Continuation of oral anticoagulation (OAC) after successful atrial fibrillation (AF) ablation remains debated. With recent randomized controlled trials addressing this question, an updated meta-analysis is needed to inform clinical decision-making. A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, and Scopus was performed through 24 November 2025, to identify studies comparing clinical outcomes in patients who continued vs. discontinued OAC after AF catheter ablation. Overall, continuing OAC was not significantly associated with the risk of stroke/TIA (OR: 1.48, 95% CI: 0.84-2.60; P = 0.16). However, when stratified by CHA2DS2-VASc score, patients with scores ≥2 had a significantly lower risk of stroke/TIA with OAC continuation (OR: 0.42, 95% CI: 0.18-0.95; P = 0.04). This protective effect was further supported in studies with well-balanced baseline risk between groups, where OAC continuation was associated with a significantly lower risk of stroke/TIA (OR: 0.50, 95% CI: 0.34-0.72; P < 0.01). Conversely, OAC continuation significantly increased the risk of major bleeding. No significant association was observed for major adverse cardiac events or all-cause mortality. In patients with CHA2DS2-VASc scores ≥2, particularly when baseline risk is well-balanced between groups, continuation of OAC after AF ablation is associated with a significantly lower risk of stroke/TIA. These findings support continuing OAC in higher-risk patients (CHA2DS2-VASc ≥2). However, given the significantly increased risk of major bleeding associated with OAC continuation, the decision to continue anticoagulation in lower-risk patients requires careful consideration, as no clear thromboembolic benefit was observed in this population.
Mafb and c-Maf transcription factors (TFs) are expressed in medial ganglionic eminence (MGE) lineages, beginning in progenitors and continuing into mature GABAergic parvalbumin-positive (PV+) and somatostatin-positive (SST+) cortical interneurons (CINs). Deleting Mafb and c-Maf in MGE before SST vs PV fate specification causes developmental anomalies, including altered numbers of CINs and seizure phenotypes, but the specific contributions of these TFs in postmitotic SST+ and PV+ CINs to epilepsy remain unknown. To address this, we conditionally deleted Mafb or c-Maf in SST+ or PV+ interneurons after interneuron fate specification in female and male mice. Deletion of c-Maf, but not Mafb, in SST+ cells was associated with reduced synaptic excitation onto these cells and with spontaneous spike-and-wave discharges, consistent with absence-like seizures. In contrast, deletion of Mafb in SST+ CINs reduced their density in superficial cortical layers but did not induce epilepsy. Neither c-Maf nor Mafb deletion in PV+ CINs produced major electrophysiological or histological abnormalities in the somatosensory cortex. These findings identify a specific requirement for c-Maf in modulating synaptic excitation of SST+ interneurons and show that its loss in SST+ cells is associated with the development of absence-like epileptiform activity in vivo. Together, our results refine the understanding of how transcriptional programs shape interneuron function in the mature cortex and highlight c-Maf/MAF-dependent pathways as candidates for investigation in epilepsy genetics.Significance Statement Disruptions in cortical circuit development and function are linked to neurodevelopmental disorders. Cortical interneurons (CINs), particularly the two major subtypes-somatostatin-positive (SST+) and parvalbumin-positive (PV+) cells-help maintain excitation/inhibition balance. Although Mafb and c-Maf transcription factors are known to regulate CIN development, their roles in mature SST+ and PV+ cells remain unclear. We show that conditional deletion of c-Maf in postmitotic SST+ interneurons alters their synaptic excitation and is associated with the development of spontaneous epileptiform activity in mice. Deletion of either gene in PV+ cells had no such effect. These findings reveal a specific vulnerability of SST+ cells to c-Maf loss and underscore the need to investigate c-MAF as a potential contributor to epilepsy and related disorders in humans.
