tbuckley/cabot-search huggingface dataset:
Human Papillomavirus Vaccination by Birth Fiscal Year in Japan
Authors: Asami Yagi, Yutaka Ueda, Emiko Oka, Satoshi Nakagawa, Tadashi Kimura
Journal: JAMA Network Open (2024)

Importance The Ministry of Health, Labour, and Welfare (MHLW) of Japan aggregates human papillomavirus (HPV) vaccination data across Japan for each fiscal year (FY) by age at vaccination. Birth FY (BFY)–specific vaccination coverage remains unknown. Objective To calculate the BFY-specific vaccination coverage for each FY and the cumulative first-dose coverage for each BFY in Japan, to understand the generation-specific vaccination coverage, and to estimate the cumulative first-dose coverage of each BFY that would be achieved by FY 2028 vs World Health Organization (WHO) targets. Design, Setting, and Participants In this cross-sectional study, MHLW-published national age-specific HPV vaccination numbers and demographic data for female individuals were used to calculate the BFY-specific first-dose coverage for each FY and the BFY-specific cumulative first-dose coverage. It was assumed that the BFYs 2007 to 2012 vaccination coverage in FY 2023 to 2028 would remain the same as the vaccination coverage of the same grade in FY 2022 to estimate the cumulative first-dose coverage that would be achieved by FY 2028. Data analysis was performed from December 2023 to January 2024. Exposure Two MHLW policy changes were the government’s suspension of proactive recommendation for HPV vaccination in June 2013 and the government’s resumption of proactive recommendation for HPV vaccination in April 2022. Main Outcomes and Measures The primary outcome was generation-specific vaccination coverage among female individuals born in BFYs 1994 to 2010 in FYs 2010 to 2022, calculated using reconfigured published data. Results In this study of vaccination data for 9 414 620 female individuals, the generation-specific vaccination coverage was 71.96% for the vaccination generation (BFYs 1994-1999), 4.62% for the vaccine-suspension generation (BFYs 2000-2003), 16.16% for the generation that received information individually (BFYs 2004-2009), and 2.83% for the vaccine-resumed generation (BFY 2010). HPV routine vaccination coverage was extremely low in BFYs 2000 to 2010 (0.84%-25.21%) vs BFYs 1994 to 1999 (53.31%-79.47%). The cumulative first-dose coverage that was estimated to be achieved in the vaccine-resumed generation by FY 2028 plateaued at 43.16%. Conclusions and Relevance Even after the resumption of MHLW’s proactive recommendations, HPV vaccination coverage has only minimally recovered in Japan. The cumulative first-dose coverage that was estimated to be achieved in the vaccine-resumed generation by FY 2028 is below the WHO target. These findings reveal that stronger cervical cancer control measures are required, particularly for the vaccine-resumed generation, which will plateau at approximately one-half the WHO target values.
DRD2 activation inhibits choroidal neovascularization in patients with Parkinson’s disease and age-related macular degeneration
Authors: Thibaud Mathis, Florian Baudin, Anne-Sophie Mariet, Sébastien Augustin, Marion Bricout, Lauriane Przegralek, Christophe Roubeix, Éric Benzenine, Guillaume Blot, Caroline Nous, Laurent Kodjikian, Martine Mauget-Faÿsse, José-Alain Sahel, Robin Plevin, Christina Zeitz, Cécile Delarasse, Xavier Guillonneau, Catherine Creuzot-Garcher, Catherine Quantin, Stéphane Hunot, Florian Sennlaub
Journal: Journal of Clinical Investigation (2024)

niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies
Authors: Lloyd D.W. King, David Pulido, Jordan R. Barrett, Hannah Davies, Doris Quinkert, Amelia M. Lias, Sarah E. Silk, David J. Pattinson, Ababacar Diouf, Barnabas G. Williams, Kirsty McHugh, Ana Rodrigues, Cassandra A. Rigby, Veronica Strazza, Jonathan Suurbaar, Chloe Rees-Spear, Rebecca A. Dabbs, Andrew S. Ishizuka, Yu Zhou, Gaurav Gupta, Jing Jin, Yuanyuan Li, Cecilia Carnrot, Angela M. Minassian, Ivan Campeotto, Sarel J. Fleishman, Amy R. Noe, Randall S. MacGill, C. Richter King, Ashley J. Birkett, Lorraine A. Soisson, Carole A. Long, Kazutoyo Miura, Rebecca Ashfield, Katherine Skinner, Mark R. Howarth, Sumi Biswas, Simon J. Draper
Journal: Cell Reports Medicine (2024)

