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Background/purpose: Depressive and anxiety symptoms were common among lesbian, gay, and bisexual (LGB) individuals during the COVID-19 pandemic. This 4-year follow-up study was conducted to investigate the predictors of depressive and anxiety symptoms in Taiwan's young adult LGB population. Methods: Baseline data, including depressive and anxiety symptoms, demographic characteristics, sexual stigma, self-identity confusion, and family support were collected from 1000 LGB individuals. The participants’ depressive and anxiety symptoms were reassessed 4 years after the baseline measurements. The predictive effects of the baseline factors on depressive and anxiety symptoms at follow-up were examined through linear regression analysis. Results: Greater lack of identity, unconsolidated identity, sexual orientation microaggression, and lower perceived family function at baseline were significantly associated with more severe depressive and anxiety symptoms at follow-up. After adjustment for baseline depressive symptoms, being men, greater lack of identity, lower perceived family function, and more severe anxiety symptoms at baseline were significantly associated with more severe depressive symptoms at follow-up. After adjustment for baseline anxiety symptoms, greater unconsolidated identity and more severe depressive symptoms at baseline were significantly associated with more severe anxiety symptoms at follow-up. Conclusions: Intervention aimed at reducing depressive and anxiety symptoms in LGB individuals should be developed considering the predictors identified in this study.

Abstract This study examined the sex-specific mortality risk and causes of death soon after hip fracture in Taiwan. The objective of this study was to evaluate the 30-day mortality risk and cause of death in patients with hip fracture and identify its associated risk factors. We conducted a retrospective cohort study using data from the National Health Insurance Research Database in Taiwan from 2000 to 2015. This study included patients aged 50 years or older who were admitted to a hospital with a hip fracture diagnosis for the first time. Of 285,891 patients hospitalized for their first hip fracture, 8,505 (2.98%) died within 30 days. The mortality risk of hip fracture declined from 3.76% in 2000 to 2.92% in 2015. Circulatory system diseases like ischemic heart disease and cerebrovascular disease were the most common cause of death and accounted for 22% of deaths within 30 days after fracture. Accidents and unintentional injuries caused 18% of deaths, followed by malignant neoplasms in 10% of deaths. Multivariate Cox regression identified older age, male sex, higher Charlson Comorbidity Index (CCI), suburban or rural residence, and lower income as risk factors for hip fracture mortality. The 30-day mortality risk of hip fractures has decreased but remains correlated with male sex, older age, and comorbidities. Circulatory diseases were the main cause of death. Early identification and treatment by experienced clinicians may optimize outcomes, minimize complications, and reduce mortality risk in the 30 days following hip fracture.

Objective: To evaluate the residual placental volume and correlated factors using three-dimensional ultrasound (3D) in patients with placenta accreta spectrum (PAS) after conservative management. Materials and methods: From January 2005 to December 2023, we retrospectively reviewed patients with PAS who underwent prophylactic transcatheter arterial embolization and retained the placenta in situ. The residual placental volume was assessed using 3D ultrasound equipped with virtual organ computer-aided analysis. We determined the resorption rate of the residual placenta (RRRP) and analyzed correlated factors. Results: Eighteen patients with PAS were included. The mean RRRP was 152.64 ± 147.97 cm3/month. The median natural resorption time was 5.5 months. According to Spearman's correlation, only the initial placental volume was significantly associated with RRRP (p = 0.001, correlation coefficient = 0.701). Initial placental volume was not associated with postpartum hemorrhage, postpartum infection, resume of menstruation, subsequent pregnancy, or mean white blood cell count. Conclusion: 3D ultrasound is useful for measuring the volume of residual placenta. A larger initial placental volume was associated with a higher RRRP.

Our previous studies have revealed a correlation between urinary phthalates (PAE) metabolites and parabens and PM2.5 exposure and susceptibility to attention-deficit/hyperactivity disorder (ADHD) in school-age children. Our goal was to examine the relationships between urinary organophosphate flame retardants (OPFRs) and their metabolites and the susceptibility to ADHD in the same cohort of children. We recruited 186 school children, including 132 with ADHD and 54 normal controls, living in southern Taiwan to investigate five OPFRs (1,3-dichloro-2-propyl phosphate (TDCPP), tri-n-butyl phosphate (TnBP), tris (2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPHP)) and five OPFR metabolites (bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-n-butyl phosphate (DNBP), bis(2-chloroethyl) hydrogen phosphate (BCEP), di-(2-butoxyethyl) phosphate (DBEP), and diphenyl phosphate (DPHP)) in urine. ADHD patients’ behavioral symptoms and neuropsychological function were assessed using the Swanson, Nolan, and Pelham Version IV Scale (SNAP-IV) and the Conners’ Continuous Performance Test 3rd Edition (Conners CPT3), respectively. BCEP was predominant among urinary OPFRs and the metabolites in both the ADHD and control groups. ADHD children had significantly higher levels of urinary BDCPP, BCEP, DBEP, DPHP, TCEP, TBEP, TNBP, TPHP, and Σ10OPFR compared to the controls. After controlling for age, gender, body mass index, PM2.5 exposure scenarios, and urinary phthalate metabolites, parabens, bisphenol-A and creatinine, levels of urinary BDCPP, TDCPP, and TBEP in ADHD children showed significant and dose-dependent effects on core behavioral symptoms of inattention. DNBP levels were positively correlated with neuropsychological deficits (CPT detectability, omission, and commission), while urinary DPHP in ADHD children were negatively related to CPT detectability and commission. Hyperactivity and impulsivity were not correlated with urinary OPFRs and their metabolites in ADHD children. In conclusion, the ADHD symptom of inattention and CPT performance may be closely associated with certain urinary OPFRs and their metabolites, independent of urinary PAE metabolites, parabens, and bisphenol-A in school-age-ADHD children.