Digital prevention courses offered by statutory health insurance funds in Germany represent a low-threshold opportunity to support health-promoting behaviors through pre-recorded, video-based programs focusing on exercise, nutrition, or stress management. However, little is known about insured individuals' motivations and barriers to participation. This study aimed to identify relevant motivating and obstructive factors for participation in digital prevention courses and to explore differences compared to on-site formats. We conducted semi-structured telephone interviews with 20 insured members of two large regional statutory health insurance funds in Germany (AOK North-East and AOK North-West) who had recently completed digital prevention courses. Participants were recruited via e-mail invitations sent by the health insurance funds following course participation. Five additional interviews were conducted with participants of on-site courses for contextual comparison. Interviews were conducted between February and December 2023, transcribed verbatim, and analyzed using qualitative content analysis with a deductive-inductive coding approach based on the study objectives and interview guide. The sample included 20 participants (mean age 41 years, range 25-72; 19 women and 1 man) who had completed digital prevention courses. Participants emphasized temporal flexibility, home-based access, and low preparation effort as key facilitators of participation. Additional motivators included health-related goals, free access, practical content, reminders, and the possibility to repeat sessions. Reported barriers included a lack of discipline, reduced social interaction and commitment compared to on-site formats, and work- and family-related demands. The availability of recorded sessions was perceived as a major advantage that facilitated course completion. Participants also valued competent instructors, but called for clearer differentiation of difficulty levels, broader course options, continued access to materials, and follow-up opportunities. The contextual comparison showed that on-site course participants particularly valued the sense of community and the possibility of individual corrections by instructors. Digital prevention courses are well accepted and can promote participation due to their flexibility and accessibility. However, challenges such as reduced social interaction and the need for self-discipline limit their full potential. To enhance their effectiveness and reach, digital prevention programs should integrate more tailored content, structured follow-up offers, and interactive or hybrid elements that foster engagement and social connectedness. German Clinical Trial Register DRKS00029761; Registration date 27.07.2022; https://drks.de/search/de/trial/DRKS00029761 .
The overall prevalence of youth nicotine and tobacco product use has declined over recent years, but the product landscape continues to change rapidly. This study examined changes between 2024 and 2025 in the prevalence of nicotine and tobacco product use among US middle and high school students and described shifts in product characteristics among current e-cigarette and nicotine pouch users. Repeated cross-sectional study using nationally representative data from the 2024 and 2025 National Youth Tobacco Survey (NYTS), a school-based survey of US students in grades 6-12 (approximately ages 11-18). The analytic sample included 29,678 students in 2024 and 23,557 students in 2025. Adjusted prevalence ratios were estimated using survey-weighted modified Poisson regression. In 2025, 7.2% (95% CI, 6.4-8.2%) of US middle and high school students reported past 30-day use of any nicotine/tobacco product, compared with 8.1% (7.4-8.9%) in 2024; this modest difference was compatible with no change (aPR 0.89; 95% CI 0.77-1.02). E-cigarettes remained the most commonly used product (5.2%, 4.5-5.9%); 1.7% (1.4-2.1%) used nicotine pouches, 1.7% (1.4-1.9%) smoked cigarettes, and 2.7% (2.4-3.1%) smoked any combustible tobacco product. Among current e-cigarette users, 40.7% (36.7-44.9%) reported frequent use and 27.0% (24.0-30.2%) reported daily use in 2025. Disposable e-cigarette use increased from 55.8% (52.6-59.0%) in 2024 to 66.7% (62.5-70.7%) in 2025, while pod/cartridge device use declined. Flavored product use was reported by 90.0% of e-cigarette users and 88.0% of nicotine pouch users. The most commonly reported brands were Geek Bar among e-cigarette users (61.1%) and ZYN among nicotine pouch users (69.4%). Overall youth nicotine and tobacco use remains relatively low, but the product landscape is being reshaped, with increasing disposable device use and shifting brand preferences. These findings highlight the importance of ongoing, product-specific surveillance to inform public health strategies and regulatory policies.
