bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1
Authors: Arif Tasleem , Shteinfer-Kuzmine Anna , Shoshan-Barmatz Varda
Published: October 2024

Mitochondria serve as central hubs for regulating numerous cellular processes that include metabolism, apoptosis, cell cycle progression, proliferation, differentiation, epigenetics, immune signaling, and aging. The voltage-dependent anion channel 1 (VDAC1) functions as a crucial mitochondrial gatekeeper, controlling the flow of ions, such as Ca2+, nucleotides, and metabolites across the outer mitochondrial membrane, and is also integral to mitochondria-mediated apoptosis. VDAC1 functions in regulating ATP production, Ca2+ homeostasis, and apoptosis, which are essential for maintaining mitochondrial function and overall cellular health. Most cancer cells undergo metabolic reprogramming, often referred to as the “Warburg effect”, supplying tumors with energy and precursors for the biosynthesis of nucleic acids, phospholipids, fatty acids, cholesterol, and porphyrins. Given its multifunctional nature and overexpression in many cancers, VDAC1 presents an attractive target for therapeutic intervention. Our research has demonstrated that silencing VDAC1 expression using specific siRNA in various tumor types leads to a metabolic rewiring of the malignant cancer phenotype. This results in a reversal of oncogenic properties that include reduced tumor growth, invasiveness, stemness, epithelial–mesenchymal transition. Additionally, VDAC1 depletion alters the tumor microenvironment by reducing angiogenesis and modifying the expression of extracellular matrix- and structure-related genes, such as collagens and glycoproteins. Furthermore, VDAC1 depletion affects several epigenetic-related enzymes and substrates, including the acetylation-related enzymes SIRT1, SIRT6, and HDAC2, which in turn modify the acetylation and methylation profiles of histone 3 and histone 4. These epigenetic changes can explain the altered expression levels of approximately 4000 genes that are associated with reversing cancer cells oncogenic properties. Given VDAC1’s critical role in regulating metabolic and energy processes, targeting it offers a promising strategy for anti-cancer therapy. We also highlight the role of VDAC1 expression in various disease pathologies, including cardiovascular, neurodegenerative, and viral and bacterial infections, as explored through siRNA targeting VDAC1. Thus, this review underscores the potential of targeting VDAC1 as a strategy for addressing high-energy-demand cancers. By thoroughly understanding VDAC1’s diverse roles in metabolism, energy regulation, mitochondrial functions, and other cellular processes, silencing VDAC1 emerges as a novel and strategic approach to combat cancer.
Glucocorticoid-Induced Leucine Zipper Protein and Yeast-Extracted Compound Alleviate Colitis and Reduce Fungal Dysbiosis
Authors: Gentili Marco , Sabbatini Samuele , Nunzi Emilia , Lusenti Eleonora , Cari Luigi , Mencacci Antonella , Ballet Nathalie , Migliorati Graziella , Riccardi Carlo , Ronchetti Simona , Monari Claudia
Published: October 2024

Inflammatory bowel diseases (IBD) have a complex, poorly understood pathogenesis and lack long-lasting effective treatments. Recent research suggests that intestinal fungal dysbiosis may play a role in IBD development. This study investigates the effects of the glucocorticoid-induced leucine zipper protein (GILZp)”, known for its protective role in gut mucosa, and a yeast extract (Py) with prebiotic properties, either alone or combined, in DSS-induced colitis. Both treatments alleviated symptoms via overlapping or distinct mechanisms. In particular, they reduced the transcription levels of pro-inflammatory cytokines IL-1β and TNF-α, as well as the expression of the tight junction protein Claudin-2. Additionally, GILZp increased MUC2 transcription, while Py reduced IL-12p40 and IL-6 levels. Notably, both treatments were effective in restoring the intestinal burden of clinically important Candida and related species. Intestinal mycobiome analysis revealed that they were able to reduce colitis-associated fungal dysbiosis, and this effect was mainly the result of a decreased abundance of the Meyerozima genus, which was dominant in colitic mice. Overall, our results suggest that combined treatment regimens with GILZp and Py could represent a new strategy for the treatment of IBD by targeting multiple mechanisms, including the fungal dysbiosis.
Neuroimaging-Based Brain Morphometry in Alzheimer’s Disease
Authors: Aniebo Nonyelum , Goswami Tarun
Published: October 2024

Background/Objectives: Alzheimer’s disease (AD) is a leading cause of death worldwide, affecting millions of older Americans and resulting in a substantial economic burden. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) aims to investigate and develop treatments for AD. Methods: This study included 60 participants, divided equally into AD and control cohorts, and utilized magnetic resonance imaging (MRI) scans to detect gray matter volumetric alterations, a key biomarker of AD. The participants’ cortical volume and surface area were quantified using an automated pipeline in MIMICS (Materialise Interactive Medical Imaging Control System). Results: A multivariate regression analysis was conducted to explore the relationship between cortical measurements and potential factors influencing AD susceptibility. The study found that both cortical volume and surface area were statistically significant predictors of AD (p = 0.0004 and p = 0.011, respectively). Age was also a significant factor, with the 65–70 age group showing the strongest association (p < 0.001). The model achieved an accuracy of 0.68 in predicting AD. Conclusions: While voxel-based morphometry (VBM) using MIMICS showed promise, further development of the automated pipeline could enhance accuracy and correlation indices. These findings contribute to our understanding of brain atrophy in AD pathophysiology and highlight the potential of MRI morphometry as a tool for AD biomarker development.
Lower Free Thyroxine Levels Are Associated with Diabetic Kidney Disease in Males with Type 2 Diabetes Mellitus: An Observational Cross-Sectional Study
Authors: Shang Jianan , Zheng Yixuan , Zhang Meng , Li Meng , Qiang Wei , Sui Jing , Guo Hui , Shi Bingyin , He Mingqian
Published: October 2024

