Digital Commons Network^™

Sting Activation Induces Cytotoxic And Immune Responses In Meningiomas Via Inflammatory Cell Death Pathways, Mark W Youngblood, Alexander H Stegh, Et Al.

2020-Current year OA Pubs

Meningiomas are common tumors of the central nervous system that are typically treated with surgery or radiation, but lack established systemic therapies. Activation of the stimulator of interferon genes pathway with an agonist such as 8803 can trigger anti-tumor immune responses. Using integrated molecular approaches, here we show that this pathway is targetable in both neoplastic and immune populations within the meningioma microenvironment. Meningioma tumor cells exhibit promoter hypomethylation and increased chromatin accessibility of the STING genomic locus, associated with robust expression of this gene. Treatment of diverse patient meningiomas ex vivo with 8803 induces direct tumor cytotoxicity through inflammatory …

Trends In The Psychedelic Renaissance: Applying Artificial Intelligence To Measure Media Portrayal Of Psychedelic Drugs In The 21st Century, David A Bender, Harrison M Dunn, Arushi D Mohite, Akila Anandarajah, Jacob Steinle, Suraj Shankar, Brandon Kiley, Sara Martin, Rishi Gonuguntla, Mia Stonov, Nithya Pippala, Rana Abdalla, Madison K Stille, Gibson Werner, Melinda Daniels-Tineo, Hannah Wang, Sonali Sharma, Jatin Sridhar, Adebusola Adeyemi, Kayla Smart, Baris C Ercal, Et Al.

2020-Current year OA Pubs

BACKGROUND: The relationship between media portrayal of psychedelic drugs, scientific research and drug policy is an area of debate.

AIMS: To apply artificial intelligence technology to measure trends in media sentiment towards the therapeutic potential of psychedelic drugs.

METHOD: Up to 300 of the most relevant articles from Google News searches for the term 'psychedelics' were sampled for each year from 2000 to 2025. A large language model, ChatGPT, evaluated subject matter and sentiment.

RESULTS: In total, 88.3% of screened URLs (3308 of 3747) were included in the analysis. The proportion of articles focusing on the therapeutic potential of psychedelics …

Targeting The Lung Innate Pathways During Tuberculosis Can Improve Vaccine-Induced Protection Via Th17 Responses In Diversity Outbred Mice, Mushtaq Ahmed, Shibali Das, Bruce A Rosa, Javier Rangel Moreno, Deepak Kaushal, Makedonka Mitreva, Shabaana A Khader

2020-Current year OA Pubs

UNLABELLED: Tuberculosis (TB), caused by the bacterium

IMPORTANCE: Bacille Calmette Guerin (BCG) vaccination in genetically diverse outbred (DO) mice provides significant protection against

Bioactive Lipid-Mediated Structural And Functional Regulation Of The Essential Human Potassium Channel Kir7.1, Qingwei Niu, Simon Vu, Yuanjian Xu, Mingxing Qian, Anastasiia Rudenko, Jin Ye, Jianwei Zeng, Wei Huang, Douglas F Covey, Rui Zhang, Ziao Fu, Polina V Lishko

2020-Current year OA Pubs

The inwardly rectifying potassium channel Kir7.1 is essential for the physiological function of diverse tissues, including the retinal pigment epithelium and the gestational myometrium. Loss-of-function mutations in KCNJ13, which encodes Kir7.1, or conditional ablation of Kir7.1 in the retinal pigment epithelium, lead to early-onset vision loss. Despite strong genetic evidence supporting Kir7.1 as a therapeutic target, its regulation by endogenous ligands-beyond phosphoinositides-remains poorly understood. Here, we report cryo-electron microscopy structures of human Kir7.1 in multiple functional states at resolutions ranging from 2.8 Å to 4.0 Å. These structures uncover the molecular basis of Kir7.1 modulation by PI

Heme And Hemozoin Induce Platelet Cell Death Through Upr-Induced Apoptosis And Ferroptosis In Vivax Malaria, Milena Tavares Gomes, Robert A Campbell, Et Al.

