tbuckley/cabot-search huggingface dataset:
Outbreak of invasive Group A streptococcus disease in a nursing home in Ireland in February 2023 caused by emm type 18
Authors: Ciara Carroll, Mary Meehan, Roisin Connolly, Jayne Prendergast, Colette Magnone, Aine Meehan, Chantal Migone, Keith Ian Quintyne, Caroline Carpenter, Helen Byrne, Robert Cunney, Paul Mullane
Journal: Eurosurveillance (2024)

An out-of-season increase in cases of invasive Group A streptococcus (iGAS) was observed in Ireland between October 2022 and August 2023. We describe the management of an iGAS outbreak involving three nursing home residents in Ireland in early 2023. A regional Department of Public Health was notified of an iGAS case in a nursing home resident in January 2023. When two further cases among residents were notified 7 days later, an outbreak was declared. Surveillance for GAS/iGAS infection in residents and staff was undertaken. The site was visited to provide infection prevention and control (IPC) support. Isolates were
Differential sex-dependent susceptibility to diastolic dysfunction and arrhythmia in cardiomyocytes from obese diabetic heart failure with preserved ejection fraction model
Authors: Juliana Mira Hernandez, Erin Y Shen, Christopher Y Ko, Zaynab Hourani, Emily R Spencer, Daria Smoliarchuk, Julie Bossuyt, Henk Granzier, Donald M Bers, Bence Hegyi
Journal: Cardiovascular Research (2024)

Sex-differences in heart failure with preserved ejection fraction (HFpEF) are important, but key mechanisms involved are incompletely understood. While animal models can inform about sex-dependent cellular and molecular changes, many previous preclinical HFpEF models have failed to recapitulate sex-dependent characteristics of human HFpEF. We tested for sex-differences in HFpEF using a two-hit mouse model (leptin receptor-deficient db/db mice plus aldosterone infusion for 4 weeks; db/db+Aldo).
Severe A(H1N1)pdm09 influenza acute encephalopathy outbreak in children in Tuscany, Italy, December 2023 to January 2024
Authors: Luca Bartolini, Silvia Ricci, Chiara Azzari, Maria Moriondo, Francesco Nieddu, Manuela L’Erario, Zaccaria Ricci, Gabriele Simonini, Marzia Mortilla, Giuseppe Indolfi, Carlotta Montagnani, Elena Chiappini, Luisa Galli, Renzo Guerrini
Journal: Eurosurveillance (2024)

A severe outbreak of influenza A(H1N1pdm09) infection in seven children (median age: 52 months) occurred between December 2023 and January 2024 in Tuscany, Italy. Clinical presentation ranged from milder encephalopathy to acute necrotizing encephalopathy (ANE) with coma and multiorgan failure; one child died. This report raises awareness for clinicians to identify and treat early acute encephalopathy caused by H1N1 influenza and serves as a reminder of severe presentations of influenza in young children and the importance of vaccination.
Enhancing prime editor flexibility with coiled-coil heterodimers
Authors: Shuangshuang Mu, Huangyao Chen, Qianru Li, Shixue Gou, Xiaoyi Liu, Junwei Wang, Wei Zheng, Menglong Chen, Qin Jin, Liangxue Lai, Kepin Wang, Hui Shi
Journal: Genome biology (2024)