Abstract Morphogenesis requires building stable macromolecular structures from highly dynamic proteins. Muscles are anchored by long-lasting integrin adhesions to resist contractile force. However, the mechanisms governing integrin diffusion, immobilization, and activation within developing tissues remain elusive. Here, we show that actin polymerization-driven membrane protrusions form nanotopographies that enable strong adhesion at Drosophila muscle attachment sites (MASs). Super-resolution microscopy reveals that integrins assemble adhesive belts around Arp2/3-dependent actin protrusions, forming invadosome-like structures with membrane nanotopographies. Single protein tracking shows that, during MAS development, integrins become immobile and confined within diffusion traps formed by the membrane nanotopographies. Actin filaments also display restricted motion and confinement, indicating strong mechanical connection with integrins. Using isolated muscle cells, we show that substrate nanotopography, rather than rigidity, drives adhesion maturation by regulating actin protrusion, integrin diffusion and immobilization. These results thus demonstrate that actin-polymerization-driven membrane protrusions are essential for the formation of strong integrin adhesions sites in the developing embryo, and highlight the important contribution of geometry to morphogenesis.

Abstract Opsins are G protein-coupled receptors (GPCRs) that have evolved to detect light stimuli and initiate intracellular signaling cascades. Their role as signal transducers is critical to light perception across the animal kingdom. Opsins covalently bind to the chromophore 11-cis retinal, which isomerizes to the all-trans isomer upon photon absorption, causing conformational changes that result in receptor activation. Monostable opsins, responsible for vision in vertebrates, release the chromophore after activation and must bind another retinal molecule to remain functional. In contrast, bistable opsins, responsible for non-visual light perception in vertebrates and for vision in invertebrates, absorb a second photon in the active state to return the chromophore and protein to the inactive state. Structures of bistable opsins in the activated state have proven elusive, limiting our understanding of how they function as bidirectional photoswitches. Here we present active state structures of a bistable opsin, jumping spider rhodopsin isoform-1 (JSR1), in complex with its downstream signaling partners, the Gi and Gq heterotrimers. These structures elucidate key differences in the activation mechanisms between monostable and bistable opsins, offering essential insights for the rational engineering of bistable opsins into diverse optogenetic tools to control G protein signaling pathways.

Abstract A mismatch in footprints of cervical total disc arthroplasty (CTDA) implants occasionally occurred in Asian population and it had been attributed solely to ethnic factor. Yet, cervical degeneration process may play a role. Our purpose was to compare the cervical vertebra morphometric data with and without degeneration. The study included patients with CT scans of cervical spine from our hospital between January, 2019, and September, 2021. The total cervical degenerative index (TCDI) of each patient were collected by adding CDI score for 5 disc-levels. Patients were categorized into normal (TCDI 0–5) and degeneration groups (TCDI 6–60). Various measurements of the C3–C7 vertebral body and endplate were taken. Forty-nine patients in the normal group and 55 in the degeneration group were included. No significant difference was noted in gender, BH, BW, or BMI except age and TCDI (p

Abstract Thyroid dyshormonogenesis (TDH) is responsible for 15%–25% of congenital hypothyroidism (CH) cases. Pathogenetic variants of this common inherited endocrine disorders vary geographically. Unraveling the genetic underpinnings of TDH is essential for genetic counseling and precise therapeutic strategies. This study aims to identify genetic variants associated with TDH in Southern Taiwan using whole exome sequencing (WES). We included CH patients diagnosed through newborn screening at a tertiary medical center from 2011 to 2022. Permanent TDH was determined based on imaging evidence of bilateral thyroid structure and the requirement for continuous medication beyond 3 years of age. Genomic DNA extracted from blood was used for exome library construction, and pathogenic variants were detected using an in‐house algorithm. Of the 876 CH patients reviewed, 121 were classified as permanent, with 47 (40%) confirmed as TDH. WES was conducted for 45 patients, and causative variants were identified in 32 patients (71.1%), including DUOX2 (15 cases), TG (8 cases), TSHR (7 cases), TPO (5 cases), and DUOXA2 (1 case). Recurrent variants included DUOX2 c.3329G>A, TSHR c.1349G>A, TG c.1348delT, and TPO c.2268dupT. We identified four novel variants based on genotype, including TSHR c.1135C>T, TSHR c.1349G>C, TG c.2461delA, and TG c.2459T>A. This study underscores the efficacy of WES in providing definitive molecular diagnoses for TDH. Molecular diagnoses are instrumental in genetic counseling, formulating treatment, and developing management strategies. Future research integrating larger population cohorts is vital to further elucidate the genetic landscape of TDH.

Abstract In the continental margin of the northeastern South China Sea, the sea level fluctuations since the Last Glacial Maximum have profoundly impacted the sedimentary environment. Our sub-bottom profiler data show a sedimentation process change from deposition to erosion during the Last Glacial Maximum. After the widespread erosion, the sedimentation process returned depositional throughout the Holocene, probably due to the rise of the sea level. This sedimentary process results in a widespread sedimentary unconformity in the continental slope, providing a benchmark for the end of the Last Glacial Maximum. Analyzing the sediment cores, we affirm that the change in current intensity is the primary factor controlling the sedimentary environments. The current intensities strengthened during the eustatic lowstand and weakened during the highstand periods, leading to alternating erosional and depositional processes. The widespread distribution of the erosive surface represents a regional-scale change in the sedimentary environment instead of a local event.

Abstract The understanding that students on varsity baseball teams exhibit lower academic performance amid the growth of baseball in Taiwan is well established. However, some studies have indicated a positive correlation between sports participation and academic achievement. Therefore, this study delved into the causal relationships between baseball-team participation and academic performance among ninth-grade students in Taiwan. It further explored the influence of various background factors based on the three facets of family capital on their academic performance. Data collected from an education longitudinal survey of secondary school students. Through bivariate analysis, factor analysis, and multiple regression analysis, the following findings emerged: (a) Baseball-team students exhibited 47.5 points lower academic performance than non-baseball-team ones. (b)The low academic performance was not exclusively a result of the poorer academic performance of indigenous students. (c)The hypothesis that three dimensions of family capital impact on academic performance was supported. (d) Baseball-team participation contributed to the low academic performance, which was not caused by the low eighth-grade results of the students. They exhibited low BCT scores after their 8th-grade results was controlled.

