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In intermittent negative airway pressure (iNAP) therapy, soft tissues are reshaped into a forward-resting position, thus reducing airway obstruction during sleep. This study investigated the effect of iNAP therapy that was administered during drug-induced sleep endoscopy with target-controlled infusion (TCI-DISE) in patients with obstructive sleep apnea (OSA) intolerant of continuous positive airway pressure (CPAP) therapy. This prospective case series study included 92 patients with polysomnography (PSG)-confirmed OSA who underwent TCI-DISE with iNAP from January 2018 to February 2020 at a tertiary referral hospital. Upper airway obstruction was evaluated and scored using the velum, oropharynx, tongue base, and epiglottis (VOTE) classification. Obstruction severity was assessed multiple times with the patient in the supine position with or without lateral rotation of the head and the application of iNAP therapy, respectively. After the application of iNAP therapy in the supine position, obstruction severity decreased significantly: from complete or partial obstruction to partial or no obstruction in 37, 12, and 36 patients (40.2%, 13%, and 39%, respectively) with velar obstruction, oropharyngeal, and tongue base obstruction, respectively. After simultaneously applying iNAP therapy with head rotation, obstruction severity decreased in 47, 43, and 19 patients (51%, 47%, and 21%, respectively) with velar, tongue base, and epiglottic obstruction, respectively. In TCI-DISE, we found that iNAP therapy relieved velar, oropharyngeal, and tongue base obstruction in the supine position in some patients. Moreover, iNAP therapy can be combined with positional therapy to alleviate velar, tongue base, and epiglottic obstruction in some patients. TCI-DISE can also be used to screen the possible responders for iNAP therapy because it is less time consuming than PSG.

Gut microbiota dysbiosis is known to be associated with diabetes; however, the findings of previous studies are conflicting. To clarify the association between type 2 diabetes and the gut microbiota, the present study analyzed the composition of fecal gut microbiota and its correlation with specific clinical parameters in newly diagnosed, treatment-naive diabetic patients and healthy controls. A total of 50 patients with newly diagnosed type 2 diabetes and 50 healthy control participants were enrolled in the study. Fecal samples, blood samples, and food diaries were collected from the diabetic patients before and 3 mo after the start of their antidiabetic treatment. These samples were also collected from the healthy controls. The gut microbiota was characterized by 16S ribosomal RNA analysis using quantitative polymerase chain reaction. The fecal count of Lactobacillus was significantly higher, whereas Clostridium coccoides and Clostridium leptum were significantly lower in the diabetic patients compared with the healthy controls. Lactobacillus was significantly positively correlated with glucose, glycated hemoglobin, and the homeostatic model assessment, whereas C. coccoides and C. leptum were significantly negatively correlated with the diabetic parameters. In addition, the newly diagnosed diabetic patients had a significant decrease in the presence of C. coccoides and C. leptum after 3 mo of treatment compared with before treatment. The amount of fecal Lactobacillus, C. coccoides, and C. leptum was significantly different between the patients with type 2 diabetes and the healthy controls. The levels of Clostridium were also significantly changed after 3 mo of treatment in the diabetic patients. Further research is needed to clarify the correlation or causal relationship between the gut microbiota dysbiosis and type 2 diabetes.

Mammography is considered the gold standard for breast cancer screening. Multiple risk factors that affect breast cancer development have been identified; however, there is an ongoing debate regarding the significance of these factors. Machine learning (ML) models and Shapley Additive Explanation (SHAP) methodology can rank risk factors and provide explanatory model results. This study used ML algorithms with SHAP to analyze the risk factors between two different age groups and evaluate the impact of each factor in predicting positive mammography. The ML model was built using data from the risk factor questionnaires of women participating in a breast cancer screening program from 2017 to 2021. Three ML models, least absolute shrinkage and selection operator (lasso) logistic regression, extreme gradient boosting (XGBoost), and random forest (RF), were applied. RF generated the best performance. The SHAP values were then applied to the RF model for further analysis. The model identified age at menarche, education level, parity, breast self-examination, and BMI as the top five significant risk factors affecting mammography outcomes. The differences between age groups ranked by reproductive lifespan and BMI were higher in the younger and older age groups, respectively. The use of SHAP frameworks allows us to understand the relationships between risk factors and generate individualized risk factor rankings. This study provides avenues for further research and individualized medicine.

