tbuckley/cabot-search huggingface dataset:
The diabetic myocardial transcriptome reveals Erbb3 and Hspa2 as a novel biomarkers of incident heart failure
Authors: Marcella S Conning-Rowland, Marilena Giannoudi, Michael Drozd, Oliver I Brown, Nadira Y Yuldasheva, Chew W Cheng, Paul J Meakin, Sam Straw, John Gierula, Ramzi A Ajjan, Mark T Kearney, Eylem Levelt, Lee D Roberts, Kathryn J Griffin, Richard M Cubbon
Journal: Cardiovascular Research (2024)

Diabetes mellitus (DM) increases heart failure incidence and worsens prognosis, but its molecular basis is poorly defined in humans. We aimed to define the diabetic myocardial transcriptome and validate hits in their circulating protein form to define disease mechanisms and biomarkers.
Heart brain axis in health and disease: role of innate and adaptive immunity
Authors: Alba Simats, Hendrik B Sager, Arthur Liesz
Journal: Cardiovascular Research (2024)

Abstract The importance of the brain–heart interaction has been increasingly recognized as a critical physiological axis that is altered in disease. In this review, we explore the intricate relationship between the central nervous system and cardiovascular health, focusing particularly on immunological mechanisms that influence the course of both neurological and cardiovascular diseases. While previous studies have established a key role of the autonomic nervous system (ANS) in linking brain and the heart, more recent studies have expanded our understanding of the multifaceted inter-organ interactions. As such, circulating mediators include immune cells of the adaptive and innate immune system and their secreted immunogenic factors have come into the focus as mediators along this bidirectional communication. Hence, in this review we briefly discuss the contribution of the ANS and then focus on innate and adaptive immune mechanisms along the heart-to-brain and brain-to-heart axes, illustrating how cardiovascular diseases affect cognitive functions and how brain pathologies lead to cardiac complications.
Multimodal fusion learning for long QT syndrome pathogenic genotypes in a racially diverse population
Authors: Joy Jiang, Ha My Thi Vy, Alexander Charney, Patricia Kovatch, Vivek Reddy, Pushkala Jayaraman, Ron Do, Rohan Khera, Sumeet Chugh, Deepak L. Bhatt, Akhil Vaid, Joshua Lampert, Girish Nitin Nadkarni
Journal: npj Digital Medicine (2024)

