Cesium Modulation in Cu(In, Ga)(S, Se)2 Solar Cells: Comprehensive Analysis on Interface, Surface, and Grain Boundary.

Cesium (Cs) incorporation and sulfurization on copper indium gallium selenide solar cells are the keys to improving the device quality. In this study, we explore the impact of Cs modulation on sulfur-containing Cu(In, Ga)(S, Se)2 (CIGSSe) absorbers, resulting in a performance increase of over 2%, reaching 18.11%. The improvement stems from a widened surface bandgap, grain boundary (GB) passivation, and a moderate injection blocking layer. The surface bandgap widens from 1.44 to 2.63 eV after Cs incorporation, confirmed by ultraviolet photoelectron spectroscopy (UPS) and low-energy inverse photoemission spectroscopy (LEIPS) analysis. Cs presence and S depletion in GBs suggest a new phase that might mitigate carrier recombination. Heightened Cs incorporation introduces interface issues, including an augmented injection blocking layer and interface defects. Our study offers insights into interface challenges and GB engineering strategies in Cs-treated CIGSSe solar cells, illuminating the multifaceted impact of heavy alkali metal ion Cs in CIGS-based photovoltaics.

High prevalence of exon-13 variants in USH2A-related retinal dystrophies in Taiwanese population.

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.

Healthcare Resource Utilization in Medicare Beneficiaries Obtaining Medication Synchronization.

BACKGROUND: An appointment-based medication synchronization (ABMS) is a service which aligns patients' chronic medications to a predetermined routine pickup date and includes a comprehensive medication review or other clinical appointment at the pharmacy. We compared healthcare utilization outcomes (outpatient, inpatient, emergency department visits, and pharmacy utilization) of Medicare beneficiaries enrolled in a med-sync program to beneficiaries not enrolled in such a program. METHODS: This retrospective cohort study included Medicare beneficiaries obtaining medications from pharmacies providing ABMS. All Medicare inpatient, outpatient, emergency, and pharmacy claims data from 2014 to 2016 obtained from the Research Data Assistance Center (ResDAC). These pharmacy claims were used to create medication-synchronized (med-sync) (n=13,193) and non-med-sync (n=156,987) cohorts. All patients were followed longitudinally for 12 months before and after a 2015 index/enrollment date. Baseline characteristics were utilized to create a logistic regression model for propensity score matching. A 1:1 greedy nearest neighbor matching algorithm was adapted for sequentially matching both cohorts. Difference-in-differences (DID) was used to compare mean changes in healthcare utilization outcomes (outpatient, inpatient, emergency department visits, and pharmacy utilization) between cohorts. RESULTS: After matching, 13,193 beneficiaries in each cohort were used for analysis. DID for mean of healthcare utilizations were significantly lower in the med-sync cohort compared to the non-med-sync cohort for outpatient visits (DID:0.012, p=0.0073) and pharmacy utilization (DID:0.013, p<0.0001). There was no significant DID for inpatient and emergency department visits between cohorts. CONCLUSION: Outpatient and pharmacy utilization changes were significantly lower in the med-sync cohort compared to the non-med-sync cohort in the 12-months after enrollment. Lower pharmacy utilization could be due to reducing duplicate prescriptions during synchronized refills or optimization of therapy during medication reviews if patients are enrolled in ABM med-sync.

