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Background: Few studies have examined the non-linear relationships of objectively-measured sedentary behavior and physical activity with insomnia symptoms in older adults. We investigated such relationships of sedentary and physically-active behaviors with total sleep time and nocturnal wakefulness. Methods: We recruited adults aged 60 years and above who have received health check-ups or been to geriatric outpatient services from a hospital setting. Sedentary and physically-active behaviors, total sleep time, and wakefulness time after sleep onset were measured by Actigraphy, and their relationships were estimated using generalized additive models. Results: The 157 older adults receiving health-related services slept 7.5 h (20.8 min awake) on average per day. Total sleep time was negatively associated with sedentary and physically-active behaviors. By contrast, a U-shape relationship was found between sedentary behavior and wakefulness time after sleep onset, with a turning point at a daily sedentary time of 10.9 h. Conclusion: Longer high-intensity physical activity time was related to a shorter wakefulness time after sleep onset. By contrast, daily sedentary time longer than 10.9 h was related to shorter total sleep time but more nocturnal wakefulness time. Future nonpharmacological strategies for sleep improvement should consider the sedentary threshold.

Abstract Background Proximity to parks has been suggested as a factor influencing physical activity in older adults. However, it remains unclear the optimal distance between residences and parks for promoting physical activity and reducing sedentary time and whether these associations vary by the time of day. We examined whether the proximity to neighbourhood parks at varying distances is associated with all-day and time-specific physical activity and sedentary behaviour in older adults. Methods Data were collected from 214 older adults receiving hospital services in Taipei, Taiwan. The number of parks within 400m, 800m, and 1,600m of participants’ residences. Physical activity and sedentary behaviour, stratified by time of day (morning, afternoon, and evening), were measured using accelerometers. Adjusted linear regression models were used to estimate associations of park proximity with activity and sedentary outcomes. Results Parks located within 400m and 800m of participants’ residences were more markedly associated with longer time in physical activity and less sedentary time compared to parks located 1,600m away. A greater number of parks within 400m and 800m was positively associated with walking steps and light-intensity physical activity while both distances were negatively associated with sedentary time. The associations between park proximity and behavioural outcomes were mainly attributable to that during the afternoon and evening. Conclusions Our findings suggest that favourable access to parks within 800m of older adults’ residences is associated with more physical activity and less sedentary time, particularly during the afternoon and evening. Future longitudinal studies are required to corroborate these associations.

Abstract Objective As the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited. Methods Thirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan–Meier survival analyses. Results The ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p

Abstract Background The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. Methods A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. Results Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p

Abstract BackgroundRecently, the phase angle (PhA) has emerged as an essential indicator of cellular health. Most studies have examined its association with physiological conditions, such as sarcopenia, frailty, and physical function, in older populations. Simultaneously, growing attention is being paid to the clinical relevance of segmental PhAs for future applications. However, few studies have explored the relationship between PhAs, especially segmental PhAs, and the psychological aspects of health, particularly cognitive function. ObjectiveWe aimed to investigate the association between whole-body and segmental PhAs and cognitive function in older adults. MethodsIndividuals aged 65 years and above were recruited from adult community groups residing in Busan, South Korea, through the 2022 Bus-based Screening and Assessment Network (BUSAN) study of Pusan National University Hospital. Participants’ whole-body and segmental PhAs were measured using a bioelectrical impedance analyzer (BWA 2.0 Body Water Analyzer, InBody), and cognitive functions (overall and subdomains, including memory, orientation, attention and calculation, and language) were self-reported using the Korean version of the Mini-Mental State Examination. Multiple linear regression analyses were performed to examine these associations. ResultsThis study included 625 older adults aged 65‐96 years (women: n=444, 71%; men: n=191, 29%). A positive association was observed between whole-body PhA and cognitive function (bPbPbPbPbPbPbPbP ConclusionsOur findings bolster the emerging evidence of a significant positive correlation between whole-body PhA and cognitive function in our sample, with nuanced relationships observed across different segmental PhAs and cognitive subdomains. Therefore, this study revealed that PhAs could be a useful tool for screening or preventing cognitive decline in the general older population, offering substantial evidence for future interventional studies. Further research should delve into the mechanisms and assess targeted interventions that enhance regional physical function to support cognitive health in older adults. Further long-term investigation on these associations is warranted.

Abstract Background Radiotherapy (RT) has numerous effects on the oral mucosa, primarily genetic alterations and changes in the microenvironment. The characteristics of oral leukoplakia (OL) may differ between patients who have received previous head and neck cancer (HNC) treatment with radiation therapy and those who have not. Due to a lack of data on this scenario, we aimed to investigate the surgical outcomes of OL by comparing these two patient groups. Methods This retrospective cohort study enrolled a total of 224 OL lesions in 124 patients who underwent carbon dioxide laser (CO2 laser) surgery from July 2002 to Aug 2021. All patients had received previous treatments for HNC, with 59 patients undergoing only surgical approach, 65 patients undergoing RT, and 46 patients undergoing concurrent chemotherapy during RT. The analysis was performed on a per-lesion basis, not a per-capita basis. We investigated the associations of clinicopathological characteristics and treatment outcomes of OL lesions that developed from irradiated or nonirradiated oral mucosa. Results The median follow-up time was 5.87 years. Postoperative recurrence of OL occurred in 30 patients. Malignant transformation occurred in 17 patients with the incidence rate 4.19% annually and 13.7% cumulatively. The average time for OL transforming into squamous cell carcinoma was 3.27 ± 3.26 years (median 1.82, range 0.11 – 11.90). In univariate analysis, non-homogeneous morphology (P = 0.042), moderate to high-grade dysplasia (P = 0.041), and nonirradiated oral mucosa (P = 0.0047) were predictors for malignant transformation. However, in the Cox proportional hazard model, only nonirradiated oral mucosa remained an independent prognostic factor related to postoperative malignant transformation of OL (P = 0.031, HR 5.08, CI95 1.16 – 22.25). Conclusion In the population whose OL is strongly aetiologically linked to environmental carcinogens such as betel nut and tobacco, OL lesions that develop on previously irradiated oral mucosa have a lower risk for postoperative malignant transformation compared to those that develop on nonirradiated mucosa. This finding highlights the potential impacts of radiation on OL. Further research is needed to confirm this observation and elucidate the underlying mechanism.