Highlights•Inhibitory antibodies from RH5.1/AS01B vaccinees target the RH5 α-helical core•A truncated and thermostabilized RH5.2 immunogen induces more potent antibodies•Bioconjugation of RH5.2 to VLPs enhances antibody immunogenicity in rodents•RH5.2-VLP/Matrix-M induces highest functional antimalarial antibodies in ratsSummaryPlasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed "RH5.2," to hepatitis B surface antigen virus-like particles (VLPs) using the "plug-and-display" SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials.Graphical abstract
Neddylation inhibition prevents acetaminophen-induced liver damage by enhancing the anabolic cardiolipin pathway
Authors: Clàudia Gil-Pitarch, Marina Serrano-Maciá, Jorge Simon, Laura Mosca, Carolina Conter, Claudia M. Rejano-Gordillo, L. Estefanía Zapata-Pavas, Patricia Peña-Sanfélix, Mikel Azkargorta, Rubén Rodríguez-Agudo, Sofía Lachiondo-Ortega, Maria Mercado-Gómez, Teresa C. Delgado, Marina Porcelli, Igor Aurrekoetxea, James D. Sutherland, Rosa Barrio, Dimitris Xirodimas, Patricia Aspichueta, Felix Elortza, Luis Alfonso Martínez-Cruz, Rubén Nogueiras, Paula Iruzubieta, Javier Crespo, Steven Masson, Misti Vanette McCain, Helen L. Reeves, Raul J. Andrade, M. Isabel Lucena, Ugo Mayor, Naroa Goikoetxea-Usandizaga, Irene González-Recio, María L. Martínez-Chantar
Journal: Cell Reports Medicine (2024)
Urinary Retention Evaluation and Catheterization Algorithm for Adult Inpatients
Authors: Kristin Chrouser, Karen E. Fowler, Jason D. Mann, Martha Quinn, Jessica Ameling, Samantha Hendren, Greta Krapohl, Ted A. Skolarus, Steven J. Bernstein, Jennifer Meddings
Journal: JAMA Network Open (2024)

