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Because the existence of linear no-threshold (LNT) hypothesis in the low-dose region has not been confirmed, we previously proposed the "hormesis-coupled LNT theory." Because this theory does not consider the effect of dose-rate, we applied our theory to different dose-rates using data from the previous reference (Yoshida et al. 2008). As a result, we calculated that the biological benefit via radiation can be observed at a dose-rate of <1 mGy/h. In the future, biologically beneficial factors may be identified by exploring the exposure region with cumulative doses of >350 mGy at this low-dose-rates.
Oral GLP-1 receptor agonists (GLP-1 RAs) offer a non-injectable option for weight management in adults with overweight/obesity without diabetes. This network meta-analysis (NMA) evaluated their effects on body weight. A frequentist random-effects NMA of RCTs comparing oral GLP-1 RAs with placebo in adults without diabetes was conducted by searching databases through 30 April 2026. The primary outcome was percent change in body weight, with secondary outcomes including other weight measures and weight thresholds. Analyses used R (netmeta), and certainty was assessed with CINeMA. Nine RCTs (N = 5766; 20-72 weeks) evaluating oral semaglutide, orforglipron, danuglipron, and lotiglipron were included. All agents except low-dose (LoD) lotiglipron outperformed placebo in percent body weight reduction; high-dose (HiD) semaglutide (MD -11.6%) and orforglipron (MD -11.8%) showed the greatest effects. Orforglipron HiD produced the greatest absolute weight loss (MD -12.2 kg), whereas semaglutide HiD reduced BMI (MD -4.7 kg/m2) and waist circumference (MD -10.0 cm) the most. Danuglipron HiD, semaglutide HiD, and semaglutide LoD ranked highest for ≥ 5%, ≥ 10%, and ≥ 15% weight loss, respectively. Evidence certainty was low to moderate. HiD oral semaglutide and orforglipron demonstrated the most consistent and substantial weight reductions though low-to-moderate certainty and lack of head-to-head comparisons constrain comparative inference.
Fresh-cut produce operations often generate work-in-process (WIP) ingredients that have undergone peeling, cutting, washing, etc., and are then subjected to temporary holding, prior to packaging, creating conditions that may favor pathogen survival and growth. The objective of this study was to evaluate the survival of Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica, and native microbiota on WIP fresh-cut carrot and yellow onion treated with deionized water, sodium hypochlorite (NaOCl, >10 ppm free chlorine), or peracetic acid (PAA, 80 ppm) and held at 4, 8, or 12°C for up to seven days. Pathogen behavior was strongly influenced by storage temperature and commodity matrix. At 4°C, E. coli O157:H7 and S. enterica populations generally declined or remained stable. Conversely, at 8°C and 12°C, which were evaluated to simulate potential temperature-abuse scenarios, E. coli O157:H7 and S. enterica proliferated in unwashed samples but were often suppressed by chlorine and PAA. L. monocytogenes on carrot did not grow under any treatment or temperature, likely due to intrinsic antimicrobial compounds, while it persisted on onion and grew by 0.5-1.6 logs under temperature abuse. PAA often provided the greatest pathogen reductions on onion, although chlorine was more effective against E. coli O157:H7 on carrot. Native mesophilic or psychrotrophic bacteria, and yeast and mold populations, increased rapidly across all treatments and storage conditions, with PAA-washed samples often having the greatest growth rates. Overall, while sanitizer efficacy was commodity-dependent, strict temperature and holding time management emerged as the most critical factor in limiting pathogen growth. These findings underscore the necessity of an integrated management approach for WIP produce, although further validation under dynamic industrial conditions and mechanisms for the rapid regrowth of microbiota in PAA-washed samples warrant further investigations.
