Research square最新文献

{"title":"Carryover of neotame, WS-23, and other additives from popular disposable e-cigarettes to aerosol.","authors":"Remi A Mellinghoff, Isabel X Maday, Elena M Bouldin, Paul T Anastas, Stephanie S O'Malley, Suchitra Krishnan-Sarin, Julie B Zimmerman, Hanno Erythropel","doi":"10.21203/rs.3.rs-11234503/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11234503/v1","url":null,"abstract":"<p><p><b>Introduction</b> : Disposable e-cigarette devices are popular among youth with fruit and candy flavored products dominating the market. While the addition of novel sweeteners and synthetic coolants has been quantified in the e-liquid of such devices, the relative amount of these compounds transferred into the aerosol and inhaled by users remains unknown. In this study, popular US disposable e-cigarette devices were analyzed for coolant, sweetener, and nicotine concentration, and subsequent carryover to aerosol was determined using an established protocol with cold-finger traps to collect aerosol. <b>Methods</b> 12 popular disposable e-cigarettes were identified and purchased between 2023-26, and 3 Sensa devices labeled as \"0-nicotine\" and 2 SpreeBar devices labeled to contain \"Metatine\" (6-methylnicotine) were also included to probe for the effect of nicotine on carryover. Menthol, nicotine, 6-methylnicotine (6MN), the synthetic coolants WS-23 and WS-3, and the artificial sweeteners neotame and sucralose were quantified in the liquids and the generated aerosol (20 puffs in triplicate) of 17 disposable e-cigarettes using GC-FID and LC-MS-MS. <b>Results</b> Neotame and WS-23 were present in all 17 devices at concentrations ranging from 0.05-2.73 mg/g and 3.52-35.0 mg/g, respectively. Nicotine was found in 11/17 devices, menthol in 9/17, WS-3 in 4/17, sucralose in 2/17, and 6MN in 2/17. Mean carryover rates to aerosol were: Neotame 40 ± 13%, WS-23 84 ± 9%, nicotine 88 ± 12%, menthol 81 ± 8%, WS-3 88 ± 10%, and sucralose and 6MN carryover ranged from 26-54% and 72-77%, respectively. <b>Conclusions</b> Although carryover rates to aerosol were lower for sweeteners compared to nicotine and coolants, users of these devices can be expected to be exposed to substantial amounts of the quantified 6 compounds. It is unclear whether neotame is thermally stable or breaks down during the aerosolization process. This study aims to provide a foundation for future toxicological and pharmacological studies that are needed to better understand the implications of chronic inhalation of neotame, WS-23 and the other tested compounds.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149280090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High frequency transcranial pulsed current stimulation improves quality of life in Parkinson's disease: A randomized controlled trial.","authors":"Zheng Li, Sandra Zhong, Lan Wang, Fengyi Hao, Wenjun Hong, Chunxia Zhao, Dongmei Ai, Zhigang Zhao, Ping Xiong, Tingting Sun, Kun Wang, Jessie Siew-Pin Leuk, Eng King Tan, Giuliana Rencricca, Esra Neufeld, Niels Kuster, Alvaro Pascual-Leone, Rong Xu","doi":"10.21203/rs.3.rs-10834572/v1","DOIUrl":"10.21203/rs.3.rs-10834572/v1","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive multisystem disorder in which motor and non-motor symptoms impair quality-of-life. High-frequency transcranial pulsed current stimulation (tPCS) modulates network-level dysfunction and may serve as an adjunct therapy in PD. In a randomized controlled trial, 38 participants with Hoehn & Yahr stage I-III PD were randomized to active 400 Hz tPCS or sham for 4 weeks while receiving stable antiparkinsonian medication. Stimulation targeted bilateral dorsolateral prefrontal cortices and motor-cerebellar circuit. Primary outcome was the Parkinson's Disease Questionnaire-39 Summary Index (PDQ-39 SI); secondary outcomes included motor and non-motor measures. Thirty participants completed the study with no serious adverse events. Compared with sham, active tPCS significantly improved PDQ-39 SI (p = 0.017; partial η² = 0.19) and reduced non-motor symptom burden (NMSS, p = 0.005). High frequency tPCS was safe, well tolerated, and improved quality of life in PD, warranting investigation in larger trials.