Importance Acute urinary retention (UR) is common, yet variations in diagnosis and management can lead to inappropriate catheterization and harm. Objective To develop an algorithm for screening and management of UR among adult inpatients. Design, Setting, and Participants In this mixed-methods study using the RAND/UCLA Appropriateness Method and qualitative interviews, an 11-member multidisciplinary expert panel of nurses and physicians from across the US used a formal multi-round process from March to May 2015 to rate 107 clinical scenarios involving diagnosis and management of adult UR in postoperative and medical inpatients. The panel ratings informed the first algorithm draft. Semistructured interviews were conducted from October 2020 to May 2021 with 33 frontline clinicians—nurses and surgeons from 5 Michigan hospitals—to gather feedback and inform algorithm refinements. Main Outcomes and Measures Panelists categorized scenarios assessing when to use bladder scanners, catheterization at various scanned bladder volumes, and choice of catheterization modalities as appropriate, inappropriate, or uncertain. Next, qualitative methods were used to understand the perceived need, usability, and potential algorithm uses. Results The 11-member expert panel (10 men and 1 woman) used the RAND/UCLA Appropriateness Method to develop a UR algorithm including the following: (1) bladder scanners were preferred over catheterization for UR diagnosis in symptomatic patients or starting as soon as 3 hours since last void if asymptomatic, (2) bladder scanner volumes appropriate to prompt catheterization were 300 mL or greater in symptomatic patients and 500 mL or greater in asymptomatic patients, and (3) intermittent was preferred to indwelling catheterization for managing lower bladder volumes. Interview findings were organized into 3 domains (perceived need, feedback on algorithm, and implementation suggestions). The 33 frontline clinicians (9 men and 24 women) who reviewed the algorithm reported that an evidence-based protocol (1) was needed and could be helpful to clinicians, (2) should be simple and graphically appealing to improve rapid clinician review, and (3) should be integrated within the electronic medical record and prominently displayed in hospital units to increase awareness. The draft algorithm was iteratively refined based on stakeholder feedback. Conclusions and Relevance In this study using a systematic, multidisciplinary, evidence- and expert opinion–based approach, a UR evaluation and catheterization algorithm was developed to improve patient safety by increasing appropriate use of bladder scanners and catheterization. This algorithm addresses the need for practical guidance to manage UR among adult inpatients.
Rare variation in non-coding regions with evolutionary signatures contributes to autism spectrum disorder risk
Authors: Taehwan Shin, Janet H.T. Song, Michael Kosicki, Connor Kenny, Samantha G. Beck, Lily Kelley, Irene Antony, Xuyu Qian, Julieta Bonacina, Frances Papandile, Dilenny Gonzalez, Julia Scotellaro, Evan M. Bushinsky, Rebecca E. Andersen, Eduardo Maury, Len A. Pennacchio, Ryan N. Doan, Christopher A. Walsh
Journal: Cell Genomics (2024)

Little is known about the role of non-coding regions in the etiology of autism spectrum disorder (ASD). We examined three classes of non-coding regions: human accelerated regions (HARs), which show signatures of positive selection in humans; experimentally validated neural VISTA enhancers (VEs); and conserved regions predicted to act as neural enhancers (CNEs). Targeted and whole-genome analysis of >16,600 samples and >4,900 ASD probands revealed that likely recessive, rare, inherited variants in HARs, VEs, and CNEs substantially contribute to ASD risk in probands whose parents share ancestry, which enriches for recessive contributions, but modestly contribute, if at all, in simplex family structures. We identified multiple patient variants in HARs near IL1RAPL1 and in VEs near OTX1 and SIM1 and showed that they change enhancer activity. Our results implicate both human-evolved and evolutionarily conserved non-coding regions in ASD risk and suggest potential mechanisms of how regulatory changes can modulate social behavior.
Increased regional activity of a pro-autophagy pathway in schizophrenia as a contributor to sex differences in the disease pathology
Authors: Kathryn J. Bjornson, Amanda M. Vanderplow, Aishwarya I. Bhasker, Michael E. Cahill
Journal: Cell Reports Medicine (2024)

Based on recent genome-wide association studies, it is theorized that altered regulation of autophagy contributes to the pathophysiology of schizophrenia and bipolar disorder. As activity of autophagy-regulatory pathways is controlled by discrete phosphorylation sites on the relevant proteins, phospho-protein profiling is one of the few approaches available for enabling a quantitative assessment of autophagic activity in the brain. Despite this, a comprehensive phospho-protein assessment in the brains of schizophrenia and bipolar disorder subjects is currently lacking. Using this direction, our broad screening identifies an increase in AMP-activated protein kinase (AMPK)-mediated phospho-activation of the pro-autophagy protein beclin-1 solely in the prefrontal cortex of female, but not male, schizophrenia subjects. Using a reverse translational approach, we surprisingly find that this increase in beclin-1 activity facilitates synapse formation and enhances cognition. These findings are interpreted in the context of human studies demonstrating that female schizophrenia subjects have a lower susceptibility to cognitive dysfunction than males.
Development of a hydrogen peroxide-inactivated vaccine that protects against viscerotropic yellow fever in a non-human primate model
Authors: Ian J. Amanna, Archana Thomas, Flora Engelmann, Erika Hammarlund, Hans-Peter Raué, Adam L. Bailey, Elizabeth A. Poore, Benjamin K. Quintel, Anne D. Lewis, Michael K. Axthelm, Amanda L. Johnson, Lois M.A. Colgin, Michael S. Diamond, Ilhem Messaoudi, Mark K. Slifka
Journal: Cell Reports Medicine (2024)

