In this study, we examined resident preferences for prospective end-of-life management of a coastal wind farm in Japan through a case study of an 11-turbine, 22 MW installation, based on a questionnaire survey of 218 households within a 4 km radius. Respondents were presented with four disposition options: repowering with unchanged capacity (56.9%), repowering with increased capacity (18.8%), decommissioning (15.1%), and lifespan extension (9.2%). Preferences were examined through perceptual, attitudinal, and demographic lenses, though inferential support remained limited across several predictors. Descriptively, negative impressions were concentrated among decommissioning proponents, yet inferential testing showed no significant predictive effect for visual or acoustic evaluations. Principal component analysis consolidated perceptual dimensions, and binary logistic regression indicated that disaster-risk cognition alone significantly predicted support for active reconstruction, whereas mitigation measures and noise annoyance were statistically non-significant. Analysis of variance followed by Tukey's honestly significant difference post-hoc tests revealed significant yet modest differences in expectations for post-operational attributes-such as landscape harmony, tourism attraction, information transparency, proper explanations, and blade length-across preference groups, though effect sizes remained limited. No demographic or geographic variables were significantly associated with end-of-life preferences, indicating limited explanatory power of conventional socio-spatial characteristics. These findings highlight the limited role of demographic determinants and the importance of disaster-risk cognition and procedural fairness in shaping wind farm end-of-life strategies. They also underscore the need to incorporate local perspectives into policy frameworks through transparent communication, locally adaptive mitigation, and sustained stakeholder engagement.
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.
Despite well-documented harms of prenatal alcohol exposure, evidence-based treatment guidelines for alcohol use disorder (AUD) during pregnancy remain limited. We systematically reviewed international clinical practice guidelines to examine how they address the full cascade of AUD care during pregnancy, including diagnosis, engagement, treatment initiation, and retention. We searched over 40 clinical practice guideline databases (including PubMed and Guidelines International Network) and gray literature sources globally, identifying 1045 records. Using the Population, Interventions, Comparators, Attributes, Recommendation Characteristics (PICAR) framework, we evaluated guidelines from medical organizations in English-speaking nations addressing alcohol use and AUD management in pregnancy. Our final analysis included 18 guidelines from the United States, Canada, the United Kingdom, Australia/New Zealand, and the World Health Organization published from 2014 to the present. Two reviewers independently assessed each guideline using the Appraisal of Guidelines Research and Evaluation-Recommendations Excellence (AGREE-REX) framework to evaluate quality and risk of bias. We used narrative synthesis to summarize findings across key concepts and care cascade stages. Nearly all guidelines (94%) described risks of alcohol exposure and recommended counseling on cessation (89%), yet few extended beyond these early cascade stages. Only 44% mentioned medications for AUD (MAUD), and merely 17% discussed specific psychosocial treatments. Among guidelines addressing MAUD, only one cautiously supported use, while three explicitly recommended against it. Most guidelines (61%) ended treatment recommendations at referral to specialty care, with half limiting guidance to acute alcohol withdrawal management. Taken together, our findings reveal a stark misalignment between screening emphasis and treatment guidance. While guidelines consistently recommend universal screening and brief intervention, they provide minimal actionable frameworks for managing AUD throughout pregnancy. This gap leaves clinicians without evidence-based pathways for comprehensive AUD treatment during the prenatal period, highlighting an urgent need to strengthen both the evidence base and clinical guidance for AUD management in pregnancy.