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry ChiCTR2000041517, Date of registration Dec 27, 2020 (URL https//www.chictr.org.cn/showprojEN.html?proj=66622).</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a combined GMMA and glycoconjugate iNTS-TCV trivalent vaccine against invasive salmonellosis.","authors":"Francesco Citiulo, Francesca Necchi, Emilia Cappelletti, Xhenti Ferhati, Maria Grazia Aruta, Ilaria Liverani, Chiara Muzzi, Marta Benincasa, Carlo Giannelli, Francesca Mancini, Omar Rossi, Francesca Micoli, Claudia G Vitali, Laura B Martin, Francesco Berlanda Scorza, Anna Maria Colucci, Rocío Canals","doi":"10.21203/rs.3.rs-10957216/v1","DOIUrl":"10.21203/rs.3.rs-10957216/v1","url":null,"abstract":"<p><p>Non-typhoidal <i>Salmonella</i> (NTS) is a leading cause of bloodstream infections associated with substantial mortality mostly in sub-Saharan Africa (sSA) in children under 5 years. <i>Salmonella enterica</i> serovars Typhimurium and Enteritidis account for more than 90% of invasive NTS (iNTS) infections. Typhoid fever is caused by <i>S. enterica</i> serovar Typhi and is relatively common in South and Southeast Asia and sSA, especially among children. While there are licensed vaccines to prevent <i>S</i>. Typhi infections, the only current intervention for iNTS disease is treatment with antibiotics. This work presents the preclinical development of a trivalent vaccine, iNTS-TCV, to prevent both iNTS disease and typhoid fever. This vaccine combines the Generalized Modules for Membrane Antigens (GMMA) technology for the iNTS components with the WHO-pre-qualified Vi-CRM₁₉₇ Typhoid Conjugate Vaccine (TCV). Immunization of mice with the iNTS-TCV candidate vaccine elicited higher anti-Vi IgG responses, characterized by a distinct IgG subclass profile, and greater serum bactericidal activity compared to responses induced by Vi-CRM₁₉₇ alone. <i>In vitro</i> immunoprofiling of human peripheral blood mononuclear cells revealed that the GMMA components drive a robust pro-inflammatory cytokine response, suggesting a potential mechanistic basis for the observed adjuvant effect on Vi-CRM₁₉₇ immunogenicity. The iNTS-TCV vaccine was well-tolerated in preclinical toxicology studies. These findings demonstrate the feasibility and potential benefits of combining GMMA and glycoconjugate vaccine technologies, offering a promising strategy for the prevention of both iNTS disease and typhoid fever. This trivalent vaccine approach may provide a sustainable and effective solution for addressing the significant burden of invasive salmonellosis in sSA.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Gut-Liver Immune Axis in Celiac Disease, Primary Sclerosing Cholangitis, and Ulcerative Colitis: Outcomes of a Rare but Significant Triad.","authors":"Samruddhi Nitin Patwardhan, Omid Yazdani, Romina Esbati, Srusti Ganesh Bhalerao, Shaikh Danish Mahmood, Ana Marenco, Natalia Rojas-Amaris, Joshua R Korzenik","doi":"10.21203/rs.3.rs-11064634/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-11064634/v1","url":null,"abstract":"<p><p>Purpose To characterize the clinical presentation, disease course, and outcomes of patients with concurrent primary sclerosing cholangitis (PSC) and celiac disease (CeD), including those with concomitant inflammatory bowel disease (IBD). Methods Retrospective EHR analysis (MGB RPDR, BIDMC Celiac Center, All of Us) identified patients with confirmed PSC and CeD (ICD-10, encounter threshold > 1, validated clinically/serologically/histologically). Primary outcomes were hepatic complications and time to liver transplantation, compared against two 3:1 age-matched cohorts (PSC + IBD, n = 54; PSC-only, n = 54). Results Among 7.5 million patients in RPDR, 18,375 had CeD and 992 had PSC, with 13 observed cases of overlap versus 2.43 expected (OR 5.35, 95% CI 3.08-9.30; p < 0.001). Eighteen patients met full inclusion criteria (67% male, 94% White, mean age 47.8 years at PSC diagnosis). IBD was present in 72%, predominantly Ulcerative Colitis (56%). With high gluten-free diet adherence (89%), hepatic complications occurred in 89% of patients, with