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Germinal center trajectories and transcriptional signatures define CLL subtypes and their pathway regulators
Chronic lymphocytic leukemia (CLL) is divided into unmutated (UM-CLL) and mutated (M-CLL) subtypes depending on somatic hypermutation (SHM) frequency in their immunoglobulin heavy chain V (IGHV) region. We previously demonstrated that CD27 bright memory B cells (MBCs) are germinal center (GC)-dependent with higher mutation rate, whereas CD27 dull MBCs accumulate fewer mutations and originate independently from the GC. We conducted a meta-transcriptomic analysis on bulk RNA data from 116 individuals combining four CLL cohorts and healthy B cell subsets (naïve, CD27 dull and CD27 bright MBCs) to decipher the transcriptional and mechanistic functions of CLL subtypes. CD27 bright MBCs showed more transcriptional similarity to M-CLL rather than UM-CLL. Functional enrichment analysis revealed that LPL , ZNF667 and ZNF667-AS1 are potential informative biomarkers for stratification of CLL subtypes. They are part of the mechanistic regulatory pathways of CLL pathology through cholesterol and Epithelial Mesenchymal Transition (EMT) regulation. We applied markers for the GC B-cell substages to map in silico the CLL cohorts to their potential GC B cell counterpart. UM-CLL represented transcriptional mimicry to an early intermediary GC substage whereas M-CLL mimicked later substages in the GC. This could potentially explain the IGHV mutational status of M-CLL as well as hypothesize that CLL subtypes could derive from a GC-dependent pathway.
A Crystalline Monomeric Diboryl Diazene
Macro-micro mechanisms of void formation and grouting strength reinforcement in concrete pavement slabs using FEM-DEM coupling method
Abstract Growing traffic and heavier vehicle loads cause voids beneath concrete pavement, significantly degrading road performance and safety. This study aimed to investigate the mechanical behavior of concrete pavement with voids and evaluate the effectiveness of grouting reinforcement. Researchers calibrated concrete surface and base layer parameters using uniaxial compression simulations and then developed a numerical model of concrete pavement void formation utilizing the FEM-DEM coupling method. The structure experienced initial cracking at approximately 76.6 kN, the load continued to increase to a peak of 139 kN, and after the peak the curve entered a descending branch, indicating that the structure began to degrade after reaching its ultimate bearing capacity. Analysis of displacement, crack patterns, and force chains revealed shear bands developing on either side of the void. A simulated grouting reinforcement, using 9,800 particles (0.5 mm diameter), demonstrated significant improvement, with the peak strength reaching 220 kN, representing a 58.3% increase. Enhanced load transmission, crack and displacement distribution, and force chain transfer confirmed the effectiveness of grouting in strengthening structural performance. This research provides vital theoretical support for addressing concrete pavement void issues.
Pragmatic, quasi-experimental, pseudo-randomized clinical trial to assess the impact of patient safety monitors on clinical and patient safety outcomes: The Akershus Clinical Trial (ACT) 1
Background The Norwegian National Action Plan for Patient Safety and Quality Improvement recommends implementing electronic patient safety monitors (PSM) in Norwegian hospitals. We hypothesized that PSM implementation would reduce hospital length of stay, with secondary endpoints related to clinical and patient safety outcomes. Methods We performed a retrospective single-center, pragmatic, quasi-experimental, pseudo-randomized controlled trial assessing differences in endpoints for patients admitted before (control group: years 2019–2020) and after PSM implementation (intervention group: years 2021–2022) in two orthopedic bays in a Norwegian teaching hospital. To account for temporal changes unrelated to PSM, we assessed the same endpoints for 2019–2020 vs. 2021–2022 in two orthopedic bays that did not implement PSM. Data extraction from the local data warehouse was controlled according to internal standards, and we predefined all statistical analyses. Results The intervention group (n = 2786) and the control group (n = 2610) were evenly distributed for baseline characteristics, including age (median 73 [quartile 1–3 55–83] vs. 72 [55–83] years, p = 0.29), female sex (76.2% vs. 76.4%, p = 0.96), and Charlson Comorbidity Index (p = 0.24). Median hospital length of stay was 4.4 (2.1–7.7) days after implementation of PSM compared to 4.3 (2.0–7.2) days in the control group (p = 0.046 for difference between the groups). Nutritional screening and fall screening within 24 hours were lower in the intervention group compared to the control group, while medical reconciliation during the hospital stay was higher in the intervention group. We found no differences between the groups in 30-day or 1-year readmission or mortality rates. Hospital length of stay was similar in 2021–2022 vs. 2019–2020 for the bays that did not implement PSM. Conclusion The implementation of PSMs in this study did not improve clinical or patient safety outcomes. Hospital length of stay was statistically longer after PSM implementation, although the difference was not clinically relevant.
