The transcription factor Tbx5-dependent epigenetic modification contributes to neuropathic allodynia by activating TRPV1 expression in dorsal horn.

Nerve injury can induce aberrant changes in the spine; these changes are due to, or at least partly governed by, transcription factors that contribute to the genesis of neuropathic allodynia. Here, we showed that spinal nerve ligation (SNL, a clinical neuropathic allodynia model) increased the expression of the transcription factor Tbx5 in the injured dorsal horn in male Sprague Dawley rats. In contrast, blocking this upregulation alleviated SNL-induced mechanical allodynia, and there was no apparent effect on locomotor function. Moreover, SNL-induced Tbx5 upregulation promoted the recruitment and interaction of GATA4 and Brd4 by enhancing its binding activity to H3K9Ac, which was enriched at the Trpv1 promotor, leading to an increase in TRPV1 transcription and the development of neuropathic allodynia. In addition, nerve injury-induced expression of Fbxo3, which abates Fbxl2-dependent Tbx5 ubiquitination, promoted the subsequent Tbx5-dependent epigenetic modification of TRPV1 expression during SNL-induced neuropathic allodynia. Collectively, our findings indicated that spinal Tbx5-dependent TRPV1 transcription signaling contributes to the development of neuropathic allodynia via Fbxo3-dependent Fbxl2 ubiquitination and degradation. Thus, we propose a potential medical treatment strategy for neuropathic allodynia by targeting Tbx5.Significance Statement Nerve injury-induced epigenetic changes in Tbx5 enhance TRPV1 expression in the dorsal horn, with Tbx5 recruiting GATA4 and Brd4 for epigenetic modification of TRPV1. The Fbxo3-mediated Fbxl2 ubiquitination pathway stabilizes Tbx5, increasing its transcriptional activity and enhancing TRPV1 expression, contributing to the initiation and maintenance of neuropathic pain via epigenetic reprogramming.

The effect of Dynamic tape's directional support on shoulder fatigue and pitching performance in amateur baseball players: a randomized crossover trial.

BACKGROUND: To evaluate whether the application of Dynamic tape to the pitching shoulder could result in reduced shoulder fatigue, reduced delayed onset muscle soreness, or improved performance. METHODS: This is a randomized crossover study, in which participants and investigators were blinded, included 20 amateur adult baseball players without shoulder pain. Sham taping and Dynamic taping were randomized, using an internal rotation support taping method in both groups. Bilateral shoulder strength and range of motion were measured with a handheld dynamometer and clinical goniometer before and after each test. The percentage of strength decrease, range of motion, pitch velocity, spin rate, and shoulder pain were recorded. The post-pitching decrease in strength and percentage of strength decrease were calculated by paired t-test and the pitching speed and spin rates in the innings for both the sham and Dynamic taping groups were analyzed using two-way ANOVA. RESULTS: Compared with the sham group, the Dynamic tape group showed a significant loss in the percentage of strength decrease in internal rotation compared to the sham group (-1.4% vs. 7.0%, p = 0.03). However, no significant differences were observed in other strength declines, shoulder range of motion, pain, pitching velocity, or spin rate. CONCLUSIONS: Dynamic tape reduced direction-specific shoulder fatigue but did not significantly enhance pitching performance or prevent delayed onset muscle soreness. TRIAL REGISTRATION: ClinicalTrials: N201912094.

Realization of a two-dimensional Weyl semimetal and topological Fermi strings.

A two-dimensional (2D) Weyl semimetal, akin to a spinful variant of graphene, represents a topological matter characterized by Weyl fermion-like quasiparticles in low dimensions. The spinful linear band structure in two dimensions gives rise to distinctive topological properties, accompanied by the emergence of Fermi string edge states. We report the experimental realization of a 2D Weyl semimetal, bismuthene monolayer grown on SnS(Se) substrates. Using spin and angle-resolved photoemission and scanning tunneling spectroscopies, we directly observe spin-polarized Weyl cones, Weyl nodes, and Fermi strings, providing consistent evidence of their inherent topological characteristics. Our work opens the door for the experimental study of Weyl fermions in low-dimensional materials.

