tbuckley/cabot-search huggingface dataset:
Physical, Sexual, and Intimate Partner Violence Among Transgender and Gender-Diverse Individuals
Authors: Kalysha Closson, Sabrina C. Boyce, Nicole Johns, David J. Inwards-Breland, Edwin Elizabeth Thomas, Anita Raj
Journal: JAMA Network Open (2024)

Importance Transgender and gender-diverse (TGD) communities experience disproportionate levels of violence, yet due to limitations in measuring TGD identity, few state-representative estimates are available. Objective To assess gender identity differences in experiences of violence among adults. Design, Setting, and Participants Cross-sectional data from the 2023 California Violence Experiences (CalVEX) survey, weighted to provide state-representative estimates, was used to assess associations between gender identity and past-year experiences of violence among adults 18 years and older. Data were analyzed from June to December 2023. Exposure Gender identity (cisgender women, cisgender men, transgender women, transgender men, and nonbinary individuals). Main Outcomes and Measures Experience of physical violence (including physical abuse and threat or use of a weapon), sexual violence (verbal sexual harassment, homophobic or transphobic slurs, cyber and physically aggressive sexual harassment, and forced sex), and intimate partner violence (IPV; emotional, physical, or sexual violence) using age-adjusted logistic regression. Results In total 3560 individuals (weighted cumulative response rate, 5%) completed the 2023 CalVEX survey, with 1978 cisgender women, 1431 cisgender men, 35 transgender women, 52 transgender men, and 64 nonbinary respondents (mean [SD] age, 47.1 [17.5] years; 635 [17%] were Asian, 839 [37%] were Hispanic, and 1159 [37%] were White). Past-year physical violence was reported by 22 transgender men (43%), 9 transgender women (24%), and 9 nonbinary respondents (14%). Past-year sexual violence was reported by 23 transgender men (42%), 11 transgender women (14%), and 31 nonbinary respondents (56%). Compared with cisgender women, transgender women and transgender men had greater risk of past-year physical violence (any form) (transgender women adjusted incidence rate ratio [AIRR], 6.7; 95% CI, 2.5-18.2; transgender men AIRR, 9.7; 95% CI, 5.3-17.7), as well as past-year IPV (any form) (transgender women AIRR, 3.2; 95% CI, 1.3-8.0; transgender men AIRR, 6.7; 95% CI, 4.0-11.3). Relative to cisgender women, transgender men (AIRR, 3.0; 95% CI, 1.7-5.1) and nonbinary respondents (AIRR, 3.3; 95% CI, 2.1-5.2) had greater risk of past-year sexual violence (any form). Conclusions and Relevance In this survey study of adults in California, results showed that TGD individuals, especially transgender men, are at higher risk of experiencing all forms of violence relative to cisgender women. Results highlight the need for gender-affirming violence prevention and intervention services as well as policies that protect TGD individuals from discriminatory violence.
The Impact of Donor Care Units—Caring Better and More Efficiently?
Authors: Carli J. Lehr, Kenneth R. McCurry
Journal: JAMA Network Open (2024)

Emily A. Vail, MD, MSc; Xingmei Wang, MS; Douglas E. Schaubel, PhD; Peter P. Reese, MD, PhD; Edward Cantu, MD; Niels D. Martin, MD; Peter L. Abt, MD; Kim M. Olthoff, MD; Meeta P. Kerlin, MD, MSCE; Jason D. Christie, MD, MSCE; Mark D. Neuman, MD, MSc
Errors in Table 1 and Figures
Journal: JAMA Network Open (2024)

Errors in Table 1 and FiguresIn the Original Investigation titled "Consumption of Olive Oil and Diet Quality and Risk of Dementia-Related Death," 1 published May 6, 2024, there were data errors in the Table 1 row for number of participants in the Health Professionals Follow-up Study, there was a typographical error in the key for panel A of Figure 1, and there were errors in the hazard ratios listed in the text next to the forest plot in panel A of Figure 2.These discrepancies did not affect the results and conclusions of this analysis.This article has been corrected.
Using a Large Language Model to Identify Adolescent Patient Portal Account Access by Guardians
Authors: April S. Liang, Shivam Vedak, Alex Dussaq, Dong-Han Yao, Keith Morse, Wui Ip, Natalie M. Pageler
Journal: JAMA Network Open (2024)

