tbuckley/cabot-search huggingface dataset:
Large language models to identify social determinants of health in electronic health records
Authors: Marco Guevara, Shan Chen, Spencer Thomas, Tafadzwa L. Chaunzwa, Idalid Franco, Benjamin H. Kann, Shalini Moningi, Jack M. Qian, Madeleine Goldstein, Susan Harper, Hugo J. W. L. Aerts, Paul J. Catalano, Guergana K. Savova, Raymond H. Mak, Danielle S. Bitterman
Journal: npj Digital Medicine (2024)

Abstract Social determinants of health (SDoH) play a critical role in patient outcomes, yet their documentation is often missing or incomplete in the structured data of electronic health records (EHRs). Large language models (LLMs) could enable high-throughput extraction of SDoH from the EHR to support research and clinical care. However, class imbalance and data limitations present challenges for this sparsely documented yet critical information. Here, we investigated the optimal methods for using LLMs to extract six SDoH categories from narrative text in the EHR: employment, housing, transportation, parental status, relationship, and social support. The best-performing models were fine-tuned Flan-T5 XL for any SDoH mentions (macro-F1 0.71), and Flan-T5 XXL for adverse SDoH mentions (macro-F1 0.70). Adding LLM-generated synthetic data to training varied across models and architecture, but improved the performance of smaller Flan-T5 models (delta F1 + 0.12 to +0.23). Our best-fine-tuned models outperformed zero- and few-shot performance of ChatGPT-family models in the zero- and few-shot setting, except GPT4 with 10-shot prompting for adverse SDoH. Fine-tuned models were less likely than ChatGPT to change their prediction when race/ethnicity and gender descriptors were added to the text, suggesting less algorithmic bias ( p &lt; 0.05). Our models identified 93.8% of patients with adverse SDoH, while ICD-10 codes captured 2.0%. These results demonstrate the potential of LLMs in improving real-world evidence on SDoH and assisting in identifying patients who could benefit from resource support.
Abstract A025: FANCI regulates Fanconi anemia pathway and counteracts the effects of DNA damaging chemotherapy in prostate cancer
Authors: Heidi Kaljunen, Sinja Taavitsainen, Roosa Kaarijärvi, Eerika Takala, Ville Paakinaho, Matti Nykter, G. Steven Bova, Kirsi Ketola
Journal: Cancer Research (2024)

Abstract Prostate cancer is one of the leading causes of death among men worldwide and thus research on the genetic factors enabling the formation of treatment resistant cancer cells is crucial for improving patient outcomes. Here, we report a cell-line specific dependence on FANCI and related signaling pathways to counteract effects of DNA damaging chemotherapy in prostate cancer. Our results reveal that FANCI depletion results in significant downregulation of Fanconi anemia (FA) pathway members in prostate cancer cells indicating that FANCI is an important regulator of FA pathway. Furthermore, we found that FANCI silencing reduces proliferation in p53-expressing prostate cancer cells. This extends the evidence that inactivation of FANCI may convert cancer cells from a resistant to an eradicable state under the stress of DNA-damaging chemotherapy. Our results also indicate that high expression of FA pathway genes correlates with poorer survival in prostate cancer patients. Moreover, genomic alterations of FA pathway members are prevalent in prostate adenocarcinoma patients; mutation and copy number information for the FA pathway genes in seven patient cohorts (N = 1732 total tumor samples) reveals that 1025 (59.2%) tumor samples have an alteration in at least one of the FA pathway genes, suggesting that genomic alteration of the pathway is a prominent feature in patients with the disease. Citation Format: Heidi Kaljunen, Sinja Taavitsainen, Roosa Kaarijärvi, Eerika Takala, Ville Paakinaho, Matti Nykter, G. Steven Bova, Kirsi Ketola. FANCI regulates Fanconi anemia pathway and counteracts the effects of DNA damaging chemotherapy in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A025.
Lack of leisure time physical activity and variations in cardiovascular mortality across US communities: a comprehensive county-level analysis (2011–2019)
Authors: Shady Abohashem, Khurram Nasir, Malak Munir, Ahmed Sayed, Wesam Aldosoky, Taimur Abbasi, Erin D Michos, Martha Gulati, Jamal S Rana
Journal: British Journal of Sports Medicine (2024)

