tbuckley/cabot-search huggingface dataset:
Massively integrated coexpression analysis reveals transcriptional regulation, evolution and cellular implications of the yeast noncanonical translatome
Authors: April Rich, Omer Acar, Anne-Ruxandra Carvunis
Journal: Genome biology (2024)

Abstract Background Recent studies uncovered pervasive transcription and translation of thousands of noncanonical open reading frames (nORFs) outside of annotated genes. The contribution of nORFs to cellular phenotypes is difficult to infer using conventional approaches because nORFs tend to be short, of recent de novo origins, and lowly expressed. Here we develop a dedicated coexpression analysis framework that accounts for low expression to investigate the transcriptional regulation, evolution, and potential cellular roles of nORFs in Saccharomyces cerevisiae . Results Our results reveal that nORFs tend to be preferentially coexpressed with genes involved in cellular transport or homeostasis but rarely with genes involved in RNA processing. Mechanistically, we discover that young de novo nORFs located downstream of conserved genes tend to leverage their neighbors’ promoters through transcription readthrough, resulting in high coexpression and high expression levels. Transcriptional piggybacking also influences the coexpression profiles of young de novo nORFs located upstream of genes, but to a lesser extent and without detectable impact on expression levels. Transcriptional piggybacking influences, but does not determine, the transcription profiles of de novo nORFs emerging nearby genes. About 40% of nORFs are not strongly coexpressed with any gene but are transcriptionally regulated nonetheless and tend to form entirely new transcription modules. We offer a web browser interface ( https://carvunislab.csb.pitt.edu/shiny/coexpression/ ) to efficiently query, visualize, and download our coexpression inferences. Conclusions Our results suggest that nORF transcription is highly regulated. Our coexpression dataset serves as an unprecedented resource for unraveling how nORFs integrate into cellular networks, contribute to cellular phenotypes, and evolve.
Establishing African genomics and bioinformatics programs through annual regional workshops
Authors: Abdoallah Sharaf, Lucky Tendani Nesengani, Ichrak Hayah, Josiah Ochieng Kuja, Sinebongo Mdyogolo, Taiwo Crossby Omotoriogun, Blessing Adanta Odogwu, Girish Beedessee, Rae Marvin Smith, Abdelhamid Barakat, Acclaim M. Moila, Adil El Hamouchi, Alia Benkahla, Amal Boukteb, Amine Elmouhtadi, Antoine Lusala Mafwila, Asmaa Mohammed Abushady, Assem Kadry Elsherif, Bulbul Ahmed, Charles Wairuri, Charlotte C. Ndiribe, Chukwuike Ebuzome, Craig J. Kinnear, Deborah-Fay Ndlovu, Driss Iraqi, Elmostafa El Fahime, Ermias Assefa, Faissal Ouardi, Fatima Zohra Belharfi, Fatim Zohra Tmimi, Fatu Badiane Markey, Fouzia Radouani, Francis Zeukeng, Georges Lelo Mvumbi, Hamilton Ganesan, Mariem Hanachi, Helen Nigussie, Hicham Charoute, Ichrak Benamri, Ikram Mkedder, Imane Haddadi, Issam Meftah-Kadmiri, Jackson Franco Mubiru, Jean-Baka Kodjo Domelevo Entfellner, Joan Bayowa Rokani, Joel Ogwang, Jude Bigoga Daiga, Judy Omumbo, Justin Eze Ideozu, Khaoula Errafii, Kim Labuschagne, Komi Koukoura Komi, Libert Brice Tonfack, Lydia Hadjeras, Madeleine Ramantswana, Mamohale Chaisi, Marietjie W. Botes, Mariëtte Kilian, Marija Kvas, Marouane Melloul, Melek Chaouch, Meriem Khyatti, Michael Abdo, Mmatshepho Phasha-Muchemenye, Mohamed Hijri, Mohammed Rida Mediouni, Mohammed Ahmed Hassan, Mohammed Piro, Monica Mwale, Mossaab Maaloum, Mudzuli Mavhunga, Nicholas Abraham Olivier, Oumaima Aminou, Oumayma Arbani, Oussema Souiai, Pierre François Djocgoue, Rachid Mentag, Renate Dorothea Zipfel, Rolland Bantar Tata, Rosette Megnekou, Sadik Muzemil, Sadye Paez, Samson Pandam Salifu, Samuel Paul Kagame, Sarra Selka, Sean Edwards, Semir Bechir Suheil Gaouar, Shaimaa Roshdy Abdullah Reda, Siham Fellahi, Slimane Khayi, Soumia Ayed, Thabang Madisha, Tulsi Sahil, Ogbuagu Ugorji Udensi, Verena Ras, Victor Ezebuiro, Vincent C. Duru, Xavier David, Yonas Geberemichael, Yves H. Tchiechoua, Zahra Mungloo-Dilmohamud, Zhiliang Chen, Christian Happi, Thomas Kariuki, Cathrine Ziyomo, Appolinaire Djikeng, Bouabid Badaoui, Ntanganedzeni Mapholi, Anne Muigai, Julian O. Osuji, ThankGod Echezona Ebenezer
Journal: Nature Genetics (2024)
Analysing common topics of secure patient messages in hidradenitis suppurativa: a text-embedding and natural language-processing approach
Authors: Michael L Chen, Jiyeong Kim, Haley B Naik, Maria A Aleshin, Kavita Y Sarin, Leandra A Barnes, Eleni Linos
Journal: British Journal of Dermatology (2024)