Imposter syndrome (IS), the phenomenon of feeling inadequate despite having the qualifications, accolades, and attributes to succeed, is prevalent among physicians in multiple fields. We sought to characterize the prevalence of imposter syndrome and determine its impact among cardiothoracic trainees and early-career surgeons. A multisection survey instrument was distributed to cardiothoracic surgery trainees in the US and early career (EC) cardiothoracic surgeons within their first 7 years after training. The survey included a validated imposter phenomenon scale, instruments to measure social support, to detect burnout, and to assess symptoms of anxiety and depression. Multivariable logistic regression analysis was performed to identify characteristics associated with significant imposter syndrome. Relationships between imposter syndrome and associated conditions were explored using Pearson correlation coefficients. A total of 1048 subjects were contacted; complete responses were received from 143 (13.6%), of which 64 (44.7%) were from trainees and 79 (55.3%) from EC surgeons. Significant imposter syndrome was present in 88 subjects (61.6%) and was more common among trainees than EC surgeons (71.9 vs. 53.2%, p = 0.01). On multivariable analysis, female gender (odds ratio (OR) 6.9, 95% CI, 2.8-19.1; p < 0.01) was predictive of clinically significant IS, while a thoracic training track (OR 0.26, 95% CI, 0.08-0.72; p = 0.03) was protective. There was a positive correlation between IS and anxiety, between IS and foregone career opportunities, and a negative correlation with social support. Imposter syndrome, associated in particular with anxiety symptoms, was common amongst respondent cardiothoracic trainees and early career surgeons. Potential links with gender, training track, social support, and missed career opportunities were identified. Further study of IS, awareness and strategies to mitigate should be considered in cardiothoracic training.
Global developmental delay (GDD) and intellectual disability (ID) are common neurodevelopmental disorders with a strong genetic basis. However, comprehensive large-cohort analyses integrating genotype-phenotype correlations and functional mechanisms remain limited. This study aimed to systematically characterize the clinical and genetic spectrum of GDD/ID in a large single-center cohort and to explore the functional attributes of disease-causing genes. We retrospectively analyzed 1024 children diagnosed with GDD or ID who underwent genetic testing, including trio whole-exome sequencing (trio-WES), proband-only WES, and clinical exome sequencing. Clinical phenotypes were categorized, and functional enrichment analyses were conducted for genes associated with diagnostic and probable diagnostic results. A genetic diagnosis was achieved in 48.1% of patients, with trio-WES demonstrating a significantly higher diagnostic yield than proband-only approaches. Pathogenic variants mainly comprised single-nucleotide variants and copy number variants. Identified genes were predominantly involved in protein homeostasis, synaptic and ion channel function, epigenetic regulation, and key developmental signaling pathways. Distinct genotype-phenotype associations were observed among clinical subgroups, including enrichment of synaptic-related genes in epilepsy-associated GDD/ID and epigenetic regulatory genes in patients with facial dysmorphism.  This study provides a comprehensive characterization of the genetic landscape of GDD/ID in a large single-center cohort and identifies distinct genotype-phenotype correlations and convergent molecular pathways underlying these disorders. • Global developmental delay (GDD) and intellectual disability (ID) are highly heterogeneous neurodevelopmental disorders with a strong genetic basis. • We report a large single-center cohort of 1024 children with GDD/ID, providing a comprehensive overview of the genetic landscape and diagnostic yield of different sequencing strategies. • Our study systematically integrates genotype-phenotype correlations with functional pathway analyses, highlighting key molecular mechanisms underlying GDD/ID and supporting refined molecular stratification.
