β for interaction [β int ] between NDD status and time, 1.67; 95% CI, 0.39-2.90). The greatest divergence was seen for ASD (β int , 2.12; 95% CI, 1.26-3.70) and learning disability (β int , 1.92; 95% CI, 0.65-3.82). Within the latest cohort (2016-2020), the 85th BMI percentile was 1.99 (95% CI, 1.08-2.89) points higher among children with NDDs compared with those without NDDs. Conclusions and Relevance In this repeated cross-sectional study, at the higher end of the BMI distribution, children with NDDs had significantly greater increases in BMI compared with peers without NDDs over a 16-year period, highlighting an increasing risk of overweight over time in youths with NDDs compared with those without NDDs. Targeted obesity prevention efforts for this high-risk population are needed.
RSV Vaccine Effectiveness Against Hospitalization Among US Adults 60 Years and Older
Authors: Diya Surie, Wesley H. Self, Yuwei Zhu, Katharine A. Yuengling, Cassandra A. Johnson, Carlos G. Grijalva, Fatimah S. Dawood, Manjusha Gaglani, Shekhar Ghamande, Tresa McNeal, Cristie Columbus, Robert L. Gottlieb, Jay S. Steingrub, Jennifer DeCuir, Meredith L. McMorrow, Sascha Ellington, Nathaniel M. Lewis, Abhijit Duggal, Laurence W. Busse, William S. Bender, Matthew E. Prekker, Anne Frosch, Ithan D. Peltan, Samuel M. Brown, David N. Hager, Michelle N. Gong, Amira Mohamed, Akram Khan, Catherine L. Hough, Jennifer G. Wilson, Jarrod M. Mosier, Nida Qadir, Steven Y. Chang, Adit A. Ginde, Nicholas M. Mohr, Anne Zepeski, Christopher Mallow, Adam S. Lauring, Emily T. Martin, Aleda M. Leis, Estelle S. Harris, Nicholas J. Johnson, Vasisht Srinivasan, H. Keipp Talbot, Natasha Halasa, James D. Chappell, Kelsey N. Womack, Jillian P. Rhoads, Adrienne Baughman, Sydney A. Swan, Todd W. Rice, Jonathan D. Casey, Paul W. Blair, Kevin W. Gibbs, Jennie H. Kwon, Bijal Parikh, Ivana A. Vaughn, Mayur Ramesh, Basmah Safdar
Journal: JAMA (2024)

This study evaluates the effectiveness of the respiratory syncytial virus vaccine against hospitalization for acute respiratory illness among US adults aged 60 years and older.
Bringing Imaging Biomarkers Into Clinical Reality in Psychiatry
Authors: Amit Etkin, Daniel H. Mathalon
Journal: JAMA Psychiatry (2024)

Importance Advancing precision psychiatry, where treatments are based on an individual’s biology rather than solely their clinical presentation, requires attention to several key attributes for any candidate biomarker. These include test-retest reliability, sensitivity to relevant neurophysiology, cost-effectiveness, and scalability. Unfortunately, these issues have not been systematically addressed by biomarker development efforts that use common neuroimaging tools like magnetic resonance imaging (MRI) and electroencephalography (EEG). Here, the critical barriers that neuroimaging methods will need to overcome to achieve clinical relevance in the near to intermediate term are examined. Observations Reliability is often overlooked, which together with sensitivity to key aspects of neurophysiology and replicated predictive utility, favors EEG-based methods. The principal barrier for EEG has been the lack of large-scale data collection among multisite psychiatric consortia. By contrast, despite its high reliability, structural MRI has not demonstrated clinical utility in psychiatry, which may be due to its limited sensitivity to psychiatry-relevant neurophysiology. Given the prevalence of structural MRIs, establishment of a compelling clinical use case remains its principal barrier. By contrast, low reliability and difficulty in standardizing collection are the principal barriers for functional MRI, along with the need for demonstration that its superior spatial resolution over EEG and ability to directly image subcortical regions in fact provide unique clinical value. Often missing, moreover, is consideration of how these various scientific issues can be balanced against practical economic realities of psychiatric health care delivery today, for which embedding economic modeling into biomarker development efforts may help direct research efforts. Conclusions and Relevance EEG seems most ripe for near- to intermediate-term clinical impact, especially considering its scalability and cost-effectiveness. Recent efforts to broaden its collection, as well as development of low-cost turnkey systems, suggest a promising pathway by which neuroimaging can impact clinical care. Continued MRI research focused on its key barriers may hold promise for longer-horizon utility.
Deaths Related to Domestic Violence in Washington State
Authors: Julie M. Kafka, Avanti Adhia, David D. Martin, Ayah Mustafa, Ali Rowhani-Rahbar, Frederick P. Rivara
Journal: JAMA Network Open (2024)

Importance Domestic violence (DV; including intimate partner and family violence) is associated with heightened lethality risks, yet limited research has comprehensively assessed the connection between DV and fatal violence considering both homicides and suicides. Understanding the fatal consequences of DV can point to missed opportunities to support individuals and their families. Objective To assess the proportion of violent deaths that were connected to DV and describe contacts with the legal system or social services prior to each DV-related fatality. Design, Setting, and Participants This cross-sectional study used quantitative and qualitative data from the National Violent Death Reporting System (NVDRS) for all individuals who died by homicide or suicide in Washington from January 1, 2015, to December 31, 2020. Analyses were conducted from August 1, 2022, to September 30, 2023. Main Outcomes and Measures A multipronged approach was used to assess DV history using existing NVDRS variables, leveraging data from prior review of NVDRS death narratives, applying a validated natural language processing tool, and linking related deaths. Domestic violence was recorded as yes or no, but the decedent’s role in the abusive relationship (ie, experiencing or enacting DV) could not be differentiated. To describe system involvement prior to each death, keyword searching and hand review of NVDRS death narratives were used. Results A total of 7352 intentional violent deaths (1192 homicides [16.2%]; 6160 suicides [83.8%]) with known circumstances were recorded in Washington during the study period. Of these, 948 deaths (12.9%) were connected to DV (624 [65.8%] among males; mean [SD] age at death, 45.3 [19.2] years), including 588 suicides (62.0%) and 360 homicides (38.0%). For 420 DV-related deaths (44.3%), there was evidence to suggest that the person who died or their intimate partner(s), family, or cohabitants had prior contacts with the legal system or social services. Specifically, 318 records (33.5%) mentioned prior contacts with law enforcement or the criminal legal system (eg, prior 9-1-1 calls, criminal convictions), and 225 (23.7%) described engagement with social services or the civil legal system (eg, civil protection order, divorce, or child custody problems). Conclusions and Relevance In this cross-sectional study, 12.9% of violent deaths in Washington were connected to DV. The findings suggest that more resources are needed to support law enforcement, court professionals, and social services specialists to proactively identify and refer families to wraparound supports before the situation can escalate to a fatality.
Telemedicine for Initiation of Alcohol Use Disorder Medications
Authors: Haiden A. Huskamp, Lori Uscher-Pines, Pushpa Raja, Sharon-Lise T. Normand, Ateev Mehrotra, Alisa B. Busch
Journal: JAMA Network Open (2024)

This case-control study examines the initiation of treatment with medications for alcohol use disorder (MAUD) among US adults and compares the characteristics of adults who initiate MAUD treatment via telemedicine vs in-person care.