A large population-based and validated study on the follow-up management and supportive strategy of locally advanced rectal cancer patients.

OBJECTIVE: Our objective was to evaluate the predictive factors and metastatic time for liver and lung metastasis in locally advanced rectal cancer (RC) patients. METHODS: Univariate and multivariate analysis were performed to identify risk factors and prognostic factors for liver metastasis and lung metastasis in RC. Survival probabilities were calculated using the Kaplan-Meier model and compared using the log-rank test between groups. The probability of time-to-event occurrence was calculated using the random survival forest model. Finally, the SEER database was used to verify our findings. RESULTS: Our results indicated that pathological T stage and pathological N stage were independent predictive factors for liver metastasis. Furthermore, CEA level, pathological T stage, and tumor deposit were independent predictive factors for lung metastasis. Based on the results of a multivariate Cox analysis, we categorized patients with liver and lung metastasis into three groups based on their scores. The results revealed that patients with higher scores had a higher probability of experiencing metastasis. For liver metastasis, Groups 1, 2, and 3 all exhibited higher occurrence rates within the first 24 months. However, for lung metastasis, Group 4 showed the highest occurrence rate at the 12th month, while Groups 5 and 6 exhibited the highest occurrence rates at the 15th month. CONCLUSIONS: In summary, we developed predictive models to determine the likelihood of liver and lung metastasis in RC patients. It is crucial to implement a more intensive surveillance program for patients with unfavorable risk profiles in order to facilitate early detection of metastasis.

Effect modification of glycemic control on association of lung function with all-cause and cardiovascular mortality in persons with type 2 diabetes - a retrospective cohort study.

BACKGROUND: Poor glucose control might deteriorate the impaired pulmonary function, which can ultimately lead to mortality. However, few studies have examined the effect modification of glucose control on the association between pulmonary function and mortality. This study aimed to examine the association of pulmonary function with mortality and determine the effect modification of glycemic level on the association of pulmonary function with mortality in persons with type 2 diabetes (T2DM). METHODS: A retrospective cohort study included 3,846 persons with T2DM with pulmonary function testing in Taiwan during 2002-2020. Expiratory volume in 1 s (FEV1) was measured as pulmonary function. Cox proportional hazards models were used and the effect modification of pulmonary function parameters and glucose control was assessed by their product terms. RESULTS: There were 733 deaths during an average follow-up of 7.83 years. Significant associations of FEV1 and mortality were found (hazards ratio [HR] for FEV1 Z-scores of < 0 to -1, <-1 to -2 and <-2: 1.47 [1.20, 1.80], 2.48 [1.95, 3.14] and 3.07 [1.74, 5.44] compared with participants with Z-score ≥0, respectively. All p for trend<0.001). Significant effect modifications were found and the association between FEV1 and mortality was stronger in persons with good glycemic control compared with poor glycemic control (FEV1-FPG effect modification, P = 0.01; FEV1-HbA1c effect modification, P = 0.03). CONCLUSION: Pulmonary function, measured by FEV1, is significantly associated with mortality in persons with T2DM. Significant effect modification of glucose control on the association between pulmonary function parameters and mortality was found.

Assessing the inhibitory effects of some secondary amines, thioureas and 1,3-dimethyluracil conjugates of (-)-cytisine and thermopsine on the RNA-dependent RNA polymerase of SARS-CoV-1 and SARS-CoV-2.