Aseptic loosening of on-lay all-polyethylene cemented glenoid components in total shoulder arthroplasty is a leading cause of revision surgery and may be accelerated by the rocking-horse phenomenon. In response to this, inset glenoid implants have been developed in hopes that they will lead to lower loosening rates. Presently, little literature exists on the ideal depth of insetting to minimize micromotion while also considering glenoid bone preservation. This study, therefore, evaluated a generic circular inset glenoid component implanted at 4 depths in osteoarthritic glenoids using finite element models. Micromotion under simulated joint loading, bone removal, and underlying bone density were compared. The goal was to determine an optimal inset depth that minimizes micromotion while preserving glenoid bone. Finite element models of 7 male osteoarthritic scapulae were generated from pre-operative computed tomography scans. Circular inset glenoid components were virtually implanted at 4 depths: 25%, 50%, 75%, and 100% (inlay). Glenohumeral joint loading was simulated in 5 directions. Tangential (parallel) and normal (perpendicular) micromotions were measured across 6 backside regions of the component for each loading direction. The volume of bone removed for implantation and bone density within a 5-mm depth region beneath each component were also evaluated. No significant relationship was found between inset depth and tangential micromotion across load directions or locations (P > .05). The 25% depth showed the greatest median tangential micromotion in 12 of 42 cases (29%), the 50% and 100% depths in 11 cases each (26%), and the 75% depth in 8 cases (19%). Similarly, no significant relationship was observed between inset depth and normal micromotion. The 25% depth had the greatest median normal micromotion in 15 of 42 cases (36%), followed by 75% in 13 cases (31%), 50% in 8 cases (19%), and 100% in 6 cases (14%).Bone removal increased significantly with increasing inset depth (P < .05). On average, the 100% depth required approximately 4 times more bone removal than the 25% depth. Bone density within the 5-mm depth region beneath the component was highest at the 25% depth. Significant differences were observed between the 25% depth and the 50% (P = .03), 75% (P = .03), and 100% depths (P = .049), while no significant differences were found among the deeper depths. Inset depth was not significantly associated with glenoid component micromotion, although a trend toward reduced micromotion with greater depth was observed. However, deeper insetting required substantially more bone removal and was associated with lower underlying bone density. Considering implant stability, bone preservation, and supporting bone density, these findings support glenoid component insetting at approximately 25-50% depth.
TAR DNA-binding protein 43 (TDP-43) inclusions are often associated with hyperphosphorylated tau, thus neurofibrillary tangles as the hallmark of Alzheimer's disease (AD) and primary age-related tauopathy (PART). TDP-43 in AD is associated with cognitive impairment, and while staging is known, the localization, cellular and inclusion characteristics of TDP-43 are yet to be elucidated. We investigate relationships between TDP-43 inclusions and the tangle maturation continuum in AD, PART, and co-pathologies by multiplex immunostaining combined with artificial intelligence (AI)-based segmentation via object recognition, reconstruction, and quantification. We performed anti-phosphorylated TDP-43 immunofluorescence with phosphorylated tau labeling different stages and modifications of tangles (AT8, pS396, TauC3, MN423, GT38) in three controls, three cases with PART and TDP-43 (PART-TDP), five cases with high likelihood AD and TDP-43 (AD-TDP), and four cases of high likelihood AD with TDP-43 and Lewy Body disease (AD-TDP-LBD). Confocal imaging was taken from eight regions: amygdala (amygdala-BL and amygdala-CM) and hippocampus (Cornu Ammonis (CA)-1, CA2/3, CA4, dentate gyrus (DG), subiculum (SUB)), and entorhinal cortex (ERC) and quantified with AI segmentation to identify 3D spatial relations, thus the maturity of neurofibrillary tangle associated TDP-43 (TAT) inclusions. TATs, which were either identified by pTDP-43 and AT8 or pTDP-43 and pS396 double positivity, were also investigated by Thioflavin S (ThioS) histochemistry. We found pS396 labeled mature TATs predominated in PART and AD in every region. Basolateral and centromedial amygdala displayed overall greatest number of pre-TATs and mature TATs. Mature TATs were homogenously distributed among hippocampal subfields whereas CA4 and DG had the greatest mature TAT composition. ERC revealed closer numbers of pre-TATs and mature TATs yet mature TATs predominated all groups. Unbiased AI-based object identification, reconstruction, and TAT maturation analysis pipeline in conjunction with TDP-43, tau, and ThioS multiplex immunostaining demonstrated unique aggregation and maturation patterns, highlighting region-specific dynamics in the neurodegenerative processes of PART and AD.