The rapid expansion of electric vehicles (EVs) and residential photovoltaic (PV) systems has created new challenges in battery charging management, particularly due to the variability of renewable energy, grid limitations, and battery aging effects. In this work, we present a machine learning-based Energy Management System (EMS) designed for PV-assisted smart charging of EVs and second-life batteries. The proposed system estimates the Optimal Charging Duration Class (OCDC) using an XGBoost model trained on real-time operating variables such as state of charge (SOC), battery temperature, available PV surplus, and degradation-related indicators. Rather than relying on conventional continuous power control, the proposed approach adopts discrete charging modes that dynamically adjust to operating conditions, aiming to improve both energy utilization and battery health. Degradation considerations are incorporated in a practical, control-oriented manner by avoiding operating regions associated with accelerated aging, instead of explicitly modeling electrochemical processes. The system is evaluated within a simulation framework that includes realistic PV generation profiles, load demand, and thermal behavior. Although hardware implementation is not yet included, it is identified as an important direction for future validation. The results show that the proposed EMS increases PV self-consumption by around 22% while reducing exposure to high-temperature operation, high state-of-charge conditions, and unnecessary cycling. These outcomes indicate a potential reduction in degradation risk, especially for second-life battery applications. Overall, the study demonstrates that integrating machine learning with real-time energy management can provide an efficient and health-aware solution for smart charging in residential and hybrid renewable energy systems.
Whether Archean arc-like volcanism reflects subduction remains debated. We present high-resolution geochemical data from a well-preserved 3.13-3.10 Ga arc-like volcanic succession in Australia's Pilbara Craton, a rare Archean analog of modern arc volcanism retaining fluid-mobile element concentrations consistent with primary magmatic values. The sequence records three primitive lava series typical of modern arcs: tholeiitic, calc-alkaline, and the oldest stratigraphically extensive genuine boninites. Geochemical modelling shows this melt diversity requires at least two mantle sources with distinct depletion histories. The mantle H2O required for fluid-assisted melting to produce these lavas substantially exceeds primitive mantle, approaching the H2O-saturated solidus of modern mantle wedges. We infer hydrous melting was triggered by dripduction, the short-lived inclined foundering of hydrated lithosphere without laterally continuous plate boundaries, in an off-plateau setting. Dripduction locally recycled surface water and generated arc-like magmas without self-sustained plate tectonics, possibly promoting mantle-ocean-atmosphere volatile exchange during the Archean.
Inorganic semiconductors are essential for modern electronics, but their inherent brittleness restricts their applications in flexible and wearable devices. This issue is particularly acute in low-symmetry structures, where the lack of slip systems further suppresses plastic deformation. Here, we reveal an intrinsic toughening mechanism in monoclinic GaTe using in situ SEM microfracture experiments. In contrast to the catastrophic brittle cleavage along the interlayer direction, cross-layer crack propagation undergoes continuous deflection, generating a highly tortuous crack path that enhances the mean fracture toughness by ∼60%. Combining high-resolution imaging with atomic simulations, we identify stress-triggered monoclinic-to-trigonal phase transitions at deflection points, which effectively impede and redirect crack propagation. The toughening mechanism is further validated in a flexible GaTe photodetector, which retains an excellent photoresponse and mechanical durability over tens of thousands of bending cycles. These findings lay a solid foundation for nanodevice applications in which both mechanical robustness and functional stability are required.