An outbreak of monkeypox (Mpox) appeared suddenly and rapidly spread worldwide during 2022. Men who have sex with men (MSM) are at a high risk of contracting Mpox compared to other cohorts. The present study examined the psychometric properties of a newly developed scale among MSM: the Motors of Mpox Vaccination Acceptance Scale (MoMVA) assessing cognitive components of the motivation to receive an Mpox vaccination. In total, 389 MSM participated in an online survey study. The factor structures of the MoMVA were first examined using exploratory factor analysis. After determining the factor structures, the MoMVA was further examined for: (i) internal consistency using Cronbach’s α; (ii) concurrent validity using correlations with risk perception of contracting Mpox and intention to receive an Mpox vaccination; and (iii) known-group validity by comparing the scores of the MoMVA between MSM who vaccinated and those who did not. The results indicated that the MoMVA had a two-factor structure (positive and negative motors). The MoMVA had acceptable internal consistency (α = 0.793 to 0.914), concurrent validity (associated with intention to receive an Mpox vaccination), and known-group validity (participants who vaccinated had higher MoMVA scores than those who did not). The results of the present study indicated that the psychometric properties of the MoMVA were good and that they can be used for assessing cognitive components of the motivation to receive an Mpox vaccination among MSM.

Background: Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, entered Taiwan at the end of 2021. The Taiwanese government ended its ''zero-COVID'' policy in March 2022. Multiple coronavirus disease 2019 (COVID-19) outbreaks began in April 2022. We monitored the replacement of Omicron subvariants after BA.1/BA.2 and analyzed their correlation with COVID-19 outbreaks. Methods: We collected SARS-CoV-2 real-time qRTPCR-positive nasopharyngeal swabs from Kaohsiung Medical University Hospital (KMUH), Kaohsiung City, Taiwan, and performed sequencing for specimens exhibiting a cytopathic effect in Vero E6 cells to determine their clades and lineages. We analyzed the medical records of COVID-19 patients and identified hospitalization risk factor(s). We retrieved SARS-CoV-2 sequences identified in Taiwan from GISAID and analyzed their correlation with COVID-19 data from the Taiwan Centers for Disease Control. Results: We analyzed the phylogenesis of KMUH-47 to KMUH-104 (SARS-CoV-2 isolates identified herein) and all of the Omicron subvariants from BA.5 to XBB.1 (n = 1930). Age and comorbidities were hospitalization risk factors. Men generally exhibited a greater fatality rate than women. COVID-19-related deaths predominantly occurred in individuals over 70 years old. The COVID-19-related case fatality rate increased as nucleotide (NT) and amino acid (AA) substitutions increased. The number of COVID-19-related cases and deaths progressively decreased with each outbreak between August 2022 and October 2023. Conclusion: Hospitalization was associated with age and the presence of comorbidities. COVID-19-related fatality was linked to sex, age, and the accumulation of NT and AA substitutions in emerging Omicron subvariants.

Objective: Hyperlipidemic patients with end-stage renal disease (ESRD) are at a higher risk of death from cardiovascular diseases, especially from acute myocardial infarction (AMI). Studies on the efficacy of statin therapy (ST) in dialysis patients after percutaneous coronary intervention (PCI) are limited. We examine the mortality associated with ST for these patients. Methods: From dialysis-dependent hyperlipidemic patients with AMI and receiving PCI in the claims data of National Health Insurance of Taiwan in 2000–2016, we identified a cohort with ST and a cohort without ST matched by propensity score at a 1:1 ratio. Both cohorts were followed up until the end of 2017. All-cause mortalities were examined for both cohorts. Other factors associated with the deaths were also examined. Results: Among 2642 enrollees in each cohort, over 99 % had hypertension. The all-cause mortality was 23 % lower in the ST cohort than in non-ST cohort (10.8 versus 14.0 per 100 person-years) with an adjusted hazard ratio of 0.77(95 % confidence interval = 0.71–0.84). Patients with comorbidities of diabetes, cerebrovascular accident (CVA) and congestive heart failure (CHF) were also at lower risk. The case-control analysis in the ST cohort showed the estimated risk of death increased with age, and higher for females and patients with peripheral artery disease. Conclusions: The ST for hyperlipidemic patients with ESRD experiencing AMI undergoing PCI could be benefited with lower all-cause mortality, even for patients with diabetes, hypertension, CVA or CHF.

Abstract Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm2 for 1 and 2 h separately. Resulting elevated caspase‐9 and ‐3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G1 phase. An elevated phosphor‐eNOSS1177 increased the production of nitric oxide and led to reactive oxygen species‐mediated oxidative stress. Shear flow also regulated epithelial–mesenchymal transition (EMT) by increasing E‐cadherin and ZO‐1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm2, the expressions of EMT were compared at lower (6.25 dynes/cm2) and at higher (25 dynes/cm2) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.