This diagnostic/prognostic study assesses the ability of a large language model (LLM) to detect guardian authorship of messages originating from adolescent patient portals.
Clinical Outcomes for <i>BRCA</i> Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation
Authors: Kerollos Nashat Wanis, Henry M. Kuerer, Susie X. Sun, Kelly K. Hunt, Alexa C. Glencer, Mediget Teshome, Anthony Lucci, Roi Weiser, Helen Johnson, Benjamin D. Smith, Angelica M. Gutierrez, Simona F. Shaitelman, Banu K. Arun
Journal: JAMA Network Open (2024)

Importance Although most women with BRCA- associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important. Objective To describe the clinical outcomes of women with BRCA -associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival. Design, Setting, and Participants This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021. Main Outcomes and Measures Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed. Results The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up. Conclusions and Relevance In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.
Modified traditional TNM staging of pyriform sinus and hypopharyngeal and laryngeal cancer based on lymph node ratio and its clinical significance: a population-based study combined with external validation
Authors: Jing Yue, Hang Cai, Guangxin Zhang, Xianping Wei, Yue Jin, Yang Sun, Xueshibojie Liu
Journal: International Journal of Surgery (2024)

Background: To evaluate the application value of a new TLNRM staging prediction model based on lymph node ratio (LNR) in patients with Pyriform Sinus and Hypopharyngeal and Laryngeal cancer (PHLC). Methods: A total of 2,257 patients with pathologically diagnosed PHLC from 2004 through 2019 were collected from the SEE database for analysis. The N staging of AJCC was replaced by LNR, and we compared the differences in patient prognosis and judgment ability between the new TLNRM staging and the 8th edition TNM staging. At the same time, data from 1,094 people in our hospital were included for external verification and validation. Results: We selected four cutoff points based on LNR and reclassified N staging into five groups (LNR1-5). Compared to the traditional TNM staging (8th edition), the new TLNRM staging showed a statistically significant 5-year OS difference. The decision curve showed that the new TLNRM staging had a higher net benefit for different decision thresholds than the traditional TNM staging system’s prediction line. The smaller AIC and BIC suggested that the new staging system had a higher sensitivity to prognosis evaluation compared to the traditional staging system. TLNRM stage III patients can benefit from radiotherapy, while TLNRM IVA and IVB patients can benefit from chemoradiotherapy. The same conclusion has been drawn from external validation data from our center. Conclusions: Compared with the traditional 8th edition AJCC staging system, the new TLNRM staging system has advantages in predicting the staging and prognosis of PHLC patients, and can independently guide postoperative chemoradiotherapy in patients.
SLC44A2 regulates vascular smooth muscle cell phenotypic switching and aortic aneurysm
Authors: Tianyu Song, Shuang Zhao, Shanshan Luo, Chuansheng Chen, Xingeng Liu, Xiaoqi Wu, Zhongxu Sun, Jiawei Cao, Ziyu Wang, Yineng Wang, Bo Yu, Zhiren Zhang, Xiaolong Du, Xiaoqiang Li, Zhijian Han, Hongshan Chen, Feng Chen, Liansheng Wang, Hong Wang, Kangyun Sun, Yi Han, Liping Xie, Yong Ji
Journal: Journal of Clinical Investigation (2024)