Autism spectrum disorder (ASD) prevalence continues to rise despite no recent changes to screening or diagnostic criteria. A complete understanding of the pathophysiology of ASD remains elusive. Gestational and postnatal inflammation correlate strongly with ASD prevalence, which is supported by maternal immune activation prevalence studies, maternal immunoglobulin found in fetal brains with ASD and altered T-cell populations in ASD children. Elevated TNF-α, interleukins, nuclear factors, and toll-like receptor levels reported in subgroups of ASD children provide evidence of a chronic inflammatory process posited to be a consequence of a cellular danger response impacting T-cells, neutrophils, macrophages, and microglia. The RAGE system is a multi-ligand receptor within the immunoglobulin (Ig) superfamily that plays a role in inflammatory gene signaling and may help explain how early prenatal and ongoing inflammatory insults are linked to the autistic phenotype. ASD patients demonstrate differences in RAGE signaling; elevations in inflammatory gene expression ligands (AGEs, HMGB1, S100 family), decreases in esRAGE, regionally altered C1q, and impaired APP metabolism. Each of these ligands serves a role as either increasing inflammatory gene expression, modulating transport of biomolecules, or mediating immune cell migration and phagocytosis. Additionally, the RAGE system has been demonstrated to be involved in gut-blood and blood-brain oxytocin transport. In the mouse model, chronic inflammation is associated with impaired oxytocin transport across these barriers. Young children with ASD have lower serum oxytocin levels than age-matched controls, and serum OXT levels correlate with social communication testing across all groups of children. ASD patients have an increased prevalence of asthma, atopic dermatitis, allergic rhinitis, and irritable bowel syndrome, indicating an ongoing inflammatory hyperactivity in some ASD subgroups that may disturb oxytocin transport, predisposing ASD symptomology. Furthermore, the gut microbiome and its metabolites influence RAGE signaling and may partially explain the differences in microbiome composition in ASD patients. Altered RAGE signaling is the proposed mechanistic link between ongoing inflammation and impaired oxytocinergic signaling contributing to ASD pathogenesis in certain subgroups. Further research into the biomarkers involved could identify subpopulations of ASD patients that would benefit from early modulation of the RAGE system.
Cardiovascular diseases (CVDs) continue to be the leading cause of death worldwide, with dyslipidemia as one of their main risk factors. Nurse-led cardiac rehabilitation (NLCR) has been shown to improve the quality of life of cardiac patients. We aim to measure its effect on lipid levels. We conducted a systematic review and meta-analysis of clinical trials comparing NLCR with usual care. Major electronic databases and grey literature sources were searched through July 31, 2025. Eligible studies reported at least one lipid outcome, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Risk of bias was assessed using RoB 2.0 for randomized controlled trials (RCTs) and ROBINS-I for non-RCTs. Random-effects models were used to calculate pooled standardized mean differences (SMDs) and mean differences (MDs) with 95% confidence intervals (CIs). Ten studies were included in the meta-analysis. NLCR was associated with a significant reduction in TG levels (SMD = - 0.19; 95% CI: -0.36 to - 0.02), corresponding to an absolute reduction of 8.38 mg/dL (MD = - 8.38; 95% CI: -13.82 to - 2.94). Changes in TC (MD = - 6.03 mg/dL; 95% CI: -14.57 to 2.51), LDL-C (MD = - 4.78 mg/dL; 95% CI: -9.89 to 0.33), and HDL-C (MD = 1.90 mg/dL; 95% CI: -2.30 to 6.10) did not reach statistical significance in the overall analysis. Subgroup analyses demonstrated a significant TG reduction among RCTs (MD = - 9.25 mg/dL; 95% CI: -14.84 to - 3.65). According to follow-up duration, studies with follow-up durations of ≤ 3 months showed a significant reduction in TC levels (MD = - 9.81 mg/dL; 95% CI: -14.13 to - 5.49), whereas studies with follow-up durations of > 3 months demonstrated a significant reduction in TG levels (MD = - 8.02 mg/dL; 95% CI: -13.95 to - 2.09). Meta-regression analyses identified study design as a significant predictor of TG and LDL changes. NLCR was associated with a significant reduction in TG levels among patients with CVD, while changes in TC, LDL-C, and HDL-C were not statistically significant. Subgroup and meta-regression analyses suggested that study design and follow-up duration may influence lipid outcomes. Further high-quality RCTs with longer follow-up are needed to confirm these findings and evaluate their long-term clinical implications.