Background: Problematic use of the internet (PUI) is prevalent, particularly among adolescents and young adults. Given the limited measures to assess specific types of PUI, which encompasses a broad spectrum of activities such as online gaming, social media use, pornography use, shopping, gambling, and web-streaming, Muller et al. (2022) developed the Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) to comprehensively assess different types of PUI (i.e., gaming, shopping, social media use, gambling, and pornography use). The present study aimed to validate the Chinese ACSID-11 among adolescents incorporating cross-cultural adaptations. Methods: Using forward-backward translation method, a culturally adapted version of the ACSID-11 was prepared. Then, a cross-sectional online survey was administered between September 8 and September 26, 2023. Adolescents, using a convenience sample (N = 11,492; mean age = 16.42 years [SD ± 0.91]; 59.1% male), were recruited from six schools to complete the translated ACSID-11, Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Bergen Social Media Addiction Scale (BSMAS), and Smartphone Application Based Addiction Scale (SABAS) via an online platform. Pearson correlation coefficients assessed convergent/discriminant validity. Factor structure and measurement invariance were examined through confirmatory factor analysis (CFA) and multi-group CFA. Cronbach's alpha and McDonald's omega tested internal consistency. Results: Associations between the ACSID-11 components and other scales supported convergent validity (i.e., ACSID-11 gaming scale with IGDS9-SF [0.37 ≤ r ≤ 0.41]; social networks use scale with BSMAS [0.24 ≤ r ≤ 0.31]) and discriminant validity (i.e., online gambling scale with BSMAS [0.16 ≤ r ≤ 0.19] and with SABAS [0.11 ≤ r ≤ 0.13]). A four-factor solution indicated good fit with comparative fit index (CFI) ranging from 0.982 to 0.958. The ACSID-11 was measurement invariant across sexes (∆CFI = -0.001 to 0.000) and different levels of related addictive behaviors (∆CFI = -0.001 to 0.000). Both Cronbach's alpha and McDonald's omega (0.63 to 0.97) were acceptable for both frequency and intensity of responses. Conclusions: The ACSID-11 is an appropriate scale to assess different kinds of PUI among Chinese adolescents and students. Psychometric assessment of the measure in other cultures and among clinical samples is recommended.

Abstract Background Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma. Case presentation A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion. Conclusion Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload.

Abstract Background Clinical practicum is crucial for strengthening nursing students' clinical competence. However, nursing students often experience considerable stress during clinical practicum, and so they employ coping strategies to alleviate it. There is almost no empirical evidence on the change trajectory of perceived stress, coping strategies, and clinical competence among nursing students during a one-year clinical practicum. This study aimed to investigate the trajectory of change in perceived stress, coping strategies, and clinical competence among undergraduate nursing students during a one-year clinical practicum. Methods This study used a longitudinal cohort design. Undergraduate nursing students were recruited from a science and technology university in Taiwan to participate from February 2021 to January 2022. Perceived stress, coping strategies, and clinical competence among students in basic training practicum (T1), advanced training practicum (T2), and comprehensive clinical nursing practicum (T3) were surveyed by using the Perceived Stress Scale (PSS), Coping Behaviour Inventory (CBI), and Clinical Competence Scale (CCS). PSS, CBI, and CCS in T1, T2, and T3 were compared using a generalized estimating equation (GEE) to deal with correlated data. The level of statistical significance was set at α = 0.05. Results A total of 315 undergraduate nursing students completed the questionnaire. The study results show that the overall perceived stress of the students is the highest in T2 and the lowest in T3. The main source of stress of the students is 'taking care of patients' at T1 and 'lack of professional knowledge and skills' at T2 and T3. Students' perceived stress in 'taking care of patients' gradually decreases over time. The four coping strategies of CBI, which are 'stay optimistic', 'problem-solving', 'transference' and 'avoidance' in this order, remain the same ranking in three surveys.The main stress coping strategy used by students is 'stay optimistic', while the coping strategy 'avoidance' is used more frequently in T2 than in T1 and T3. Students' mean scores of the overall clinical competence and in the 'general nursing' and 'management' subscales in T3 are higher than those in T1 and T2. However, their mean scores in 'self-growth' and 'positivity' subscales are the highest in T1 and the lowest in T2. Conclusions The results show that through experiential learning in clinical practicum at different stages time after time, students' overall perceived stress is the lowest and their overall clinical competence is the highest in T3. The main coping strategy used when students managed stress is 'stay optimistic'. According to the results, we suggest that clinical educators provide students with appropriate guidance strategies at different stages of stress and continue to follow up the clinical competence and retention rates of these nursing students in the workplace in the future.

Background: The COVID-19 pandemic has substantially impacted healthcare systems and obstetric practices worldwide. Labor induction is a common procedure for preventing obstetric complications in high-risk populations. This study evaluated perinatal outcomes of labor induction using a modified management protocol in a tertiary care center during the COVID-19 pandemic. Methods: We conducted a retrospective study by reviewing electronic structured delivery records of women who underwent elective labor induction between June 2020 and October 2022. We analyzed maternal characteristics, maternal outcomes, and neonatal outcomes during the pre-pandemic (June 2020 to May 2021) and pandemic periods (May 2021 to October 2022). Results: The study included 976 cases: 325 pregnancies in the pre-pandemic group and 651 in the pandemic group. The pandemic group showed earlier gestational age at delivery (39 vs. 40 weeks, p < 0.01) and lower body mass index (27.1 vs. 27.5 kg/m2, p = 0.03). During the pandemic period, we observed a significant increase in labor induction cases and a decrease in cesarean sections. Neonatal outcomes, including Apgar scores and intensive care admissions, showed no significant differences between groups. Subgroup analysis identified advanced maternal age (OR = 1.08; 95% CI = 1.03–1.14; p < 0.01) and primiparity (OR = 5.24; 95% CI = 2.75–9.99; p < 0.01) as independent risk factors for cesarean delivery. Conclusions: Even under modified protocols for labor induction during the COVID-19 pandemic, more pregnancies underwent labor induction while achieving a significant reduction in cesarean sections. Advanced maternal age and primiparity were identified as independent risk factors associated with cesarean delivery.