Objectives: We aimed to explore the correlation between thyroid function and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 7516 T2DM patients were enrolled and grouped according to DKD status. Clinical parameters, including blood glucose parameters, thyroid function, and indicators of renal impairment, were collected and compared between the DKD and Non-DKD groups. Correlation analysis and univariate/multivariate logistic regression analyses were performed. Results: Age, T2DM duration, the use of insulin and lipid-lowering drugs, systolic and diastolic blood pressure, body mass index, and fasting blood glucose levels were greater in the DKD group than in the Non-DKD group (p < 0.001). Notably, compared with those in the Non-DKD group, patients in the DKD group had lower triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) levels and higher thyrotropin levels (p < 0.001). Univariate logistic regression analysis revealed that T3, T4, FT3, and FT4 levels were negatively correlated with the risk of DKD. Spearman correlation analysis confirmed that T3, T4, FT3, and FT4 levels were negatively correlated with blood urea nitrogen levels, blood creatinine levels, and the urinary albumin-to-creatinine ratio (p < 0.05). Multivariate logistic regression analysis revealed that a greater FT4 level was a protective factor against DKD in T2DM patients, especially in males, with a cut-off value of 13.35 pmol/L (area under the curve = 0.604). Conclusions: Thyroid hormone levels, especially FT4 levels, were significantly negatively correlated with DKD in T2DM patients.
Innovations in Microfluidics to Enable Novel Biomedical Applications
Authors: Xiang Nan , Ni Zhonghua
Published: October 2024

As a new technique for precisely controlling micro-/nanoparticles and fluids at the microscale, microfluidics has been attracting increased interest in the fields of material science, medical diagnosis, biological research, and even soft robotics [...]
High-Performance Flexible PLA/BTO-Based Pressure Sensor for Motion Monitoring and Human–Computer Interaction
Authors: Sui Xuguang , Mu Qingmiao , Li Jia , Zhao Bo , Gu Hongxi , Yu Han , Du Juan , Ren Lijun , Hu Dengwei
Published: October 2024

Flexible electronics show wide application prospects in electronic skin, health monitoring, and human–machine interfacing. As an essential part of flexible electronics, flexible pressure sensors have become a compelling subject of academic research. There is an urgent need to develop piezoelectric sensors with high sensitivity and stability. In this work, the high flexibility of polylactic acid (PLA) film and the excellent ferroelectric properties and high dielectric constant of tetragonal barium titanate (BTO) led to their use as filling materials to fabricate flexible piezoelectric composite films by spinning coating. PLA is used to produce flexible binding substrates, and BTO is added to the composite to enhance its electrical output by improving its piezoelectric performance. The peak output voltage of the PLA/BTO tetragonal piezoelectric film is 22.57 V, and the maximum short-circuit current was 3041 nA. Durability tests showed that during 40,000 s of continuous operation, in the range of 15~120 kPa, the linear relationship between pressure and the film was excellent, the sensitivity for the output voltage is 0.176 V/kPa, and the output current is 27.77 nA/kPa. The piezoelectric pressure sensor (PPS) also enables accurate motion detection, and the extensive capabilities of the PENG highlight its potential in advancing motion sensing and human–computer interactions.
Language Experience Influences Sociolinguistic Development: The Role of Speaker Race and Language Attitudes on Bilingual and Monolingual Adults’ Accent Processing
Authors: Ritsema Vanessa , Workye Rebeka , Weatherhead Drew
Published: October 2024

Background/Objectives: Speaker race and the listener’s language experience (i.e., monolinguals vs. bilinguals) have both been shown to influence accent intelligibility independently. Speaker race specifically is thought to be informed by learned experiences (exemplar model) or individual biases and attitudes (bias-based model). The current study investigates speaker race and the listener’s language experience simultaneously as well as listeners’ attitudes toward non-native speakers and their ability to identify the accent. Methods: Overall, 140 White English monolinguals and 140 English/Norwegian bilinguals transcribed 60 Mandarin-accented English sentences presented in noise in the context of a White or East Asian face. Following sentence transcription, participants were asked to rate the strength of the accent heard and completed a short questionnaire that assessed their accent identification ability and their language usage, proficiency, familiarity, and attitudes. Results: Results show that a listeners’ ability to identify an accent and their attitudes toward non-native speakers had a significant impact on accent intelligibility and accentedness ratings. Speaker race by itself did not play a role in accent intelligibility and accentedness ratings; however, we found evidence that speaker race interacted with participants’ accent identification scores and attitudes toward non-native speakers, and these interactions differed as a function of language experience. Conclusions: Our results suggest that bilinguals’ sociolinguistic processing may be more in line with a bias-based model than monolinguals.
Neurosurgical Microvascular Anastomosis: Systematic Review of the Existing Simulators and Proposal of a New Training Classification System
Authors: Guida Lelio , Sebök Martina , Oliveira Marcelo Magaldi , van Niftrik Christiaan Hendrik Bas , Charbel Fady T. , Cenzato Marco , Regli Luca , Esposito Giuseppe
Published: October 2024

