tbuckley/cabot-search huggingface dataset:
Coaching inexperienced clinicians before a high stakes medical procedure: randomized clinical trial
Authors: Stephen G Flynn, Raymond S Park, Anupam B Jena, Steven J Staffa, Samuel Y Kim, Julia D Clarke, Ivy V Pham, Karina E Lukovits, Sheng Xiang Huang, Georgios D Sideridis, Rachel S Bernier, John E Fiadjoe, Peter H Weinstock, James M Peyton, Mary Lyn Stein, Pete G Kovatsis
Journal: BMJ (2024)

To assess whether training provided to an inexperienced clinician just before performing a high stakes procedure can improve procedural care quality, measuring the first attempt success rate of trainees performing infant orotracheal intubation.
Gaza: UK doctors recount horrific hospital scenes as they urge Keir Starmer to act
Authors: Elisabeth Mahase
Journal: BMJ (2024)

Chetna Malhotra, Mahham Shafiq, Ada Portia Macarubbo Batcagan-AbuegLien Centre for Palliative Care, Duke-NUS Medical School, Singapore Dr Chetna Malhotra; chetna.malhotra{at}duke-nus.edu.sgReceived 22 December 2021Accepted 4 July 2022
Medical education fit for the future requires radical change
Authors: Hamaad Ahmad Khan, George Gillett, Katie Choi, Zeynep Tugce Tugcu, Yasmin Baker, Emma Tonner, Bogdan Chiva Giurca
Journal: BMJ (2024)

Jin Jiang1,*, Qizhe Shao1, Sisi Xie2, Xiaoying Xiao2, Ruisi Guo2, Min Jin3 and Di Chen1,4,*Center for Reproductive Medicine of The Second Affiliated Hospital, Center for Regeneration and Cell Therapy of Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, ChinaZhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, ChinaCenter for Reproductive Medicine of The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, ChinaNational Key Laboratory of Biobased Transportation Fuel Technology, Haining, Zhejiang, 314400, China↵Corresponding author. E-mail: dichen{at}intl.zju.edu.cn (DC) jinjiang{at}intl.zju.edu.cn (JJ)
Broken chords: the music of grief
Authors: Desmond O'Neill
Journal: BMJ (2024)

With the aging of the world population, age-related hearing loss (presbycusis) and other hearing disorders such as tinnitus become more prevalent, leading to reduced quality of life and social isolation. Unveiling the genetic and environmental factors leading to age-related auditory disorders could suggest lifestyle and therapeutic interventions to slow auditory aging. In the following, we built the first machine learning-based hearing age predictor by training models to predict chronological age from hearing test results (root mean squared error=7.10±0.07 years; R-Squared=31.4±0.8%). We defined hearing age as the prediction outputted by the model on unseen samples, and accelerated auditory aging as the difference between a participant's hearing age and age. We then performed a genome wide association study [GWAS] and found that accelerated hearing aging is 14.1±0.4% GWAS-heritable. Specifically, accelerated auditory aging is associated with 662 single nucleotide polymorphisms in 243 genes (e.g OR2B4P, involved in smell perception). Similarly, it is associated with biomarkers (e.g cognitive tests), clinical phenotypes (e.g chest pain), diseases (e.g depression), environmental (e.g smoking, sleep) and socioeconomic (e.g income, education, social support) variables. The hearing age predictor could be used to evaluate the efficiency of emerging rejuvenation therapies on hearing.
Italy abolishes fines for refusing covid-19 vaccination
Authors: Marta Paterlini
Journal: BMJ (2024)

Maxim Zvyagin1,†, Alexander Brace1,2,†, Kyle Hippe1,†, Yuntian Deng3,4,†, Bin Zhang5, Cindy Orozco Bohorquez5, Austin Clyde1,2, Bharat Kale6, Danilo Perez-Rivera1, Heng Ma1, Carla M. Mann1, Michael Irvin1, J. Gregory Pauloski2, Logan Ward1, Valerie Hayot2, Murali Emani1, Sam Foreman1, Zhen Xie1, Diangen Lin2, Maulik Shukla1, Weili Nie3, Josh Romero3, Christian Dallago3,7, Arash Vahdat3, Chaowei Xiao3, Thomas Gibbs3, Ian Foster1,2, James J. Davis1,2, Michael E. Papka1,8, Thomas Brettin1, Rick Stevens1,2, Anima Anandkumar3,9,*, Venkatram Vishwanath1,* and Arvind Ramanathan1,*,**Argonne National LaboratoryUniversity of ChicagoNVIDIA Inc.Harvard UniversityCerebras Inc.Northern Illinois UniversityTechnical University of MunichUniversity of Illinois ChicagoCalifornia Institute of Technology↵ Corresponding author; email: ramanathana{at}anl.gov
BMJ’s approach to deceased authors
Authors: Helen Macdonald, Helen Beynon, Kamran Abbasi
Journal: BMJ (2024)