Enhancing the quality and nutrient composition of citrus fruits is essential for ensuring food and nutritional security. In the present study, twenty-four newly developed interspecific citrus scion hybrids (16 Orangelos and 8 Tangelos) from 'Pummelo' × 'Mosambi' sweet orange and 'Pummelo' × 'Dancy' tangerine crosses, along with their parental genotypes, were evaluated for fruit physico-chemical attributes, bioactive composition, and mineral nutrient profiles. Significant variation was observed due to heterozygosity-driven transgressive segregation in the interspecific hybrid progenies. Fruit physico-chemical parameters ranged as follows: juice recovery (6.20-49.52%), juice pH (3.30-4.73), juice TA (0.65-3.42%), juice TSS (7.90-13.33), ascorbic acid (26.00-52.00 mg 100 ml- 1 juice), total phenols (35.33-199.83 mg GAE 100 ml- 1 juice), total flavonoids (17.67-85.33 mg QE 100 ml- 1 juice), and antioxidant activity (1.21-5.20 µmol TE ml- 1 juice). Juice mineral nutrient levels were in the following descending order: potassium (94.87-1467.13 mg L- 1) > calcium (290.20-561.07 mg L- 1) > phosphorus (43.41-171.29 mg L- 1) > magnesium (29.76-82.02 mg L- 1) > iron (1.33-7.08 mg L- 1) > zinc (1.34-2.32 mg L- 1) > manganese (0.56-1.29 mg L- 1) > copper (0.54-0.86 mg L- 1), suggesting considerable genotypic variation following interspecific hybridization. Higher estimates of genetic variability and heritability for juice mineral nutrients and bioactive compounds indicate strong potential for trait-based selection and efficient genetic improvement of citrus fruits. Multivariate analysis and the MGIDI-based approach identified four interspecific scion hybrids, namely 'Orangelo 2-3', 'Tangelo 8-19', 'Orangelo 13 - 6', and 'Orangelo 7 - 4', as the most promising.
High biocompatibility and three-dimensional printability of gels make them highly promising for the food industries. Appropriateness of gels for the food industry depends heavily on their mechanical characteristics and molecular dynamics. For identifying dynamic molecular information at the atomic level, molecular docking (MD) and molecular dynamics simulation (MDS) are thought to be viable methods. They can be used as a tool in creating food gels because they may investigate chemical bonding, particular binding sites, changes in spatial structure, and binding energy between molecules, as well as assess the ideal conformation. MD techniques can reveal the biopolymer interactions. Promising methods include data-driven protein engineering, which designs proteins using computer techniques. The history and evolution of MD techniques are discussed in this article, with a focus on their uses in the food-based gel field. Lastly, research avenues for enhancing the quality attributes of food-based gels via MD and MDS are discussed.
Respiratory illness contributes to substantial global morbidity and mortality. In Madagascar, an island nation off the southeastern coast of the African continent, hospital-based public health surveillance for respiratory pathogens screens for common respiratory viruses. However, many cases remain undiagnosed. We conducted metagenomic Next Generation Sequencing (mNGS) to identify the pathogen profile of 102 undiagnosed febrile patients who presented to public hospitals with respiratory symptoms and screened negative on a 14-virus multiplex RT-qPCR. We analyzed the diversity of the respiratory microbiome of each patient from mNGS data and identified viral infections potentially linked to undiagnosed fever. We assembled whole genome consensus sequences of viruses with sufficient read depth and coverage, characterized each phylogenetically, and identified any discrepancies with the primers used in the multiplex RT-qPCR panel. Finally, we compared all whole genome sequences against publicly available global databases in a phylogenetic analysis. We identified evidence of infection by a wide range of known human viruses in approximately two thirds (64.7%) of study participants from nine different families of viruses and generated 30 complete or nearly complete consensus sequences of known respiratory viruses including orthopneumoviruses, metapneumoviruses, rhinoviruses, coronaviruses, parainfluenza virus, and bocaparvovirus. mNGS-attributed evidence of infection was predominantly due to orthopneumovirus (also called respiratory syncytial virus [RSV]; n = 24; n = 8 previously diagnosed) and rhinovirus (n = 18) detections, despite previous negative RT-qPCR results for the majority of these cases. Finally, phylogenetic analysis identified two distinct phylogenetic clusters of RSV subtype A, suggesting local transmission following distinct international introductions for this virus. mNGS provides a sensitive pan-pathogenic tool for virus detection. We demonstrate the diversity of viruses associated with undiagnosed respiratory fevers in Madagascar, emphasize the importance and relevance of the existing respiratory surveillance in the country, and highlight the interconnectedness of regional respiratory infection dynamics with global networks of respiratory pathogen transmission.