An Inverse Electron-Demand Diels–Alder Approach to Selective Activity-Based Sensing of Acetaldehyde in Living Cells
Visual feature-based multi-scale hybrid attention network for fine-grained Hawthorn varieties identification
How urban residential land transfer policies affect the housing market—evidence from Beijing, China
The stable and healthy development of the residential market has always been one of the important tasks of the Government, and is of great significance to the maintenance of social stability and the well-being of residents. This paper utilizes the VAR model, the housing filtering model and the four-quadrant theoretical model to explore the comprehensive impact and mechanism of the land supply system on China’s housing market from the logical framework and institutional environment of land and housing. The results of the study show that the price of residential land supply has a positive effect on house prices, while the quantity of residential land supply has a negative effect on house prices; The land transfer patterns of “Restricted Land Price, on-site Lottery” and “Restricted Land Price, Restricted Selling Price and Compete for Quality” are conducive to the healthy development of the real estate market, but an excessive supply of land for leasing may push up the prices of commercial properties. Finally, in combination with China’s policy objective of “stabilizing land prices, housing prices and expectations”, it puts forward a number of policy recommendations to rationally control and guide the healthy development of real estate.
Excited State Dynamics of CO <sub>2</sub> Reduction Catalyst under Vibrational Strong Coupling
Spatial–temporal variations of river water quality under human-induced land use changes in large river basins
Abstract Land use patterns and anthropogenic activities exert diverse impacts on river water quality and ecosystem health across spatial and temporal scales. Under ongoing pressures from human activities and climate change, it is urgently needed to understand the pollution mechanisms and associated ecological risks in surface waters through cross-basin assessments that incorporate a broad set of water quality parameters. This study investigated the spatial–temporal variations of 22 water quality parameters, including physico-biochemical indicators, nutrients, and heavy metals, at 39 sampling sites across the Daliao River (DLR), Shuangtaizi River (STR), and Naoli River (NLR). Field observations were conducted in September 2019, December 2020, and June 2020, covering the wet, dry, and agricultural seasons to assess the influencing mechanisms of natural factors and human activities on river water quality and human health. Principal Component Analysis revealed a notable seasonal variation in water quality components for DLR and STR, which indicated substantially high concentrations of TN, NO 3 - and NH 4 + in the dry season. The heavy metal risk for children was calculated at 8.44E-05 year -1 in NLR during the agricultural season, which exceeded the maximum acceptable limit, with carcinogenic arsenic being the primary contributor. Redundancy analysis (RDA) was employed to examine the influence of land use patterns on water quality across different seasons and spatial scales. DO and COD showed a strong correlation with dry land and woodland, while nutrients and Chl-a were strongly correlated with paddy fields and building areas. This study underscores the critical role of land use management in harmonizing development with ecological sustainability and provides scientific evidence supporting the achievement of Sustainable Development Goal 6 (SDG 6), which focuses on clean and safe water.
