tbuckley/cabot-search huggingface dataset:
Genomic evolution of human respiratory syncytial virus during a decade (2013–2023): bridging the path to monoclonal antibody surveillance
Authors: Maria Piñana, Alejandra González-Sánchez, Cristina Andrés, Jorgina Vila, Anna Creus-Costa, Ignasi Prats-Méndez, Maria Arnedo-Muñoz, Narcís Saubi, Juliana Esperalba, Ariadna Rando, Patricia Nadal-Baron, Josep Quer, Juan José González-López, Pere Soler-Palacín, Jaime Martínez-Urtaza, Nieves Larrosa, Tomàs Pumarola, Andrés Antón
Journal: Journal of Infection (2024)

OBJECTIVESThis study investigated the prevalence, genetic diversity, and evolution of human respiratory syncytial virus (HRSV) in Barcelona from 2013 to 2023.METHODSRespiratory specimens from patients with RTI suspicion at Hospital Universitari Vall d'Hebron were collected from October/2013 to May/2023 for laboratory-confirmation of respiratory viruses. Next-generation sequencing was performed in randomly-selected samples with Illumina technology. Phylogenetic analyses of whole genome sequences were performed with BEAST v1.10.4. Signals of selection and evolutionary pressures were inferred by population dynamics and evolutionary analyses. Mutations in major surface proteins were genetic and structurally characterised, emphasizing those within antigenic epitopes.RESULTSAnalyzing 139,625 samples, 5.3% were HRSV-positive (3,008 HRSV-A, 3,882 HRSV-B, 56 HRSV-A and –B, and 495 unsubtyped HRSV), with a higher prevalence observed in the paediatric population. Pandemic-related shifts in seasonal patterns returned to normal in 2022-2023. A total of 198 whole-genome sequences were obtained for HRSV-A (6.6% of the HRSV-A positive samples) belonging to GA2.3.5 lineage. For HRSV-B, 167 samples were sequenced (4.3% of the HRSV-B positive samples), belonging to GB5.0.2, GB5.0.4a and GB5.0.5a. HRSV-B exhibited a higher evolution rate. Post-SARS-CoV-2 pandemic, both subtypes showed increased evolutionary rates and decreased effective population size initially, followed by a sharp increase. Analyses indicated negative selective pressure on HRSV. Mutations in antigenic epitopes, including S276N and M274I in palivizumab-targeted site II, and I206M, Q209R, and S211N in nirsevimab-targeted site Ø, were identified.DISCUSSIONParticularly in the context of the large-scale use in 2023-2024 season of nirsevimab, continuous epidemiological and genomic surveillance is crucial.
Viruses associated with measles-like illnesses in Uganda
Authors: Prossy Namuwulya, Shirin Ashraf, Marc Niebel, Alfred Ssekagiri, Phionah Tushabe, Proscovia Kakooza, Lily Tong, Henry Bukenya, Hanna Jerome, Chris Davis, Molly Birungi, Irene Turyahabwe, Arnold Mugaga, James Peter Eliku, Aine Francis, Lucy Nakabazzi, Fred Nsubuga, Edson Katushabe, Annet Kisakye, Immaculate Ampeire, Ann Nanteza, Pontiano Kaleebu, Barnabas Bakamutumaho, Peninah Nsamba, Anne Kazibwe, Ana da Silva Filipe, Robert Tweyongyere, Josephine Bwogi, Emma C. Thomson
Journal: Journal of Infection (2024)