Background: The literature lacks a combined analysis of neurosurgical microvascular anastomosis training models. We performed a systematic literature search to provide an overview of the existing models and proposed a classification system based on the level of simulation and reproducibility of the microvascular anastomosis. Methods: The systematic literature search followed the PRISMA guidelines. We consulted MEDLINE, Web of Knowledge, and EMBASE independently for papers about bypass training models. Every training model was analyzed according to six tasks supposed to esteem their fidelity to the real operative setting by using a scoring system from zero to two. Finally, authors classified the models into five classes, from A to E, by summing the individual scores. Results: This study included 109 papers for analysis. Training models were grouped into synthetic tubes, ex vivo models (animal vessels, fresh human cadavers, human placentas) and in vivo simulators (live animals—rats, rabbits, pigs). By applying the proposed classification system, live animals and placentas obtained the highest scores, falling into class A (excellent simulators). Human cadavers and animal vessels (ex vivo) were categorized in class B (good simulators), followed by synthetic tubes (class C, reasonable simulators). Conclusions: The proposed classification system helps the neurosurgeon to analyze the available training models for microvascular anastomosis critically, and to choose the most appropriate one according to the skills they need to improve
Determinants of Fertility Intentions among South Koreans: Systematic Review and Meta-Analysis
Authors: Kim Eungyung , Yi Jee-Seon
Published: October 2024

(1) Background/objectives: This study aims to systematically review and conduct a meta-analysis of factors influencing fertility intentions among South Koreans. This research is crucial given South Korea’s lowest-in-the-world fertility rate of 0.72 in 2023, necessitating rapid and effective policies to address this demographic challenge; (2) Methods: Articles published from database inception through April 2024 were collected from five Korean databases using keywords based on the PEO (Population, Exposure, Outcome) framework. Following PRISMA guidelines, 35 articles were selected. The effect sizes and network of predictors related to fertility intention were analyzed using the R statistical package; (3) Results: A meta-analysis of the effect sizes of factors influencing fertility intentions revealed that the husband’s involvement in parenting (ESr = 0.131), women’s education level (ESr = 0.127), socioeconomic status (ESr = 0.116), and the expected gender of the child (ESr = 0.068) showed statistically significant positive effects. Conversely, women’s age (ESr = −0.175), parental stress (ESr = −0.146), and household labor ratio (ESr = −0.117) showed statistically significant negative effects. The network analysis further elucidated the complex interrelationships among these factors; (4) Conclusions: This study suggests the need for multifaceted policy approaches to address Korea’s low fertility, emphasizing promoting men’s participation in parenting, supporting women’s education and career development, reducing parenting stress, supporting work–family balance, and ensuring economic stability. These findings provide important insights for policymakers and researchers addressing the complex issue of low fertility in South Korea and may inform more effective interventions to boost fertility rates.
How Is Rejection Sensitivity Linked to Non-Suicidal Self-Injury? Exploring Social Anxiety and Regulatory Emotional Self-Efficacy as Explanatory Processes in a Longitudinal Study of Chinese Adolescents
Authors: Zhao Junyan , Li Anna , Li Kunlin , Zhao Fengqing
Published: October 2024

Early adolescents are at high risk for non-suicidal self-injurious behavior (NSSI). Based on the Rejection Sensitivity Model, the Experiential Avoidance Model, and the Affect Regulation Model of Self-Injury, this study aimed to explain how rejection sensitivity was related to NSSI among adolescents by unraveling the mediating role of social anxiety and the moderating role of regulatory emotional self-efficacy (RESE) in this relationship. A three-wave longitudinal investigation with a three-month interval was conducted among 726 adolescents (Mage = 13.47, SD = 0.95; 46.0% girls) from a middle school in North China. The Cross-Lagged Panel Models (RI-CLPMs) were utilized to estimate the associations among the study variables. The results indicated that the incidence rates of NSSI in the three measurements among adolescents were 33.3%, 30.3%, and 24.1%, respectively. Adolescents’ rejection sensitivity and NSSI showed a declining trend over time. Furthermore, rejection sensitivity predicted NSSI through the longitudinal mediating effect of social anxiety. RESE played a protective role in adolescents’ NSSI, but its moderating effect was not significant. The findings increase our understanding of the association between rejection sensitivity and NSSI in adolescents, and they benefit educators in conducting targeted interventions through improving adolescents’ rejection sensitivity and social anxiety to reduce the risk of NSSI.
Methodological Variations to Explore Conflicting Results in the Existing Literature of Masking Smile Judgment
Authors: Pelot Annalie , Gallant Adèle , Mazerolle Marie-Pier , Roy-Charland Annie
Published: October 2024

