tbuckley/cabot-search huggingface dataset:
What rheumatologists need to know about mRNA vaccines: current status and future of mRNA vaccines in autoimmune inflammatory rheumatic diseases
Authors: Jin Kyun Park, Eun Bong Lee, Kevin L Winthrop
Journal: Annals of the Rheumatic Diseases (2024)

Messenger RNA (mRNA) vaccines as a novel vaccine platform offer new tools to effectively combat both emerging and existing pathogens which were previously not possible. The 'plug and play' feature of mRNA vaccines enables swift design and production of vaccines targeting complex antigens and rapid incorporation of new vaccine constituents as needed. This feature makes them likely to be adopted for widespread clinical use in the future.Currently approved mRNA vaccines include only those against SARS-CoV-2 virus. These vaccines demonstrate robust immunogenicity and offer substantial protection against severe disease. Numerous mRNA vaccines against viral pathogens are in the early to late phase of development. Several mRNA vaccines for influenza are tested in clinical trials, with some already in phase 3 studies. Other vaccines in the early and late phases of development include those targeting
Stem cell-derived CAR T cells show greater persistence, trafficking, and viral control compared to ex vivo transduced CAR T cells
Authors: Mayra A. Carrillo, Anjie Zhen, Wenli Mu, Valerie Rezek, Heather Martin, Christopher W. Peterson, Hans-Peter Kiem, Scott G. Kitchen
Journal: Molecular Therapy (2024)

Adoptive cell therapy (ACT) using T cells expressing chimeric antigen receptors (CARs) is an area of intense investigation in the treatment of malignancies and chronic viral infections. One of the limitations of ACT-based CAR therapy is the lack of in vivo persistence and maintenance of optimal cell function. Therefore, alternative strategies that increase the function and maintenance of CAR-expressing T cells are needed. In our studies using the humanized bone marrow/liver/thymus (BLT) mouse model and nonhuman primate (NHP) model of HIV infection, we evaluated two CAR-based gene therapy approaches. In the ACT approach, we used cytokine enhancement and preconditioning to generate greater persistence of anti-HIV CAR
Hnrnpk protects against osteoarthritis through targeting WWC1 mRNA and inhibiting Hippo signaling pathway
Authors: Shun Zhang, Baolin Zhang, Zhiheng Liao, Yuyu Chen, Weimin Guo, Jinna Wu, Hengyu Liu, Ricong Weng, Deying Su, Gengjia Chen, Zhenzhen Zhang, Chuan Li, Jiahui Long, Ya Xiao, Yuan Ma, Taifeng Zhou, Caixia Xu, Peiqiang Su
Journal: Molecular Therapy (2024)

Osteoarthritis (OA) is an age-related or post-traumatic degenerative whole joint disease characterized by the rupture of articular cartilage homeostasis, the regulatory mechanisms of which remain elusive. This study identifies the essential role of heterogeneous nuclear ribonucleoprotein K (hnRNPK) in maintaining articular cartilage homeostasis. Hnrnpk expression is markedly downregulated in human and mice OA cartilage. The deletion of Hnrnpk effectively accelerates the development of post-traumatic and age-dependent OA in mice. Mechanistically, the KH1 and KH2 domain of Hnrnpk bind and degrade the mRNA of WWC1. Hnrnpk deletion increases WWC1 expression, which in turn leads to the activation of Hippo signaling and ultimately aggravates OA. In particular, intra-articular injection of LPA and adeno-associated virus serotype 5 expressing WWC1 RNA interference ameliorates cartilage degeneration induced by Hnrnpk deletion, and intra-articular injection of adeno-associated virus serotype 5 expressing Hnrnpk protects against OA. Collectively, this study reveals the critical roles of Hnrnpk in inhibiting OA development through WWC1-dependent downregulation of Hippo signaling in chondrocytes and defines a potential target for the prevention and treatment of OA.
Gene and Allele-Specific Expression Underlying the Electric Signal Divergence in African Weakly Electric Fish
Authors: Feng Cheng, Alice B Dennis, Otto Baumann, Frank Kirschbaum, Salim Abdelilah-Seyfried, Ralph Tiedemann
Journal: Molecular Biology and Evolution (2024)