To investigate the associations between county-level proportions of adults not engaging in leisure-time physical activity (no LTPA) and age-adjusted cardiovascular mortality (AACVM) rates in the overall US population and across demographics.
Endoscopic submucosal dissection for a large cecal adenoma covering an appendiceal orifice after appendectomy
Authors: Yuya Asada, Takashi Kanesaka, Tomoki Michida, Hidetoshi Satomi, Keiichiro Honma, Ryu Ishihara
Journal: Endoscopy (2024)

Endoscopic submucosal dissection (ESD) is recommended for colorectal tumors that cannot be completely removed by snare-based techniques. Endoscopic resection for appendiceal orifice lesions (Toyonaga's type 3: lesion entirely covers the orifice) is technically challenging because the appendiceal portion cannot be incised accurately [1]. Such lesions can be endoscopically removed if the patient has undergone an appendectomy, but submucosal fibrosis is a potential issue. Several reports have shown that ESD using a traction device or underwater strategies are useful for such lesions [2] [3] [4]. We demonstrate ESD for a lesion using the water pressure method ([Video 1]), which is a technique that uses the waterjet function of an endoscope to secure the working space [5].
Abstract B021: Assessing replication stress as an actionable therapeutic opportunity in chordoma
Authors: Nindo Punturi, Wendy Leung, Joan Levy, Lee Zou, Gregory M. Cote, Dan M. Freed
Journal: Cancer Research (2024)

Abstract Chordoma is a rare bone cancer with a high rate of disease recurrence and no approved systemic therapies. Tumor profiling and functional genomics studies suggest a significant number of chordomas are characterized by molecular alterations associated with increased replication stress, and a dependence on replication stress response pathways. We confirm here in preclinical models that chordomas exhibit a replication stress phenotype, which creates an actionable therapeutic vulnerability exploitable by induction of replication stress and/or inhibition of the ATR-dependent replication stress response. A panel of chordoma cell lines was treated with gemcitabine or the ATR inhibitor (ATRi) elimusertib (BAY 1895344). In a subset of cell lines, gemcitabine or elimusertib demonstrated low-nanomolar EC50 values. Upon treatment with the ATRi ceralasertib (AZD6738), DNA fiber assays revealed a mild decrease in replication fork speed and a significant increase in fork asymmetry in cells sensitive to ATR inhibition, suggesting possible fork stalling or collapse. Alkaline and neutral comet assays were performed to determine the presence of genome-wide ssDNA and/or dsDNA breaks, respectively, with orthogonal evaluation of H2A.X activation during S-phase to assess DNA strand integrity after ATR and DNA synthesis inhibition. In a panel of chordoma PDX models, striking differential sensitivity to ATR inhibition was observed. In sensitive models, elimusertib (50 mg/kg, po, bidx3) promoted 85-90% tumor growth inhibition, in contrast to resistant models, where elimusertib treatment had no effect on tumor growth. PDX models sensitive to ATR inhibition were also highly sensitive to gemcitabine, further suggesting gemcitabine induces an ATR-dependent replication stress response in chordoma models. Indeed, combining gemcitabine with ATRi revealed exceptional synergy in chordoma cell lines. Collectively, our data indicate that a subset of chordomas are characterized by intrinsic replication stress that can be therapeutically exploited through the synergistic activity of gemcitabine and ATRi. Citation Format: Nindo Punturi, Wendy Leung, Joan Levy, Lee Zou, Gregory M. Cote, Dan M. Freed. Assessing replication stress as an actionable therapeutic opportunity in chordoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B021.
Research and application of deep learning-based sleep staging: Data, modeling, validation, and clinical practice
Authors: Huijun Yue, Zhuqi Chen, Wenbin Guo, Lin Sun, Yidan Dai, Yiming Wang, Wenjun Ma, Xiaomao Fan, Weiping Wen, Wenbin Lei
Journal: Sleep Medicine Reviews (2024)

