tbuckley/cabot-search huggingface dataset:
Impact of nirsevimab prophylaxis on paediatric respiratory syncytial virus (RSV)-related hospitalisations during the initial 2023/24 season in Luxembourg
Authors: Corinna Ernst, Dritan Bejko, Leo Gaasch, Emilie Hannelas, Isaline Kahn, Charlotte Pierron, Nesrine Del Lero, Claude Schalbar, Elsa Do Carmo, Michel Kohnen, Emmanuelle Andlauer, Pauline Hublart, Silvana Masi, Isabel de la Fuente Garcia, Anne Vergison, Joël Mossong
Journal: Eurosurveillance (2024)

After Luxembourg introduced nirsevimab immunisation against respiratory syncytial virus (RSV), estimated neonatal coverage was 84% (1,277 doses/1,524 births) in 2023. That year, paediatric RSV-related hospitalisations, especially concerning infants < 6 months old (n = 72) seemed to decrease compared to the same period in 2022 (n = 232). In 2023, hospitalised children's mean age increased (14.4 months vs 7.8 months in 2022; p < 0.001) and hospital-stay length decreased (3.2 days vs 5.1 days; p < 0.001). In infants < 6 months old, intensive-care unit admissions appeared to drop (n = 28 vs 9). This suggests that nirsevimab prophylaxis reduced severe RSV infections, particularly in infants < 6 months old, thereby alleviating healthcare strain.
Age-dependent influenza infection patterns and subtype circulation in Denmark, in seasons 2015/16 to 2021/22
Authors: Hanne-Dorthe Emborg, Amanda Bolt Botnen, Jens Nielsen, Lasse S. Vestergaard, Frederikke Kristensen Lomholt, Charlotte Munkstrup, Karina Lauenborg Møller, Charlotte Kjelsø, Steen Hulthin Rasmussen, Ramona Trebbien
Journal: Eurosurveillance (2024)

Background Influenza was almost absent for 2 years following the implementation of strict public health measures to prevent the spread of SARS-CoV-2. The consequence of this on infections in different age groups is not yet known. Aim To describe the age groups infected with the influenza virus in 2021/22, the first post-pandemic influenza season in Denmark, compared with the previous six seasons, and subtypes circulating therein. Methods Infection and hospitalisation incidences per season and age group were estimated from data in Danish registries. Influenza virus subtypes and lineages were available from samples sent to the National Influenza Centre at Statens Serum Institut. Results Test incidence followed a similar pattern in all seasons, being highest in 0–1-year-olds and individuals over 75 years, and lowest in 7–14-year-olds and young people 15 years to late twenties. When the influenza A virus subtypes A(H3N2) and A(H1N1)pdm09 co-circulated in seasons 2015/16 and 2017/18 to 2019/20, the proportion of A(H1N1)pdm09 was higher in 0–1-year-olds and lower in the over 85-year-olds compared with the overall proportion of A(H1N1)pdm09 in these seasons. The proportion of A(H3N2) was higher in the over 85 years age group compared with the overall proportion of A(H3N2). The 2016/17 and 2021/22 seasons were dominated by A(H3N2) but differed in age-specific trends, with the over 85 years age group initiating the 2016/17 season, while the 2021/22 season was initiated by the 15–25-year-olds, followed by 7–14-year-olds. Conclusion The 2021/22 influenza season had a different age distribution compared with pre-COVID-19 pandemic seasons.