ObjectivesIn this study, we investigated the causes of measles-like illnesses (MLI) in the Uganda national surveillance programme in order to inform diagnostic assay selection and vaccination strategies.MethodsWe used metagenomic next-generation sequencing (M-NGS) on the Illumina platform to identify viruses associated with MLI (defined as fever and rash in the presence of either cough, coryza or conjunctivitis) in patient samples that had tested IgM negative for measles between 2010 and 2019.ResultsViral genomes were identified in 87/271 (32%) of samples, of which 44/271 (16%) contained 12 known viral pathogens. Expected viruses included rubella, human parvovirus B19, Epstein Barr virus, human herpesvirus 6B, human cytomegalovirus, varicella zoster virus and measles virus (detected within the seronegative window-period of infection) and the blood-borne hepatitis B virus. We also detected Saffold virus, human parvovirus type 4, the human adenovirus C2 and vaccine-associated poliovirus type 1.ConclusionsThe study highlights the presence of undiagnosed viruses causing MLI in Uganda, including vaccine-preventable illnesses. NGS can be used to monitor common viral infections at a population level, especially in regions where such infections are prevalent, including low and middle income countries to guide vaccination policy and optimize diagnostic assays.
Cultural challenges for adapting behavioral intervention frameworks: A critical examination from a cultural psychology perspective
Authors: Ronald Fischer, Yuki Bailey, Megha Shankar, Nadia Safaeinili, Johannes A. Karl, Adam Daly, Finley Ngarangi Johnson, Taylor Winter, Hitaua Arahanga-Doyle, Ririwai Fox, Amina Abubakar, Donna Michelle Zulman
Journal: Clinical Psychology Review (2024)
Characterization of Responses to Lenvatinib plus Pembrolizumab in Patients with Advanced Renal Cell Carcinoma at the Final Prespecified Survival Analysis of the Phase 3 CLEAR Study
Authors: Robert J. Motzer, Toni K. Choueiri, Thomas Hutson, Sun Young Rha, Javier Puente, Aly-Khan A. Lalani, Eric Winquist, Masatoshi Eto, Naveen S. Basappa, Nizar M. Tannir, Ulka Vaishampayan, Georg A. Bjarnason, Stéphane Oudard, Viktor Grünwald, Joseph Burgents, Ran Xie, Jodi McKenzie, Thomas Powles
Journal: European Urology (2024)

In the phase 3 CLEAR trial, lenvatinib plus pembrolizumab (L + P) showed superior efficacy versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (aRCC). The combination treatment was associated with a robust objective response rate of 71%. Here we report tumor responses for patients in the L + P arm in CLEAR, with median follow-up of ∼4 yr at the final prespecified overall survival (OS) analysis. Tumor responses were assessed by independent review using Response Evaluation Criteria in Solid Tumors v1.1. Patients with a complete response (CR; n = 65), partial response (PR) with maximum tumor shrinkage ≥75% (near-CR; n = 59), or PR with maximum tumor shrinkage <75% (other PR; n = 129), were characterized in terms of their baseline characteristics. The median duration of response was 43.7 mo (95% confidence interval [CI] 39.2-not estimable) for the CR group, 30.5 mo (95% CI 22.4-not estimable) for the near-CR group, and 17.2 mo (95% CI 12.5-21.4) for the other PR group. The 36-mo OS rates were consistently high in the CR (97%), near-CR (86%), and other PR (62%) groups. Robust objective response rates were observed across International Metastatic RCC Database Consortium favorable-risk (69%, 95% CI 60-78%), intermediate-risk (73%, 95% CI 67-79%), and poor-risk (70%, 95% CI 54-85%) subgroups. The robust response to L + P supports this combination as a standard-of-care first-line treatment for patients with aRCC. PATIENT SUMMARY: The CLEAR trial enrolled patients with advanced kidney cancer who had not previously received any treatment for their cancer. Here we report results for tumor shrinkage observed in the group that received lenvatinib plus pembrolizumab combination treatment during the trial. Shrinkage of target tumors with this combination was long-lasting and was observed in patients irrespective of their disease severity. This trial is registered on ClinicalTrials.gov as NCT02811861.
Transient TCR-based T cell therapy in a patient with advanced treatment-resistant MSI-high colorectal cancer
Authors: Solrun Melkorka Maggadottir, Svein Dueland, Nadia Mensali, Hanne Hamre, Per Arne Andresen, Marit Renée Myhre, Hedvig V. Juul, Iris Bigalke, Marianne Lundby, Turid Kirsti Hønnåshagen, Stein Sæbøe-Larssen, Dag Josefsen, Trond Hagtvedt, Sébastien Wälchli, Gunnar Kvalheim, Else Marit Inderberg
Journal: Molecular Therapy (2024)