Diseases of the skin and subcutaneous tissue represent a crucial yet understudied contributor to morbidity and mortality, particularly in older adults. Despite an aging population and substantial disease burden, national mortality patterns, temporal trends, and demographic disparities remain poorly described. This study utilized CDC WONDER Underlying Cause of Death data from 1968 to 2023 to identify deaths amongst U.S adults aged ≥65 years attributed to skin and subcutaneous tissue diseases. Age-adjusted mortality rates (AAMRs) per 100,000, crude mortality rates (CMRs) per 100,000, average annual percent change (AAPC), and annual percent change (APC) by period were calculated and stratified by sex, race, age, census region, and state. A total of 161,822 deaths from skin and subcutaneous tissue disease occurred among U.S. adults ≥65 years from 1968 to 2023. Overall AAMRs increased from 6.74 in 1968 to 9.83 in 2023 (AAPC: 0.91; 95% CI: 0.76 to 1.12, p < 0.001), and the greatest rate of increase in AAMRs was from 7.60 in 2017 to 9.83 in 2023 (APC: 5.65; 95% CI: 3.60 to 10.14, p < 0.001). Women had a similar mean AAMR (9.10) to men (8.75); however, men had a greater rise in AAMR, increasing from 6.41 in 1968 to 10.00 in 2023 (AAPC: 1.17; 95% CI 1.01 to 1.39, p < 0.001). White Americans had a lower mean AAMR (7.87) than Black or African Americans (23.15), but had a greater rise in AAMR, increasing from 6.37 in 1968 to 9.59 in 2023 (AAPC: 1.02; 95% CI 0.87 to 1.20, p < 0.001). Regionally, the South had the greatest mean AAMR (10.72), but had the lowest rate of increase in AAMR, increasing from 8.23 in 1968 to 9.54 in 2023 (AAPC: 0.65; 95% CI: 0.47 to 0.90, p < 0.001). State-wise deaths were highest in New York (n = 12,682, 7.92%) and lowest in Alaska (n = 119, 0.07%). Skin and subcutaneous tissue-related disease mortality significantly rose from 1968 to 2023, with recent mortality trends highlighting a cause for concern. The marked heterogeneity in disease burden between demographic and geographical groups highlights the urgent need for equitable and targeted public health interventions.
This study aimed to quantify the match-running performance of Vietnamese professional football players utilizing global positioning system (GPS) technology and investigate variations based on competition level and position and establish a composite performance score (CPS) framework for player assessment and categorization. A longitudinal observational study was executed throughout the 2024-2025 season, encompassing 57 official matches involving six professional clubs from V-League 1 and V-League 2, comprised 497 player-match observations from 160 outfield players. External-load variables were gathered utilizing 10 Hz GPS devices and encompassed total distance (TD), maximum velocity (Vmax), high-speed running distance (HSR), sprint distance and accelerations/decelerations. Statistical analyses included independent-samples t-tests, one-way ANOVA with Tukey HSD post hoc comparisons and correlation analyses. V-League 1 players displayed significantly greater HSR, sprint distance, Vmax, accelerations and decelerations (p < 0.05) than V-League 2 players but TD was similar between competition levels. There were significant differences between positions for TD, TD/90, Vmax, HSR and sprint distance (all p < 0.001) with forwards showing the greatest high-intensity locomotor outputs and defenders covering the greatest running volumes. The performance of Vietnamese players in HSR and sprint-related areas was significantly lower than elite European benchmarks. CPS classification indicated that the majority of observations were classified as Average (57.5%) with Elite classifications only accounting for 3.1% of observations. These findings indicate that high-intensity locomotor capacity is an important physical determinant in professional Vietnamese football and that the CPS framework provides a practical multidimensional tool for performance profiling, individualized training and longitudinal athlete monitoring.
