tbuckley/cabot-search huggingface dataset:
Use of Artificial Intelligence in Improving Outcomes in Heart Disease: A Scientific Statement From the American Heart Association
Authors: Antonis A. Armoundas, Sanjiv M. Narayan, Donna K. Arnett, Kayte Spector-Bagdady, Derrick A. Bennett, Leo Anthony Celi, Paul A. Friedman, Michael H. Gollob, Jennifer L. Hall, Anne E. Kwitek, Elle Lett, Bijoy K. Menon, Katherine A. Sheehan, Salah S. Al-Zaiti
Journal: Circulation (2024)

A major focus of academia, industry, and global governmental agencies is to develop and apply artificial intelligence and other advanced analytical tools to transform health care delivery. The American Heart Association supports the creation of tools and services that would further the science and practice of precision medicine by enabling more precise approaches to cardiovascular and stroke research, prevention, and care of individuals and populations. Nevertheless, several challenges exist, and few artificial intelligence tools have been shown to improve cardiovascular and stroke care sufficiently to be widely adopted. This scientific statement outlines the current state of the art on the use of artificial intelligence algorithms and data science in the diagnosis, classification, and treatment of cardiovascular disease. It also sets out to advance this mission, focusing on how digital tools and, in particular, artificial intelligence may provide clinical and mechanistic insights, address bias in clinical studies, and facilitate education and implementation science to improve cardiovascular and stroke outcomes. Last, a key objective of this scientific statement is to further the field by identifying best practices, gaps, and challenges for interested stakeholders.
Global, neuronal or β cell-specific deletion of inceptor improves glucose homeostasis in male mice with diet-induced obesity
Authors: Gerald Grandl, Gustav Collden, Jin Feng, Sreya Bhattacharya, Felix Klingelhuber, Leopold Schomann, Sara Bilekova, None Ansarullah, Weiwei Xu, Fataneh Fathi Far, Monica Tost, Tim Gruber, Aimée Bastidas-Ponce, Qian Zhang, Aaron Novikoff, Arkadiusz Liskiewicz, Daniela Liskiewicz, Cristina Garcia-Caceres, Annette Feuchtinger, Matthias H. Tschöp, Natalie Krahmer, Heiko Lickert, Timo D. Müller
Journal: Nature Metabolism (2024)

Abstract Insulin resistance is an early complication of diet-induced obesity (DIO) 1 , potentially leading to hyperglycaemia and hyperinsulinaemia, accompanied by adaptive β cell hypertrophy and development of type 2 diabetes 2 . Insulin not only signals via the insulin receptor (INSR), but also promotes β cell survival, growth and function via the insulin-like growth factor 1 receptor (IGF1R) 3–6 . We recently identified the insulin inhibitory receptor (inceptor) as the key mediator of IGF1R and INSR desensitization 7 . But, although β cell-specific loss of inceptor improves β cell function in lean mice 7 , it warrants clarification whether inceptor signal inhibition also improves glycaemia under conditions of obesity. We assessed the glucometabolic effects of targeted inceptor deletion in either the brain or the pancreatic β cells under conditions of DIO in male mice. In the present study, we show that global and neuronal deletion of inceptor, as well as its adult-onset deletion in the β cells, improves glucose homeostasis by enhancing β cell health and function. Moreover, we demonstrate that inceptor-mediated improvement in glucose control does not depend on inceptor function in agouti-related protein-expressing or pro-opiomelanocortin neurons. Our data demonstrate that inceptor inhibition improves glucose homeostasis in mice with DIO, hence corroborating that inceptor is a crucial regulator of INSR and IGF1R signalling.
Tim4 deficiency reduces CD301b+ macrophage and aggravates periodontitis bone loss
Authors: Ziming Wang, Hao Zeng, Can Wang, Jiaolong Wang, Jing Zhang, Shuyuan Qu, Yue Han, Liu Yang, Yueqi Ni, Wenan Peng, Huan Liu, Hua Tang, Qin Zhao, Yufeng Zhang
Journal: International Journal of Oral Science (2024)