Yellow fever virus (YFV) is endemic in >40 countries and causes viscerotropic disease with up to 20%–60% mortality. Successful live-attenuated yellow fever (YF) vaccines were developed in the mid-1930s, but their use is restricted or formally contraindicated in vulnerable populations including infants, the elderly, and people with compromised immune systems. In these studies, we describe the development of a next-generation hydrogen peroxide-inactivated YF vaccine and determine immune correlates of protection based on log neutralizing index (LNI) and neutralizing titer-50% (NT50) studies. In addition, we compare neutralizing antibody responses and protective efficacy of hydrogen peroxide-inactivated YF vaccine candidates to live-attenuated YFV-17D (YF-VAX) in a rhesus macaque model of viscerotropic YF. Our results indicate that an optimized, inactivated YF vaccine elicits protective antibody responses that prevent viral dissemination and lethal infection in rhesus macaques and may be a suitable alternative for vaccinating vulnerable populations who are not eligible to receive replicating live-attenuated YF vaccines.
Metformin synergizes with gilteritinib in treating FLT3-mutated leukemia via targeting PLK1 signaling
Authors: Meiling Chen, Chao Shen, Yi Chen, Zhenhua Chen, Keren Zhou, Yuanzhong Chen, Wei Li, Chengwu Zeng, Ying Qing, Dong Wu, Caiming Xu, Tingting Tang, Yuan Che, Xi Qin, Zhaoxu Xu, Kitty Wang, Keith Leung, Lillian Sau, Xiaolan Deng, Jianda Hu, Yong Wu, Jianjun Chen
Journal: Cell Reports Medicine (2024)

Highlights•Metformin substantially sensitizes FLT3-mutated AML cells to gilteritinib in vitro•Metformin synergizes with gilteritinib in treating FLT3-ITD AML in vivo•Metformin and gilteritinib cooperatively target PLK1/STAT5-ERK-mTOR in FLT3-ITD AML•Metformin plus TKI offers a potent and cost-effective therapy for FLT3-ITD AMLSummaryFms-like tyrosine kinase 3 (FLT3) mutations, present in over 30% of acute myeloid leukemia (AML) cases and dominated by FLT3-internal tandem duplication (FLT3-ITD), are associated with poor outcomes in patients with AML. While tyrosine kinase inhibitors (TKIs; e.g., gilteritinib) are effective, they face challenges such as drug resistance, relapse, and high costs. Here, we report that metformin, a cheap, safe, and widely used anti-diabetic agent, exhibits a striking synergistic effect with gilteritinib in treating FLT3-ITD AML. Metformin significantly sensitizes FLT3-ITD AML cells (including TKI-resistant ones) to gilteritinib. Metformin plus gilteritinib (low dose) dramatically suppresses leukemia progression and prolongs survival in FLT3-ITD AML mouse models. Mechanistically, the combinational treatment cooperatively suppresses polo-like kinase 1 (PLK1) expression and phosphorylation of FLT3/STAT5/ERK/mTOR. Clinical analysis also shows improved survival rates in patients with FLT3-ITD AML taking metformin. Thus, the metformin/gilteritinib combination represents a promising and cost-effective treatment for patients with FLT3-mutated AML, particularly for those with low income/affordability.Graphical abstract
Mature enteric neurons have the capacity to reinnervate the intestine with glial cells as their guide
Authors: Rhian Stavely, Ahmed A Rahman, Jessica L Mueller, Abigail R Leavitt, Christopher Y Han, Weikang Pan, Kyla N Kaiser, Leah C Ott, Takahiro Ohkura, Richard A Guyer, Alan J Burns, Abigail N Koppes, Ryo Hotta, Allan M Goldstein
Journal: Neuron (2024)
Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus
Authors: Francesca Bertino, Dibyanti Mukherjee, Massimo Bonora, Christoph Bagowski, Jeannette Nardelli, Livia Metani, Diletta Isabella Zanin Venturini, Diego Chianese, Nicolas Santander, Iris Chiara Salaroglio, Andreas Hentschel, Elisa Quarta, Tullio Genova, Arpana Arjun McKinney, Anna Lucia Allocco, Veronica Fiorito, Sara Petrillo, Giorgia Ammirata, Francesco De Giorgio, Evan Dennis, Garrett Allington, Felicitas Maier, Moneef Shoukier, Karl-Philipp Gloning, Luca Munaron, Federico Mussano, Ettore Salsano, Davide Pareyson, Maja di Rocco, Fiorella Altruda, Georgia Panagiotakos, Kristopher T. Kahle, Pierre Gressens, Chiara Riganti, Paolo P. Pinton, Andreas Roos, Thomas Arnold, Emanuela Tolosano, Deborah Chiabrando
Journal: Cell Reports Medicine (2024)

