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Soils are unique in their intricate, 3D structure, harbouring 59% of global biodiversity. Yet, this structure is easily destroyed. Soils have no formal protected status, and we do not know where the oldest undisturbed soils are located. In this forum article, I argue that applying the old-growth concept to soils will aid their protection.
Asthma and chronic obstructive pulmonary disease (COPD) are the most prevalent chronic inflammatory airway diseases worldwide, significantly affecting patients' quality of life and mortality and imposing a substantial socioeconomic burden. Increasing insights into their pathophysiology have led to the recognition of both conditions as complex syndromes encompassing distinct pheno-endotypes. Asthma patients can be broadly stratified into type 2 (T2)-high and T2-low phenotypes based on biomarker expression and clinical features. More than half of asthma patients exhibit a T2-high phenotype, which includes two principal endotypes: allergic eosinophilic and non-allergic eosinophilic asthma. In COPD, traditionally associated with type 1 and type 3 immune responses and neutrophilic inflammation, around 20-30% of patients display a marked T2 signature, defining a novel T2-COPD endotype. In both diseases, epithelial and innate immune cells cooperate to orchestrate adaptive and effector T2 responses characterized by blood and airway eosinophilia and elevated fractional exhaled nitric oxide (FeNO). In asthma, 6 biologics targeting key T2 inflammatory pathways are approved as add-on treatment (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab). In T2 COPD, 2 biologics have recently been approved (dupilumab and mepolizumab) and others are under clinical evaluation. Other emerging strategies, including next-generation allergen-specific immunotherapy and trained immunity-based vaccines, offer promising new therapeutic avenues. A better understanding of the molecular mechanisms driving T2-high asthma and T2 COPD endotypes is essential to identify reliable biomarkers and novel therapeutic targets. Such advances will improve patient stratification, optimize disease management, and foster the development of preventive and precision medicine approaches in chronic airway diseases.
Most spinal muscular atrophy (SMA) carrier screening assays quantify SMN1 exon 7 copy number, providing limited information about the prevalence or structure of SMN1-SMN2 hybrid alleles generated through gene conversion. As long-read sequencing (LRS) studies begin to resolve these alleles at high resolution, typically in modest cohorts, large population-scale data remain essential for defining the broader allele-frequency context in which such structural signatures occur. We evaluated SMN1 exon 7 and exon 8 copy number in 18,015 individuals undergoing expanded carrier screening using a SNP-based array. Carriers were classified by deletion pattern, and representative cases underwent droplet digital PCR (ddPCR) to distinguish contiguous deletions from gene-conversion-derived hybrid alleles based on coordinated SMN1/SMN2 exon and intron copy number profiles. Among 457 carriers (2.5%), exon 7-only deletions accounted for ~ 53%, while exon 7 + 8 deletions comprised ~ 47%. ddPCR showed that exon 7-only deletions predominantly represented SMN1-SMN2 hybrid alleles, whereas exon 7 + 8 deletions reflected contiguous loss of both exons. Isolated exon 8 deletions were rare (~ 0.05%) and likewise exhibited hybrid architecture. This distribution contrasts with earlier population studies reporting a predominance of exon 7 + 8 deletions and indicates that hybrid alleles constitute a substantial proportion of SMN1 deletion alleles in the general population. While hybrid resolution is not required for routine SMA carrier detection, the unexpectedly high prevalence of hybrid alleles highlights an important category of SMN1 structural variation that merits deeper investigation. These population-scale data provide a framework to guide and contextualize future LRS-based analyses aimed at resolving SMN1 gene-conversion tracts, allele structures, and potential modifier variants relevant to SMA pathogenesis and therapeutic response. Together, these findings support a more comprehensive understanding of SMN1 allele diversity as genomic technologies advance toward high-resolution characterization of the SMN locus. Clinical trial number: not applicable.
The gene has remained a central organizing concept in biology for more than a century, yet its definition has become increasingly difficult to reconcile with contemporary molecular and genomic evidence. This article combines a historical review with a conceptual perspective to examine the evolution of the gene concept from Mendelian heredity to postgenomic biology. Early gene concepts assumed discreteness and stable relationships between genes and traits. These assumptions were highly productive but became inadequate as gene regulation, RNA processing, epigenetic modification, and long-range genomic interactions were discovered. Rather than converging on a refined definition, biological research progressively expanded the range of phenomena that gene concepts were required to accommodate. By synthesizing key developments across classical genetics, molecular biology, and genomics, this review explains why defining the gene has become empirically challenging while the gene itself remains indispensable in biological practice. On this basis, a pragmatic working definition of the gene is proposed that is grounded in DNA sequence and reproducible transcriptional output under regulatory control, while remaining compatible with contemporary genomic research.