Adjusting for genetic confounders in transcriptome-wide association studies improves discovery of risk genes of complex traits
Authors: Siming Zhao, Wesley Crouse, Sheng Qian, Kaixuan Luo, Matthew Stephens, Xin He
Journal: Nature Genetics (2024)

Abstract Many methods have been developed to leverage expression quantitative trait loci (eQTL) data to nominate candidate genes from genome-wide association studies. These methods, including colocalization, transcriptome-wide association studies (TWAS) and Mendelian randomization-based methods; however, all suffer from a key problem—when assessing the role of a gene in a trait using its eQTLs, nearby variants and genetic components of other genes’ expression may be correlated with these eQTLs and have direct effects on the trait, acting as potential confounders. Our extensive simulations showed that existing methods fail to account for these ‘genetic confounders’, resulting in severe inflation of false positives. Our new method, causal-TWAS (cTWAS), borrows ideas from statistical fine-mapping and allows us to adjust all genetic confounders. cTWAS showed calibrated false discovery rates in simulations, and its application on several common traits discovered new candidate genes. In conclusion, cTWAS provides a robust statistical framework for gene discovery.
A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS–FTD
Authors: Katherine E. Irwin, Pei Jasin, Kerstin E. Braunstein, Irika R. Sinha, Mark A. Garret, Kyra D. Bowden, Koping Chang, Juan C. Troncoso, Abhay Moghekar, Esther S. Oh, Denitza Raitcheva, Dan Bartlett, Timothy Miller, James D. Berry, Bryan J. Traynor, Jonathan P. Ling, Philip C. Wong
Journal: Nature Medicine (2024)

Although loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well documented in postmortem tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), whether this abnormality occurs during early-stage disease remains unresolved. Cryptic exon inclusion reflects loss of function of TDP-43, and thus detection of proteins containing cryptic exon-encoded neoepitopes in cerebrospinal fluid (CSF) or blood could reveal the earliest stages of TDP-43 dysregulation in patients. Here we use a newly characterized monoclonal antibody specific to a TDP-43-dependent cryptic epitope (encoded by the cryptic exon found in HDGFL2) to show that loss of TDP-43 splicing repression occurs in ALS-FTD, including in presymptomatic C9orf72 mutation carriers. Cryptic hepatoma-derived growth factor-like protein 2 (HDGFL2) accumulates in CSF at significantly higher levels in familial ALS-FTD and sporadic ALS compared with controls and is elevated earlier than neurofilament light and phosphorylated neurofilament heavy chain protein levels in familial disease. Cryptic HDGFL2 can also be detected in blood of individuals with ALS-FTD, including in presymptomatic C9orf72 mutation carriers, and accumulates at levels highly correlated with those in CSF. Our findings indicate that loss of TDP-43 cryptic splicing repression occurs early in disease progression, even presymptomatically, and that detection of the HDGFL2 cryptic neoepitope serves as a potential diagnostic biomarker for ALS, which should facilitate patient recruitment and measurement of target engagement in clinical trials.
Hypertension care cascades and reducing inequities in cardiovascular disease in low- and middle-income countries
Authors: Dorit Talia Stein, Marissa B. Reitsma, Pascal Geldsetzer, Kokou Agoudavi, Krishna Kumar Aryal, Silver Bahendeka, Luisa C. C. Brant, Farshad Farzadfar, Mongal Singh Gurung, David Guwatudde, Yessito Corine Nadège Houehanou, Deborah Carvalho Malta, João Soares Martins, Sahar Saeedi Moghaddam, Kibachio Joseph Mwangi, Bolormaa Norov, Lela Sturua, Zhaxybay Zhumadilov, Till Bärnighausen, Justine I. Davies, David Flood, Maja E. Marcus, Michaela Theilmann, Sebastian Vollmer, Jennifer Manne-Goehler, Rifat Atun, Nikkil Sudharsanan, Stéphane Verguet
Journal: Nature Medicine (2024)
Hyperdiploid acute lymphoblastic leukemia in children with <i>LZTR1</i> germline variants