Abstract Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss. With the progression of periodontitis, the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption. CD301b + macrophages are specific to the osteoimmunology microenvironment, and are emerging as vital booster for conducting bone regeneration. However, the key upstream targets of CD301b + macrophages and their potential mechanism in periodontitis remain elusive. In this study, we concentrated on the role of Tim4, a latent upstream regulator of CD301b + macrophages. We first demonstrated that the transcription level of Timd4 (gene name of Tim4) in CD301b + macrophages was significantly upregulated compared to CD301b − macrophages via high-throughput RNA sequencing. Moreover, several Tim4-related functions such as apoptotic cell clearance, phagocytosis and engulfment were positively regulated by CD301b + macrophages. The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages. The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b + macrophages as periodontitis progressed. Furthermore, the deficiency of Tim4 in mice decreased CD301b + macrophages and eventually magnified alveolar bone resorption in periodontitis. Additionally, Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b + macrophages phenotype. In a word, Tim4 might regulate CD301b + macrophages through p38 MAPK signaling pathway in periodontitis, which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.
The osteoclastic activity in apical distal region of molar mesial roots affects orthodontic tooth movement and root resorption in rats
Authors: Wenhao Zheng, Xiaofeng Lu, Guangjin Chen, Yufeng Shen, Xiaofei Huang, Jinfeng Peng, Jiajia Wang, Ying Yin, Wencheng Song, Mengru Xie, Shaoling Yu, Lili Chen
Journal: International Journal of Oral Science (2024)

Abstract The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment. However, the sensitivity of existing detection techniques is not sufficient, and the criteria for evaluating optimal force have not been yet established. Here, by employing 3D finite element analysis methodology, we found that the apical distal region (A-D region) of mesial roots is particularly sensitive to orthodontic force in rats. Tartrate-resistant acidic phosphatase (TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams (g), leading to alveolar bone resorption and tooth movement. When the force reached 80 g, TRAP-positive osteoclasts started appearing on the root surface in the A-D region. Additionally, micro-computed tomography revealed a significant root resorption at 80 g. Notably, the A-D region was identified as a major contributor to whole root resorption. It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement, inclination, and hyalinization. These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model. Collectively, our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients’ orthodontic treatment.
Correction: Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib – interim results from the DAstop2 trial
Authors: Hjalmar Flygt, Stina Söderlund, Johan Richter, Susanne Saussele, Perttu Koskenvesa, Leif Stenke, Satu Mustjoki, Andreja Dimitrijevic, Jesper Stentoft, Waleed Majeed, Lydia Roy, Dominik Wolf, Arta Dreimane, Bjørn Tore Gjertsen, Tobias Gedde-Dahl, Erik Ahlstrand, Berit Markevärn, Henrik Hjorth-Hansen, Jeroen Janssen, Ulla Olsson-Strömberg
Journal: Leukemia (2024)
Genetic Basis and Evolution of Structural Color Polymorphism in an Australian Songbird
Authors: Simon Yung Wa Sin, Fushi Ke, Guoling Chen, Pei-Yu Huang, Erik D Enbody, Jordan Karubian, Michael S Webster, Scott V Edwards
Journal: Molecular Biology and Evolution (2024)

Abstract Island organisms often evolve phenotypes divergent from their mainland counterparts, providing a useful system for studying adaptation under differential selection. In the white-winged fairywren (Malurus leucopterus), subspecies on two islands have a black nuptial plumage whereas the subspecies on the Australian mainland has a blue nuptial plumage. The black subspecies have a feather nanostructure that could in principle produce a blue structural color, suggesting a blue ancestor. An earlier study proposed independent evolution of melanism on the islands based on the history of subspecies divergence. However, the genetic basis of melanism and the origin of color differentiation in this group are still unknown. Here, we used whole-genome resequencing to investigate the genetic basis of melanism by comparing the blue and black M. leucopterus subspecies to identify highly divergent genomic regions. We identified a well-known pigmentation gene ASIP and four candidate genes that may contribute to feather nanostructure development. Contrary to the prediction of convergent evolution of island melanism, we detected signatures of a selective sweep in genomic regions containing ASIP and SCUBE2 not in the black subspecies but in the blue subspecies, which possesses many derived SNPs in these regions, suggesting that the mainland subspecies has re-evolved a blue plumage from a black ancestor. This proposed re-evolution was likely driven by a preexisting female preference. Our findings provide new insight into the evolution of plumage coloration in island versus continental populations, and, importantly, we identify candidate genes that likely play roles in the development and evolution of feather structural coloration.
Functional and Evolutionary Integration of a Fungal Gene With a Bacterial Operon
Authors: Liang Sun, Kyle T David, John F Wolters, Steven D Karlen, Carla Gonçalves, Dana A Opulente, Abigail Leavitt LaBella, Marizeth Groenewald, Xiaofan Zhou, Xing-Xing Shen, Antonis Rokas, Chris Todd Hittinger
Journal: Molecular Biology and Evolution (2024)