Abstract In the African weakly electric fish genus Campylomormyrus, electric organ discharge signals are strikingly different in shape and duration among closely related species, contribute to prezygotic isolation, and may have triggered an adaptive radiation. We performed mRNA sequencing on electric organs and skeletal muscles (from which the electric organs derive) from 3 species with short (0.4 ms), medium (5 ms), and long (40 ms) electric organ discharges and 2 different cross-species hybrids. We identified 1,444 upregulated genes in electric organ shared by all 5 species/hybrid cohorts, rendering them candidate genes for electric organ–specific properties in Campylomormyrus. We further identified several candidate genes, including KCNJ2 and KLF5, and their upregulation may contribute to increased electric organ discharge duration. Hybrids between a short (Campylomormyrus compressirostris) and a long (Campylomormyrus rhynchophorus) discharging species exhibit electric organ discharges of intermediate duration and showed imbalanced expression of KCNJ2 alleles, pointing toward a cis-regulatory difference at this locus, relative to electric organ discharge duration. KLF5 is a transcription factor potentially balancing potassium channel gene expression, a crucial process for the formation of an electric organ discharge. Unraveling the genetic basis of the species-specific modulation of the electric organ discharge in Campylomormyrus is crucial for understanding the adaptive radiation of this emerging model taxon of ecological (perhaps even sympatric) speciation.
Lactate modulates RNA splicing to promote CTLA-4 expression in tumor-infiltrating regulatory T cells
Authors: Rui Ding, Xiaoyan Yu, Zhilin Hu, Yu Dong, Haiyan Huang, Yuerong Zhang, Qiaoqiao Han, Zhi-Yu Ni, Ren Zhao, Youqiong Ye, Qiang Zou
Journal: Immunity (2024)
Ancient genomes illuminate Eastern Arabian population history and adaptation against malaria
Authors: Rui Martiniano, Marc Haber, Mohamed A. Almarri, Valeria Mattiangeli, Mirte C.M. Kuijpers, Berenice Chamel, Emily M. Breslin, Judith Littleton, Salman Almahari, Fatima Aloraifi, Daniel G. Bradley, Pierre Lombard, Richard Durbin
Journal: Cell Genomics (2024)

The harsh climate of Arabia has posed challenges in generating ancient DNA from the region, hindering the direct examination of ancient genomes for understanding the demographic processes that shaped Arabian populations. In this study, we report whole-genome sequence data obtained from four Tylos-period individuals from Bahrain. Their genetic ancestry can be modeled as a mixture of sources from ancient Anatolia, Levant, and Iran/Caucasus, with variation between individuals suggesting population heterogeneity in Bahrain before the onset of Islam. We identify the G6PD Mediterranean mutation associated with malaria resistance in three out of four ancient Bahraini samples and estimate that it rose in frequency in Eastern Arabia from 5 to 6 kya onward, around the time agriculture appeared in the region. Our study characterizes the genetic composition of ancient Arabians, shedding light on the population history of Bahrain and demonstrating the feasibility of studies of ancient DNA in the region.
Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial
Authors: James Larkin, Richard Marais, Nuria Porta, David Gonzalez de Castro, Lisa Parsons, Christina Messiou, Gordon Stamp, Lisa Thompson, Kim Edmonds, Sarah Sarker, Jane Banerji, Paul Lorigan, Thomas R. Jeffry Evans, Pippa Corrie, Ernest Marshall, Mark R. Middleton, Paul Nathan, Steve Nicholson, Christian Ottensmeier, Ruth Plummer, Judith Bliss, Sara Valpione, Samra Turajlic
Journal: Cell Reports Medicine (2024)