DNA-encoded small molecule library technology has recently emerged as a new paradigm for identifying ligands against drug targets. To date, it has been used to identify ligands against targets that are soluble or overexpressed on cell surfaces. Here, we report applying cell-based selection methods to profile surfaces of mouse C2C12 myoblasts and myotube cells in an unbiased, target agnostic manner. A panel of on-DNA compounds were identified and confirmed for cell binding selectivity. We optimized the cell selection protocol and employed a novel data analysis method to identify cell selective ligands against a panel of human B and T lymphocytes. We discuss the generality of using this workflow for DNA encoded small molecule library selection and data analysis against different cell types, and the feasibility of applying this method to profile cell surfaces for biomarker and target identification.

Background: Exploring the epigenetic regulations, such as microRNA, in newborns holds significant promise for enhancing our ability to address and potentially prevent early-life developmental delays. Objectives: Hence, this research seeks to investigate if the expression of miRNA in the umbilical cord blood of infants can forecast their developmental outcomes as they grow older. Design and method: We enrolled 143 full-term newborns, delivered either via cesarean section (CS) or through natural spontaneous delivery (NSD). We then analyzed the profiles of specific miRNAs (miR-486-5p, miR-126-5p, miR-140-3p, miR-151a-3p, miR-142-5p, and miR-30e-5p) in the umbilical cord blood of these infants. Subsequently, we performed follow-up assessments using Bayley-III scores when the cohort reached 1 year of age. Furthermore, we conducted pathway-enrichment analyses on the target genes associated with these examined miRNAs. Results: When comparing newborns delivered via cesarean section (CS) to those born via natural spontaneous delivery (NSD), we observed notable differences. Specifically, newborns through NSD displayed significantly higher ΔCt values for miR-486-5p, alongside lower ΔCt values for miR-126-5p and miR-151a-3p in their cord blood. At 1 year of age, cognitive development was significantly linked to the ΔCt values of miR-140-3p and miR-142-5p, while language development showed a significant association with the ΔCt values of miR-140-3p. Moreover, our pathway enrichment analyses revealed that the target genes of these miRNAs were consistently involved in the pathways related to neurons, such as axon guidance and the neurotrophin signaling pathway. Conclusion: In summary, this study represents a pioneering effort in elucidating the potential connections between miRNA levels in cord blood and the health indicators and neurodevelopment of newborns at 1 year of age. Our findings underscore the significance of miRNA levels at birth in influencing mechanisms related to neurodevelopment.

Previous studies have reported a role of alterations in the brain’s inhibitory control mechanism in addiction. Mounting evidence from neuroimaging studies indicates that its key components can be evaluated with brain oscillations and connectivity during inhibitory control. In this study, we developed an internet-related stop-signal task with electroencephalography (EEG) signal recorded to investigate inhibitory control. Healthy controls and participants with Internet addiction were recruited to participate in the internet-related stop-signal task with 19-channel EEG signal recording, and the corresponding event-related potentials and spectral perturbations were analyzed. Brain effective connections were also evaluated using direct directed transfer function. The results showed that, relative to the healthy controls, participants with Internet addiction had increased Stop-P3 during inhibitory control, suggesting that they have an altered neural mechanism in impulsive control. Furthermore, participants with Internet addiction showed increased low-frequency synchronization and decreased alpha and beta desynchronization in the middle and right frontal regions compared to healthy controls. Aberrant brain effective connectivity was also observed, with increased occipital-parietal and intra-occipital connections, as well as decreased frontal-paracentral connection in participants with Internet addiction. These results suggest that physiological signals are essential in future implementations of cognitive assessment of Internet addiction to further investigate the underlying mechanisms and effective biomarkers.

Abstract Background Prisoner health is a topic of significant importance; however, it has received limited attention in epidemiological studies, likely because of challenges in obtaining relevant data. Specifically, research on ocular disorders among elderly prisoners is lacking. Thus, the aim of this study was to evaluate the prevalence of disorders of the eye and adnexa among elderly prisoners in Taiwan. Methods We investigated the presence of eye and adnexal disorders in elderly prisoners in Taiwan using data from the Taiwan National Health Insurance Research Database. The ocular disorders were identified using the appropriate disease codes in the International Classification of Diseases, 9th revision Clinical Modification (codes 360–379). In addition, the most common types of eye and adnexal disorders among the prisoners were identified. Results A total of 2215 elderly prisoners (age ≥ 65 years; 2073 men and 142 women) were examined. The prevalence of eye and adnexal disorders among the prisoners was 18.87%. The elderly female prisoners exhibited a higher prevalence of eye and adnexal disorders than the elderly male prisoners. The most common disorders were disorders of the conjunctiva, cataract, and disorders of the lacrimal system. Conclusions A considerable proportion of elderly prisoners have disorders of the eye and adnexa. The overall quality of life of elderly prisoners can be improved by addressing their visual health, which contributes to the fulfillment of their basic human rights.

Abstract Background and purpose Seizures commonly occur in patients with intracerebral hemorrhage (ICH). Anticonvulsants are commonly used for preventing seizures in patients with ICH. Thus, patients with ICH at high risk of seizures must be identified. The study aims to elucidate whether double the score of cortex involvement in ICH patients can increase accuracy of CAVE score for predicting late seizures. Method This retrospective analysis of the medical records of surviving patients admitted between June 1, 2013, and December 31, 2019. Validated the CAVE score and modified it (CAVE2). The main outcome of patients with ICH was seizures. The first seizures occurring within 7 days after a stroke were defined as early seizures. Seizures occurring after 1 week of stroke onset, including patients who had experienced early seizures or patients who had not, were defined as late seizures. CAVE and CAVE2 scores were validated using the cohort. The accuracy and discrimination of those two scores were accessed by the area under the operating characteristic curve. Akaike information criterion, integrated discrimination improvement, and continuous net reclassification improvement were used to assess the performance of the CAVE and CAVE2 scores. Results In the cohort showed that late seizures occurred in 12.7% (52/408) of patients with ICH. Male sex, age > 65 years, cortex involvement, and early seizures were associated with the occurrence of late seizures, with odds ratios of 2.09, 2.04, 4.12, and 3.78, respectively. The risk rate of late seizures was 6.66% (17/255), 14.8% (17/115), and 47.4% (18/38) for CAVE scores ≤ 1, 2, and ≥ 3, and 4.6% (12/258), 18.3% (13/71), and 54.4 (20/37) for CAVE2 scores ≤ 1, 2, and ≥ 3 respectively. The C-statistics for the CAVE and CAVE2 scores were 0.73 and 0.74 respectively. Conclusion The CAVE score can identify patients with ICH and high risk for late seizures. The CAVE can be modified by changing the score of cortex involvement to 2 points to improve accuracy in predicting late seizures in patients with ICH.