The physician-patient relationship can be undermined by biased behaviours. There is a lack of epidemiological data in Europe and in the field of anaesthesia. BiPAC is a prospective and bicentric survey study, conducted in a public and a private hospital. We recruited both the patient and the physician during consultation. A biased behaviour is defined as any action or statement perceived as degrading. A total of 1980 patients were included, and physicians returned 258 questionnaires. Biased behaviour from the physician was experienced by 3.7% of the patients. The consequences were poor answers, disrespectful remarks, and denial of care. Patients encountering difficulties with the French language were more likely to be experiencing biased behaviour (OR = 6.90 [1.34-35.48]; p < 0.001), as were LGBTQ patients (OR=3.32 [1.38-7.97] ; p = 0.007). In contrast, being seen in a private centre was a protective factor (OR=0.52 [0.27-0.99]; p = 0.046). Biased behaviour from patients was experienced by 2.1% (n=63) of the physicians. Being a woman (p = 0.039) and European (p < 0.001) were risk factors. In multivariate analyses, being 60 years or older was a protective factor (OR=0.21 [0.09-0.54]; p = 0.001) while being a resident was a risk factor (OR=2.7 [1.38-5.68]; p = 0.004). Biased behaviours during pre-anaesthesia consultations, even when perceived as harmless, undermined patient trust, understanding, and perceptions of physician competence. Language barriers and identifying as LGBTQ were risk factors for patients, whereas belonging to an ethnic minority group was not. Among physicians, being a woman, a resident, or younger in age was associated with greater exposure.
Ratings of perceived effort (RPE) are used to prescribe and monitor training. Yet, the influence of how the upper anchor ("10") is defined remains underexplored, despite holding theoretical and practical value. Here, we examined whether modifying the upper anchor predictably modifies RPEs during isometric exercises. We conducted a within-subject, randomized crossover study in 26 resistance-trained adults. Participants performed isometric contractions at 20-100% of maximal voluntary contraction (MVC) in three exercises: unilateral plantar flexion, unilateral knee extension, and the isometric mid-thigh pull. After each contraction, participants reported RPE (0-10) relative to one session-specific anchor: same-task (maximal effort in the task performed), different-task (maximal effort in the isometric mid-thigh pull), or self-selected (the most effortful task ever experienced or imagined). We estimated expected RPEs and slopes relating RPE to %MVC for each exercise-anchor combination. Preregistered comparisons assessed anchor effects, muscle-mass dose-response, and approximate scale invariance across anchors. Anchor type substantially influenced RPE. Same-task anchors consistently produced the highest RPEs, self-selected the lowest, and different-task anchors intermediate values, with effects most pronounced at 80-100% MVC. The ratings increased with %MVC across all conditions. Under the self-selected anchors, exercises engaging greater muscle mass tended to yield higher RPEs. The relative differences between exercises were largely preserved across anchors, indicating that anchor choice alters RPE while maintaining approximate scale invariance. Upper anchors predictably shape RPE across tasks and intensities. Researchers and applied practitioners using RPE in resistance training should explicitly define, justify, and consistently report anchoring procedures, and align anchor choice with the intended purpose to support valid interpretation and comparisons.