2020-Current year OA Pubs

Malaria is a highly prevalent infectious disease caused by Plasmodium parasites. Plasmodium intraerythrocytic replication leads to hemolysis-driven intermittent febrile crises in patients. In addition, the lysis of unparasitized red blood cells contributes to anemia and endotoxemia. Because thrombocytopenia is an important feature of vivax and severe falciparum malaria, we hypothesized that increased hemolysis in malaria contributes to severe thrombocytopenia by releasing endogenous and parasite toxins (ie, heme and hemozoin) capable of inducing programmed cell death in platelets. Using complementary biochemical, ultrastructural, pharmacological, and molecular approaches, we examined response to stress and cell death pathways that were elevated in the transcriptome …

Outcomes Following Matched Sibling Donor Transplantation For Severe Combined Immunodeficiency: A Report From The Pidtc, Ahmad Rayes, Jeffrey J Bednarski, Et Al.

2020-Current year OA Pubs

The Primary Immune Deficiency Treatment Consortium performed a retrospective analysis of 133 patients with severe combined immunodeficiency (SCID) receiving matched sibling donor (MSD) hematopoietic cell transplantation (HCT) between 1980 and 2023 at 30 North American institutions. In this largest cohort of MSD outcomes in patients with SCID to date, we examined the impact of conditioning regimen and graft-versus-host disease (GVHD) prophylaxis on survival and immune recovery. Outcomes after MSD HCT for SCID were excellent. Patients without an active infection or failure to thrive (FTT) at the time of HCT had 5-year overall survival superior to those with infection or FTT. …

Derivation And External Validation Of A Venous Thromboembolism Risk Prediction Model In Asparaginase-Treated All, Daniela R Anderson, Kristen Sanfilippo, Et Al.

2020-Current year OA Pubs

The incidence of venous thromboembolism (VTE) in patients with acute lymphoblastic leukemia (ALL) receiving asparaginase-based induction is high despite primary thromboprophylaxis. Our aim was to derive and externally validate a VTE risk prediction model in patients with ALL receiving asparaginase-based induction. We conducted a multicenter retrospective cohort study of patients (aged ≥18 years) with newly diagnosed ALL receiving asparaginase-based induction. The derivation and external validation cohorts included 306 and 94 patients, respectively. Primary outcome was VTE at any site. A cause-specific Cox proportional hazards model stratified by thromboprophylaxis and center was performed to identify VTE risk factors in the derivation …

Smoldering Multiple Myeloma In The United States: A Population-Based Analysis, Shi-Yi Wang, Rong Wang, Martin Schoen, John H Huber, Eric J Feuer, Jennifer Ruhl, Natalia Neparidze, Xiaomei Ma, Amy J Davidoff, Su-Hsin Chang

2020-Current year OA Pubs

No abstract provided.

Decitabine-Cedazuridine In Patients With Mds And Tp53 Mutations, Samuel Urrutia, Koji Sasaki, Alex Bataller, Hagop Kantarjian, Guillermo Montalban-Bravo, James Mccloskey, Elizabeth A Griffiths, Karen Yee, Amer Zeidan, Michael Savona, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

2020-Current year OA Pubs

No abstract provided.

Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither

2020-Current year OA Pubs

Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. …

Phytic Acid (Insp6) Activates Hdac3 Epigenetic Axis To Maintain Intestinal Barrier Function, Sujan Chatterjee, Katherine Huang, Kayci Huff-Hardy, Richard Rood, Anas Gremida, Martin Gregory, Chien-Huan Chen, Parakkal Deepak, Et Al.

2020-Current year OA Pubs

HDAC inhibition shows promise in cancer treatment but pan-HDAC inhibitors cause gastrointestinal issues in 48% of patients. Understanding HDAC activation mechanisms is crucial to treating diverse diseases beyond cancer. Our study reveals that inositol polyphosphate multikinase (IPMK) and inositol hexakisphosphate (InsP

Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither

2020-Current year OA Pubs

Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. …

Therapeutic Reprogramming Of Tumour-Associated Macrophages In Pancreatic Cancer Using A Cytotoxic Ccr2-Targeted Nanotheranostic, Vikas Kumar Somani, Xiaohui Zhang, Timothy Hung-Po Chen, Ashenafi Bulle, Sapana Bansod, Lin Li, Yutong Geng, Liang-I Kang, Gyu Seong Heo, Hannah Luehmann, Yuena Zhang, Muhammad A Saeed, Kory J Lavine, David G Denardo, Russell K Pachynski, Yongjian Liu, Kian-Huat Lim