SARS-CoV-2 causes COVID-19, with symptoms ranging from mild to severe, including pneumonia and death. This beta coronavirus has a 30-kilobase RNA genome and shares about 80 % of its nucleotide sequence with SARS-CoV-1. The replication/transcription complex, essential for viral RNA synthesis, includes RNA-dependent RNA polymerase (RdRp, nsp12) enhanced by nsp7 and nsp8. Antivirals like molnupiravir and remdesivir, which are RdRp inhibitors, treat severe COVID-19 but have limitations, highlighting the need for new therapies. This study assessed (-)-cytisine, methylcytisine, and thermopsine derivatives against SARS-CoV-1 and SARS-CoV-2 in vitro, focusing on their RdRp inhibition. Selected compounds from a previous study were evaluated using a SARS-CoV-2 RNA polymerase assay kit to investigate their structure-activity relationships. Compound 17 (1,3-dimethyluracil conjugate with (-)-cytisine and thermopsine) emerged as a potent inhibitor of SARS-CoV-1 and SARS-CoV-2 RdRp, with an IC50 value of 7.8 µM against SARS-CoV-2 RdRp. It showed a dose-dependent reduction in cytopathic effects in cells infected with SARS-CoV-1 and SARS-CoV-2 replicon-based single-round infectious particles (SRIPs) and significantly inhibited SARS-CoV N protein expression, with EC50 values of 0.12 µM for SARS-CoV-1 and 1.47 µM for SARS-CoV-2 SRIPs. Additionally, compound 17 reduced viral subgenomic RNA levels in a concentration-dependent manner in SRIP-infected cells. The structure-activity relationships of compound 17 with SARS-CoV-1 and SARS-CoV-2 RdRp were also investigated, highlighting it as a promising lead for developing antiviral agents against SARS and COVID-19.

Efficacy analysis of immunotherapy­based combinations for patients with EGFR­mutant advanced non­small cell lung cancer after TKI failure.

Treatment options for epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC) following tyrosine kinase inhibitor (TKI) failure are limited, and platinum-based chemotherapy remains the main treatment. The development of effective immunotherapy for this disease has been challenging. In the present study, 37 patients with EGFR-mutant advanced NSCLC who were treated with programmed cell death-1 (PD-1) inhibitor-based combinations after TKI failure were reviewed. The total cohort had a median progression-free survival (mPFS) of 5.2 months (95% CI, 4.077-6.323 months) and a median overall survival (mOS) of 18.3 months (95% CI, 12.932-23.668 months). Patients with Eastern Cooperative Oncology Group performance-status (ECOG-PS) scores of 0 or 1 had longer mPFS than those with ECOG-PS scores of 2 (5.4 vs. 2.4 months; P=0.006). In addition, a PFS benefit was observed in patients with EGFR T790M-negative compared with EGFR T790M-positive tumors (mPFS 6.2 vs. 4.4 months; P=0.041). Patients treated with immunotherapy-based combinations as a front-line therapy had a longer mPFS than those in which the combinations were used as a late-line therapy (6.2 vs. 2.4 months; P<0.001). PD-1 inhibitor combined with chemotherapy and bevacizumab did not show a clear advantage over PD-1 inhibitor combined with chemotherapy alone (mPFS, 6.2 vs. 4.4 months; P=0.681), although it resulted in an improved overall response rate (ORR) and disease control rate. Notably, the 7 patients with a programmed cell death ligand-1 (PD-L1) tumor proportion score of ≥50% had an ORR of 100% and an mPFS of 8.3 months. Therefore, it is suggested that PD-1 inhibitor-based combinations should be a priority treatment option in selective populations, such as those with low ECOG-PS scores, T790M-negative status or high PD-L1 expression in EGFR-mutant NSCLC after TKI failure. The use of immunotherapy and chemotherapy in combination with antiangiogenic agents appears to be a promising combination therapy for such patients.

Why do thoracic epidurals fail? A literature review on thoracic epidural failure and catheter confirmation.

Thoracic epidural anesthesia (TEA) has been the gold standard of perioperative analgesia in various abdominal and thoracic surgeries. However, misplaced or displaced catheters, along with other factors such as technical challenges, equipment failure, and anatomic variation, lead to a high incidence of unsatisfactory analgesia. This article aims to assess the different sources of TEA failure and strategies to validate the location of thoracic epidural catheters. A literature search of PubMed, Medline, Science Direct, and Google Scholar was done. The search results were limited to randomized controlled trials. Literature suggests techniques such as electrophysiological stimulation, epidural waveform monitoring, and x-ray epidurography for identifying thoracic epidural placement, but there is no one particular superior confirmation method; clinicians are advised to select techniques that are practical and suitable for their patients and practice environment to maximize success.