Although a smile can serve as an expression of genuine happiness, it can also be generated to conceal negative emotions. The traces of negative emotion present in these types of smiles can produce micro-expressions, subtle movements of the facial muscles manifested in the upper or lower half of the face. Studies examining the judgment of smiles masking negative emotions have mostly employed dichotomous rating measures, while also assuming that dichotomous categorization of a smile as happy or not is synonymous with judgments of the smile’s authenticity. The aim of the two studies was to explore the judgment of enjoyment and masking smiles using unipolar and bipolar continuous rating measures and examine differences in the judgment when instruction varied between judgments of happiness and authenticity. In Experiment 1, participants rated smiles on 7-point scales on perceived happiness and authenticity. In Experiment 2, participants rated the smiles on bipolar 7-point scales between happiness and a negative emotion label. In both studies, similar patterns were observed: faces with traces of fear were rated significantly less happy/authentic and those with traces of anger in the brows were rated significantly happier/more authentic. Regarding varied instruction type, no effect was found for the two instruction types, indicating that participants perceive and judge enjoyment and masking smiles similarly according to these two instructions. Additionally, the use of bipolar scales with dimensions between a negative emotion label and happiness were not consistently effective in influencing the judgement of the masking smile.
The Relationship between Marital Satisfaction and Spiritual Well-Being of Chinese Older Adults: The Mediating Effect of Psychological Security and Aging Expectations
Authors: Tang Longxing , Yang Yachi , An Zhiwei , Huang Yalian , Tang Ping
Published: October 2024

This study explores the relationship between marital satisfaction and spiritual well-being in older adults and the role of psychological security and aging expectations in older adult relationships. A convenient sample cross-sectional research method collected data from 367 older adults in Sichuan Province, China. A chain mediation model was constructed using quantitative analysis methods to test the relationship between marital satisfaction and older adults’ spiritual well-being and the potential mediating roles of psychological security and aging expectations. The research conclusions are as follows: marital satisfaction positively correlates with spiritual well-being, and psychological security and aging expectations play independent chain mediating roles.
Secondary Female Anorgasmia in Patients with Obsessive Traits: A Study
Authors: Perrotta Giulio , Eleuteri Stefano
Published: October 2024

Background: In the literature, female anorgasmia (AO) is closely related to obsessive–compulsive disorder (OCD), but no publication has explored the role of individual obsessive traits that may also be typical of other disorders, assuming that repetitive thoughts and compulsions must necessarily correspond to an obsessive-type neurotic profile. It is worth investigating and assessing the specific weight of other morbid conditions involved, beyond OCD. Materials and Methods: This study was conducted during 2022–2023 by selecting 208 Italian clinical patients from private databases. They submitted to individual clinical interviews and two psychometric questionnaires (Perrotta Integrative Clinical Interviews 3, PICI-3-TA, and Perrotta Individual Sexual Matrix Questionnaire, PSM-Q). Results: Among the 208 patients (M: 39.05 years), divided into subgroups by age and obsessive symptomatology, no significant differences were found between the subgroups in the comparisons of the data obtained from the administration of the PSM-Q. Conclusions: This study confirms that it is not OCD that correlates with OA but obsessive traits, which are also common to other psychopathological disorders, such as bipolar disorder, borderline disorder, manic, and psychotic disorders and, therefore, in psychotherapy, it is necessary to intervene with a clinical approach that has in mind the patient’s psychopathological personality picture and the causes that originated or reinforced OA.
Aspects of Quality of Life: Single vs. Mated People
Authors: Apostolou Menelaos , Tekeş Burcu , Kagialis Antonios , Lajunen Timo Juhani
Published: October 2024

Not having an intimate partner constitutes a common state in contemporary post-industrial societies. The current research aimed to address the question of whether single people score higher than mated people in various dimensions of quality of life. For this purpose, we employed quantitative research methods, measuring different aspects of quality of life that we treated as the dependent variables, with relationship status as the independent variable. In a sample of 1929 participants from Greece and Turkey, we found that relationship status was not significantly associated with physical health, relationships with friends and family, self-development, independence, recreation, or participation in social and communal activities. On the other hand, it was significantly associated with material goods, disposable income, social support, sexual satisfaction, and having children, with mated people scoring higher than single people. Despite using different methodologies for data collection, similar results were obtained in the two cultural contexts.
Assessment and Treatment of Target Behavior Maintained by Social Avoidance
Authors: Slocum Sarah K. , Gottlieb Emily , Scheithauer Mindy , Muething Colin
Published: October 2024

Past research has identified that some individuals with intellectual and developmental disabilities who engage in target behavior (e.g., aggression, self-injury) maintained by negative reinforcement engage in the behavior to escape or avoid social interaction specifically (i.e., social avoidance). However, assessment and treatment strategies for this function are understudied when compared to target behavior maintained by other forms of negative reinforcement. The current study builds on this limited research and demonstrates (a) a replication of functional analysis conditions and a negative reinforcement latency assessment to identify the specific types of social interaction that evoke target behavior, and (b) an intervention that includes stimulus fading, social conditioning, and differential reinforcement for five participants with autism spectrum disorder. Participant target behavior decreased within the intervention phase for four out of five participants. The implications of strategies to guide the use of antecedent-based treatment strategies are discussed for target behavior maintained by social avoidance.
Shedding Light on the Aftermath: Childhood Maltreatment’s Role in Modifying the Association Between Recent Life Stress and Resting-State Network Connectivity
Authors: Luo Jingjing , Zhu Jianjun ,   The NSPN Consortium, Chen Yuanyuan
Published: October 2024