Closed-loop aeroponics exposes suspended roots to repeated pulses of nutrient solution and humid air, so nozzle and misting settings shape the root-zone water, nutrient, and gas environment. We evaluated how root-zone droplet delivery and stage-specific ion management affected growth and nutrient solution-use efficiency of Centella asiatica in a natural-light greenhouse. Six nozzle classes were characterized by laser diffraction, and three misting schedules were screened using shoot dry-mass production efficiency. A separate bed-level experiment compared fresh and dry biomass under four operationally feasible nozzles, while a nutrient-management experiment compared fixed Hoagland, EC-adjusted Hoagland, and a stage-specific formulation using shoot and root biomass, leaf and runner number, SPAD, canopy cover, and solution-use efficiency. The plantable bed area was 63.9 m² within a 165 m² greenhouse, at a density of approximately 16-25 plants m-². VF and F treatments achieved the highest dry-mass production efficiency, and the 5 min × 288 events day-¹ schedule performed best across nozzle classes. At 53 days after transplanting (DAT), VF produced the greatest fresh and dry biomass per bed area within the tested C-M-F-VF range. The stage-specific formulation produced greater shoot and root biomass, canopy cover, and solution-use efficiency than either Hoagland treatment. Reservoir corrections were greatest for nitrate during leaf expansion, potassium during biomass accumulation, and Ca, Fe, and B during late maturation. Taken together, the complementary experiments associated root-zone delivery and stage-specific nutrient supply with coordinated whole-plant growth and resource-use responses. Because root-surface wetness, oxygen availability, root respiration, and tissue ion accumulation were not measured directly, nozzle effects should be interpreted as integrated root-zone treatment effects rather than effects of droplet diameter alone. Multi-season factorial experiments with direct physiological measurements are needed to confirm the underlying mechanisms.
To evaluate stage-dependent performance of same-session [18F]FDG PET/contrast-enhanced CT (PET/ceCT) for initial breast cancer staging and PET/ceCT-detected relapse patterns during follow-up. This retrospective single-centre study included a primary staging cohort with one index PET/ceCT per patient and a longitudinal cohort of follow-up/restaging examinations. PET/ceCT-derived endpoints were assessed against clinically adjudicated reference standards established through multidisciplinary team review, pathology when available and follow-up imaging. SUVmax and ceCT lesion diameter were analysed as exploratory biomarkers. The staging cohort included 116 patients. Baseline stage was evaluable in 106 patients: 65 had cN-positive disease, 9 had cT3-4 cN0 disease and 32 had cT1-2 cN0 disease. Overall nodal staging performance showed sensitivity 64.8%, specificity 88.9%, PPV 92.0%, NPV 56.1% and accuracy 72.9%. In cT3-4 and/or cN-positive disease, PET-positive nodal findings had a PPV of 100%. Baseline M-stage assessment was limited by the low number of clinically confirmed M1 cases. SUVmax correlated with Ki-67 (rho = 0.322, p = 0.003, q = 0.022). The longitudinal cohort included 176 patients and 429 examinations. In 311 adjudicated examinations, restaging performance for disease progression showed sensitivity 100%, specificity 93.5%, PPV 97.3%, NPV 100% and accuracy 98.1%. First confirmed relapse was multiorgan/multisystem in 48/82 patients and visceral-only in 15/82; visceral conversion occurred in 5/16 patients with initial bone-only or nodal/locoregional relapse. Same-session [18F]FDG PET/ceCT showed greatest baseline utility in higher-risk breast cancer and was useful for longitudinal characterization of relapse phenotype and metastatic evolution.
Current ACS NSQIP benchmarking relies primarily on the principal Current Procedural Terminology (CPT) code for procedure-related risk adjustment because conventional regression methods cannot efficiently accommodate numerous sparse CPT variables. Although CatBoost (CATB) can incorporate multiple CPT codes to improve risk estimation, it is computationally intensive and may produce unstable estimates for infrequently performed procedures. This study evaluated Bayesian automatic differentiation variational inference (ADVI) as an alternative approach. CATB and ADVI were applied to 2019-2023 ACS NSQIP data to estimate CPT-based risk adjustment using all available CPT codes (up to 21 per patient) across 31 outcomes. Performance was compared using calibration (Hosmer-Lemeshow statistic), discrimination (area under the receiver operating characteristic curve), computational time, and effects on hospital-level morbidity benchmarking relative to principal CPT-only risk adjustment. Both approaches demonstrated similar discrimination across all 31 outcomes, whereas ADVI consistently achieved superior calibration and markedly lower computational time, with the greatest advantages observed in larger datasets. Among the 15 largest models, mean Hosmer-Lemeshow statistics were 125.23 for ADVI versus 764.72 for CATB, while mean computation times were 9.8 versus 1447.7 minutes, respectively. ADVI and CATB produced similar, although not identical, hospital benchmarking results. ADVI is a computationally efficient and statistically robust alternative to CATB for incorporating multiple CPT codes into ACS NSQIP risk adjustment. Improved calibration and more stable estimation for sparse procedure combinations may enhance the reliability and scalability of procedure-based benchmarking.