Abstract Siderophores are crucial for iron-scavenging in microorganisms. While many yeasts can uptake siderophores produced by other organisms, they are typically unable to synthesize siderophores themselves. In contrast, Wickerhamiella/Starmerella (W/S) clade yeasts gained the capacity to make the siderophore enterobactin following the remarkable horizontal acquisition of a bacterial operon enabling enterobactin synthesis. Yet, how these yeasts absorb the iron bound by enterobactin remains unresolved. Here, we demonstrate that Enb1 is the key enterobactin importer in the W/S-clade species Starmerella bombicola. Through phylogenomic analyses, we show that ENB1 is present in all W/S clade yeast species that retained the enterobactin biosynthetic genes. Conversely, it is absent in species that lost the ent genes, except for Starmerella stellata, making this species the only cheater in the W/S clade that can utilize enterobactin without producing it. Through phylogenetic analyses, we infer that ENB1 is a fungal gene that likely existed in the W/S clade prior to the acquisition of the ent genes and subsequently experienced multiple gene losses and duplications. Through phylogenetic topology tests, we show that ENB1 likely underwent horizontal gene transfer from an ancient W/S clade yeast to the order Saccharomycetales, which includes the model yeast Saccharomyces cerevisiae, followed by extensive secondary losses. Taken together, these results suggest that the fungal ENB1 and bacterial ent genes were cooperatively integrated into a functional unit within the W/S clade that enabled adaptation to iron-limited environments. This integrated fungal-bacterial circuit and its dynamic evolution determine the extant distribution of yeast enterobactin producers and cheaters.
Multi-omics reveals deoxycholic acid modulates bile acid metabolism via the gut microbiota to antagonize carbon tetrachloride-induced chronic liver injury
Authors: Li Zhang, Zhiyi Zheng, Huanhuan Huang, Ya Fu, Tianbin Chen, Can Liu, Qiang Yi, Caorui Lin, Yongjun Zeng, Qishui Ou, Yongbin Zeng
Journal: Gut Microbes (2024)

Deoxycholic acid (DCA) serves essential functions in both physiological and pathological liver processes; nevertheless, the relationship among DCA, gut microbiota, and metabolism in chronic liver injury remain insufficiently understood. The primary objective of this study is to elucidate the potential of DCA in ameliorating chronic liver injury and evaluate its regulatory effect on gut microbiota and metabolism via a comprehensive multi-omics approach. Our study found that DCA supplementation caused significant changes in the composition of gut microbiota, which were essential for its antagonistic effect against CCl4-induced chronic liver injury. When gut microbiota was depleted with antibiotics, the observed protective efficacy of DCA against chronic liver injury became noticeably attenuated. Mechanistically, we discovered that DCA regulates the metabolism of bile acids (BAs), including 3-epi DCA, Apo-CA, and its isomers 12-KLCA and 7-KLCA, IHDCA, and DCA, by promoting the growth of A.muciniphila in gut microbiota. This might lead to the inhibition of the IL-17 and TNF inflammatory signaling pathway, thereby effectively countering CCl4-induced chronic liver injury. This study illustrates that the enrichment of A. muciniphila in the gut microbiota, mediated by DCA, enhances the production of secondary bile acids, thereby mitigating chronic liver injury induced by CCl4. The underlying mechanism may involve the inhibition of hepatic IL-17 and TNF signaling pathways. These findings propose a promising approach to alleviate chronic liver injury by modulating both the gut microbiota and bile acids metabolism.
Rare <i>SH2B3</i> coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity
Authors: Yaoyuan Zhang, Rhiannon Morris, Grant J. Brown, Ayla May D. Lorenzo, Xiangpeng Meng, Nadia J. Kershaw, Pamudika Kiridena, Gaétan Burgio, Simon Gross, Jean Y. Cappello, Qian Shen, Hao Wang, Cynthia Turnbull, Tom Lea-Henry, Maurice Stanley, Zhijia Yu, Fiona D. Ballard, Aaron Chuah, James C. Lee, Ann-Maree Hatch, Anselm Enders, Seth L. Masters, Alexander P. Headley, Peter Trnka, Dominic Mallon, Jeffery T. Fletcher, Giles D. Walters, Mario Šestan, Marija Jelušić, Matthew C. Cook, Vicki Athanasopoulos, David A. Fulcher, Jeffrey J. Babon, Carola G. Vinuesa, Julia I. Ellyard
Journal: The Journal of Experimental Medicine (2024)