The risk of malignant transformation and recurrence of Sacrococcygeal Teratoma (SCT) is relatively high, while it is possibly lower in cases associated with Currarino Syndrome (CS). However, the existing literature gives contradictory results. We aimed to examine the risk of malignant transformation in a large cohort of SCT and CS patients. In a global retrospective cohort study, data of consecutive SCT patients and CS patients with presacral teratoma was obtained from 132 institutes in 62 countries. Malignant transformation, defined as malignancy at initial resection, malignant recurrence, or death due to malignancy was analysed for SCT and CS patients. The rate of malignant transformation was analysed with log-rank test and compared between groups. Of 3612 patients with presacral teratoma, 3388 entered analysis; 3183 SCT and 205 CS patients. The percentage of patients with malignant transformation at initial resection was higher in the SCT versus the CS group, 10·3 % and 31·9 % after one and two years, versus 4·2 % in CS patients after two years, respectively (p < 0.001). Histology in recurrent teratoma was malignant in 35·4 % (n = 114) of SCT patients and 5·9 % (n = 1) of CS patients (p = 0.005). Survival in both groups was equivalent at 94·9 % in SCT patients versus 96·9 % in CS patients (p = 0·343) CONCLUSION: The SCT-study shows that malignancy is more often present in SCT than in CS patients with an increasing risk of malignant transformation with age compared to CS patients in whom malignancy is rare. Recurrence after resection was more often malignant in the SCT group. level III.
Alcohol consumption is a significant and growing public health concern in Ghana, where it contributes to rising rates of non-communicable diseases, social dysfunction, and economic burden. Despite its impact, municipality-level data on alcohol use among the general adult population remains scarce, creating an evidence gap that limits the development of targeted, context-specific interventions. Prior studies in Hohoe Municipality have been restricted to youth and tertiary student populations, leaving the broader adult population unexamined. This study aimed to determine the prevalence of current and lifetime alcohol consumption, assess knowledge of the long-term health effects of alcohol, and identify sociodemographic and behavioral factors associated with alcohol consumption among adults in Hohoe Municipality, Volta Region, Ghana. A quantitative cross-sectional design was used among 318 adults aged 18 years and above in Hohoe Municipality. Participants were recruited from residential households and alcohol-selling points in Hohoe Municipality using stratified random sampling and a balloting procedure. A structured questionnaire was administered face-to-face by trained interviewers. Current alcohol consumption was defined as consuming at least one standard drink in the 30 days preceding the survey. Knowledge of the long-term effects of alcohol was assessed, scored dichotomously and summed into a composite score, with the sample median used to classify participants into high and low knowledge groups Data were analyzed using Stata Version 17. Descriptive statistics summarized the sample, and chi-square tests examined bivariate associations. Binary and multivariable logistic regression were used for inferential analysis, with statistical significance set at p < 0.05 and 95% confidence intervals reported. Of the 318 participants, 122 (38.4%) were current alcohol consumers; those who had consumed alcohol in the past 30 days while an additional 48 (15.1%) were former consumers. Combined, 170 participants (53.5%, 95% CI: 48.0-59.0%) reported any lifetime alcohol exposure, representing the study's overall lifetime prevalence. Among the 56.2% of male participants and 50.6% of female participants who were consumers, sex was not a statistically significant predictor of consumption (p = 0.323). Local gin (akpeteshie) was the most consumed beverage (47.6%). Knowledge of the long-term effects of alcohol was low, as only 53.5% of respondents demonstrated high knowledge of chronic consequences, despite 85.6% acknowledging general health harm. Accessibility (55.3%) and peer influence (18.9%) were the primary self-reported drivers of consumption. Ewe ethnicity (aOR = 5.6; 95% CI: 1.97-15.95; p = 0.001), Guan ethnicity (aOR = 3.9; 95% CI: 1.06-14.55; p = 0.039), and Islamic religious affiliation (aOR = 0.22; 95% CI: 0.05-0.90; p = 0.036) were the significant independent predictors of alcohol consumption. Ethnicity likely reflects the influence of cultural norms, community-level alcohol availability, and social practices rather than any inherent characteristic. Alcohol consumption is prevalent among adults in Hohoe Municipality, with over half reporting lifetime exposure and more than a third identified as current consumers. Knowledge of specific long-term health risks remains limited, particularly awareness of recommended drinking limits. Ethnicity and religion are the strongest independent predictors of consumption, pointing to the central role of sociocultural context in shaping drinking behavior. These findings call for multi-level, culturally sensitive public health responses combining targeted health education, regulatory action on alcohol accessibility, and engagement with community and faith-based structures to reduce alcohol-related harm and support Ghana's national NCD prevention agenda.