Select gene mutations associated with survival outcomes in ER-positive ERBB2-negative early-stage invasive breast cancer: A single-institutional tissue bank study.

INTRODUCTION: The prognostic capability of targeted sequencing of primary tumors in patients with estrogen receptor-positive, human epidermal growth factor receptor-2-negative early-stage invasive breast cancer (EBC) in a real-world setting is uncertain. Therefore, we aimed to determine the correlation between a 22-gene mutational profile and long-term survival outcomes in patients with ER+/ERBB2- EBC. PATIENTS AND METHODS: A total of 73 women diagnosed with ER+/ERBB2- EBC between January 10, 2004, and June 2, 2008, were followed up until December 31, 2022. Univariate and multivariate Cox models were constructed to plot the relapse-free survival (RFS) and overall survival (OS). The log-rank test derived p-value was obtained. For external validation, we performed a survival analysis of 1163 comparable patients retrieved from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset. RESULTS: At follow-up, 16 (21.9%) patients had relapsed, while 21 (nearly 29%) harbored mutant genes. Thirty-three missense mutations were detected in 14 genes. The median ages were 51 and 46 years in patients with and without mutations, respectively. Patients with any mutation had a 1.85-fold higher risk of relapse (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 0.60-5.69) compared to those without any mutation. Patients who harbored any of the six genes (MAP2K4, FGFR3, APC, KIT, RB1, and PTEN) had a nearly 6-fold increase in the risk of relapse (HR: 5.82, 95% CI: 1.31-18.56; p = 0.0069). Multivariate Cox models revealed that the adjusted HR for RFS and OS were 6.67 (95% CI: 1.32-27.57) and 8.31 (p = 0.0443), respectively. METABRIC analysis also demonstrated a trend to significantly worse RFS (p = 0.0576) in the subcohort grouped by having a mutation in any of the six genes. CONCLUSIONS: Our single-institution tissue bank study of Taiwanese women with ER+/ERBB2- EBC suggests that a novel combination of six gene mutations might have prognostic capability for survival outcomes.

In vivo proximity proteomics uncovers palmdelphin (PALMD) as a Z-disc-associated mitigator of isoproterenol-induced cardiac injury.

Z-discs are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-disc-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-disc proteome in vivo. We found palmdelphin (PALMD) as a novel Z-disc-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific Palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed the transverse tubule (T-tubule)-sarcoplasmic reticulum (SR) ultrastructures, which formed the Z-disc-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with the reduction of nexilin (NEXN), a crucial Z-disc-associated protein that is essential for both Z-disc and JMC structures and functions. PALMD interacted with NEXN and enhanced its protein stability while the Nexn mRNA level was not affected. AAV-based NEXN addback rescued the exacerbated cardiac injury in isoproterenol-treated PALMD-depleted mice. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis.

Multi-Scale Feature and Multi-Channel Selection toward Parkinson's Disease Diagnosis with EEG.

OBJECTIVE: Motivated by Health Care 4.0, this study aims to reducing the dimensionality of traditional EEG features based on manual extracted features, including statistical features in the time and frequency domains. METHODS: A total of 22 multi-scale features were extracted from the UNM and Iowa datasets using a 4th order Butterworth filter and wavelet packet transform. Based on single-channel validation, 29 channels with the highest R2 scores were selected from a pool of 59 common channels. The proposed channel selection scheme was validated on the UNM dataset and tested on the Iowa dataset to compare its generalizability against models trained without channel selection. RESULTS: The experimental results demonstrate that the proposed model achieves an optimal classification accuracy of 100%. Additionally, the generalization capability of the channel selection method is validated through out-of-sample testing based on the Iowa dataset Conclusions: Using single-channel validation, we proposed a channel selection scheme based on traditional statistical features, resulting in a selection of 29 channels. This scheme significantly reduced the dimensionality of EEG feature vectors related to Parkinson's disease by 50%. Remarkably, this approach demonstrated considerable classification performance on both the UNM and Iowa datasets. For the closed-eye state, the highest classification accuracy achieved was 100%, while for the open-eye state, the highest accuracy reached 93.75%.