Childhood maltreatment has been demonstrated to impact brain development. However, whether childhood maltreatment can influence the effects of recent stress on brain networks remains unclear. This study aimed to investigate whether childhood maltreatment moderates the longitudinal relationship between recent life stress and within- and between-network connectivity in key brain networks, including the anterior salience (ASN), central executive (CEN), default mode (DMN), and emotional regulation network (ERN). A cohort of 172 individuals from the Neuroscience in Psychiatry Network (NSPN) underwent MRI scans at two specific time points and undertook evaluations of childhood maltreatment and recent life stress. The results showed that childhood abuse moderated the association of recent life stress with the within-network connectivity of ASN and ERN but not DMN and CEN. Furthermore, recent life stress significantly interacted with childhood abuse to be associated with the between-network connectivity of ASN-DMN, ASN-CEN, ASN-ERN, DMN-ERN and CEN-ERN. Overall, among youth exposed to higher degrees of childhood abuse, greater recent life stress was longitudinally associated with increased network connectivity. Understanding these interactions can provide valuable insights for developing prevention strategies and interventions aimed at mitigating the lasting impact of childhood maltreatment on brain development and overall well-being.
Start Task Crafting, Stay Away from Cyberloafing: The Moderating Role of Supervisor Developmental Feedback
Authors: Hai Man , Wu Xuyao , Zhou Bingping , Li Ye
Published: October 2024

Cyberloafing as a production deviance behavior raises organizational concerns. Unfortunately, it is unknown how to minimize cyberloafing from a bottom-up perspective, particularly different types of cyberloafing. This study draws on the job crafting and dual-process theory to construct a framework for understanding the relationship between task crafting and passive–active cyberloafing, as well as their boundary condition (i.e., supervisor developmental feedback). We adopted a convenient sampling method, following a two-stage sampling with a time interval of 2 weeks. A sample of 614 full-time employed adults were recruited from the online survey. The results showed that: (1) Task crafting was negatively related to passive and active cyberloafing, respectively. (2) The impact of task crafting on passive cyberloafing rather than active cyberloafing was moderated by supervisor developmental feedback, such that task crafting had significant negative relations with passive cyberloafing when supervisor developmental feedback was higher (vs. lower). Overall, our research findings indicate that passive cyberloafing seems more sensitive to the organizational environment than active cyberloafing, thus different types of cyberloafing have different intervention strategies.
Parent–Child Relationships and Adolescents’ Non-Cognitive Skills: Role of Social Anxiety and Number of Friends
Authors: Kuang Xiaoxue , Ren Fen , Lee John Chi-Kin , Li Hui
Published: October 2024

This study aimed to examine the association between parent–child relationships and adolescents’ non-cognitive skills, while also investigating the mediating effect of social anxiety and number of friends. A survey was conducted with 773 students, ranging from grade 4 to 9, in five public schools of Guangdong Province of China (49.9% male), with a mean age of 12.20 years old. Latent mediation structural equation modeling was used to analyze the data. The findings revealed that (1) the father–child relationship and mother–child relationship both had a positive influence on grit, innovation, conscientiousness, and hope; (2) social anxiety had a negative effect on adolescent non-cognitive skills including innovation, conscientiousness, and hope; (3) the number of positive friends was found to be positively associated with the development of non-cognitive skills in adolescents, whereas the presence of negative friends correlated negatively with grit but positively with innovation; (4) social anxiety emerged as a significant mediating variable between parent–child relationships and adolescents’ non-cognitive skills, including innovation, conscientiousness, and hope; and (5) the mediating effect of the number of positive friends on the relationship between parent–child relationships and grit, innovation, conscientiousness, and hope was also found to be significant. Educational programs and family interventions should take these factors into account, providing a more holistic approach to supporting adolescent growth.
Theoretical Research and Numerical Analysis of a New Assembled Shuttle-Shaped Self-Centering Mild Steel Energy Dissipation Brace
Authors: Chen Yao , Liu Zhonghua , Zhao Jianchao
Published: October 2024

To solve the problem of large residual deformation and high repair cost of traditional frame structures after an earthquake, a new type of assembled shuttle-shaped self-centering mild steel energy dissipation brace (ASSSEDB) with stable stiffness, material saving, and easy replacement was proposed. The plastic deformation of mild steel is used to dissipate energy, and the disc spring system provides a reset function. Based on the working mechanism of energy dissipation brace, a restoring force model for the ASSSEDB was established, and then the numerical analysis was carried out by ANSYS to verify the accuracy of the proposed model. The results confirm that the ASSSEDB has stable energy dissipation ability and a resetting function, with a full hysteresis curve. The finite element analysis results align well with the developed restoring force model, and the maximum deviations of initial stiffness and ultimate capacity are, respectively, 1.4% and 2.3%, which indicates that the established restoring force model can provide a theoretical basis for design of the ASSSEDB. Furthermore, the time history analysis was carried out to assess the seismic performance of a six-story steel frame structure using the proposed ASSSEDB. The results show that compared with the steel frame structure with BRBs, the proposed ASSSEDB can decrease the residual deformation of structures by up to 93.41%. The self-centering ratio of the ASSSEDB is crucial in controlling residual deformation of structures, and it is recommended to be greater than 1.0.
Exploring Recovery Exercises to Enhance Construction Workers’ Willingness for Career Continuity under the Dual-Process Theory: A Perspective from Physical Exercise
Authors: Zhao Zimo , Xu Zhengke , Zhang Jia , Tan Sijie
Published: October 2024