cirrhosis in 50%. Liver transplantation was required in 22%, at a mean of 5.4 years from PSC diagnosis among transplants with dated intervals, with no post-transplant PSC recurrence observed among the 4 transplanted patients. Compared with matched PSC + IBD (n = 54) and PSC-only (n = 54) control cohorts, liver transplantation was numerically more frequent in the PSC + CeD cohort than in either control cohort, though this difference did not reach significance (22.2% vs 5.6% vs 13.0%; chi-square p = 0.127). Conclusion PSC and CeD co-occur at a significantly higher frequency than expected, suggesting shared autoimmune pathogenic mechanisms. The substantial hepatic complication burden and frequent IBD co-occurrence highlight the clinical importance of this overlap and the need for multidisciplinary management and routine autoimmune screening in affected patients. Matched-cohort comparisons further suggest a numerically elevated, though not statistically significant, risk of liver transplantation in PSC + CeD patients relative to PSC + IBD patients without celiac disease, alongside a significantly elevated risk of cirrhosis and PSC-autoimmune hepatitis overlap.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malaria among children living in flood-prone villages in the Kasese District of Western Uganda: prevalence and risk factors from a cross-sectional study.","authors":"Rogers Kalyetsi, Ronnie Ndizeye, Michael Reiskind, Raquel Reyes, Kaylin Lewandowski, Mbusa Rapheal, Abel Bwambale, Baguma Emmanuel, Liao Huipeng, Dana Anne Giandomenico, Bonnie E Shook-Sa, Moses Ntaro, Peter Chris Kawungezi, Hope Mudondo, Charles Nkubi Bagenda, Paul E Alele, Jerome Kabakyenga, Gertrude Kiwanuka, Edgar M Mulogo, Ross M Boyce","doi":"10.21203/rs.3.rs-10535941/v1","DOIUrl":"10.21203/rs.3.rs-10535941/v1","url":null,"abstract":"<p><strong>Background: </strong><i>Plasmodium falciparum</i> infections pose significant health and economic challenges in Uganda. This study evaluated the prevalence of <i>P. falciparum</i> malaria among children in flood-prone villages in Kasese District, Western Uganda, and examined associated factors.</p><p><strong>Methods: </strong>A total of 7,987 children 2-12 years of age from 3,702 unique households consented to participate. Demographic data and malaria prevention and treatment behaviours were documented. Capillary blood samples were aseptically collected and tested for <i>P. falciparum</i> circulating HRP1&2 using mRDT. Chi-square or Fisher's exact tests were used to compare malaria prevalence, while logistic regression identified factors associated with malaria positivity. Generalized estimating equations were used to estimate associations between malaria positivity and factors including age, sex, terrain, LLIN usage.</p><p><strong>Results: </strong>The <i>P. falciparum</i> positivity rate was 3.3% (267 of 7.987; 95% CI: 3.0-3.8) by RDT.. Among those who had fever (temp ≥ 37.5°C) at the time of the visit, the PfPR was 10.1% (40/396), compared to 3.0% (227/7,591) among those without a fever. Of the 3,702 households, 213 (5.75%, 95% CI 5.05-6.55) had at least one positive malaria case. The positivity rates varied with sub-county of residence (Kyarumba 8.0% and Karusandara 10.0%); sex (female 2.7% vs. 4.1% males); LLIN use (4.2% No vs. 2.0% yes); and altitude (low 3.8% vs. high 0.5%). Individual positivity clustered at the sub-villages was independently associated with 5-12 years (aOR 2.15, 95% CI 1.37, 3.39; p < 0.001), male sex (aOR 1.46, 95% CI 1.18, 1.81; p = 0.001), fever (aOR 3.08, 95% CI 2.00, 4.74; p < 0.001) and use of LLIN a previous night (aOR 0.57, 95% CI 0.43, 0.74; p < 0.001). The household positivity was independently associated with LLIN ownership status (aOR 0.53, 95% CI 0.39, 0.72; p < 0.001), surface water for domestic use (aOR 5.17, 95% CI 3.60, 7.42; p < 0.001), and > 6 occupants in the household (aOR 2.7, 95% CI 1.62, 4.63; p < 0.001).</p><p><strong>Conclusion: </strong>The findings illustrate ongoing malaria transmission. Household clustering with malaria highlights the presence of hotspots in Kyarumba and Karusandara sub-counties. Targeted campaigns to enhance household ownership and usage of LLINs could further protect against malaria following severe flooding events.