Laparoscopic training workshop to assess medical students' skill acquisition and interest in surgical careers.

BACKGROUND: With its minimally invasive approach, laparoscopic surgery has transformed the medical landscape. As the demand for these procedures escalates, there is a pressing need for adept surgeons trained in laparoscopic techniques. However, current training often falls short of catering to medical school education. This study evaluates the impact of a custom-designed laparoscopic training workshop on medical students' surgical skills and career aspirations. METHODS: This prospective experimental study was conducted at the E-Da hospital in Kaohsiung City, Taiwan. Medical students from Taiwanese medical schools undergoing Clerk 5, Clerk 6, and Postgraduate Year 1 and 2 were invited to participate. Medical students (n = 44) underwent an endoscopic skill training workshop consisting of lectures, box training, and live tissue training. The trainees performed multiple tasks before and after training using our objective evaluation system. The primary outcome was assessed before and after training through a questionnaire assessing the influence of training on students' interest in surgery as a career. The secondary outcome measured improvement in skill acquisition, comparing the task completion time pre- and post-workshop. For the primary outcome, descriptive statistics were used to summarize the questionnaire responses, and paired t-tests were performed to determine significant changes in interest levels post-workshop. For the secondary outcome, paired t-tests were used to compare the time recorded pre- and post-training. RESULTS: Post-training, participants exhibited significant proficiency gains, with task completion times reducing notably: 97 s (p = 0.0015) for Precision Beads Placement, 88.5 s (p < 0.0001) for Beads Transfer Exercise, 95 s (p < 0.0001) for Precision Balloon Cutting, and 137.8 s (p < 0.0001) for Intracorporeal Suture. The primary outcome showcased an increased mean score from 8.15 pre-workshop to 9.3 post-workshop, indicating a bolstered interest in surgery as a career. Additionally, post-training sentiment analysis underscored a predominant inclination toward surgery among 88% of participants. CONCLUSION: The custom-designed laparoscopic workshop significantly improved technical skills and positively influenced students' career aspirations toward surgery. Such hands-on training workshops can play a crucial role in medical education, bridging the gap between theoretical knowledge and practical skills and potentially shaping the future of budding medical professionals.

Automatic Detection and Assessment of Freezing of Gait Manifestations.

Freezing of gait (FOG) is an episodic and highly disabling symptom of Parkinson's disease (PD). Although described as a single phenomenon, FOG is heterogeneous and can express as different manifestations, such as trembling in place or complete akinesia. We aimed to analyze the efficacy of deep learning (DL) trained on inertial measurement unit data to classify FOG into both manifestations. We adapted and compared four state-of-the-art FOG detection algorithms for this task and investigated the advantages of incorporating a refinement model to address oversegmentation errors. We evaluated the model's performance in distinguishing between trembling and akinesia, as well as other forms of movement cessation (e.g., stopping and sitting), against gold-standard video annotations. Experiments were conducted on a dataset of eighteen PD patients completing a FOG-provoking protocol in a gait laboratory. Results showed our model achieved an F1 score of 0.78 and segment F1@50 of 0.75 in detecting FOG manifestations. Assessment of FOG severity was strong for trembling (ICC=0.86, [0.66,0.95]) and moderately strong for akinesia (ICC=0.78, [0.51,0.91]). Importantly, our model successfully differentiated FOG from other forms of movement cessation during 360-degree turning-in-place tasks. In conclusion, our study demonstrates that DL can accurately assess different types of FOG manifestations, warranting further investigation in larger and more diverse verification cohorts.

Clinical performance of ultrasonic backscatter parametric and nonparametric statistics in detecting early hepatic steatosis.