Congenital long QT syndrome (LQTS) diagnosis is complicated by limited genetic testing at scale, low prevalence, and normal QT corrected interval in patients with high-risk genotypes. We developed a deep learning approach combining electrocardiogram (ECG) waveform and electronic health record data to assess whether patients had pathogenic variants causing LQTS. We defined patients with high-risk genotypes as having ≥1 pathogenic variant in one of the LQTS-susceptibility genes. We trained the model using data from United Kingdom Biobank (UKBB) and then fine-tuned in a racially/ethnically diverse cohort using Mount Sinai BioMe Biobank. Following group-stratified 5-fold splitting, the fine-tuned model achieved area under the precision-recall curve of 0.29 (95% confidence interval [CI] 0.28–0.29) and area under the receiver operating curve of 0.83 (0.82–0.83) on independent testing data from BioMe. Multimodal fusion learning has promise to identify individuals with pathogenic genetic mutations to enable patient prioritization for further work up.
Inflammation, Physical Activity, and Disease-Free Survival in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance)
Authors: Justin C Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M Goldberg, Eileen M O’Reilly, Anthony F Shields, Jeffrey A Meyerhardt
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown. Methods This cohort study was nested within the Cancer and Leukemia Group B (now part of the Alliance for Clinical Trials in Oncology) and Southwest Oncology Group randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free survival. Results The 3-year disease-free survival rate was 88.4% among patients with low inflammation and sufficient physical activity (referent group for all comparisons), 84.9% with low inflammation and insufficient physical activity (absolute risk difference = −3.5 percentage points, 95% confidence interval [CI] = −11.3 to 4.3; P = .38), 78.0% with intermediate inflammation and insufficient physical activity (absolute risk difference = −10.4 percentage points, 95% CI = −17.4 to −3.3; P = .007), and 79.7% with high inflammation and insufficient physical activity (absolute risk difference = −8.7 percentage points, 95% CI = −15.7 to −1.6; P = .022). In contrast, the 3-year disease-free survival rate was 87.3% among patients with intermediate inflammation and sufficient physical activity (absolute risk difference = −1.1 percentage points, 95% CI = −7.5 to 5.3; P = .74) and 84.4% with high inflammation and sufficient physical activity (absolute risk difference = −4.0 percentage points, 95% CI = −12.3 to 4.3; P = .34). Conclusion In this observational study of stage III colon cancer patients, physical activity was associated with improved disease-free survival despite high inflammation. Patients with intermediate or high inflammation who were physically active had disease-free survival rates that were not statistically significantly different from those with low inflammation.
Erratum to “Brief Report: Canadian Cancer Trials Group IND.227: A Phase II randomized study of pembrolizumab in patients with advanced malignant pleural mesothelioma (NCT02784171). [Journal of Thoracic Oncology Vol. 18 No. 6: 813–819]”
Authors: Maria Carmela Piccirillo, Quincy Chu, Penelope Bradbury, Wei Tu, Courtney H Coschi, Federica Grosso, Marie Florescu, Manlio Mencoboni, John R Goffin, Maria Pagano, Fortunato Ciardiello, Fabiana Letizia Cecere, Mark Vincent, Roberto Ferrara, David E Dawe, Desiree Hao, Christopher W Lee, Alessandro Morabito, Cesare Gridelli, Luigi Cavanna, Mussawar Iqbal, Normand Blais, Natasha B Leighl, Paul Wheatley-Price, Ming-Sound Tsao, Francesca Ugo, Hazem El-Osta, Piera Gargiulo, Pierre-Olivier Gaudreau, Dongsheng Tu, Joana Sederias, Pamela Brown-Walker, Francesco Perrone, Lesley Seymour, Scott A Laurie
Journal: Journal of Thoracic Oncology (2024)
Cost-effectiveness of incorporating self-imaging optical coherence tomography into fundus photography-based diabetic retinopathy screening
Authors: Zitian Liu, Xiaotong Han, Le Gao, Shida Chen, Wenyong Huang, Peng Li, Zhiyan Wu, Mengchi Wang, Yingfeng Zheng
Journal: npj Digital Medicine (2024)

Diabetic macular edema (DME) has emerged as the foremost cause of vision loss in the population with diabetes. Early detection of DME is paramount, yet the prevailing screening, relying on two-dimensional and labor-intensive fundus photography (FP), results in frequent unwarranted referrals and overlooked diagnoses. Self-imaging optical coherence tomography (SI-OCT), offering fully automated, three-dimensional macular imaging, holds the potential to enhance DR screening. We conducted an observational study within a cohort of 1822 participants with diabetes, who received comprehensive assessments, including visual acuity testing, FP, and SI-OCT examinations. We compared the performance of three screening strategies: the conventional FP-based strategy, a combination strategy of FP and SI-OCT, and a simulated combination strategy of FP and manual SD-OCT. Additionally, we undertook a cost-effectiveness analysis utilizing Markov models to evaluate the costs and benefits of the three strategies for referable DR. We found that the FP + SI-OCT strategy demonstrated superior sensitivity (87.69% vs 61.53%) and specificity (98.29% vs 92.47%) in detecting DME when compared to the FP-based strategy. Importantly, the FP + SI-OCT strategy outperformed the FP-based strategy, with an incremental cost-effectiveness ratio (ICER) of $8016 per quality-adjusted life year (QALY), while the FP + SD-OCT strategy was less cost-effective, with an ICER of $45,754/QALY. Our results were robust to extensive sensitivity analyses, with the FP + SI-OCT strategy standing as the dominant choice in 69.36% of simulations conducted at the current willingness-to-pay threshold. In summary, incorporating SI-OCT into FP-based screening offers substantial enhancements in sensitivity, specificity for detecting DME, and most notably, cost-effectiveness for DR screening.
Spatial multi-omics: deciphering technological landscape of integration of multi-omics and its applications
Authors: Xiaojie Liu, Ting Peng, Miaochun Xu, Shitong Lin, Bai Hu, Tian Chu, Binghan Liu, Yashi Xu, Wencheng Ding, Li Li, Canhui Cao, Peng Wu
Journal: Journal of Hematology & Oncology (2024)

