tbuckley/cabot-search huggingface dataset:
A reassuringly routine trial
Authors: Joerg Albrecht
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript A reassuringly routine trial Get access Joerg Albrecht Joerg Albrecht Division of Dermatology, Department of Medicine, J.H. Stroger Hospital of Cook County, Chicago, Illinois, USADepartment of Medicine, Rush Medical College, Chicago, Illinois, USA Email:joerg.albrecht@gmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae468, https://doi.org/10.1093/bjd/ljae468 Published: 25 November 2024 Article history Received: 11 November 2024 Editorial decision: 21 November 2024 Revision received: 21 November 2024 Accepted: 22 November 2024 Published: 25 November 2024
Cost-Effectiveness of Extending Human Papillomavirus Vaccination to Population Subgroups Older Than 26 Years Who Are at Higher Risk for Human Papillomavirus Infection in the United States
Authors: Jean-François Laprise, Harrell W. Chesson, Lauri E. Markowitz, Mélanie Drolet, Marc Brisson
Journal: Annals of Internal Medicine (2024)

In June 2019, the U.S. Advisory Committee on Immunization Practices recommended shared clinical decision making regarding potential human papillomavirus (HPV) vaccination of men and women aged 27 to 45 years ("mid-adults").
Single-Cell RNA Sequencing to Guide Autologous Preterm Cord Mesenchymal Stromal Cell-Therapy
Authors: Chanèle Cyr-Depauw, Ivana Mižik, David P Cook, Flore Lesage, Arul Vadivel, Laurent Renesme, Yupu Deng, Shumei Zhong, Pauline Bardin, Liqun Xu, Marius A. Möbius, Jenny Marzahn, Daniel Freund, Duncan J. Stewart, Barbara C Vanderhyden, Mario Rüdiger, Bernard Thébaud
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

The chronic lung disease bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity (<28 weeks of gestation). Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) represent an opportunity for autologous cell-therapy, as UC-MSCs have been shown to improve lung function and structure in experimental BPD. However, characterization and repair capacity of UC-MSCs derived from donors with pregnancy-related complications associated with prematurity remain unexplored. To characterize UC-MSCs' transcriptome and determine if pregnancy-related complications (preeclampsia and chorioamnionitis) alter their therapeutic potential. Single-cell RNA sequencing (scRNA-seq) was used to compare the transcriptome of UC-MSCs derived from five term donors, 16 preterm donors, and human neonatal dermal fibroblasts (HNDFs, control cells of mesenchymal origin), and correlated with their therapeutic potential in experimental BPD. Using publicly available neonatal lung single-nuclei RNA sequencing data, we also determined putative communication networks between UC-MSCs and resident lung cell populations. Most UC-MSCs displayed a similar transcriptome despite of their pregnancy-related conditions and mitigated hyperoxia-induced lung injury in newborn rats. Conversely, HNDFs, one term and two preeclampsia preterm UC-MSC donors exhibited a distinct transcriptome enriched in genes related to fibroblast function and senescence and were devoid of therapeutic benefit in hyperoxia-induced BPD. Conversely, therapeutic UC-MSCs displayed a unique transcriptome active in cell proliferation and distinct cell-cell interactions with neonatal lung cell populations, including NEGR and NRNX pathways. Term and preterm UC-MSCs are lung protective in experimental BPD. scRNA-seq allows to identify donors with a distinct UC-MSC transcriptome characteristic of reduced therapeutic potential.
Prenatal Indoor PM<sub>2.5</sub> Exposure is Associated with Worse Maternal Asthma Health and Lung Function
Authors: Jing Gennie Wang, Hsiao-Hsien Leon Hsu, Rachel Meislin, Vi Le, Robert Wharton, Noah Mathis, Kevin Rurak, Corrine Hanson, Sonali Bose
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
Succinate-producing microbiota drives tuft cell hyperplasia to protect against <i>Clostridioides difficile</i>
Authors: Tasia D. Kellogg, Simona Ceglia, Benedikt M. Mortzfeld, Tanvi M. Tanna, Abigail L. Zeamer, Matthew R. Mancini, Sage E. Foley, Doyle V. Ward, Shakti K. Bhattarai, Beth A. McCormick, Andrea Reboldi, Vanni Bucci
Journal: The Journal of Experimental Medicine (2024)

