tbuckley/cabot-search huggingface dataset:
GTax: improving de novo transcriptome assembly by removing foreign RNA contamination
Authors: Roberto Vera Alvarez, David Landsman
Journal: Genome biology (2024)

Abstract The cost and complexity of generating a complete reference genome means that many organisms lack an annotated reference. An alternative is to use a de novo reference transcriptome. This technology is cost-effective but is susceptible to off-target RNA contamination. In this manuscript, we present GTax, a taxonomy-structured database of genomic sequences that can be used with BLAST to detect and remove foreign contamination in RNA sequencing samples before assembly. In addition, we use a de novo transcriptome assembly of Solanum lycopersicum (tomato) to demonstrate that removing foreign contamination in sequencing samples reduces the number of assembled chimeric transcripts.
When I use a word . . . Medical anniversaries in 2024
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

My list of 63 medically related anniversaries for 2024 (events in years ending '24 and'74) includes: ● 23 births: Daniel Arnoldi, Canadian physician; Gaspard Laurent Bayle, French physician; Charles Bell, British anatomist, neurologist, surgeon, and artist; Johann Jakob Bernhardi, German physician and botanist; Paul Broca, French physician, anatomist, and anthropologist; Jean-Francois Coindet, French physician; Franz von Paula Gruithuisen, Bavarian physician and astronomer; Roger Charles Louis Guillemin, French-born, American neuroscientist; Anton Ludwig Ernst Horn, German physician; Andrew Jukes, British surgeon; Nikolai Korotkov, Russian surgeon; August Krogh, Danish physiologist; William Lattimore, American physician; Jonathan Letterman, American surgeon; Constantin Levaditi, Romanian physician and microbiologist; William George Maton, English physician; António Egas Moniz, Portuguese physician and neurologist; John Conrad Otto, American physician; Georges-Simon Serullas, French professor of pharmacy; Thomas Sydenham, English physician; Francisco Vallés, Spanish physician; Robert Watt, Scottish physician and bibliographer; Torsten Wiesel, Swedish neurophysiologist; ● 14 deaths: Johann Conrad Ammann, Swiss-born physician and naturalist; Anthony Askew, English physician and book collector; William Browne, English physician; Bartolomeo Eustachio, Italian anatomist; Samuel Gottlieb Gmelin, German physician, botanist, and explorer; Oliver Goldsmith, Anglo-Irish writer, poet, playwright, and apothecary's assistant; William Hewson, British surgeon, anatomist, and physiologist; Thomas Linacre, English physician; Jacques Loeb, German-born, American physiologist; William Macewen, Scottish surgeon; James Parkinson, English surgeon, apothecary, geologist, palaeontologist, and political activist; Johann Jakob Reiske, German philologist; Earl Wilbur Sutherland, American physiologist; Ijsbrand van Diemerbroek, Dutch physician and anatomist; ● 4 biomedical texts published, written by Ulisse Aldrovandi, John Floyer, William Hunter, and Thomas Willis; ● clinical therapies introduced by Henry Hill Hickman (anaesthesia), Franz Anton Mesmer (mesmerism), and Robert Wood Johnson with George J Seabury (surgical dressings); ● observations on chemical elements by Jöns Jacob Berzelius (silicon, thorium, and zirconium), Paul-Émile Lecoq de Boisbaudran (gallium), Johan Gottlieb Gahn (manganese), and Carl Wilhelm Scheele (manganese and chlorine); ● biochemical, chemical, microbiological, and physiological observations by Theodor Billroth, spouses George Frederick Dick and Gladys Henry Dick, Bernardo Alberto Houssay, Jacobus Henricus van 9t Hoff with Joseph Le Bel, and Thomas Willis; ● establishment of the first British medical school to train women doctors, The London School of Medicine for Women; ● Nobel prizes awarded to Willem Einthoven (1924) and to Albert Claude, Christian de Duve, and George E Palade (1974).
Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation
Authors: Emeline Joulia, Michaël F. Michieletto, Arantxa Agesta, Cindy Peillex, Virginie Girault, Anne-Louise Le Dorze, Romain Peroceschi, Florence Bucciarelli, Marion Szelechowski, Adeline Chaubet, Nawad Hakim, Rémi Marrocco, Emeline Lhuillier, Manuel Lebeurrier, Rafael J. Argüello, Abdelhadi Saoudi, Hicham El Costa, Veronique Adoue, Thierry Walzer, Jean-Emmanuel Sarry, Anne S. Dejean
Journal: The Journal of Experimental Medicine (2024)

