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Abstract Background Acute ischemic stroke (AIS) is one of the most common cerebrovascular diseases which accompanied by a disruption of aminothiols homeostasis. To explore the relationship of aminothiols with neurologic impairment severity, we investigated four aminothiols, homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CG) and glutathione (GSH) in plasma and its influence on ischemic stroke severity in AIS patients. Methods A total of 150 clinical samples from AIS patients were selected for our study. The concentrations of free reduced Hcy (Hcy), own oxidized Hcy (HHcy), free reduced Cys (Cys), own oxidized Cys (cysteine, Cyss), free reduced CG (CG) and free reduced GSH (GSH) were measured by our previously developed hollow fiber centrifugal ultrafiltration (HFCF-UF) method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration ratio of Hcy to HHcy (Hcy/HHcy), Cys to Cyss (Cys/Cyss) were also calculated. The neurologic impairment severity of AIS was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Spearman correlation coefficient and logistic regression analysis was used to estimate and perform the correlation between Hcy, HHcy, Cys, Cyss, CG, GSH, Hcy/HHcy, Cys/Cyss and total Hcy with NIHSS score. Results The reduced Hcy and Hcy/HHcy was both negatively correlated with NIHSS score in AIS patients with P = 0.008, r=-0.215 and P = 0.002, r=-0.249, respectively. There was no significant correlation of Cys, CG, GSH, HHcy, Cyss, Cys/Cyss and total Hcy with NIHSS score in AIS patients with P value > 0.05. Conclusions The reduced Hcy and Hcy/HHcy, not total Hcy concentration should be used to evaluate neurologic impairment severity of AIS patient.

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients.

Abstract Malignant tumours of the digestive system cover a wide range of diseases that affect the health of people to a large extent. Angiogenesis is indispensable in the development, and metastasis of tumours, mainly in two ways: occupation or formation. Vessels can provide nutrients, oxygen, and growth factors for tumours to encourage growth and metastasis, so cancer progression depends on simultaneous angiogenesis. Recently, exosomes have been proven to participate in the angiogenesis of tumours. They influence angiogenesis by binding to tyrosine kinase receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 with different affinities, regulating Yap-VEGF pathway, Akt pathway or other signaling pathway. Additionally, exosomes are potential therapeutic vectors that can deliver many types of cargoes to different cells. In this review, we summarize the roles of exosomes in the angiogenesis of digestive system tumours and highlight the clinical application prospects, directly used as targers or delivery vehicles, in antiangiogenic therapy.

AbstractWorkplace flexibility has become increasingly popular and important within the landscape of human resource management especially during and even after the COVID19-pandemic among young working adults. The objective of this study is to identify the influence of four forms of workplace flexibility on employee engagement. The study used online questionnaire and were answered by 185 young working adults below 30 years old as of 2022 through Google Form. The data were analyzed by using partial least square (PLS) structural equation modelling (SEM) technique. The study found that workspace flexibility and operational flexibility have significant positive relationships with employee engagement. This study provides practical and direct implications for business and society. Besides that, this research also adds values to the understanding of workplace flexibility and employee engagement for human resource scholars.

Background Geriatric assessment (GA) has been shown to be pivotal to the prognosis of elderly cancer patients. A G8 screening tool could act as a potential surrogate to identify patients who would benefit from further GA in a busy oncology clinic and a digital version would allow for a wider application. Objectives To develop a digital self-reported version of G8, and to compare its outcomes with in-person G8 administered by a healthcare professional. Methods A total of 483 cancer patients aged 70 years and older who received an in-person G8 assessment at the National Cancer Centre Singapore (NCCS) clinic, and another 544 who completed the digital self-reported G8 were analysed. Total G8 score ≤14 was defined as positive screen. Results Response rate of the digital self-reported G8 was 50%. Median G8 total score was lower among online screeners than in-person screeners (11 vs 12.5, p < 0.001). The odds of a G8 positive screen among online screeners was higher than that of in-person screeners on multivariable logistic regression analysis (odds ratio = 1.56, 95% CI 1.08-2.26). Some 20 in-person screeners had also completed the digital self-reported G8, and the agreement between their in-person and online G8 total scores was high (concordance correlation coefficient = 0.798, 95% CI 0.635-0.962). Conclusions A digital self-reported G8 is feasible. However, given the higher positive screen rate among the online screeners, replacement of the in-person G8 with the digital self-reported G8 should be implemented only after more conclusive evidence on the agreement between in-person and online G8 score is available.