The role of microbes and their metabolites in modulating tuft cell (TC) dynamics in the large intestine and the relevance of this pathway to infections is unknown. Here, we uncover that microbiome-driven colonic TC hyperplasia protects against Clostridioides difficile infection. Using selective antibiotics, we demonstrate increased type 2 cytokines and TC hyperplasia in the colon but not in the ileum. We demonstrate the causal role of the microbiome in modulating this phenotype using fecal matter transplantation and administration of consortia of succinate-producing bacteria. Administration of succinate production–deficient microbes shows a reduced response in a Pou2f3-dependent manner despite similar intestinal colonization. Finally, antibiotic-treated mice prophylactically administered with succinate-producing bacteria show increased protection against C. difficile–induced morbidity and mortality. This effect is nullified in Pou2f3−/− mice, confirming that the protection occurs via the TC pathway. We propose that activation of TCs by the microbiota in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by pathogens.
Alcohol Use and Antiobesity Medication Treatment
Authors: Lisa R. Miller-Matero, Hsueh-Han Yeh, Lisiyu Ma, Rebecca A. Jones, Spencer Nadolsky, Adam Medcalf, Gary D. Foster, Michelle I. Cardel
Journal: JAMA Network Open (2024)

This cohort study examines the association of antiobesity medication use and alcohol use among participants enrolled in a weigh loss program.
Geographic Disparities in Gynecologic Oncology Clinical Trial Availability in the US
Authors: Mary Regina Boland, Elizabeth Tubridy, Sebastian Spataro Solorzano, Fiona Simpkins, Anna Jo Bodurtha Smith, Emily M. Ko
Journal: JAMA Network Open (2024)

Disparities in minoritized racial and ethnic populations' participation in gynecologic cancer clinical trials are well documented despite the high rates of endometrial cancer in these populations. Geographic proximity to trials is a critical component to ensure equitable trial access.
Collaborative Care Model for Patients With Opioid Use Disorder and Mental Illness
Authors: Katherine E. Watkins, Rebecca Weir, Lia Pak, Beth Ann Griffin, Amber Griffo, Allison Trosclair Sutherland, Colleen M. McCullough, Lisa S. Meredith, Michael Schoenbaum, Miriam Komaromy, Valerie Carrejo, Karen Chan Osilla
Journal: JAMA Network Open (2024)

This cohort study uses data from a randomized clinical trial for opioid use disorder (OUD) co-occurring with mental illness to examine patient characteristics associated with collaborative care model engagement and fidelity.
Virtual Home Care for Patients With Acute Illness
Authors: Josh Banerjee, Christopher Lynch, Hugh Gordon, Charles E. Coffey, Catherine P. Canamar, Soodtida Tangpraphaphorn, Karla Gonzalez, Neha Mahajan, Jan Shoenberger, Michael Menchine, Andrew Oh, Emily Johnson, Molly Grassini, Rachel Baden, Paul Holtom, Douglass Hutcheon, Brandon M. Wiley, Kusha Davar, Sheila Mallet-Smith, Margaret Sanfratello, Brenda Gallardo, Meixine Song, Nikole Swain, Maria Lydia Solis, Jenny Silva, Charmaine Pablico, Eduardo Aceves, Erica Bonilla, Ria Ashley Legaspi, Deisy M. Guevara, Karissa Lee, Christina Martinez, Michelle Banh, Dana Russell, Lissette Cervantes, Jacqueline Cervantes, Cesar Gonzalez, Phillip Sheth, Shadi Dowlatshahi, Alex Rosenberg, Pruthul Patel, Wei-An Lee, Tanzim Khan, Tze-Woei Tan, Michael Fong, Samuel S. Gordon, Brandi Clark, Victor Pena, Steven Dohi, Beatrisa Bannister, Roman Villalta, Priya Induru, Pauline Vuong, David Lwe, Karen Stoffel, Sam Oh, Christian Voyageur, Andrew Cool, Yong Lee, Stephen Lenh, Janet Luong, Gary Hanna, Jason N. Doctor, Bryan Munoz, Concepcion Castro, Edgar Solis, Nancy Blake, Roza Sakzalyan, Christopher J. Rodriguez, Christina Ghaly, Jorge Orozco, Hal F. Yee, Brad Spellberg
Journal: JAMA Network Open (2024)