Authors: Lisa Zipper, Rabea Wagener, Ute Fischer, Anna Hoffmann, Layal Yasin, Danielle Brandes, Stavrieta Soura, Ammarah Anwar, Carolin Walter, Julian Varghese, Julia Hauer, Franziska Auer, Sanil Bhatia, Martin Dugas, Stefanie V. Junk, Martin Stanulla, Oskar A. Haas, Arndt Borkhardt, Tobias Reiff, Triantafyllia Brozou
Journal: HemaSphere (2024)
High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T‐cell therapy for large B‐cell lymphoma
Authors: Maeve A. O'Reilly, Lorna Neill, Simon M. Collin, Neil Stone, Deborah Springell, Jeremy Mensah, Kathleen P. L. Cheok, Katarzyna Jalowiec, Reuben Benjamin, Andrea Kuhnl, Claire Roddie, Robin Sanderson
Journal: HemaSphere (2024)

Abstract Infection has emerged as the chief cause of non‐relapse mortality (NRM) post CD19‐targeting chimeric antigen receptor T‐cell therapy (CAR‐T) therapy. Even though up to 50% of patients may remain infection‐free, many suffer multiple severe, life‐threatening, or fatal infectious events. The primary aim of this study was to explore severe and life‐threatening infections post licensed CAR‐T therapy in large B‐cell lymphoma, with a focus on the role of disease burden and disease sites in assessing individual risk. We sought to understand the cohort of patients who experience ≥2 infections and those at the highest risk of infectious NRM. Our analysis identifies a higher disease burden after bridging therapy as associated with infection events. Those developing ≥2 infections emerged as a uniquely high‐risk cohort, particularly if the second (or beyond) infection occurred during an episode of immune effector cell‐associated neurotoxicity syndrome (ICANS) or while on steroids and/or anakinra for ICANS. Herein, we also describe the first reported cases of “CAR‐T cold sepsis,” a phenomenon characterized by the lack of an appreciable systemic inflammatory response at the time of detection of infection. We propose a risk‐based strategy to encourage heightened clinician awareness of cold sepsis, with a view to reducing NRM.
A single‐center cohort study of patients with hereditary spherocytosis in Central Europe reveals a high frequency of novel disease‐causing genotypes
Authors: Leo Kager, Raúl Jimenez‐Heredia, Petra Zeitlhofer, Wolfgang Novak, Sebastian K. Eder, Anna Segarra‐Roca, Alexandra Frohne, Karin Nebral, Matthias Haimel, René Geyeregger, Katharina Roetzer‐Londgin, Oskar A. Haas, Kaan Boztug
Journal: HemaSphere (2024)
Oxygen Self‐Supplied Nanoplatform for Enhanced Photodynamic Therapy against <i>Enterococcus Faecalis</i> within Root Canals
Authors: Jiawen Chen, Hong Zhang, Tiancong Zhao, Yiyan Yu, Jiazhuo Song, Yuanhang Zhao, Hamed Alshawwa, Xinying Zou, Zhimin Zhang
Journal: Advanced Healthcare Materials (2024)

The successful treatment of persistent and recurrent endodontic infections hinges upon the eradication of residual microorganisms within the root canal system, which urgently needs novel drugs to deliver potent yet gentle antimicrobial effects. Antibacterial photodynamic therapy (aPDT) is a promising tool for root canal infection management. Nevertheless, the hypoxic microenvironment within the root canal system significantly limits the efficacy of this treatment. Herein, a nanohybrid drug, Ce6/CaO
Accelerating pediatric Hodgkin lymphoma research: the Hodgkin Lymphoma Data Collaboration (NODAL)
Authors: Kirk D Wyatt, Suzi Birz, Sharon M Castellino, Tara O Henderson, John T Lucas, Qinglin Pei, Yiwang Zhou, Samuel L Volchenboum, Brian Furner, Michael Watkins, Kara M Kelly, Jamie E Flerlage, Bhavya Achen, Burt Appel, Melissa Beauchemin, Jenny Belsky, Dana Casey, Peter Cole, Louis Constine, Hema Dave, Richard Drachtman, Chris Forlenza, Debra Friedman, Paul Harker-Murray, David Hodgson, Brad Hoppe, Shana Jacobs, Justine Kahn, Kala Kamdar, Frank Keller, Andrea Lo, Raymond Mailhot, Lianna Marks, Kathleen McCarten, Sarah Milgrom, Tomi Mori, Susan Parsons, Angela Punnett, Cindy Schwartz, Jenn Seelisch, Yue Wu, Sharon Castellino, Jamie Flerlage, Tara Henderson, Kara Kelly, John Lucas, Qinglin Pei, Samuel Volchenboum, Yiwang Zhou, Suzi Birz