Medical imaging devices are large consumers of electricity. This study aims to estimate potential energy savings through optimized CT examination scheduling using an ideal (hypothetical) lower-bound and a clinically realistic model. Examination timestamps and power consumption data of all CT examinations (n = 13,153) performed on three CT scanners in a tertiary care radiology department across 261 workdays in 2015 were retrospectively analyzed. CT examination scheduling was optimized using binary linear programming to minimize total scanner energy consumption. Two models were evaluated: a lower-bound model (LB model) allowing shutdown of all nonemergency scanners and a realistic model (R model) keeping one additional routine scanner continuously available during operating hours. Optimization problems were solved within seconds for each workday. Compared with observed clinical operation, the LB model achieved a reduction in daily energy consumption of 34.8% (34.2-35.5%), whereas the R model yielded an 11.0% (10.7-11.3%) reduction. These corresponded to estimated annual energy savings of 10,933 kWh and 3,460 kWh, respectively. For the R model, this translated to approximately $692 in annual cost savings and a reduction of 998 kgCO2-equivalent emissions, while preserving clinically feasible scanner availability. Optimization-based CT examination scheduling can substantially reduce energy consumption without additional hardware. Even under realistic workflow constraints, meaningful sustainability and cost benefits were observed. Automated, optimization-guided CT scheduling may represent a practical strategy to reduce the environmental footprint of radiology departments.
The imidazoline receptor (IR) system, comprising the I1R, I2R, and I3R subtypes, consists of binding sites involved in cardiovascular, metabolic, and neurological disorders. This review updates the 2004 compilation by Dardonville and Rozas on IR ligands, emphasizing promising ligands, subtype selectivity, and pharmacological profiling. Representative ligands for each subtype are analyzed to highlight key pharmacological aspects, including affinity, selectivity, and functional activity, integrating findings from preclinical and clinical studies. Critical molecular targets such as Nischarin/IRAS for I1R and MAO-B-associated sites for I2R are discussed in the context of ligand design and CNS penetration. I1R-selective ligands, exemplified by rilmenidine, show improved selectivity over α2-adrenoceptors and exhibit antihypertensive, metabolic, and neuroprotective effects. I2R ligands display neuroprotective, anti-inflammatory, and analgesic activities, with CR4056 progressing to Phase II trials. PET imaging with [11C]BU99008 has validated I2R upregulation as a biomarker for neurodegeneration. Overall, the IR system presents therapeutic opportunities: I1R for cardiovascular and metabolic disorders, I2R for pain and neurodegeneration, and I3R for diabetes. Continued ligand optimization and receptor characterization are essential for clinical translation.
Globally, colorectal cancer continues to be a major cause of cancer-related death. Clinical application of 5‑fluorouracil (5‑FU) is constrained by reduced bioavailability and dose‑limiting toxicity. To overcome these restrictions, a ternary drug delivery system was developed in this study. Chitosan and β‑cyclodextrin were physically assembled into a pseudopolyrotaxane complex, and 5‑FU was incorporated by solvent evaporation to form a solid dispersion. The resulting nanocomposite had a mean hydrodynamic diameter of 187 nm and a zeta potential of + 32.5 mV. Fourier transform infrared spectroscopy revealed peak shifts consistent with non‑covalent interactions. X‑ray diffraction confirmed amorphization of 5‑FU within the formulation. The ternary system released 5‑FU more rapidly at pH 5.5 than at pH 7.4. In HCT‑116 colorectal cancer cells, the 5‑FU/chitosan/β‑cyclodextrin formulation showed an IC50 of 16.5 µM, compared with 42.5 µM for free 5‑FU and 27.5 µM for the binary 5‑FU/β‑cyclodextrin complex. Gene expression analysis indicated upregulation of P53 and Caspase‑3 and downregulation of BCL2 and VEGF. A complementary in silico analysis of 5-FU-responsive genes (from public dataset GSE183977) identified a protein‑protein interaction network enriched in apoptosis and cell‑cycle pathways, with IL6, MYC, EGR1, and ATF3 as central hub genes. The obtained results show that incorporation of 5‑FU into a chitosan/β‑cyclodextrin matrix improves its activity against colorectal cancer cells. This effect is attributed to enhanced solubility, pH‑responsive release, and modulation of apoptotic and angiogenic pathways.