Abstract Background Dengue virus serotype 2 (DENV-2) was the major serotype in the 2015 dengue outbreak in Taiwan, while DENV-1 and DENV-3 were dominant between 2005 and 2014. We aimed to investigate whether DENV-2 contributed to disease severity and mortality in the outbreak in Kaohsiung city, Taiwan. Methods We collected serum samples from dengue patients to detect the presence of DENV and determine the serotypes by using quantitative reverse transcription-polymerase chain reaction. Our cohorts comprised 105 DENV-1-infected cases and 1,550 DENV-2-infected cases. Demographic data, DENV serotype, and comorbidities were covariates for univariate and multivariate analyses to explore the association with severity and mortality. Results The results suggested that DENV-1 persisted and circulated, while DENV-2 was dominant during the dengue outbreak that occurred between September and December 2015. However, DENV-2 did not directly contribute to either severity or mortality. Aged patients and patients with diabetes mellitus (DM) or moderate to severe chronic kidney disease (CKD) had a higher risk of developing severe dengue. The mortality of dengue patients was related to a higher Charlson comorbidity index score and severe dengue. Among DENV-2-infected patients and older patients, preexisting anti-dengue IgG, DM, and moderate to severe CKD were associated with severe dengue. Moreover, female sex and severe dengue were associated with a significantly higher risk of death. Conclusions Our findings highlight the importance of timely serological testing in elderly patients to identify potential secondary infections and focus on the meticulous management of elderly patients with DM or moderate to severe CKD to reduce dengue-related death.

This study investigates the wave pressure on an Oscillating Water Column (OWC) device, which features a perforated wall positioned in front of the OWC chamber and is integrated with a caisson breakwater. The perforated wall is designed to mitigate wave impacts on the OWC device under storm wave conditions. To achieve this, a series of laboratory experiments were conducted using a 1:25 scale model, considering both regular and irregular waves. Wave pressure measurements and analyses were performed on various configurations to assess the effects of the perforated wall on the wave pressure exerted against the front wall of the OWC chamber and the caisson breakwater. The results indicate that the perforated wall effectively reduces the amplitude of water column oscillations within the OWC chamber during storm conditions, thereby significantly reducing wave pressure on the OWC chamber wall by approximately 14% and on the breakwater by about 20.3%.

Background: Although the human body generally exhibits bilateral symmetry, achieving perfect symmetry is exceedingly uncommon. During preadolescent development, a face that approximates symmetry is considered both aesthetically and functionally ideal. This study aimed to investigate the relationship between craniofacial traits and hand predominance, using three-dimensional (3D) stereophotogrammetry to discern whether facial soft-tissue characteristics are correlated with hand preference. Materials and Methods: The study involved children aged 9 and 10 years who were free from any diagnosed craniofacial anomalies. Three-dimensional stereophotogrammetry was conducted to analyze their facial morphology, and 37 distinct anatomical landmarks were manually identified using a MATLAB-developed program. Results: A total of 188 Taiwanese children participated in the study. All participants were healthy, with a mean age of 9.79 years. Among them, 93.1% (175) were right-hand predominant, and 6.9% (13) were left-hand predominant. There were no significant differences in linear parameters or facial asymmetry between right-hand-predominant and left-hand-predominant participants (p > 0.05). However, a consistent trend toward right laterality, especially in the right lateral frontal region of the cranium, was observed, as illustrated by heat maps of the average three-dimensional model. Conclusions: The study found no association between facial morphology and hand predominance. A normal asymmetry with a rightward tendency was noted in children aged 9 to 10 years, which was particularly notable in the lateral frontal region of the head.

Background: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in trauma patients, necessitating reliable prognostic tools. The segmented neutrophil-to-monocyte (SeMo) ratio, indicative of the inflammatory response, has emerged as a valuable biomarker. This study evaluates the prognostic value of dynamic changes in the SeMo ratio in predicting outcomes for patients with moderate to severe TBI. Methods: A retrospective analysis was conducted on data from 1118 TBI patients admitted to the surgical intensive care unit at a level I trauma center between January 2009 and December 2020. Patients were selected based on an Abbreviated Injury Scale (AIS) score ≥ 3 in the head region. Initial and follow-up SeMo ratios were calculated upon admission and 48–72 h later, respectively. The dynamic SeMo ratio was defined as the difference between the second and initial SeMo ratios. Statistical analyses included receiver operating characteristic (ROC) curve analysis to determine the optimal threshold for mortality prediction, and comparative analysis of clinical outcomes. Results: The study cohort included 121 deceased and 997 surviving patients. Deceased patients had significantly higher second SeMo ratios (20.9 ± 16.1 vs. 15.8 ± 17.2, p = 0.001) and dynamic SeMo ratios (2.4 ± 19.8 vs. −2.1 ± 19.5, p = 0.019) than those survival patients. In the multivariate analysis, the dynamic SeMo is a significant independent risk factor for in-hospital mortality (OR 1.01, 95%CI: 1.01–1.03, p = 0.031). The optimal cut-off for the dynamic SeMo ratio was 5.96, above which patients exhibited higher mortality (21.4% vs. 8.5%, p < 0.001), higher adjusted mortality (adjusted odds ratio: 2.98; 95% confidence interval: 1.95–4.56; p = 0.005), and longer hospital stays (23.6 days vs. 19.7 days, p = 0.005). Discussion: Dynamic SeMo ratio changes serve as a prognostic marker for in-hospital mortality and hospital stay duration in moderate to severe TBI patients. A higher dynamic SeMo ratio indicates increased risk, highlighting the importance of early monitoring and intervention. Future prospective studies should validate these findings and explore integration with other biomarkers for enhanced prognostication.