In situ detection of paramagnetic ions, including ions and biological macromolecules, is critical for fundamental research and applications in biology, chemistry, and medicine. The negatively charged boron vacancy (VB-) defects in hexagonal boron nitride (hBN) have emerged as versatile, highly sensitive quantum sensors for detecting various physical quantities. To further extend the scope and make practical applications of the quantum sensing, in this work, we demonstrate in situ quantum detection of the paramagnetic Mn2+ ions and ferritin in both solution and dry states using VB- defects in hBN. The experiments show that the optically detected magnetic resonance (ODMR) contrasts of VB- defects decrease with increasing concentrations of Mn2+ and ferritin in solution states; however, the ODMR contrasts remain unchanged in the case of dry states. This phenomenon is attributed to magnetic-noise-induced depopulation and modulated solution conductivity by solution paramagnetic ions. At the same time, the spin longitudinal relaxation rates monotonically increase with concentration in both solution and dried states as a function of ions concentration due to the magnetic noise from paramagnetic ions. Moreover, VB- defects can also distinguish different ionic species based on their distinct relaxation rates, requiring no prior knowledge. Finally, the all-optical relaxation method is also adopted to efficiently detect ferritin and paramagnetic ions. Collectively, our work establishes VB- defects in hBN-based sensors as a versatile quantum sensing platform for different species of paramagnetic ions in biology and chemistry, offering dual-modal detection methods including ODMR and T1 relaxation with operational flexibility and high sensitivity.
Accurately measuring vaccination coverage is crucial for programmatic and policy decision making, however accurate measurement of coverage can be challenging. We aimed to understand the extent of, and reasons for, inaccurate vaccination card records in a rural, low-income setting in Jigawa state, Nigeria. We conducted an explanatory sequential mixed-methods study in Kiyawa Local Government Area, Jigawa State, from September 2022 to July 2023, using data from the INSPIRING Jigawa trial (ISRCTN39213655). Quantitative data was gathered from surveyed women aged 16-49 in sampled compounds, who presented their child's vaccine card. Vaccine documentation was defined as inaccurate when the vaccine card is discordant with caregiver report. Adjusted logistic regression identified factors associated with inaccuracies. We conducted in-depth interviews with healthcare workers and focus groups with community members, analyzing transcripts using conventional content analysis, and triangulated findings with quantitative results. Records for 4258 children under five-years, from 3232 women, were examined. Of these children, 441 (10.4%) had vaccine cards that were deemed inaccurate by their caregivers. Inaccuracies were primarily attributed to cards being filled despite the child not receiving the vaccine, misplacement or loss of vaccine cards, vaccine stock-out when cards had already been filled, and vaccine card stock-out when the vaccine had been administered. Our adjusted logistic regression results show the following variables were associated with reporting inaccurate vaccine cards (under or over-reporting): any education compared to none (adjusted odds ratio (aOR): 1.33, 95%CI: 1.03, 1.75), having co-wives compared to no co-wife (aOR: 0.78, 95%CI: 0.62, 0.98), and child's age: 12-24 months compared to < 12 months (aOR: 2.70, 95%CI: 1.94, 3.75) and 25 months and above compared to < 12 months (aOR: 2.30, 95%CI: 1.69, 3.12). Our qualitative findings highlighted maternal lack of knowledge of vaccination schedule and forgetfulness about the vaccination schedule as common reasons for vaccine card inaccuracy. We identified health system failures and caregiver barriers leading to inaccurate reports in vaccine cards. It is essential to sensitize caregivers and healthcare providers on the importance of accurately documenting vaccines and validating immunization recording systems. Not applicable.