Diagnosis of early hepatic steatosis would allow timely intervention. B-mode ultrasound imaging was in question for detecting early steatosis, especially with a variety of concomitant parenchymal disease. This study aimed to use the surgical specimen as a reference standard to elucidate the clinical performance of ultrasonic echogenicity and backscatter parametric and nonparametric statistics in real-world scenarios. Ultrasound radio-frequency (RF) signals of right liver lobe and patient data were collected preoperatively. Surgical specimen was then used to histologically determine staging of steatosis. A backscatter nonparametric statistic (h), a known backscatter parametric statistic, i.e., the Nakagami parameter (m), and a quantitative echo intensity (env) were calculated. Among the 236 patients included in the study, 93 were grade 0 (<5% fat) and 143 were with steatosis. All the env, m and h statistics had shown significant discriminatory power of steatosis grades (AUC = 0.643-0.907 with p-value < 0.001). Mann-Whitney U tests, however, revealed that only the backscatter statistics m and h were significantly different between the groups of grades 0 and 1 steatosis. The two-way ANOVA showed a significant confounding effect of the elevated ALT on env (p-value = 0.028), but no effect on m or h. Additionally, the severe fibrosis was found to be a significant covariate for m and h. Ultrasonic signals acquired from different scanners were found linearly comparable.

DNA methylation in peripheral blood is associated with renal aging and renal function decline: a national community study.

BACKGROUND: Older patients are at risk for acute kidney injury and chronic kidney disease. Age-related increases in DNA methylation at CpG islands have been linked to aging-related diseases like cancer and cardiovascular disease, but the exact causal relationship between methylation in renal aging and other kidney diseases remains unclear. This study aimed to elucidate the methylation status of peripheral blood mononuclear cells (PBMCs) in the Asian population. Using human whole blood DNA methylation analysis from the Taiwan Biobank, we included participants with both whole blood genome-wide methylation data and follow-up data on serum creatinine. We investigated hyper- and hypomethylated genes in comparison of participants with higher and lower estimated glomerular filtration (eGFR) decline rate in overall cohort as well as in comparison of old and young participants in subgroup of participants with higher eGFR decline rate. Common genes and signaling pathways in both comparative analyses were identified. RESULTS: Among 1587 participants in the analysis, 187 participants had higher eGFR decline rate. According to the comparison of methylation in participants with different eGFR declines and at different ages, respectively, we identified common hypermethylated genes, including DNMT3A and GGACT, as well as hypomethylated genes such as ARL6IP5, CYB5D1, BCL6, RPRD2, ZNF451, and MIAT in both participants with higher eGFR decline and those of older age. We observed associations between the methylation status of signaling pathways and aging as well as renal function decline. These pathways notably included autophagy, p38 mitogen-activated protein kinases, and sirtuins, which were associated with autophagy process and cytokine production. CONCLUSIONS: Through methylation analysis of PBMCs, we identified genes and signaling pathways which could play crucial roles in the interplay of renal aging and renal function decline. These findings contribute to the development of novel biomarkers for identifying at-risk groups and even for therapeutic agent discovery.

Intravenous calcitriol administration improves the liver redox status and attenuates ferroptosis in mice with high-fat diet-induced obesity complicated with sepsis.