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-Sectional Associations of Screen Media Use Patterns with Executive Functioning and Emotional Self-Regulation Among U.S. Preschool-Aged Children.","authors":"Soyang Kwon, Bridget Armstrong, Sarah B Welch, Courtney A Zulauf-McCurdy","doi":"10.21203/rs.3.rs-11221493/v1","DOIUrl":"10.21203/rs.3.rs-11221493/v1","url":null,"abstract":"<p><strong>Background: </strong>Children's screen media use increases substantially during the preschool years, a period of rapid development in executive functioning and emotional self-regulation. Greater screen time has been associated with difficulties in both domains, but most studies have focused on total screen time. This approach may obscure distinct associations with developmental domains because screen media use varies in activity (video viewing vs. digital game playing) and device type (mobile devices vs. television). We examined whether associations between screen media use and executive functioning and emotional self-regulation differed by activity and device type among preschool-aged children.</p><p><strong>Methods: </strong>A study design was cross-sectional. The study sample consisted of 238 mother-child dyads with children aged 3-4 years participating in the Behavioral and Emotional Development in Early Childhood Study (BEES). Mothers reported child media use using the Media Assessment Questionnaire, which assessed daily minutes spent viewing video content and playing digital games on mobile devices and television, along with background television and reasons for allowing screen use. Primary outcomes were executive-function difficulty measured using the Childhood Executive Functioning Inventory and emotional self-regulation difficulty using the Emotion Regulation Checklist. Multivariable linear regression models estimated associations between screen media use and the outcomes, adjusted for child age, child sex, maternal education, and neighborhood opportunity.</p><p><strong>Results: </strong>Children averaged 109 minutes/day (SD = 92) of screen time, including 60 minutes/day (SD = 40) of television video viewing, 30 minutes/day (SD = 39) of mobile video viewing, 13 minutes/day (SD = 25) of mobile game playing, and 6 minutes/day (SD = 20) of television game playing. Total video viewing was correlated with background television (ρ = 0.48; p < 0.001), and mobile video viewing was correlated with parental use of screens to calm the child (ρ = 0.50; p < 0.001). Each additional 30 minutes/day of total screen time was associated with greater executive-function difficulty (B = 0.03; 95% CI = 0.01, 0.06), but not emotional-regulation difficulty. In decomposition analyses, longer video viewing was associated with greater executive-function difficulty (B = 0.06; 95% CI = 0.01, 0.11), whereas longer mobile-device use was associated with greater emotional-regulation difficulty (B = 0.05; 95% CI = 0.01, 0.08).</p><p><strong>Conclusions: </strong>In this cross-sectional examination of U.S. preschool-aged children, greater video viewing was associated with greater executive-function difficulty, whereas greater mobile-device use was associated with greater emotional-regulation difficulty. Findings highlight the importance of considering activity and device type when examining the impact of screen media use on child development.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Brain-Body Processes in Postural Tachycardia Syndrome: A Pilot Trial of POts Reprocessing Therapy.","authors":"Taylor B Crouch, Spencer Chase, Tammy Redman, Mary Wells, Yoni Ashar, Howard Schubiner, Madison Maxwell, Elliot Popoff, Gisela Chelimsky, Thomas Chelimsky","doi":"10.21203/rs.3.rs-11010997/v1","DOIUrl":"10.21203/rs.3.rs-11010997/v1","url":null,"abstract":"<p><strong>Purpose: </strong>Postural tachycardia syndrome (POTS) is a chronic autonomic disorder characterized by orthostatic intolerance and frequently accompanied by a broad constellation of debilitating symptoms. Emerging evidence suggests that dysregulation within central-autonomic regulatory networks may contribute to symptom persistence. We developed POts Reprocessing Therapy (PORT), a neuroplasticity-informed behavioral intervention adapted from Pain Reprocessing Therapy. This pilot study evaluated PORT's feasibility, acceptability, and preliminary clinical outcomes.