Electronic nicotine delivery system (ENDS) components and e-liquid containers may influence the chemical composition of inhaled aerosols, potentially impacting user exposure and the product's appropriateness for the protection of public health. Extractable and leachable (E&L) studies are crucial for identifying the chemicals that migrate to the e-liquids from the components and containers housing the e-liquids during storage and inform the potential ENDS risks to public health. There are few published ENDS E&L studies that provide limited information regarding the components and e-liquid containers. Thus, this study includes extractable testing followed by leachable testing that are designed to comprehensively examine and determine the chemicals that migrate to the e-liquid from closed ENDS components and e-liquid containers (low-density polyethylene (LDPE) bottles, polyethylene terephthalate (PET) bottles). Testing was conducted by Eurofins BioPharma Product Testing laboratory, a contract laboratory specializing in pharmaceutical extractable and leachable analyses. Semiquantitative and nontargeted analyses were conducted using gas chromatography-mass spectrometry (GC-MS) for volatile compounds and ultra-high-performance liquid chromatography-photo diode array-mass spectrometry (UPLC-PDA-MS) for semi- and nonvolatile compounds. Semiquantitative and targeted analyses were conducted using GC-MS-selected ion monitoring (GC-MS-SIM) for polycyclic aromatic hydrocarbons (PAHs) and inductively coupled plasma MS (ICP-MS) for metals. All relevant peaks were tentatively identified using mass spectral libraries and identification criteria. Across all 47 products examined in the extractable study, 19 unique (i.e., distinct, identified compounds after removing duplicates) and 101 unknown semi- and nonvolatile compounds, 1591 unique and 18 unknown volatile compounds, 9 unique PAHs, and 12 unique metals were observed. The five products from each product type with the highest number and concentration of extractables above the preestablished thresholds across all four analytical methods were examined in the leachable study. Closed ENDS had the greatest number of leachables (243 compounds), while LDPE and PET bottles had comparable numbers of leachables (53-65 compounds). In summary, this study details a comprehensive E&L analysis and peak identification approach for ENDS. These findings demonstrate that established pharmaceutical E&L methodology can be applied to ENDS components and e-liquid containers, and certain methodological parameters (e.g., selection of solvents and libraries) may need to be optimized for ENDS products.
Intracranial infections such as meningitis and brain abscesses remain difficult to diagnose early because of their nonspecific clinical presentation. Serum procalcitonin (PCT) has been identified as a promising biomarker for bacterial infections, but its diagnostic value in intracranial infections is not well defined. To systematically evaluate the diagnostic accuracy of serum PCT for detecting intracranial infections in adults. A meta-analysis of 10 studies was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Databases including PubMed, Scopus, Medline, and ClinicalTrials.gov were searched. Pooled sensitivity, specificity, and diagnostic accuracy were calculated using a random-effects model. The pooled sensitivity of serum PCT for diagnosing intracranial infections was 83% (95% confidence interval: 76-89), and the pooled specificity was 78% (95% confidence interval: 69-86). The summary receiver operating characteristic curve yielded an area under the curve of 0.86, indicating moderate diagnostic accuracy. Heterogeneity was moderate (I2 = 42%). PCT demonstrated good ability to identify patients with infection, though specificity varied across studies. Serum PCT shows moderate diagnostic accuracy for intracranial infections and can support, but not replace, standard diagnostic methods such as cerebrospinal fluid analysis and neuroimaging. Its greatest value lies in integration into a multimodal diagnostic strategy. Further prospective studies are warranted to define standardized cutoff values and optimize its clinical application.