Hailey Scotta, David Grynspanb, Laura N Andersonc and Kristin L Connora,1Department of Health Sciences, Carleton UniversityDepartment of Pathology and Laboratory Medicine, University of British ColumbiaHealth Research Methods, Evidence, and Impact, McMaster University↵Correspondence: Dr. Kristin Connor, Department of Health Sciences, Carleton University, Ottawa, Ontario, Canada, K1S5B6, E: kristin.connor{at}carleton.ca, Tel.: +1 613-520-2600 ext. 4202
Ethics of posthumous scholarly authorship in the sciences
Authors: David Nunan, Jeffrey K Aronson
Journal: BMJ (2024)

Toll-like receptor 9 (TLR9), primarily expressed in human dendritic and B cells, recognizes double-stranded DNA motifs from pathogens, initiating an inflammatory response. Recent studies have revealed TLR9's involvement beyond its conventional role in immune response, notably during the tumorigenesis of various cancers such as head and neck, cervical, and ovarian cancers. Here we show that immunohistochemistry analysis demonstrated significantly lower TLR9 levels in breast cancer tumors compared to normal breast tissue epithelium. Similarly, TLR9 downregulation was also observed in several transformed breast cancer cell lines versus untransformed breast epithelial cell lines. Furthermore, overexpression of TLR9 led to reduced proliferation potential of breast cancer cell associated with activation of senescence as was evident by upregulation of proinflammatory cytokine IL-6, chemokines IL-8 and CXCL1; and growth factor GM-CSF. These findings support TLR9's regulatory role in mitigating breast cancer and highlight its critical connection between the inflammatory response and tumor immunity.
Reducing the risk of preterm birth
Authors: Jane Sandall, Jenny Carter, Naomi Carlisle
Journal: BMJ (2024)

Ryan W. Holly1,*, Yi-Zhen Hu1, Vaishnavi Beena Valsan2, Christos Kougentakis2, Nektaria Petronikolou2, Tao Chen2, Diana Li2, Aimei Chen1, Steve Rank2, Kyle H. Doran2, Eric Turtle2, Christopher Langsdorf1 and Matthew J. Shurtleff2,*Thermo Fisher Scientific, Eugene, OR 97402Lycia Therapeutics, South San Franscisco, CA 94080↵Corresponding authors ryan.holly{at}thermofisher.com (R.W.H.); mshurtleff{at}lyciatx.com (M.J.S.)
Turn towards the hand in the fire: to care is to witness and condemn atrocities everywhere
Authors: Fares Alahdab, Victor M Montori
Journal: BMJ (2024)

Brian Johnson†,2, Yubo Shuai†,2, Jason Schweinsberg*,2 and Kit Curtius*,1,3Division of Biomedical Informatics, Department of Medicine, University of California San Diego, 9500 Gilman Dr., La Jolla, 92093, CA, USADepartment of Mathematics, University of California San Diego, 9500 Gilman Dr., La Jolla, 92093, CA, USAMoores Cancer Center, University of California San Diego, 9500 Gilman Dr., La Jolla, 92093, CA, USA↵Corresponding Authors: kcurtius{at}health.ucsd.edu and jschweinsberg{at}ucsd.edu↵† These authors contributed equally to this work.
Living happily ever after? The hidden health risks of Disney princesses
Authors: Sanne H B van Dijk, Michael Bui, Anouk H Eijkelboom
Journal: BMJ (2024)

While much current research on Disney princesses focuses on the harmful impact of unrealistic ideals on young viewers' self-esteem, there is a critical need to shift attention towards the health risks faced by the princesses themselves, <b>Sanne H B van Dijk and colleagues</b> argue
Just-in-time training could be just what the doctor ordered
Authors: Justine M Naylor
Journal: BMJ (2024)

Sophie G Kellaway1,*, Sandeep Potluri1, Peter Keane1, Helen Blair2, Paulynn S Chin1, Anetta Ptasinska1, Alice Worker1, Luke Ames1, Assunta Adamo1, Daniel JL Coleman1, Naeem Khan3, Salam Assi1, Anja Krippner-Heidenreich4, Manoj Raghavan1,5, Peter N Cockerill1, Olaf Heidenreich4,6 and Constanze Bonifer1,6,7,*Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UKNorthern Institute of Cancer Research, University of Newcastle upon Tyne, Newcastle, UKInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UKPrincess Maxima Center of Pediatric Oncology, Utrecht, NetherlandsCentre of Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK↵Corresponding authors: Sophie Kellaway: S.G.Kellaway{at}bham.ac.uk); Constanze Bonifer: c.bonifer{at}bham.ac.uk
Non-pharmaceutical treatments for irritable bowel syndrome
Authors: Xiao Jing Wang, Elyse Thakur, Jordan Shapiro
Journal: BMJ (2024)

Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction that impacts a significant portion of the population and is associated with substantial morbidity, reduced quality of life, and economic impact globally. The pathophysiology of IBS is complex and incompletely understood, and the heterogeneity of IBS is reflected in the variety of pharmaceutical and non-pharmaceutical therapies utilized for the management of IBS. Given limitations with pharmaceutical treatments, many patients with IBS seek non-pharmaceutical options. Several non-pharmaceutical treatments such as the low FODMAP diet and brain-gut behavior interventions such as gut directed hypnosis and cognitive behavioral therapy are now considered standard of care and are part of all major guidelines for the treatment of IBS. However, challenges with access to and optimal implementation of these therapies remain. This review focuses on the current evidence for common non-pharmaceutical treatments for IBS, including the latest advances in dietary and brain-gut behavioral care, in addition other complementary and integrative health practices and emerging therapies.
Rota gaps: Paediatric services only operating at 80% capacity, report warns
Authors: Jacqui Wise
Journal: BMJ (2024)

Huijin Lee1,2, Jihee Hwang2,3, Fahad Rashid1, James A. London4, Richard Fishel4, James M. Berger1, Sua Myong1,2,3 and Taekjip Ha1,2,3,5,*Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland, 21205, USAPrograms in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, 02115, USADepartment of Pediatrics, Harvard Medical School, Boston, Massachusetts, 02115, USADepartment of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, Ohio, 43210, USAHoward Hughes Medical Institute, Boston, Massachusetts, 02115, USA↵To whom correspondence should be addressed. Tel: +1 217 398 0865; Email: Taekjip.Ha{at}childrens.harvard.edu
Multiomic Integration Analysis for Monitoring Severe Asthma Treated With Mepolizumab or Omalizumab
Authors: Nuria Contreras, Andrea Escolar‐Peña, María I. Delgado‐Dolset, Paloma Fernández, David Obeso, Elena Izquierdo, Heleia González Cuervo, José Ángel Cumplido, Victoria Múgica, Carolina Cisneros, Santiago Angulo‐Díaz‐Parreño, Coral Barbas, Carlos Blanco, Teresa Carrillo, Domingo Barber, Alma Villaseñor, María M. Escribese
Journal: Allergy (2024)

ABSTRACT Rationale Biologics are becoming increasingly important in the management of severe asthma. However, little is known about the systemic immunometabolic consequences of Th2 response blockage. Objectives To provide a better immunometabolic understanding of the effects of mepolizumab and omalizumab treatments by identifying potential biomarkers for monitoring. Methods In this exploratory longitudinal study severe asthmatic patients were followed for 18 months after initiating mepolizumab ( n = 36) or Omalizumab ( n = 20) treatment. Serum samples were collected before, 6, and 18 months after treatment. Targeted omic approaches were performed to analyze inflammatory metabolites ( n = 35) and proteins ( n = 45). Multiomic integration was performed individually for each treatment applying supervised analysis Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) framework. Then, potential biomarkers were confirmed using multivariate ROC analyses and correlated with clinical variables along treatment. Measurements and Main Results Mepolizumab and omalizumab were both effective (improved clinical variables) and showed different and specific metabolic and protein profiles in severe asthmatic patients during treatment. Multiomic integration and multivariate ROC analyses identified specific biomarkers, such as arachidonic acid, palmitoleic acid, oleic acid, propionylcarnitine, bilirubin, CCL11, and TNFSF10, which can explain the differences observed with Mepolizumab treatment over 18 months and significantly correlate with clinical improvement. However, no significant biomolecules and no discriminative multivariate ROC curves were found for Omalizumab treatment. Conclusions Our results provide a comprehensive insight into the differential effects of mepolizumab and omalizumab on the immunometabolic kinetics of the inflammatory response in severe asthma. We identified a set of biomolecules with potential for monitoring mepolizumab treatment which could be useful for personalized medicine.
Deciphering Dysfunctional Regulatory T Cells in Atopic Dermatitis
Authors: Seong‐Jun Kang, Jeong‐Ryeol Gong, Seon‐Pil Jin, Jin‐Mi Oh, Hyunjin Jin, Yuji Lee, Yewon Moon, Dongjun Kim, Hyo Jeong Nam, Hyun Seung Choi, Sanha Hwang, Yun Jung Huh, Kyung Yeon Han, Jihwan Moon, Jongsuk Chung, Woong‐Yang Park, Chung‐Gyu Park, Hyun Je Kim, Jeong Eun Kim
Journal: Allergy (2024)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Transcriptomic clustering of chronic lymphocytic leukemia: molecular subtypes based on Bruton’s tyrosine kinase expression levels
Authors: Gorkem Kismali, Ganiraju Manyam, Nitin Jain, Cristina Ivan, Betty Lamothe, Mary L. Ayres, LaKesla R. Iles, William G. Wierda, Varsha Gandhi
Journal: Blood Cancer Journal (2024)