Abstract Severe trauma is a critical aspect of medical practice, profoundly impacting patient care and outcomes. Over the past 20 years, advancements in trauma care concepts and the utilization of advanced technologies have led to substantial growth in severe trauma research, evidenced by a notable increase in research activity and subsequent publications. To understand the publication landscape in severe trauma, identify prevailing research trends, and highlight areas requiring further development for future insights, we conducted a bibliometric analysis. Our analysis indicates that there are 16,939 severe trauma‐related publications from the past 20 years, with a continuous increase in publication volume, particularly showing a rapid growth trend from 2018 to 2021. The United States leads in both volume and citation frequency. Moreover, we synthesized data on productive countries/regions and research institutions, showcasing extensive collaboration across diverse geographic locations and institutional affiliations. Substantial progress has been achieved in severe trauma research, particularly in clinical diagnosis, treatment, epidemiology, prevention, and pathogenesis. However, there is still a gap in adopting cutting‐edge interdisciplinary methodologies. This study provides a comprehensive overview of the current state of severe trauma research and suggests pathways for future advancement.

Abstract Recent studies have highlighted the biological significance of cuproptosis in disease occurrence and development. However, it remains unclear whether cuproptosis signaling also has potential impacts on tumor initiation and prognosis of gastric cancer (GC). In this study, 16 cuproptosis‐related genes (CRGs) transcriptional profiles were harnessed to perform the regularized latent variable model‐based clustering in GC. A cuproptosis signature risk scoring (CSRS) scheme, based on a weighted sum of principle components of the CRGs, was used to evaluate the prognosis and risk of individual tumors of GC. Four distinct cuproptosis signature‐based clusters, characterized by differential expression patterns of CRGs, were identified among 1136 GC samples across three independent databases. The four clusters were also associated with different clinical outcomes and tumor immune contexture. Based on the CSRS, GC patients can be divided into CSRS‐High and CSRS‐Low subtypes. We found that DBT, MTF1, and ATP7A were significantly elevated in the CSRS‐High subtype, while SLC31A1, GCSH, LIAS, DLAT, FDX1, DLD, and PDHA1 were increased in the CSRS‐Low subtype. Patients with CSRS‐Low score were characterized by prolonged survival time. Further analysis indicated that CSRS‐Low score also correlated with greater tumor mutation burden (TMB) and higher mutation rates of significantly mutated genes (SMG) in GC. In addition, the CSRS‐High subtype harbored more significantly amplified focal regions related to tumorigenesis (3q27.1, 12p12.1, 11q13.3, etc.) than the CSRS‐Low tumors. Drug sensitivity analyses revealed the potential compounds for the treatment of gastric cancer with CSRS‐High score, which were experimentally validated using GC cells. This study highlights that cuproptosis signature‐based subtyping is significantly associated with different clinical features and molecular landscape of GC. Quantitative evaluation of the CSRS of individual tumors will strengthen our understanding of the occurrence and development of cuproptosis and the treatment progress of GC.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

Abstract Background Consolidation therapy improves the duration of response among patients with primary central nervous system lymphoma (PCNSL). Lenalidomide maintenance has shown encouraging results in older patients with PCNSL. Herein, we performed a retrospective, single‐center analysis to evaluate the effect of lenalidomide maintenance on the duration of response in patients with newly‐diagnosed PCNSL. Methods Sixty‐nine adult patients with PCNSL who achieved complete remission or partial remission (PR) after induction therapy were enrolled. The median age of patients was 58.0 years. The maintenance group (n = 35) received oral lenalidomide (25 mg/day) for 21 days, every 28 days for 24 months; the observation group did not undergo any further treatment. Results After a median follow‐up of 32.6 months, the maintenance group experienced fewer relapse events. However, the median progression‐free survival (PFS) was similar between groups (36.1 vs. 30.6 months; hazard ratio, 0.78; 95% confidence interval, 0.446). Lenalidomide maintenance significantly improved PFS and overall survival (OS) only among patients who experienced PR after induction. The median duration of lenalidomide maintenance was 18 months; lenalidomide was well tolerated and minimally impacted the quality of life. Conclusions The present study was the first to evaluate lenalidomide maintenance as a frontline treatment among patients with PCNSL, PFS and OS did not improve, although the safety profile was satisfactory.

