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Trans-synaptic molecular context of NMDA receptor nanodomains
GPER1 is involved in shaping tumor immune microenvironment and its expression is decreased in NSCLC tumorigenesis
Network biomarkers of Alzheimer’s disease risk derived from joint volume and texture covariance patterns in mouse models
Alzheimer’s disease (AD) lacks effective cures and is typically detected after substantial pathological changes have occurred, making intervention challenging. Alzheimer’s disease (AD) intervention requires early detection of risk factors and understanding their complex interactions before substantial pathological changes manifest. Current research often examines individual risk factors in isolation, limiting our understanding of their combined effects. We present a novel multivariate analytical framework to simultaneously assess multiple AD risk factors using mouse models expressing human ApoE alleles. Our methodological innovation lies in combining high-resolution magnetic resonance diffusion imaging with a comprehensive multifactorial analysis that integrates genotype, age, sex, diet, and immunity as interacting variables. This approach enables the simultaneous examination of regional brain volume and fractional anisotropy changes across multiple risk factors, providing a more holistic view than traditional univariate analyses. Our proposed method effectively identified how these factors converge on specific brain regions – with genotype influencing the caudate putamen, pons, cingulate cortex, and cerebellum; sex affecting the amygdala and piriform cortex; and immune status impacting association cortices and cerebellar nuclei. Importantly, our integrated approach revealed factor interactions that would remain undetected in single-variable studies, particularly in the amygdala, thalamus, and pons. While many findings align with previous research, our multidimensional framework offers a methodological advancement for studying AD risk factors by modeling their combined effects rather than isolated impacts. This approach creates a template for future studies to investigate mechanisms underlying coordinated changes in brain structure through network analyses of gene expression, metabolism, and structural pathways involved in neurodegeneration.
Normal meiosis in the fungus Sclerotinia sclerotiorum despite the irregular distribution of haploid chromosomes between two nuclei
Analysis of blood biomarkers and sports performance in crossfit athletes using the elevation training mask 2.0 post SARS-CoV-2 infection
A machine learning approach for estimating forage maize yield and quality in NW Spain
Crop models simulate crop growth and development according to different climatic, soil and crop management conditions. The CSM-CERES-Maize model (DSSAT) was adapted to simulate forage maize yields by calibrating the genetic parameters of six cultivars: SE1–200, SE2–300 and SE3–400 in three sites and three years in Asturias, and XU1–220, XU2–300 and XU3–400 in four sites and three years in Galicia. Calibration using the CSM-CERES-Maize model, together with the use of historical meteorological data (2000–2022) from the study sites, enabled simulation of forage maize yield (whole plant dry matter yield) and quality (whole plant net energy for lactation yield and whole plant crude protein yield) for six cultivars during the 23-year period. LightGBM models (a machine learning technique) were used with the simulated forage maize yield, quality data, historical weather, soil, and management data to capture non-linear relationships in the data and to identify the most influential variables for crop yield and quality predictions. The results of the model evaluation yielded an accuracy of 94.7%, (R2 score = 0.86) for forage maize yield, an accuracy of 94.0% (R2 score = 0.84) for the net energy for lactation yield and an accuracy of 93.0% (R2 score = 0.85) for the crude protein yield. Variable importance plots revealed Growing Season and Radiation from sowing to harvest to be the top two most influential predictor variables. In Asturias and Galicia, the cultivars with the longest cycle (cultivars cycle 400) are those with the highest values for the variables studied in the 23 years of historical meteorological data (average of three sites in Asturias and four sites in Galicia with three sowing dates in each site). The models will be available to make predictions for forage maize yield and quality by non-specialist users, using the geographical location of the crop field, cultivar type, sowing and harvest date and probable values of weather variables during the growing season as input data.
A clonally expanded nodal T-cell population diagnosed as T-cell lymphoma after CAR-T therapy
Abstract Reports of secondary malignancies after chimeric antigen receptor (CAR)-T and possible CAR-T derived malignant transformation necessitate caution. Here we describe a patient with diffuse large B-cell lymphoma who developed new lymphadenopathy 2.5 years after CAR-T in the context of COVID-19 infection with histopathologic features consistent with T-cell lymphoma (TCL). Deep molecular interrogation with genomic sequencing and single-cell spatial transcriptomics reveals a highly proliferative clonal T-cell population co-expressing CD4 and CD8 with biallelic TCR rearrangement and no evidence of the CAR construct. The expanded clonotype displayed T follicular helper (TFH) cell transcriptomic programs and occupies immune-excluded spatial niches within the lymph node, supportive of TFH-like neoplastic T cell behavior. Remarkably, the lymphadenopathy spontaneously resolved on interval imaging. Our data underscore the need for better understanding of post-CAR-T clonal T-cell lymphoproliferative disorders to avoid unnecessary treatment and higher specificity in diagnostic methods for TCL.