Abstract Background Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype–phenotype correlations of USH2A-related retinal dystrophies in Taiwan. Results In our cohort, the mean age at first visit was 47.66 ± 13.54 years, and the mean age at symptom onset, which was referred to the onset of nyctalopia and/or visual field constriction, was 31.21 ± 15.24 years. Among the variants identified, 23 (50%) were missense, 10 (22%) were splicing variants, 8 (17%) were nonsense, and 5 (11%) were frameshift mutations. The most predominant variant was c.2802T>G, which accounted for 21% of patients, and was located in exon 13. Patients with truncated alleles had significantly earlier symptom onset and seemly poorer disease progression regarding visual acuity, ellipsoid zone line length, and hypofluorescent lesions in the macula than those who had the complete gene. However, the clinical presentation revealed similar progression between patients with and without the c.2802T>G variant. During long-term follow-up, the patients had different ellipsoid zone line progression rates and were almost evenly distributed in the fast, moderate, and slow progression subgroups. Although a younger onset age and a smaller baseline intact macular area was observed in the fast progression subgroup, the results showed no significant difference. Conclusions This is the first cohort study to provide detailed genetic and longitudinal clinical analyses of patients with USH2A-related retinal dystrophies in Taiwan. The mutated allele frequency in exon 13 was high in Taiwan due to the predominant c.2802T>G variant. Moreover, truncated variants greatly impacted disease progression and determined the length of therapeutic windows. These findings provide insight into the characteristics of candidates for future gene therapies.

Background: The global impact of COVID-19 has prompted profound shifts in public health policies. The epidemiology of respiratory infectious disease may change in the post-covid era. This study investigates the repercussions of these policies on respiratory infectious diseases, specifically the resurgence of severe influenza and enterovirus infections in the post-COVID-19 era. Methods: Examining the period from January 2020 to December 2023, our nationwide study analyzes data from the Taiwan Centers for Disease Control and Our World in Data. Two distinct phases, containing (Week 1, 2020, to Week 43, 2022) and coexisting (Week 44, 2022, to Week 50, 2023), are scrutinized, emphasizing policy changes and their potential impact on epidemiology. Results: Epidemiological trends reveal a decline in COVID-19 and all-cause pneumonia during the co-existing period but a notable rise in severe influenza and enterovirus infections. Interrupted time series analysis confirms the surge in severe influenza and enterovirus cases post-restriction ease. Conclusion: The post-COVID-19 era introduces challenges with the resurgence of traditional respiratory diseases, necessitating continuous surveillance, timely non-pharmaceutical interventions, and vaccination as crucial strategies. Vigilance and targeted measures by policymakers and healthcare providers are imperative to navigate the evolving landscape of respiratory infectious diseases in the aftermath of the pandemic.

Purpose: Glyphosate and glyphosate-based herbicides (GBH), widely used globally, were initially considered harmless to humans. Experimental studies have suggested that these substances can disrupt iron homeostasis by interfering with iron uptake or triggering inflammatory responses. However, their potential impact on human iron homeostasis remains underexplored. Approach and results: We analyzed data from 5812 participants aged three and older from the 2013 to 2018 NHANES. We investigated the relationships between urinary glyphosate levels, oral iron intake, and markers of iron homeostasis, including serum iron, unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin saturation, ferritin, and transferrin receptor. Higher urinary glyphosate levels were positively associated with oral iron intake (β = 1.310, S.E. = 0.382, P = 0.001). A one-unit increase in the natural logarithm (ln)-glyphosate was associated with lower serum iron (β = − 4.236, 95 % CI = − 6.432 to − 2.039, P < 0.001) and ferritin (β = − 9.994, 95 % CI = − 17.342 to − 2.647, P = 0.009), and higher UIBC (β = 5.431, 95 % CI = 1.061–9.800, P = 0.018) and transferrin receptor levels (β = 0.139, 95 % CI = 0.015–0.263, P = 0.029). Increasing glyphosate exposure was associated with significant decreases in serum iron and ferritin across exposure quintiles (trend P-values = 0.003 and 0.018, respectively). Conclusions: Higher glyphosate exposure is associated with reduced iron availability, suggesting potential disruptions in iron absorption. These findings underscore the need for further research into the health implications of glyphosate exposure on iron homeostasis.

Abstract Phase angle (PhA) is an indicator of cellular health and is positively associated with overall physical activity (PA). However, varied associations between different intensities of PA and PhA by body segment in older populations remain unexplored. We investigated the associations between overall and different intensities of PA and upper-, lower-, and whole-body PhA in older adults. Overall exposure to light-intensity (LPA), moderate-intensity (MPA), and vigorous-intensity physical activity (VPA) was assessed using a triaxial accelerometer (GT3X + , ActiGraph). The outcome variables were upper-, lower-, and whole-body PhA measured using bioelectrical impedance analysis (MC-780MA, TANITA). Multiple linear regression helped examine the associations between the exposure and outcome variables after adjusting for age, gender, body mass index, and accelerometer wear time. A cross-sectional analysis involved 166 community-dwelling older participants (mean age = 72.1 ± 5.5 years; 78.3% women). Overall PA was associated with larger upper- (B: 0.057, 95% confidence interval [CI] 0.018–0.095) and whole-body PhA (B: 0.044, 95% CI 0.006–0.081). LPA was associated with larger upper-body PhA (B: 0.059, 95% CI 0.017–0.101), and MPA was associated with larger lower- (B: 0.273, 95% CI 0.128–0.419) and whole-body PhA (B: 0.141, 95% CI 0.002–0.280). VPA and PhA were not associated. Future interventions targeting PhA in older adults should consider the differential impact of PA intensity on various body segments of the PhA.

Background/Objectives: Monoterpenes, a class of organic compounds with the molecular formula C10H16, have garnered significant attention for their potential medicinal benefits. Emerging evidence suggests they may positively influence skeletal muscle function. However, the impact of monoterpene exposure on muscle strength and mass in humans remains unclear. Methods: To explore this relationship, we analyzed data from 1202 adults (aged ≥ 18 years) who participated in the 2013–2014 National Health and Nutrition Examination Survey (NHANES), focusing on serum levels of three specific monoterpenes—α-pinene, β-pinene, and limonene—and their association with hand grip strength and lean muscle mass. Results: Our analysis revealed that, except for test 2 of hand 1, all grip strength measures showed a positive correlation with ln-limonene levels. The β coefficient for combined grip strength was 2.409 (S.E. = 0.891, p = 0.015). Positive associations were also found between serum limonene levels and lean muscle mass. The β coefficient for the Appendicular Skeletal Muscle Mass Index (ASMI) was 0.138 (S.E. = 0.041, p = 0.004). Furthermore, combined grip strength and ASMI significantly increased across limonene quintiles (p for trend = 0.005 and 0.006, respectively). However, none of the three monoterpene levels showed a significant association with clinically defined low muscle mass or low muscle strength. Conclusions: Our findings suggest a plausible association between exposure to limonene, hand grip strength, and lean muscle mass among adults in the United States. Further investigation is needed to fully understand the underlying mechanisms and medical significance of this association.