The emergence of spatial multi-omics has helped address the limitations of single-cell sequencing, which often leads to the loss of spatial context among cell populations. Integrated analysis of the genome, transcriptome, proteome, metabolome, and epigenome has enhanced our understanding of cell biology and the molecular basis of human diseases. Moreover, this approach offers profound insights into the interactions between intracellular and intercellular molecular mechanisms involved in the development, physiology, and pathogenesis of human diseases. In this comprehensive review, we examine current advancements in multi-omics technologies, focusing on their evolution and refinement over the past decade, including improvements in throughput and resolution, modality integration, and accuracy. We also discuss the pivotal contributions of spatial multi-omics in revealing spatial heterogeneity, constructing detailed spatial atlases, deciphering spatial crosstalk in tumor immunology, and advancing translational research and cancer therapy through precise spatial mapping.
Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice
Authors: Fuminori Sakurai, Shunsuke Iizuka, Tomohito Tsukamoto, Aoi Shiota, Kahori Shimizu, Kazuo Ohashi, Hiroyuki Mizuguchi
Journal: Journal of Controlled Release (2024)

Hemophilia B is an inherited hemorrhagic disorder characterized by a deficiency of blood coagulation factor IX (FIX) that results in abnormal blood coagulation. The blood coagulation is already evident in hemophiliacs at the fetal stage, and thus intracranial hemorrhage and other bleeding complications can occur at birth, leading to sequelae. Therefore, it is important to develop effective treatments for hemophiliacs in utero. In this study, in order to transplacentally deliver FIX from pregnant mice to their fetuses, an improved adenovirus (Ad) vector expressing human FIX fused with the IgG Fc domain (FIX Fc fusion protein), which plays a crucial role in neonatal Fc receptor (FcRn)-mediated transcytosis across the placenta, was intravenously administered to E13.5 pregnant mice. Significant levels of FIX Fc fusion protein were detected in 0-day-old newborn mice whose mothers were administered an Ad vector expressing FIX Fc fusion protein. Wild-type FIX overexpressed in the pregnant mice was not delivered to the fetuses. Plasma FIX levels in the newborn mice were relatively well correlated with those in their mothers, although transplacental delivery efficiencies of FIX Fc fusion protein were slightly reduced when the FIX Fc fusion protein was highly expressed in the mother mice. Plasma FIX levels in the newborn mice were about 3.6-6.4% of those in their mothers, Transplacental delivery of FIX Fc fusion protein to their fetuses successfully improved the blood clotting ability in the newborn mice.
Epigenetic reprogramming in gastrointestinal cancer: biology and translational perspectives
Authors: Yingjie Wang, Hongyu Liu, Mengsha Zhang, Jing Xu, Liuxian Zheng, Pengpeng Liu, Jingyao Chen, Hongyu Liu, Chong Chen
Journal: MedComm (2024)

Gastrointestinal tumors, the second leading cause of human mortality, are characterized by their association with inflammation. Currently, progress in the early diagnosis and effective treatment of gastrointestinal tumors is limited. Recent whole-genome analyses have underscored their profound heterogeneity and extensive genetic and epigenetic reprogramming. Epigenetic reprogramming pertains to dynamic and hereditable alterations in epigenetic patterns, devoid of concurrent modifications in the underlying DNA sequence. Common epigenetic modifications encompass DNA methylation, histone modifications, noncoding RNA, RNA modifications, and chromatin remodeling. These modifications possess the potential to invoke or suppress a multitude of genes associated with cancer, thereby governing the establishment of chromatin configurations characterized by diverse levels of accessibility. This intricate interplay assumes a pivotal and indispensable role in governing the commencement and advancement of gastrointestinal cancer. This article focuses on the impact of epigenetic reprogramming in the initiation and progression of gastric cancer, esophageal cancer, and colorectal cancer, as well as other uncommon gastrointestinal tumors. We elucidate the epigenetic landscape of gastrointestinal tumors, encompassing DNA methylation, histone modifications, chromatin remodeling, and their interrelationships. Besides, this review summarizes the potential diagnostic, therapeutic, and prognostic targets in epigenetic reprogramming, with the aim of assisting clinical treatment strategies.
Mechanisms of resistance to tyrosine kinase inhibitor‐targeted therapy and overcoming strategies
Authors: Xuejin Ou, Ge Gao, Inbar A. Habaz, Yongsheng Wang
Journal: MedComm (2024)