Historically, CLL prognostication relied on disease burden, reflected in clinical stage. Later, chromosome abnormalities and genomics suggested several CLL subtypes which were aligned with response to therapy. Gene expression profiling data identified pathways associated with CLL progression. We hypothesized that transcriptome and proteome may identify functional omics associated with CLL nosology. As a test cohort, we utilized publicly available treatment-naïve CLL transcriptomics data (n = 130) and did consensus clustering that identified BTK-expression-based clusters. The BTK-High and BTK-Low clusters were validated in public and our in-house databases (n = >550 CLL patients). To associate with functional relevance, we took samples from 151 previously treated patient with CLL and analyzed them using RNA sequencing and reverse-phase protein array. Transcript levels were strongly correlated with BTK protein levels. BTK-High subtype showed increased CCL3/CCL4 levels and disease burden such as high WBC. BTK-Low subtype showed down-regulated mRNA/proteins of DNA-repair pathway and increased DNA-damage-response, which may have contributed to enrichment of inflammatory pathway. BTK-Low subtype was rich in proapoptotic gene and protein expression and relied less on BCR pathway. High-BTK subgroup was enriched in replication/repair pathway and transcription machinery. In conclusion, profiling of 5 datasets of ~700 patients revealed unique BTK-associated expression clusters in CLL.
Elranatamab monotherapy in the real-word setting in relapsed-refractory multiple myeloma: results of the French compassionate use program on behalf of the IFM
Authors: Florent Malard, Arthur Bobin, Myriam Labopin, Lionel Karlin, Laurent Frenzel, Murielle Roussel, Marguerite Vignon, Sophie Godet, Thomas Chalopin, Perrine Moyer, Emilie Chalayer, Frederique Orsini Piocelle, Clara Mariette, Carolyne Croizier, Claudine Sohn, Mamoun Dib, Ronan Le Calloch, Nadia Ali-Ammar, Marion Loirat, Omar Benbrahim, Alexandre Payssot, Adrien Trebouet, Aurore Perrot, Xavier Leleu, Mohamad Mohty
Journal: Blood Cancer Journal (2024)
Single-cell transcriptomic and spatial analysis reveal the immunosuppressive microenvironment in relapsed/refractory angioimmunoblastic T-cell lymphoma
Authors: Mengyan Zhu, Ning Li, Lei Fan, Rongrong Wu, Lei Cao, Yimin Ren, Chuanyang Lu, Lishen Zhang, Yun Cai, Yuzhu Shi, Zihan Lin, Xueying Lu, Jiayan Leng, Shiyang Zhong, Xingfei Hu, Bin Huang, Runheng Huang, Wanting Zhou, Diru Yao, Lingxiang Wu, Wei Wu, Quanzhong Liu, Peng Xia, Ruize Chen, Wenyu Shi, Ruohan Zhang, Sali Lv, Chunling Wang, Liang Yu, Jianyong Li, Qianghu Wang, Kening Li, Hui Jin
Journal: Blood Cancer Journal (2024)