2020-Current year OA Pubs

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) exhibits a profoundly immunosuppressive tumour microenvironment (TME) dominated by inflammatory monocytes (IMs) and tumour-associated macrophages (TAMs), which restrict adaptive immunity and drive resistance to immune checkpoint blockade (ICB). Recruitment of CCR2⁺ IMs by tumour-derived CCL2 is a central mechanism underlying TAM accumulation. Conventional gemcitabine (GEM) and small-molecule CCR2 inhibitors provide limited benefit due to poor intratumoural delivery, transient target engagement, and compensatory myeloid recruitment. METHODS: We engineered a CCR2-targeted nanotheranostic by conjugating a CCR2-binding peptide (ECL1i) and GEM onto ultrasmall copper nanoclusters (CuNCs-ECL1i-GEM; C-E-G). Therapeutic efficacy and immune remodelling were evaluated using orthotopic subcutaneous and …

Schwannomatosis Tumor Modeling: Progress And Prospects For Translational Research, Mackenzie S Madison, Huazhen Xu, Yarelis Gonzalez-Vargas, Marybeth G Yonk, Charee M Thompson, Hurley Haney, Danielle Babbitt, Yuhong Du, Angela C Hirbe, Nicholas M Boulis, Ren-Yuan Bai, Kecheng Lei

2020-Current year OA Pubs

BACKGROUND: Schwannomatosis (SWN) is a rare genetic condition characterized by the development of benign schwannomas along peripheral and spinal nerves, and this tumor development often results in chronic peripheral pain and significant neurological deficits. Despite surgical resection being the current standard of care for SWN-related pain, scientists are searching for accurate preclinical models that can be used for drug efficacy testing, but existing models often fail to fully recapitulate the complex genotypic diversity and tumor-nerve interface pathology seen in patients. MAIN TEXT: This review first summarizes the genotypic and phenotypic characteristics of SWN subtypes resulting from key mutations in NF2, …

Toward Integrating Clinical And Non-Clinical Associates Of Suicidality To Inform Potential Intervention Points Among Youth In Nairobi Metropolitan, Kenya, David Ndetei, Danuta Wasserman, Victoria Mutiso, Kamaldeep Bhui, Jenelle Shanley, Christine Musyimi, Samantha Winter, Pascalyne Nyamai, Samuel Walusaka, Veronica Onyango, Eric Jeremiah, Tom Lee Osborn, Monica Swahn, Andre Sourander, Daniel Mamah

2020-Current year OA Pubs

Suicide is a significant global public health concern, particularly among adolescents, with substantial implications for economies, societies and individuals' mental well-being. Understanding its patterns and intention and psychosocial determinants in a given context can suggest potential intervention points. This population-based cross-sectional study aimed to document suicidal ideas, behaviors and intensity among youths aged 14 to 25 in the Nairobi metropolitan area and associated socio-economic position, demographic indicators and potential intervention points. A diverse sample of 1,972 participants was recruited from urban and peri-urban settings within the Nairobi metropolitan area. Data analysis included descriptive statistics, chi-square tests and logistic regression. Our …

Leveraging The Translational Science Benefits Model To Plan And Measure Early Impact In The Heart Failure Polypill Implementation Trial In Sri Lanka, Adam Hively, Anna La Manna, Ella Clark, Douglas Luke, Asita De Silva, Mansi Agarwal, Mark D Huffman, Abdul Salam, Anubha Agarwal, Emmanuel K Tetteh

2020-Current year OA Pubs

No abstract provided.

Targeting Tau In Alzheimer's Disease: Rationale, Approach And Challenges, Aram Aslanyan, Martha S Foiani, Tatiana A Giovannucci, Eric Mcdade, Karen E Duff, Catherine J Mummery, Michael Schöll, Kristin R Wildsmith, Ross W Paterson

2020-Current year OA Pubs

Alzheimer’s Disease (AD) is the most common neurodegenerative disorder and the leading cause of dementia characterised by the accumulation of beta amyloid (Aβ) plaques and neurofibrillary tangles (NFT). Several monoclonal antibodies against amyloid in early AD have shown the utility of reducing brain amyloid in large phase 3 studies, resulting in modest clinical benefit. To further slow, or even halt disease progression, targeting additional pathobiological pathways is likely to be necessary. In this review, we aim to appraise the scientific rationale for targeting tau in AD. The burden of tau pathology is correlated with disease severity and its role in …