Our study of 410 patients with hidradenitis suppurativa (HS) and 12 805 direct patient messages identified common message topics, including scheduling; medication refills; itch, bleeding and burning symptoms; insurance and cost; pain; and wound care. Compared with the overall cohort of patients with HS, a lower proportion of Black and Hispanic patients utilized patient portal messaging. Our study provides insights into message topics among patients with HS and identifies opportunities for optimizing care via secure messaging.
The ethics of ChatGPT in medicine and healthcare: a systematic review on Large Language Models (LLMs)
Authors: Joschka Haltaufderheide, Robert Ranisch
Journal: npj Digital Medicine (2024)

With the introduction of ChatGPT, Large Language Models (LLMs) have received enormous attention in healthcare. Despite potential benefits, researchers have underscored various ethical implications. While individual instances have garnered attention, a systematic and comprehensive overview of practical applications currently researched and ethical issues connected to them is lacking. Against this background, this work maps the ethical landscape surrounding the current deployment of LLMs in medicine and healthcare through a systematic review. Electronic databases and preprint servers were queried using a comprehensive search strategy which generated 796 records. Studies were screened and extracted following a modified rapid review approach. Methodological quality was assessed using a hybrid approach. For 53 records, a meta-aggregative synthesis was performed. Four general fields of applications emerged showcasing a dynamic exploration phase. Advantages of using LLMs are attributed to their capacity in data analysis, information provisioning, support in decision-making or mitigating information loss and enhancing information accessibility. However, our study also identifies recurrent ethical concerns connected to fairness, bias, non-maleficence, transparency, and privacy. A distinctive concern is the tendency to produce harmful or convincing but inaccurate content. Calls for ethical guidance and human oversight are recurrent. We suggest that the ethical guidance debate should be reframed to focus on defining what constitutes acceptable human oversight across the spectrum of applications. This involves considering the diversity of settings, varying potentials for harm, and different acceptable thresholds for performance and certainty in healthcare. Additionally, critical inquiry is needed to evaluate the necessity and justification of LLMs' current experimental use.
2023 American College of Rheumatology (<scp>ACR</scp>)/American College of Chest Physicians (<scp>CHEST</scp>) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases
Authors: Sindhu R. Johnson, Elana J. Bernstein, Marcy B. Bolster, Jonathan H. Chung, Sonye K. Danoff, Michael D. George, Dinesh Khanna, Gordon Guyatt, Reza D. Mirza, Rohit Aggarwal, Aberdeen Allen, Shervin Assassi, Lenore Buckley, Hassan A. Chami, Douglas S. Corwin, Paul F. Dellaripa, Robyn T. Domsic, Tracy J. Doyle, Catherine Marie Falardeau, Tracy M. Frech, Fiona K. Gibbons, Monique Hinchcliff, Cheilonda Johnson, Jeffrey P. Kanne, John S. Kim, Sian Yik Lim, Scott Matson, Zsuzsanna H. McMahan, Samantha J. Merck, Kiana Nesbitt, Mary Beth Scholand, Lee Shapiro, Christine D. Sharkey, Ross Summer, John Varga, Anil Warrier, Sandeep K. Agarwal, Danielle Antin‐Ozerkis, Bradford Bemiss, Vaidehi Chowdhary, Jane E. Dematte D'Amico, Robert Hallowell, Alicia M. Hinze, Patil A. Injean, Nikhil Jiwrajka, Elena K. Joerns, Joyce S. Lee, Ashima Makol, Gregory C. McDermott, Jake G. Natalini, Justin M. Oldham, Didem Saygin, Kimberly Showalter Lakin, Namrata Singh, Joshua J. Solomon, Jeffrey A. Sparks, Marat Turgunbaev, Samera Vaseer, Amy Turner, Stacey Uhl, Ilya Ivlev
Journal: Arthritis & Rheumatology (2024)