Angioimmunoblastic T-cell lymphoma (AITL) is a kind of aggressive T-cell lymphoma with significant enrichment of non-malignant tumor microenvironment (TME) cells. However, the complexity of TME in AITL progression is poorly understood. We performed single-cell RNA-Seq (scRNA-seq) and imaging mass cytometry (IMC) analysis to compare the cellular composition and spatial architecture between relapsed/refractory AITL (RR-AITL) and newly diagnosed AITL (ND-AITL). Our results showed that the malignant T follicular helper (Tfh) cells showed significantly increased proliferation driven by transcriptional activation of YY1 in RR-AITL, which is markedly associated with the poor prognosis of AITL patients. The CD8+ T cell proportion and cytotoxicity decreased in RR-AITL TME, resulting from elevated expression of the inhibitory checkpoints such as PD-1, TIGIT, and CTLA4. Notably, the transcriptional pattern of B cells in RR-AITL showed an intermediate state of malignant transformation to B-cell-lymphoma, and contributed to immune evasion by highly expressing CD47 and PD-L1. Besides, compared to ND-AITL samples, myeloid-cells-centered spatial communities were more prevalent but showed reduced phagocytic activity and impaired antigen processing and presentation in RR-AITL TME. Furthermore, specific inhibitory ligand-receptor interactions, such as CLEC2D-KLRB1, CTLA4-CD86, and MIF-CD74, were exclusively identified in the RR-AITL TME. Our study provides a high-resolution characterization of the immunosuppression ecosystem and reveals the potential therapeutic targets for RR-AITL patients.
Sex-Specific Dominance of Gene Expression in Seed Beetles
Authors: Philipp Kaufmann, Johanna Liljestrand Rönn, Elina Immonen, Göran Arnqvist
Journal: Molecular Biology and Evolution (2024)

Abstract When different alleles are favored in different environments, dominance reversal where alternate alleles are dominant in the environment in which they are favored can generate net balancing selection. The sexes represent two distinct genetic environments and sexually antagonistic (SA) selection can maintain genetic variation, especially when the alleles involved show sex-specific dominance. Sexual dimorphism in gene expression is pervasive and has been suggested to result from SA selection. Yet, whether gene-regulatory variation shows sex-specific dominance is poorly understood. We tested for sex-specific dominance in gene expression using three crosses between homozygous lines derived from a population of a seed beetle, where a previous study documented a signal of dominance reversal for fitness between the sexes. Overall, we found that the dominance effects of variants affecting gene expression were positively correlated between the sexes (r = 0.33 to 0.44). Yet, 586 transcripts showed significant differences in dominance between the sexes. Sex-specific dominance was significantly more common in transcripts with more sex-biased expression, in two of three of our crosses. Among transcripts showing sex-specific dominance, lesser sexual dimorphism in gene expression among heterozygotes was somewhat more common than greater. Gene ontology enrichment analyses showed that functional categories associated with known SA phenotypes in Callosobruchus maculatus were overrepresented among transcripts with sex-specific dominance, including genes involved in metabolic processes and the target-of-rapamycin pathway. Our results support the suggestion that sex-specific dominance of regulatory variants contributes to the maintenance of genetic variation in fitness mediated by SA selection in this species.
Diagnostic work-up of bile duct strictures: European Society of Gastrointestinal Endoscopy (ESGE) Guideline
Authors: Antonio Facciorusso, Stefano Francesco Crinò, Paraskevas Gkolfakis, Marco Spadaccini, Marianna Arvanitakis, Torsten Beyna, Michiel Bronswijk, Jahnvi Dhar, Mark Ellrichmann, Rodica Gincul, Istvan Hritz, Leena Kylänpää, Belen Martinez-Moreno, Martina Pezzullo, Mihai Rimbaş, Jayanta Samanta, Roy L.J. van Wanrooij, George Webster, Konstantinos Triantafyllou
Journal: Endoscopy (2024)

Main recommendations 1 ESGE recommends the combination of endoscopic ultrasound-guided tissue acquisition (EUS-TA) and endoscopic retrograde cholangiopancreatography (ERCP)-based tissue acquisition as the preferred diagnostic approach for tissue acquisition in patients with jaundice and distal extrahepatic biliary stricture in the absence of a pancreatic mass. 2 ESGE suggests that brushing cytology should be completed along with fluoroscopy-guided biopsies, wherever technically feasible, in patients with perihilar biliary strictures. 3 ESGE suggests EUS-TA for perihilar strictures when ERCP-based modalities yield insufficient results, provided that curative resection is not feasible and/or when cross-sectional imaging has shown accessible extraluminal disease. 4 ESGE suggests using standard ERCP diagnostic modalities at index ERCP. In the case of indeterminate biliary strictures, ESGE suggests cholangioscopy-guided biopsies, in addition to standard ERCP diagnostic modalities. Additional intraductal biliary imaging modalities can be selectively used, based on clinical context, local expertise, and resource availability.
Letter to the editor: A positive step toward cost-effective and accessible HCC detection awaits further validation
Authors: Junqing Han, Siru Zhao, Rong Fan
Journal: Hepatology (2024)

Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China Junqing Han and Siru Zhao: These authors contributed equally to this work as the first authors Correspondence Rong Fan, Department of Infectious Diseases, Nanfang Hospital, Southern Medical, University, Guangzhou, 510515, China. Email: [email protected]