Aortic aneurysm is a life-threatening disease with limited interventions that is closely related to vascular smooth muscle cell (VSMC) phenotypic switching. SLC44A2, a member of the solute carrier series 44 (SLC44) family, remains undercharacterized in the context of cardiovascular diseases. Venn diagram analysis based on microarray and single-cell RNA sequencing identified SLC44A2 as a major regulator of VSMC phenotypic switching in aortic aneurysm. Screening for Slc44a2 among aortic cell lineages demonstrated its predominant location in VSMCs. Elevated levels of SLC44A2 were evident in the aorta of both patients with abdominal aortic aneurysm and angiotensin II-infused (Ang II-infused) Apoe-/- mice. In vitro, SLC44A2 silencing promoted VSMCs toward a synthetic phenotype, while SLC44A2 overexpression attenuated VSMC phenotypic switching. VSMC-specific SLC44A2-knockout mice were more susceptible to aortic aneurysm under Ang II infusion, while SLC44A2 overexpression showed protective effects. Mechanistically, SLC44A2's interaction with NRP1 and ITGB3 activates TGF-β/SMAD signaling, thereby promoting contractile gene expression. Elevated SLC44A2 in aortic aneurysm is associated with upregulated runt-related transcription factor 1 (RUNX1). Furthermore, low-dose lenalidomide (LEN; 20 mg/kg/day) suppressed aortic aneurysm progression by enhancing SLC44A2 expression. These findings reveal that the SLC44A2-NRP1-ITGB3 complex is a major regulator of VSMC phenotypic switching and provide a potential therapeutic approach (LEN) for aortic aneurysm treatment.
Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis
Authors: Noriyoshi Ogino, M. Fatima Leite, Mateus T. Guerra, Emma Kruglov, Hiromitsu Asashima, David A. Hafler, Takeshi Ito, João P. Pereira, Brandon J. Peiffer, Zhaoli Sun, Barbara E. Ehrlich, Michael H. Nathanson
Journal: Journal of Clinical Investigation (2024)

Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well. More recently, non-destructive actions of neutrophil granule proteins have been reported, such as modulation of tissue remodeling and metabolism. Here we report a completely different mechanism by which neutrophils act non-destructively, by inserting granules directly into hepatocytes. Specifically, elastase-containing granules were transferred to hepatocytes where elastase selectively degraded intracellular calcium channels to reduce cell proliferation without cytotoxicity. In response, hepatocytes increased expression of serpin E2 and A3, which inhibited elastase activity. Elastase insertion was seen in patient specimens of alcohol-associated hepatitis, and the relationship between elastase-mediated ITPR2 degradation and reduced cell proliferation was confirmed in mouse models. Moreover, neutrophils from patients with alcohol-associated hepatitis were more prone to degranulation and more potent in reducing calcium channel expression than neutrophils from healthy subjects. This non-destructive and reversible action on hepatocytes defines a previously unrecognized role for neutrophils in the transient regulation of epithelial calcium signaling mechanisms.
Synthetic DNA barcodes identify singlets in scRNA-seq datasets and evaluate doublet algorithms
Authors: Ziyang Zhang, Madeline E. Melzer, Keerthana M. Arun, Hanxiao Sun, Carl-Johan Eriksson, Itai Fabian, Sagi Shaashua, Karun Kiani, Yaara Oren, Yogesh Goyal
Journal: Cell Genomics (2024)
Oncogene induced TIM-3 ligand expression dictates susceptibility to anti-TIM-3 therapy in mice
Authors: Nana Talvard-Balland, Lukas M. Braun, Karen O. Dixon, Melissa Zwick, Helena Engel, Alina Hartmann, Sandra Duquesne, Livius Penter, Geoffroy Andrieux, Lukas Rindlisbacher, Andrea Acerbis, Jule Ehmann, Christoph Köllerer, Michela Ansuinelli, Andres Rettig, Kevin Moschallski, Petya Apostolova, Tilman Brummer, Anna L. Illert, Markus A. Schramm, Yurong Cheng, Anna Köttgen, Justus Duyster, Hans D. Menssen, Jerome Ritz, Bruce R. Blazar, Melanie Boerries, Annette Schmitt-Gräff, Nurefsan Sariipek, Peter Van Galen, Joerg M. Buescher, Nina Cabezas-Wallscheid, Heike L. Pahl, Erika L. Pearce, Robert J. Soiffer, Catherine J. Wu, Luca Vago, Burkhard Becher, Natalie Köhler, Tobias Wertheimer, Vijay K. Kuchroo, Robert Zeiser
Journal: Journal of Clinical Investigation (2024)