Heritability of carotid intima-media thickness and inflammatory factors of atherosclerosis in a Chinese population.

Carotid intima-media thickness (cIMT), a marker of subclinical atherosclerosis, has been found to be associated with incident stroke. High-sensitivity C-reactive protein (CRP) and fibrinogen have been demonstrated to be associated with atherosclerosis. Previous studies on heritability estimates of IMT, CRP, and fibrinogen among Chinese populations are limited. This study aims to estimate the heritability of these risk factors in residents who participated in the Taichung Community Health Study (TCHS) and their family members. A total of 2671 study subjects from 805 families were enrolled in the study, selected from a random sample of TCHS participants and their family members. CRP, and fibrinogen were obtained from each participant, and a questionnaire interview was conducted. cIMT was measured by high-resolution B-mode ultrasound and expressed as the mean of the maximum. Heritability estimates and the familial correlation of cIMT, CRP, and fibrinogen among family pairs were determined with SAGE software. With multivariate adjustments, significant heritability was found for cIMT (h2 = 0.26, P < 0.001), CRP (h2 = 0.34, P < 0.001), and fibrinogen (h2 = 0.48, P < 0.001). The intrafamilial correlation coefficients for the three indexes in the parent-offspring pairs were significant (P < 0.001) and ranged from 0.17 to 0.41. The full sibship correlations were also significant (P < 0.001) for the three indexes and ranged from 0.19 to 0.47. This study indicates that a moderate proportion of the variability in CRP, fibrinogen, and cIMT can be attributed to genetic factors in Chinese populations. The findings suggest that CRP is associated with cIMT, whereas no significant association exists between fibrinogen and cIMT.

Structural basis of main proteases of coronavirus bound to Bofutrelvir.

Globally, the continuous spread and evolution of SARS-CoV-2, along with its variants, profoundly impact human well-being, health, security, and the growth of socio-economic. In the field of development of drugs against COVID-19, the main protease (Mpro) is a critical target as it plays a core role in the lifecycle of SARS-CoV-2. Bofutrelvir acts as a potent inhibitor of SARS-CoV-2 Mpro, demonstrating high efficacy and broad-spectrum antiviral activity. Compared to therapies that require pharmacokinetic boosters, such as ritonavir, the monotherapy approach of Bofutrelvir reduces the risk of potential drug interactions, making it suitable for a wider patient population. However, further studies on the potency and mechanism of inhibition of Bofutrelvir against the Mpro of COVID-19 and its variants, together with other coronaviruses, are needed to prepare for the possibility of a possible re-emerging threat from an analogous virus in the future. Here, we reveal the effective inhibition of Bofutrelvir against the Mpro of SARS-CoV-2, SARS-CoV, and HCoV-229E through FRET and crystallographic analysis. Furthermore, the inhibitory mechanisms of Bofutrelvir against two SARS-CoV-2 Mpro mutants (G15S and K90R) were also elucidated through FRET and crystallographic studies. Through detailed analysis and comparison of these crystal structures, we identified crucial structural determinants of inhibition and elucidated the binding mode of Bofutrelvir to Mpros from different coronaviruses. These findings are hopeful to accelerate the development of safer and more potent inhibitors against the Mpro of coronavirus, and to provide important references for the prevention and treatment of similar viruses that may emerge in the future.

Reliability Issues of Mobile Nutrition Apps for Cardiovascular Disease Prevention: Comparative Study.