Surface morphology effects on droplet spreading and rebound dynamics on subcooled superhydrophobic surfaces
Abstract Subcooled superhydrophobic surfaces have notable applications in aerospace, energy, and refrigeration industries. Superhydrophobic behavior can be achieved with different microscale surface morphologies which can impact the water repellency and icephobicity of the surface. To comprehensively study how surface microstructure influences the spreading, rebounding, and freezing behavior of impacting droplets at various surface temperatures and droplet velocities, several types of surfaces were prepared within this study. Specifically, the effect of structure depth (approx. 3–30 μm) and of the structure type (randomized structure or directional microchannels) was investigated by preparing deep and shallow laser-made structures with either stochastic or deterministic features. Droplet impact tests were performed at Weber numbers between 50 and 185 and across surface temperatures from 25 °C to -30 °C. Surface morphology had a minimal effect on the maximum spreading factor, which was otherwise found to decrease by up to 9.5% when reducing the surface temperature from 25 °C to -30 °C. High-speed imaging revealed that the poorest rebound performance across all surfaces occurred at We ≅ 120, where the transition from the regular rebound to the splashing regime led to a higher prevalence of partial rebounds or full adhesion compared to We ≅ 50 or We ≅ 185. An average contact time of 11.1 ms was recorded across all four superhydrophobic surfaces and was largely independent of the surface microstructure. Under subcooled conditions with possible phase change, surface micro-/nanostructure affects droplet impact dynamics beyond static wetting consideration. Our findings show that microstructure depth and solid-liquid contact fraction significantly influence droplet rebound and/or adhesion on subcooled surfaces. Contact times increased significantly as the surface temperature was decreased and partial adhesion of the droplet was detected if the contact time exceeded ~ 20 ms. Higher relative humidity led to frost formation and hence to greater energy dissipation and droplet pinning during the receding phase, preventing a full rebound, which was independent of the surface morphology. Overall, shallow-featured surfaces exhibited superior water repellency at subcooled temperatures, attributed to their lower solid-liquid contact fraction.
The feasibility of the virtually delivered dementia lifestyle intervention for getting healthy together (DELIGHT) program for people living with dementia and their family/friend care partners
Background Improving supports to enhance quality of life for people living with dementia is a priority of research and practice. The DEmentia Lifestyle Intervention Program for Getting Healthy Together (DELIGHT) was co-designed by people with dementia, care partners, community stakeholders, and researchers with the goal of promoting ‘living well’ with dementia. Objective A mixed methods study design was used to assess the feasibility of the 8-week virtual DELIGHT program, which incorporates group exercise and shared learning on topics related to health and wellbeing. Methods Feasibility was evaluated through recruitment rate, attendance, and retention, along with semi-structured interviews that probed the program impact and recommended changes. Interviews were transcribed and analyzed using thematic analysis. Quality of life, physical activity, balance confidence, exercise self-efficacy, nutrition risk, social connection, balance, and strength were also assessed pre- and post-program. Results A total of 19 participants were recruited to the two virtual program offerings (average of 4.75 participants/month). Of these, 17 (89.5%) completed the pre- and post-program evaluations. Average attendance was 78% demonstrating feasibility of the program. Four themes related to the impact of and satisfaction with the DELIGHT program were identified: Creating and Strengthening Connections described the sense of community felt among participants and study leaders, Sharing Knowledge and Learning described participants enjoyment in learning from one another and sharing their own valuable knowledge, Motivation to Improve Health and Wellbeing described improvements in participants’ functional abilities and motivation to continue healthy habits beyond the program, and Providing Hope and Challenging Stigma described a mindset shift to believing in the possibility of living well with dementia and challenging stigma. Conclusion DELIGHT is a feasible lifestyle intervention for people living with dementia and their care partners. Further research to evaluate the feasibility of the in-person DELIGHT program and the effectiveness of both in-person and virtual offerings is warranted.