The mechanisms whereby Eomes controls tissue accumulation of T cells and strengthens inflammation remain ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. While Eomes is dispensable for the initial priming of CD4+ T cells, it is required for long-term maintenance of CNS-infiltrating CD4+ T cells. We reveal that the impact of Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and functions. Accordingly, epigenetic studies demonstrate that Eomes supports mitochondrial function by direct binding to either metabolism-associated genes or mitochondrial transcriptional modulators. Besides, the significance of these findings was confirmed in CD4+ T cells from healthy donors and multiple sclerosis patients. Together, our data reveal a new mechanism by which Eomes promotes severity and chronicity of inflammation via the enhancement of CD4+ T cell mitochondrial functions and resistance to stress-induced cell death.
Author Correction: Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy
Authors: Nisha M. Badders, Ane Korff, Helen C. Miranda, Pradeep K. Vuppala, Rebecca B. Smith, Brett J. Winborn, Emmanuelle R. Quemin, Bryce L. Sopher, Jennifer Dearman, James Messing, Nam Chul Kim, Jennifer Moore, Brian D. Freibaum, Anderson P. Kanagaraj, Baochang Fan, Heather Tillman, Ping-Chung Chen, Yingzhe Wang, Burgess B. Freeman, Yimei Li, Hong Joo Kim, Albert R. La Spada, J. Paul Taylor
Journal: Nature Medicine (2024)
Locus folding mechanisms determine modes of antigen receptor gene assembly
Authors: Brittney M. Allyn, Katharina E. Hayer, Clement Oyeniran, Vincent Nganga, Kyutae Lee, Bikash Mishra, Ahmet Sacan, Eugene M. Oltz, Craig H. Bassing
Journal: The Journal of Experimental Medicine (2024)

The dynamic folding of genomes regulates numerous biological processes, including antigen receptor (AgR) gene assembly. We show that, unlike other AgR loci, homotypic chromatin interactions and bidirectional chromosome looping both contribute to structuring Tcrb for efficient long-range V(D)J recombination. Inactivation of the CTCF binding element (CBE) or promoter at the most 5′Vβ segment (Trbv1) impaired loop extrusion originating locally and extending to DβJβ CBEs at the opposite end of Tcrb. Promoter or CBE mutation nearly eliminated Trbv1 contacts and decreased RAG endonuclease-mediated Trbv1 recombination. Importantly, Trbv1 rearrangement can proceed independent of substrate orientation, ruling out scanning by DβJβ-bound RAG as the sole mechanism of Vβ recombination, distinguishing it from Igh. Our data indicate that CBE-dependent generation of loops cooperates with promoter-mediated activation of chromatin to juxtapose Vβ and DβJβ segments for recombination through diffusion-based synapsis. Thus, the mechanisms that fold a genomic region can influence molecular processes occurring in that space, which may include recombination, repair, and transcriptional programming.
Multi-omics of the gut microbial ecosystem in patients with microsatellite-instability-high gastrointestinal cancer resistant to immunotherapy
Authors: Siyuan Cheng, Zihan Han, Die Dai, Fang Li, Xiaotian Zhang, Ming Lu, Zhihao Lu, Xicheng Wang, Jun Zhou, Jian Li, Xiaohuan Guo, Panwei Song, Chuangzhao Qiu, Wei Shen, Qi Zhang, Ning Zhu, Xi Wang, Yan Tan, Yan Kou, Xiaochen Yin, Lin Shen, Zhi Peng
Journal: Cell Reports Medicine (2024)