Congenital hydrocephalus (CH), occurring in approximately 1/1,000 live births, represents an important clinical challenge due to the limited knowledge of underlying molecular mechanisms. The discovery of novel CH genes is thus essential to shed light on the intricate processes responsible for ventricular dilatation in CH. Here, we identify FLVCR1 (feline leukemia virus subgroup C receptor 1) as a gene responsible for a severe form of CH in humans and mice. Mechanistically, our data reveal that the full-length isoform encoded by the FLVCR1 gene, FLVCR1a, interacts with the IP3R3-VDAC complex located on mitochondria-associated membranes (MAMs) that controls mitochondrial calcium handling. Loss of Flvcr1a in mouse neural progenitor cells (NPCs) affects mitochondrial calcium levels and energy metabolism, leading to defective cortical neurogenesis and brain ventricle enlargement. These data point to defective NPCs calcium handling and metabolic activity as one of the pathogenetic mechanisms driving CH.
PARP11 inhibition inactivates tumor-infiltrating regulatory T cells and improves the efficacy of immunotherapies
Authors: Raghavendra Basavaraja, Hongru Zhang, Ágnes Holczbauer, Zhen Lu, Enrico Radaelli, Charles-Antoine Assenmacher, Subin S. George, Vamshidhar C. Nallamala, Daniel P. Beiting, Mirella L. Meyer-Ficca, Ralph G. Meyer, Wei Guo, Yi Fan, Andrew J. Modzelewski, Vladimir S. Spiegelman, Michael S. Cohen, Serge Y. Fuchs
Journal: Cell Reports Medicine (2024)

Tumor-infiltrating regulatory T cells (TI-Tregs) elicit immunosuppressive effects in the tumor microenvironment (TME) leading to accelerated tumor growth and resistance to immunotherapies against solid tumors. Here, we demonstrate that poly-(ADP-ribose)-polymerase-11 (PARP11) is an essential regulator of immunosuppressive activities of TI-Tregs. Expression of PARP11 correlates with TI-Treg cell numbers and poor responses to immune checkpoint blockade (ICB) in human patients with cancer. Tumor-derived factors including adenosine and prostaglandin E2 induce PARP11 in TI-Tregs. Knockout of PARP11 in the cells of the TME or treatment of tumor-bearing mice with selective PARP11 inhibitor ITK7 inactivates TI-Tregs and reinvigorates anti-tumor immune responses. Accordingly, ITK7 decelerates tumor growth and significantly increases the efficacy of anti-tumor immunotherapies including ICB and adoptive transfer of chimeric antigen receptor (CAR) T cells. These results characterize PARP11 as a key driver of TI-Treg activities and a major regulator of immunosuppressive TME and argue for targeting PARP11 to augment anti-cancer immunotherapies.
Aberrant bowel movement frequencies coincide with increased microbe-derived blood metabolites associated with reduced organ function
Authors: Johannes P. Johnson-Martínez, Christian Diener, Anne E. Levine, Tomasz Wilmanski, David L. Suskind, Alexandra Ralevski, Jennifer Hadlock, Andrew T. Magis, Leroy Hood, Noa Rappaport, Sean M. Gibbons
Journal: Cell Reports Medicine (2024)