Association between dietary B vitamins intake and age-specific blood pressure: A cross-sectional study in American adults
Objective To explore the relationship between B vitamins and blood pressure across distinct age groups. Methods We analyzed 3654 participants aged ≥20 years after excluding pregnant/lactating individuals and those with incomplete data. B-vitamin intake was calculated from two 24-hour dietary recalls and supplement surveys. Exposure variables included 7 kinds of B vitamins intake, while outcomes comprised hypertension prevalence, systolic and diastolic pressure. The covariates include basic demographics, lifestyle factors, chronic Comorbidities, and nutrient intake. Based on the cross-sectional study, the statistical analyses incorporated NHANES sampling weights. Weighted logistic regression evaluated hypertension association, while linear regression assessed systolic/diastolic pressure differences. RCS model explored nonlinear dose-response relationships. Results Weighted logistic regression and RCS model revealed age-specific and nonlinear characteristics in the b vitamin–blood pressure relationship. Vitamin B1 was negatively correlated with hypertension in ≥60 years old (Q4: Q1 OR (95%CI) =0.27 (0.08, 0.91)). Vitamin B2 was negatively correlated with hypertension in total population at Q4 (OR (95%CI) =0.39 (0.15, 0.99)), and in aged 40–59 years, OR (95%CI) =0.52 (0.33, 0.83). Choline was positively correlated with hypertension in the total population (OR (95%CI) =1.30 (1.08, 1.58)) but negatively correlated with ≥60 years old (OR (95%CI = 0.73 (0.56, 0.95)). Vitamin B12 shown positive associations with hypertension in the total population, 20–39 years old and ≥60 years old OR (95%CI) =1.39 (1.13, 1.71), 1.82 (1.23, 2.69), and 1.63 (1.04, 2.54), respectively. For diastolic pressure, vitamin B1, B2, niacin, B6, and folate displayed significant negative associations in the total population and ≥60 years old. Vitamin B2 was also negatively associated in 40–59 years old. Vitamin B12 exhibited a negative association with diastolic pressure in ≥60 years old. Weight RCS analysis revealed the linear or nonlinear relationships between specific B vitamins and hypertension and systolic/diastolic pressure, with age stratification improving the discernment of these associations. Conclusions Associations between B vitamins intake and hypertension/blood pressure exhibited age-dependent variations. Age-specific considerations are essential for optimizing B vitamins supplementation or restriction.
Dynamic Shape Modulation of Deflated and Adhered Lipid Vesicles
Pharmacokinetics and in vivo efficacy of epetraborole against Burkholderia pseudomallei
Three-year assessment of cadmium exposure and bone mineral density changes in cadmium-contaminated areas in northwestern Thailand
Chronic cadmium exposure is linked to bone loss, but its effect on the short-term progression of bone mineral density (BMD) in previously exposed populations is not well understood. This study aimed to investigate the association between baseline urinary cadmium (U-Cd) levels and the subsequent three-year change in BMD in a chronically exposed cohort in northwestern Thailand. We conducted a three-year longitudinal study of 393 residents (40 men, 353 women) aged 35 and older. Baseline (2019) U-Cd was the primary exposure, and BMD at the calcaneus was measured in 2019 and 2022. Dual-energy X-ray absorptiometry was used for BMD measurements and atomic absorption spectrometry for U-Cd analysis. The mean U-Cd levels in males (7.18 ± 1.35 μg/g creatinine) were significantly higher (p < 0.001) than in females (3.68 ± 2.13 μg/g creatinine). This study found a statistically significant decrease in BMD in the group with the lowest U-Cd levels (<2.0 μg/g creatinine, p = 0.001) and in the overall sample (from 0.392 ± 0.079 μg/g creatinine in 2019 to 0.384 ± 0.094 μg/g creatinine in 2022, p = 0.004). However, no statistically significant changes were observed in groups with U-Cd levels above 2.0 μg/g creatinine. Osteoporosis prevalence remained stable in both males and females. The Linear Mixed-Effects Model analysis revealed significant associations between BMD and several factors: increasing age, female sex, diabetes status and BMI. Age and female sex were negatively associated with BMD, while BMI showed a positive relationship. U-Cd levels were not significantly associated with BMD changes over the three-year period (coefficient = −0.002, p = 0.073), though a slight downward trend in BMD was observed across all cadmium exposure levels. This study underscores the complexity of cadmium’s effects on bone health and emphasizes the need for longer-term follow-up studies to better understand the potential cumulative impact of cadmium exposure on BMD.