Abstract Background Prime editing enables precise base substitutions, insertions, and deletions at targeted sites without the involvement of double-strand DNA breaks or exogenous donor DNA templates. However, the large size of prime editors (PEs) hampers their delivery in vivo via adeno-associated virus (AAV) due to the viral packaging limit. Previously reported split PE versions provide a size reduction, but they require intricate engineering and potentially compromise editing efficiency. Results Herein, we present a simplified split PE named as CC-PE, created through non-covalent recruitment of reverse transcriptase to the Cas9 nickase via coiled-coil heterodimers, which are widely used in protein design due to their modularity and well-understood sequence-structure relationship. We demonstrate that the CC-PE maintains or even surpasses the efficiency of unsplit PE in installing intended edits, with no increase in the levels of undesired byproducts within tested loci amongst a variety of cell types (HEK293T, A549, HCT116, and U2OS). Furthermore, coiled-coil heterodimers are used to engineer SpCas9-NG-PE and SpRY-PE, two Cas9 variants with more flexible editing scope. Similarly, the resulting NG-CC-PE and SpRY-CC-PE also achieve equivalent or enhanced efficiency of precise editing compared to the intact PE. When the dual AAV vectors carrying CC-PE are delivered into mice to target the Pcsk9 gene in the liver, CC-PE enables highly efficient precise editing, resulting in a significant reduction of plasma low-density lipoprotein cholesterol and total cholesterol. Conclusions Our innovative, modular system enhances flexibility, thus potentially facilitating the in vivo applicability of prime editing.
Five-Year Outcomes among U.S. Bronchiectasis and NTM Research Registry Patients
Authors: Timothy R Aksamit, Nicholas Locantore, Doreen Addrizzo-Harris, Juzar Ali, Alan Barker, Ashwin Basavaraj, Megan Behrman, Amanda E Brunton, Sarah Chalmers, Radmila Choate, Nathan C Dean, Angela DiMango, David Fraulino, Margaret M. Johnson, Nicole C. Lapinel, Diego J Maselli, Pamela J McShane, Mark L Metersky, Bruce E Miller, Edward T Naureckas, Anne E. O'Donnell, Kenneth N. Olivier, Elly Prusinowski, Marcos I Restrepo, Christopher J Richards, Gloria Rhyne, Andreas Schmid, George M Solomon, Ruth Tal-Singer, Byron Thomashow, Gregory Tino, Kevin Tsui, Sumith Abraham Varghese, Heather E. Warren, Kevin Winthrop, Beth Shoshanna Zha
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described.
Achieving more equitable access to assisted reproduction
Authors: Silke J Dyer, G David Adamson, Marcia C Inhorn, Fernando Zegers-Hochschild
Journal: BMJ (2024)

Equitable access to fertility care must be recognised as a human right so that it can be better balanced with other societal needs, say <b>Silke Dyer</b>, <b>David Adamson</b>, <b>Marcia Inhorn,</b> and <b>Fernando Zegers-Hochschild</b>
Impact of blood salvage therapy during oncologic liver surgeries on allogenic transfusion events, survival, and recurrence: an ambidirectional cohort study
Authors: Liav Lugassy, Samuel Marion, Frédéric Balthazar, Sonia Gabriela Cheng Oviedo, Yves Collin
Journal: International Journal of Surgery (2024)

The use of autologous blood transfusions in oncologic surgeries is somewhat controversial due to the potential risk of disease dissemination through the salvage process. On the other hand, autologous blood transfusion can prevent the potential negative effects of allogenic blood transfusions and reduce use of valuable resources.
Evacuation and Health Care Outcomes Among Assisted Living Residents After Hurricane Irma
Authors: Cassandra L. Hua, Sweta Patel, Kali S. Thomas, Dylan J. Jester, Cyrus M. Kosar, Lindsay J. Peterson, Debra Dobbs, Ross Andel, David M. Dosa
Journal: JAMA Network Open (2024)