Leukemia relapse is a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). We tested the potential of targeting TIM-3 for improving graft-versus-leukemia (GVL) effects. We observed differential expression of TIM-3 ligands when hematopoietic stem cells overexpressed certain oncogenic-driver mutations. Anti-TIM-3 Ab-treatment improved survival of mice bearing leukemia with oncogene-induced TIM-3 ligand expression. Conversely, leukemia cells with low ligand expression were anti-TIM-3 treatment-resistant. In vitro, TIM-3 blockade or genetic deletion in CD8+ T cells (Tc) enhanced Tc activation, proliferation and IFN-γ production while enhancing GVL effects, preventing Tc exhaustion and improving Tc cytotoxicity and glycolysis in vivo. Conversely, TIM-3 deletion in myeloid cells did not affect allogeneic Tc proliferation and activation in vitro, suggesting that anti-TIM-3-treatment-mediated GVL effects are Tc-induced. In contrast to anti-PD-1 and anti-CTLA-4-treatment, anti-TIM-3-treatment did not enhance acute graft-versus-host-disease (aGVHD). TIM-3 and its ligands were frequently expressed in acute myeloid leukemia (AML) cells of patients with post-allo-HCT relapse. We deciphered the connection between oncogenic mutations found in AML and TIM-3 ligands expression and identify anti-TIM-3-treatment as a strategy to enhance GVL effects via metabolic and transcriptional Tc-reprogramming, without exacerbation of aGVHD. Our findings support clinical testing of anti-TIM-3 Abs in patients with AML relapse post-allo-HCT.
The decision to randomise specialised foundation programme places must be revised, if not reversed
Authors: Narut Pakunwanich, Jeremy Bjørndal, Alexander Demby
Journal: BMJ (2024)

The decision by statutory health education bodies to randomise specialised foundation programme places across the UK must be revised, write <b>Narut Pakunwanich</b>, <b>Jeremy Bjørndal</b>, and <b>Alexander Demby</b>
Neurobehavioral meaning of pupil size
Authors: Nikola Grujic, Rafael Polania, Denis Burdakov
Journal: Neuron (2024)

Pupil size is a widely used metric of brain state. It is one of the few signals originating from the brain that can be readily monitored with low-cost devices in basic science, clinical, and home settings. It is, therefore, important to investigate and generate well-defined theories related to specific interpretations of this metric. What exactly does it tell us about the brain? Pupils constrict in response to light and dilate during darkness, but the brain also controls pupil size irrespective of luminosity. Pupil size fluctuations resulting from ongoing "brain states" are used as a metric of arousal, but what is pupil-linked arousal and how should it be interpreted in neural, cognitive, and computational terms? Here, we discuss some recent findings related to these issues. We identify open questions and propose how to answer them through a combination of well-defined tasks, neurocomputational models, and neurophysiological probing of the interconnected loops of causes and consequences of pupil size.
Splice_sim: a nucleotide conversion-enabled RNA-seq simulation and evaluation framework
Authors: Niko Popitsch, Tobias Neumann, Arndt von Haeseler, Stefan L. Ameres
Journal: Genome biology (2024)

Abstract Nucleotide conversion RNA sequencing techniques interrogate chemical RNA modifications in cellular transcripts, resulting in mismatch-containing reads. Biases in mapping the resulting reads to reference genomes remain poorly understood. We present splice_sim, a splice-aware RNA-seq simulation and evaluation pipeline that introduces user-defined nucleotide conversions at set frequencies, creates mixture models of converted and unconverted reads, and calculates mapping accuracies per genomic annotation. By simulating nucleotide conversion RNA-seq datasets under realistic experimental conditions, including metabolic RNA labeling and RNA bisulfite sequencing, we measure mapping accuracies of state-of-the-art spliced-read mappers for mouse and human transcripts and derive strategies to prevent biases in the data interpretation.
3D Multispheroid Assembly Strategies towards Tissue Engineering and Disease Modeling
Authors: Tong Zhu, Yan Hu, Haitao Cui, Haijun Cui
Journal: Advanced Healthcare Materials (2024)