Sclerostin Deficiency Sensitizes White Adipocytes To Thermogenic Signals That Induce Beiging In Mice, Gillian M Choquette, Soohyun P Kim, Kevin J Wilkinson, Belen C Avelar, Sushrut Pathy, Zhu Li, Jasmine Wu, Susan Aja, Daniel L J Thorek, Michael J Wolfgang, Ryan C Riddle

2020-Current year OA Pubs

Maintenance of bone mass is coordinated with adipose tissue function through the secretion of hormones and endocrine factors that act on the opposing tissue. Sclerostin, a small glycoprotein produced by osteocytes embedded within the bone matrix, potently suppresses bone formation by antagonizing Wnt/β-catenin signaling while stimulating adipose tissue accumulation via the same mechanism of action. Since sclerostin-deficient mice develop pockets of multilocular adipocytes in subcutaneous adipose, we investigate the influence of sclerostin on thermogenic and β3-adrenergic stimuli-induced white adipose tissue beiging. Here, we report that Sost gene expression in bone and serum sclerostin levels are induced by β3-adrenergic agonists via …

Protocol For Personalised Prediction Of Persistent Postsurgical Pain, Katherine J Holzer, Harutyun Alaverdyan, Ziqi Xu, Madelyn R Frumkin, Karen A Frey, Stephen H Gregory, Thomas L Rodebaugh, Chenyang Lu, Christopher R King, Denise Head, Thomas Kannampallil, Simon Haroutounian

2020-Current year OA Pubs

INTRODUCTION: Persistent postsurgical pain (PPSP) affects up to 15% of patients after major surgery, impairing physical function, quality of life and increasing risk for long-term opioid use. Current PPSP prediction models rely on static or retrospective data and fail to incorporate dynamic perioperative factors. The Personalised Prediction of Persistent Postsurgical Pain (P5) study aims to develop individualised, multimodal prediction models by integrating preoperative behavioural, psychophysical and neurocognitive assessments and high-frequency symptom monitoring.

METHODS AND ANALYSIS: P5 is a prospective, single-centre cohort study enrolling 2500 adults aged 18-75 undergoing major surgery at a tertiary academic hospital. Participants complete baseline surveys, cognitive …

Heterogeneity In The Association Of Genetic Risk For Ra And Resultant Ra Phenotypes, Thomas R Riley, Iris Lee, Et Al.

2020-Current year OA Pubs

OBJECTIVES: The impact of the genetic risk for RA on resultant disease phenotype in RA is incompletely understood. Using individual genetic variants associated with RA and a polygenic score (PGS), we hypothesized that those with higher genetic risk for RA would demonstrate a more severe disease course.

METHODS: We genotyped participants from the Veterans Affairs RA registry (VARA), a prospective cohort of RA. We evaluated associations between PTPN22 R620W genotype, HLA-DRB1 shared epitope (SE; 0, 1, or 2 copies of a high-risk HLA allele), and a non-HLA PGS with RA disease activity scores and disease characteristics using linear and logistic …

Time Trends In The Male To Female Ratio For Autism Incidence: Population Based, Prospectively Collected, Birth Cohort Study, Caroline Fyfe, Henric Winell, Joseph Dougherty, David H Gutmann, Alexander Kolevzon, Natasha Marrus, Kristina Tedroff, Tychele N Turner, Lauren A Weiss, Benjamin H K Yip, Weiyao Yin, Sven Sandin

2020-Current year OA Pubs

OBJECTIVES: To examine changes in the male to female ratio in diagnoses of autism spectrum disorder (ASD) over a 35 year period, providing temporal trends in diagnosis (incidence rate), the male to female ratio, and the age-cohort specific cumulative male to female ratio (cMFR).

DESIGN: Population based, prospectively collected birth cohort study.

PARTICIPANTS: 2 756 779 liveborn children recorded in the Swedish medical birth register between 1985 and 2020.

SETTING: Sweden.