We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups. This was a 12-month, Phase IV, multicenter, open-label study. The initial dose of ferric citrate was administered by patients' clinical condition and further adjusted to maintain serum phosphorus at 3.5-5.5 mg/dL. The primary endpoint was to assess the safety profiles of ferric citrate. The secondary endpoints were to evaluate the efficacy by the time-course changes and the number of subjects who achieved the target range of serum phosphorus. A total of 202 patients were enrolled. No apparent or unexpected safety concerns were observed. The most common treatment-emergent adverse events were gastrointestinal-related with discolored feces (41.6%). Serum phosphorus was well controlled, with a mean dose of 3.35±1.49 g/day, ranging from 1.5 to 6.0 g/day. Iron parameters were significantly improved. The change from baseline of ferritin and TSAT were 227.17 ng/mL and 7.53%, respectively (p-trend<0.001), and the increase started to slow down after 3-6 months of treatment. In addition, the increase trend was found only in patients with lower baseline level of ferritin (≤500 ng/mL) and TSAT (<30%). Ferric citrate is an effective phosphate binder with favorable safety profile in ESRD patients. The iron-repletion by ferric citrate is effective, and the increase is limited in patients with a higher baseline. In addition to controlling hyperphosphatemia, ferric citrate also shows additional benefits in the treatment of renal anemia. ClinicalTrials.gov ID: NCT03256838; 12/04/2017.

Introduction: Engaging in a secondary task while walking increases motor-cognitive interference and exacerbates fall risk in older adults with mild cognitive impairment (MCI). Previous studies have demonstrated that Tai Chi (TC) may improve cognitive function and dual-task gait performance. Intriguingly, with emerging studies also indicating the potential of transcranial direct current stimulation (tDCS) in enhancing such motor-cognitive performance, whether combining tDCS with TC might be superior to TC alone is still unclear. The purpose of this study was to investigate the effects of combining tDCS with TC on dual-task gait in patients with MCI. Materials and Methods: Twenty patients with MCI were randomly assigned to receive either anodal or sham tDCS, both combined with TC, for 36 sessions over 12 weeks. Subjects received 40 min of TC training in each session. During the first 20 min, they simultaneously received either anodal or sham tDCS over the left dorsolateral prefrontal cortex. Outcome measures included dual-task gait performance and other cognitive functions. Results: There were significant interaction effects between groups on the cognitive dual task walking. Compared to sham, the anodal tDCS group demonstrated a greater improvement on cadence and dual task cost of speed. Conclusion: Combining tDCS with TC may offer additional benefits over TC alone in enhancing dual-task gait performance in patients with MCI. Clinical Trial Registration: [ www.ClinicalTrials.gov ], identifier [TCTR20201201007].

Acute coronary syndrome (ACS) patients have a wide spectrum of risks for subsequent cardiovascular events and death. However, there is no simple, convenience scoring system to identify risk of adverse outcomes. We investigated whether CHADS₂ and CHA₂DS₂-VASc scores were useful tools to assess the risk for adverse events among ACS patients. This observational prospective study was conducted at 39 hospitals. Totally 3,183 patients with ACS were enrolled, and CHADS₂ and CHA₂DS₂-VASc scores were calculated. The primary endpoint was occurrence of adverse event, including subsequent myocardial infarction, stroke, or death, within 1 year of discharge. CHADS₂ and CHA₂DS₂-VASc scores were significant predictors of adverse events in separate multivariate regression analyses. A Kaplan-Meier analysis of CHADS₂ and CHA₂DS₂-VASc scores of ≥2 showed a higher rate of adverse events as compared with scores of <2 (P<0.001;log-rank test). CHA₂DS₂-VASc score was better than CHADS₂ score in predicting subsequent adverse events; the area under the receiver operating characteristic curve increased from 0.66 to 0.70 (p<0.001). Patients with CHADS₂ scores of 0 or 1 were further classified according to CHA₂DS₂-VASc score, using a cutoff value of 2. The rate of adverse events significantly differed between those with a score of <2 and those with a score of ≥2 (4.1% vs.10.7%, P<0.001). CHADS₂ and CHA₂DS₂-VASc scores were useful predictors of subsequent adverse events in ACS patients.

Cisplatin-based chemotherapy is the first line treatment for several cancers including bladder cancer (BC). Autophagy induction has been implied to contribute to cisplatin resistance in ovarian cancer; and a high basal level of autophagy has been demonstrated in human bladder tumors. Therefore, it is reasonable to speculate that autophagy may account for the failure of cisplatin single treatment in BC. This study investigated whether cisplatin induces autophagy and the mechanism involved using human BC cell lines. Human BC cells (5637 and T24) were used in this study. Cell viability was detected using water soluble tetrazolium-8 reagents. Autophagy induction was detected by monitoring the levels of light chain 3 (LC3)-II and p62 by Western blot, LC3-positive puncta formation by immunofluorescence, and direct observation of the autophagolysosome (AL) formation by transmission electron microscopy. Inhibitors including bafilomycin A1 (Baf A1), chloroquine (CQ), and shRNA-based lentivirus against autophagy-related genes (ATG7 and ATG12) were utilized. Apoptosis level was detected by caspase 3/7 activity and DNA fragmentation. Cisplatin decreased cell viability and induced apoptosis of 5637 and T24 cells in a dose-and time-dependent manner. The increased LC3-II accumulation, p62 clearance, the number of LC3-positive puncta, and ALs in cisplatin-treated cells suggested that cisplatin indeed induces autophagy. Inhibition of cisplatin-induced autophagy using Baf A1, CQ, or ATG7/ATG12 shRNAs significantly enhanced cytotoxicity of cisplatin toward BC cells. These results indicated that cisplatin induced protective autophagy which may contribute to the development of cisplatin resistance and resulted in treatment failure. Mechanistically, upregulation of beclin-1 (BECN1) was detected in cisplatin-treated cells, and knockdown of BECN1 using shRNA attenuated cisplatin-induced autophagy and subsequently enhanced cisplatin-induced apoptosis. Collectively, the study results indicated that cisplatin-induced autophagy is mediated by BECN1 in BC cells. Therefore, combinative treatment using cisplatin and autophagy inhibitors could potentially overcome cisplatin resistance related to autophagy induction.