We previously demonstrated the antitumor effectiveness of transiently T cell receptor (TCR)-redirected T cells recognizing a frameshift mutation in transforming growth factor beta receptor 2. We here describe a clinical protocol using mRNA TCR-modified T cells to treat a patient with progressive, treatment-resistant metastatic microsatellite instabilityhigh (MSI-H) colorectal cancer.Following 12 escalating doses of autologous T cells electroporated with in-vitro-transcribed Radium-1 TCR mRNA, we assessed T cell cytotoxicity, phenotype, and cytokine production.Tumor markers and growth on computed tomography scans were evaluated and immune cell tumor infiltrate at diagnosis assessed.At diagnosis, tumorinfiltrating CD8+ T cells had minimal expression of exhaustion markers, except for PD-1.Injected Radium-1 T cells were mainly naive and effector memory T cells with low expression of exhaustion markers, except for TIGIT.We confirmed cytotoxicity of transfected Radium-1 T cells against target cells and found key cytokines involved in tumor metastasis, growth, and angiogenesis to fluctuate during treatment.The treatment was well tolerated, and despite his advanced cancer, the patient obtained a stable disease with 6 months survival post-treatment.We conclude that treatment of metastatic MSI-H colorectal cancer with autologous T cells electroporated with Radium-1 TCR mRNA is feasible, safe, and well tolerated and that it warrants further investigation in a phase 1/2 study.
A Multimodal Video-Based AI Biomarker for Aortic Stenosis Development and Progression
Authors: Evangelos K. Oikonomou, Gregory Holste, Neal Yuan, Andreas Coppi, Robert L. McNamara, Norrisa A. Haynes, Amit N. Vora, Eric J. Velazquez, Fan Li, Venu Menon, Samir R. Kapadia, Thomas M. Gill, Girish N. Nadkarni, Harlan M. Krumholz, Zhangyang Wang, David Ouyang, Rohan Khera
Journal: JAMA Cardiology (2024)

Aortic stenosis (AS) is a major public health challenge with a growing therapeutic landscape, but current biomarkers do not inform personalized screening and follow-up. A video-based artificial intelligence (AI) biomarker (Digital AS Severity index [DASSi]) can detect severe AS using single-view long-axis echocardiography without Doppler characterization.
Cause-Specific Health Care Costs Following Hospitalization for Heart Failure and Cost Offset With SGLT2i Therapy
Authors: Veraprapas Kittipibul, Muthiah Vaduganathan, Uchechukwu Ikeaba, Karen Chiswell, Javed Butler, Adam D. DeVore, Paul A. Heidenreich, Joanna C. Huang, Michelle M. Kittleson, Karen E. Joynt Maddox, Karthik K. Linganathan, James J. McDermott, Anjali Tiku Owens, Pamela N. Peterson, Scott D. Solomon, Orly Vardeny, Clyde W. Yancy, Gregg C. Fonarow, Stephen J. Greene
Journal: JACC Heart Failure (2024)
Empagliflozin after Acute Myocardial Infarction
Authors: Javed Butler, W. Schuyler Jones, Jacob A. Udell, Stefan D. Anker, Mark C. Petrie, Josephine Harrington, Michaela Mattheus, Isabella Zwiener, Offer Amir, M. Cecilia Bahit, Johann Bauersachs, Antoni Bayes-Genis, Yundai Chen, Vijay K. Chopra, Gemma Figtree, Junbo Ge, Shaun G. Goodman, Nina Gotcheva, Shinya Goto, Tomasz Gasior, Waheed Jamal, James L. Januzzi, Myung Ho Jeong, Yuri Lopatin, Renato D. Lopes, Béla Merkely, Puja B. Parikh, Alexander Parkhomenko, Piotr Ponikowski, Xavier Rossello, Morten Schou, Dragan Simic, P. Gabriel Steg, Joanna Szachniewicz, Peter van der Meer, Dragos Vinereanu, Shelley Zieroth, Martina Brueckmann, Mikhail Sumin, Deepak L. Bhatt, Adrian F. Hernandez
Journal: New England Journal of Medicine (2024)

Empagliflozin improves cardiovascular outcomes in patients with heart failure, patients with type 2 diabetes who are at high cardiovascular risk, and patients with chronic kidney disease. The safety and efficacy of empagliflozin in patients who have had acute myocardial infarction are unknown.
Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases
Authors: Zarah R. Haniff, Mariia Bocharova, Tim Mantingh, James J. Rucker, Latha Velayudhan, David M. Taylor, Allan H. Young, Dag Aarsland, Anthony C. Vernon, Sandrine Thuret
Journal: Pharmacology & Therapeutics (2024)