Recent evolutions in clinical care and remote monitoring suggest that some acute illnesses no longer require intravenous therapy and inpatient hospitalization.
The Proliferation of Multiplex Molecular Testing for Urinary Tract Infections
Authors: Margaret A. Fitzpatrick, Daniel J. Morgan
Journal: JAMA Network Open (2024)

Kelly M. Hatfield, DrPH, MSPH; Sarah Kabbani, MD; Isaac See, MD; Dustin W. Currie, PhD; Christine Kim, PhD; Kara Jacobs Slifka, MD; Shelley S. Magill, MD, PhD; Lauri A. Hicks, DO; L. Clifford McDonald, MD; John Jernigan, MD, MS; Sujan C. Reddy, MD, MSc; Joseph D. Lutgring, MD
Changing Perceptions of Health Care Among Patients With Kidney Disease
Authors: Beatrice P. Concepcion, Milda R. Saunders
Journal: JAMA Network Open (2024)

Miriam Vélez-Bermúdez, PhD, MPH; Yuridia Leyva, MS; Jamie M. Loor, PhD; Mary Amanda Dew, PhD; Yiliang Zhu, PhD; Mark L. Unruh, MD, MS; L. Ebony Boulware, MD, MPH; Amit Tevar, MD; Larissa Myaskovsky, PhD
Phase 1/2 Study of the Aurora Kinase A Inhibitor Alisertib and Pembrolizumab in Refractory, Rb-Deficient Head and Neck Squamous Cell Carcinomas
Authors: Faye M. Johnson, Madison P. O'Hara, Lacin Yapindi, Peixin Jiang, Hai T. Tran, Alexandre Reuben, Weihong Xiao, Maura Gillison, Xiaowen Sun, Alexander Khalaf, J. Jack. Lee, Jagannadha K. Sastry, Soma Ghosh
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers. Experimental Design: Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase 1) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase 2). Results: The recommended phase 2 alisertib dose was 40 mg which had only the expected toxicity including cytopenia that led to dose reductions in two phase 2 patients at cycles 13 and 16. We saw no objective responses, but the combination led to prolonged stable disease (SD) in several patients, including 2 of 10 phase 1 patients (8 and 27 months). Eight of the 15 HPV-positive patients had SD; four of them (heavily pretreated) for ≥6 months, with median overall and progression-free survival durations of 16.8 and 1.4 months, respectively. In circulating immune cells and plasma patients with SD had markedly higher levels of HLA-DR–expressing natural killer cells than did progressive disease patients who demonstrated a more immunosuppressive and inflammatory profile. Pharmacokinetics did not indicate any significant drug-drug interactions between pembrolizumab and alisertib. Conclusions: The combination of alisertib and pembrolizumab was well tolerated and led to prolonged SD in some immunotherapy-resistant patients, supporting our hypothesis that Aurora kinase A inhibition can reverse immunotherapy resistance of retinoblastoma protein-deficient HNSCC.
Total (Immuno)Therapy: Version 2.0
Authors: Susan Bal, Luciano J. Costa
Journal: Blood Cancer Discovery (2024)