</p><p><strong>Methods: </strong>We conducted a non-randomized, two-arm, open-label pilot feasibility trial. Adults with clinically significant POTS symptoms received eight weekly PORT sessions (<i>n</i> = 14). A comparison group of adults with POTS receiving community care while awaiting entry to an autonomic clinic served as controls (<i>n</i> = 15). Self-report measures were collected at baseline and 8-week follow-up, including POTS symptom severity, symptom catastrophizing, anxiety, depression, pain, fatigue, and quality of life. Feasibility and acceptability were assessed via recruitment, retention, and treatment satisfaction.</p><p><strong>Results: </strong>PORT demonstrated strong feasibility and acceptability, with 83% retention and strong satisfaction ratings among completers. Participants receiving PORT reported greater symptom improvement compared with community care controls. Mixed ANOVA analyses revealed significant group × time interactions for POTS symptoms (ηp² = 0.283), anxiety (ηp² = 0.363), symptom catastrophizing (ηp² = 0.193), and depression (ηp² = 0.186), reflecting moderate-to-large effects.</p><p><strong>Conclusion: </strong>This pilot study suggests that PORT is feasible and acceptable and may be associated with improvements in POTS symptoms and psychological processes. Findings provide preliminary support for targeting central-autonomic processes through neuroplasticity-based interventions and warrant larger randomized controlled trials to evaluate efficacy and mechanisms.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Exhaustion Limits CAR-NK Therapy in Glioblastoma but Can Be Mitigated by Early Repeated Dosing.","authors":"Kajal Chaudhry, Nethaji Muniraj, Haili Lang, Ashley Geiger, Gage Paul, Ehsan Dowlati, Danielle Sohai, Joshua Terao, Sridevi Yadavilli, Carlos Sanchez, Eric Yvon, Christopher Lazaraski, Eugene Hwang, Matthias Holdhoff, Barbara Savoldo, Conrad Russell Cruz, Catherine Bollard","doi":"10.21203/rs.3.rs-10808000/v1","DOIUrl":"10.21203/rs.3.rs-10808000/v1","url":null,"abstract":"<p><p>With the commercial success of Chimeric Antigen Receptor T (CAR-T) cell therapies in the blood cancer setting, there are increasing numbers of clinical trials evaluating this treatment modality in patients with solid tumors, including brain tumors. Allogeneic CAR-natural killer (NK) cell therapy offers an attractive \"off-the-shelf\" option using the CAR platform. However, this approach remains comparatively untested clinically, with only one published clinical trial to date in patients with central nervous system (CNS) tumors. Building on our prior in vitro characterization of allogeneic B7H3-CAR-NK for brain tumors, we compared B7H3/CD28z CAR-NK and CAR-T cells in an aggressive adult Glioblastoma Multiforme (GBM) model in vitro and in an orthotopic murine xenograft system. CAR-NK cells killed GBM targets more rapidly than CAR-T cells in vitro, and secreted higher levels of IFN-γ. However, in vivo, CAR-T cells controlled tumor growth and prolonged survival while CAR-NK cells failed to restrict tumor outgrowth despite confirmed tumor infiltration and persistence. Neither B7H3 antigen upregulation on NK cells nor trogocytosis-driven fratricide accounted for this discrepancy. Instead, we discovered that CAR-NK cells lost cytolytic activity, proliferative capacity, and cytokine secretion after multiple rounds of tumor challenge. This coincided with a downregulation of activating receptors and upregulation of inhibitory receptors. In contrast, CAR-T cells retained their cytolytic activity through four rounds of tumor challenge. While negating the consequences of tumor-induced suppression (by abrogating TGF-β signaling and increasing IL15 signaling), restored in vitro serial killing capacity and reduced in vivo tumor burden, these engineering strategies were insufficient to enhance overall survival. In contrast, administering multiple doses of NK cell products early did confer a survival benefit in preclinical models, suggesting that the CAR-NK cell platform may be more effective when utilized clinically in the adjuvant setting for patients with high-risk brain tumors such as GBM.