Background: Controlling saturated fat and cholesterol intake is important for the prevention of cardiovascular diseases. Although the use of mobile diet-tracking apps has been increasing, the reliability of nutrition apps in tracking saturated fats and cholesterol across different nations remains underexplored. Objective: This study aimed to examine the reliability and consistency of nutrition apps focusing on saturated fat and cholesterol intake across different national contexts. The study focused on 3 key concerns: data omission, inconsistency (variability) of saturated fat and cholesterol values within an app, and the reliability of commercial apps across different national contexts. Methods: Nutrient data from 4 consumer-grade apps (COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!) and an academic app (Formosa FoodApp) were compared against 2 national reference databases (US Department of Agriculture [USDA]-Food and Nutrient Database for Dietary Studies [FNDDS] and Taiwan Food Composition Database [FCD]). Percentages of missing nutrients were recorded, and coefficients of variation were used to compute data inconsistencies. One-way ANOVAs were used to examine differences among apps, and paired 2-tailed t tests were used to compare the apps to national reference data. The reliability across different national contexts was investigated by comparing the Chinese and English versions of MyFitnessPal with the USDA-FNDDS and Taiwan FCD. Results: Across the 5 apps, 836 food codes from 42 items were analyzed. Four apps, including COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, significantly underestimated saturated fats, with errors ranging from -13.8% to -40.3% (all P<.05). All apps underestimated cholesterol, with errors ranging from -26.3% to -60.3% (all P<.05). COFIT omitted 47% of saturated fat data, and MyFitnessPal-Chinese missed 62% of cholesterol data. The coefficients of variation of beef, chicken, and seafood ranged from 78% to 145%, from 74% to 112%, and from 97% to 124% across MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, respectively, indicating a high variability in saturated fats across different food groups. Similarly, cholesterol variability was consistently high in dairy (71%-118%) and prepackaged foods (84%-118%) across all selected apps. When examining the reliability of MyFitnessPal across different national contexts, errors in MyFitnessPal were consistent across different national FCDs (USDA-FNDSS and Taiwan FCD). Regardless of the FCDs used as a reference, these errors persisted to be statistically significant, indicating that the app's core database is the source of the problems rather than just mismatches or variances in external FCDs. Conclusions: The findings reveal substantial inaccuracies and inconsistencies in diet-tracking apps' reporting of saturated fats and cholesterol. These issues raise concerns for the effectiveness of using consumer-grade nutrition apps in cardiovascular disease prevention across different national contexts and within the apps themselves.

Antihyperlipidemic drugs mitigate the elevated incidence of peptic ulcer disease caused by Hyperlipidemia: A cohort study.

BACKGROUND: Several risk factors for peptic ulcer disease (PUD) have been identified; however, the recurrence rates of PUD are still high even with standard ulcer treatments. A high cholesterol level has been proposed as a risk factor for PUD, but clinical evidence remains limited. Therefore, this database study investigated whether hyperlipidemia increases PUD risk and whether antihyperlipidemic drugs reduce this risk. METHODS: A long-term cohort design was adopted, and Taiwan's National Health Insurance Research Database was used to enroll patients diagnosed as having hyperlipidemia between 2000 and 2016. Patients without hyperlipidemia were randomly matched based on variables such as age and gender to establish a comparison cohort at a 1:1 ratio. Another cohort study was conducted to determine whether antihyperlipidemic drugs or red yeast rice prescriptions (LipoCol Forte®) can reduce the incidence of PUD in patients with hyperlipidemia. RESULTS: The overall incidence of PUD was 1.48 times higher in the hyperlipidemia cohort (203,235 patients) than in the nonhyperlipidemia cohort (adjusted hazard ratio, 1.48; 95% CI, 1.46-1.50; p < 0.001). Among the patients with hyperlipidemia, those who used antihyperlipidemic drugs with or without red yeast rice prescriptions exhibited a lower risk of developing PUD relative to those who did not use them; the adjusted hazard ratios were 0.33 (95% CI, 0.21-0.52) and 0.81 (95% CI, 0.78-0.84), respectively. When the cumulative exposure to antihyperlipidemic drugs and red yeast rice prescriptions increased, the risk of developing PUD showed a decreasing trend, which was statistically significant for antihyperlipidemic drugs but not for red yeast rice. CONCLUSION: Hyperlipidemia is associated with a higher risk of PUD, which can be reduced through antihyperlipidemic drugs with or without red yeast rice prescriptions administration.