Serum cystatin C is a well-established marker of renal function and a valuable predictor of health risks and mortality. DNA methylation-predicted cystatin C (DNAmCystatinC), an advanced epigenetic biomarker, serves as a proxy for serum cystatin C levels. However, the relationships between serum cystatin C, DNAmCystatinC, renal function, and mortality outcomes have not been previously examined. This study aimed to examine the associations between serum cystatin C, DNAmCystatinC, renal function, and their joint and independent relationships with mortality in U.S. adults. We analyzed data from 1642 participants aged 50 and older from the National Health and Nutrition Examination Survey (NHANES) 1999–2002, linked to mortality information from the National Center for Health Statistics (NCHS), with follow-up through 2019. Our analysis demonstrated a positive association between ln-DNAmCystatinC and ln-serum cystatin C (Adjusted β (SE) = 0.773 (0.267), p = 0.007), while ln-DNAmCystatinC was negatively correlated with ln-Estimated glomerular filtration rate, calculated using both creatinine and cystatin C (eGFRcr-cys) (Adjusted β (SE) = −1.123 (0.449), p = 0.018). In a weighted Cox regression model, a one-unit increase in ln-serum cystatin C was linked to an increased hazard ratio (HR) of 2.87 (95% CI: 1.938–4.26, p < 0.001) for all-cause mortality and 3.04 (95% CI: 1.34–6.88, p = 0.010) for cardiovascular mortality. Additionally, a one-unit increase in ln-DNAmCystatinC was associated with an HR of 135.86 (95% CI: 5.51–3349.69, p = 0.004) for all-cause mortality. This association was particularly pronounced in participants without chronic kidney disease (CKD), with a p-value for the interaction between DNAmCystatinC and CKD on all-cause mortality of 0.002. Furthermore, individuals with serum cystatin C and DNAmCystatinC levels above the 50th percentile showed the highest all-cause mortality risk when compared to other subgroups. In conclusion, our findings demonstrate that DNAmCystatinC is a stronger predictor of all-cause mortality than serum cystatin C, with potential additive effects when both biomarkers are considered together. These results suggest their utility as valuable clinical indicators for risk stratification and early intervention. Future research should validate these findings and further explore the clinical and public health implications of epigenetic biomarkers.

IntroductionMonoterpenes, a subset of the terpene family composed of two isoprene units, have garnered significant attention in research circles owing to their potential medicinal benefits. Recent experimental studies indicate that they might exert positive effects on bone health. Nevertheless, the impact of monoterpenes exposure on bone health remains unexplored in humans.MethodsWe examined 748 adults (age ≥ 40 years) from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 to explore the correlation between three monoterpenes (α-pinene, β-pinene, and limonene), bone mineral density (BMD) in the total lumbar spine and proximal femur, FRAX® scores, and prior bone fracture history.Results and discussionOur analysis unveiled a significant inverse association between a one-unit increase in the natural logarithm (ln) of α-pinene and limonene and total proximal femur BMD (ß = −0.027, S.E. = 0.008, P = 0.004 and ß = −0.019, S.E. = 0.007, P = 0.016, respectively). As serum α-pinene levels ascended across quintiles, there was a notable decrease in total proximal femur BMD (P for trend = 0.025). The inverse relationship between ln α-pinene levels and total proximal femur BMD was more pronounced in women, especially pre-menopausal women. Compared to subjects with α-pinene and limonene levels at or below the 50th percentiles, those exceeding this threshold exhibited the lowest mean value of total proximal femur BMD (0.8628 g/cm2, S.E. = 0.026, P = 0.009). However, the trend was not statistically significant (P = 0.070). Additionally, all three monoterpenes were linked to a higher prevalence of previous spine fractures, whereas β-pinene showed a reduced incidence of other types of fractures. In this comprehensive survey of American adults aged 40 and above, higher serum levels of α-pinene and limonene correlated with decreased total proximal femur BMD. Furthermore, our findings suggest a potential combined effect of α-pinene and limonene on total proximal femur BMD. Further investigation is essential to elucidate the clinical relevance and causative nature of our findings.

Abstract Background While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery. Methods We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)‐matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1–T4b tumors, clinical N0–3 disease, and clinical stage I–IV. Results In the PS‐matched cohort, the 5‐year disease‐specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5‐year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5‐year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5‐year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2–3, cN1, and c‐Stage II disease in the IC + OP group were significantly more likely to achieve pT0–1 status (p

Background: An association between the gut microbiome and cognitive function has been demonstrated in prior studies. However, whether the oral microbiome, the second largest microbial habitant in humans, has a role in cognition remains unclear. Design, setting, participants: Using weighted data from the 2011 to 2012 National Health and Nutrition Examination Survey, we examined the association between oral microbial composition and cognitive function in older adults. The oral microbiome was characterized by 16S ribosomal RNA gene sequencing. Cognitive status was assessed using the Consortium to Establish a Registry for Alzheimer’s Disease immediate recall and delayed recall, Animal Fluency Test, and Digit Symbol Substitution Test (DSST). Subjective memory changes over 12 months were also assessed. Linear and logistic regression models were conducted to quantify the association of α-diversity with different cognitive measurements controlling for potential confounding variables. Differences in β-diversity were analyzed using permutational analysis of variance. Results: A total of 605 participants aged 60–69 years were included in the analysis. Oral microbial α-diversity was significantly and positively correlated with DSST (β, 2.92; 95% CI, 1.01–4.84). Participants with higher oral microbial α-diversity were more likely to have better cognitive performance status based on DSST (adjusted odds ratio, 2.35; 95% CI, 1.28–4.30) and were less likely to experience subjective memory changes (adjusted odds ratio, 0.43; 95% CI, 0.25–0.74). In addition, β-diversity was statistically significant for the cognitive performance status based on DSST (P = 0.031) and subjective memory changes (P = 0.023). Conclusions: Oral microbial composition was associated with executive function and subjective memory changes among older adults among older U.S. adults in a nationally representative population sample. Oral dysbiosis is a potential biomarker or therapeutic target for cognitive decline. Further work is needed to elucidate the mechanisms underpinning the association between the oral microbiome and cognitive function.

Monoterpenes are organic compounds which have been studied for their medicinal benefits. However, the association between monoterpene exposure and metabolic parameters in humans is unknown. We investigated the connection between three specific monoterpenes (α-pinene, β-pinene, and limonene), glucose homeostasis biomarkers, lipid profiles, and metabolic syndrome (MS) in 1627 adults from the National Health and Nutrition Examination Survey (NHANES) 2013–2014. We found serum levels of α-pinene and β-pinene were positively associated with fasting glucose, total cholesterol, triglyceride, and apolipoprotein B. In addition, increased levels of limonene and Σmonoterpene (sum of three monoterpene chemicals) were linked to higher insulin, β-cell function, total cholesterol, low density lipoprotein cholesterol (LDL-C), triglycerides, and apolipoprotein B. Participants with all three monoterpenes above the 50th percentile had notably higher values for total cholesterol and triglycerides compared to those with all three monoterpenes below the 50th percentile (P for trend