Over the past few decades, researchers have attempted to simplify and accelerate the process of sleep stage classification through various approaches; however, only a few such approaches have gained widespread acceptance. Artificial intelligence technology, particularly deep learning, is promising for earning the trust of the sleep medicine community in automated sleep-staging systems, thus facilitating its application in clinical practice and integration into daily life. We aimed to comprehensively review the latest methods that are applying deep learning for enhancing sleep staging efficiency and accuracy. Starting from the requisite "data" for constructing deep learning algorithms, we elucidated the current landscape of this domain and summarized the fundamental modeling process, encompassing signal selection, data pre-processing, model architecture, classification tasks, and performance metrics. Furthermore, we reviewed the applications of automated sleep staging in scenarios such as sleep-disorder screening, diagnostic procedures, and health monitoring and management. Finally, we conducted an in-depth analysis and discussion of the challenges and future in intelligent sleep staging, particularly focusing on large-scale sleep datasets, interdisciplinary collaborations, and human-computer interactions.
Genetically modified ZIKA virus as a microRNA-sensitive oncolytic virus against central nervous system tumors
Authors: Gabriela Machado Novaes, Caroline Lima, Carla Longo, Pedro Henrique Machado, Thais Peron Silva, Giovanna Gonçalves de Oliveira Olberg, Diego Grando Módolo, Márcia Cristina Leite Pereira, Tiago Goss Santos, Mayana Zatz, David Lagares, Marcelo de Franco, Paulo Lee Ho, Harry Bulstrode, Oswaldo Keith Okamoto, Carolini Kaid
Journal: Molecular Therapy (2024)

Here we introduce a first-in-class microRNA-sensitive oncolytic Zika virus (ZIKV) for virotherapy application against central nervous system (CNS) tumors. The described methodology produced two synthetic modified ZIKV strains that are safe in normal cells, including neural stem cells, while preserving brain tropism and oncolytic effects in tumor cells. The microRNA-sensitive ZIKV introduces genetic modifications in two different virus sites: first, in the established 3′UTR region, and secondly, in the ZIKV protein coding sequence, demonstrating for the first time that the miRNA inhibition systems can be functional outside the UTR RNA sites. The total tumor remission in mice bearing human CNS tumors, including metastatic tumor growth, after intraventricular and systemic modified ZIKV administration, confirms the promise of this virotherapy as a novel agent against brain tumors—highly deadly diseases in urgent need of effective advanced therapies.Graphical abstract
Multimodal digital phenotyping of diet, physical activity, and glycemia in Hispanic/Latino adults with or at risk of type 2 diabetes
Authors: Amruta Pai, Rony Santiago, Namino Glantz, Wendy Bevier, Souptik Barua, Ashutosh Sabharwal, David Kerr
Journal: npj Digital Medicine (2024)

Abstract Digital phenotyping refers to characterizing human bio-behavior through wearables, personal devices, and digital health technologies. Digital phenotyping in populations facing a disproportionate burden of type 2 diabetes (T2D) and health disparities continues to lag compared to other populations. Here, we report our study demonstrating the application of multimodal digital phenotyping, i.e., the simultaneous use of CGM, physical activity monitors, and meal tracking in Hispanic/Latino individuals with or at risk of T2D. For 14 days, 36 Hispanic/Latino adults (28 female, 14 with non-insulin treated T2D) wore a continuous glucose monitor (CGM) and a physical activity monitor (Actigraph) while simultaneously logging meals using the MyFitnessPal app. We model meal events and daily digital biomarkers representing diet, physical activity choices, and corresponding glycemic response. We develop a digital biomarker for meal events that differentiates meal events into normal and elevated categories. We examine the contribution of daily digital biomarkers of elevated meal event count and step count on daily time-in-range 54-140 mg/dL (TIR 54–140 ) and average glucose. After adjusting for step count, a change in elevated meal event count from zero to two decreases TIR 54–140 by 4.0% ( p = 0.003). An increase in 1000 steps in post-meal step count also reduces the meal event glucose response by 641 min mg/dL ( p = 0.0006) and reduces the odds of an elevated meal event by 55% ( p &lt; 0.0001). The proposed meal event digital biomarkers may provide an opportunity for non-pharmacologic interventions for Hispanic/Latino adults facing a disproportionate burden of T2D.
Minireview: Understanding and targeting inflammatory, hemodynamic and injury markers for cardiorenal protection in type 1 diabetes
Authors: Luxcia Kugathasan, Vikas S. Sridhar, Kalie L. Tommerdahl, Cheng Xu, Petter Bjornstad, Andrew Advani, David Z.I. Cherney
Journal: Metabolism (2024)