Complementary Chinese Herbal Medicine Treatment is Associated with a Reduction of Surgical Rate in Patients with Dysfunctional Uterine Bleeding: A Propensity-Score Matched Cohort Study.

Background: Many patients with dysfunctional uterine bleeding (DUB) seek traditional medicine consultations. This study intended to investigate the association of complementary Chinese herbal medicine (CHM) with the surgery rate in patients with DUB in Taiwan. Methods: We enrolled 43,027 patients with newly diagnosed DUB (ICD-9-CM codes 626.8) from the National Health Insurance Research Database in Taiwan during the period of 1997 to 2010. Among them, 38,324 were CHM users, and 4703 did not receive CHM treatment. After performing a 1:1 propensity-score match based on patients' age (per 5 years), comorbidities, conventional drugs, childbirth status, duration from the diagnosis year of DUB and index year, there were an equal number (n=4642) of patients in the CHM cohort and non-CHM cohort. The outcome measurement was the comparison of incidences of surgical events, including hysterectomy and endometrial ablation, in the two cohorts before the end of 2013. Results: CHM users had a lower incidence of surgery than non-CHM users (adjusted HR 0.27, 95% CI: 0.22-0.33). The cumulative incidence of surgery was significantly lower in the CHM cohort during the follow-up period (Log rank test, p < 0.001). A total of 146 patients in the CHM cohort (4.99 per 1000 person-years) and 485 patients in the non-CHM cohort (20.19 per 1000 person-years) received surgery (adjusted HR 0.27, 95% CI: 0.22-0.33). CHM also reduced the risk of surgery in DUB patients with or without comorbidities. Regardless of childbirth status or whether patients took NSAIDs, tranexamic acid or progesterone, fewer patients in the CHM cohort underwent surgery than in the non-CHM cohort. The most commonly prescribed single herb and formula were Yi-Mu-Cao (Herba Leonuri) and Jia-Wei-Xiao-Yao-San, respectively. Conclusion: The real-world data revealed that CHM is associated with a reduced surgery rate in DUB patients. This information may be provided for further clinical investigations and policy-making.

van der Waals-bonded graphene clusters enhance thermal conductivity of phase-change materials for advanced thermal energy management.

Organic phase-change materials possess immense application potential, but their low thermal conductivity (≤0.5 W m-1 K-1) severely limits the thermal energy charge/discharge rate, impeding their practical implementation in the field of advanced energy. While incorporating thermally conductive fillers into the phase-change matrix can address this issue, achieving a thermal conductivity exceeding 10 W m-1 K-1 at a filler content below 30 vol% remains challenging, attributed to the absence of a well-designed filler interface and structure. Herein, a strategy for developing planar graphene clusters and subsequently integrating them with phase-change microcapsules to fabricate composites using compression molding was demonstrated. The proposed graphene clusters are formed by closely aligned and overlapping graphene sheets that bond together through van der Waals forces, resulting in a significant decrease in junction thermal resistance within the composites. Combining this interface design with compression-induced construction of a highly oriented structure, the composites achieved a remarkable thermal conductivity of 103 W m-1 K-1 with ≈29 vol% filler addition, enhancing the thermal energy charge/discharge rate by over two orders of magnitude. Furthermore, we demonstrated that the composites possess the essential enthalpy values, competent strength, and ease of shaping, making them applicable across various domains of thermal energy management.

Mycoplasma pneumoniae infection outbreak in Guangzhou, China after COVID-19 pandemic.