Distinct effects of long-term Tai Chi Chuan and aerobic exercise interventions on motor and neurocognitive performance in early-stage Parkinson's disease: a randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative condition characterized by movement disorders and probable cognitive impairment. Exercise plays an important role in PD management, and recent studies have reported improvement in motor symptoms and cognitive function following aerobic and Tai Chi Chuan exercise. AIM: To explore the different effects of Tai Chi Chuan and aerobic exercise on the clinical motor status and neurocognitive performance of patients with early-stage PD. DESIGN: A randomized controlled trial. SETTING: Parkinson's Disease Center at Kaohsiung Chang Gung Memorial Hospital and National Cheng Kung University Hospital. POPULATION: Patients with idiopathic PD. METHODS: Fifty-six patients with PD were recruited and divided into three groups: aerobic exercise (AE, N.=14), Tai Chi Chuan exercise (TE, N.=16), and control (CG, N.=13). Before and after a 12-week intervention period, we used unified Parkinson's disease rating scale Part III (UPDRS-III) scores and neuropsychological (e.g., accuracy rates [ARs] and reaction times [RTs]) and neurophysiological (e.g., event-related potential [ERP] N2 and P3 latencies and amplitudes) parameters to respectively assess the patients' clinical motor symptoms and neurocognitive performance when performing a working memory (WM) task. RESULTS: Compared to baseline, UPDRS-III scores were significantly lower in the AE and TE groups after the intervention period, whereas those for the CG group were higher. In terms of the neurocognitive parameters, when performing the WM task after the intervention period, the AE group exhibited significantly faster RTs and larger ERP P3 amplitudes, the TE group exhibited an improvement only in ERP P3 amplitude, and the CG group exhibited a significantly reduced ERP P3 amplitude. However, neither the TE nor the AE group exhibited improved ARs and ERP N2 performance. CONCLUSIONS: The present study supported the distinct effectiveness of Tai Chi Chuan and aerobic exercise for improving motor symptoms and providing neurocognitive benefits in PD patients. CLINICAL REHABILITATION IMPACT: These results have important implications regarding the use of these exercise interventions for managing PD, particularly in the early stages.

Dependency of mitochondrial quantity on blastocyst timeline obscures its actual effect to pregnancy outcomes.

Objectives: To explore the correlation between mitochondrial quantity and the blastocyst development timeline as well as their respective contributions to early pregnancy. Methods: A retrospective study was conducted using a dataset comprising 2,633 embryos that underwent preimplantation genetic testing for aneuploidy (PGT-A) between January 2016 and December 2023. The study was divided into three subsets to address distinct aspects: the representativeness of a single trophectoderm (TE) biopsy for mitochondrial quantity (n=43), the correlation between morphokinetic features and mitochondrial quantity (n=307), and the association analysis among mitochondrial quantity, blastocyst timeline factor, and reproductive outcomes (n=2,283). Distribution assessment of mitochondrial quantity across an individual blastocyst involved the identification within multiple biopsies and spent culture media. Timeline evaluation included correlating mitochondrial quantity with time-lapse datasets. Finally, multivariate logistic regression models, incorporating potential effectors alongside mitochondrial quantity, were employed to analyze their respective contributions to early pregnancy endpoints. Results: Of distribution assessment, mitochondrial quantity exhibited an even distribution across the entire trophectoderm (Spearman's ρ=0.82), while no detectable mtDNAs in the corresponding spent culture media. Then the timeline correlation study revealed significant association between mitochondrial quantity and blastocyst features of both the day of expanded blastocyst formation (95% Confidence intervals, CIs: 0.27~4.89, p=0.03) and the timing of expanded blastocyst formation (tEB) (95% CIs: -0.24~-0.01, p=0.04) in the regression model, indicating a strong dependency between mitochondrial quantity and the blastocyst development timeline. For the contribution to early pregnancy, multivariate logistic regression models showed that the day of expanded blastocyst formation contributed to four endpoints persistently: positive for HCG (odd ratio, OR: 0.71, p=0.006), gestational sac (OR: 0.78, p=0.04), fetal heartbeat (OR: 0.71, p=0.004), and progression to 14 weeks (OR: 0.69, p=0.002). Contrastingly, no notable correlation was observed between the mitochondrial quantity and these endpoints. Conclusions: Strong interaction was observed between mitochondrial quantity and the blastocyst timeline, particularly the timing of expanded blastocyst formation. It suggests that the primary determinant influencing pregnancy outcomes lies in the time-dependent parameter of blastocyst rather than in the specific mitochondrial quantity.

Prognostic impact of elective tracheotomy in resected oral cavity squamous cell carcinoma: A nationwide cohort study.

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 < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001). CONCLUSIONS: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays.

Neurocognitive performance of badminton players at different competitive levels in visuospatial attention tasks.