Evacuation has been found to be associated with adverse outcomes among nursing home residents during hurricanes, but the outcomes for assisted living (AL) residents remain unknown. To examine the association between evacuation and health care outcomes (ie, emergency department visits, hospitalizations, mortality, and nursing home visits) among Florida AL residents exposed to Hurricane Irma. Retrospective cohort study using 2017 Medicare claims data. Participants were a cohort of Florida AL residents who were aged 65 years or older, enrolled in Medicare fee-for-service, and resided in 9-digit zip codes corresponding to US assisted living communities with 25 or more beds on September 10, 2017, the day of Hurricane Irma's landfall. Propensity score matching was used to match evacuated residents to those that sheltered-in-place based on resident and AL characteristics. Data were analyzed from September 2022 to February 2024. Whether the AL community evacuated or sheltered-in-place before Hurricane Irma made landfall. Thirty- and 90-day emergency department visits, hospitalizations, mortality, and nursing home admissions. The study cohort included 25 130 Florida AL residents (mean [SD] age 81 [9] years); 3402 (13.5%) evacuated and 21 728 (86.5%) did not evacuate. The evacuated group had 2223 women (65.3%), and the group that sheltered-in-place had 14 556 women (67.0%). In the evacuated group, 42 residents (1.2%) were Black, 93 (2.7%) were Hispanic, and 3225 (94.8%) were White. In the group that sheltered in place, 490 residents (2.3%) were Black, 707 (3.3%) were Hispanic, and 20 212 (93.0%) were White. After 1:4 propensity score matching, when compared with sheltering-in-place, evacuation was associated with a 16% greater odds of emergency department visits (adjusted odds ratio [AOR], 1.16; 95% CI, 1.01-1.33; P = .04) and 51% greater odds of nursing home visits (AOR, 1.51; 95% CI, 1.14-2.00; P = .01) within 30 days of Hurricane Irma's landfall. Hospitalization and mortality did not vary significantly by evacuation status within 30 or 90 days after the landfall date. In this cohort study of Florida AL residents, there was an increased risk of nursing home and emergency department visits within 30 days of Hurricane Irma's landfall among residents from communities that evacuated before the storm when compared with residents from communities that sheltered-in-place. The stress and disruption caused by evacuation may yield poorer immediate health outcomes after a major storm for AL residents. Therefore, the potential benefits and harms of evacuating vs sheltering-in-place must be carefully considered when developing emergency planning and response.
Endometrioid Endometrial RNA Index Predicts Recurrence in Stage I Patients
Authors: Corrine A. Nief, Phoebe M. Hammer, Aihui Wang, Vivek Charu, Amina Tanweer, Babak Litkouhi, Elizabeth Kidd, Andrew J. Gentles, Brooke E. Howitt
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Risk prediction with genomic and transcriptomic data has the potential to improve patient outcomes by enabling clinicians to identify patients requiring adjuvant treatment approaches, while sparing low-risk patients from unnecessary interventions. Endometrioid endometrial carcinoma (EEC) is the most common cancer in women in developed countries, and rates of endometrial cancer are increasing. Experimental Design: We collected a 105-patient case-control cohort of stage I EEC comprising 45 patients who experienced recurrence less than 6 years after excision, and 60 Fédération Internationale de Gynécologie et d'Obstétrique grade-matched controls without recurrence. We first utilized two RNA-based, previously validated machine learning approaches, namely, EcoTyper and Complexity Index in Sarcoma (CINSARC). We developed Endometrioid Endometrial RNA Index (EERI), which uses RNA expression data from 46 genes to generate a personalized risk score for each patient. EERI was trained on our 105-patient cohort and tested on a publicly available cohort of 263 patients with stage I EEC. Results: EERI was able to predict recurrences with 94% accuracy in the training set and 81% accuracy in the test set. In the test set, patients assigned as EERI high-risk were significantly more likely to experience recurrence (30%) than the EERI low-risk group (1%) with a hazard ratio of 9.9 (95% CI, 4.1–23.8; P &amp;lt; 0.001). Conclusions: Tumors with high-risk genetic features may require additional treatment or closer monitoring and are not readily identified using traditional clinicopathologic and molecular features. EERI performs with high sensitivity and modest specificity, which may benefit from further optimization and validation in larger independent cohorts.
Spatial Profiling of Ovarian Carcinoma and Tumor Microenvironment Evolution under Neoadjuvant Chemotherapy
Authors: Elisa Yaniz-Galende, Qinghe Zeng, Juan F. Bejar-Grau, Christophe Klein, Felix Blanc-Durand, Audrey Le Formal, Eric Pujade-Lauraine, Laure Chardin, Elodie Edmond, Virginie Marty, Isabelle Ray-Coquard, Florence Joly, Gwenael Ferron, Patricia Pautier, Dominique Berton-Rigaud, Alain Lortholary, Nadine Dohollou, Christophe Desauw, Michel Fabbro, Emmanuelle Malaurie, Nathalie Bonichon-Lamaichhane, Diana Bello Roufai, Justine Gantzer, Etienne Rouleau, Catherine Genestie, Alexandra Leary
Journal: Clinical Cancer Research (2024)