Abstract Cell spheroids (esp. organoids) as 3D culture platforms are popular models for representing cell–cell and cell–extracellular matrix (ECM) interactions, bridging the gap between 2D cell cultures and natural tissues. 3D cell models with spatially organized multiple cell types are preferred for gaining comprehensive insights into tissue pathophysiology and constructing in vitro tissues and disease models because of the complexities of natural tissues. In recent years, an assembly strategy using cell spheroids (or organoids) as living building blocks has been developed to construct complex 3D tissue models with spatial organization. Here, a comprehensive overview of recent advances in multispheroid assembly studies is provided. The different mechanisms of the multispheroid assembly techniques, i.e., automated directed assembly, noncontact remote assembly, and programmed self‐assembly, are introduced. The processing steps, advantages, and technical limitations of the existing methodologies are summarized. Applications of the multispheroid assembly strategies in disease modeling, drug screening, tissue engineering, and organogenesis are reviewed. Finally, this review concludes by emphasizing persistent issues and future perspectives, encouraging researchers to adopt multispheroid assembly techniques for generating advanced 3D cell models that better resemble real tissues.
Artificial intelligence-enhanced electrocardiography derived body mass index as a predictor of future cardiometabolic disease
Authors: Libor Pastika, Arunashis Sau, Konstantinos Patlatzoglou, Ewa Sieliwonczyk, Antônio H. Ribeiro, Kathryn A. McGurk, Sadia Khan, Danilo Mandic, William R. Scott, James S. Ware, Nicholas S. Peters, Antonio Luiz P. Ribeiro, Daniel B. Kramer, Jonathan W. Waks, Fu Siong Ng
Journal: npj Digital Medicine (2024)

Abstract The electrocardiogram (ECG) can capture obesity-related cardiac changes. Artificial intelligence-enhanced ECG (AI-ECG) can identify subclinical disease. We trained an AI-ECG model to predict body mass index (BMI) from the ECG alone. Developed from 512,950 12-lead ECGs from the Beth Israel Deaconess Medical Center (BIDMC), a secondary care cohort, and validated on UK Biobank (UKB) ( n = 42,386), the model achieved a Pearson correlation coefficient (r) of 0.65 and 0.62, and an R 2 of 0.43 and 0.39 in the BIDMC cohort and UK Biobank, respectively for AI-ECG BMI vs. measured BMI. We found delta-BMI, the difference between measured BMI and AI-ECG-predicted BMI (AI-ECG-BMI), to be a biomarker of cardiometabolic health. The top tertile of delta-BMI showed increased risk of future cardiometabolic disease (BIDMC: HR 1.15, p &lt; 0.001; UKB: HR 1.58, p &lt; 0.001) and diabetes mellitus (BIDMC: HR 1.25, p &lt; 0.001; UKB: HR 2.28, p &lt; 0.001) after adjusting for covariates including measured BMI. Significant enhancements in model fit, reclassification and improvements in discriminatory power were observed with the inclusion of delta-BMI in both cohorts. Phenotypic profiling highlighted associations between delta-BMI and cardiometabolic diseases, anthropometric measures of truncal obesity, and pericardial fat mass. Metabolic and proteomic profiling associates delta-BMI positively with valine, lipids in small HDL, syntaxin-3, and carnosine dipeptidase 1, and inversely with glutamine, glycine, colipase, and adiponectin. A genome-wide association study revealed associations with regulators of cardiovascular/metabolic traits, including SCN10A , SCN5A , EXOG and RXRG . In summary, our AI-ECG-BMI model accurately predicts BMI and introduces delta-BMI as a non-invasive biomarker for cardiometabolic risk stratification.