Visuospatial attention (VSA) is a cognitive function that enables athletes, particularly those engaged in open-skill sports, to allocate attentional resources efficiently to the appropriate target and in the appropriate direction. Studies have indicated that expert players exhibit superior cognitive performance to that of novices. However, no study has investigated differences in VSA performance among elite, expert, and intermediate badminton players or the potential neurophysiological mechanisms underlying such differences. Accordingly, the present study explored neuropsychological and neurophysiological parameters during VSA tasks among badminton players of varying competitive levels. The study included 54 participants and divided them into three groups according to their competition records: elite (n = 18), expert (n = 18), and intermediate (n = 18). Their neuropsychological performance and brain event-related potentials (ERPs) during the Posner cueing paradigm were collected. Although the three groups did not differ in their accuracy rates, ERP N2 amplitudes, or N2 or P3 latencies, the elite and expert groups exhibited notably faster reaction times and more pronounced P3 amplitudes than did the intermediate group during the cognitive task. However, we did not observe these between-group differences when we controlled for the covariate training years. Additionally, the elite and expert groups exhibited comparable neurocognitive performance. These findings indicate that badminton players' competitive levels influence their VSA. However, the beneficial effects on neuropsychological and neurophysiological performance could stabilize after a certain level of badminton competence is reached. Year of training could also be a major factor influencing badminton players' neurocognitive performance in VSA tasks.

Anisotropic thermal conductivity of antigorite along slab subduction impacts seismicity of intermediate-depth earthquakes.

Double seismic zones (DSZs) are a feature of some subducting slabs, where intermediate-depth earthquakes (~70-300 km) align along two separate planes. The upper seismic plane is generally attributed to dehydration embrittlement, whereas mechanisms forming the lower seismic plane are still debated. Thermal conductivity of slab minerals is expected to control the temperature evolution of subducting slabs, and therefore their seismicity. However, effects of the potential anisotropic thermal conductivity of layered serpentine minerals with crystal preferred orientation on slab's thermal evolution remain poorly understood. Here we measure the lattice thermal conductivity of antigorite, a hydrous serpentine mineral, along its crystallographic b- and c-axis at relevant high pressure-temperature conditions of subduction. We find that antigorite's thermal conductivity along the c-axis is ~3-4 folds smaller than the b-axis. Our numerical models further reveal that when the low-thermal-conductivity c-axis is aligned normal to the slab dip, antigorite's strongly anisotropic thermal conductivity enables heating at the top portion of the slab, facilitating dehydration embrittlement that causes the seismicity in the upper plane of DSZs. Potentially, the antigorite's thermal insulating effect also hinders the dissipation of frictional heat inside shear zones, promoting thermal runaway along serpentinized faults that could trigger intermediate-depth earthquakes.

Discrepancies in dengue burden estimates: a comparative analysis of reported cases and global burden of disease study, 2010-2019.

BACKGROUND: Dengue is a significant mosquito-borne disease. Several studies have utilized estimates from the Global Burden of Disease (GBD) study to assess the global, regional or national burden of dengue over time. However, our recent investigation suggests that GBD's estimates for dengue cases in Taiwan are unrealistically high. The current study extends the scope to compare reported dengue cases with GBD estimates across 30 high-burden countries and territories, aiming to assess the accuracy and interpretability of the GBD's dengue estimates. METHODS: Data for this study were sourced from the GBD 2019 study and various national and international databases documenting reported dengue cases. The analysis targeted the top 30 countries and territories with the highest 10-year average of reported cases from 2010 to 2019. Discrepancies were quantified by computing absolute differences and ratios between the 10-year average of reported cases and GBD estimates. Coefficients of variation (CV) and estimated annual percentage changes (EAPCs) were calculated to assess variations and trends in the two data sources. RESULTS: Significant discrepancies were noted between reported data and GBD estimates in the number of dengue cases, incidence rates, and EAPCs. GBD estimates were substantially higher than reported cases for many entities, with the most notable differences found in China (570.0-fold), India (303.0-fold), Bangladesh (115.4-fold), Taiwan (85.5-fold) and Indonesia (23.2-fold). Furthermore, the GBD's estimates did not accurately reflect the extensive yearly fluctuations in dengue outbreaks, particularly in non-endemic regions such as Taiwan, China and Argentina, as evidenced by high CVs. CONCLUSIONS: This study reveals substantial discrepancies between GBD estimates and reported dengue cases, underscoring the imperative for comprehensive analysis in areas with pronounced disparities. The failure of GBD estimates to represent the considerable annual fluctuations in dengue outbreaks highlights the critical need for improvement in disease burden estimation methodologies for dengue.

Excess glucose alone depress young mesenchymal stromal/stem cell osteogenesis and mitochondria activity within hours/days via NAD+/SIRT1 axis.