Abstract Purpose: This study investigates changes in CD8+ cells, CD8+/Foxp3 ratio, HLA I expression, and immune coregulator density at diagnosis and upon neoadjuvant chemotherapy (NACT), correlating changes with clinical outcomes. Experimental Design: Multiplexed immune profiling and cell clustering analysis were performed on paired matched ovarian cancer samples to characterize the immune tumor microenvironment (iTME) at diagnosis and under NACT in patients enrolled in the CHIVA trial (NCT01583322). Results: Several immune cell (IC) subsets and immune coregulators were quantified pre/post-NACT. At diagnosis, patients with higher CD8+ T cells and HLA I+-enriched tumors were associated with a better outcome. The CD8+/Foxp3+ ratio increased significantly post-NACT in favor of increased immune surveillance, and the influx of CD8+ T cells predicted better outcomes. Clustering analysis stratified pre-NACT tumors into four subsets: high Binf, enriched in B clusters; high Tinf and low Tinf, according to their CD8+ density; and desert clusters. At baseline, these clusters were not correlated with patient outcomes. Under NACT, tumors were segregated into three clusters: high BinfTinf, low Tinf, and desert. The high BinfTinf, more diverse in IC composition encompassing T, B, and NK cells, correlated with improved survival. PDL1 was rarely expressed, whereas TIM3, LAG3, and IDO1 were more prevalent. Conclusions: Several iTMEs exist during tumor evolution, and the NACT impact on iTME is heterogeneous. Clustering analysis of patients unravels several IC subsets within ovarian cancer and can guide future personalized approaches. Targeting different checkpoints such as TIM3, LAG3, and IDO1, more prevalent than PDL1, could more effectively harness antitumor immunity in this anti-PDL1–resistant malignancy.
Axon guidance cue SEMA3A promotes the aggressive phenotype of basal-like PDAC
Authors: Francesca Lupo, Francesco Pezzini, Davide Pasini, Elena Fiorini, Annalisa Adamo, Lisa Veghini, Michele Bevere, Cristina Frusteri, Pietro Delfino, Sabrina D'agosto, Silvia Andreani, Geny Piro, Antonia Malinova, Tian Wang, Francesco De Sanctis, Rita Teresa Lawlor, Chang-il Hwang, Carmine Carbone, Ivano Amelio, Peter Bailey, Vincenzo Bronte, David Tuveson, Aldo Scarpa, Stefano Ugel, Vincenzo Corbo
Journal: Gut (2024)

The dysregulation of the axon guidance pathway is common in pancreatic ductal adenocarcinoma (PDAC), yet our understanding of its biological relevance is limited. Here, we investigated the functional role of the axon guidance cue SEMA3A in supporting PDAC progression.
Targeted depletion of PD-1–expressing cells induces immune tolerance through peripheral clonal deletion
Authors: Jikai Cui, Heng Xu, Jizhang Yu, Shuan Ran, Xi Zhang, Yuan Li, Zhang Chen, Yuqing Niu, Song Wang, Weicong Ye, Wenhao Chen, Jie Wu, Jiahong Xia
Journal: Science Immunology (2024)

Thymic negative selection of the T cell receptor (TCR) repertoire is essential for establishing self-tolerance and acquired allograft tolerance following organ transplantation. However, it is unclear whether and how peripheral clonal deletion of alloreactive T cells induces transplantation tolerance. Here, we establish that programmed cell death protein 1 (PD-1) is a hallmark of alloreactive T cells and is associated with clonal expansion after alloantigen encounter. Moreover, we found that diphtheria toxin receptor (DTR)-mediated ablation of PD-1
When I use a word . . . The languages of medicines—British Approved Names
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