Obesity aggravates ferroptosis, and vitamin D (VD) may inhibit ferroptosis. We hypothesized that weight reduction and/or calcitriol administration have benefits against the sepsis-induced liver redox imbalance and ferroptosis in obese mice. Mice were fed a high-fat diet for 11 weeks, then half of the mice continued to consume the diet, while the other half were transferred to a low-energy diet for 5 weeks. After feeding the respective diets for 16 weeks, sepsis was induced by cecal ligation and puncture (CLP). Septic mice were divided into four experimental groups: OS group, obese mice injected with saline; OD group, obese mice with calcitriol; WS group, weight-reduction mice with saline; and WD group, weight-reduction mice with calcitriol. Mice in the respective groups were euthanized at 12 or 24 h after CLP. Results showed that the OS group had the highest inflammatory mediators and lipid peroxide levels in the liver. Calcitriol treatment reduced iron content, enhanced the reduced glutathione/oxidized glutathione ratio, upregulated nuclear factor erythroid 2-related factor 2, ferroptosis-suppressing protein 1, and solute carrier family 7 member 11 expression levels. Also, mitochondrion-associated nicotinamide adenine dinucleotide phosphate oxidase 1, peroxisome proliferator-activated receptor-γ coactivator 1, hypoxia-inducible factor-1α, and heme oxidase-1 expression levels increased in the late phase of sepsis. These results were not noted in the WS group. These findings suggest that calcitriol treatment elicits a more-balanced glutathione redox status, alleviates liver ferroptosis, and enhances mitochondrial biogenesis-associated gene expressions. Weight reduction alone had minimal influences on liver ferroptosis and mitochondrial biogenesis in obese mice with sepsis.

The lower incidence of endometrial cancer after sodium-glucose cotransporter 2 inhibitors administration in type 2 diabetes mellitus population: a nationwide cohort study.

The Sodium-glucose co-transporter 2 (SGLT2) inhibitor is an anti-glycemic agent that frequently used in type 2 diabetes mellitus (T2DM) with antioxidant effects. Endometrial cancer (EC) is a common gynecological malignancy that correlates with oxidative stress. The aim in the present study is to survey the potential association between the SGLT2 inhibitor administration and the incidence of EC by the application of the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was directed and the T2DM participants were divided into the SGLT2 inhibitors users and non-SGLT2 inhibitors users. After matching, a total of 163,668 and 327,336 participants were included into the SGLT2 inhibitors and control groups, respectively. The primary outcome is regarded as the development of EC according to the diagnostic, image, and procedure codes. Cox proportional hazard regression was employed to generate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of EC between the two groups. There were 422 and 876 EC events observed in the SGLT2 inhibitors and control groups, respectively. The SGLT2 inhibitors group demonstrated a significantly lower incidence of EC formation compared to the control groups (aHR: 0.87, 95% CI: 0.76-0.99). In the subgroup analysis, the correlation between SGLT2 inhibitor administration and lower rate of EC existed in the T2DM individuals with aged under 60. Moreover, the association between SGLT2 inhibitor administration and lower EC incidence only presented in the T2DM population with SGLT2 inhibitor administration under one year (aHR: 0.58, 95% CI: 0.45-0.73). In conclusion, the administration of SGLT2 inhibitors correlates to lower incidence of EC in T2DM population.

The use of sodium-glucose cotransporter 2 inhibitors and the incidence of uveitis in type 2 diabetes: a population-based cohort study.

Introduction: To survey the potential correlation between the application of sodium-glucose cotransporter 2 (SGLT2) inhibitors and the incidence of uveitis in individuals with type 2 diabetes mellitus (T2DM). Material and methods: A retrospective cohort study using the National Health Insurance Research Database (NHIRD) was conducted. The T2DM patients using SGLT2 inhibitors and those taking other anti-diabetic medications were assigned to the SGLT2 group and the control group, respectively, with a 1 : 2 ratio via the propensity score-matching (PSM) method. The major outcome in this study is the development of uveitis according to the diagnostic codes. The Cox proportional hazard regression was adopted to yield the adjusted hazard ratio (aHR) with 95% confidence interval (CI) between the groups. Results: There were 147 and 371 new uveitis episodes in the SGLT2 and control groups after the follow-up period up to 5 years. The incidence of uveitis in the SGLT2 group (aHR = 0.736, 95% CI: 0.602-0.899, p = 0.0007) was significantly lower than that in the control group after adjusting for the effect of all the confounders. In the subgroup analyses, the SGLT2 inhibitors showed a higher correlation with low uveitis incidence in T2DM patients aged under 50 than T2DM individuals aged over 50 years (p = 0.0012), while the effect of SGLT2 inhibitors on the incidence of anterior and posterior uveitis development was similar (p = 0.7993). Conclusions: The use of SGLT2 inhibitors could be an independent protective factor for uveitis development in T2DM population.