Mucosal (MM) and acral melanomas (AM) are rare melanoma subtypes of unmet clinical need; 15%-20% harbor KIT mutations potentially targeted by small-molecule inhibitors, but none yet approved in melanoma. This multicenter, single-arm Phase II trial (NICAM) investigates nilotinib safety and activity in KIT mutated metastatic MM and AM. KIT mutations are identified in 39/219 screened patients (18%); of 29/39 treated, 26 are evaluable for primary analysis. Six patients were alive and progression free at 6 months (local radiology review, 25%); 5/26 (19%) had objective response at 12 weeks; median OS was 7.7 months; ddPCR assay correctly identifies KIT alterations in circulating tumor DNA (ctDNA) in 16/17 patients. Nilotinib is active in KIT-mutant AM and MM, comparable to other KIT inhibitors, with demonstrable activity in nonhotspot KIT mutations, supporting broadening of KIT evaluation in AM and MM. Our results endorse further investigations of nilotinib for the treatment of KIT-mutated melanoma. This clinical trial was registered with ISRCTN (ISRCTN39058880) and EudraCT (2009-012945-49).
Single-nucleus RNA sequencing demonstrates an autosomal dominant Alzheimer’s disease profile and possible mechanisms of disease protection
Authors: Maria Camila Almeida, Sarah J. Eger, Caroline He, Morgane Audouard, Arina Nikitina, Stella M.K. Glasauer, Dasol Han, Barbara Mejía-Cupajita, Juliana Acosta-Uribe, Nelson David Villalba-Moreno, Jessica Lisa Littau, Megan Elcheikhali, Erica Keane Rivera, Daniel Carneiro Carrettiero, Carlos Andrés Villegas-Lanau, Diego Sepulveda-Falla, Francisco Lopera, Kenneth S. Kosik
Journal: Neuron (2024)
A conserved antigen induces respiratory Th17-mediated broad serotype protection against pneumococcal superinfection
Authors: Xue Liu, Laurye Van Maele, Laura Matarazzo, Daphnée Soulard, Vinicius Alves Duarte da Silva, Vincent de Bakker, Julien Dénéréaz, Florian P. Bock, Michael Taschner, Jinzhao Ou, Stephan Gruber, Victor Nizet, Jean-Claude Sirard, Jan-Willem Veening
Journal: Cell Host & Microbe (2024)

Several vaccines targeting bacterial pathogens show reduced efficacy upon concurrent viral infection, indicating that a new vaccinology approach is required. To identify antigens for the human pathogen Streptococcus pneumoniae that are effective following influenza infection, we performed CRISPRi-seq in a murine model of superinfection and identified the conserved lafB gene as crucial for virulence. We show that LafB is a membrane-associated, intracellular protein that catalyzes the formation of galactosyl-glucosyl-diacylglycerol, a glycolipid important for cell wall homeostasis. Respiratory vaccination with recombinant LafB, in contrast to subcutaneous vaccination, was highly protective against S. pneumoniae serotypes 2, 15A, and 24F in a murine model. In contrast to standard capsule-based vaccines, protection did not require LafB-specific antibodies but was dependent on airway CD4+ T helper 17 cells. Healthy human individuals can elicit LafB-specific immune responses, indicating LafB antigenicity in humans. Collectively, these findings present a universal pneumococcal vaccine antigen that remains effective following influenza infection.
Inhibition of transcriptional coactivator YAP Impairs the expression and function of transcription factor WT1 in diabetic podocyte injury
Authors: Jianchun Chen, Xiaoyong Wang, Qian He, Hai-Chun Yang, Agnes B. Fogo, Raymond C. Harris
Journal: Kidney International (2024)