This study examines corneal densitometry recovery and influencing factors following accelerated corneal cross‐linking (CXL) for progressive keratoconus. Corneal densitometry, measured using Scheimpflug tomography, provides an objective assessment of corneal clarity, especially in tracking the resolution of postoperative haze. We conducted a retrospective case‐control analysis of 24 patients (31 eyes) who underwent CXL with 0.25% riboflavin and 18 mW/cm 2 irradiation between 2021 and 2023. Variables included patient age, maximum keratometry ( K max ), central corneal thickness (CCT), and demarcation line depth (DLD), defined as the depth of the CXL region. Results revealed a significant increase in densitometry values across most corneal zones at 1‐month postoperation, followed by a gradual return to baseline by 12 months. Notably, younger patients exhibited a faster recovery, with mean densitometry values returning to baseline in 11.4 months compared to 14.9 months in older patients ( p = 0.02). Similarly, corneas with deeper DLDs demonstrated faster densitometry recovery, suggesting a potentially more efficient corneal remodeling process. Additional analysis indicated a trend toward higher densitometry values in shallower DLDs at 1 month, although this difference was not statistically significant. These findings support the use of densitometry as a reliable measure of post‐CXL healing. While DLD depth and patient age were associated with a faster recovery, they did not directly predict final corneal clarity. Our study suggests that factors such as age and DLD depth should be considered in patient prognosis, although further research is needed to confirm these findings across varying CXL protocols.

Background/Objectives: This study examined the prevalence of adverse childhood experiences (ACEs) among patients with myasthenia gravis (MG) and explored associations between ACE exposure and psychological outcomes. In addition, this study conducted a preliminary evaluation of an online “Positive Mental Health BMI Learning Program” and its association with changes in psychological well-being. Methods: A total of 77 patients with MG were included, with data collected between January 2024 and January 2025. Sociodemographic characteristics, ACE exposure, and psychological and disease-related indicators were assessed, including the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL), the Myasthenia Gravis Quality of Life 15-item scale (MG-QOL15), the indicator of mental health BMI on well-being (mBMI), and the Patient Health Questionnaire-9 (PHQ-9). Using a single-group pre–post design, this exploratory pilot study examined associations between ACEs and psychological outcomes, along with pre–post changes among participants who completed the online program. Results: Among the 32 participants who completed the online program, mBMI scores showed an increase, primarily reflecting improvements in emotional stability (21.41 ± 4.70 to 23.03 ± 4.49, p < 0.01); however, in the absence of a control group, these changes cannot be attributed solely to the intervention. In contrast, no significant pre–post changes were observed in PHQ-9, MG-ADL, and MG-QOL15. Across the full sample, higher ACE exposure was associated with greater depressive symptom severity, as measured by the PHQ-9 (p < 0.05). Overall, 42.9% of participants reported at least one ACE, with emotional abuse being the most frequently endorsed, followed by parental separation or divorce and emotional neglect. Conclusions: ACE exposure was common among patients with MG and was associated with greater depressive symptoms. Participation in the online positive mental health BMI learning program was associated with improvements in positive psychological well-being.

The present study investigated the annual prevalence of cerebral palsy (CP) among children aged <7 years in Taiwan and the association between socioeconomic status and CP prevalence. Data from the Taiwan National Health Insurance Research Database for the 2002-2008 period were used in this population-based study. Severe and total CP were defined according to catastrophic illness certificate and medical claim records, respectively. The annual CP prevalence was calculated as the number of children with CP among all children aged <7 years. From 2002 to 2008, the annual prevalence of total and severe CP ranged from 1.9 to 2.8 and from 1.1 to 1.4 per 1000 children, respectively. Boys were 30% more likely to have CP than girls [adjusted relative risk (RR) and 95% confidence interval (CI) ranged from 1.3 (1.2-1.4) to 1.4 (1.2-1.5)]. Low family income was associated with a higher CP prevalence [adjusted RR (95% CI) ranged from 5.1 (4.2-6.2) to 6.4 (5.4-7.6)]. The prevalence of CP in rural area was higher than that in urban or suburban areas. The mortality rate of severe CP ranged from 12.2-22.7 per 1000 children within the 7 years study period. The prevalence of CP in Taiwan is similar to that in Western countries. A higher prevalence of CP is associated with male sex, low income, and rural residential location. Our findings provide insights into CP epidemiology among the Chinese population.