NT-proBNP point-of-care testing for predicting mortality in end-stage renal disease: A survival analysis.

This study examines the predictive value of elevated N-terminal-pro brain natriuretic peptide (NT-pro BNP) levels for mortality among patients with end-stage renal disease (ESRD). Data from 768 ESRD patients, excluding those with cancer or lost follow-up, were analyzed using Kaplan-Meier curves and Cox proportional hazards models over three years. Results indicated that patients with very high NT-pro BNP levels had shorter average survival times and a significantly higher risk of mortality (hazard ratio 1.43). Advanced age, ICU admission, and comorbidities like cerebrovascular diseases and chronic obstructive pulmonary disease also contributed to increased mortality risks. Thus, elevated NT-pro BNP is an independent risk factor for mortality in ESRD patients.

Lithium-Ion Dynamic and Storage of Atomically Precise Halogenated Nanographene Assemblies via Bottom-Up Chemical Synthesis.

Graphene has received much scientific attention as an electrode material for lithium-ion batteries because of its extraordinary physical and electrical properties. However, the lack of structural control and restacking issues have hindered its application as carbon-based anode materials for next generation lithium-ion batteries. To improve its performance, several modification approaches such as edge-functionalization and electron-donating/withdrawing substitution have been considered as promising strategies. In addition, group 7A elements have been recognized as critical elements due to their electronegativity and electron-withdrawing character, which are able to further improve the electronic and structural properties of materials. Herein, we elucidated the chemistry of nanographenes with edge-substituted group 7A elements as lithium-ion battery anodes. The halogenated nanographenes were synthesized via bottom-up organic synthesis to ensure the structural control. Our study reveals that the presence of halogens on the edge of nanographenes not only tunes the structural and electronic properties but also impacts the material stability, reactivity, and Li+ storage capability. Further systematic spectroscopic studies indicate that the charge polarization caused by halogen atoms could regulate the Li+ transport, charge transfer energy, and charge storage behavior in nanographenes. Overall, this study provides a new molecular design for nanographene anodes aiming for next-generation lithium-ion batteries.

Effects of Reishimmune-S, a Fungal Immunomodulatory Peptide Supplement, on the Quality of Life and Circulating Natural Killer Cell Profiles of Patients With Early Breast Cancer Receiving Adjuvant Endocrine Therapy.

OBJECTIVES: To evaluate the effects of Reishimmune-S, a fungal immunomodulatory peptide, on the quality of life (QoL) and natural killer (NK) cell subpopulations in patients receiving adjuvant endocrine therapy (ET) for breast cancer (BC). METHODS: Patients who received adjuvant ET for stage I-III hormone receptor-positive BC without active infection were enrolled in this prospective pilot study. Reishimmune-S was administered sublingually daily for 6 months. QoL scores, circulating immune cell levels, including lymphocyte/NK cell subpopulations, and plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured at baseline and every 4 weeks. Data were analyzed using linear mixed-effect regression models. RESULTS: Nineteen participants were included in the analyses. One patient with underlying asthma did not complete the study owing to the occurrence of skin rashes 15 days after the initiation of Reishimmune-S. No other adverse events were reported. Reishimmune-S supplementation significantly improved the cognitive function at 3 months and significantly decreased the fatigue and insomnia levels at 3 and 6 months, respectively. There was no significant change in the global health/QoL score between baseline and week 4 of treatment. The proportion of CD19+ lymphocytes was significantly higher at 3 and 6 months, and that of NKG2A+ and NKp30+ NK cells was significantly lower at 6 months than at baseline. In addition, fatigue positively correlated with the proportion of NKp30+ NK cells (ß ± standard error: 24.48 ± 8.75, P = .007 in the mixed-effect model). CONCLUSIONS: Short-term supplementation with Reishimmune-S affected the circulating immune cell composition and exerted positive effects on cognitive function, fatigue, and insomnia in patients with BC undergoing adjuvant ET, providing a potential approach for the management of treatment-related adverse reactions in this patient population.