Summary: Among patients with poly-refractory myeloma, autologous chimeric antigen receptor T-cell therapy offers exceptional promise. With the availability of bispecific antibodies, a total immunotherapeutic strategy in combination with chimeric antigen receptor T-cell therapy is now feasible. See related article by Fandrei, p. XX
Electrical Impedance Tomography Changes Following Surfactant Administration: Signs to Be Explored
Authors: Walusa A. Gonçalves-Ferri, Felipe S. Rossi, Maisa Ribeiro, Thais Iwashita-Lages, Maria A. M. Nakamura, Letícia C. Correa, Eduardo L. V. Costa, Marcelo B. P. Amato
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
Cognitive Reserve and Cluster Analysis: New Pieces in the Puzzle of Cognitive Impairment after ICU?
Authors: Sol Fernández-Gonzalo, Marta Godoy-González, Guillem Navarra-Ventura, Antoni Berenguer-Llergo, Mercè Jodar, Lluís Blanch, Josefina López-Aguilar
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
Comparison of <scp>CD30L</scp> and <scp>OX40L</scp> Reveals <scp>CD30L</scp> as a Promising Therapeutic Target in Atopic Dermatitis
Authors: Rinkesh K. Gupta, Daniela Salgado Figueroa, Ferhat Ay, Benjamin Causton, Shahla Abdollahi, Michael Croft
Journal: Allergy (2024)

Blocking IL-13 is highly efficacious in patients with Th2-biased atopic dermatitis (AD), and recent clinical data have highlighted that targeting the T cell costimulatory molecules OX40 and OX40L (TNFSF4) holds promise for future treatment of AD. We asked whether targeting another T cell costimulatory molecule, CD30L (TNFSF8), might also be a possible treatment option in AD. Single-cell RNA-seq data from human AD skin lesions was analyzed to identify pathogenic IL-13- or IL-22-producing T cells and assess expression of CD30 and its ligand in comparison to OX40 and its ligand. Additionally, a murine model of AD with repetitive exposure to house dust mite allergen was used to compare neutralizing antibodies against CD30L with those against IL-13 or OX40L. Analysis of several scRNA-seq datasets from skin lesions of AD patients showed that transcripts for CD30 or CD30L were found expressed with OX40 or OX40L in the primary T cell populations that also expressed mRNA for IL13 and/or IL22. Suggesting that this could be therapeutically relevant, mice treated prophylactically with a blocking CD30L antibody were protected from developing maximal allergen-induced AD features, including epidermal and dermal thickening, immune cell infiltration, and expression of AD-related genes, similar to mice treated with a blocking IL-13 antibody. Moreover, therapeutic neutralization of CD30L in mice with experimental AD also reduced all of the pathological skin lesion features to a comparable extent as blocking OX40L. These data suggest that targeting the CD30-CD30L axis might hold promise as a future therapeutic intervention in human AD, similar to targeting the OX40-OX40L axis.
Human VCP mutant ALS/FTD microglia display immune and lysosomal phenotypes independently of GPNMB
Authors: Benjamin E. Clarke, Oliver J. Ziff, Giulia Tyzack, Marija Petrić Howe, Yiran Wang, Pierre Klein, Claudia A. Smith, Cameron A. Hall, Adel Helmy, Michael Howell, Gavin Kelly, Rickie Patani
Journal: Molecular Neurodegeneration (2024)

Abstract Background Microglia play crucial roles in maintaining neuronal homeostasis but have been implicated in contributing to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the role of microglia in ALS/FTD remains incompletely understood. Methods Here, we generated highly enriched cultures of VCP mutant microglia derived from human induced pluripotent stem cells (hiPSCs) to investigate their cell autonomous and non-cell autonomous roles in ALS pathogenesis. We used RNA-sequencing, proteomics and functional assays to study hiPSC derived VCP mutant microglia and their effects on hiPSC derived motor neurons and astrocytes. Results Transcriptomic, proteomic and functional analyses revealed immune and lysosomal dysfunction in VCP mutant microglia. Stimulating healthy microglia with the inflammatory inducer lipopolysaccharide (LPS) showed partial overlap with VCP mutant microglia in their reactive transformation. LPS-stimulated VCP mutant microglia displayed differential activation of inflammatory pathways compared with LPS-stimulated healthy microglia. Conserved gene expression changes were identified between VCP mutant microglia, SOD1 mutant mice microglia, and postmortem ALS spinal cord microglial signatures, including increased expression of the transmembrane glycoprotein GPNMB . While knockdown of GPNMB affected inflammatory and phagocytosis processes in microglia, this was not sufficient to ameliorate cell autonomous phenotypes in VCP mutant microglia. Secreted factors from VCP mutant microglia were sufficient to activate the JAK-STAT pathway in hiPSC derived motor neurons and astrocytes. Conclusions VCP mutant microglia undergo cell autonomous reactive transformation involving immune and lysosomal dysfunction that partially recapitulate key phenotypes of microglia from other ALS models and post mortem tissue. These phenotypes occur independently of GPNMB . Additionally, VCP mutant microglia elicit non cell autonomous responses in motor neurons and astrocytes involving the JAK-STAT pathway.
CAR-T cell therapy in Multiple Myeloma: current status and future challenges
Authors: Dawn Swan, Deepu Madduri, Jay Hocking
Journal: Blood Cancer Journal (2024)