Reconciling flexibility and efficiency: medial entorhinal cortex represents a compositional cognitive map
Preparation and characterization of chitosan clay beads for water adsorption
Exploring the association between socioeconomic status and cardiopulmonary exercise testing measures: A cohort study based on routinely collected data
Background Cardiopulmonary exercise testing (CPET) provides objective measures of cardiorespiratory fitness and can support surgical risk stratification. As socioeconomic status is a factor known to influence patient health and outcomes, we analysed how CPET-derived measures vary across levels of socioeconomic status in patients being considered for elective surgery. Methods A database of patients who underwent CPET between 2011 and 2024 was analysed. Measures including oxygen consumption (V̇O₂) at gas exchange threshold (GET), peak V̇O₂, and ventilatory equivalent for carbon dioxide (VE/V̇CO₂) were compared across socioeconomic deprivation quintiles. Multivariable linear and logistic regression models assessed the effects of age, sex, body mass index (BMI), Revised Cardiac Risk Index (RCRI), and deprivation quintiles on CPET measures. Hierarchical regression models incorporating the Indices of Deprivation (IoD) domains and Access to Healthy Assets and Hazards (AHAH) scores determined whether wider social determinants of health explained the variance in CPET measures. Results A total of 3344 patients (2476 male) were included, referred prior to procedures in vascular (2006), colorectal (650), upper GI (267), urology (205), and other (216) surgical specialties. Lower socioeconomic status was associated with younger age (p < 0.001), higher BMI (p = 0.022), higher smoking prevalence (p < 0.001), and RCRI ≥3 (p = 0.013). CPET measures were lower in the most deprived quintile (Q1) compared to the least (Q5): mean GET was 11.0 vs. 11.5 ml·kg-1·min-1 and peak V̇O2 was 14.8 vs. 16.3 ml·kg-1·min-1 (p < 0.05). Deprivation remained an independent predictor of lower GET and peak V̇O2, even after adjustment. Several IoD and AHAH domains explained small but significant variance in CPET measures. Conclusion Patients from more deprived areas exhibit risk factors for poor health and lower cardiorespiratory fitness as measured by CPET. These findings add to our understanding of socioeconomic disparities in physiological reserve among surgical patients and may support the need for more holistic approaches to peri-operative care.
Mapping the coupling between tract reachability and cortical geometry of the human brain
RB1 expression and HR proficiency define a poor prognosis subtype of high grade serous ovarian cancer
Abstract High-grade serous ovarian carcinoma (HGSOC) is a molecularly heterogeneous and lethal malignancy, with late-stage diagnosis contributing to high risk of recurrence and poor clinical outcomes. Although homologous recombination (HR) deficiency and retinoblastoma gene ( RB1 ) expression have been implicated in prognosis, their combined role in shaping tumor biology and survival outcomes is not well defined. To investigate the relationship between HR status and RB1 expression and explore their potential as a combined prognostic marker, we analyzed data from two cohorts: (1) 272 HGSOC cases from The Cancer Genome Atlas (TCGA) with RB1 mRNA expression data and HR status previously annotated by Takaya et al. (HR-deficient, HRD; HR-proficient, HRP), and (2) 226 clinical HGSOC cases profiled by comprehensive genomic and immune profiling (CGIP) at OmniSeq, categorized as either HR-intact (HRi) or harboring BRCA1/2 alterations (BRCAa). Cases were additionally stratified according to RB1 mRNA expression level as RB1-high (> 25th percentile; RBH) or RB1-low (≤ 25th percentile; RBL). HRP-RBH tumors ( n = 120, 44.1%) were associated with significantly worse overall survival (OS) and progression free survival (PFS) compared to all other subgroups. Survival metrics were evaluated from the TCGA cohort and demonstrated that median OS for HRP-RBH was 35.9 mo, shorter than HRP-RBL (52.0 mo), HRD-RBL (57.1 mo), and HRD-RBH subgroups (53.3 mo; all p < 0.0001). PFS demonstrated a similar trend (15.1 mo vs. 20.6, 20.2 and 20.4 mo, respectively, p = 0.0021). HRP-RBH tumors also showed higher aneuploidy scores (median 18 vs. ≤ 10.5 in other subgroups, all p < 0.01). From the OmniSeq cohort, HRi-RBH tumors exhibited a distinct immune gene signature, including elevated mRNA expression of 213 differentially expressed genes and enrichment of pathways such as EMT, PI3K/AKT signaling, and interleukin signaling. Overall, this study suggests that molecular subtyping of HGSOC based on HR status and RB1 expression may provide valuable prognostic insight. HRP tumors with high RB1 expression represent a high-risk subgroup with a distinct molecular profile and poor clinical outcomes, underscoring the need for novel therapeutic strategies targeting this aggressive subset. These findings provide a foundation for future studies aimed at developing biomarkers and treatments tailored to this challenging subset of HGSOC patients.