Major depression is an established risk factor for subsequent dementia, and depression in late life may also represent a prodromal state of dementia. Considering current challenges in the clinical development of disease modifying therapies for dementia, the focus of research is shifting towards prevention and modification of risk factors to alter the neurodegenerative disease trajectory. Understanding mechanistic commonalities underlying affective symptoms and cognitive decline may reveal biomarkers to aid early identification of those at risk of progressing to dementia during the preclinical phase of disease, thus allowing for timely intervention. Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases. Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk.
Decoding and overcoming T cell exhaustion: Epigenetic and transcriptional dynamics in CAR-T cells against solid tumors
Authors: Taeyoung Ahn, Eun-Ah Bae, Hyungseok Seo
Journal: Molecular Therapy (2024)

T cell exhaustion, which is observed in various chronic infections and malignancies, is characterized by elevated expression of multiple inhibitory receptors, impaired effector functions, decreased proliferation, and reduced cytokine production. Notably, while adoptive T cell therapies, such as chimeric antigen receptor (CAR)-T therapy, have shown promise in treating cancer and other diseases, the efficacy of these therapies is often compromised by T cell exhaustion. It is imperative, therefore, to understand the mechanisms underlying this exhaustion to promote advances in T cell-related therapies. Here, we divided exhausted T cells into three distinct subsets according to their developmental and functional profiles: stem-like progenitor cells, intermediately exhausted cells, and terminally exhausted cells. These subsets are carefully regulated by synergistic mechanisms that involve transcriptional and epigenetic modulators. Key transcription factors, such as TCF1, BACH2, and TOX, are crucial for defining and sustaining exhaustion phenotypes. Concurrently, epigenetic regulators, such as TET2 and DNMT3A, shape the chromatin dynamics that direct T cell fate. The interplay of these molecular drivers has recently been highlighted in CAR-T research, revealing promising therapeutic directions. Thus, a profound understanding of exhausted T cell hierarchies and their molecular complexities may reveal innovative and improved tumor treatment strategies.
Extensive Macular Atrophy with Pseudodrusen-like appearance
Authors: Alessio Antropoli, Lorenzo Bianco, Christel Condroyer, Aline Antonio, Julien Navarro, Dorothée Dagostinoz, Amine Benadji, José-Alain Sahel, Christina Zeitz, Isabelle Audo
Journal: Ophthalmology (2024)

To describe the clinical outcome and late-stage findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP).
The authors reply
Authors: Winston W.S. Fung, Valerie A. Luyckx, Katherine R. Tuttle, Alessandro Balducci, Vassilios Liakopoulos, Li-Li Hsiao, Ricardo Correa-Rotter, Ifeoma Ulasi, Latha Kumaraswami, Siu Fai Lui, Dina Abdellatif, Ágnes Haris
Journal: Kidney International (2024)
Psychological wellbeing in parents of children with Down syndrome: A systematic review and meta-analysis
Authors: T.L. Rutter, R.P. Hastings, C.A. Murray, N. Enoch, S. Johnson, C. Stinton
Journal: Clinical Psychology Review (2024)

We report a review examining the psychological wellbeing of parents of children with Down syndrome (DS) relative to that of parents of typically developing (TD) children. A systematic search identified 57 relevant studies, which were synthesised meta-analytically. Relative to their counterparts with TD children, mothers and fathers of children with DS reported higher levels of parenting stress (mothers: g = 0.57, 95% CI [0.33, 0.81]; fathers: g = 0.40, [0.24, 0.56]), depressive symptoms (mothers: g = 0.42, [0.23, 0.61]; fathers: g = 0.25, [0.02, 0.48]) and psychological distress (mothers: g = 0.45, [0.30, 0.60]; fathers: g = 0.63, [0.26, 0.99]). Small effects were found for anxiety for mothers (g = 0.16, [0.03, 0.29]), with no differences for fathers (g = 0.03, [-0.25, 0.32]). No group differences were found for positive impact of parenting (mothers: g = -0.09, [-0.25, 0.07]; fathers: g = -0.04, [-0.30, 0.22]), while evidence concerning other positive wellbeing outcomes was limited. No significant moderating effects of child age range, country income level, or group differences in parental education level were identified, but limited subgroup analyses were possible. Raising a child with DS may be associated with elevated stress, depressive symptoms, and psychological distress for mothers and fathers. However, levels of parenting reward appear equivalent to those experienced by parents raising TD children.
A p21-ATD mouse model for monitoring and eliminating senescent cells and its application in liver regeneration post injury
Authors: Miaomiao Chen, Guoxiu Wu, Yanli Lu, Shiwen Sun, Zhao Yu, Xin Pan, Wenjian Chen, Hongyu Xu, Hua Qiu, Weizhi He, Xiuhua Li, Xicheng Wang, Yi Luo, Yuan Du, Jialing Wu, Ke Wei, Wencheng Zhang, Zhongmin Liu, Zhiying He
Journal: Molecular Therapy (2024)
Tertiary lymphoid structural heterogeneity determines tumour immunity and prospects for clinical application
Authors: Yuyuan Zhang, Mengjun Xu, Yuqing Ren, Yuhao Ba, Shutong Liu, Anning Zuo, Hui Xu, Siyuan Weng, Xinwei Han, Zaoqu Liu
Journal: Molecular Cancer (2024)