The treatment of multiple myeloma has changed dramatically in recent years, with huge strides forward made in the field. Chimeric antigen receptor T-cell therapy targeting the B cell maturation antigen (BCMA) is now widely approved in relapsed refractory patients and is moving into earlier treatment lines. In this review, we discuss the evidence underpinning current regulatory approvals and consider mechanisms through which CAR-T cell efficacy could be improved. These include tackling BCMA-loss, harnessing the immunosuppressive tumour microenvironment, manufacturing concerns including the potential role of other cellular sources, safety issues such as cytokine release syndrome and neurotoxicity, and optimal patient selection.
IL-17 signaling protects against <i>Helicobacter pylori-</i> induced gastric cancer
Authors: Lee C. Brackman, Matthew S. Jung, Emily H. Green, Nikhita Joshi, Frank L. Revetta, Mark S. McClain, Nicholas O. Markham, M. Blanca Piazuelo, Holly M. Scott Algood
Journal: Gut Microbes (2024)

infection is the predominant risk factor for the development of gastric cancer. Risk is enhanced by specific
Age-related decline in CD8+ tissue resident memory T cells compromises antitumor immunity
Authors: Siyu Pei, Xiuyu Deng, Ruirui Yang, Hui Wang, Jian-Hong Shi, Xueqing Wang, Jia Huang, Yu Tian, Rongjing Wang, Sulin Zhang, Hui Hou, Jing Xu, Qingcheng Zhu, Huan Huang, Jialing Ye, Cong-Yi Wang, Wei Lu, Qingquan Luo, Zhi-Yu Ni, Mingyue Zheng, Yichuan Xiao
Journal: Nature Aging (2024)
Genetic basis of early onset and progression of type 2 diabetes in South Asians
Authors: Sam Hodgson, Alice Williamson, Margherita Bigossi, Daniel Stow, Benjamin M. Jacobs, Miriam Samuel, Joseph Gafton, Julia Zöllner, Marie Spreckley, Shaheen Akhtar, Ana Angel, Omar Asgar, Samina Ashraf, Saeed Bidi, Gerome Breen, James Broster, Raymond Chung, David Collier, Charles J. Curtis, Shabana Chaudhary, Grainne Colligan, Panos Deloukas, Ceri Durham, Faiza Durrani, Fabiola Eto, Joseph Gafton, Chris Griffiths, Joanne Harvey, Teng Heng, Qin Qin Huang, Karen A. Hunt, Matt Hurles, Shapna Hussain, Kamrul Islam, Vivek Iyer, Georgios Kalantzis, Ahsan Khan, Cath Lavery, Sang Hyuck Lee, Daniel MacArthur, Eamonn Maher, Daniel Malawsky, Sidra Malik, Hilary Martin, Dan Mason, Mohammed Bodrul Mazid, John McDermott, Caroline Morton, Bill Newman, Vladimir Ovchinnikov, Elizabeth Owor, Iaroslav Popov, Asma Qureshi, Mehru Raza, Jessry Russell, Stuart Rison, Nishat Safa, Annum Salman, Michael Simpson, John Solly, Michael Taylor, Richard C. Trembath, Karen Tricker, David A. Van Heel, Klaudia Walter, Jan Whalley, Caroline Winckley, Suzanne Wood, John Wright, Sabina Yasmin, Ishevanhu Zengeya, Claudia Langenberg, David A. van Heel, Rohini Mathur, Moneeza K. Siddiqui, Sarah Finer
Journal: Nature Medicine (2024)