We aimed to examine the prevalence of frailty in older adults with hypertension and its association with suboptimal blood pressure (BP), with a particular focus on differences by sex. The study was conducted at two major hospitals in Vietnam from 2023 to 2024. Frailty was defined by a Clinical Frailty Scale of ≥ 4. Suboptimal BP was defined as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. There were 1038 participants (326 female, mean age 73 years). The prevalence of frailty was 28.6%, higher in female (35.3%) than male participants (25.6%). The overall rate of suboptimal BP was 26.7%. In female participants, the frail had a significantly higher rate of suboptimal BP (33.9%) compared to the non-frail (20.9%), but no significant differences among male. In the logistic model adjusted for age, education, marital status, physical exercise, falls, coronary heart disease, diabetes, chronic kidney disease, osteoarthritis, heart failure, stroke, atrial fibrillation, osteoporosis, chronic obstructive pulmonary disease, duration of hypertension, monotherapy/combination therapy, and medication adherence score, the odds ratios of frailty on suboptimal BP were 2.01 (95% CI 1.08-3.76) in female participants, 0.92 (95% CI 0.59-1.44) in male, female-to-male ratio of odds ratios 2.18 (95% CI 1.01-4.70). These findings highlight the need for sex-specific approaches in managing hypertension in older populations.
Chronic myelomonocytic leukemia (CMML) is defined as a clonal disorder of the myeloid cell lineage, with the characteristic feature being monocytosis. Chromosomal abnormalities are common, but translocations involving chromosome 1p36 are rare. Here, we document a case of CMML that carried an unreported translocation involving t(1;3)(p36.2;p12). The patient showed rapid progression and died within six days post-diagnosis. The 1p36.2 chromosomal region harbors tumor suppressors such as PR domain containing 16 (PRDM16), Tumor Protein 73 (TP73), Cadherin 5 or VE-cadherin (CHD5), and Kinase Family Member 1B (KIF1B), while the 3p12 chromosomal location plays a role in the malignant transformation and disruption of the tumor suppressors, focusing on the genomic instability observed in the case. These changes may partially harbor the capacity to contribute to the pathogenesis of aggressive behaviors in leukemia through failure of apoptosis, chromatin remodeling pathways, and enhanced self-renewal capabilities of stem cells.
This study sought to evaluate the clinical implications of thrombocytopenia in pediatric patients diagnosed with systemic lupus erythematosus (SLE) and to explore its relationship with various disease features. Furthermore, the research aimed to identify risk factors that affect the occurrence of SLE-associated thrombocytopenia. A single-center retrospective study was conducted involving 236 pediatric patients diagnosed with SLE at Children's Hospital of Fudan University from January 2020 and December 2025. Clinical information and laboratory parameters, such as complement levels, autoantibody profiles, and platelet counts, were systematically collected. Participants were divided into two groups and those without, based on their platelet counts at the time they were diagnosed with SLE. The presence of thrombocytopenia was determined at diagnosis, and further subgroup analyses were carried out based on the severity of the condition. All statistical analyses, such as logistic regression and one-way ANOVA, were conducted using SPSS version 26.0. Thrombocytopenia was observed in 19.5% (46 out of 236) of the patients. In comparison to the cohort without thrombocytopenia, the thrombocytopenia group demonstrated significantly increased incidences of leukopenia, leukocyte reduction, and positivity for antiphospholipid antibody IgM, anti-β2-glycoprotein-1 antibody, and lupus anticoagulant (P < 0.05). Furthermore, severe thrombocytopenia (defined as a platelet count below 50 × 10⁹/L) was correlated with a markedly higher prevalence of lupus anticoagulant positivity relative to the mild-to-moderate thrombocytopenia subgroup. Logistic regression analysis revealed that leukopenia, elevated erythrocyte sedimentation rate (ESR), positivity for Anti-β2 glycoprotein 1 antibodies, high lupus anticoagulant, and neuropsychiatric manifestations were significantly associated with the presence of thrombocytopenia. Thrombocytopenia frequently occurs in pediatric patients with SLE and demonstrates a significant correlation with leukopenia, the presence of antiphospholipid antibodies, and involvement of major organs. Additionally, further multicenter prospective investigations are necessary to clarify the contribution of platelets to the pathogenesis of SLE. In clinical practice, when thrombocytopenia is identified in pediatric SLE patients, thorough evaluation for antiphospholipid antibodies and neuropsychiatric systemic lupus erythematosus (NPSLE) is warranted.