Bowel movement frequency (BMF) directly impacts the gut microbiota and is linked to diseases like chronic kidney disease or dementia. In particular, prior work has shown that constipation is associated with an ecosystem-wide switch from fiber fermentation and short-chain fatty acid production to more detrimental protein fermentation and toxin production. Here, we analyze multi-omic data from generally healthy adults to see how BMF affects their molecular phenotypes, in a pre-disease context. Results show differential abundances of gut microbial genera, blood metabolites, and variation in lifestyle factors across BMF categories. These differences relate to inflammation, heart health, liver function, and kidney function. Causal mediation analysis indicates that the association between lower BMF and reduced kidney function is partially mediated by the microbially derived toxin 3-indoxyl sulfate (3-IS). This result, in a generally healthy context, suggests that the accumulation of microbiota-derived toxins associated with abnormal BMF precede organ damage and may be drivers of chronic, aging-related diseases.
Astrocytes modulate brain phosphate homeostasis via polarized distribution of phosphate uptake transporter PiT2 and exporter XPR1
Authors: Xuewen Cheng, Miao Zhao, Lei Chen, Chenwei Huang, Qiwu Xu, Jia Shao, Hong-Tao Wang, Yuxian Zhang, Xuequan Li, Xuan Xu, Xiang-Ping Yao, Kai-Jun Lin, Hui Xue, Han Wang, Qi Chen, Yong-Chuan Zhu, Jia-Wei Zhou, Woo-Ping Ge, Shu-Jia Zhu, Jing-Yu Liu, Wan-Jin Chen, Zhi-Qi Xiong
Journal: Neuron (2024)
A hypothalamic-amygdala circuit underlying sexually dimorphic aggression
Authors: Zhenggang Zhu, Lu Miao, Kaiyuan Li, Qingqing Ma, Lina Pan, Chenjie Shen, Qianqian Ge, Yonglan Du, Luping Yin, Hongbin Yang, Xiaohong Xu, Ling-Hui Zeng, Yijun Liu, Han Xu, Xiao-Ming Li, Li Sun, Yan-Qin Yu, Shumin Duan
Journal: Neuron (2024)
Photothermal Iron‐Based Riboflavin Microneedles for the Treatment of Bacterial Keratitis via Ion Therapy and Immunomodulation
Authors: Jun Zhou, Lisha Zhang, Yaqi Wei, Qiang Wu, Kaibo Mao, Xiaoli Wang, Jinfeng Cai, Xia Li, Yongxiang Jiang
Journal: Advanced Healthcare Materials (2024)

Bacterial biofilm formation protects bacteria from antibiotics and the immune system, excessive inflammation further complicates treatment. Here, iron-based metal-organic framework (MIL-101)-loaded riboflavin nanoparticles are designed for the therapeutic challenge of biofilm infection and hyperinflammation in bacterial keratitis. Specifically, MIL-101 produces a thermal effect under exogenous near-infrared light irradiation, which synergizes with ferroptosis-like bacterial death induced by iron ions to exert an effective biofilm infection eradication effect. On the other hand, the disintegration of MIL-101 sustains the release of riboflavin, which inhibits the pro-inflammatory response of macrophage over-activation by modulating their phenotypic switch. In addition, to solve the problems of short residence time, poor permeability, and low bioavailability of corneal medication, the MR@MN microneedle patch is further prepared by loading nanoparticles into SilMA hydrogel, which ultimately achieves painless, transepithelial, and highly efficient drug delivery. In vivo and ex vivo experiments demonstrate the effectiveness of this approach in eliminating bacterial infection and promoting corneal healing. Therefore, the MRMN patch, acting as an ocular drug delivery system with the ability of rapid corneal healing, promises a cost-effective solution for the treatment of bacterial keratitis, which may also lead to a new approach for treating bacterial keratitis in clinics.