Principal component guided DCGAN for mitigating mode collapse in electromagnetic pulse signal synthesis
Respiratory incidents in response to air quality deterioration in the summer and early autumn season
The paper presents the results of an ecological study completed within the warm seasonal period of 01/07/2024–31/10/2024. The aim is to assess the relationship between ambient air quality deterioration and acute respiratory incidents occurring in the inhabitants of Gliwice (Poland; Upper Silesian agglomeration). The number of daily medical services (MS) due to respiratory diseases and illnesses was obtained from the register of the National Health Fund (Silesian Voivodeship Branch in Katowice). The daily mean values of aerosanitary factors in Gliwice came from the mobile air pollution laboratory of the Silesian University of Technology in Poland. The relative risk ( RR ) of MS was estimated using a Poisson log-linear model considering independent environmental factors (meteorological factors and air pollutant concentrations) or confounding factors (astronomical season and day of the week). The highest number of MS due to respiratory diseases refers to acute nasopharyngitis and asthma exacerbation, mostly in children aged 0–9 years. A significant impact was observed in the case of particulate matter concentration increase and number of MS due to acute nasopharyngitis, laryngitis and tracheitis, pneumonia, asthma exacerbation, in the case of nitrogen oxides appropriately acute nasopharyngitis, bronchitis and/or bronchiolitis, pneumonia, asthma exacerbation. Additionally, a longer time of exposure was associated with a higher risk of MS due to respiratory incidents. The increase in wind speed and relative humidity was significantly associated with a higher number of bronchitis and asthma exacerbation while a higher temperature and higher 8-hour ozone concentration remain protective of both MS. The results are essential for effectively communicating environmental health risks, educating the public about potential threats, and pressuring legislators responsible for legislation and risk management.
Photochemical Generation and Characterization of Alanine Imine: A Key Intermediate in Prebiotic Amino Acid Formation
Later-life migration and depression among older adults in India: examining the role of functional limitations
Abstract The prevalence of depression is increasing in low- and middle-income countries (LMICs) such as India; migration is often associated with this rise. Nevertheless, there is limited knowledge about the moderating effect of functional limitations in the association between age at migration and depression in the middle and old age population. This study aimed to examine how functional limitations moderate the association between age at migration and depression in older adults in India. We utilized Longitudinal Aging Study in India data, comprising a sample of 61,855 adults aged 45 and above. Depression was the outcome variable. We employed negative binomial regression and interaction analyses to fulfill the study objective. Migrants (9.94) reported higher mean depressive scores than non-migrants (9.44). Migrants with Activities of Daily Living limitations (ADL) who migrated at a younger age (< 20 years) had 1.12 times higher risk, those at the age of 20–39 had 1.13 times higher risk, and those who migrated at the age of 40–59 had 1.15 times higher risk of depression than their non-migrant counterparts without any ADL limitations. The findings suggest that migrating at older ages comes with a higher psychological risk. Functional limitations significantly amplify the development of depression among migrants. The results advocate specific interventions aimed at reducing psychological stress among migrants who migrate at later ages and have functional limitations.
Association of ultrasound-assisted combined with conventional anatomical landmark paramedian spinal anesthesia and its impact on first pass success rate in patients with lower limb fractures- A retrospective cohort study
Background The association between ultrasound-assisted combined with conventional anatomical landmark paramedian spinal anesthesia regarding the first-pass success rate remains contentious. This study aims to clarify this relationship. Methods In this retrospective cohort analysis of 146 patients with lower limb fractures, patients were divided into two groups based on their spinal anesthesia technique:ultrasound-assisted combined with conventional anatomical landmark (median or paramedian). The primary endpoint was the first-pass success rate, while secondary endpoints included total procedure time and discomfort score. Recorded covariates encompassed sex, age, BMI, ASA class, preoperative preparation time, pre-injury physical activity, number of needle insertions, pain intensity (VAS), satisfaction score, puncture-related pain, and postoperative low back pain. Outcomes were evaluated via logistic regression. Results After adjusting for potential confounders, the ultrasound-assisted paramedian approach demonstrated a significantly higher first-pass success rate (OR = 6.11, 95% CI 2.09–17.86, P = 0.001). Secondary benefits included reduced procedure duration and improved patient comfort. Sensitivity analysis using propensity score matching confirmed the robustness of the results (E-value = 4.379), indicating minimal influence from unmeasured confounders. Conclusions In patients with lower limb fractures, ultrasound-assisted paramedian spinal anesthesia using anatomical landmarks increased first-pass success rates, reduced procedural time, and improved patient comfort compared to the median approach.