Globally, the construction industry is facing a severe labor shortage, and attracting and retaining workers has become a pressing challenge. This study examined the effect of rehabilitation exercise on construction workers’ willingness to sustain their careers through a questionnaire survey of 479 construction workers using a quantitative research methodology. It aims to reveal how the self-efficacy, perceived usefulness, and self-regulation of rehabilitation exercise affect construction workers’ occupational sustainability through physical and psychological recovery. The results of the study show that (1) the rehabilitation exercise self-efficacy and perceived usefulness of recovery exercise positively affect construction workers’ career sustainability intentions and (2) psychological recovery and physical recovery play parallel mediating roles in the effects of rehabilitation exercise self-efficacy, the perceived usefulness of recovery exercise, and self-regulation of recovery exercise on construction workers’ career sustainability intentions. The findings suggest that improving the physical and psychological capital of construction workers through recovery exercise can effectively enhance their career commitment and willingness to be sustainable. This study provides a reference for the design of more comprehensive and systematic rehabilitation and health management programs in the future and offers suggestions from the perspective of recovery exercise for the development of sustainable construction workers.
Characterization of Three-Dimensional Strong Force Chain Properties of Mineral Aggregate Mixtures Based on the Discrete Element Method
Authors: Gao Yuan , Liu Guoqiang , Jiang Nan
Published: October 2024

The skeleton structure composed of mineral aggregates is the main body to bear and transfer external loading in asphalt mixtures. To investigate the loading transfer mechanism of the mineral aggregate skeleton, the uniaxial penetration test and Discrete Element Method (DEM) were conducted for the Mineral Aggregate Mixture (MAM) to analyze its mechanical behavior. The three-dimensional strong force chain (SFC) was identified and evaluated based on the proposed recognition criterion and evaluation indices. The results indicate that 4.75 mm should be the boundary to distinguish the coarse and fine aggregates. The skeleton composed of aggregates located on SFCs has better bearing and transferring loading capacity due to its SFC number, average length, and total length decreasing with an increase in the aggregate size. Compared to SMA-16 and OGFC-16, AC-16 exhibits a higher number and total length of its SFC, a smaller average length of its SFC, and a lower average strength of its SFC. Consequently, AC-16 has a lower bearing and transferring loading capacity than that of SMA-16 and OGFC-16. In addition, approximately 90% of SFCs can only transfer external loading downward through 3–5 aggregates. The average direction angle of the SFC formed by fine aggregates is significantly higher than those formed by coarse aggregates. This indicates that the load transfer range of MAM composed of fine aggregates is noticeably larger, leading to lower loading transfer efficiency.
Local Stability Analysis of a Composite Corrugated Steel Plate Pipe-Arch in Soil
Authors: Che Chengwen , Hu Pingping , Shi Feng , Xu Pengsen , Liu Junxiu , Li Kai
Published: October 2024

The straight part of the corrugated steel plate (CSP) pipe-arch structure in soil may cause local buckling instability due to insufficient load-bearing capacity. Recently, composite CSP pipe-arch has been widely utilized to enhance structural stability, and their stability needs to be thoroughly investigated. This paper studies the local buckling stability problem of the straight part of composite CSP pipe-arch in soil by simplifying the soil support and introducing the inter-layer bonding effect. Based on elastic stability theory, a theoretical mechanical model of composite CSP pipe-arch was proposed. The Rayleigh–Ritz method and the semi-combined composite structure stiffness approximation were used to derive the critical buckling conditions for the straight part of the composite CSP pipe-arch. Through numerical calculation and influencing factors analysis, it is concluded that the critical buckling load of the straight part of the composite CSP pipe-arch structure is affected by the elastic modulus, thickness, Poisson’s ratio, rotational restraint stiffness and side length of the straight part of the material. In particular, it is found that as the inter-layer bonding coefficient increases, the critical buckling load is improved, while the critical buckling wave number is mainly influenced by the width of the straight part, elastic modulus, and inter-layer bonding coefficient. Additionally, we discussed the coupling effect of several key parameters on the stability of the structure. The results of this study offer theoretical foundations and guidance for the application of composite CSP pipe-arch in soil engineering, such as culverts, tunnels, and pipeline transportation.
Do Environmental, Social, and Governance (ESG) Factors Matter? Analyzing the Relationships Between Firm Characteristics and ESG Scores
Authors: Krishnan C. N. V. , Yang Jiemin , Tan Xiyao
Published: October 2024

We used three different databases that cover different years from 2006 through 2023 that provide different insights into the associations of firm features with their E, S, and G scores, as well as the composite ESG score. We find that large market capitalization firms are associated with higher ESG and environmental scores as well as with ESG-related strengths. These associations likely stem from the increased scrutiny and expectations from investors, regulators, and the public for large-cap firms. However, we find that changes in ESG scores have no significant associations with changes in basic firm characteristics—market cap, growth options, or profitability. That is, changes in ESG scores over time do not seem to significantly enhance or alter these basic features of a firm.
Overall Survival in Real-World Patients with Unresectable Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab Versus Sorafenib or Lenvatinib as First-Line Therapy: Findings from the National Veterans Health Administration Database
Authors: Kaplan David E. , Tan Ruoding , Xiang Cheryl , Mu Fan , Hernandez Sairy , Ogale Sarika , Li Jiayang , Lin Yilu , Shi Lizheng , Singal Amit G.
Published: October 2024