Approved names of medicines, later known as British Approved Names, were introduced in the UK in the 1940s, as part of wartime efforts to ensure the supply of important medicines, including antimalarial drugs manufactured in Germany. Giving them approved names allowed any manufacturer to market a product containing the medicine, which would otherwise only be available as a branded product. Such products were also cheaper than the originators. The 1968 Medicines Act made it a statutory requirement that approved names be used as the headings of monographs in publications such as the British Pharmacopoeia and the British Pharmaceutical Codex. Today, almost all British Approved Names (BANs), lists of which are published at regular intervals, are the same as the WHO's International Nonproprietary Names (INNs).
High efficacy of CD19 CAR T cells in patients with transformed Waldenström macroglobulinemia
Authors: Eric Durot, Damien Roosweil, Adrien Chauchet, Justine Decroocq, Roberta Di Blasi, Thomas Gastinne, Hedi Bensaber, Morgane Cheminant, Caroline Jacquet, Stéphanie Guidez, Francois-Xavier Gros, Emmanuel Bachy, Arthur Coste, Pascale Cony-Makhoul, Steven P. Treon, Alain Jacques Delmer, Ran Reshef, Steven Le Gouill, Jorge J. Castillo, Roch Houot
Journal: Blood (2024)
Obinutuzumab vs rituximab for transplant-eligible patients with mantle cell lymphoma
Authors: Clémentine Sarkozy, Mary Bridgid Callanan, Catherine Thieblemont, Lucie Obéric, Barbara Burroni, Krimo Bouabdallah, Ghandi Damaj, Benoit Tessoulin, Vincent Ribrag, Roch Huout, Franck Morschhauser, Samuel Griolet, Clémentine Joubert, Victoria Cacheux, Vincent Delwail, Violaine Safar, Remy Gressin, Morgane Cheminant, Marie-Helene Delfau-Larue, Olivier Hermine, Elizabeth A. Macintyre, Steven Le Gouill
Journal: Blood (2024)
Clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation
Authors: Clara Philine Wienecke, Bennet Heida, Letizia Venturini, Razif Gabdoulline, Katja Krüger, Katrin Teich, Konstantin Büttner, Martin Wichmann, Wolfram Puppe, Blerina Neziri, Marlene Reuter, Elke Dammann, Michael Stadler, Arnold Ganser, Lothar Hambach, Felicitas Thol, Michael Heuser
Journal: Blood (2024)
RNA splicing analysis deciphers developmental hierarchies and reveals therapeutic targets in adult glioma
Authors: Xiao Song, Deanna Tiek, Shunichiro Miki, Tianzhi Huang, Minghui Lu, Anshika Goenka, Rebeca Iglesia, Xiaozhou Yu, Runxin Wu, Maya Walker, Chang Zeng, Hardik Shah, Shao Huan Samuel Weng, Allen Huff, Wei Zhang, Tomoyuki Koga, Christopher Hubert, Craig M. Horbinski, Frank B. Furnari, Bo Hu, Shi-Yuan Cheng
Journal: Journal of Clinical Investigation (2024)

Widespread alterations in RNA alternative splicing (AS) have been identified in adult gliomas. However, their regulatory mechanism, biological significance, and therapeutic potential remain largely elusive. Here, using a computational approach with both bulk and single cell RNA-sequencing, we uncover a prognostic AS signature linked with neural developmental hierarchies. Using advanced iPSC glioma models driven by glioma driver mutations, we show that this AS signature could be enhanced by EGFRvIII and inhibited by in situ IDH1 mutation. Functional validation of two isoform switching events in CERS5 and MPZL1 shows regulations of sphingolipid metabolism and SHP2 signaling, respectively. Analysis of upstream RNA binding proteins reveals PTBP1 as a key regulator of the AS signature where targeting of PTBP1 suppresses tumor growth and promotes the expression of a neuron marker TUJ1 in glioma stem-like cells. Overall, our data highlights the role of AS in impacting glioma malignance and heterogeneity and its potential as a therapeutic vulnerability for treating adult gliomas.
Serine protease inhibitor, SerpinA3n, regulates cardiac remodelling after myocardial infarction
Authors: Qihao Sun, Wei Chen, Rimao Wu, Bo Tao, Ping Wang, Baiming Sun, Juan F Alvarez, Feiyang Ma, David Ceja Galindo, Sean P Maroney, Anthony J Saviola, Kirk C Hansen, Shen Li, Arjun Deb
Journal: Cardiovascular Research (2024)