MAIN OUTCOME MEASURE: Age-period cohort analysis investigating associations between ASD and age at diagnosis, calendar period, birth cohort, and sex, quantified by incidence rate ratios and associated two sided …

Generational Trends In Reproductive Factors Among Women In The Us: Implications For Breast Cancer Incidence, Lin Yang, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Reproductive factors are key breast cancer risk factors, yet contemporary generational patterns remain unclear. We aimed to evaluate trends in reproductive factors among US women born between 1910 and 2000.

METHODS: We conducted a serial, cross-sectional analysis of reproductive factors using data from the US National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2020. Female participants were grouped by birth cohorts (1910-1930, then by 10-year to 2000). Self-reported data were used to derive age at menarche, prevalence of age at menarche <  12 years, age at natural menopausal, prevalence of first live birth after age 30, and lifetime number of live births.

RESULTS: Data on 28,481 US women were analyzed. From birth cohort 1910-1930 to 1990-2000, the …

Rapid Urinary Lipoarabinomannan Test With Laboratory-Level Sensitivity For Tuberculosis Detection: A Performance Evaluation, Qisheng Jiang, Harisha Ramachandraiah, Carolyn Duncan, Sumanth Gandra, Ige A George, Jingyi Luan, Marcos Perez, Lorraine Lillis, David S Boyle, Scott Crick, Morten Ruhwald, Srikanth Singamaneni

2020-Current year OA Pubs

UNLABELLED: Developing rapid, non-sputum-based tests is a global priority to improve the diagnosis and timely treatment of tuberculosis (TB). In this study, we evaluated the detection limit, precision, stability, and lot-to-lot variation of a next-generation rapid diagnostic test (RDT), the plasmonic fluor (PF)-enhanced urinary lipoarabinomannan lateral flow assay (PF-LAM). We also assessed the diagnostic performance of PF-LAM, Alere Determine TB LAM Ag (AlereLAM), and electrochemiluminescence LAM assay (EclLAM), a highly sensitive laboratory-based test by comparing with microbiology reference standard (MRS) that includes molecular testing (Xpert MTB/RIF) and culture. Two sub-studies were conducted using banked urine samples. First, a preclinical study …

Rev-Erb-Alpha And -Beta Coordinately Regulate Astrocyte Reactivity And Proteostatic Function, Collin J Nadarajah, Michelle Y Li, Elsa I Quillin, Kevin Boyer, Julie M Dimitry, Yining Chen, Melvin W King, Ibrahim O Saliu, Jiyeon Lee, Patrick W Sheehan, Albert A Davis, Mitchell A Lazar, Guoyan Zhao, Erik S Musiek

2020-Current year OA Pubs

The molecular circadian clock is a ubiquitous transcriptional-translational feedback loop that regulates CNS function, glial responses, and neurodegenerative pathology. The nuclear receptors REV-ERB-α (

Intercalated Bacterial Biofilms Are Intrinsic Internal Components Of Calcium-Based Kidney Stones, William C Schmidt, Henry L Schreiber, Rachael E S Hammann, Chloe L P Obernuefemann, Karla Bergeron, Aleksandra Klim, Daniel Wong, Kefu Du, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Calcium oxalate stones comprise greater than 70% of all kidney stones. In the current conceptual framework, the initial stone nidus is thought to include the aggregation of inorganic crystallites, the formation of which is favored by elevated concentrations of dissolved constituents. Here, we show that this highly prevalent stone type comprises a form of organic-inorganic polycrystalline biocomposite with integrated bacterial biofilms. Evidence from electron microscopy and fluorescence microscopy reveal the unanticipated internal structure of kidney stones from human patients, where bacterial biofilms are intercalated between polycrystalline mineral layers, even in stones identified as "noninfectious" clinically, including those in patients without …

A Multicomponent Strategy To Increase Human Papillomavirus Vaccination Rates In Primary Care: A Cluster Randomized Clinical Trial, Ruoyun Wang, Lei Liu, Sherry Dodd, Sharon Graham, Shannon Rook, Lauren Ericson, Katie Plax, Abigail Barker, Virginia Mckay, Michelle I Silver, Jason G Newland, Allison A King

2020-Current year OA Pubs

IMPORTANCE: Human papillomavirus (HPV) vaccination prevents multiple cancers, yet vaccination rates by the recommended age remain well below national goals.