Podocyte injury and loss are hallmarks of diabetic nephropathy (DN). However, the molecular mechanisms underlying these phenomena remain poorly understood. YAP (Yes-associated protein) is an important transcriptional coactivator that binds with various other transcription factors, including the TEAD family members (nuclear effectors of the Hippo pathway), that regulate cell proliferation, differentiation, and apoptosis. The present study found an increase in YAP phosphorylation at S127 of YAP and a reduction of nuclear YAP localization in podocytes of diabetic mouse and human kidneys, suggesting dysregulation of YAP may play a role in diabetic podocyte injury. Tamoxifen-inducible podocyte-specific Yap gene knockout mice (Yap
Targeting WIP1 phosphatase promotes partial remission in experimental collapsing glomerulopathy
Authors: Lou C. Duret, Tynhinane Hamidouche, Nicholas J. Steers, Catherine Pons, Nicolas Soubeiran, Delphine Buret, Eric Gilson, Ali G. Gharavi, Vivette D. D’Agati, Marina Shkreli
Journal: Kidney International (2024)

Collapsing focal segmental glomerulosclerosis (FSGS), also known as collapsing glomerulopathy (CG), is the most aggressive variant of FSGS and is characterized by a rapid progression to kidney failure. Understanding CG pathogenesis represents a key step for the development of targeted therapies. Previous work implicated the telomerase protein component TERT in CG pathogenesis, as transgenic TERT expression in adult mice resulted in a CG resembling that seen in human primary CG and HIV-associated nephropathy (HIVAN). Here, we used the telomerase-induced mouse model of CG (i-TERTci mice) to identify mechanisms to inhibit CG pathogenesis. Inactivation of WIP1 phosphatase, a p53 target acting in a negative feedback loop, blocked disease initiation in i-TERTci mice. Repression of disease initiation upon WIP1 deficiency was associated with senescence enhancement and required transforming growth factor-β functions. The efficacy of a pharmacologic treatment to reduce disease severity in both i-TERTci mice and in a mouse model of HIVAN (Tg26 mice) was then assessed. Pharmacologic inhibition of WIP1 enzymatic activity in either the telomerase mice with CG or in the Tg26 mice promoted partial remission of proteinuria and ameliorated kidney histopathologic features. Histological as well as high-throughput sequencing methods further showed that selective inhibition of WIP1 does not promote kidney fibrosis or inflammation. Thus, our findings suggest that targeting WIP1 may be an effective therapeutic strategy for patients with CG.
Cardiovascular Eligibility Criteria and Adverse Event Reporting in Combined Immune Checkpoint and VEGF Inhibitor Trials
Authors: Stephen Rankin, Benjamin Elyan, Robert Jones, Balaji Venugopal, Patrick B. Mark, Jennifer S. Lees, Mark C. Petrie, Ninian N. Lang
Journal: JACC CardioOncology (2024)

Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors (VEGFIs) has improved cancer outcomes and is increasingly used. These drug classes are associated with cardiovascular toxicities when used alone, but heterogeneity in trial design and reporting may limit knowledge of toxicities in patients receiving these in combination.
Assessment of suicidality in trials of psychological interventions for depression: a meta-analysis
Authors: Clara Miguel, Jessica Cecconi, Mathias Harrer, Wouter van Ballegooijen, Shalini Bhattacharya, Eirini Karyotaki, Pim Cuijpers, Claudio Gentili, Ioana A Cristea
Journal: The Lancet Psychiatry (2024)
Gender composition and geographical representation of American Society of Hematology clinical practice guideline authors
Authors: Jeremy W Jacobs, Amarilis A Martin, Laura D Stephens, Brian D Adkins, Jennifer S Woo, Deva Sharma, Allison P Wheeler, Raeshun T Glover, Jennifer C Yui, Shannon C Walker, Shazia S Khan, Garrett S Booth, Julie K Silver
Journal: The Lancet Haematology (2024)
Health-related quality of life in patients with triple-class exposed relapsed and refractory multiple myeloma treated with idecabtagene vicleucel or standard regimens: patient-reported outcomes from the phase 3, randomised, open-label KarMMa-3 clinical trial
Authors: Michel Delforge, Krina Patel, Laurie Eliason, Devender Dhanda, Ling Shi, Shien Guo, Thomas S Marshall, Bertrand Arnulf, Michele Cavo, Ajay Nooka, Salomon Manier, Natalie Callander, Sergio Giralt, Hermann Einsele, Sikander Ailawadhi, Mihaela Popa McKiver, Mark Cook, Paula Rodríguez-Otero
Journal: The Lancet Haematology (2024)
Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation
Authors: Vipawee S. Chat, Christoph T. Ellebrecht, Paige Kingston, George Gondo, Stacie Bell, Kelly M. Cordoro, Seemal R. Desai, Kristina C. Duffin, Steven R. Feldman, Amit Garg, Joel M. Gelfand, Dafna Gladman, Lawrence J. Green, Johann Gudjonsson, George Han, Jason E. Hawkes, Leon Kircik, John Koo, Richard Langley, Mark Lebwohl, G. Michael Lewitt, Wilson Liao, George Martin, Ana-Maria Orbai, Soumya M. Reddy, Veronica Richardson, Christopher T. Ritchlin, Sergio Schwartzman, Evan L. Siegel, Abby S. Van Voorhees, Elizabeth B. Wallace, Jeffrey M. Weinberg, Kevin L. Winthrop, Paul Yamauchi, April W. Armstrong
Journal: Journal of the American Academy of Dermatology (2024)
Quasi‐MOF‐Engineered MnO<i><sub>x</sub></i>/CeBTC Multinanozyme as a Robust Self‐Cascade ROS Generator toward Antibacterial Face Mask
Authors: Yuqi Meng, Ruiting Han, Qing Tian, Yao Chen, Lianbing Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract It is of great importance to endow personal protective equipments with bactericidal property combating against infected pathogens. Nanozyme that can generate reactive oxygen species (ROS) in an enzyme‐catalytic manner is regarded as a novel and promising nanobactericide. But until now, very rare of them is designed specifically for personal protective equipments. In this study, a multinanozyme of manganese oxide supported on Ce‐containing MOF (CeBTC) is constructed with post‐engineering via a quasi‐metal‐organic framework (MOF) strategy (denoted as MnO x /q‐CeBTC). The strategy enables a full exposure of the metal cluster nodes, introduction of new active Mn─O─Ce bonds and strengthens interaction between the metal nodes and the guest oxide. As an advanced multinanozyme, the MnO x /q‐CeBTC exhibits excellent multiple enzymatic activities at low temperature, and enables abundant and self‐cascade ROS generation without H 2 O 2 addition. This empowers it with high efficiency in bacteria killing, which is also reflected when incorporated into face mask to combat against pathogen invasion even at low temperature. The results achieved in this work provide guidance for rational design of effective bactericide based on nanozyme and broaden their application in personal protective equipment and other fields.
Innovations for colonic endoscopic submucosal dissection: combination of the latest game changers
Authors: Mathieu Pioche, Louis Jean Masgnaux, Romain Legros, Timothée Wallenhorst, Jérémie Albouys, Jérôme Rivory, Jeremie Jacques
Journal: Endoscopy (2024)

Endoscopic submucosal dissection (ESD) in 2023 is nothing like it was originally in 2001, with major changes in equipment and strategies. However, the spread of ESD has been slow because it is a challenging procedure, and major new developments are expected to simplify it further.
Simple versus Radical Hysterectomy in Women with Low-Risk Cervical Cancer
Authors: Marie Plante, Janice S Kwon, Sarah Ferguson, Vanessa Samouëlian, Gwenael Ferron, Amandine Maulard, Cor de Kroon, Willemien Van Driel, John Tidy, Karin Williamson, Sven Mahner, Stefan Kommoss, Frederic Goffin, Karl Tamussino, Brynhildur Eyjólfsdóttir, Jae-Weon Kim, Noreen Gleeson, Lori Brotto, Dongsheng Tu, Lois E Shepherd
Journal: New England Journal of Medicine (2024)

BackgroundRetrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking.MethodsWe conducted a multicenter, randomized, noninferiority trial comparing radical hysterectomy with simple hysterectomy including lymph-node assessment in patients with low-risk cervical cancer (lesions of ≤2 cm with limited stromal invasion). The primary outcome was cancer recurrence in the pelvic area (pelvic recurrence) at 3 years. The prespecified noninferiority margin for the between-group difference in pelvic recurrence at 3 years was 4 percentage points.Download a PDF of the Research Summary.ResultsAmong 700 patients who underwent randomization (350 in each group), the majority had tumors that were stage IB1 according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria (91.7%), that had squamous-cell histologic features (61.7%), and that were grade 1 or 2 (59.3%). With a median follow-up time of 4.5 years, the incidence of pelvic recurrence at 3 years was 2.17% in the radical hysterectomy group and 2.52% in the simple hysterectomy group (an absolute difference of 0.35 percentage points; 90% confidence interval, −1.62 to 2.32). Results were similar in a per-protocol analysis. The incidence of urinary incontinence was lower in the simple hysterectomy group than in the radical hysterectomy group within 4 weeks after surgery (2.4% vs. 5.5%; P=0.048) and beyond 4 weeks (4.7% vs. 11.0%; P=0.003). The incidence of urinary retention in the simple hysterectomy group was also lower than that in the radical hysterectomy group within 4 weeks after surgery (0.6% vs. 11.0%; P<0.001) and beyond 4 weeks (0.6% vs. 9.9%; P<0.001).ConclusionsIn patients with low-risk cervical cancer, simple hysterectomy was not inferior to radical hysterectomy with respect to the 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov number, NCT01658930.) Quick Take Simple Hysterectomy for Low-Risk Cervical Cancer 2m 3s
The End of B/Yamagata Influenza Transmission — Transitioning from Quadrivalent Vaccines
Authors: Arnold S Monto, Maria Zambon, Jerry P Weir
Journal: New England Journal of Medicine (2024)

Since the Yamagata lineage of type B influenza has not circulated since early 2020, experts agree that countries using a quadrivalent influenza vaccine should return to a trivalent one.
Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3
Authors: Ishmael A. Jaiyesimi, Natasha B. Leighl, Nofisat Ismaila, Krishna Alluri, Narjust Florez, Shirish Gadgeel, Gregory Masters, Erin L. Schenk, Bryan J. Schneider, Lecia Sequist, Navneet Singh, Lyudmila Bazhenova, Elizabeth Blanchard, Janet Freeman-Daily, Naoki Furuya, Balazs Halmos, Ibrahim Hanna Azar, Sara Kuruvilla, Michael Mullane, Jarushka Naidoo, Joshua E. Reuss, David R. Spigel, Dwight H. Owen, Jyoti D. Patel
Journal: Journal of Clinical Oncology (2024)

To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer with driver alterations.
The colibactin-producing <i>Escherichia coli</i> alters the tumor microenvironment to immunosuppressive lipid overload facilitating colorectal cancer progression and chemoresistance
Authors: Nilmara de Oliveira Alves, Guillaume Dalmasso, Darja Nikitina, Amaury Vaysse, Richard Ruez, Lea Ledoux, Thierry Pedron, Emma Bergsten, Olivier Boulard, Lora Autier, Sofian Allam, Laurence Motreff, Pierre Sauvanet, Diane Letourneur, Pragya Kashyap, Johan Gagnière, Denis Pezet, Catherine Godfraind, Michel Salzet, Emmanuel Lemichez, Mathilde Bonnet, Imène Najjar, Christophe Malabat, Marc Monot, Denis Mestivier, Nicolas Barnich, Pankaj Yadav, Isabelle Fournier, Sean Kennedy, Amel Mettouchi, Richard Bonnet, Iradj Sobhani, Mathias Chamaillard
Journal: Gut Microbes (2024)

Intratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling technologies and 16SrRNA sequencing, we herein report that right-sided colorectal tumors are predominantly populated with Colibactin-producing