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a clear genetic component. While most SLE patients carry rare gene variants in lupus risk genes, little is known about their contribution to disease pathogenesis. Amongst them, SH2B3—a negative regulator of cytokine and growth factor receptor signaling—harbors rare coding variants in over 5% of SLE patients. Here, we show that unlike the variant found exclusively in healthy controls, SH2B3 rare variants found in lupus patients are predominantly hypomorphic alleles, failing to suppress IFNGR signaling via JAK2-STAT1. The generation of two mouse lines carrying patients’ variants revealed that SH2B3 is important in limiting the number of immature and transitional B cells. Furthermore, hypomorphic SH2B3 was shown to impair the negative selection of immature/transitional self-reactive B cells and accelerate autoimmunity in sensitized mice, at least in part due to increased IL-4R signaling and BAFF-R expression. This work identifies a previously unappreciated role for SH2B3 in human B cell tolerance and lupus risk.
Deep-Learning Model for Tumor-Type Prediction Using Targeted Clinical Genomic Sequencing Data
Authors: Madison Darmofal, Shalabh Suman, Gurnit Atwal, Michael Toomey, Jie-Fu Chen, Jason C. Chang, Efsevia Vakiani, Anna M. Varghese, Anoop Balakrishnan Rema, Aijazuddin Syed, Nikolaus Schultz, Michael F. Berger, Quaid Morris
Journal: Cancer Discovery (2024)

Abstract Tumor type guides clinical treatment decisions in cancer, but histology-based diagnosis remains challenging. Genomic alterations are highly diagnostic of tumor type, and tumor-type classifiers trained on genomic features have been explored, but the most accurate methods are not clinically feasible, relying on features derived from whole-genome sequencing (WGS), or predicting across limited cancer types. We use genomic features from a data set of 39,787 solid tumors sequenced using a clinically targeted cancer gene panel to develop Genome-Derived-Diagnosis Ensemble (GDD-ENS): a hyperparameter ensemble for classifying tumor type using deep neural networks. GDD-ENS achieves 93% accuracy for high-confidence predictions across 38 cancer types, rivaling the performance of WGS-based methods. GDD-ENS can also guide diagnoses of rare type and cancers of unknown primary and incorporate patient-specific clinical information for improved predictions. Overall, integrating GDD-ENS into prospective clinical sequencing workflows could provide clinically relevant tumor-type predictions to guide treatment decisions in real time. Significance: We describe a highly accurate tumor-type prediction model, designed specifically for clinical implementation. Our model relies only on widely used cancer gene panel sequencing data, predicts across 38 distinct cancer types, and supports integration of patient-specific nongenomic information for enhanced decision support in challenging diagnostic situations. See related commentary by Garg, p. 906. This article is featured in Selected Articles from This Issue, p. 897
A scoping review of the literature exploring experiences in the trans and gender diverse community with chest binding practices
Authors: Serena Pehlivanidis, Joel R. Anderson
Journal: International Journal of Transgender Health (2024)

Introduction In an effort to address disproportionate levels of poor mental health, stigma, and discrimination outcomes experienced by the Australian trans and gender diverse population, gender affirming care has become an important part of state government health priorities. One form of this affirming care is chest binding, and despite its historic use in the trans community, little is known about experiences and outcomes of this practice.
Common Bile Duct Injury in Cholecystectomy—Reply
Authors: Stanley Kalata, Jyothi R. Thumma, Kyle H. Sheetz
Journal: JAMA Surgery (2024)

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Glioblastoma-Infiltrating <i>CD8</i>+ T Cells Are Predominantly a Clonally Expanded <i>GZMK</i>+ Effector Population
Authors: Anthony Z. Wang, Bryce L. Mashimo, Maximilian O. Schaettler, Ngima D. Sherpa, Lydia A. Leavitt, Alexandra J. Livingstone, Saad M. Khan, Mao Li, Markus I. Anzaldua-Campos, Joseph D. Bradley, Eric C. Leuthardt, Albert H. Kim, Joshua L. Dowling, Michael R. Chicoine, Pamela S. Jones, Bryan D. Choi, Daniel P. Cahill, Bob S. Carter, Allegra A. Petti, Tanner M. Johanns, Gavin P. Dunn
Journal: Cancer Discovery (2024)

Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing with paired V(D)J sequencing, respectively, on TILs from two cohorts of patients totaling 15 patients with high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis of the CD8+ TIL landscape reveals an enrichment of clonally expanded GZMK+ effector T cells in the tumor compared with matched blood, which was validated at the protein level. Furthermore, integration with other cancer types highlights the lack of a canonically exhausted CD8+ T-cell population in GBM TIL. These data suggest that GZMK+ effector T cells represent an important T-cell subset within the GBM microenvironment and may harbor potential therapeutic implications.