BACKGROUNDS: Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Throat swab samples were obtained from 5405 hospitalized patients with symptoms of acute respiratory infections to detect M. pneumoniae. Differences in epidemiological and clinical characteristics of M. pneumoniae: infections were investigated during 2020-2022 and after COVID-19 pandemic (2023). RESULTS: M. pneumoniae were detected in 849 (15.6%, 849/5405) patients. The highest annual positive rate was 29.4% (754/2570) in 2023, followed by 5.3% (72/1367) in 2022, 1.2% (12/1015) in 2021, and 2.0% (11/553) in 2020, with significantly increasing annual prevalence from 2020 to 2023. M. pneumoniae incidence peaked between July and December post-COVID-19 pandemic in 2023, with the highest monthly positive rate (56.4%, 165/293). Clinical characteristics and outcomes of patients with M. pneumoniae did not vary between periods during and after COVID-19 pandemic except that patients with M. pneumoniae post-COVID-19 pandemic were more likely to develop fever. Patients with severe M. pneumoniae pneumonia (SMPP) were more likely to develop respiratory complications, myocardial damage, and gastrointestinal dysfunction than those with non-SMPP. Patients with SMPP had lower lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP. Bronchoalveolar lavage fluid specimens from infected patients were obtained to identify macrolide resistance mutations. Macrolide-resistant M. pneumoniae (MRMP) proportion in 2023 was 91.1% (215/236). CONCLUSION: Outbreaks of M. pneumoniae: occurred in Guangzhou, China in 2023 upon Non-pharmaceutical interventions easing. Despite the increasing incidence of M. pneumoniae, the disease severity remained similar during and after the COVID-19 pandemic.

Engineering a NanoBiT biosensor for detecting angiotensin-converting enzyme-2 (hACE2) interaction with SARS-CoV-2 spike protein and screening the inhibitors to block hACE2 and spike interaction.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated by its trimeric surface spike protein, which binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. This critical interaction facilitates viral entry and is a primary target for therapeutic intervention against COVID-19. However, it is difficult to fully optimize viral infection using existing protein-protein interaction methods. Herein, we introduce a nano-luciferase binary technology (NanoBiT)-based pseudoviral sensor designed to stimulate the dynamics of viral infection in both living cells and animals. Infection progression can be dynamically visualized via a rapid increase in luminescence within 3 h using an in vivo imaging system (IVIS). Inhibition of viral infection by baicalein and baicalin was evaluated using a NanoBiT-based pseudoviral sensor. These results indicate that the inhibitory efficacy of baicalein was strengthened by targeting the spike protein, whereas baicalin targeted the hACE2 protein. Additionally, under optimized conditions, baicalein and baicalin provided a synergistic combination to inhibit pseudoviral infection. Live bioluminescence imaging was used to evaluate the in vivo effects of baicalein and baicalin treatment on LgBiT-hACE2 mice infected with the BA.2-SmBiT spike pseudovirus. This innovative bioluminescent system functions as a sensitive and early-stage quantitative viral transduction in vitro and in vivo. This platform provides novel opportunities for studying the molecular biology of animal models.

Enhanced Electrochemical Sensing of Oxalic Acid Based on VS2 Nanoflower-Decorated Glassy Carbon Electrode Prepared by Hydrothermal Method.

Oxalic acid (OA) is a predominant constituent in kidney stones, contributing to 70-80% of all cases. Rapid detection of OA is vital for the early diagnosis and treatment of kidney stone conditions. This work introduces a novel electrochemical sensing approach for OA, leveraging vanadium disulfide (VS2) nanoflowers synthesized via hydrothermal synthesis. These VS2 nanoflowers, known for their excellent electrocatalytic properties and large surface area, are used to modify glassy carbon electrodes for enhanced OA sensing. The proposed OA sensor exhibits high sensitivity and selectivity across a wide linear detection range of 0.2-20 µM, with an impressively low detection limit of 0.188 µM. The practicality of this sensor was validated through interference studies, offering a promising tool for the early diagnosis and monitoring of kidney stone diseases.

Treatment with autophagic inhibitors enhances oligonol­induced apoptotic effects in nasopharyngeal carcinoma cells.