Sepsis is a life-threatening organ dysfunction caused by the host’s dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.

The purpose of this paper is to examine the role of customers’ perceived value in mediating the relationship between Electronic Service Quality (ESQ) and customer satisfaction in online banking in Malaysia. The research model is developed based on the disconfirmation theory. Non-probability purposive sampling was adopted for data collection. A cross-sectional technique with a self-administered questionnaire was applied. The unit of analysis in this study is bank customers using online banking in Selangor, Malaysia. One hundred twenty-eight usable responses were received and analyzed. The Statistical Package for the Social Sciences (SPSS) was applied to analyze the data. Findings showed that the variance in customer satisfaction can be significantly explained via E-service quality dimensions (R2 = 0.52). The ease of use, security, reliability, responsiveness (ESQ) have a significant and positive impact on customer satisfaction among online banking users (p = 0.000). Furthermore, it was found that the customers’ perceived value significantly mediates the relationship between E-service quality and customer satisfaction (p-value = 0.0004). The experimental findings for this paper strengthen and expand the theoretical understanding of the relationship between ESQ, customer perceived value, and customer satisfaction that helps the banks in Malaysia to perform more successfully in the rapid business environment. This study also contributed to diminishing the gap in the ESQ literature between developed and developing countries, especially in the Malaysian context.

Abstract Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration. The expression of LHPP was assessed in human GC specimens and cell lines. Various assays were employed to evaluate the impact of LHPP on GC cells. RNA sequencing and Gene Set Enrichment Analysis were conducted to unravel the mechanism through which LHPP regulates GC cell behavior. Additionally, xenograft nude mouse models were utilized to investigate the in vivo effects of LHPP. The findings indicate that LHPP, functioning as a tumor suppressor, is downregulated in both GC tissues and cells. LHPP emerges as an independent risk factor for GC patients, and its expression level exhibits a positive correlation with patient prognosis. LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin‐like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.

In the fiercely competitive landscape of the peer-to-peer accommodation platform Airbnb, understanding customers’ online recommendation behavior is essential for optimizing competitiveness and harnessing the potential of electronic word-of-mouth. This study aims to provide comprehensive insights into the factors driving customers’ issuance of positive or negative recommendations based on their experiences. Leveraging 10,101 online reviews from Airbnb users, we employ the Structural Topic Model to determine latent topics relating to customers’ recommendation intentions. This study reveals that positive recommendations are primarily influenced by hedonic values tied to the overall experience, including crucial aspects such as convenience for exploring points of interest, local authenticity, social interaction, and emotional fulfillment. These findings highlight the significance of providing memorable and enriching experiences to elicit positive reviews from customers. On the other hand, negative recommendations are closely linked to utilitarian values focused on practical concerns such as check-in procedures, cleanliness, comfortableness, and amenities. Understanding these utilitarian factors is vital for hosts and platform administrators to improve service quality and address potential issues that may lead to negative reviews. Furthermore, this study emphasizes the significant role of hosts in shaping both positive and negative recommendations. This research contributes valuable insights to the field of peer-to-peer accommodation, highlighting the significance of various factors influencing customers’ recommendation behavior.

Eggshell concrete is an innovative green material that helps to recycle eggshell waste while reducing the environmental harm caused by excessive cement production. However, recent studies on eggshell concrete are limited, and the outcomes may vary due to the variation of mix design. The design of the experiment is used to simplify and optimize the study of sustainable concrete, yet analysis involving eggshell concrete is still scarce. This paper aimed to develop mathematical models for the prediction of eggshell concrete compressive strength using mixed regression (MR) and response surface methodology (RSM). Overall, 43 datasets were collected from available studies in the literature on eggshell powder as partial cement replacement. The input variables used were the percentage of eggshell, percentage of Ground Granulated Blast-furnace Slag (GGBS), cement content, fine aggregate, coarse aggregate, water, and Conplast SP-430 superplasticizer. The analysis of the contour plot concluded that eggshell powder increased the concrete compressive strength at an optimal replacement percentage between 5% and 10%. However, the partial cement replacement with eggshell powder is more optimal for mix design with higher water content. The statistical results of the model, such as R2, adjusted R2, and root-mean-square error (RMSE), indicated that both MR and RSM models are powerful tools to formulate and predict the eggshell concrete compressive strength. However, RSM models showed better accuracy and lower deviation.