Abstract Tertiary lymphoid structures (TLS) are clusters of immune cells that resemble and function similarly to secondary lymphoid organs (SLOs). While TLS is generally associated with an anti-tumour immune response in most cancer types, it has also been observed to act as a pro-tumour immune response. The heterogeneity of TLS function is largely determined by the composition of tumour-infiltrating lymphocytes (TILs) and the balance of cell subsets within the tumour-associated TLS (TA-TLS). TA-TLS of varying maturity, density, and location may have opposing effects on tumour immunity. Higher maturity and/or higher density TLS are often associated with favorable clinical outcomes and immunotherapeutic response, mainly due to crosstalk between different proportions of immune cell subpopulations in TA-TLS. Therefore, TLS can be used as a marker to predict the efficacy of immunotherapy in immune checkpoint blockade (ICB). Developing efficient imaging and induction methods to study TA-TLS is crucial for enhancing anti-tumour immunity. The integration of imaging techniques with biological materials, including nanoprobes and hydrogels, alongside artificial intelligence (AI), enables non-invasive in vivo visualization of TLS. In this review, we explore the dynamic interactions among T and B cell subpopulations of varying phenotypes that contribute to the structural and functional diversity of TLS, examining both existing and emerging techniques for TLS imaging and induction, focusing on cancer immunotherapies and biomaterials. We also highlight novel therapeutic approaches of TLS that are being explored with the aim of increasing ICB treatment efficacy and predicting prognosis.
Accurate identification of a precursor <scp>B</scp>‐cell neoplasm
Authors: Abdalla Dikair, Kirsteen Harper, Mike Leach, Barbara J. Bain
Journal: American Journal of Hematology (2024)

A 23-year-old man with a history of Crohn's disease and liver transplantation for sclerosing cholangitis developed pancytopenia during corticosteroid therapy. His blood count showed hemoglobin concentration 81 g/L, white cell count 7.1 × 109/L, neutrophils 0.7 × 109/L, and platelets 34 × 109/L. His blood film showed a population of medium sized lymphoid cells with a high nucleocytoplasmic ratio, some with prominent nucleoli and vacuolation (top left, all images ×100 objective). A large population of these cells were noted in the bone marrow aspirate (top center) and trephine biopsy sections (top right). Immunophenotyping of the CD45weak cells (purple events plot 1) showed these cells to express CD19, CD79a (plot 2), CD22, HLA-DR, and CD15 (plot 3). Importantly, CD34, CD117, myeloperoxidase, CD10, cytoplasmic CD3, CD79b, and terminal deoxynucleotidyl transferase (TdT) (plot 4), were not expressed, nor was cytoplasmic or surface membrane immunoglobulin (Ig). The morphology in this case is indicative of a precursor neoplasm and B lineage was indicated by expression of CD19, CD79a, and CD22. Unusually CD34 and TdT were not expressed. The lack of surface and cytoplasmic Ig, weak CD45, absent CD79b and aberrant expression of CD15 are, however, all features of a precursor B-cell neoplasm. Pro-B acute lymphoblastic leukemia, despite arising from an early precursor, may fail to express TdT and sometimes CD34.1 It is often associated with a KMT2A translocation and this was shown in this case with t(4;11)(q21;q23.3) confirming the diagnosis. Furthermore, the glucocorticoid therapy used in the management of Crohn's disease in this patient may have induced downregulation of precursor antigen expression similar to that reported during induction chemotherapy.2, 3 The authors declare no conflicts of interest.
Distinct bone marrow findings associated with a noncanonical <scp><i>UBA1</i></scp> variant in <scp>VEXAS</scp> syndrome
Authors: Devin R. Allison, Bhagirathbhai Dholaria, Ashwin Kishtagari, Sanjay Mohan, Eli Steigelfest, Aaron C. Shaver, Emily F. Mason
Journal: American Journal of Hematology (2024)