Glycosylation is a critical post-translational modification (PTM) in biotherapeutics that influences protein structure, stability, pharmacokinetics, biological activity, and immunogenicity. Comprehensive characterization of glycosylation and other PTMs is therefore important for biopharmaceutical development and quality assessment. Aflibercept is a recombinant fusion protein containing five N-glycosylation sites and multiple potential O-glycosylation sites. Although site-specific N-glycosylation of aflibercept has been previously investigated, integrated characterization of glycosylation heterogeneity and aspartic acid (Asp) isomerization using an electron-transfer/higher-energy collision dissociation (EThcD) based workflow remains limited. In this study, EThcD data-dependent MS2 (ddMS2) peptide mapping was performed on a Thermo Scientific Orbitrap Excedion Pro mass spectrometer equipped with the EASY-ETD option for detailed characterization of aflibercept. Site-specific N-glycosylation profiles at all five glycosylation sites were identified and relatively quantified. In addition, an O-glycopeptide localized at S12 was detected, providing direct experimental evidence supporting site-specific O-glycosylation in aflibercept. The EThcD fragmentation approach also enabled differentiation and localization of isoAsp residues through characteristic diagnostic fragment ions, including low-abundance peptides containing multiple Asp residues. Several additional PTMs, including deamidation and oxidation, were simultaneously characterized within the same analytical workflow. The results also indicate that EThcD peptide mapping can support the integrated multi-attribute method (MAM) concept for complex glycoproteins by combining glycosylation analysis, Asp/isoAsp differentiation, and PTM profiling in a single experiment. This workflow may be useful for detailed structural characterization and analytical comparability assessment of therapeutic glycoproteins and biosimilars.
Urinary stone disease (USD, or urolithiasis) is common and poses a substantial healthcare and economic burden on the working-age population. This study aimed to provide epidemiological insights into the prevalence, incidence, trends, and risk factors of USD among the Chinese population. We conducted a prospective cohort study involving 966,481 participants from the CHinese Electronic health Records Research during 2009-2022 in Yinzhou, China (CHERRY). Temporal trends were estimated using annual percentage changes (APC) via Joinpoint regression analyses. Stratified Cox proportional hazards regression and propensity score analyses were employed to evaluate potential risk factors, population attribution factor (PAF) and number needed to prevent (NNTP). From 2014/2015 to 2021, there was an annualized increase in USD incidence by 5.3-6.8% (P < 0.05). Identified risk factors for USD included tobacco smoking, alcohol drinking, high body mass index, diabetes, hyperlipidemia, hypertension, and cardiovasculardisease while regular exercising served as a protective factor of USD. The PAF ranged from 1.3% for non-drinking behavior to 22.5% for regular exercising (weekly). Correspondingly, the NNTP ranged from 182 for non-smoking behavior to 21 for weekly exercising. USD is a common disease affecting approximately 1 in 10 Chinese, with the incidence rate increasing by 5-6% annually over the past 6-7 years. Lifestyle factors and metabolic syndromes are potential risk factors for the development of USD.
The aim of this paper is to contribute to the increased understanding of research methods on meditation as a tool for preventing and improving mental health by addressing the key challenges that research faces. Different definitions of meditation have been analyzed, and the complexity of the phenomenon, as well as the problems in conceptualization, have been highlighted. It has been emphasized that comparing the results of research is complicated by the fact that meditation encompasses a wide range of practices that differ in techniques, goals, and expected outcomes. A solution to this problem is the operationalization of the type of meditation being investigated and the standardization of protocols. In addition to this, meditators represent a diverse group of individuals who differ in experience, motivation, and characteristics. Therefore, it is essential to track the characteristics of the participants closely and, when conducting quantitative research, stratify the sample according to relevant characteristics. Repeated measurements do not always yield the same results, which is attributed to numerous methodological shortcomings and a lack of a theoretical framework. The successful outcomes of meditation are often determined in various ways, so it is necessary to define measurable outcomes that are specific to the research goals. Given the difficulty of quantifying the subjective experiences resulting from meditation practice, it is beneficial to combine qualitative and quantitative measurements. Due to the complexity of the meditation phenomenon, research should be interdisciplinary, incorporating knowledge and insights from psychology, philosophy, anthropology, neuroscience, biology, sociology, and comparative studies of cultures and religions. More high-quality, qualitative, and interdisciplinary research is needed to understand better the process of meditation and its impact on mental processes, personality, and behavior, and subsequently to improve its application in the field of mental health.