Abstract Objectives The aim of this meta‐analysis is to evaluate the potential benefits of postoperative radiotherapy (PORT) in patients with pN1 oral cavity squamous cell carcinoma. Methods A literature search through major databases was conducted until January 2023. The adjusted hazard ratio (aHR) or risk ratio (RR) with 95% confidence intervals (CIs) of different survival outcomes were extracted and pooled. Results Ten studies published between 2005 and 2022, with a pooled patient population of 2888, were included in this meta‐analysis. Due to differences in study design and reported outcomes, the studies were categorized into distinct groups. In pN1 patients without extranodal extension (ENE), PORT was associated with a significant improvement in overall survival (OS) (aHR 0.76, 95% CI: 0.61–0.94). In pN1 patients without ENE and positive margins, PORT improved OS (aHR 0.71, 95% CI: 0.56–0.89) and was associated with a lower regional recurrence rate (RR 0.35, 95% CI: 0.15–0.83). However, in pN1 patients without ENE, positive margins, perineural invasion, and lymphovascular invasion, there were no significant differences observed between the PORT and observation groups in either 5‐year OS (RR 0.48, 95% CI: 0.07–3.41) or 5‐year disease‐free survival (RR 0.37, 95% CI: 0.07–2.06). Conclusions The current study demonstrated that PORT has the potential to improve OS in pN1 disease. However, the decision of whether to administer PORT still hinges on diverse clinical scenarios, and additional research is necessary to furnish a more conclusive resolution. Level of Evidence 2.

Abstract Background Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in‐hospital stay and long‐term survival outcomes in patients with OCSCC. Methods A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5‐year disease‐specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)‐matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS‐matched analysis. Results Prior to PS matching, patients with tracheotomy had significantly lower 5‐year DSS and OS rates compared to those without (71% vs. 82%, p

Background: Tricuspid valve disease significantly affects 1.6 million Americans. The gold standard treatment for tricuspid disease is the implantation of annuloplasty devices. These ring-like devices come in various shapes and sizes. Choices for both shape and size are most often made by surgical intuition rather than scientific rationale. Methods: To understand the impact of shape and size on valve mechanics and to provide a rational basis for their selection, we used a subject-specific finite element model to conduct a virtual case study. That is, we implanted 4 different annuloplasty devices of 6 different sizes in our virtual patient. After each virtual surgery, we computed the coaptation area, leaflet end-systolic angles, leaflet stress, and chordal forces. Results: We found that contoured devices are better at normalizing end-systolic angles, whereas the one flat device, the Edwards Classic, maximized the coaptation area and minimized leaflet stress and chordal forces. We further found that reducing device size led to increased coaptation area but also negatively impacted end-systolic angles, stress, and chordal forces. Conclusions: Based on our analyses of the coaptation area, leaflet motion, leaflet stress, and chordal forces, we found that device shape and size have a significant impact on valve mechanics. Thereby, our study also demonstrates the value of simulation tools and device tests in “virtual patients.” Expanding our study to many more valves may, in the future, allow for universal recommendations.

Abstract Background To investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods. Methods We retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan–Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC. Results Compared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p

Abstract Background To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1−2N0M0 oral cavity squamous cell carcinoma (OCSCC). Methods Between 2011 and 2019, we analyzed data for 13,542 cT1−2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well‐balanced study groups (initial surgery, n = 580; definitive RT, n = 145). Results Before PS matching, the 5‐year disease‐specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5‐year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5‐year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p

This article - Recommendations and Guidelines of Integrative Medicine (IM) for COVID-19 Care - was one of the outcomes from an Asia-Pacific Economic Cooperation (APEC) Project (Integrative Medicine (IM) and COVID -19 Care) during the time between May 2022 and March 2023. With the efforts from care providers, researchers, health policy makers and healthcare administrative leaders among APEC economies, the purpose of this file was to provide comprehensive IM systems for COVID-19 care as recommendations and suggestive guidelines including care methods, tools, procedures, symptom conditions and targets selections, and points need to be considered during care applications. All cited COVID-19 care practices have confirmed their efficacy and usefulness either used alone or combined with conventional medicine. This article provides current useful medical information on IM for COVID-19 care which could benefit APEC economies and world health communities on their healthcare system.

Background: The effectiveness of cetuximab (CTX) combined with methotrexate (MTX) has not yet been evaluated in patients with recurrent and/or metastatic head-and-neck squamous cell carcinoma (RM-HNSCC). Materials and Methods: A retrospective analysis of patients with RM-HNSCC who received 50 mg MTX weekly plus a standard dose of CTX for a maximum of 18 weeks, without maintenance CTX. Results: A total of 164 patients were included (cisplatin-sensitive, 88; cisplatin-refractory, 76). Among 58 cisplatin-sensitive patients receiving CTX/MTX as the first-line treatment, the outcomes were 39.7% response rate (RR), 70.7% disease control rate (DCR), 6.0 months of median progression-free survival (PFS), and 9.0 months of overall survival (OS). Among cisplatin-refractory patients, results were 31.6% RR, 51.3% DCR, 4.0 months of PFS, and 6.0 months of OS. Multivariable analyses revealed PFS and OS were not associated with cisplatin-refractory status, age, performance status, or the lines of CTX/MTX treatments. In cisplatin-refractory patients, those with only locoregional-recurrence disease had significantly worse PFS, but this did not affect OS; a similar trend was observed in cisplatin-sensitive patients. Conclusion: A CTX/MTX regimen, without maintenance CTX, is a safe and effective palliative treatment for both patients with cisplatin-sensitive or cisplatin-refractory RM-HNSCC. The low adverse events and easy administration makes this treatment a suitable option in various contexts, particularly for cisplatin-unfit or frail patients with RM-HNSCC.

Abstract Background Some prospective studies have shown that second‐generation tyrosine kinase inhibitors (TKIs) provide better control in patients with non‐small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations. However, studies comparing second‐line chemotherapy efficacy between NSCLC patients with common and uncommon EGFR mutations remain rare. This retrospective study compared treatment outcomes in these patients. Methods Patients with EGFR‐mutated advanced‐stage NSCLC who received first‐line EGFR‐TKIs in a tertiary referral center were retrospectively reviewed between January 2010 and August 2022. Patients with a negative T790M test at disease progression who received second‐line chemotherapy were enrolled. We compared progression‐free (PFS) and overall (OS) survival between advanced NSCLC patients with common and uncommon EGFR mutations using Kaplan–Meier and log‐rank tests. Results In total, 209 (54.8%) patients had a negative T790M mutation test and received second‐line chemotherapy, of which 192 (91.8%) had a common EGFR mutation (exon 19 deletion or exon 21 L858R substitution), and 17 (8.2%) had an uncommon EGFR mutation. Patients with common EGFR mutations had significantly longer PFS than those with uncommon EGFR mutations (4.57 vs. 2.57 months, p = 0.031). A Cox proportional hazard regression analysis controlling for potential confounding factors indicated that an uncommon EGFR mutation was an independent prognostic factor for PFS. Conclusion This study suggests that patients with uncommon EGFR mutations have poorer chemotherapy responses and shorter survival than those with common EGFR mutations. The development of new treatment strategies for these patients remains an unmet need.

Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease in infants and children with potential for fatal complications such as encephalitis and acute flaccid myelitis. This study examined the long-term immunity conferred by EV71vac, an inactivated EV-A71 vaccine adjuvanted with aluminum phosphate, in children from the age of 2 months to

In the field of dentistry, the presence of dental calculus is a commonly encountered issue. If not addressed promptly, it has the potential to lead to gum inflammation and eventual tooth loss. Bitewing (BW) images play a crucial role by providing a comprehensive visual representation of the tooth structure, allowing dentists to examine hard-to-reach areas with precision during clinical assessments. This visual aid significantly aids in the early detection of calculus, facilitating timely interventions and improving overall outcomes for patients. This study introduces a system designed for the detection of dental calculus in BW images, leveraging the power of YOLOv8 to identify individual teeth accurately. This system boasts an impressive precision rate of 97.48%, a recall (sensitivity) of 96.81%, and a specificity rate of 98.25%. Furthermore, this study introduces a novel approach to enhancing interdental edges through an advanced image-enhancement algorithm. This algorithm combines the use of a median filter and bilateral filter to refine the accuracy of convolutional neural networks in classifying dental calculus. Before image enhancement, the accuracy achieved using GoogLeNet stands at 75.00%, which significantly improves to 96.11% post-enhancement. These results hold the potential for streamlining dental consultations, enhancing the overall efficiency of dental services.

Carotid blowout syndrome (CBS) is a rare yet life-threatening complication that occurs after radiation therapy (RT). This study aimed to determine the incidence of CBS in patients with head and neck cancer (HNC) undergoing contemporary RT and to explore potential discrepancies in the risk of CBS between nasopharyngeal cancer (NPC) and non-NPC patients. A total of 1084 patients with HNC who underwent RT between 2013 and 2023 were included in the study. All patients were under regular follow-ups at the radio-oncology department, and underwent annual contrast-enhanced computed tomography and/or magnetic resonance imaging for cancer recurrence surveillance. Experienced neuroradiologists and vascular neurologists reviewed the recruited patients’ images. Patients were further referred to the neurology department for radiation vasculopathy evaluation. The primary outcome of this study was CBS. Patients were categorized into NPC and non-NPC groups and survival analysis was employed to compare the CBS risk between the two groups. A review of the literature on CBS incidence was also conducted. Among the enrolled patients, the incidence of CBS in the HNC, NPC, and non-NPC groups was 0.8%, 0.9%, and 0.7%, respectively. Kaplan–Meier analysis revealed no significant difference between the NPC and non-NPC groups (p = 0.34). Combining the findings for our cohort with those of previous studies revealed that the cumulative incidence of CBS in patients with HNC is 5% (95% CI = 3–7%) after both surgery and RT, 4% (95% CI = 2–6%) after surgery alone, and 5% (95% CI = 3–7%) after RT alone. Our findings indicate a low incidence of CBS in patients with HNC undergoing contemporary RT. Patients with NPC may have a CBS risk close to that of non-NPC patients. However, the low incidence of CBS could be a potentially cause of selection bias and underestimation bias.

IntroductionGlyphosate, a widely utilized herbicide globally, has been linked to various health issues, including cancer, birth abnormalities, and reproductive issues. Additionally, there is growing experimental support indicating potential harm to skeletal muscles. Despite this, the impact of glyphosate on human muscle health remains unclear.MethodsWe examined information gathered from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), which included 1466 adults aged 18 or older. Our primary aim was to investigate the relationship between glyphosate exposure and hand grip strength, as well as its influence on lean muscle mass.Results and discussionOur investigation uncovered a detrimental correlation between glyphosate exposure and all measures of grip strength, except for the second test of the first hand. Specifically, we observed a statistically significant adverse association between glyphosate exposure and combined grip strength, which is calculated as the sum of the highest readings from both hands (ß coefficient of −2.000, S.E. = 0.891, p = 0.040). We did not observe a significant correlation between glyphosate levels, lean muscle mass, and the likelihood of reaching maximum grip strength meeting sarcopenia criteria. Additionally, we observed an interaction between age and glyphosate, as well as between body mass index (BMI) and glyphosate, concerning the association with combined grip strength. In this comprehensive analysis of NHANES data, our study reveals a potential association between glyphosate exposure and hand grip strength in the adult population. Our findings suggest the need for deeper exploration into the health effects of glyphosate exposure and its impact on muscle strength, shedding light on possible public health concerns.

BackgroundA jaundice-predominant presentation of Kawasaki disease (KD) is atypical.MethodsA total of 12 children with KD with a predominant manifestation of jaundice at MacKay Children's Hospital were reviewed, along with 42 cases reported in the literature since 1990.ResultsThe median age of the 12 patients was 1.85 years (range: 3 months–4 years), and 66.6% were male. All of the patients had elevated liver function at presentation, 50% had hydrops of the gallbladder, and almost 60% had gastrointestinal symptoms and signs. Complete KD was evident in 11 of the 12 patients (91.7%), and two patients (16.7%) had recurrent episodes. All of the patients received intravenous immunoglobulin (IVIG); however, one-third were refractory to treatment. Corticosteroids were used in five (41.7%) of the patients. Three (25%) of the patients had shock, and seven (58.3%) had coronary artery abnormalities, of whom one (8.3%) had persistent coronary artery aneurysm and the others recovered. A review of the 42 cases in the literature showed that the children with a jaundice-predominant presentation of KD had high rates of IVIG-refractory disease (25%), coronary artery abnormalities (25%), shock (13.2%), and corticosteroid treatment (24.2%).ConclusionsChildren with KD presenting with a jaundice-predominant manifestation are at a higher risk of IVIG-refractory disease, coronary artery abnormalities, and more recurrent episodes. Physicians should be aware of the risk of shock in this population.

Abstract Background The current NCCN guidelines recommend considering elective neck dissection (END) for early‐stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. Methods We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). Results Patients who underwent END had better 5‐year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p

Background: Nasopharyngeal carcinoma (NPC) is associated with Epstein–Barr virus (EBV) infection. To test preclinical NPC drugs, we established two patient-derived xenograft (PDX) mouse models, EBV-positive PDX-B13 and EBV-negative PDX-Li41, for drug screening. Methods: Based on next generation sequencing (NGS) studies, PDX-B13 had CCND1 copy number (CN) gain but CDKN2A CN loss, whereas PDX-Li41 had CDKN2A and RB1 CN loss, TSC1 (negative regulator of mTOR) frameshift deletion mutation, and increased activation of mTOR, a serine/threonine kinase that governs metabolism, autophagy, and apoptosis. Increased mTOR was also associated with poor NPC prognosis. Results: Everolimus, an mTOR inhibitor, suppressed tumor growth in the two PDX NPC models and had an additive antitumor effect with palbociclib, a CDK4/6 inhibitor. PDX tumors treated with various drugs or untreated were subjected to RNA sequencing, transcriptome profile analysis, and selective Western blotting to understand the interactions between these drugs and gene expression profiles. Palbociclib also suppressed EB viral nuclear antigen (EBNA1) expression in PDX-B13. Everolimus together with autophagy inhibitor, hydroxychloroquine, had additive anti-tumor effect on PDX-B13 tumor. Immunohistochemistry revealed that high mTOR levels were correlated with poor overall survival in patients with metastatic NPC (N = 90). Conclusions: High mTOR levels are a poor prognostic factor in NPC, and cell cycle, mTOR and autophagy pathways may serve as therapeutic targets in NPC. In addition, PDX models can be used for efficiently testing potential NPC drugs.