Objective We provide evidence‐based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. Methods We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. Results Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high‐resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6‐minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. Conclusion This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.
AI-based selection of individuals for supplemental MRI in population-based breast cancer screening: the randomized ScreenTrustMRI trial
Authors: Mattie Salim, Yue Liu, Moein Sorkhei, Dimitra Ntoula, Theodoros Foukakis, Irma Fredriksson, Yanlu Wang, Martin Eklund, Hossein Azizpour, Kevin Smith, Fredrik Strand
Journal: Nature Medicine (2024)

Abstract Screening mammography reduces breast cancer mortality, but studies analyzing interval cancers diagnosed after negative screens have shown that many cancers are missed. Supplemental screening using magnetic resonance imaging (MRI) can reduce the number of missed cancers. However, as qualified MRI staff are lacking, the equipment is expensive to purchase and cost-effectiveness for screening may not be convincing, the utilization of MRI is currently limited. An effective method for triaging individuals to supplemental MRI screening is therefore needed. We conducted a randomized clinical trial, ScreenTrustMRI, using a recently developed artificial intelligence (AI) tool to score each mammogram. We offered trial participation to individuals with a negative screening mammogram and a high AI score (top 6.9%). Upon agreeing to participate, individuals were assigned randomly to one of two groups: those receiving supplemental MRI and those not receiving MRI. The primary endpoint of ScreenTrustMRI is advanced breast cancer defined as either interval cancer, invasive component larger than 15 mm or lymph node positive cancer, based on a 27-month follow-up time from the initial screening. Secondary endpoints, prespecified in the study protocol to be reported before the primary outcome, include cancer detected by supplemental MRI, which is the focus of the current paper. Compared with traditional breast density measures used in a previous clinical trial, the current AI method was nearly four times more efficient in terms of cancers detected per 1,000 MRI examinations (64 versus 16.5). Most additional cancers detected were invasive and several were multifocal, suggesting that their detection was timely. Altogether, our results show that using an AI-based score to select a small proportion (6.9%) of individuals for supplemental MRI after negative mammography detects many missed cancers, making the cost per cancer detected comparable with screening mammography. ClinicalTrials.gov registration: NCT04832594 .
A vagal–brainstem interoceptive circuit for cough-like defensive behaviors in mice
Authors: Noam Gannot, Xingyu Li, Chrystian D. Phillips, Ayse Bilge Ozel, Karin Harumi Uchima Koecklin, John P. Lloyd, Lusi Zhang, Katie Emery, Tomer Stern, Jun Z. Li, Peng Li
Journal: Nature Neuroscience (2024)
Evaluation of sodium borocaptate (BSH) and boronophenylalanine (BPA) as boron delivery agents for neutron capture therapy (NCT) of cancer: an update and a guide for the future clinical evaluation of new boron delivery agents for NCT
Authors: Rolf F. Barth, Nilendu Gupta, Shinji Kawabata
Journal: Cancer Communications (2024)