BACKGROUND: Environmental exposures to toxicants, such as per- and polyfluoroalkyl substances (PFAS), during gestation can disrupt immune development, causing long-term impacts on a child's ability to generate a well-regulated, protective immune response. T-cells coordinate with all immune cell types to orchestrate both cellular and antibody-mediated responses. While there is compelling evidence that PFAS alters immunity in humans, the specific effects of early life PFAS exposure on infant T-cell development are unreported. Because of their central role in immunity, altered T-cell development in infants would have implications on immune responses broadly and long-term. OBJECTIVES: We seek to model longitudinal changes in the frequency of functionally distinct CD4+ T-cell subpopulations from birth through 12 months and their association with in utero PFAS exposure. METHODS: Maternal-infant dyads were recruited as part of the UPSIDE-ECHO cohort during the first trimester between 2015 and 2019 in Rochester, New York; dyads were followed through the infant's first birthday. Maternal PFAS concentrations (PFOS, PFOA, PFNA, PFHXS and PFDA) were quantified in serum during the second trimester using high-performance liquid chromatography and tandem mass spectrometry. Infant lymphocyte frequencies were assessed at birth, 6- and 12-months using mass cytometry and high-dimensional clustering methods. Linear mixed-effects models were employed to analyze the relationship between maternal PFAS concentrations and CD4+ T-cell subpopulations (n = 200). All models included a PFAS and age interaction and were adjusted for parity, infant sex, and prepregnancy body mass index. RESULTS: In utero PFAS exposure correlated with multiple CD4+ T-cell subpopulations in infants. The greatest effect sizes were seen in T follicular helper (Tfh) and T-helper 2 (Th2) cells at 12 months. A log2-unit increase in PFOS was associated with lower Tfh [0.17% (95% CI: -0.30, -0.40)] and greater Th2 [0.27% (95% CI: 0.18, 0.35)] cell percentages at 12 months. Similar trends were observed for PFOA, PFNA, PFHXS, and PFDA. DISCUSSION: Maternal PFAS exposures correlate with cell-specific changes in the infant T-cell compartment, including key CD4+ T-cell subpopulations that play central roles in coordinating well-regulated protective immunity. Future studies into the role of PFAS-associated T-cell distribution and the risk of adverse immune-related health outcomes in children are warranted.
This investigation examined the effect of plasma on the quality of wheat bran (WB). WB was treated with plasma at different applied powers (500-1000 W) and exposure times (15, 30, and 60 s). Micrographs displayed morphological changes in the treated samples. Plasma demonstrated the lowest and the best ratio of omega-6/omega-3 ratio and enzyme activity. Treated samples at lower power (500-700 W) showed the greatest enhancement in phytochemicals. The highest increases in total cinnamic and benzoic acid derivatives were observed at 600 W/60 s (216.09% and 1110.77%, respectively). Under the same conditions, total phenolic content and in vitro bioaccessibility were also highest, increasing by 258.29% and 264.52%, respectively, and total antioxidant activity increased by 94.61% compared with the control. Principal component analysis supported the efficacy of plasma as a nonthermal treatment to enhance WB quality, potentially supporting its use as a functional ingredient.
Acupuncture, a common intervention in traditional Chinese medicine (TCM), has been widely applied for regulating hormonal fluctuations in perimenopausal women. However, the efficacy of various acupuncture modalities is not comprehensively compared. This network meta-analysis (NMA) evaluated the effects of different acupuncture approaches on sex hormone levels, specifically estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), in perimenopausal women. PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang, and the VIP Database were searched until March 17, 2026. Randomized controlled trials (RCTs) on acupuncture interventions for perimenopausal women were included. The risk of bias was assessed for included studies, and data were synthesized based on a Bayesian NMA framework. 36 studies on 1, 480 participants were included. Compared with control interventions, acupoint application (AA) and acupuncture therapy (AT) significantly reduced Kupperman scores. In terms of FSH reduction, AA, abdominal moxibustion (AM), and AT were superior to control. For LH, AA, AT, and AM demonstrated notable reductions compared with control. As for E2 elevation, AA, AT, and compression acupuncture (PN) achieved statistically significant improvements. AM, AT, and AA significantly improved Kupperman scores, with AM being the most effective. Catgut implantation acupoint (CA) and PN showed significant effects in reducing FSH levels, followed by AT and AM, whereas plum blossom needling exhibited the greatest efficacy in increasing E2 levels. Overall, acupuncture presents a promising non-pharmacological strategy for modulating hormonal balance and alleviating menopausal symptoms in perimenopausal women. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251066613.