Abstract Background Adiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood. Methods This study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12–30 from Taiwan. Results Results showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (− 0.095 vs. − 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG. Conclusions In this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

Background: Since 2015, 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program in Taiwan. Subsequently, the serotypes of the main circulating Streptococcus pneumoniae strains have changed. PCV administration is also associated with changes in the antimicrobial susceptibility of S. pneumoniae strains. Therefore, in this study, we analyzed the serotype distribution and antimicrobial susceptibility of S. pneumoniae in pediatric infections. Methods: Children with S. pneumoniae infections, including invasive pneumococcal disease (IPD) and non-IPD, were enrolled from January 2010 to December 2020. The samples were collected from Mackay Memorial Hospital, MacKay Children's Hospital, and Hsinchu Mackay Hospital in Taiwan. We analyzed the epidemiology of sample collection site, infection diagnosis, and the serotype and antimicrobial susceptibility of S. pneumoniae strains. The study period was divided into time points before and after PCV13 administration. Results: In total, 322 isolates were collected during the study period. The incidence of IPD declined annually, from 29.7% before 2015 to 7.3% after 2015 (p

Abstract Background Osteoradionecrosis (ORN) of the jaw requires a differential diagnosis to exclude cancer recurrence. Here, we sought to develop a scoring system comprising 18F-FDG PET/CT parameters for distinguishing between the two conditions in patients with oral squamous cell carcinoma (OSCC). Methods The study consisted of 103 OSCC patients with suspected ORN of the jaw. All participants underwent 18F-FDG PET/CT imaging within 6 months of diagnostic histopathology. Following extraction of PET parameters, we identified clinical and imaging predictors of mandibular recurrence-free survival (MRFS) using receiver operating characteristic curve analysis and multivariate Cox regression models. Results The results of histopathology revealed mandibular cancer recurrence in 24 patients (23.3%). Multivariate Cox regression analyses identified an age at diagnosis ≤ 52 years (P = 0.013), a location of the SUVmax voxel with soft tissue predominance (P = 0.019), and mandibular total lesion glycolysis (TLG) > 62.68 g (P

Abstract Background The association of breaks in sedentary time with outcomes of physical function can vary according to the time of day. We examined the association of the diurnal pattern of breaks in sedentary time with physical function outcomes in older adults. Methods A cross-sectional analysis was conducted among 115 older adults (≥60 years). The overall and time-specific breaks (morning: 06:00–12:00; afternoon: 12:00–18:00; evening: 18:00–24:00) in sedentary time were assessed using a triaxial accelerometer (Actigraph GT3X+). A break in sedentary time was defined as at least 1 min where the accelerometer registered ≥100 cpm following a sedentary period. Five physical function outcomes were assessed: handgrip strength (dynamometer), balance ability (single leg stance), gait speed (11-m walking), basic functional mobility (time up and go), and lower-limb strength (five times sit-to-stand). Generalized linear models were used to examine the associations of the overall and time-specific breaks in sedentary time with the physical function outcomes. Results Participants showed an average of 69.4 breaks in sedentary time during the day. Less frequent breaks in the evening (19.3) were found than that in the morning (24.3) and the afternoon (25.3) (p

Abstract The role of Programmed Cell Death Ligand 1 (PD-L1) expression in predicting epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) efficacy remains controversial. Recent studies have highlighted that tumor-intrinsic PD-L1 signaling can be modulated by STAT3, AKT, MET oncogenic pathway, epithelial–mesenchymal transition, or BIM expression. This study aimed to investigate whether these underlying mechanisms affect the prognostic role of PD-L1. We retrospectively enrolled patients with EGFR mutant advanced stage NSCLC who received first-line EGFR-TKI between January 2017 and June 2019, the treatment efficacy of EGFR-TKI was assessed. Kaplan–Meier analysis of progression-free survival (PFS) revealed that patients with high BIM expression had shorter PFS, regardless of PD-L1 expression. This result was also supported by the COX proportional hazard regression analysis. In vitro, we further proved that the knockdown of BIM, instead of PDL1, induced more cell apoptosis following gefitinib treatment. Our data suggest that among the pathways affecting tumor-intrinsic PD-L1 signaling, BIM is potentially the underlying mechanism that affects the role of PD-L1 expression in predicting response to EGFR TKI and mediates cell apoptosis under treatment with gefitinib in EGFR-mutant NSCLC. Further prospective studies are required to validate these results.

Abstract Background The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC. Methods Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse. Results The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p

Abstract Mercaptopurine intolerance is an adverse effect of mercaptopurine administration in pediatric patients with acute lymphoblastic leukemia (ALL). NUDT15 variants have emerged as major determinants of mercaptopurine intolerance, especially in the Asian population. Two variants, c.55_56insGAGTCG in exon 1 and c.415C > T in exon 3, were commonly detected in the same allele, named NUDT15*1/*2. Although rare, compound heterozygous mutations also occur, with the two variants on different alleles (NUDT15*3/*6), which may confer tolerance to considerably lesser mercaptopurine dosage. Sanger sequencing or pyrosequencing can determine the NUDT15 variants but not the phase. Here, we designed an allele-specific PCR (AS-PCR) with locked nucleic acid-modified primers. A cohort of 63 patients harboring heterozygous c.55_56insGAGTCG and c.415C > T NUDT15 variations was selected for haplotyping using AS-PCR. Of the 63 patients, 60 harbored the NUDT15*1/*2 variant and three harbored compound heterozygous mutations, including two NUDT15*3/*6 and one NUDT15*2/*7 variants. These findings suggest that AS-PCR can determine NUDT15 diplotype and identify patients with compound heterozygous NUDT15 variants, which may enable precise genetic diagnosis of NUDT15. Nevertheless, a larger clinical trial is required to understand the clinical significance of NUDT15*3/*6 in pediatric patients with ALL because of its low incidence rate and challenges in detecting this variant.