Infections represent major but underrecognized complications of type 1 diabetes (T1D), type 2 diabetes (T2D), and prediabetes. This recent overview includes use of linked U.K. primary care, hospitalization, and mortality data to examine infection risk for >800,000 individuals with diabetes or prediabetes, compared with an age-, sex-, and ethnicity-matched group without diabetes. We assessed 1) infections in primary care and requiring a prescription, 2) infections leading to hospitalization, and 3) infection-related mortality, over 5 years (2015-2019). Infection risks were consistently elevated across all forms of diabetes, compared with risk for those without diabetes. The highest relative risks were observed in T1D and lowest in prediabetes. While relative risks were similar across different ethnicities, the population burden of infections attributable to diabetes was highest among South Asians. There were independently strong graded associations for average HbA1c level and visit-to-visit HbA1c variability with infection risk, particularly for hospitalization infections. Among individuals with T1D, the strongest associations with infection risk were seen for elevated HbA1c levels, whereas for T2D, variability contributed more to the excess burden of infections. Infection-related mortality across all ICD-10 chapters was substantial, representing the third leading cause of death in T2D after cardiovascular disease and cancer. Further, it might be underreported, as sepsis is rarely coded as the underlying cause of death. These findings highlight the importance of improved glycemic control, earlier recognition and treatment of infections, and stronger emphasis on infection management in clinical guidelines. Incorporation of HbA1c variability into diabetes risk algorithms, and evaluation of interventions that might stabilize control, such as continuous glucose monitoring, may enhance infection prevention and reduce complications.
Terminal sterilisation is a critical process for pharmaceutical products intended for parenteral or invasive administration, yet conventional sterilisation approaches can compromise thermolabile or chemically sensitive drug substances. In this study, the compatibility of crystalline and amorphous solid forms of five drug substances (betamethasone dipropionate (BMD), estradiol (E2), itraconazole (ITZ), vismodegib (VDG), and zolmitriptan (ZMT)) with sterilising gamma irradiation and ethylene oxide (EtO) cycles was evaluated in terms of chemical and physical stability. Physical stability was assessed by visual inspection of crystalline powders and amorphous solids pre- and post-sterilisation and by differential scanning calorimetry (DSC) to characterise the melting behaviour of crystalline drugs, and glass transition and recrystallisation events in amorphous forms. Chemical stability was examined using reverse phase-high-performance liquid chromatography (RP-HPLC), liquid chromatography-mass spectrometry (LC-MS), and proton nuclear magnetic resonance spectroscopy (¹H-NMR). Gamma irradiation and EtO preserved the chemical integrity of BMD, E2, ITZ, and VDG. A reversible colour change observed for ITZ was attributed to radical formation as confirmed by gentle heating, HPLC and LC-MS. E2 demonstrated alterations in crystallinity and thermal behaviour after sterilisation, despite maintaining chemical integrity. ZMT exhibited pronounced sensitivity to sterilisation: gamma irradiation induced physical softening and oxidative degradation, particularly in the amorphous form, while EtO sterilisation induced ZMT hydroxyethylation, as confirmed by LC-MS identification of multiple alkylated derivatives. Overall, sterilisation compatibility was governed primarily by molecular structure rather than the drug solid-state. These findings provide an insight for selecting sterilisation strategies and facilitate the translation of crystalline and amorphous pharmaceutical solids toward clinical application.
It has been a long, interesting, and mysterious nonequilibrium phenomenon that hot water may freeze faster than warm water, which is known as Mpemba effect. Studying its physical origin and exploring new Mpembalike effects have attracted broad interests. Here, we report experimental evidence of a novel Mpembalike effect in the aging process of glasses: a glass with an initial higher energy state ages (enthalpy decreases) faster and surpasses the glass with an initial lower energy state. This phenomenon is universally observed in different types of structural glasses, including metallic, polymer, and molecular glasses. The underlying thermodynamic mechanism is also studied using high-precision nanocalorimetry. It is found that preannealing at a higher temperature is critical to triggering the faster aging kinetics of the Mpembalike effect. This is attributed to the activation of a secondary β relaxation peak with a substantially lower kinetic barrier than the primary α relaxation peak. Thus, besides the α relaxation, the β relaxation plays a pivotal role in the enthalpy aging process, which is very sensitive to the thermal history. These findings may have broad implications for optimizing the thermal treatment and relaxations of different types of glasses.