Abstract The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in October 2021, possessed many mutations compared to previous variants. We aimed to identify and analyze SARS-CoV-2 Omicron subvariants among coronavirus disease 2019 (COVID-19) patients between January 2022 and September 2022 in Taiwan. The results revealed that BA.2.3.7, featuring K97E and G1251V in the spike protein compared with BA.2, emerged in March 2022 and persistently dominated between April 2022 and August 2022, resulting in the largest COVID-19 outbreak since 2020. The accumulation of amino acid (AA) variations, mainly AA substitution, in the spike protein was accompanied by increasing severity in Omicron-related COVID-19 between April 2022 and January 2023. Older patients were more likely to have severe COVID-19, and comorbidity was a risk factor for COVID-19-related mortality. The accumulated case fatality rate (CFR) dropped drastically after Omicron variants, mainly BA.2.3.7, entered Taiwan after April 2022, and the CFR was 0.16% in Taiwan, which was lower than that worldwide (0.31%) between April 2021 and January 2023. The relatively low CFR in Omicron-related COVID-19 patients can be attributed to adjustments to public health policies, promotion of vaccination programs, effective antiviral drugs, and the lower severity of the Omicron variant.

Abstract Background Bioactive materials have now raised considerable attention for the treatment of osteoarthritis (OA), such as knee OA, rheumatoid OA, and temporomandibular joint (TMJ) OA. TMJ-OA is a common disease associated with an imbalance of cartilage regeneration, tissue inflammation, and disability in mouth movement. Recently, biological materials or molecules have been developed for TMJ-OA therapy; however, ideal treatment is still lacking. In this study, we used the combination of a human platelet rich plasma with hyaluronic acid (hPRP/HA) for TMJ-OA therapy to perform a clinical trial in dish to humans. Method Herein, hPRP was prepared, and the hPRP/HA combined concentration was optimized by MTT assay. For the clinical trial in dish, pro-inflammatory-induced in-vitro and in-vivo mimic 3D TMJ-OA models were created, and proliferation, gene expression, alcian blue staining, and IHC were used to evaluate chondrocyte regeneration. For the animal studies, complete Freund’s adjuvant (CFA) was used to induce the TMJ-OA rat model, and condyle and disc regeneration were investigated through MRI. For the clinical trial in humans, 12 patients with TMJ-OA who had disc displacement and pain were enrolled. The disc displacement and pain at baseline and six months were measured by MRI, and clinical assessment, respectively. Results Combined hPRP/HA treatment ameliorated the proinflammatory-induced TMJ-OA model and promoted chondrocyte proliferation by activating SOX9, collagen type I/II, and aggrecan. TMJ-OA pathology–related inflammatory factors were efficiently downregulated with hPRP/HA treatment. Moreover, condylar cartilage was regenerated by hPRP/HA treatment in a proinflammatory-induced 3D neocartilage TMJ-OA-like model. During the animal studies, hPRP/HA treatment strongly repaired the condyle and disc in a CFA-induced TMJ-OA rat model. Furthermore, we performed a clinical trial in humans, and the MRI data demonstrated that after 6 months of treatment, hPRP/HA regenerated the condylar cartilage, reduced disc displacement, alleviated pain, and increased the maximum mouth opening (MMO). Overall, clinical trials in dish to human results revealed that hPRP/HA promoted cartilage regeneration, inhibited inflammation, reduced pain, and increased joint function in TMJ-OA. Conclusion Conclusively, this study highlighted the therapeutic potential of the hPRP and HA combination for TMJ-OA therapy, with detailed evidence from bench to bedside. Trial registration Taipei Medical University Hospital (TMU-JIRB No. N201711041). Registered 24 November 2017. https://tmujcrc.tmu.edu.tw/inquiry_general.php .

Abstract A molecular and functional link between neurotrophin signaling and cerebellar foliation is lacking. Here we show that constitutive knockout of two homologous genes encoding the RNA binding protein RBM4 results in foliation defects at cerebellar lobules VI–VII and delayed motor learning in mice. Moreover, the features of Rbm4 double knockout (dKO), including impaired differentiation of cerebellar granule cells and dendritic arborization of Purkinje cells, are reminiscent of neurotrophin deficiency. Loss of RBM4 indeed reduced brain-derived neurotrophic factor (BDNF). RBM4 promoted the expression of BDNF and full-length TrkB, implicating RBM4 in efficient BDNF-TrkB signaling. Finally, prenatal supplementation with 7,8-dihydroxyflavone, a TrkB agonist, restored granule cell differentiation, Purkinje cell dendritic complexity and foliation—the intercrural fissure in particular—in the neonatal cerebellum of Rbm4dKO mice, which also showed improved motor learning in adulthood. This study provides evidence that prenatal activation of TrkB signaling ameliorates cerebellar malformation caused by BDNF deficiency.

Background: The short-term impact of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) combined with antiretroviral therapy (ART) on renal function in patients with HIV/HCV-coinfection remains controversial. Methods: This multicenter, retrospective study aimed to sequentially record the estimated glomerular filtration rate (eGFR) at baseline, end of therapy (EOT), 12 weeks off-treatment (SVR12), and at time points after SVR12 (post-SVR12) and to identify the factors associated with an eGFR decline to 60 ml/min/1.73 m2 were included. We found that eGFRs declined during the on-treatment period in the tenofovir-containing ART and SOF-based DAA groups. There were no differences in the slope coefficient during the on-treatment and post-treatment periods among all risk groups except for people who inject drug. Increasing age and plasma HIV RNA >20 copies/ml before DAA treatment were factors independently associated with AKD during the on-treatment period while increasing age was independently associated with AKD during the all-course period. Conclusion: Only increasing age was an independent factor associated with AKD among HIV/HCV-coinfected patients during and after DAA treatments.