Background/purpose: Central nervous system infections can cause severe complications and even death in children. Early diagnosis of the causative pathogen can guide appropriate treatment and improve outcomes. The BioFire® FilmArray® Meningitis/Encephalitis Panel (FA-ME) is a multiplex polymerase chain reaction (PCR) assay targeting 14 pathogens. We aimed to examine FA-ME performance compared with conventional assays and its effect on antimicrobial usage. Methods: We prospectively enrolled 55 pediatric patients with suspected meningitis or encephalitis and simultaneously performed FA-ME and conventional assays. Sixty-three hospitalized patients with CNS infection before implementing FA-ME were considered controls. We compared the FA-ME results with conventional assays and the empiric antimicrobial usage and hospital stay between the two study groups. Results: Nine patients (16.4%) tested positive by FA-ME, four were bacterial, and five were viral. Three additional pathogens were detected by conventional assays: Enterococcus faecalis, Leptospira, and herpes simplex virus type 2. In the control group, two bacterial pathogens were detected by CSF culture and four viral pathogens by single PCRs. Compared with the control group, the FA-ME group had a shorter time for pathogen detection, but there were no significant differences in pathogen detection rate, duration of empiric antimicrobial therapy, and length of hospital stay. Conclusion: Although no significant difference was found in empiric antimicrobial duration and length of stay between patients tested with FA-ME and conventional assays, FA-ME had the advantage of a shorter detection time and early exclusion of potential causative pathogens. The FA-ME results should be interpreted carefully based on the clinical presentation.

Background: To predict the outcome of reirradiation (re-RT) for oral cavity squamous cell carcinoma (OSCC). Methods: Eighty-three patients met the criterion of having previously irradiated OSCC treated via curative intent re-RT for recurrent or new primary OSCC. The exclusion criteria were a suboptimal dose (

Abstract Adolescents and children play an important role in SARS-CoV-2 transmission and epidemiology. MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on stabilized spike protein adjuvanted with CpG 1018 and aluminum hydroxide that has received emergency use approval (EUA) for adults in Taiwan. In this study, we have investigated the safety and immunogenicity of two doses of MVC-COV1901 in adolescents. Healthy adolescents from the age of 12–17 years were randomly assigned to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups, with the most commonly reported adverse events being pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups. The results here advocate the use of MVC-COV1901 in adolescents in the ongoing efforts to control the pandemic. ClinicalTrials.gov registration: NCT04951388.

Background: Invasive pulmonary aspergillosis (IPA) can negatively impact cancer patients’ survival. It remains uncertain whether IPA’s impact on patient outcomes varies by treatment approach in advanced lung cancer. Objectives: To explore the association between IPA and outcomes in patients with advanced lung cancer receiving different treatments. Design: A retrospective cohort study. Methods: We enrolled patients with advanced-stage lung cancer between 2013 and 2021 at a college hospital in Taiwan and used the 2021 European Organization for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium consensus for IPA diagnosis. Multivariable logistic regression was used to identify the IPA risk factors. We compared overall survival (OS) and postgalactomannan (GM) test survival between the IPA and control groups using multivariable Cox proportional hazards regression and the Kaplan–Meier method with propensity score matching (PSM). Results: Among 2543 patients with advanced-stage lung cancer, 290 underwent a GM test, of which 34 (11.7%) were diagnosed with IPA. Patients undergoing chemotherapy (HR = 4.02, p = 0.027) and immunotherapy [hazard ratio (HR) = 3.41, p = 0.076] tended to have IPA. Compared to the control group, the IPA group had shorter median OS (14.4 versus 9.9 months, p = 0.030) and post-GM test survival (4.5 versus 1.9 months, p = 0.003). IPA was associated with shorter OS (log-rank p = 0.014 and 0.018 before and after PSM, respectively) and shorter 1-year and 2-year survival post-GM test (HR = 1.65 and 1.66, respectively). Patients receiving chemotherapy or immunotherapy had a shorter post-GM test survival if they had IPA. Conclusions: IPA tended to be diagnosed more frequently in patients receiving chemotherapy or immune checkpoint inhibitors. Patients diagnosed with IPA are associated with shorter survival. Larger cohort studies are needed to verify the observations.

Background: A high incidence rate of nasopharyngeal carcinoma (NPC) has been observed in Southeast Asia compared to other parts of the world. Radiomics is a computational tool to predict outcomes and may be used as a prognostic biomarker for advanced NPC treated with concurrent chemoradiotherapy. Recently, radiomic analysis of the peripheral tumor microenvironment (TME), which is the region surrounding the gross tumor volume (GTV), has shown prognostic usefulness. In this study, not only was gross tumor volume (GTVt) analyzed but also tumor peripheral regions (GTVp) were explored in terms of the TME concept. Both radiomic features and delta radiomic features were analyzed using CT images acquired in a routine radiotherapy process. Methods: A total of 50 patients with NPC stages III, IVA, and IVB were enrolled between September 2004 and February 2014. Survival models were built using Cox regression with clinical factors (i.e., gender, age, overall stage, T stage, N stage, and treatment dose) and radiomic features. Radiomic features were extracted from GTVt and GTVp. GTVp was created surrounding GTVt for TME consideration. Furthermore, delta radiomics, which is the longitudinal change in quantitative radiomic features, was utilized for analysis. Finally, C-index values were computed using leave-one-out cross-validation (LOOCV) to evaluate the performances of all prognosis models. Results: Models were built for three different clinical outcomes, including overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). The range of the C-index in clinical factor models was (0.622, 0.729). All radiomics models, including delta radiomics models, were in the range of (0.718, 0.872). Among delta radiomics models, GTVt and GTVp were in the range of (0.833, 0.872) and (0.799, 0.834), respectively. Conclusions: Radiomic analysis on the proximal region surrounding the gross tumor volume of advanced NPC patients for survival outcome evaluation was investigated, and preliminary positive results were obtained. Radiomic models and delta radiomic models demonstrated performance that was either superior to or comparable with that of conventional clinical models.

Accurate organ at risk (OAR) segmentation is critical to reduce the radiotherapy post-treatment complications. Here, the authors develop an automated OAR segmentation system to delineate a comprehensive set of 42 H&N OARs.

Abstract Background Gout is a highly hereditary disease, but not all those carrying well-known risk variants have developing gout attack even in hyperuricemia status. We performed a genome-wide association study (GWAS) and polygenic risk score (PRS) analysis to illustrate the new genetic architectures of gout and asymptomatic hyperuricemia (AH). Methods GWAS was performed to identify variants associated with gout/AH compared with normouricemia. The participants were males, enrolled from the Taiwan Biobank and China Medical University, and divided into discovery (n=39,594) and replication (n=891) cohorts for GWAS. For PRS analysis, the discovery cohort was grouped as base (n=21,814) and target (n=17,780) cohorts, and the score was estimated by grouping the polymorphisms into protective or not for the phenotypes in the base cohort. Results The genes ABCG2 and SLC2A9 were found as the major genetic factors governing gouty and AH, and even in those carrying the rs2231142 (ABCG2) wild-genotype. Surprisingly, variants on chromosome 1, such as rs7546668 (DNAJC16), rs10927807 (AGMAT), rs9286836 (NUDT17), rs4971100 (TRIM46), rs4072037 (MUC1), and rs2974935 (MTX1), showed significant associations with gout in both discovery and replication cohorts (all p-values < 1e−8). Concerning the PRS, the rates of gout and AH increased with increased quartile PRS in those SNPs having risk effects on the phenotypes; on the contrary, gout/AH rates decreased with increased quartile PRS in those protective SNPs. Conclusions We found new variants on chromosome 1 significantly relating to gout, and PRS predicts the risk of developing gout/AH more robustly based on the SNPs’ effect types on the trait.