BACKGROUND: The impact of global overconsumption of simple sugars on bone health, which peaks in adolescence/early adulthood and correlates with osteoporosis (OP) and fracture risk decades, is unclear. Mesenchymal stromal/stem cells (MSCs) are the progenitors of osteoblasts/bone-forming cells, and known to decrease their osteogenic differentiation capacity with age. Alarmingly, while there is correlative evidence that adolescents consuming greatest amounts of simple sugars have the lowest bone mass, there is no mechanistic understanding on the causality of this correlation. METHODS: Bioinformatics analyses for energetics pathways involved during MSC differentiation using human cell information was performed. In vitro dissection of normal versus high glucose (HG) conditions on osteo-/adipo-lineage commitment and mitochondrial function was assessed using multi-sources of non-senescent human and murine MSCs; for in vivo validation, young mice was fed normal or HG-added water with subsequent analyses of bone marrow CD45- MSCs. RESULTS: Bioinformatics analyses revealed mitochondrial and glucose-related metabolic pathways as integral to MSC osteo-/adipo-lineage commitment. Functionally, in vitro HG alone without differentiation induction decreased both MSC mitochondrial activity and osteogenesis while enhancing adipogenesis by 8 h' time due to depletion of nicotinamide adenine dinucleotide (NAD+), a vital mitochondrial co-enzyme and co-factor to Sirtuin (SIRT) 1, a longevity gene also involved in osteogenesis. In vivo, HG intake in young mice depleted MSC NAD+, with oral NAD+ precursor supplementation rapidly reversing both mitochondrial decline and osteo-/adipo-commitment in a SIRT1-dependent fashion within 1 ~ 5 days. CONCLUSIONS: We found a surprisingly rapid impact of excessive glucose, a single dietary factor, on MSC SIRT1 function and osteogenesis in youthful settings, and the crucial role of NAD+-a single molecule-on both MSC mitochondrial function and lineage commitment. These findings have strong implications on future global OP and disability risks in light of current worldwide overconsumption of simple sugars.

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Enhancement of Efficiency of Perovskite Solar Cells with Hole-Selective Layers of Rationally Designed Thiazolo[5,4-d]thiazole Derivatives.

We introduce thiazolo[5,4-d]thiazole (TT)-based derivatives featuring carbazole, phenothiazine, or triphenylamine donor units as hole-selective materials to enhance the performance of wide-bandgap perovskite solar cells (PSCs). The optoelectronic properties of the materials underwent thorough evaluation and were substantially fine-tuned through deliberate molecular design. Time-of-flight hole mobility TTs ranged from 4.33 × 10-5 to 1.63 × 10-3 cm2 V-1 s-1 (at an electric field of 1.6 × 105 V cm-1). Their ionization potentials ranged from -4.93 to -5.59 eV. Using density functional theory (DFT) calculations, it has been demonstrated that S0 → S1 transitions in TTs with carbazolyl or ditert-butyl-phenothiazinyl substituents are characterized by local excitation (LE). Mixed intramolecular charge transfer (ICT) and LE occurred for compounds containing ditert-butyl carbazolyl-, dimethoxy carbazolyl-, or alkoxy-substituted triphenylamino donor moieties. The selected derivatives of TT were used for the preparation of hole-selective layers (HSL) in PSC with the structure of glass/ITO/HSLs/Cs0.18FA0.82Pb(I0.8Br0.2)3/PEAI/PC61BM/BCP/Ag. The alkoxy-substituted triphenylamino containing TT (TTP-DPA) has been demonstrated to be an effective material for HSL. Its layer also functioned well as an interlayer, improving the surface of control HSL_2PACz (i.e., reducing the surface energy of 2PACz from 66.9 to 52.4 mN m-1), thus enabling precise control over perovskite growth energy level alignment and carrier extraction/transportation at the hole-selecting contact of PSCs. 2PACz/TTP-DPA-based devices showed an optimized performance of 19.1 and 37.0% under 1-sun and 3000 K LED (1000 lx) illuminations, respectively. These values represent improvements over those achieved by bare 2PACz-based devices, which attained efficiencies of 17.4 and 32.2%, respectively. These findings highlight the promising potential of TTs for the enhancement of the efficiencies of PSCs.

A Phase 3, Randomized, Controlled Trial Evaluating the Efficacy and Safety of Ropeginterferon Alfa-2b in Patients with Moderate COVID-19.