Role of Epstein-Barr Virus in Breast Cancer: Correlation with Clinical Outcome and Survival Analysis.

Background: Breast cancer is the most prevalent cancer among women worldwide. The potential involvement of Epstein-Barr virus (EBV) in breast cancer pathogenesis has been a subject of debate, but its correlation with clinical outcomes remains uncertain. Methods: In this study, we collected 276 pathologically confirmed breast cancer tissue samples from the tissue bank of MacKay Memorial Hospital and the National Health Research Institutes in Taiwan. DNA was extracted from frozen tissue using The QIAamp DNA Mini Kit. The Taqman quantitative PCR method was employed to assess the EBV copy number per cell in these samples, using NAMALWA cells as a reference. We performed statistical analyses, including 2 × 2 contingency tables, Cox regression analysis, and Kaplan-Meier survival curves, to explore the association between clinicopathologic factors and survival outcomes in breast cancer patients. We analyzed both relapse survival, which reflects the period patients remain free from cancer recurrence post-treatment, and overall survival, which encompasses all-cause mortality. Results: Our results revealed a significant association between EBV status and relapse survival (hazard ratio: 2.75, 95% CI: 1.30, 5.86; p = 0.008) in breast cancer patients. However, no significant association was found in overall survival outcomes. Additionally, we observed significant associations between ER status and tumor histologic grade with both overall and relapse survival. Patients with EBV-positive tumors exhibited higher recurrence rates compared to those with EBV-negative tumors. Furthermore, we noted significant correlations between EBV status and HER-2 (p = 0.0005) and histological grade (p = 0.02) in our cohort of breast cancer patients. Conclusions: The presence of EBV in breast cancer tumors appears to exert an impact on patient outcomes, particularly concerning recurrence rates. Our findings highlight the significance of considering EBV status as a potential prognostic marker in breast cancer patients. Nonetheless, further research is essential to elucidate the underlying molecular mechanisms and develop novel therapeutic approaches.

Comparative Study of the Orientation and Order Effects on the Thermoelectric Performance of 2D and 3D Perovskites.

Calcium titanium oxide has emerged as a highly promising material for optoelectronic devices, with recent studies suggesting its potential for favorable thermoelectric properties. However, current experimental observations indicate a low thermoelectric performance, with a significant gap between these observations and theoretical predictions. Therefore, this study employs a combined approach of experiments and simulations to thoroughly investigate the impact of structural and directional differences on the thermoelectric properties of two-dimensional (2D) and three-dimensional (3D) metal halide perovskites. Two-dimensional (2D) and three-dimensional (3D) metal halide perovskites constitute the focus of examination in this study, where an in-depth exploration of their thermoelectric properties is conducted via a comprehensive methodology incorporating simulations and experimental analyses. The non-equilibrium molecular dynamics simulation (NEMD) was utilized to calculate the thermal conductivity of the perovskite material. Thermal conductivities along both in-plane and out-plane directions of 2D perovskite were computed. The NEMD simulation results show that the thermal conductivity of the 3D perovskite is approximately 0.443 W/mK, while the thermal conductivities of the parallel and vertical oriented 2D perovskites increase with n and range from 0.158 W/mK to 0.215 W/mK and 0.289 W/mK to 0.309 W/mK, respectively. Hence, the thermal conductivity of the 2D perovskites is noticeably lower than the 3D ones. Furthermore, the parallel oriented 2D perovskites exhibit more effective blocking of heat transfer behavior than the perpendicular oriented ones. The experimental results reveal that the Seebeck coefficient of the 2D perovskites reaches 3.79 × 102 µV/K. However, the electrical conductivity of the 2D perovskites is only 4.55 × 10-5 S/cm, which is one order of magnitude lower than that of the 3D perovskites. Consequently, the calculated thermoelectric figure of merit for the 2D perovskites is approximately 1.41 × 10-7, slightly lower than that of the 3D perovskites.