Although combination therapy including chemotherapy and immune checkpoint inhibitors (ICIs) improves overall survival (OS) of patients with non-small-cell lung cancer (NSCLC), there is a higher incidence of adverse events and treatment discontinuation. Since programmed death-ligand 1 (PD-L1) could not serve as a predictive biomarker, we investigated the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker. In our previous research, we demonstrated that a low NLR could predict survival benefits when patients with high PD-L1 expression (> 50%) received chemoimmunotherapy as opposed to immunotherapy alone. In this current study, our objective is to evaluate this predictive capacity in patients with low PD-L1 expression (< 50%). A total of 142 patients were enrolled, 28 receiving combination therapy and 114 receiving chemotherapy alone. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method and compared using the log-rank test. Patients who received combination therapy had significantly better PFS and OS than those who received monotherapy. In the subgroup of patients with low NLR, those who received combination therapy exhibited extended PFS and OS with clinical significance, which was also confirmed by multivariate Cox regression analysis. Our study demonstrates the potential use of NLR as a biomarker for predicting survival benefits when receiving combination therapy with chemotherapy and ICIs in patients with advanced NSCLC and low PD-L1 expression.

BackgroundCoronavirus disease 2019 (COVID-19) had caused huge impacts worldwide. Polymerase chain reaction (PCR) is the mainstay diagnostic modality. In most hospitals in Taiwan, samples for PCR are collected at emergency department (ER) or outdoor clinics to avoid virus spread inside hospitals. Home rapid antigen test (RAT) is a feasible, low-cost, and convenient tool with moderate sensitivity and high specificity, which can be performed at home to reduce hospital visits. Due to comparably low severity of omicron variant and high vaccine coverage (~80% residents fully vaccinated with AstraZeneca, Moderna, or Pfizer BioNTech COVID-19 vaccines as of March 2022), the policy was shifted from containment to co-existing with COVID-19 in Taiwan. Virus spread rapidly in the community after the ease of social restrictive measurements. To acquire a confirmed diagnosis, PCR testing was requested for people with suspected COVID-19 infection. As a consequence, people with respiratory symptoms or contact history surged into hospitals for PCR testing, thus, the medical capacity was challenged. The diagnostic policy was altered from PCR to RAT, but the impact of diagnostic policy change remains unclear.ObjectivesWe conducted this study to investigate the number of COVID-19 cases, PCR testing, hospitalizations, mortalities, and hospital visits during the epidemic and evaluate the impact of diagnostic policy change on hospital visits.MethodsThe diagnostic policy change was implemented in late May 2022. We used nationwide and hospital-based data of COVID-19 cases, PCR testing, hospitalizations, mortalities, and hospital visits before and after policy change as of 31 Jul 2022.ResultsDuring the omicron epidemic, significant and synchronous increase of COVID-19 patients, PCR testing, hospital visits were observed. COVID-19 cases increased exponentially since April 2022 and the COVID-19 patients peaked in June (1,943, 55,571, and 61,511 average daily new cases in April, May, and June, respectively). The PCR testing peaked in May (85,788 daily tests) with high positive rate (81%). The policy of RAT as confirmatory diagnosis was implemented on 26 May 2022 and a substantial decline of PCR testing numbers occurred (85,788 and 83,113 daily tests in May and June). People hospitalized for COVID-19 peaked in June (821.8 patients per day) and decreased in July (549.5 patients). The mortality cases also peaked in June (147 cases/day). This trend was also validated by the hospital-based data with a significant decrease of emergency department visits (11,397 visits in May while 8,126 visits in June) and PCR testing (21,314 in May and 6,158 in June). The proportion of people purely for PCR testing also decreased (10–26 vs. 5–14%, before and after policy change, respectively).ConclusionsThe impact of diagnostic policy change was a complicated issue and our study demonstrated the huge impact of diagnostic policy on health seeking behavior. The PCR testing numbers and emergency department visits had substantial decrease after diagnostic policy change, and the plateau of epidemic peak eased gradually in ~1 month later. Widespread RAT application may contribute to the decreased hospital visits and preserve medical capacity. Our study provides some evidences for policy maker's reference.

Objectives: Perineural invasion (PNI) was quantitatively analyzed in oral squamous cell carcinoma (OSCC) specimens obtained by radical surgery to correlate with survival outcomes. Methods: This is a retrospective study that reviewed the Cancer registry data between 2009 and 2015. Inclusion criteria were oral cavity cancer, treatment by radical surgery, presence of PNI, and available pathologic samples for S100 staining. Patients with M1 disease and those with synchronous or metachronous cancer during staging work-up were excluded. All pathologic samples were reviewed to confirm PNI status and processed by immunohistochemical staining for S100 to quantify PNI. Pathologic information and staging results were also reviewed, and clinical outcomes were analyzed. Results: The retrospective study included 92 patients; 63 had intratumoral PNI (IPNI) and 29 had extratumoral PNI (EPNI). The average number of PNI foci (APNI) was higher in the EPNI group than in the IPNI group (6.7 vs 3.8, t -test 2-tail significance = 0.021). The 3-year overall survival (OS) and time-to-recurrence (TTR) rates of all patients were 82.5% and 81.2%, respectively. Univariate analysis showed that pathological T4 or N2-3 stage correlated with poor OS, whereas APNI ≥4 correlated with poor TTR. In multivariate analysis, only the pathological N2-3 stage was significantly correlated with poor OS, whereas only APNI ≥ 4 was an independent factor of poor TTR. The 3-year TTR rates were 92.4% and 65.6% for diseases with APNI

Matrix metalloproteinase-1 (MMP-1) is associated with lung cancer, and thus the monitoring of the concentration of this protein may be useful for assessing lung cancer progression. In this work, poly(triphenylamine rhodanine-3-acetic acid-co-3,4-ethoxylene dioxy thiophene)s were incorporated onto a continuous monolayer (cML) of molybdenum disulfide (MoS2) by peptide-imprinted electropolymerization, in which peptides of MMP-1 were used as the templates in epitope imprinting. The morphology of the MoS2 thin film was monitored using optical and scanning electron microscopy. The imprinted MoS2 thin film electrode electrochemically responseded (at 1.0 pg/mL MMP-1) 1.4 times than ordinary imprinted electrodes. Moreover, MoS2 cML coating with PIPs can extend the sensing range of the PIP-coated electrodes from 1.0 pg/mL up to 10.0 pg/mL. The MoS2 cML electrode was used to determine that the MMP-1 concentration in the A549 cell line culture medium was 800 ng/mL. Comparison with results from a commercially available ELISA kit indicated an accuracy of 95 ± 5%.