The coexistence of cardiovascular disease (CVD) and diabetic kidney disease (DKD) is common in people with type 1 diabetes (T1D) and is strongly associated with an increased risk of morbidity and mortality. Hence, it is imperative to explore robust tools that can accurately reflect the development and progression of cardiorenal complications. Several cardiovascular and kidney biomarkers have been identified to detect at-risk individuals with T1D. The primary aim of this review is to highlight biomarkers of injury, inflammation, or renal hemodynamic changes that may influence T1D susceptibility to CVD and DKD. We will also examine the impact of approved pharmacotherapies for type 2 diabetes, including renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on candidate biomarkers for cardiorenal complications in people with T1D and discuss how these changes may potentially mediate kidney and cardiovascular protection. Identifying predictive and prognostic biomarkers for DKD and CVD may highlight potential drug targets to attenuate cardiorenal disease progression, implement novel risk stratification measures in clinical trials, and improve the assessment, diagnosis, and treatment of at-risk individuals with T1D.
Transperineal Versus Transrectal Magnetic Resonance Imaging–targeted and Systematic Prostate Biopsy to Prevent Infectious Complications: The PREVENT Randomized Trial
Authors: Jim C. Hu, Melissa Assel, Mohamad E. Allaf, Behfar Ehdaie, Andrew J. Vickers, Andrew J. Cohen, Benjamin T. Ristau, David A. Green, Misop Han, Michael E. Rezaee, Christian P. Pavlovich, Jeffrey S. Montgomery, Keith J. Kowalczyk, Ashley E. Ross, Shilajit D. Kundu, Hiten D. Patel, Gerald J. Wang, John N. Graham, Jonathan E. Shoag, Ahmed Ghazi, Nirmish Singla, Michael A. Gorin, Anthony J. Schaeffer, Edward M. Schaeffer
Journal: European Urology (2024)
Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation
Authors: Junhui Chen, Qian Zhang, Jinan Guo, Di Gu, Jing Liu, Piao Luo, Yunmeng Bai, Jiayun Chen, Xinzhou Zhang, Sheng Nie, Chunbo Chen, Yulin Feng, Jigang Wang
Journal: Acta Pharmaceutica Sinica B (2024)

Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by changes in kidney structure and function. The natural product rosmarinic acid (RA) has demonstrated therapeutic effects, including anti-inflammation and anti-oxidative-stress, in renal damage or dysfunction. In this study, we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell levels. Our results demonstrated that RA significantly alleviated renal tubular epithelial injury, particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes, while attenuating the inflammatory response of macrophages, oxidative stress, and cytotoxicity of natural killer cells. These findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage, oxidative stress, and inflammation, offering valuable guidance for the clinical application of RA in the treatment of DN.
Validation of the new nomenclature of steatotic liver disease in patients with a history of excessive alcohol intake: an analysis of data from a prospective cohort study
Authors: Mads Israelsen, Nikolaj Torp, Stine Johansen, Camilla Dalby Hansen, Emil Deleuran Hansen, Katrine Thorhauge, Johanne Kragh Hansen, Ida Villesen, Katrine Bech, Charlotte Wernberg, Peter Andersen, Katrine Prier Lindvig, Emmanuel A Tsochatzis, Maja Thiele, Mary E Rinella, Aleksander Krag
Journal: The Lancet. Gastroenterology & hepatology (2024)
Distinct roles of vaccine-induced SARS-CoV-2-specific neutralizing antibodies and T cells in protection and disease
Authors: Jingyi Yan, Chandrashekar Ravenna Bangalore, Negin Nikouyan, Sofia Appelberg, Daniela Nacimento Silva, Haidong Yao, Anna Pasetto, Friedemann Weber, Sofie Weber, Olivia Larsson, Urban Höglund, Gordana Bogdanovic, Malin Grabbe, Soo Aleman, Laszlo Szekely, Attila Szakos, Ola Tuvesson, Eva-Karin Gidlund, Matteo Cadossi, Simona Salati, Hanna Tegel, Sophia Hober, Lars Frelin, Ali Mirazimi, Gustaf Ahlén, Matti Sällberg
Journal: Molecular Therapy (2024)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) lack cross-reactivity between SARS-CoV species and variants and fail to mediate long-term protection against infection. The maintained protection against severe disease and death by vaccination suggests a role for cross-reactive T cells. We generated vaccines containing sequences from the spike or receptor binding domain, the membrane and/or nucleoprotein that induced only T cells, or T cells and NAbs, to understand their individual roles. In three models with homologous or heterologous challenge, high levels of vaccine-induced SARS-CoV-2 NAbs protected against neither infection nor mild histological disease but conferred rapid viral control limiting the histological damage. With no or low levels of NAbs, vaccine-primed T cells, in mice mainly CD8+ T cells, partially controlled viral replication and promoted NAb recall responses. T cells failed to protect against histological damage, presumably because of viral spread and subsequent T cell-mediated killing. Neither vaccine- nor infection-induced NAbs seem to provide long-lasting protective immunity against SARS-CoV-2. Thus, a more realistic approach for universal SARS-CoV-2 vaccines should be to aim for broadly cross-reactive NAbs in combination with long-lasting highly cross-reactive T cells. Long-lived cross-reactive T cells are likely key to prevent severe disease and fatalities during current and future pandemics.Graphical abstract
Correction: A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
Authors: Yang Gao, Yuying Wang, Huiyang Lei, Zhendong Xu, Shihong Li, Haitao Yu, Jiazhao Xie, Zhentao Zhang, Gongping Liu, Yao Zhang, Jie Zheng, Jian‑Zhi Wang
Journal: Translational Neurodegeneration (2024)
Abstract B011: CDK9-55 guides the anaphase-promoting complex/cyclosome (APC/C) in choosing the DNA repair pathway by affecting the UFL1 ubiquitination
Authors: Luigi Alfano
Journal: Cancer Research (2024)