OBJECTIVE: To evaluate the effectiveness of a multicomponent strategy in increasing HPV vaccination rates in primary care settings by 13 years of age.

DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized clinical trial with a parallel-group design and 1:1 allocation was conducted at 20 pediatrics primary care practices from a practice-based research network in the St Louis, Missouri, metropolitan area by clinicians delivering routine well-child visits within participating practices. The intervention was implemented over 24 months (July 1, 2020, to September …

Longitudinal Multiomic Signatures Of Ards And Sepsis Inflammatory Phenotypes Identify Pathways Associated With Mortality, Narges Alipanah-Lechner, Pratik Sinha, Et Al.

2020-Current year OA Pubs

BACKGROUNDCritically ill patients with acute respiratory distress syndrome (ARDS) and sepsis exhibit distinct inflammatory phenotypes with divergent clinical outcomes, but the underlying molecular mechanisms remain poorly understood. These phenotypes, derived from clinical data and protein biomarkers, were associated with metabolic differences in a pilot study.METHODSWe performed integrative multiomics analysis of blood samples from 160 patients with ARDS in the ROSE trial, randomly selecting 80 patients from each latent class analysis-defined inflammatory phenotype (hyperinflammatory and hypoinflammatory) with phenotype probability greater than 0.9. Untargeted plasma metabolomics and whole-blood transcriptomics at day 0 and day 2 were analyzed using multimodal factor analysis (MEFISTO). …

Slc7a8 Is Essential For Metabolic Fitness And Function Of Th2 Cells, Santosh K Panda, Do-Hyun Kim, Pritesh Desai, Shitong Wu, Patrick Fernandes Rodrigues, Raki Sudan, Yizhou Liu, Haerin Jung, Intelly Lee, Susan Gilfillan, Marina Cella, Steven J Van Dyken, Marco Colonna

2020-Current year OA Pubs

Amino acids are essential for the activation and function of CD4 T helper (Th) cells, which differentiate into Th1, Th2, Th17, and Treg subsets to coordinate immune responses. While specific amino acid transporters have been identified for Th1, Th17, and Tregs, a transporter regulating Th2 cells remains unknown. This study identifies SLC7A8 as a Th2-specific amino acid transporter in the Th compartment. We found that Slc7a8 expression is upregulated in Th2 cells compared with other T helper subsets, and Slc7a8 deficiency impairs Th2 cell proliferation and cytokine production. Furthermore, SLC7A8 was found to be crucial for an effective type 2 …

Amyloidosis Of Bridging Veins Is A Pathologic Feature Of Alzheimer's Disease, Leon C D Smyth, Daan Verhaege, Elio Standen-Bloom, Yue Wu, Steffen E Storck, Pavle Boskovic, Benjamin A Plog, Tornike Mamuladze, Jose A Mazzitelli, Zhuoying Wang, Daniel D Lee, Gwendalyn J Randolph, Katherine E Schwetye, Song Hu, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) is characterized by the accumulation of extracellular aggregated amyloid beta, resulting from impaired waste clearance. We recently identified new cerebrospinal fluid (CSF) efflux structures termed arachnoid cuff exit (ACE) points and speculated that these may be impacted in AD, leading to impaired waste clearance function. Using 5XFAD mice, we found progressive amyloidosis of bridging veins at ACE points. Indeed, in 5XFAD mice, there is impaired CSF efflux to the dura mater, impaired CSF flow along bridging veins, and impaired blood flow through bridging veins. These observations suggest that ACE point amyloidosis plays a role in waste clearance …

Estimated Effectiveness Of 2024-2025 Covid-19 Vaccination Against Severe Covid-19, Kevin C Ma, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: As SARS-CoV-2 JN.1 lineage descendants continue to evolve, evaluating COVID-19 vaccine effectiveness (VE) against severe COVID-19 remains important to guide vaccination strategies.

OBJECTIVE: To estimate the VE of the 2024-2025 COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes overall and by time since dose (7-89, 90-179, and ≥180 days), JN.1 descendant lineage (KP.3.1.1, XEC, LP.8.1), and spike protein mutations associated with immune evasion.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, test-negative, case-control study conducted by the Investigating Respiratory Viruses in the Acutely Ill Network included adult patients (aged ≥18 years) hospitalized between September 1, 2024, and April 30, 2025, …