Enhancing gutta-percha with silver mesoporous calcium silicate nanoparticles for advanced endodontic applications
Aim This study aimed to develop a modified gutta-percha (GP) multifunctional endodontic material by incorporating mesoporous calcium silicate nanoparticles (MCSNs) or silver-incorporated mesoporous calcium silicate nanoparticles (Ag-MCSNs) as bioactive nanoparticle fillers to enhance bioactivity, biomineralization, and radiopacity while achieving low cytotoxicity and improved antibacterial activity. Methodology MCSNs and Ag-MCSNs were synthesized and incorporated into GP at concentrations of 1%, 5%, and 10% by weight. The chemical and structural characterization of the new GP materials was performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy-dispersive spectrometry (EDS), and field emission-scanning electron microscopy (FE-SEM) to assess filler distribution. Biomineralization was evaluated using XRD, EDS, and scanning electron microscopy (SEM). Ion release, pH changes, MTT assays, and culture-based techniques were employed to assess bioactivity, biocompatibility, and antibacterial properties. Finally, radiopacity testing was conducted. Results All samples of the newly developed GP exhibited uniform particle distribution within the GP matrix. Bioactivity and biomineralization tests revealed hydroxyapatite (HA) layer precipitation at 3, 7, 14, and 28 days, with maximum HA formation observed with prolonged immersion. Samples containing MCSNs or Ag-MCSNs created a weakly alkaline microenvironment initially, maintaining a suitable pH over time. All groups demonstrated non-cytotoxicity, with cell viability exceeding 70%. Antibacterial tests showed larger inhibition zones in all experimental groups compared to the control, with GP containing 10% MCSNs or Ag-MCSNs exhibiting the highest antibacterial activity, particularly Ag-MCSNs. Radiopacity tests indicated no significant difference between the experimental and control groups. Conclusion Gutta-percha materials incorporated with 10% MCSNs or Ag-MCSNs demonstrated enhanced bioactivity, biomineralization, and antibacterial properties compared to the control GP, while maintaining suitable levels of biocompatibility in accordance with ISO 10993/2009 standards. The incorporation of Ag-MCSNs significantly improved antibacterial effects, particularly against Enterococcus faecalis, and increased radiopacity, making it a promising material for root canal therapy.
Comparative genomic analyses reveal different genetic basis of two types of fruit in Maloideae
Automated home-cage-like monitoring for assessing innate behaviors in a murine hangover model
What is the impact of structural changes in society on diabetes self-management and trajectories of HbA1c? A cohort study before, during and after the COVID-19 pandemic in people with diabetes treated at outpatient clinics
Background The impact of COVID-19-related changes in diabetes self-management and trajectories of HbA1c throughout COVID-19 is not fully understood. Here, we describe HbA1c trajectories, changes in diabetes self-management and their association before, during and after the COVID-19 pandemic (2019–2022). Methods During the spring of 2021, we invited 13,641 outpatients from diabetes clinics in the Region of Southern Denmark to complete a questionnaire regarding changes in diabetes self-management during COVID-19. We linked the questionnaire and registry HbA1c data from before, during and after the COVID-19 pandemic and conducted multivariable adjusted linear mixed-effect regression to assess the association between changes in diabetes self-management and HbA1c. Results 5,581 (40.9%) people responded to the questionnaire (median age: 65 years, males: 59.7%). HbA1c decreased in people with type 2-diabetes and was unchanged for people with type 1-diabetes (interaction: p < 0.001). The majority of people reported unchanged diet (65–71%) and usual medication taking (89–90%). No changes in physical activity were reported by 43%, while 42% reported decreased physical activity. HbA1c trajectories did not differ according to change in physical activity and change in diet intake, while taking medication more regularly was associated with a decrease in HbA1c, from approximately 65/66 mmol/mol (8.1/8.2%) to 60/61 mmol/mol (7.6/7.7%) in both diabetes types. Conclusions During COVID-19, HbA1c trajectories differed between diabetes types. Most of the sample maintained usual diabetes self-management, although some decreased physical activity levels. Improved medication taking was associated with decreased HbA1c. This information is crucial for health professionals, in order to provide support aimed at reducing HbA1c.