This study explored the development of professional and collective identities and coping, resilience, and functioning, among mental health practitioners experiencing shared trauma during a period of collective trauma. Twenty-four Israeli mental health practitioners (social workers, psychologists, and psychiatrists) who were displaced following the October 7th events participated in semi-structured interviews conducted shortly after evacuation. The thematic analysis identified four central themes reflecting the role of professional and collective identity in coping and professional functioning under conditions of shared trauma: (a) Professional identity supported emotional containment and ethical decision-making, enabling participants to maintain clinical functioning under conditions of ongoing stress and uncertainty; (b) Collective identity was associated with solidarity, shared meaning-making, and strengthened commitment to clients and colleagues; (c) The two identity dimensions were reported as interdependent and continuously influencing one another, forming a dynamic process rather than separate constructs; and (d) This interaction was described as sustaining coping efforts and facilitating continued professional engagement in the context of shared trauma. Professional and collective identities appear to function as interconnected processes that support adaptive coping and clinical functioning following exposure to mass trauma.
Lower respiratory tract infections represent a major public health burden, but adult data on respiratory viruses except influenza and COVID-19 are limited. Most European surveillance systems report aggregate data lacking patient-level detail. We utilised the multicountry id.DRIVE surveillance study data to describe the epidemiology, clinical characteristics, and outcomes of adults hospitalised with pathogen-specific severe acute respiratory infections (SARI) during 2024-2025. Adults (≥ 18 years) hospitalised with SARI across 17 hospitals in Spain, Italy, and Germany between 1 September 2024 and 31 August 2025 were included. All participants were tested using reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), and influenza A/B (testing additional respiratory pathogens varied by hospital). Descriptive analyses were stratified by pathogen. Of 8730 included participants (median age, 77 years), 14.3% (n = 1249) tested positive for influenza A, 6.9% (n = 606) SARS-CoV-2, 6.4% (n = 554) RSV, and 0.8% (n = 74) for influenza B. Positivity peaked for influenza and RSV in December-January, and for SARS-CoV-2 in July. Comorbidity burden was substantial: 51.9% of all SARI participants had ≥ 3 chronic conditions, reaching 62.3% in those with RSV. RSV-positive SARI patients were older (median age, 80 years); oxygen therapy was required in 72.0%, non-invasive ventilation in 12.3%, and in-hospital mortality was 9.4%. Over 75.0% of SARI cases positive for a respiratory virus received antibiotics during hospitalisation. Viral pathogens remain a major cause of adult SARI hospitalisations in Europe. Our findings highlight the continued burden and seasonal diversity of viral respiratory pathogens, supporting the value of integrated, pathogen-specific SARI surveillance guiding prevention strategies.
Cardiometabolic multimorbidity (CMM), the co-occurrence of at least two cardiometabolic diseases, poses a significant public health threat. The Cholesterol, High-density Lipoprotein, and Glucose (CHG) index is an emerging surrogate marker of insulin resistance, yet its association with CMM, particularly when integrated with obesity indices, remains unexplored.This prospective cohort study analyzed 6991 adults aged ≥ 45 years without baseline CMM from the China Health and Retirement Longitudinal Study (CHARLS). Multivariable Cox regression, Kaplan-Meier curves, and restricted cubic splines were used to assess associations between CHG-obesity composite indices and CMM risk. Predictive performance was evaluated using time-dependent receiver operating characteristic (ROC) analysis, Harrell's C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). A Fine-Gray competing-risks model, subgroup analyses, and sensitivity analyses were also conducted. Over a median follow-up of 9 years, 677 participants developed CMM. Each 1-unit increase in CHG-related indices was significantly associated with elevated CMM risk, with fully adjusted HRs ranging from 1.01 to 1.86. The Fine-Gray competing risk model confirmed this robust association. CHG-WC and CHG-WHtR yielded the highest C-index (both 0.701). All CHG-related indices significantly improved risk reclassification and discrimination relative to conventional risk factors (all continuous NRI and IDI, p < 0.05). Hypertension significantly modified the association. Sensitivity analyses confirmed robustness. CHG-composite indices are significantly associated with increased CMM risk and show potential as practical tools for risk stratification in middle-aged and older adults.