Abstract Boron neutron capture therapy (BNCT) is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron‐10, a stable isotope, is irradiated with neutrons of the appropriate energy to produce boron‐11 in an unstable form, which undergoes instantaneous nuclear fission to produce high‐energy, tumoricidal alpha particles. The primary purpose of this review is to provide an update on the first drug used clinically, sodium borocaptate (BSH), by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug, boronophenylalanine (BPA), which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous melanomas. Subsequently, BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers, specifically brain tumors and recurrent tumors of the head and neck region. The focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high‐grade gliomas and their subsequent clinical use to treat patients with high‐grade gliomas. First , we will summarize the studies that were carried out in Japan with BSH and subsequently at our own institution, The Ohio State University, and those of several other groups. Second , we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for BNCT. Third , although there have been intense efforts to develop new and better boron delivery agents for BNCT, none of these have yet been evaluated clinically. The present report will provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.
Unsupervised representation learning on high-dimensional clinical data improves genomic discovery and prediction
Authors: Taedong Yun, Justin Cosentino, Babak Behsaz, Zachary R. McCaw, Davin Hill, Robert Luben, Dongbing Lai, John Bates, Howard Yang, Tae-Hwi Schwantes-An, Yuchen Zhou, Anthony P. Khawaja, Andrew Carroll, Brian D. Hobbs, Michael H. Cho, Cory Y. McLean, Farhad Hormozdiari
Journal: Nature Genetics (2024)

Abstract Although high-dimensional clinical data (HDCD) are increasingly available in biobank-scale datasets, their use for genetic discovery remains challenging. Here we introduce an unsupervised deep learning model, Representation Learning for Genetic Discovery on Low-Dimensional Embeddings (REGLE), for discovering associations between genetic variants and HDCD. REGLE leverages variational autoencoders to compute nonlinear disentangled embeddings of HDCD, which become the inputs to genome-wide association studies (GWAS). REGLE can uncover features not captured by existing expert-defined features and enables the creation of accurate disease-specific polygenic risk scores (PRSs) in datasets with very few labeled data. We apply REGLE to perform GWAS on respiratory and circulatory HDCD—spirograms measuring lung function and photoplethysmograms measuring blood volume changes. REGLE replicates known loci while identifying others not previously detected. REGLE are predictive of overall survival, and PRSs constructed from REGLE loci improve disease prediction across multiple biobanks. Overall, REGLE contain clinically relevant information beyond that captured by existing expert-defined features, leading to improved genetic discovery and disease prediction.
Telomere-to-telomere Citrullus super-pangenome provides direction for watermelon breeding
Authors: Yilin Zhang, Mingxia Zhao, Jingsheng Tan, Minghan Huang, Xiao Chu, Yan Li, Xue Han, Taohong Fang, Yao Tian, Robert Jarret, Dongdong Lu, Yijun Chen, Lifang Xue, Xiaoni Li, Guochen Qin, Bosheng Li, Yudong Sun, Xing Wang Deng, Yun Deng, Xingping Zhang, Hang He
Journal: Nature Genetics (2024)