Bacterial wound infections are often complicated by biofilm formation, which leads to persistent inflammation and multidrug resistance, severely impeding the healing process. Conventional antibiotic therapies are challenged by both overuse and rising antimicrobial resistance. To address this, we designed and fabricated a dual-mode responsive delivery system (CSOAC@MN) based on chitosan (CS) and oleanolic acid (OA) composite microneedles for synergistic sono-photodynamic therapy (SPDT). This system employs chlorin e6 (Ce6), which exhibits both photodynamic and sonodynamic activities, as the core antibacterial component. It utilizes the self-assembly properties of OA to form nanoparticles for Ce6 encapsulation, and reinforces the microneedle mechanical strength through composite formation with CS, enabling efficient transdermal delivery. In vitro experiments demonstrated that under combined laser and ultrasound irradiation, the system exhibited strong antibacterial activity against both standard strains (Staphylococcus aureus and Escherichia coli) and a clinically relevant drug-resistant strain and effectively disrupted pre-formed biofilms. The antibacterial effect is attributed to the reactive oxygen species generated during synergistic SPDT. Cytocompatibility assays confirmed good biocompatibility with normal fibroblast cells at effective antibacterial concentrations. This study presents an integrated strategy combining transdermal microneedles with SPDT to combat biofilm-associated infections, showing promising potential for clinical translation.
Human social interactions rely on the ability to reflect on one's own and others' internal states and traits-a process known as mentalizing. Impaired or altered mentalizing is a hallmark of multiple psychiatric and neurodevelopmental conditions. Yet, replicable and easily testable brain markers of mentalizing have so far been lacking. Here, we apply an interpretable machine learning approach to multiple datasets (total n = 390) to train and validate fMRI brain signatures that predict i) mentalizing about the self, ii) mentalizing about another person, and iii) both types of mentalizing. Self-mentalizing and other-mentalizing classifiers had positive weights in anterior/medial and posterior/lateral brain areas, respectively, with accuracy rates of 82% and 77% for out-of-sample prediction. The classifier trained across both types of mentalizing showed 98% predictive accuracy and separated (mental) attributional from factual inferences. Classifier patterns revealed better self/other separation in healthy adults compared to individuals with schizophrenia and with increasing age in adolescence. Together, our findings reveal consistent and separable neural patterns subserving trait-based mentalizing about self and others-present at least from the age of adolescence and functionally altered in severe neuropsychiatric disorders. These mentalizing signatures hold promise as candidate neuromarkers of social-cognitive processes in different contexts and clinical conditions.