The rapid expansion of short-form educational video platforms has substantially increased public access to health information; however, the characteristics and quality of videos concerning patent ductus arteriosus (PDA) have not been systematically evaluated. This study aimed to evaluate the quality and reliability of short-form videos related to PDA posted on TikTok and Bilibili. The Chinese keyword "patent ductus arteriosus" was used to retrieve relevant videos from TikTok and Bilibili, yielding 140 videos for the final analysis. Uploaders were classified according to publicly available account information. Professional uploaders were defined as accounts identifying the uploader as a healthcare professional and displaying official platform verification and/or an explicit affiliation with a recognized medical institution. Credentials were verified using publicly visible profile elements, including verification badges, profile descriptions, professional titles, and stated institutional affiliations. All included videos were independently evaluated by two reviewers. Because paired reviewer-level ratings were available for the Global Quality Score (GQS), inter-rater reliability for GQS was assessed before consensus adjudication using the intraclass correlation coefficient (ICC) and quadratic weighted Cohen's kappa. Video quality and reliability were assessed using five established instruments: the Global Quality Score (GQS), Video Information and Quality Index (VIQI), Patient Education Materials Assessment Tool (PEMAT), the JAMA benchmark criteria, and modified DISCERN (mDISCERN). Only the first 100 algorithm-ranked videos from each platform were screened, in order to reflect the content most likely to be encountered by typical users, although this approach may preferentially capture videos favored by platform recommendation systems. No independent clinical subject-matter expert (such as a neonatologist or cardiologist) was separately involved in the formal scoring process; instead, the evaluation focused on quality, reliability, transparency, and understandability using established assessment instruments. Clinical accuracy was not independently assessed or adjudicated in this study. A total of 140 short videos related to patent ductus arteriosus (PDA) were included in the analysis, with 57 from Bilibili and 83 from TikTok. TikTok videos demonstrated significantly higher audience engagement than those on Bilibili, with markedly greater numbers of likes, favorites, shares, and comments. Bilibili videos were slightly longer in duration, and there was no significant difference in posting time between the two platforms. Videos on TikTok also achieved significantly higher scores across all five quality assessment tools-mDISCERN, GQS, VIQI, PEMAT, and the JAMA benchmark-and most high-quality videos were uploaded by professional individuals. In the present study, these professional individuals were defined on the basis of publicly visible healthcare-related identity information and platform verification status. When stratified by uploader type, videos created by professionals consistently outperformed those from non-professional individuals and institutions in both quality scores and engagement metrics. Professional videos were predominantly found on TikTok. Correlation analyses indicated weak to moderate positive associations between most quality indicators and likes, favorites, and shares on both platforms, although the correlation coefficients remained low. Notably, the average JAMA benchmark score was approximately half of the maximum possible score on both platforms. Inter-rater reliability for GQS was acceptable, with a single-measure ICC of 0.632, an average-measure ICC of 0.774, and a quadratic weighted Cohen's kappa of 0.630. The overall quality of PDA-related health information on major Chinese short-video platforms appears to be moderate. TikTok and professional uploaders demonstrated clear advantages in reliability, comprehensibility, and communication effectiveness. Platform attributes and uploader background exert significant influence on video quality and dissemination performance. Future efforts should focus on strengthening platform oversight, encouraging greater involvement of qualified healthcare professionals, and standardizing the disclosure of information sources and conflicts of interest. Such measures are essential for improving the accuracy, quality, and trustworthiness of online cardiovascular health information and for better supporting parents of children with PDA and the general public. These findings should be interpreted as reflecting informational quality, structure, transparency, and understandability rather than independently verified clinical accuracy.
Structured planar materials known as metasurfaces enable versatile manipulation of electromagnetic waves at subwavelength scales. Especially, metasurfaces can serve as spatial sampling lattices that encode prescribed in-plane momentum profiles, as commonly employed in phase-gradient and Pancharatnam-Berry metasurfaces. However, such momentum-encoded metasurfaces typically lose global periodicity, complicating rigorous analyses. Here, we introduce a universal geometric framework that interprets momentum-encoded metasurfaces as directional Moiré lattices formed by imposing one-dimensional periodic perturbations onto two-dimensional Bravais lattices. We derive explicit commensurability conditions that reveal hidden periodicity in otherwise aperiodic structures and enable their representation as compact periodic superlattices. This supercell representation allows the discretization of radiation channels into defined diffraction orders, enabling clear, intuitive performance characterization. We validate the framework by applying it to local metasurfaces, obtaining diffraction results consistent with two-dimensional sampling theory, and to non-local metasurfaces with spin-dependent Rashba momentum, precisely identifying their superlattice conditions and their valley-addressable character. We further experimentally demonstrate the predicted valley addressability using fabricated momentum-encoded photonic crystal slabs. Our method thus provides an efficient and generalizable basis for analyzing complex metasurface architectures and exploring diverse lattice phenomena in wave physics.