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Data commons have proven to be an indispensable avenue for advancing pediatric cancer research by serving as unified information technology platforms that, when coupled with data standards, facilitate data sharing. The Pediatric Cancer Data Commons, the flagship project of Data for the Common Good (D4CG), collaborates with disease-based consortia to facilitate development of clinical data standards, harmonization and pooling of clinical data from disparate sources, establishment of governance structure, and sharing of clinical data. In the interest of international collaboration, researchers developed the Hodgkin Lymphoma Data Collaboration and forged a relationship with the Pediatric Cancer Data Commons to establish a data commons for pediatric Hodgkin lymphoma. Herein, we describe the progress made in the formation of Hodgkin Lymphoma Data Collaboration and foundational goals to advance pediatric Hodgkin lymphoma research.
DNA-methylation variability in normal mucosa: a field cancerization marker in patients with adenomatous polyps
Authors: Josephine Yates, Helen Schaufelberger, Roland Steinacher, Primo Schär, Kaspar Truninger, Valentina Boeva
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background The phenomenon of field cancerization reflects the transition of normal cells into those predisposed to cancer. Assessing the scope and intensity of this process in the colon may support risk prediction and colorectal cancer prevention. Methods The Swiss Epigenetic Colorectal Cancer Study (SWEPIC) study, encompassing 1111 participants for DNA methylation analysis and a subset of 84 for RNA sequencing, was employed to detect field cancerization in individuals with adenomatous polyps (AP). Methylation variations were evaluated for their discriminative capability, including in external cohorts, genomic localization, clinical correlations, and associated RNA expression patterns. Results Normal cecal tissue of individuals harboring an AP in the proximal colon manifested dysregulated DNA methylation compared to tissue from healthy individuals at 558 unique loci. Leveraging these adenoma-related differentially variable and methylated CpGs (aDVMCs), our classifier discerned between healthy and AP-adjacent tissues across SWEPIC datasets (cross-validated area under the receiver operating characteristic curve [ROC AUC] = 0.63-0.81), including within age-stratified cohorts. This discriminative capacity was validated in 3 external sets, differentiating healthy from cancer-adjacent tissue (ROC AUC = 0.82-0.88). Notably, aDVMC dysregulation correlated with polyp multiplicity. More than 50% of aDVMCs were significantly associated with age. These aDVMCs were enriched in active regions of the genome (P &amp;lt; .001), and associated genes exhibited altered expression in AP-adjacent tissues. Conclusions Our findings underscore the early onset of field cancerization in the right colon during the neoplastic transformation process. A more extensive validation of aDVMC dysregulation as a stratification tool could pave the way for enhanced surveillance approaches, especially given its linkage to adenoma emergence.
Developing the next-generation cancer research workforce in the National Institutes of Health Intramural Research Program
Authors: Nina F Schor
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Although the National Institutes of Health is renowned for being the largest funder of biomedical research in the world, the research and associated career development programs on its own campuses are relatively unknown. These intramural programs provide many outstanding and programmatically unique opportunities for research-intensive careers and training in cancer biology, prevention, diagnosis, and therapeutics. Their complementary foci, structures, and review mechanisms make the extramural and intramural cancer research contributions of the National Institutes of Health the perfect partners in the quest to rid the world of cancer as we know it.