To compare the temperature changes with laser activation when providing irrigation with a pressure bag vs a fluid management system (FMS). Benchtop experiments were performed with a LithoVue™ Elite (Boston Scientific Corp., Marlborough, MA, USA) flexible ureteroscope placed through an 11/13-F ureteric access sheath into a benchtop pelvicalyceal kidney model. Room temperature saline irrigation, via the scope, was provided either with a pressure bag or FMS. Both systems were pressurised to 200 mmHg and left for 10 min. After 10 min, a holmium:yttrium-aluminium-garnet laser was activated at 20, 40, or 60 W for 90 s. Flow rate, irrigation pressure, intrarenal pressure and calyceal temperature were recorded continuously. Experiments were repeated five times. Benchtop empirical temperature data were compared to mathematical model predictions. The mathematical model was then used to predict calyx temperature as a function of flow rate in in vivo conditions. Pressure-bag irrigation flow rate declined from ~38 to ~25 mL/min (36%) over 10 min, whereas the FMS maintained stable flow of ~45 mL/min. Intrarenal pressure remained ≤30 mmHg in all experiments. Consequently, the benchtop calyx mean (standard deviation) temperature rise with pressure bag vs FMS irrigation was: at 20 W 7.9 (1.0)°C vs 6.4 (0.6)°C (P = 0.02); at 40 W 12.8 (3.2)°C vs 10.3 (1.7)°C (P = 0.15); at 60 W 17 (3.4)°C vs 12.4 (1.2)°C (P = 0.02). Irrigation flow rate is a key determinant of thermal risk during laser lithotripsy. An automated FMS can maintain consistent flow; mitigating temperature rise and thermal dose in a benchtop model.
Mutations are a continuous source of new alleles and genetic diversity in populations. Domestication and selection influence the accumulation of alleles occurring across a range of deleteriousness. Evidence suggests that mildly deleterious mutations (DelMut) can be purged out of breeding populations, increasing favorable allele accumulation. We used phylogeny-based analyses among 36 legume genomes to identify selection signatures and trained a random forest (RF) model using conservation and protein information for the prediction of DelMut in common bean populations, including a newly developed multiparent advanced generation intercrossed (MAGIC) population of black beans. Genes involved in nitrogen metabolism showed signs of positive selection in the Middle American genome, whereas genes related to phosphorylation were positively selected in the Andean genome. By combining conservation and protein information with machine learning (ML) for high-dimensional feature analysis, we characterized 82,442 sites in the MAGIC founders (36,558 polymorphic) and 4753 sites evenly sequenced among RILs that could be potentially deleterious. Variation in the number of highly DelMut (high predicted deleterious scores) among lines was observed and later correlated with agronomic traits. Phenotypic analyses showed that calculated genetic load (and number of highly DelMut) was negatively correlated with flowering time, maturity, and yield. A detailed in silico analysis of predicted mutations showed presence in highly conserved protein regions, which is likely to affect protein functionality. Our results show that variation in genetic load can be observed in breeding populations and potentially impact plant performance. These results contribute to understanding the genome-wide accumulation patterns of DelMut in breeding populations. Our study supports future development of strategies to reduce genetic load in promising germplasm and accelerate breeding programs.