INTRODUCTION: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection. METHODS: This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value < 30 and symptom onset within 4 days were enrolled. Eligible patients were randomized in a 2:1 ratio to receive a single 250-µg dose of ropeginterferon alfa-2b subcutaneously plus standard of care (SOC) or to receive SOC alone. The primary endpoint was the proportion of patients with a negative RT-PCR result for SARS-CoV-2 or discharged from the hospital before Day 8. Change in clinical status based on the World Health Organization (WHO) clinical progression scale and pulmonary infiltrations through chest radiograph were also evaluated. RESULTS: A total of 132 patients were enrolled and treated with study medication. Higher percentages of patients who achieved Ct ≥ 30 or were discharged from the hospital were observed on Day 8 and every other time point of assessment, i.e., Days 5, 11, 15, and 22, in the ropeginterferon alfa-2b group compared to the SOC alone group. However, the difference was statistically significant on Day 11 but not on Day 8. The primary endpoint was not met. The ropeginterferon alfa-2b group showed a higher improvement rate in lung infiltration on Day 5 (27.6% vs. 0.0%, p = 0.0087) and a higher improvement rate in WHO clinical progression scores on Day 8 (69.4% vs. 35.3%, p = 0.03) than those in the SOC group. No ropeginterferon alfa-2b-related serious adverse event was observed. CONCLUSION: Our data show that ropeginterferon alfa-2b with SOC shortened the duration of SARS-CoV-2 shedding compared with SOC alone. In addition, ropeginterferon alfa-2b as an additional therapy could be beneficial by improving lung infiltration.

Association of the oral microbiome with cognitive function among older adults: NHANES 2011-2012.

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 ß-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 (ß, 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, ß-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.

Lymphocyte-Infiltrated Periportal Region Detection With Structurally-Refined Deep Portal Segmentation and Heterogeneous Infiltration Features.

Goal: The early diagnosis and treatment of hepatitis is essential to reduce hepatitis-related liver function deterioration and mortality. One component of the widely-used Ishak grading system for the grading of periportal interface hepatitis is based on the percentage of portal borders infiltrated by lymphocytes. Thus, the accurate detection of lymphocyte-infiltrated periportal regions is critical in the diagnosis of hepatitis. However, the infiltrating lymphocytes usually result in the formation of ambiguous and highly-irregular portal boundaries, and thus identifying the infiltrated portal boundary regions precisely using automated methods is challenging. This study aims to develop a deep-learning-based automatic detection framework to assist diagnosis. Methods: The present study proposes a framework consisting of a Structurally-REfined Deep Portal Segmentation module and an Infiltrated Periportal Region Detection module based on heterogeneous infiltration features to accurately identify the infiltrated periportal regions in liver Whole Slide Images. Results: The proposed method achieves 0.725 in F1-score of lymphocyte-infiltrated periportal region detection. Moreover, the statistics of the ratio of the detected infiltrated portal boundary have high correlation to the Ishak grade (Spearman's correlations more than 0.87 with p-values less than 0.001) and medium correlation to the liver function index aspartate aminotransferase and alanine aminotransferase (Spearman's correlations more than 0.63 and 0.57 with p-values less than 0.001). Conclusions: The study shows the statistics of the ratio of infiltrated portal boundary have correlation to the Ishak grade and liver function index. The proposed framework provides pathologists with a useful and reliable tool for hepatitis diagnosis.

Strategic Use of Biodegradable Temporizing Matrix (BTM) in Wound Healing: A Case Series in Asian Patients.