Predation risk for depleted prey populations is known to be influenced by prey abundance. However, predation risk may also be influenced by the abundance of sympatric prey species, particularly when the sympatric species is abundant. This suggests that predation risk estimates for low-abundance prey may also need to account for the abundance of sympatric species. To understand how sympatry between two prey species with differing abundances affects predation risk, we used an unstudied system in arid Southern California where the co-occurrence of federally Endangered Peninsular bighorn sheep (Ovis canadensis nelsoni) and southern mule deer (Odocoileus hemionus fuliginatus) is thought to affect the predation risk bighorn experience from pumas (Puma concolor). We characterized predation risk for bighorn and deer across their ranges to understand how topography, habitat, forage, and prey habitat suitability affect where pumas are likely to kill both species. The presence of the second ungulate species increased predation risk for both species, but had the greatest effect on bighorn, with predation risk strongly increasing with deer habitat suitability. The importance of deer habitat suitability to bighorn predation risk confirmed how spatial overlap between low and high abundance prey species can lead to increased predation risk, particularly for lower density ungulate populations. Our results provide more accurate estimates of bighorn predation risk, which is critical to the success of ongoing population recovery, and demonstrate how the density of sympatric species can be considered in population models and management.
Hypertension remains one of the leading causes of cardiovascular morbidity and mortality; however, patient adherence to treatment remains inadequate. In the context of a digital society, search queries can serve as an additional source of information regarding the population's information needs and patterns of interaction with medications. To conduct a comprehensive longitudinal infodemiological study of the Russian population's interest in angiotensin-converting enzyme (ACE) inhibitors based on an analysis of search queries for the period 2018-2025. A retrospective study was conducted using aggregated data from the Yandex search engine (Wordstat) covering 84 months. Search queries were analyzed for six major ACE inhibitors (captopril, enalapril, lisinopril, perindopril, ramipril, fosinopril), as well as for their brand names (21 drugs in total). We analyzed time series (Mann-Kendall test), seasonality (Kruskal-Wallis test), and variability, as well as performed multidimensional semantic analysis (Latent Dirichlet Allocation (LDA), Term Frequency-Inverse Document Frequency (TF-IDF) + k-means, k-medoids, n-grams). The total volume of analyzed queries exceeded 102 million. The greatest informational interest was identified for the captopril (30.1% of all queries), perindopril (27.9%), and enalapril (21.3%) groups. Perindopril demonstrated the strongest positive trend (τ = 0.762; p < 0.001). Statistically significant seasonality (p < 0.05) was observed for all six main International Nonproprietary Names (INN), with a peak during the winter months and a decline in activity during the summer. Semantic analysis revealed distinct differentiation in information patterns: captopril was associated with emergency use and sublingual administration, enalapril with manufacturer selection, lisinopril with searches for instructions and reviews, and perindopril with fixed-dose combinations. The proportion of queries related to emergency use was highest for captopril (0.53%) and lowest for the other drugs. Users' search activity reflects consistent differences in the perception of ACE inhibitors and demonstrates pronounced seasonal dynamics. The identified digital patterns may indirectly reflect medication-related information needs and potential gaps in the population's health literacy. The infodemiological approach represents a promising tool for monitoring patients' information needs and optimizing clinical communication and preventive programs.