Although the combination of chemotherapy and radiotherapy has increased the survival rate of patients with nasopharyngeal carcinoma (NPC), certain patients do not respond well to the treatment and have a poor prognosis. Therefore, novel therapeutic drugs and strategies to improve prognosis of patients with NPC are required. As certain plant extracts can suppress the viability of cancer cells, the present study investigated whether oligonol, a polyphenolic compound primarily found in lychee fruit, exerts anticancer activities in NPC cells. MTT, ELISA and immunoblotting were performed to investigate cell survival, cytokeratin-18 fragment release, and the expression of apoptosis and autophagy markers, respectively. Oligonol decreased the viability of NPC-TW01 and NPC/HK1NPC cell lines. Oligonol increased the protein expression of several apoptosis markers, including cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment. Moreover, it also increased expression of autophagy markers Beclin 1 and LC3-II, as well as LC3-II/LC3-I ratio in both NPC cell lines. Furthermore, treatment with autophagy inhibitors 3-methyladenine or LY294002 significantly increased oligonol-induced viability inhibition in NPC-TW01 cells. Combined treatment of oligonol + LY294002 reduced LC3-II expression and the LC3II/LC3I ratio while increasing cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment expression in NPC-TW01 cells. These findings indicated autophagy inhibitors could enhance viability inhibition and apoptotic effects induced by oligonol in NPC cells.

Generative Adversarial Networks with Radiomics Supervision for Lung Lesion Generation.

Data-driven methods for lesion generation are quickly emerging due to the need for realistic imaging targets for image quality assessment and virtual clinical trials. We proposed a generative adversarial network (GAN) architecture for conditional generation of lung lesions based on user-specified classes of lesion size and solidity. The network consists of two discriminators, one for volumetric lesion data, and one for radiomics features derived from the lesion volume. A Wasserstein loss with gradient penalty was adopted for each discriminator. Training data were drawn from contoured and annotated lesions from a public lung CT database. Four quantitative evaluation methods were devised to assess the network performance: 1) overfitting (similarity between generated and real lesions), 2) diversity (similarity among generated lesions), 3) conditional consistency (capability of generating lesions according to user-specified classes), and 4) similarity in distributions of various lesion properties between the generated and real lesions. Ablation studies were also performed to investigate the importance of individual network component. The proposed network was found to generate lesions that resemble real lesions by visual inspection. Solid lesions are distinct from non-solid ones, and lesion sizes largely correspond to their specified classes. With a classifier trained on real lesions, the classification accuracies of generated and real lesions in both solid and non-solid classes are similar. Radiomics features of generated and real lesions were found to have similar distributions, indicated by the relatively low Kullback-Leibler (KL) divergence values. Furthermore, the correlations between pairwise radiomics features in generated lesions were comparable to those of real lesions. The proposed network presents a promising approach for generating realistic lesions with clinically relevant features crucial for the comprehensive assessment of medical imaging systems.

A cross-sectional study of perception toward university social responsibility and environmental sustainability practices in medical university students under promotion of sustainable thinking within the university.

This study aims to assess the associations among students' perceptions of climate change, university social responsibility (USR), and environmental sustainability practices at a medical university. It also aims to identify the factors associated with these elements. A cross-sectional self-report study was conducted with a total sample of 416 undergraduate students from a medical university in Taiwan during October 2019. Data gathered comprised sociodemographic characteristics, perceptions of climate change issues, environmental sustainability practices, measure for perception toward USR, and transportation modes. Chi-square test, Fisher's exact test, two-sample t test, and multiple linear regression models were used. Results of multiple linear regression demonstrated that the level of certainty in climate change existence (extremely and mostly certain vs somewhat or not certain at all, 1.45 [0.68]), score for usage of nonpublic transportation (per 1-point increase, 0.52 [0.25]), and students' perception toward USR (per 1-point increase, 0.14 [0.04]) were associated with the total score of environmental sustainability practice (R-square = 11.47%). In addition, school year (non-freshmen vs freshmen, -1.64 [0.65]) and environmental sustainability practices (per 1-point increase, 0.23 [0.06]) were associated with the total score of students' perception of USR (R-square = 6.57%). Promoting environmental sustainability among university students can be achieved by implementing USR-oriented courses or activities. Our research is pioneering in investigating and discussing the perceived USR and environmental sustainability practices among university students in Taiwan.