Tyrosine kinase inhibitor (TKI)-targeted therapy has revolutionized cancer treatment by selectively blocking specific signaling pathways crucial for tumor growth, offering improved outcomes with fewer side effects compared with conventional chemotherapy. However, despite their initial effectiveness, resistance to TKIs remains a significant challenge in clinical practice. Understanding the mechanisms underlying TKI resistance is paramount for improving patient outcomes and developing more effective treatment strategies. In this review, we explored various mechanisms contributing to TKI resistance, including on-target mechanisms and off-target mechanisms, as well as changes in the tumor histology and tumor microenvironment (intrinsic mechanisms). Additionally, we summarized current therapeutic approaches aiming at circumventing TKI resistance, including the development of next-generation TKIs and combination therapies. We also discussed emerging strategies such as the use of dual-targeted antibodies and PROteolysis Targeting Chimeras. Furthermore, we explored future directions in TKI-targeted therapy, including the methods for detecting and monitoring drug resistance during treatment, identification of novel targets, exploration of dual-acting kinase inhibitors, application of nanotechnologies in targeted therapy, and so on. Overall, this review provides a comprehensive overview of the challenges and opportunities in TKI-targeted therapy, aiming to advance our understanding of resistance mechanisms and guide the development of more effective therapeutic approaches in cancer treatment.
Corrigendum to “Dissolving microarray patches loaded with a rotigotine nanosuspension: A potential alternative to Neupro® patch” [Journal of Controlled Release 372 (2024) 304–317]
Authors: Yaocun Li, Jiawen Wang, Lalitkumar K Vora, Akmal Hidayat Bin Sabri, Mary B McGuckin, Helen O McCarthy, Alejandro J Paredes, Ryan F Donnelly
Journal: Journal of Controlled Release (2024)
Bi<sub>2</sub>Se<sub>3</sub>/PAAS Hydrogels with Photothermal and Antioxidant Properties for Bacterial Infection Wound Therapy by Improving Vascular Function and Regulating Glycolipid Metabolism
Authors: Ying Zang, Wei Zhang, Peisan Wang, Can Zhu, Xueting Guo, Wenqi Wang, Liang Cheng, Xu‐Lin Chen, Xianwen Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Skin is the largest organ in the human body, and it is also the most important natural barrier. However, some accidents can cause skin damage. Bacterial infections and inflammatory reactions can hinder wound healing. Therefore, eliminating bacterial infections and regulating oxidative stress are essential. The use of antibiotics is no longer sufficient because of bacterial resistance. The development of new nanomaterials provides another way of thinking about bacterial drug resistance. In this study, bismuth selenide is modified with polyethylpyrrolidone to obtain a 2D nanomaterial with negligible toxicity and then added to a sodium polyacrylate hydrogel, which is nontoxic and has strong tissue adhesion and a weak antibacterial effect. To further enhance antibacterial performance, photothermal therapy is a good strategy. Under near‐infrared light, Bi 2 Se 3 /PAAS shows a strong bactericidal effect. Bi 2 Se 3 /PAAS hydrogels also have certain antioxidant effects and are used to remove excess free radicals from wound infections. The effective therapeutic effect of Bi 2 Se 3 /PAAS/NIR on methicillin‐resistant Staphylococcus aureus ( MRSA ) infection is further verified in animal models. Transcriptome analysis reveals that the Bi 2 Se 3 /PAAS hydrogel improves the function of vascular endothelial cells, regulates glucose and lipid metabolism, and promotes the healing of infected wounds.
Emergence of extensively drug-resistant Pseudomonas aeruginosa ST308 co-producing Klebsiella pneumoniae carbapenemase and New Delhi metallo-β-lactamase in Viet Nam
Authors: Dennis Nurjadi, Truong Nhat My, Lisa Göpel, Sébastien Boutin, Le Huu Song, Thirumalaisamy P Velavan
Journal: The Lancet Microbe (2024)
Deep learning-based prediction of Clostridioides difficile infection caused by antibiotics using longitudinal electronic health records
Authors: Junmo Kim, Joo Seong Kim, Sae-Hoon Kim, Sooyoung Yoo, Jun Kyu Lee, Kwangsoo Kim
Journal: npj Digital Medicine (2024)