This paper describes the initial release of annotated datasets from the advanced robotics and artificial intelligence for critical raw materials recycling in the circular economy (XBAT+) project. Relatively small battery waste electrical and electronic equipment (WEEE) devices were sorted from cages of general WEEE during visits to recycling facilities and collection events. From 50 initially defined battery-WEEE categories, applying a frequency criterion reduced them to 15 categories comprising 421 battery-WEEE devices. Optical and x-ray imaging of battery-WEEE devices produced multiple images per device in some cases, resulting in 3045 static images. These were organised into high-quality, varying-quality, and RGB datasets, semi-automatically annotated, and split into training and test sets. Specifically, within each of the 15 categories, 20% of the images were allocated to the test sets, the rest to the training sets. Evaluation using YOLO26 and RF-DETR demonstrated promising mAP@50 and recall for supervised learning-based battery-WEEE identification and battery/nobattery detection, highlighting the potential of XBAT+ datasets to enable WEEE filtering and mitigate battery-based fire hazards in recycling facilities.
Breast-conserving surgery (BCS) is the standard treatment for early-stage breast cancer; however, defects in the upper inner quadrant (UIQ) remain a significant reconstructive challenge due to paucity of local tissue and heightened cosmetic sensitivity of this quadrant. Chest wall perforator flaps (CWPFs) have emerged as a reliable volume replacement option with minimal donor-site morbidity, yet data focusing specifically on their use in UIQ defects are limited. This retrospective study included 20 female patients with UIQ breast tumors who underwent partial breast reconstruction using CWPFs between January 2022 and December 2023. Data regarding patient and tumor characteristics, flap type, operative details, and postoperative complications were collected. Aesthetic outcomes were objectively assessed using BCCT.core software (version 3.1), while patient-reported outcome measures (PROMs) were evaluated at 12 months postoperatively using the BREAST-Q questionnaire. The mean patient age was 40.7 ± 5.0 years. The most commonly used flap was the anterior intercostal artery perforator (AICAP) flap (40%), followed by combined LICAP/LTAP flaps (25%). The mean operative time was 79.0 ± 7.5 min. Postoperative complications occurred in 20% of patients, including seroma (10%), wound infection (5%), and fat necrosis (5%), with no cases of major flap loss or positive surgical margins. According to BCCT assessment, excellent and good cosmetic outcomes were achieved in 95% of patients. PROMs demonstrated favorable outcomes, with mean scores of 73.4 ± 4.7 for physical well-being, 73.8 ± 4.2 for psychological well-being, and 70.1 ± 6.3 for satisfaction with the breast. CWPFs were used for reconstruction of UIQ defects following breast-conserving surgery with acceptable postoperative complication rates and favorable cosmetic assessment in this retrospective cohort. These findings describe the surgical and aesthetic outcomes observed in this challenging breast quadrant. Further prospective studies with larger patient populations are needed to better define the role of CWPFs in UIQ reconstruction. Retrospectively registered after the approval of Baheya Ethical Committee, IRB no. 202,506,300,026.
Hypertension (HTN) increasingly originates in childhood and adolescence, with obesity and smoking as modifiable risk factors. However, longitudinal evidence on their independent and joint effects on HTN risk into early adulthood remains limited in non-Western populations. Using data from the Tehran Lipid and Glucose Study (TLGS), we followed 985 adolescents (mean age 15.01 years) for a median of 15.05 years. Adolescent overweight/obesity was defined using national BMI percentiles, and smoking status was self-reported. Incident adulthood HTN was defined as blood pressure ≥ 140/90 mmHg or use of antihypertensive medication. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential confounders. Over follow-up, 95 participants developed HTN. In adjusted analyses, adolescent overweight/obesity was independently associated with higher adulthood HTN risk (HR: 1.73; 95% CI: 1.11-2.71). Adolescent smoking was not independently associated with adulthood HTN after adjustment (HR: 1.15; 95% CI: 0.63-2.09). In joint exposure analyses, overweight/obese non-smokers had a higher risk than normal-weight non-smokers (HR: 1.77; 95% CI: 1.10-2.84), whereas smokers did not show statistically significant excess risk regardless of weight status. The obesity-smoking interaction suggested a possible synergistic effect on HTN risk in adulthood. Adolescent overweight/obesity is an independent predictor of adulthood HTN. Although smoking was not independently associated after adjustment, the potential interaction between obesity and smoking merits further study. Prevention efforts should prioritize adolescent weight management to reduce long-term cardiovascular risk. Not applicable.