Despite the encouraging efficacy of anti-PD-1/PD-L1 immunotherapy in microsatellite-instability-high/deficient mismatch repair (MSI-H/dMMR) advanced gastrointestinal cancer, many patients exhibit primary or acquired resistance. Using multi-omics approaches, we interrogate gut microbiome, blood metabolome, and cytokines/chemokines of patients with MSI-H/dMMR gastrointestinal cancer (N = 77) at baseline and during the treatment. We identify a number of microbes (e.g., Porphyromonadaceae) and metabolites (e.g., arginine) highly associated with primary resistance to immunotherapy. An independent validation cohort (N = 39) and mouse model are used to further confirm our findings. A predictive machine learning model for primary resistance is also built and achieves an accuracy of 0.79 on the external validation set. Furthermore, several microbes are pinpointed that gradually changed during the process of acquired resistance. In summary, our study demonstrates the essential role of gut microbiome in drug resistance, and this can be utilized as a preventative diagnosis tool and therapeutic target in the future.
Author Correction: Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial
Authors: Shu-Qiang Yuan, Run-Cong Nie, Ying Jin, Cheng-Cai Liang, Yuan-Fang Li, Rui Jian, Xiao-Wei Sun, Ying-Bo Chen, Wen-Long Guan, Zi-Xian Wang, Hai-Bo Qiu, Wei Wang, Shi Chen, Dong-Sheng Zhang, Yi-Hong Ling, Shao-Yan Xi, Mu-Yan Cai, Chun-Yu Huang, Qiu-Xia Yang, Zhi-Min Liu, Yuan-Xiang Guan, Yong-Ming Chen, Ji-Bin Li, Xiong-Wen Tang, Jun-Sheng Peng, Zhi-Wei Zhou, Rui-Hua Xu, Feng Wang
Journal: Nature Medicine (2024)
Author Correction: Metabolomic epidemiology offers insights into disease aetiology
Authors: Harriett Fuller, Yiwen Zhu, Jayna Nicholas, Haley A. Chatelaine, Emily M. Drzymalla, Afrand K. Sarvestani, Sachelly Julián-Serrano, Usman A. Tahir, Nasa Sinnott-Armstrong, Laura M. Raffield, Ali Rahnavard, Xinwei Hua, Katherine H. Shutta, Burcu F. Darst
Journal: Nature Metabolism (2024)
Diagnostic Errors in Hospitalized Adults Who Died or Were Transferred to Intensive Care
Authors: Andrew D. Auerbach, Tiffany M. Lee, Colin C. Hubbard, Sumant R. Ranji, Katie Raffel, Gilmer Valdes, John Boscardin, Anuj K. Dalal, Alyssa Harris, Ellen Flynn, Jeffrey L. Schnipper, David Feinbloom, Bethany N. Roy, Shoshana J. Herzig, Mohammed Wazir, Esteban F. Gershanik, Abhishek Goyal, Pooja R. Chitneni, Sharran Burney, Janice Galinsky, Sarah Rastegar, Danielle Moore, Carl Berdahl, Edward G. Seferian, Krithika Suri, Tea Ramishvili, Deepak Vedamurthy, Daniel P. Hunt, Amisha S. Mehta, Haritha Katakam, Stephanie A. Field, Barbara Karatasakis, Katharina Beeler, Allison M. Himmel, Shaker Eid, Sonal Gandhi, Ivonne M. Pena, Zachary S. Ranta, Samuel D. Lipten, David J. Lucier, Beth Walker-Corkery, Jennifer Kleinman Sween, Robert W. Kirchoff, Katie M. Rieck, Gururaj J. Kolar, Riddhi S. Parikh, Caroline Burton, Chandrasagar Dugani, Kwame Dapaah-Afriyie, Arkadiy Finn, Sushma B. Raju, Asif Surani, Ankur Segon, Sanjay Bhandari, Gopi J. Astik, Kevin J. O’Leary, A. Shams Helminski, James Anstey, Mengyu Zhou, Angela E. Alday, Stephanie A.C. Halvorson, Armond M. Esmaili, Peter Barish, Cynthia Fenton, Molly Kantor, Kwang Jin Choi, Andrew W. Schram, Gregory Ruhnke, Hemali Patel, Anunta Virapongse, Marisha Burden, Li-Kheng Ngov, Angela Keniston, Preetham Talari, John B. Romond, Sarah E. Vick, Mark V. Williams, Ruby A. Marr, Ashwin B. Gupta, Jeffrey M. Rohde, Frances Mao, Michele M. Fang, S. Ryan Greysen, Pranav Shah, Christopher S. Kim, Maya Narayanan, Benjamin Wolpaw, Sonja M. Ellingson, Farah A. Kaiksow, Jordan S. Kenik, David Sterken, Michelle E. Lewis, Bhavish R. Manwani, Russell W. Ledford, Chase J. Webber, Eduard E. Vasilevskis, Ryan J. Buckley, Sunil B. Kripalani, Christopher Sankey, Sharon R. Ostfeld-Johns, Katherine Gielissen, Thilan Wijesekera, Eric Jordan, Abhishek Karwa, Bethlehem Churnet, David Chia, Katherine Brooks
Journal: JAMA Internal Medicine (2024)