As cancer survivorship increasingly overlaps with chronic disease management, understanding how comorbidity shapes survivors' care experiences is essential. This study aimed to explore how comorbidity influences cancer survivors' experiences of follow-up care and their expectations of primary care within China's evolving health system. A multicenter qualitative study using a descriptive phenomenological approach was conducted across 9 community-level sites in Shandong Province, China. Semi-structured, face-to-face interviews were undertaken with 50 adult cancer survivors living with at least one chronic non-cancer comorbidity. Participants were purposively selected from a larger survey sample using maximum variation sampling. Interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. Data collection continued until saturation was achieved. Three overarching themes emerged. First, comorbidity amplified fragmentation across specialist-driven care pathways, placing survivors in the role of self-coordinators and reinforcing the need for a central primary care provider. Second, overlapping symptoms across cancer and chronic conditions generated persistent uncertainty, increasing survivors' demand for interpretive support from primary care. Third, comorbidity reframed survivorship as a long-term, chronic experience, heightening expectations for continuity, emotional support, and assistance with daily-life management. Comorbidity fundamentally reshapes cancer survivorship care needs, underscoring the importance of integrating oncology follow-up within primary care-based chronic disease management frameworks. Strengthening primary care coordination and continuity may reduce uncertainty, ease self-management burdens, and improve the overall survivorship experience for individuals living with cancer and comorbidity.
Despite the prominence of sustainment as a construct in implementation science frameworks, there is limited literature on factors influencing the continued delivery and reach of evidence-based interventions in carceral settings after initial funding periods end. Extending previously published research on initial establishment of these programs with federally funded implementation support, this study reports on the post-intervention impact of jail-based programming to link people with opioid use disorder to medication treatment upon community reentry to assess whether and how linkage programming was maintained. In the five jails that sustained linkage program staff, only 4.9% of participants enrolled during the sustainment phase were successfully linked to community-based treatment, compared with 11.8% during the intervention phase. Interviews with linkage staff supervisors revealed that several factors salient to initial program implementation - adopter training and support, services and access, and systems and training - exerted ongoing effects during the sustainment period, demonstrating that preliminary implementation conditions may shape long-term reach. During the program sustainment period, these issues included restrictions on program eligibility criteria to reduce jail healthcare costs and deterioration of related clinical offerings (i.e., provision of in-house medication treatment). Additionally, challenges with maintaining data collection consistency after termination of the study's data management infrastructure and reporting requirements resulted in significant missing data. Findings emphasize the need for enduring technical assistance and data-tracking infrastructure to support and monitor the impact of jail-based linkage programs as a component of the overall opioid use disorder continuum of care.
This study explores the effects and mechanisms of haze pollution on entrepreneurial activities to provide evidence on the "pollution constraining development" dilemma and guide coordinated environmental and economic governance. Using firm registration data of 2,822 Chinese counties from 2003 to 2022, we examine the impact of haze on overall regional entrepreneurial activity and the proportion of environmental protection entrepreneurship. Results show that haze reduces overall entrepreneurial activity, but increases the proportion of environmental entrepreneurship. The effect on general entrepreneurship follows the environmental Kuznets curve and has a double threshold effect. Mechanism analysis indicates that haze leads to the outflow of human capital and the increase of environmental regulatory costs, which reduces the overall quantity of entrepreneurial activities, but it enhances the government's support and market demand for green technologies, promoting the development of environmental entrepreneurship. Heterogeneity analysis shows that the effects are more pronounced in the eastern and central regions of China, and in regions with higher industrial agglomeration, weaker developed green finance development or lower information transparency, and that with continuous economic growth, this effect exhibits the characteristic of "being initially pronounced, then insignificant, and subsequently pronounced again". These results highlight the significance of regional policy design, resource allocation coordination and environmental entrepreneurship promotion support for promoting the sustainable development of the economy and the improvement of the environment.