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and colitis. It is recognized as one of the most significant hospital-acquired infections. Although CDI can develop severe complications and spores of Clostridioides difficile can be transmitted by the fecal-oral route, CDI is occasionally overlooked in clinical settings. Thus, it is necessary to monitor high CDI risk groups, particularly those undergoing antibiotic treatment, to prevent complications and spread. We developed and validated a deep learning-based model to predict the occurrence of CDI within 28 days after starting antibiotic treatment using longitudinal electronic health records. For each patient, timelines of vital signs and laboratory tests with a 35-day monitoring period and a patient information vector consisting of age, sex, comorbidities, and medications were constructed. Our model achieved the prediction performance with an area under the receiver operating characteristic curve of 0.952 (95% CI: 0.932–0.973) in internal validation and 0.972 (95% CI: 0.968–0.975) in external validation. Platelet count and body temperature emerged as the most important features. The risk score, the output value of the model, exhibited a consistent increase in the CDI group, while the risk score in the non-CDI group either maintained its initial value or decreased. Using our CDI prediction model, high-risk patients requiring symptom monitoring can be identified. This could help reduce the underdiagnosis of CDI, thereby decreasing transmission and preventing complications.
Imaging Identifies Superior Inflammation Targeting of M1 Macrophages for Cryo‐Shocked Cell Pulmonary Drug Delivery to Treat Acute Lung Injury
Authors: Xinyu Wang, Yuhang Liu, Yeli Fan, Junjie Yan, Ge Yan, Qingfeng Liu, Qian Xu, Lizhen Wang, Donghui Pan, Yuping Xu, Chongyang Chen, Yu Chen, Min Yang
Journal: Advanced Healthcare Materials (2024)

In the realm of combating acute lung injury (ALI) induced by a myriad of triggers including sepsis, pneumonia, aspiration, trauma, and pancreatitis, macrophages emerge as crucial players. However, traditional treatments such as systemic administration of glucocorticoids come with the baggage of severe side effects, curtailing their utility. Enter an innovative solution: a biomimetic drug delivery system fashioned from cryo-shocked macrophages, tailored for pulmonary drug delivery. Positron emission tomography (PET) imaging has shed light on the remarkable targeting abilities of live M1 macrophages, showcasing their unparalleled efficacy in homing in on local inflammatory foci when contrasted with naive, M1, and M2 macrophages. Building upon this foundation, liquid nitrogen-treated (LNT) M1 macrophages are developed, engineered to preserve their inflammation-targeting prowess while sidestepping the release of pro-inflammatory cytokines. This breakthrough allows for the delivery of glucocorticoids directly to inflamed lung tissues, efficiently quelling inflammation and mitigating pulmonary edema while drastically reducing systemic drug exposure. Inspired by the effectiveness of live M1 macrophages, the potential of glucocorticoid-loaded LNT M1 macrophages are harnessed, utilizing them as a stealthy "Trojan horse" in the battle against pneumonia-induced ALI. This innovative approach holds promise as a safe and potent treatment avenue for acute lung injury.
Deep near infrared light-excited stable synergistic photodynamic and photothermal therapies based on P-IR890 nano-photosensitizer constructed via a non-cyanine dye
Authors: Dawei Jiang, Chao Chen, Peng Dai, Caiyan Li, Zhiyi Feng, Na Dong, Fenzan Wu, Junpeng Xu, Ping Wu, Liuxi Chu, Shengcun Li, Xiaokun Li, Youjun Yang, Weian Zhang, Zhouguang Wang
Journal: Asian Journal of Pharmaceutical Sciences (2024)

The cyanine dyes represented by IR780 can achieve synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) under the stimulation of near-infrared (NIR) light (commonly 808 nm). Unfortunately, the stability of NIR-excited cyanine dyes is not satisfactory. These cyanine dyes can be attacked by self-generated reactive oxygen species (ROS) during PDT processes, resulting in structural damage and rapid degradation, which is fatal for phototherapy. To address this issue, a novel non-cyanine dye (IR890) was elaborately designed and synthesized by our team. The maximum absorption wavelength of IR890 was located in the deep NIR region (
The intersection of bisexuality and gender modality: exploring differences in sexual interest and satisfaction
Authors: Jenn J. Soros, Kimberly A. Fuller, Caleb Sargent
Journal: International Journal of Transgender Health (2024)

Background Sexual well-being is crucial for overall health, but research on bisexual individuals' sexual experiences across gender modalities is limited. This study aims to address this gap by examining differences in sexual interest and satisfaction among bisexual adults of various gender modalities.