Abstract Aims Following myocardial infarction (MI), the heart repairs itself via a fibrotic repair response. The degree of fibrosis is determined by the balance between deposition of extracellular matrix (ECM) by activated fibroblasts and breakdown of nascent scar tissue by proteases that are secreted predominantly by inflammatory cells. Excessive proteolytic activity and matrix turnover has been observed in human heart failure, and protease inhibitors in the injured heart regulate matrix breakdown. Serine protease inhibitors (Serpins) represent the largest and the most functionally diverse family of evolutionary conserved protease inhibitors, and levels of the specific Serpin, SerpinA3, have been strongly associated with clinical outcomes in human MI as well as non-ischaemic cardiomyopathies. Yet, the role of Serpins in regulating cardiac remodelling is poorly understood. The aim of this study was to understand the role of Serpins in regulating scar formation after MI. Methods and results Using a SerpinA3n conditional knockout mice model, we observed the robust expression of Serpins in the infarcted murine heart and demonstrate that genetic deletion of SerpinA3n (mouse homologue of SerpinA3) leads to increased activity of substrate proteases, poorly compacted matrix, and significantly worse post-infarct cardiac function. Single-cell transcriptomics complemented with histology in SerpinA3n-deficient animals demonstrated increased inflammation, adverse myocyte hypertrophy, and expression of pro-hypertrophic genes. Proteomic analysis of scar tissue demonstrated decreased cross-linking of ECM peptides consistent with increased proteolysis in SerpinA3n-deficient animals. Conclusion Our study demonstrates a hitherto unappreciated causal role of Serpins in regulating matrix function and post-infarct cardiac remodelling.
Understanding the patient experience of drug reaction with eosinophilia and systemic symptoms: A qualitative study
Authors: Upeka Samarakoon, Anna R. Wolfson, Li Zhou, Fatima Bassir, Elizabeth Phillips, Daniela Kroshinsky, Bethany Cucka, Bianca Biglione, Neelam A. Phadke, Jordon Jaggers, Emily C. Byrne, Allen D. Judd, Kimberly G. Blumenthal
Journal: Journal of the American Academy of Dermatology (2024)
The patterns of codon usage between chordates and arthropods are different but co-evolving with mutational biases
Authors: Ioanna Kotari, Carolin Kosiol, Rui Borges
Journal: Molecular Biology and Evolution (2024)

Abstract Different frequencies amongst codons that encode the same amino acid (i.e. synonymous codons) have been observed in multiple species. Studies focused on uncovering the forces that drive such codon usage showed that a combined effect of mutational biases and translational selection works to produce different frequencies of synonymous codons. However, only few have been able to measure and distinguish between these forces that may leave similar traces on the coding regions. Here, we have developed a codon model that allows the disentangling of mutation, selection on amino acids and synonymous codons, and GC-biased gene conversion (gBGC) which we employed on an extensive dataset of 415 chordates and 191 arthropods. We found that chordates need 15 more synonymous codon categories than arthropods to explain the empirical codon frequencies, which suggests that the extent of codon usage can vary greatly between animal phyla. Moreover, methylation at CpG sites seems to partially explain these patterns of codon usage in chordates but not in arthropods. Despite the differences between the two phyla, our findings demonstrate that in both, GC-rich codons are disfavored when mutations are GC-biased, and the opposite is true when mutations are AT-biased. This indicates that selection on the genomic coding regions might act primarily to stabilize its GC/AT content on a genome-wide level. Our study shows that the degree of synonymous codon usage varies considerably among animals, but is likely governed by a common underlying dynamic.