Diagnostic errors contribute to patient harm, though few data exist to describe their prevalence or underlying causes among medical inpatients.
The Case of Anticoagulation for Progressing Stroke
Authors: Brett Cucchiara, Jennifer J. Majersik
Journal: JAMA Neurology (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Increasing Clinical Complexity—Implications for Care Delivery, Payment Models, and the Health Care Workforce
Authors: Daniel M. Blumenthal
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Publication of Results of Registered Trials With Published Study Protocols, 2011-2022
Authors: Colby J. Vorland, Andrew W. Brown, Halil Kilicoglu, Xiangji Ying, Evan Mayo-Wilson
Journal: JAMA Network Open (2024)

Importance Publishing study protocols might reduce research waste because of unclear methods or incomplete reporting; on the other hand, there might be few additional benefits of publishing protocols for registered trials that are never completed or published. No study has investigated the proportion of published protocols associated with published results. Objective To estimate the proportion of published trial protocols for which there are not associated published results. Design, Setting, and Participants This cross-sectional study used stratified random sampling to identify registered clinical trials with protocols published between January 2011 and August 2022 and indexed in PubMed Central. Ongoing studies and those within 1 year of the primary completion date on ClinicalTrials.gov were excluded. Published results were sought from August 2022 to March 2023 by searching ClinicalTrials.gov, emailing authors, and using an automated tool, as well as through incidental discovery. Main Outcomes and Measures The primary outcome was a weighted estimate of the proportion of registered trials with published protocols that also had published main results. The proportion of trials with unpublished results was estimated using a weighted mean. Results From 1500 citations that were screened, 308 clinical trial protocols were included, and it was found that 87 trials had not published their main results. Most included trials were investigator-initiated evaluations of nonregulated products. When published, results appeared a mean (SD) of 3.4 (2.0) years after protocol publications. With the use of a weighted mean, an estimated 4754 (95% CI, 4296-5226) eligible clinical trial protocols were published and indexed in PubMed Central between 2011 and 2022. In the weighted analysis, 1708 of those protocols (36%; 95% CI, 31%-41%) were not associated with publication of main results. In a sensitivity analysis excluding protocols published after 2019, an estimated 25% (95% CI, 20%-30%) of 3670 (95% CI, 3310-4032) protocol publications were not associated with publication of main results. Conclusions and Relevance This cross-sectional study of clinical trial protocols published on PubMed Central between 2011 and 2022 suggests that many protocols were not associated with subsequent publication of results. The overall benefits of publishing study protocols might outweigh the research waste caused by unnecessary protocol publications.
Associations Among Optimal Lung Cancer Treatment, Clinical Outcomes, and Health Care Utilization in Patients Who Underwent Comprehensive Genomic Profiling
Authors: Adam C. Powell, Elifnur Yay Donderici, Nicole J. Zhang, Shaun P. Forbes, Julie Wiedower, Amy C. McNeal, Mark D. Hiatt
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: Although immune checkpoint inhibitor immunotherapies are contraindicated as first-line treatment of advanced non–small cell lung cancer (NSCLC) in patients with ALK rearrangement and EGFR mutation, many receive them. The purpose of this study was to examine the association between optimal first-line treatment in this population and clinical outcomes. Methods: Claims and genomic data from patients with advanced or metastatic NSCLC were extracted from a nationally representative GuardantINFORM dataset. Patients who had their first claim mentioning advanced or metastatic NSCLC between March 2019 and February 2020 and had ALK rearrangement or EGFR mutation detected by comprehensive genomic profiling were included in this study. Patients were classified as having received optimal or suboptimal first-line treatment. Claims were reviewed to determine real-world time to next treatment, real-world time to discontinuation, and health services utilization (emergency department, inpatient, and outpatient) in the 12 months following first-line treatment initiation. Survival analyses were conducted using Kaplan-Meier plots and Cox proportional hazard models. Health services utilization was compared between the groups using t tests and negative binomial models. Results: Of the 359 patients included, 280 (78.0%) received optimal first-line treatment. Optimally treated patients had longer median real-world time to next treatment (11.2 vs 4.4 months; P &lt;.01) and real-world time to discontinuation (10.4 vs 1.9 months; P &lt;.01). The optimal group had significantly fewer emergency department presentations (0.76 vs 1.27; P &lt;.01) and outpatient visits (22.9 vs 42.7; P &lt;.01) than the suboptimal group but did not significantly differ in inpatient utilization. Adjusted utilization analysis yielded similar findings. Conclusions: Patients with NSCLC who received optimal treatment, as determined by comprehensive genomic profiling using next-generation sequencing–based circulating tumor DNA testing (Guardant360), had significantly superior clinical and utilization outcomes, reinforcing existing guidelines recommending profiling at the onset of treatment.
Sibling Death in Childhood and Early Adulthood and Risk of Early-Onset Cardiovascular Disease
Authors: Chen Huang, Jiahuan Peng, Priscilla Ming Yi Lee, Ce Wang, Kecheng Wei, Minhong Liang, Guoyou Qin, Yongfu Yu, Jiong Li
Journal: JAMA Network Open (2024)