The primary objective of this study was to explore the existence and identify predictors of incongruent perceptions of pain, fatigue, and sleep disturbance, and to examine their associations with negative mood, intimate relationship, and quality of life in colorectal cancer patient- caregiver dyads. 271 colorectal cancer dyads completed questionnaires designed to assess a range of outcomes, including patient symptoms (pain, fatigue, sleep disturbance), negative mood, intimate relationship, and quality of life. Pearson's correlation, multiple linear regression analysis and structural equation modeling were used to analyze the data. There were significant disparities in incongruent perceptions of sleep disturbance between patients and caregivers (t=-3.241, p < 0.001). For incongruent sleep disturbance, regression analysis showed patient education level (B=-1.014, p = 0.001) and caregiver education level (B=-1.140, p < 0.001) demonstrated significant negative associations. Longer patient diagnosis duration (B=-1.876, p = 0.010) was negatively associated. Caregiver religious affiliation (B=-1.611, p = 0.027) and marital status (B= -3.097, p = 0.001) showed negative associations. Patient gender (B= 1.361, p = 0.037) and caregiver gender (B = 1.803, p = 0.004) exhibited positive associations. Dyadic relationship type (B = 1.568, p = 0.043) was positively associated. The analysis revealed that incongruent perceptions of sleep disturbance exhibited a significant correlation with the quality of life and negative mood of both individuals within colorectal cancer patient-caregiver dyads. The model fit estimates were as follows: χ2/df = 1.570, GFI = 0.967, CFI = 0.957, IFI = 0.922, RMSEA = 0.036, SRMR = 0.053. Pathway analysis demonstrated that incongruent perceptions of sleep disturbance exerted a significantly direct effect on the quality of life of both individuals in colorectal cancer patient-caregiver dyads, albeit in opposite directions (B=-0.238, p < 0.001; B = 0.358, p < 0.001, respectively). Furthermore, the analysis revealed an actor-partner mediating effect of incongruent perceptions of sleep disturbance, negative mood, intimate relationship, and quality of life. The findings of the present study indicated that incongruent perceptions of sleep disturbance were associated with negative mood, low intimate relationship satisfaction, and low quality of life. The individual attributes of patients (gender, educational level and time since diagnosis) and caregivers (gender, educational level, religious beliefs and marital status), as well as dyadic factors such as relationship, could predict patient-caregiver concordance on assessing patients' symptoms. It is recommended that healthcare providers should reinforce patient-caregiver dyadic symptom education to reduce incongruent perceptions of sleep disturbance in colorectal cancer dyads with a view to enhancing their quality of life. More sleep management and substantial emotional support should be provided by family caregivers and healthcare providers.
To evaluate the effects of cardiopulmonary bypass (CPB) on peripheral white blood cell counts, neutrophil surface marker expression, and neutrophil function by comparing patients undergoing on-pump CABG (ONCAB) versus off-pump CABG (OPCAB), and to identify CPB-related immunological and inflammatory alterations. Patients undergoing on-pump CABG (ONCAB) or off-pump CABG (OPCAB) were recruited. Blood samples were collected preoperatively and at 24 h postoperatively. The primary outcome was the neutrophil-to-lymphocyte ratio (NLR) measured at 24 h after surgery. Secondary outcomes included monocyte Human leukocyte antigen-DR (HLA-DR) expression, lymphocyte programmed cell death protein-1 (PD-1) expression, and neutrophil surface markers (CD11b, CD18, CXCR2, CD35, CD63, CD66b, CD88, and programmed cell death-ligand 1). Neutrophil apoptosis, reactive oxygen species (ROS) production, and plasma inflammatory mediators (interleukin-6, tumor necrosis factor-alpha, interleukin-10) were also measured. Postoperative clinical outcomes and laboratory parameters were recorded. Data from 36 ONCAB patients and 18 OPCAB patients were analyzed. Postoperative NLR was significantly higher in the ONCAB group than in the OPCAB group (16.6 ± 6.1 vs. 13.1 ± 3.9; p = 0.015). This difference was attributable to lower lymphocyte counts in the ONCAB group (0.7 ± 0.2 vs. 0.8 ± 0.2 × 109/L; p = 0.002), whereas neutrophil counts did not differ significantly between groups. In both groups, monocyte HLA‑DR expression decreased and lymphocyte PD-1 expression increased after surgery. CPB did not result in significant alterations in neutrophil adhesion, chemotaxis, degranulation markers, ROS production, or apoptosis. ONCAB patients had higher postoperative levels of aspartate aminotransferase (AST), cardiac troponin I (cTnI), and procalcitonin (PCT), as well as longer durations of mechanical ventilation and intensive care unit stay. CPB elevates the NLR after CABG primarily, accompanied by reduced level of lymphocyte count, but not neutrophil count or molecular markers of neutrophil functional. These results might reflect a higher risk of short-term complications after on-pump CABG.