Skin and soft tissue reconstruction has long been based on the reconstructive ladder. However, a skin substitute has become popular due to its predictable outcomes, without donor-site morbidity. The biodegradable temporizing matrix (BTM; NovoSorb, PolyNovo Ltd., Port Melbourne, Australia) is a synthetic skin substitute that has recently gained its clinical application. Compared with those of other dermal templates, the clinical efficacy and performance of the BTM are not well established, especially among the Asian population. This study aims to share our experience and strategy of using BTM in various wound conditions. The data of patients who underwent skin and soft tissue reconstruction with BTM at a single institution between January 2022 and December 2023 were reviewed. The patient demographics, wound characteristics, surgical details, secondary procedures, and complications were recorded and analyzed. Postoperative 6-month photographs were collected and independently evaluated by two plastic surgeons and two wound care center nurses using the Manchester Scar Scale (MSS). This study included 37 patients, consisting of 22 males and 15 females with a mean age of 51.8 years (range, 18-86 years old). The wound etiologies included trauma (67.6%), necrotizing soft tissue infection (16.2%), burns (10.8%), toe gangrene (2.7%), and scar excision (2.7%). The average wound area covered by BTM was 50.6 ± 47.6 cm2. Among the patients, eight received concomitant flap surgery and BTM implantation, 20 (54.1%) underwent subsequent split-thickness skin grafts (STSG), and 17 had small wounds (mean: 21.6 cm2) healed by secondary intention. Infection was the most common complication, affecting six patients (n = 6 [16.2%]), five of whom were treated conservatively, and only one required debridement. Thirty-three patients (89.2%) had good BTM take, and only four had BTM failure, requiring further reconstruction. At the last follow-up, 35 out of the 37 patients (94.6%) achieved successful wound closure, and the total MSS score was 10.44 ± 2.94, indicating a satisfactory scar condition. The patients who underwent BTM grafting without STSG had better scar scores than those who received STSG (8.71 ± 2.60 vs. 11.18 ± 2.84, p = 0.039). In conclusion, the BTM is effective and feasible in treating various wounds, with relatively low complication rates, and it can thus be considered as an alternative for skin and soft tissue reconstruction. When combined with adipofasical flap reconstruction, it achieves a more comprehensive anatomical restoration.

Methane Hydrate Structure I Dissociation Process and Free Surface Analysis.

Methane hydrates are crystalline solids of water that contain methane molecules trapped inside their molecular cavities. Gas hydrates with methane as a guest molecule form structure I hydrates with two small dodecahedral cages and six tetra decahedral large cages. This study assesses the influence of occupation and the behavior of methane release from the molecular perspective during the dissociation process, particularly for the purpose of testing a series of molecular dynamics simulations. The dissociation cases conducted include an ideal 4 × 4 × 4 and 2 × 2 × 2 supercell methane hydrate system while inducing dissociation with two different types of temperature-rising functions for understanding the limitation and capability. These temperature-rising functions are temperature ramping and a single temperature step simulating in 5-7 various conditions. Temperature step results showed the earliest dissociation starting 50 ps into the simulation at an ΔT of 100 K, while at an ΔT of 80 K, dissociation was not observed. There was not a distinct dissociation preference observed between large and small cages, so it appears that the dissociation affects the entire structure uniformly when temperature increases are applied throughout the system rather than transport from a boundary. Temperature ramping simulations showed that the dissociation temperature increased with a higher heating rate. The mean-squared displacement results for the oxygen atoms in the water molecules at a high heating rate of 400 TK/s showed behavior similar to that for methane gas. As in the temperature step simulation, there were no clear differences in dissociation between large and small cages, which suggested homogeneous dissociation in all cases. Finally, a coordination analysis was performed on a 3 × 4 × 4 structure I methane hydrate with two free surfaces to demonstrate clear free surface boundaries and its location.

Nanoparticle-enhanced PD-1/PD-L1 targeted combination therapy for triple negative breast cancer.

Breast cancer with triple-negative subtype (TNBC) presents significant challenges with limited treatment options and a poorer prognosis than others. While PD-1/PD-L1 checkpoint inhibitors have shown promise, their efficacy in TNBC remains constrained. In recent years, nanoparticle (NP) technologies offer a novel approach to enhance cancer therapy by optimizing the tumor microenvironment and augmenting chemo- and immunotherapy effects in various preclinical and clinical settings. This review discusses recent investigations in NP strategies for improving PD-1/PD-L1 blockade-based combination therapy for TNBC. Those include single or multi-therapeutic NPs designed to enhance immunogenicity of the tumor, induce immunogenic cell death, and target immunosuppressive elements within the tumor microenvironment. The investigations also include NPs co-loaded with PD-L1 inhibitors and other therapeutic agents, leveraging targeted delivery and synergistic effects to maximize efficacy while minimizing systemic toxicity. Overall, NP approaches represent a promising avenue for enhancing PD-1/PD-L1 checkpoint blockade-based combination therapy in TNBC and encourage further developmental studies.

Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1-2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study.

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 < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.