Background/Objectives: This study evaluated comparative overall survival (OS) of United States veterans with unresectable hepatocellular carcinoma (uHCC) receiving first-line (1L) atezolizumab plus bevacizumab vs. sorafenib or lenvatinib, overall and across racial and ethnic groups. Methods: In this retrospective study, patients with uHCC who initiated atezolizumab plus bevacizumab (post-2020) or sorafenib or lenvatinib (post-2018) were identified from the Veterans Health Administration National Corporate Data Warehouse (1 January 2017–31 December 2022). Patient characteristics were evaluated in the year prior to 1L treatment initiation. Kaplan–Meier and multivariable Cox regression methods were used to compare OS starting from treatment between cohorts, both overall and by race and ethnicity. Results: Among the 1874 patients included, 405 (21.6%) received 1L atezolizumab plus bevacizumab, 1016 (54.2%) received sorafenib, and 453 (24.2%) received lenvatinib, with a median follow-up time of 8.5, 7.6, and 8.2 months, respectively. Overall, patients receiving atezolizumab plus bevacizumab had longer unadjusted median OS (12.8 [95% CI: 10.6, 17.1] months) than patients receiving sorafenib (8.0 [7.1, 8.6] months) or lenvatinib (9.5 [7.8, 11.4] months; both log-rank p < 0.001). After adjustment, atezolizumab plus bevacizumab was associated with a reduced risk of death by 30% vs. sorafenib (adjusted HR: 0.70 [95% CI: 0.60, 0.82]) and by 26% vs. lenvatinib (0.74 [0.62, 0.88]; both p < 0.001). OS trends in the White, Black, and Hispanic patient cohorts were consistent with that of the overall population. Conclusions: Atezolizumab plus bevacizumab was associated with improved survival outcomes compared with sorafenib and lenvatinib in patients with uHCC, both overall and across racial and ethnic subgroups.
Targeting the Leloir Pathway with Galactose-Based Antimetabolites in Glioblastoma
Authors: Sharpe Martyn A. , Ijare Omkar B. , Raghavan Sudhir , Baskin Alexandra M. , Baskin Brianna N. , Baskin David S.
Published: October 2024

Background: Glioblastoma (GBM) uses Glut3 and/or Glut14 and the Leloir pathway to catabolize D-Galactose (Gal). UDP-4-deoxy-4-fluorogalactose (UDP-4DFG) is a potent inhibitor of the two key enzymes, UDP-galactose-4-epimerase (GALE) and UDP-Glucose 6-dehydrogenase (UGDH), involved in Gal metabolism and in glycan synthesis. The Gal antimetabolite 4-deoxy-4-fluorogalactose (4DFG) is a good substrate for Glut3/Glut14 and acts as a potent glioma chemotherapeutic. Methods: Primary GBM cell cultures were used to examine toxicity and alterations in glycan composition via lectin binding in fixed cells and by Western blots. Toxicity/efficacy in vivo data was performed in mouse flank and intracranial models. The effect of 4DFG on D-glucose (Glc) metabolism in GBM cells was assessed by using 13C NMR-based tracer studies. Results: 4DFG is moderately potent against GBM cells (IC50: 125–300 µM). GBM glycosylation is disrupted by 4DFG. Survival analysis in an intracranial mouse model showed that treatment with 4DFG (6 × 25 mg/kg of 4DFG, intravenously) improved outcomes by three-fold (p < 0.01). Metabolic flux analysis revealed that both glycolytic and mitochondrial metabolic fluxes of [U-13C]Glc were significantly decreased in the presence of 4DFG in GBM cells. Conclusion: A functional Gal-scavenging pathway in GBM allows Gal-based antimetabolites to act as chemotherapeutics. 4DFG is metabolized by GBM in vitro and in vivo, is lethal to GBM tumors, and is well tolerated in mice.
Insights into Metabolic Reprogramming in Tumor Evolution and Therapy
Authors: Chiu Ching-Feng , Guerrero Jonathan , Regalado Ric , Zhou Jiayan , Notarte Kin , Lu Yu-Wei , Encarnacion Paolo , Carles Cidne , Octavo Edrian , Limbaroc Dan , Saengboonmee Charupong , Huang Shih-Yi
Published: October 2024