Abstract DNA double-strand breaks (DSBs) contribute to genome instability, a key feature of cancer. DSBs are mainly repaired by homologous recombination (HR) and non-homologous end-joining (NHEJ). We investigated the role of an isoform of the multifunctional cyclin-dependent kinase 9, CDK9-55, in DNA repair, by generating CDK9-55-knockout HeLa clones (through CRISPR-Cas9), which showed potential HR dysfunction. A phosphoproteomic screening in these clones treated with camptothecin (CPT) revealed that CDC23 (cell division cycle 23), a component of the E3-ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome), is a new substrate of CDK9-55, with S588 being its putative phosphorylation site. Mutated non-phosphorylatable CDC23(S588A) affected the repair pathway choice by impairing HR and favoring error prone NHEJ. Moreover, CDC23(S588A) promoted the ubiquitination of UFL1, a recently identified HR player. Overall, CDK9-55 could guide APC/C in choosing the correct DNA repair pathway, possibly by regulating UFL1 stability. This CDK9 role should be considered when designing CDK-inhibitor-based cancer therapies. Citation Format: Luigi Alfano. CDK9-55 guides the anaphase-promoting complex/cyclosome (APC/C) in choosing the DNA repair pathway by affecting the UFL1 ubiquitination [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B011.
Effect of carvedilol versus placebo on cardiac function in anthracycline-exposed survivors of childhood cancer (PREVENT-HF): a randomised, controlled, phase 2b trial
Authors: Saro H Armenian, Melissa M Hudson, Lanie Lindenfeld, Sitong Chen, Eric J Chow, Steven Colan, Willem Collier, Xiaohong Su, Edward Marcus, Meagan Echevarria, Aleksi Iukuridze, Leslie L Robison, F Lennie Wong, Ming Hui Chen, Smita Bhatia
Journal: The Lancet Oncology (2024)
Value Creation Through Artificial Intelligence and Cardiovascular Imaging: A Scientific Statement From the American Heart Association
Authors: Kate Hanneman, David Playford, Damini Dey, Marly van Assen, Domenico Mastrodicasa, Tessa S. Cook, Judy Wawira Gichoya, Eric E. Williamson, Geoffrey D. Rubin
Journal: Circulation (2024)

Multiple applications for machine learning and artificial intelligence (AI) in cardiovascular imaging are being proposed and developed. However, the processes involved in implementing AI in cardiovascular imaging are highly diverse, varying by imaging modality, patient subtype, features to be extracted and analyzed, and clinical application. This article establishes a framework that defines value from an organizational perspective, followed by value chain analysis to identify the activities in which AI might produce the greatest incremental value creation. The various perspectives that should be considered are highlighted, including clinicians, imagers, hospitals, patients, and payers. Integrating the perspectives of all health care stakeholders is critical for creating value and ensuring the successful deployment of AI tools in a real-world setting. Different AI tools are summarized, along with the unique aspects of AI applications to various cardiac imaging modalities, including cardiac computed tomography, magnetic resonance imaging, and positron emission tomography. AI is applicable and has the potential to add value to cardiovascular imaging at every step along the patient journey, from selecting the more appropriate test to optimizing image acquisition and analysis, interpreting the results for classification and diagnosis, and predicting the risk for major adverse cardiac events.