Importance Sibling death is a highly traumatic event, but empirical evidence on the association of sibling death in childhood and early adulthood with subsequent risk of incident cardiovascular disease (CVD) remains limited. Objective To evaluate the association between sibling death in the early decades of life and subsequent risk of incident early-onset CVD. Design, Setting, and Participants This population-based cohort study included 2 098 659 individuals born in Denmark from 1978 to 2018. Follow-up started at age 1 year or the date of the first sibling’s birth, whichever occurred later, and it ended at the first diagnosis of CVD, the date of death, emigration, or December 31, 2018, whichever came first. Data analyses were conducted from November 1, 2021, through January 10, 2022. Exposures The death of a sibling. Main Outcomes and Measures The outcome was early-onset CVD. Cox models were used to estimate hazard ratios (HRs) with 95% CIs. Results This study included 2 098 659 individuals (1 076 669 [51.30%] male; median [IQR] age at death of sibling, 11.48 [4.68-21.32] years). During the median (IQR) follow-up of 17.52 (8.85-26.05) years, 1286 and 76 862 individuals in the bereaved and nonbereaved groups, respectively, were diagnosed with CVD. Sibling death in childhood and early adulthood was associated with a 17% increased risk of overall CVD (HR, 1.17; 95% CI, 1.10-1.23; cumulative incidence in bereaved individuals, 1.96% [1.61%-2.34%]; cumulative incidence in nonbereaved individuals at age 41 years, 1.35% [1.34%-1.37%]; cumulative incidence difference: 0.61% [95% CI, 0.24%-0.98%]). Increased risks were also observed for most type-specific CVDs, in particular for myocardial infarction (HR, 1.66; 95% CI, 1.12-2.46), ischemic heart disease (HR, 1.52; 95% CI, 1.22-1.90), and heart failure (HR, 1.50; 95% CI, 1.00-2.26). The association was observed whether the sibling died due to CVD (HR, 2.54; 95% CI, 2.04-3.17) or non-CVD (HR, 1.13; 95% CI, 1.06-1.19) causes. The increased risk of CVD was more pronounced for individuals who lost a twin or younger sibling (HR, 1.25; 95% CI, 1.15-1.36) than an elder sibling (HR, 1.11; 95% CI, 1.03-1.20). Conclusions and Relevance In this cohort study of the Danish population, sibling death in childhood and early adulthood was associated with increased risks of overall and most type-specific early-onset CVDs, with the strength of associations varying by cause of death and age difference between sibling pairs. The findings highlight the need for extra attention and support to the bereaved siblings to reduce CVD risk later in life.
Ischemic preconditioning in liver resection surgery: insights and future directions
Authors: Kuo-Chuan Hung, I-Wen Chen, Ping-Hsin Liu
Journal: International Journal of Surgery (2024)

aDepartment of Anesthesiology, Chi Mei Medical Center, Tainan city, Taiwan bDepartment of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan city, Taiwan cDepartment of Anesthesiology, E-Da Dachang Hospital, I-Shou University, Kaohsiung City, Taiwan Short title: Ischemic Preconditioning for Liver Surgery Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Anesthesiology, E-Da Dachang Hospital, I-Shou University, No. 305, Dachang 1st Road, Sanmin District, Kaohsiung City, Taiwan. Tel: +886-7-6150011 ext 1007. Fax: +886-7-6150915. E-mail address: [email protected] (P-H Liu). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/