Abstract Background Nivolumab and pembrolizumab have not been directly compared in clinical trials, and the aim of this study is to investigate the efficacy and safety of nivolumab versus pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) in real-world practice. Methods We retrospectively reviewed patients with HCC who received intravenous nivolumab or pembrolizumab alone as second-line and later therapy. The objective response was determined according to the Response Evaluation Criteria in Solid Tumors criteria version 1.1. Adverse events (AEs) were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The Kaplan–Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Prognostic values were estimated using hazard ratios with 95% confidence intervals (CIs). Results In total, 120 patients were enrolled, including 95 who received nivolumab and 25 who received pembrolizumab. All patients were staged as Barcelona Clinic Liver Cancer stage C, and 29 patients were classified as Child-Pugh classification B (7). The response rate of the pembrolizumab and nivolumab groups were 8.0% and 7.4%, respectively. There was no significant difference in the median PFS between the pembrolizumab and nivolumab groups (2.7 months versus 2.9 months). The median OS in the nivolumab group was longer than that in the pembrolizumab group (10.8 months versus 8.1 months); however, the difference was not statistically significant. The effects of pembrolizumab and nivolumab on the median PFS and OS were consistent across the subgroups based on baseline characteristics. The severity of all AEs was grades 1–2 without treatment interruption or dose adjustment; there was no statistically significant difference in the incidence of treatment-related AEs between these two groups. Additionally, the percentage of patients receiving subsequent therapy was consistent between the two groups. Conclusion The efficacy and safety of pembrolizumab and nivolumab were comparable in the management of patients with pretreated HCC in real-world practice.

IntroductionThe easy albumin-bilirubin (EZ-ALBI) score is calculated using the equation: total bilirubin (mg/dl) − 9 × albumin (g/dl), and is used to evaluate liver functional reserve. This study was designed to investigate whether the EZ-ALBI score serves as an independent risk factor for mortality and is useful for stratifying the mortality risk in adult trauma patients.MethodsWe retrospectively reviewed data from the registered trauma database of the hospital and included 3,637 adult trauma patients (1,241 deaths and 2,396 survivors) due to all trauma caused between January 1, 2009, and December 31, 2021. The patients were allocated to the two study groups based on the best EZ-ALBI cutoff point (EZ-ALBI = −28.5), which was determined based on the area under the receiver operating characteristic curve.ResultsResults revealed that the non-survivors had a significantly higher EZ-ALBI score than the survivors (−26.4 ± 6.5 vs. −31.5 ± 6.2, p

Introduction: Fractures affect people's quality of life especially in the elders. One of the most important risk factors is osteoporosis. There are many screening tools to predict osteoporosis and fractures. We aimed to compare the predictive validity of three commonly used screening tools: fracture risk assessment tool (FRAX), osteoporosis self-assessment tool for Asians (OSTA) and one-minute osteoporosis risk test. Among them, OSTA and one-minute osteoporosis risk test were originally developed to predict osteoporosis risks and FRAX was to predict fracture risks. Methods: This is an 11-year longitudinal study. We enrolled 708 senior people from health examinees in Taiwan in 2010. A standardized questionnaire and blood tests were provided. Annual telephone interview was conducted to assess the real fracture status. We calculated risk scores of FRAX, OSTA, and one-minute osteoporosis risk test and compared with real-world fracture records. Results: The mean age of the participants were 74.9 (SD 6.4). There were 356 (50.3 %) men. From 2010 to 2020, a total of 105 (14.8 %) persons suffered from fractures. Compared to people without fractures, people with fractures had higher FRAX major osteoporotic fracture risk scores (14.0 % ± 7.6 % vs.11.3 % ± 5.7 %), higher hip fracture risk scores, and higher OSTA risk (5.9 % ± 1.4 % vs. 5.3 % ± 1.3 %). Cox regression analysis showed that hazard ratios for fracture of high FRAX risk was 1.53 (95 % confidence interval (CI) 1.05–2.21), and for high OSTA risk was 1.37 (95 % CI 1.04–1.82). Conclusions: Only OSTA and FRAX scores were satisfactory in predicting 10-year fractures.

BackgroundPoor sleep hygiene persists in college students today, despite its heavy implications on adolescent development and academic performance. Although sleep patterns in undergraduates have been broadly investigated, no study has exclusively assessed the sleep patterns of premedical undergraduate students. A gap also exists in the knowledge of how students perceive their sleep patterns compared to their actual sleep patterns. ObjectiveThis study aims to address 2 research questions: What are the sleep patterns of premedical undergraduate students? Would the proposed study protocol be feasible to examine the perception of sleep quality and promote sleep behavioral changes in premedical undergraduate students? MethodsAn anonymous survey was conducted with premedical students in the Medical Science Baccalaureate program at an R1: doctoral university in the Midwest United States to investigate their sleep habits and understand their demographics. The survey consisted of both Pittsburg Sleep Quality Index (PSQI) questionnaire items (1-9) and participant demographic questions. To examine the proposed protocol feasibility, we recruited 5 students from the survey pool for addressing the perception of sleep quality and changes. These participants followed a 2-week protocol wearing Fitbit Inspire 2 watches and underwent preassessments, midassessments, and postassessments. Participants completed daily reflections and semistructured interviews along with PSQI questionnaires during assessments. ResultsAccording to 103 survey responses, premedical students slept an average of 7.1 hours per night. Only a quarter (26/103) of the participants experienced good sleep quality (PSQI