Abstract To decipher the genetic diversity within the cucurbit genus Citrullus , we generated telomere-to-telomere (T2T) assemblies of 27 distinct genotypes, encompassing all seven Citrullus species. This T2T super-pangenome has expanded the previously published reference genome, T2T-G42, by adding 399.2 Mb and 11,225 genes. Comparative analysis has unveiled gene variants and structural variations (SVs), shedding light on watermelon evolution and domestication processes that enhanced attributes such as bitterness and sugar content while compromising disease resistance. Multidisease-resistant loci from Citrullus amarus and Citrullus mucosospermus were successfully introduced into cultivated Citrullus lanatus . The SVs identified in C. lanatus have not only been inherited from cordophanus but also from C. mucosospermus , suggesting additional ancestors beyond cordophanus in the lineage of cultivated watermelon. Our investigation substantially improves the comprehension of watermelon genome diversity, furnishing comprehensive reference genomes for all Citrullus species. This advancement aids in the exploration and genetic enhancement of watermelon using its wild relatives.
A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy
Authors: David M. Cordas dos Santos, Tobias Tix, Roni Shouval, Anat Gafter-Gvili, Jean-Baptiste Alberge, Edward R. Scheffer Cliff, Sebastian Theurich, Michael von Bergwelt-Baildon, Irene M. Ghobrial, Marion Subklewe, Miguel-Angel Perales, Kai Rejeski
Journal: Nature Medicine (2024)
Single cell <scp>RNA</scp> and T‐cell receptor sequencing reveals substantive similarities between synovial fluid and synovial tissue T‐cells in inflammatory arthritis
Authors: Lucy E. Durham, Frances C. Humby, Nora Ng, Sarah Ryan, Rosamond Nuamah, Kathy Fung, Athul Menon Kallayil, Pawan Dhami, Bruce W. Kirkham, Leonie S. Taams
Journal: Arthritis & Rheumatology (2024)

Synovial fluid (SF)-derived T cells are frequently studied as a proxy for investigating the synovial tissue (ST) T cell infiltrate in inflammatory arthritis. However, because ST is the primary site of inflammatory activity, there is debate as to whether SF provides a true reflection of the ST T cell population.
Genetically Proxied Interleukin‐13 Inhibition Is Associated With Risk of Psoriatic Disease: A Mendelian Randomization Study
Authors: Sizheng Steven Zhao, Kimme Hyrich, Zenas Yiu, Anne Barton, John Bowes
Journal: Arthritis & Rheumatology (2024)

Objective Inhibitors of the interleukin 13 (IL‐13) pathway, such as dupilumab, are licensed for atopic dermatitis and asthma. Adverse events resembling psoriatic disease after dupilumab initiation have been reported, but evidence is limited to case reports with uncertain causality. We aimed to investigate whether genetically mimicked IL‐13 inhibition (IL‐13i) is associated with risk of psoriatic arthritis (PsA) and psoriasis. Methods We instrumented IL‐13i using a protein‐coding variant in the IL13 gene, rs20541, that is associated with circulating eosinophil count (biomarker of IL‐13i) at genome‐wide significance in a study of 563,946 individuals. Outcome genetic data were taken from studies of PsA, psoriasis, and related spondyloarthritis traits in up to 10,588 cases and 209,287 controls. Colocalization analysis was performed to examine genetic confounding. We additionally used circulating IgE as a biomarker to test whether associations were replicated, both in the test and in an independent genetic dataset. We also replicated analyses using individual‐level data from the UK Biobank. Results Genetically proxied IL‐13i was associated with increased risk of PsA (odds ratio [OR] 37.39; 95% confidence interval [95% CI] 11.52–121.34; P = 1.64 × 10 −9 ) and psoriasis (OR 20.08; 95% CI 4.38–92.01; P = 1.12 × 10 −4 ). No consistent associations were found for Crohn disease, ulcerative colitis, ankylosing spondylitis, or iritis. Colocalization showed no strong evidence of genetic confounding for psoriatic disease. Results were replicated using circulating IgE for the exposure, using independent outcome data and using individual‐level data. Conclusion We provide supportive genetic evidence that IL‐13i is linked to increased risk of PsA and psoriasis. Physicians prescribing IL‐13 inhibitors should be vigilant for these adverse events. image
Weighing the Cardiovascular Risks of Low‐Dose Glucocorticoids in Rheumatoid Arthritis from Real‐World Data
Authors: Tate M. Johnson
Journal: Arthritis & Rheumatology (2024)

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