Issue Information
Authors: Daniel Solomon, Richard Bucala, New Haven, Mariana Kaplan, Peter Nigrovic, Boston Co, Karen Costenbader, David Felson, Richard Loeser, Chapel Hill, Amr Sawalha, Susan Boackle, Aileen Davis, Daniel Horton, New Brunswick, Bharat Kumar, Iowa City, Brandon Law, Michelle Ormseth, Suraj Rajasimhan, Kimberly Murphy, Maggie Parry, Georgia Production, Brian Robinson, Chris Reynolds, Georgia Austin, Audra Jenson, Marta Alarcón-Riquelme, Granada Basu, Edward Behrens, Bryce Binstadt, Nunzio Bottini, San Diego, John Carrino, New York, Andrew Cope, Adam Croft, Nicola Dalbeth, Brian Feldman, Richard Furie, Great Neck, J Kahlenberg, Ann Arbor, Benjamin Leder, Yvonne Lee, Katherine Liao, Bing Lu, Stephen Messier, Winston-Salem Rachel, E Miller, Janet Pope, Lisa Rider, Christopher Ritchlin, Rochester Robinson, Carla Scanzello, Georg Schett, Sakae Tanaka, Maria Trojanowska, Betty Tsao, Fredrick Wigley, Edith Williams, Ayaz Aghayev, Joshua Baker, Bonnie Bermas, Jamie Collins, Kristen Demoruelle, Denver Denton, Anisha Dua, John Fitzgerald, Angeles Henderson, Monique Hinchcliff, Hui-Chen Hsu, Mohit Kapoor, Seoyoung Kim, Vasileios Kyttaris, Carl Langefeld, Winston-Salem Dennis Mcgonagle, Julie Paik, Julie Zikherman, Francisco American, Douglas White, La Crosse, Deborah Desir, Carol Langford, Steven Echard, Alejandro Gomez, R Brewer, Jae-Seung Moon, Suman Acharya, Sarah Kongpachith, Qian Wang, Shaghayegh Jahanbani, Heidi Wong, Tobias Lanz, Yu Kuang, Ruiru Li, Jingnan Wang, Siqi Xu, Qian Qiu, Shuibin Lin, Di Liu, Keith Colaco, Ker-Ai Lee, Shadi Akhtari, Raz Winer, Vinod Chandran, Paula Harvey, Brad Rovin, Jorge Terres, Sophia Giang, Jérôme Avouac, Anne Cauvet, Cindy Orvain, Morgane Boulch, Françoise Tilotta, Kailey Brodeur, Meng Liu, Daniel Ibanez, Mareike De Groot, Liang Chen, Yan Du, Eman Seyal, Raquel Laza-Briviesca, Annette Baker, Joyce Chang, Margaret Chang, Megan Day-Lewis, Fatma Dedeoglu, Audrey Dionne, Sarah De Ferranti, Kevin Friedman, Olha Halyabar, Mindy Lo, Esra Meidan, Robert Sundel, Maria Suñol, Jon Dudley, Michael Payne, Han Tong, Tracy Ting, Susmita Kashikar, Marco Gattorno, Laura Obici, Inmaculada Penadés, Tilmann Kallinich, Susanne Benseler
Journal: Arthritis & Rheumatology (2024)
The role of the epithelial sentinels, Langerhans cells and <scp>γδT</scp> cells, in oral squamous cell carcinoma
Authors: Avi‐Hai Hovav, Asaf Wilensky
Journal: Periodontology 2000 (2024)

Abstract Oral squamous cell carcinoma (OSCC) arises in the oral epithelium, a tissue in which immune surveillance is mediated by its primary resident leukocytes, Langerhans cells (LCs), and γδT cells. Under steady‐state conditions, LCs and γδT cells play a critical role in maintaining oral mucosal homeostasis. As antigen‐presenting cells of stratified epithelia, LCs respond to various challenges faced by the epithelium, orchestrating innate, and adaptive immune responses in order to resolve them. γδT cells also sense diverse epithelial insults and react rapidly through cytokine production and cytolytic activity. These epithelial sentinels are also considered to be the first leukocytes in the oral epithelium to encounter early carcinogenic events that have the potential of becoming OSCC. As evident in many malignancies, leukocyte populations help prevent cancer development although they also promote tumor progression. OSCC is no exception, as studies have reported both anti‐ and pro‐tumor roles of LCs and γδT cells. In this review, we summarize the ontogeny of LCs and γδT cells in the oral epithelium and discuss their role in OSCC.