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing geospatial interpolation techniques for estimating ambient PM2.5 mass concentrations from sugarcane burning in South Florida.","authors":"Anne Mielnik, Olivia Sablan, Jeffrey R Pierce, Lilah M Besser, Juyoung Park, Diana Mitsova, Diane Cook, Sherry WeMott, Christine L Williams, Lisa A K Wiese, Sheryl Magzamen","doi":"10.21203/rs.3.rs-10743669/v1","DOIUrl":"10.21203/rs.3.rs-10743669/v1","url":null,"abstract":"<p><p>Few studies quantify air pollutant exposures from agricultural burning - a potentially significant source of fine particulate matter (PM_2.5) in rural regions - due to sparse air quality monitoring outside of urban areas. Using a dense network of low-cost sensors, we evaluated several interpolation-based approaches (e.g., inverse distance weighting and kriging) to estimate 24-hour average PM_2.5 exposures from sugarcane burning in the Everglades Agricultural Area (EAA) for future regional health studies. Measurements were taken at 46 unique locations from June 8th, 2024, to December 1st, 2025, capturing the EAA's burn and non-burn seasons. Model performance was evaluated using leave-one-out cross-validation and overall, varied by model and fit, meteorological season, and the presence of smoke, with R² values ranging from 0 to 0.99. Based on the placement of sensors and number of measurements each day, inverse distance weighting models performed best - maintaining the highest R² and the lowest root mean squared error and mean absolute error values for the most days. However, combining approaches, choosing the \"best\" model each day, provided the most robust exposure estimates for future studies. Independent of interpolation technique, estimated PM_2.5 mass concentrations were highest in the presence of sugarcane burning smoke, increasing 1.65 μg/m³ (standard error = 0.13 μg/m³), and were localized inland, near sugarcane burning regions and the EAA. Notably, PM_2.5 was lowest along the coast - highlighting air quality disparities in South Florida.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Food competition, but not other common assays, reveals social dominance in female and male CD1 mice.","authors":"Elizabeth Illescas-Huerta, Hannah Casselman, Logan Taylor, Sequioa Smith, Nancy Padilla-Coreano","doi":"10.21203/rs.3.rs-11078463/v1","DOIUrl":"10.21203/rs.3.rs-11078463/v1","url":null,"abstract":"<p><p>Social dominance is fundamental to social organization across species and plays a critical role in shaping behavior, physiology, and health. Despite the complexity of social organization, researchers have successfully developed animal models to investigate social dominance under controlled experimental conditions across a variety of species, including male rodents. However, measures of social rank among female mice remain poorly understood, limiting the generalizability of commonly used social dominance assays. Here, we systematically evaluated four commonly used behavioral assays of social dominance in female CD1 mice and directly compared their performance with that observed in males. We found that three traditional assays-agonistic behavior, urine marking, and the tube test-failed to distinguish social rank in female CD1 mice. In contrast, the food competition task reliably identified social ranks in both female and male CD1 mice, revealing linear dominance hierarchies and demonstrating that this assay effectively assesses social dominance across sexes in an outbred mouse strain. By systematically comparing multiple behavioral assays in female and male CD1 mice, our study expands the current understanding of how social dominance is expressed across sexes and establishes a valuable platform for future studies aimed at uncovering the neural mechanisms underlying social hierarchy.</p>","PeriodicalId":519972,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}