A scoring system based on inflammatory and nutritional indicators to predict the long-term survival of patients with non-metastatic nasopharyngeal carcinoma.

To develop a simple scoring system based on baseline inflammatory and nutritional markers to predict the long-term prognosis of patients with nasopharyngeal carcinoma (NPC). Conducted a retrospective analysis of clinical data from 1024 newly diagnosed non-metastatic NPC patients. A total of 15 pre-treatment inflammatory and nutritional markers were collected as candidate variables. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff points for each parameter. Survival analysis was performed using Kaplan-Meier method and Cox regression analysis. Besides, the Inflammation Nutrition Risk Score (INRS) was calculated for each patient by assigning each independent prognostic factor a score of 1. Multivariate Cox regression analysis showed that serum albumin (ALB), systemic immune-inflammation index, and monocyte count (M) were independent prognostic factors for OS (P < 0.05). Survival analysis showed that higher INRS was associated with a worsened prognosis. Patients in the high-risk group had shorter OS than in the low-risk group. In the training group, the 3-, 5-, and 8-years OS rates for the low-risk group versus high-risk group were 92.5% versus 87.8%, 87.4% versus 75.1%, and 84.6% versus 62.2%, respectively (P < 0.05). In the validation group, the 3-, 5-, and 8-years OS rates for the low-risk group vs. high-risk group were 95.0% versus 86.4%, 92.1% versus 82.2%, and 89.5% versus 74.3%, respectively (P < 0.05). Further subgroup analysis showed a significant difference in the OS between the high-risk group and low-risk group in patients with locally advanced disease (P < 0.05). The ROC curve demonstrated that INRS had a similar predictive value for long-term survival in NPC patients compared to TNM staging and serum EBV-DNA levels. Pretreatment ALB, M, and SIRI are independent prognostic factors for long-term survival in patients with NPC. INRS constructed based on these three factors can serve as a long-term prognostic indicator for NPC.

Orthogonal Electrochemical Stability of Bulk and Surface in Lead Halide Perovskite Thin Films and Nanocrystals.

Lead halide perovskites have attracted significant attention for their wide-ranging applications in optoelectronic devices. A ubiquitous element in these applications is that charging of the perovskite is involved, which can trigger electrochemical degradation reactions. Understanding the underlying factors governing these degradation processes is crucial for improving the stability of perovskite-based devices. For bulk semiconductors, the electrochemical decomposition potentials depend on the stabilization of atoms in the lattice-a parameter linked to the material's solubility. For perovskite nanocrystals (NCs), electrochemical surface reactions are strongly influenced by the binding equilibrium of passivating ligands. Here, we report a spectro-electrochemical study on CsPbBr3 NCs and bulk thin films in contact with various electrolytes, aimed at understanding the factors that control cathodic degradation. These measurements reveal that the cathodic decomposition of NCs is primarily determined by the solubility of surface ligands, with diminished cathodic degradation for NCs in high-polarity electrolyte solvents where ligand solubilities are lower. However, the solubility of the surface ligands and bulk lattice of NCs are orthogonal, such that no electrolyte could be identified where both the surface and bulk are stabilized against cathodic decomposition. This poses inherent challenges for electrochemical applications: (i) The electrochemical stability window of CsPbBr3 NCs is constrained by the reduction potential of dissolved Pb2+ complexes, and (ii) cathodic decomposition occurs well before the conduction band can be populated with electrons. Our findings provide insights to enhance the electrochemical stability of perovskite thin films and NCs, emphasizing the importance of a combined selection of surface passivation and electrolyte.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.