Medium-chain carboxylic acids, such as n-caproate, are attractive sustainable platform chemicals. However, their microbial production is often limited by electron availability and low product selectivity. This study investigated the effect of hydrogen supplementation on glucose-based n-caproate production by Caproiciproducens galactitolivorans. Batch fermentation was performed under various hydrogen pressures (0 to 600 kPa). At 600 kPa hydrogen,n-caproate reached 8.0 g L-1, accompanied by a 66% increase in n-caproate selectivity and a tenfold increase in the intracellular redox-cofactor ratio, consistent with enhanced redox-cofactor turnover. Multi-omics analysis indicated metabolic remodeling under hydrogen-enriched conditions, including the increased abundance of key enzymes in the reverse β-oxidation pathway and redox-associated functions. In contrast, although fatty acid biosynthesis genes were transcriptionally induced, this transcriptional increase was not reflected at the protein level, suggesting a metabolic response more consistent with reverse β-oxidation-supported n-caproate synthesis than with fatty acid biosynthesis. These results support the use of hydrogen as a clean external reducing agent for improving n-caproate yield and redox efficiency in defined microbial systems. This study provides mechanistic insights into redox-driven metabolic control and selective n-caproate production in a defined microbial chain elongation system.
Mitochondrial dysfunction has been proposed as a contributor to neurodegeneration in multiple sclerosis (MS). While the accumulation of somatic mitochondrial DNA (mtDNA) mutations with age is well documented in other neurodegenerative conditions, its role in MS progression remains largely unexplored. The aim of this study was to investigate the association between age and somatic mtDNA mutation burden in MS patients and evaluate whether any difference exists according to disease course. A total of 404 MS patients were recruited. Whole mtDNA was sequenced from blood-derived DNA using long-range PCR and the Illumina® Nextera XT kit. Somatic mutations were defined based on heteroplasmy levels between 1-5%. Linear regression models were used to assess the association between age and mutation rate. We observed a significant age-dependent increase in low-frequency non-synonymous mtDNA mutations in MS. Analyses stratified by disease course revealed that this effect was substantially driven by PPMS patients (n = 238, P = 2.71 × 10-3), while no association was seen in RRMS (n = 155, P = 0.35), suggesting course-specific mitochondrial trajectories. Furthermore, fast-progressing patients showed a positive linear relationship between age and mtDNA mutation rate (P = 0.017), while slow-progressing ones showed an opposite trend (test for interaction P = 0.013). These findings support the existence of a differential age-related accumulation of somatic mtDNA mutations detected in blood across MS courses.
Developing safe, effective, and practically useful clinical prediction models (CPMs) traditionally requires extensive collaboration between clinical experts, data scientists, and informaticists to refine the many small but critical details of the model building process. When incorporating unstructured clinical notes, this challenge magnifies, as notes essentially contain an infinite number of concepts that can be used for modeling. We introduce HACHI, an iterative human-in-the-loop framework that uses AI agents to accelerate the development of fully interpretable CPMs from clinical notes, where CPMs are defined as linear models of yes-no questions. HACHI alternates between an AI agent that uses statistical tools and embedded knowledge to explore candidate concepts and domain experts who provide feedback to the AI agent. The framework optimizes for transparency, steerability, and reciprocal learning to ensure effective collaboration between the clinical AI team and the AI agent. In two real-world prediction tasks (acute kidney injury and traumatic brain injury), HACHI outperforms existing approaches, discovers clinically relevant concepts, and improves model generalizability across clinical sites and time periods. HACHI also highlights the critical role of human oversight, such as in directing the AI agent to explore new concept categories, adjusting concept granularity, and identifying data bias and leakage.