JAK/STAT in leukemia: a clinical update
Authors: Dong Liang, Qiaoli Wang, Wenbiao Zhang, Hailin Tang, Cailu Song, Zhimin Yan, Yang Liang, Hua Wang
Journal: Molecular Cancer (2024)

Abstract Over the past three decades, considerable efforts have been expended on understanding the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in leukemia, following the identification of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs). The aim of this review is to summarize the latest progress in our understanding of the involvement of the JAK/STAT signaling pathway in the development of leukemia. We also attempt to provide insights into the current use of JAK/STAT inhibitors in leukemia therapy and explore pertinent clinical trials in this field.
Update on Hemodialysis-Induced Multiorgan Ischemia
Authors: Christopher W. McIntyre
Journal: Journal of the American Society of Nephrology (2024)

Hemodialysis is a life-saving treatment for patients with kidney failure. However, patients requiring hemodialysis have a 10–20 times higher risk of cardiovascular morbidity and mortality than that of the general population. Patients encounter complications such as episodic intradialytic hypotension, abnormal perfusion to critical organs (heart, brain, liver, and kidney), and damage to vulnerable vascular beds. Recurrent conventional hemodialysis exposes patients to multiple episodes of circulatory stress, exacerbating and being aggravated by microvascular endothelial dysfunction. This promulgates progressive injury that leads to irreversible multiorgan injury and the well-documented higher incidence of cardiovascular disease and premature death. This review aims to examine the underlying pathophysiology of hemodialysis-related vascular injury and consider a range of therapeutic approaches to improving outcomes set within this evolved rubric.‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬
Publisher Correction: Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability
Authors: Bob T. Rosier, William Johnston, Miguel Carda-Diéguez, Annabel Simpson, Elena Cabello-Yeves, Krystyna Piela, Robert Reilly, Alejandro Artacho, Chris Easton, Mia Burleigh, Shauna Culshaw, Alex Mira
Journal: International Journal of Oral Science (2024)
Heat shock protein 90: biological functions, diseases, and therapeutic targets
Authors: Huiyun Wei, Yingying Zhang, Yilin Jia, Xunan Chen, Tengda Niu, Aniruddha Chatterjee, Pengxing He, Guiqin Hou
Journal: MedComm (2024)

Abstract Heat shock protein 90 (Hsp90) is a predominant member among Heat shock proteins (HSPs), playing a central role in cellular protection and maintenance by aiding in the folding, stabilization, and modification of diverse protein substrates. It collaborates with various co‐chaperones to manage ATPase‐driven conformational changes in its dimer during client protein processing. Hsp90 is critical in cellular function, supporting the proper operation of numerous proteins, many of which are linked to diseases such as cancer, Alzheimer's, neurodegenerative conditions, and infectious diseases. Recognizing the significance of these client proteins across diverse diseases, there is a growing interest in targeting Hsp90 and its co‐chaperones for potential therapeutic strategies. This review described biological background of HSPs and the structural characteristics of HSP90. Additionally, it discusses the regulatory role of heat shock factor‐1 (HSF‐1) in modulating HSP90 and sheds light on the dynamic chaperone cycle of HSP90. Furthermore, the review discusses the specific contributions of HSP90 in various disease contexts, especially in cancer. It also summarizes HSP90 inhibitors for cancer treatment, offering a thoughtful analysis of their strengths and limitations. These advancements in research expand our understanding of HSP90 and open up new avenues for considering HSP90 as a promising target for therapeutic intervention in a range of diseases.