Sex hormones exert profound effects on brain structure and function throughout the female reproductive lifespan. While previous studies have documented hormone-dependent changes in neuronal morphology and synaptic connectivity, the impact of oestrogen on brain tissue mechanical properties has been unexplored. Alterations to hippocampal microstructure are particularly sensitive to fluctuations in sex steroids, and studies in peripheral tissues reveal that oestrogen is a powerful modulator of tissue elasticity and organization. Here, we employed magnetic resonance elastography (MRE) to quantify whole-brain and hippocampal viscoelastic properties across the oestrous cycle in female rats in vivo and following targeted α oestrogen receptor antagonism. We demonstrate that hippocampal stiffness and damping ratio (viscosity) exhibit dynamic, phase-dependent fluctuations that correlate with hormonal status. Notably, hippocampal damping ratio, a measure of relative viscosity, increased by nearly 40% during the transition from proestrus to oestrus phases, mirroring the steep drop in oestrogen production that is characteristic of this phase progression. Pharmacological inhibition of oestrogen receptors with Fulvestrant prevented this cyclical change and instead maintained an elevated hippocampal damping ratio that was comparable to that measured during oestrus in normally cycling rats. Histological analyses revealed that these mechanical changes were accompanied by alterations in astrocyte and neuronal number, receptor expression and dendritic spine morphology in the CA1 subregion. Notably, oestrogen signalling was crucial for maintaining both astrocyte and neuronal populations and receptor density was elevated with the greatest effect on astrocytes (+48%) following Fulvestrant administration. These findings establish a mechanistic link between oestrogen fluctuations, cellular architecture and tissue mechanical properties in the female brain, offering novel insights into how reproductive endocrinology may influence hippocampal microstructure through mechanobiological pathways. Understanding these hormone-dependent mechanical changes may provide new therapeutic targets for addressing altered cognitive capacity associated with reproductive transitions and ageing in women.
The apolipoprotein E ε4 (APOE ε4) allele confers the greatest genetic risk for sporadic Alzheimer's disease (AD). To identify APOE ε4-associated metabolic factors related to AD risk and to provide preliminary insights into their biological and nutritional context. We leveraged multi-omics analyses across two independent cohorts to characterize biomarkers associated with AD. The effects of metabolite × APOE ε4 interactions were tested on incident AD and the ε4-specific metabolic signatures were pinpointed. Multimodal analyses were used to test the underlying mechanisms, including neuroimaging, cerebrospinal fluid (CSF), and PET biomarkers within the A/T/N framework, as well as plasma proteomics combined with bioinformatics enrichment analyses. Across both cohorts, valine emerged as the only metabolite associated with a reduced risk of incident AD specifically among APOE ε4 carriers (P < 0.005). Significant interaction effects between valine and APOE ε4 were detected in both cohorts (P for meta-analyses < 0.005). Higher levels of valine were associated with greater total white matter and posterior cingulate cortex volumes, as well as with lower levels of CSF tau proteins. Higher valine levels also predicted a slower decline in FDG-PET metabolism. No association was found between valine and Aβ. Mediation analyses of plasma proteomic data suggested statistically significant mediation effects involving GFAP, NEFL, and APOE (P < 2 × 10-16). Valine is a metabolite associated with lower AD risk in APOE ε4 carriers, with potential associations with tau pathology, neurodegeneration, and neuroinflammation-related processes. As this was an observational study, causality cannot be inferred.
Healthcare-associated infection (HAI) surveillance relies on standardized case definitions, yet variation in diagnostic criteria across surveillance frameworks may affect interpretation and comparability of infection indicators. Official surveillance manuals and guidance documents from 13 international, regional, and national HAI surveillance frameworks were reviewed. Seven systems with sufficiently detailed diagnostic criteria were included in a structured comparative analysis. Four infection categories (CLABSI, CAUTI, pneumonia, and surgical site infection) were evaluated across four diagnostic domains: clinical criteria, microbiological evidence, device/procedure association, and temporal thresholds. Seven surveillance systems yielded 52 surveillance definitions and 208 coded diagnostic elements. Comparative analysis identified variation in how surveillance frameworks operationalized clinical criteria, microbiological evidence, device/procedure association, and temporal thresholds. Device/procedure association and temporal thresholds were consistently specified, whereas microbiological requirements varied across infection types and surveillance contexts. Pneumonia definitions demonstrated the greatest heterogeneity in diagnostic specification across surveillance frameworks. Structural differences in surveillance definitions may influence how infections are identified and reported within surveillance systems, potentially affecting interpretation of benchmarking data and cross-system comparisons. Structural variation in HAI surveillance definitions should be considered when comparing infection indicators, implementing automated surveillance systems, or adapting surveillance frameworks across healthcare settings.