Abstract South Asians develop type 2 diabetes (T2D) early in life and often with normal body mass index (BMI). However, reasons for this are poorly understood because genetic research is largely focused on European ancestry groups. We used recently derived multi-ancestry partitioned polygenic scores (pPSs) to elucidate underlying etiological pathways British Pakistani and British Bangladeshi individuals with T2D ( n = 11,678) and gestational diabetes mellitus (GDM) ( n = 1,965) in the Genes &amp; Health study ( n = 50,556). Beta cell 2 (insulin deficiency) and Lipodystrophy 1 (unfavorable fat distribution) pPSs were most strongly associated with T2D, GDM and younger age at T2D diagnosis. Individuals at high genetic risk of both insulin deficiency and lipodystrophy were diagnosed with T2D 8.2 years earlier with BMI 3 kg m − 2 lower compared to those at low genetic risk. The insulin deficiency pPS was associated with poorer HbA1c response to SGLT2 inhibitors. Insulin deficiency and lipodystrophy pPSs were associated with faster progression to insulin dependence and microvascular complications. South Asians had a greater genetic burden from both of these pPSs than white Europeans in the UK Biobank. In conclusion, genetic predisposition to insulin deficiency and lipodystrophy in British Pakistani and British Bangladeshi individuals is associated with earlier onset of T2D, faster progression to complications, insulin dependence and poorer response to medication.
Genome-aware annotation of CRISPR guides validates targets in variant cell lines and enhances discovery in screens
Authors: Simon Lam, John C. Thomas, Stephen P. Jackson
Journal: Genome Medicine (2024)

Abstract Background CRISPR-Cas9 technology has revolutionised genetic screens and can inform on gene essentiality and chemo-genetic interactions. It is easily deployed and widely supported with many pooled CRISPR libraries available commercially. However, discrepancies between the reference genomes used in the design of those CRISPR libraries and the cell line under investigation can lead to loss of signal or introduction of bias. The problem is particularly acute when dealing with variant cell lines such as cancer cell lines. Results Here, we present an algorithm, EXOme-guided Re-annotation of nuCleotIde SEquences (Exorcise), which uses sequence search to detect and correct mis-annotations in CRISPR libraries. Exorcise verifies the presence of CRISPR targets in the target genome and applies corrections to CRISPR libraries using existing exome annotations. We applied Exorcise to re-annotate guides in pooled CRISPR libraries available on Addgene and found that libraries designed on a more permissive reference sequence had more mis-annotations. In simulated CRISPR screens, we modelled common mis-annotations and found that they adversely affect discovery of hits in the intermediate range. We then confirmed this by applying Exorcise on datasets from Dependency Map (DepMap) and the DNA Damage Response CRISPR Screen Viewer (DDRcs), where we found improved discovery power upon Exorcise while retaining the strongest hits. Conclusions Pooled CRISPR libraries map guide sequences to genes and these mappings might not be ready to use due to permissive library design or investigating a variant cell line. By re-annotating CRISPR guides, Exorcise focuses CRISPR experiments towards the genome of the cell line under investigation. Exorcise can be applied at the library design stage or the analysis stage and allows post hoc re-analysis of completed screens. It is available under a Creative Commons Zero v1.0 Universal licence at https://github.com/SimonLammmm/exorcise .
Indolent nodal T follicular helper cell lymphomas—A case series
Authors: Jie Wang, Chun En Yau, Chen Ee Low, Mohamed Haniffa Bin Hasan Mohamed, Chee Leong Cheng, Jadee L. Neff, Jing Quan Lim, Soon Thye Lim, Jason Yongsheng Chan, Choon Kiat Ong, Valerie Shiwen Yang
Journal: Blood Cancer Journal (2024)