Background: Cancer remains a global health challenge, characterized not just by uncontrolled cell proliferation but also by the complex metabolic reprogramming that underlies its development and progression. Objectives: This review delves into the intricate relationship between cancer and its metabolic alterations, drawing an innovative comparison with the cosmological concepts of dark matter and dark energy to highlight the pivotal yet often overlooked role of metabolic reprogramming in tumor evolution. Methods: It scrutinizes the Warburg effect and other metabolic adaptations, such as shifts in lipid synthesis, amino acid turnover, and mitochondrial function, driven by mutations in key regulatory genes. Results: This review emphasizes the significance of targeting these metabolic pathways for therapeutic intervention, outlining the potential to disrupt cancer’s energy supply and signaling mechanisms. It calls for an interdisciplinary research approach to fully understand and exploit the intricacies of cancer metabolism, pointing toward metabolic reprogramming as a promising frontier for developing more effective cancer treatments. Conclusion: By equating cancer’s metabolic complexity with the enigmatic nature of dark matter and energy, this review underscores the critical need for innovative strategies in oncology, highlighting the importance of unveiling and targeting the “dark energy” within cancer cells to revolutionize future therapy and research.
Histologic Characterization of Tumor-Adjacent Mammary Adipose Tissue in Normal-Weight and Overweight/Obese Patients with Triple-Negative Breast Cancer
Authors: Wolf Marietta , Brochhausen Christoph , Ramakrishnan Vignesh , Iberl Sabine , Roth Jonas , Seitz Stephan , Burkhardt Ralph , Stadler Sonja C.
Published: October 2024

Background: Obesity is a risk factor of several types of cancer, including breast cancer. In this study, we aimed to histologically characterize the adipose tissue of the tumor microenvironment (TME) of triple-negative breast cancer (TNBC) in overweight/obese versus normal-weight patients. Methods: TNBC tissue sections from normal-weight (BMI<25) and overweight/obese patients (BMI≥25) were stained with antibodies against CD68, CD163, CD31, CD34, and vimentin. At the invasive tumor front, positive cells were counted in tumor adjacent adipose tissue (AT) and within cancer tissue (CT). Further, the size of the tumor-adjacent and distant mammary adipocytes was determined in perilipin stained sections. Expression of ANGPTL4, CD36 and FABP4, proteins involved in fatty acid metabolism, was analyzed in marginal tumor cells using an immune reactive score. Results: Overweight/obese TNBC patients had significantly larger adipocytes, higher numbers of CD163+ macrophages (BMI<25: 2.80 vs. BMI≥25: 10.45; p = 0.011) and lower numbers of CD31+ (BMI<25: 4.20 vs. BMI≥25: 2.40; p = 0.018) and CD34+ (BMI<25: 14.60 vs. BMI≥25: 5.20; p = 0.045) cells as markers of angiogenesis in the AT as well as a higher frequency of cancer-associated-fibroblast-like cells in the AT and CT (BMI<25: 7.60 vs. BMI≥25: 25.39 in total; p = 0.001). Moreover, expression of CD36 (BMI<25: 2.15 vs. BMI≥25: 2.60; p = 0.041) and ANGPTL4 (BMI<25: 6.00 vs. BMI≥25: 9.80; p = 0.026) was elevated in the TNBC cells of overweight/obese patients. Conclusions: Our data suggest BMI-related changes in the TME of overweight/obese TNBC patients, including hypertrophied adipocytes, reduced vascularization, more M2-like macrophages and CAF-like cells, and an increase in the expression of fatty acid metabolizing proteins in marginal tumor cells, all contributing to a more tumor-promoting, immunosuppressive environment.
Artificial Intelligence and Machine Learning in Ocular Oncology, Retinoblastoma (ArMOR): Experience with a Multiracial Cohort
Authors: Vempuluru Vijitha S. , Viriyala Rajiv , Ayyagari Virinchi , Bakal Komal , Bhamidipati Patanjali , Dhara Krishna Kishore , Ferenczy Sandor R. , Shields Carol L. , Kaliki Swathi
Published: October 2024

Background: The color variation in fundus images from differences in melanin concentrations across races can affect the accuracy of artificial intelligence and machine learning (AI/ML) models. Hence, we studied the performance of our AI model (with proven efficacy in an Asian-Indian cohort) in a multiracial cohort for detecting and classifying intraocular RB (iRB). Methods: Retrospective observational study. Results: Of 210 eyes, 153 (73%) belonged to White, 37 (18%) to African American, 9 (4%) to Asian, 6 (3%) to Hispanic races, based on the U.S. Office of Management and Budget’s Statistical Policy Directive No.15 and 5 (2%) had no reported race. Of the 2473 images in 210 eyes, 427 had no tumor, and 2046 had iRB. After training the AI model based on race, the sensitivity and specificity for detection of RB in 2473 images were 93% and 96%, respectively. The sensitivity and specificity of the AI model were 74% and 100% for group A; 88% and 96% for group B; 88% and 100% for group C; 73% and 98% for group D, and 100% and 92% for group E, respectively. Conclusions: The AI models built on a single race do not work well for other races. When retrained for different races, our model exhibited high sensitivity and specificity in detecting RB and classifying RB.
The Emerging Role of Phosphodiesterase 5 Inhibition in Neurological Disorders: The State of the Art
Authors: Crescioli Clara , Paronetto Maria Paola
Published: October 2024

Growing evidence suggests that neuroinflammation is not just a consequence of neurodegeneration in pathologies such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease or Amyotrophic lateral sclerosis, but it is rather a determinant factor, which plays a pivotal role in the onset and progression of these disorders. Neuroinflammation can affect cells and processes in the central nervous system (CNS) as well as immune cells, and might precede protein aggregation, which is a hallmark of the neurodegenerative process. Standard treatment methods are far from being able to counteract inflammation and delay neurodegeneration. Remarkably, phosphodiesterase 5 inhibitors (PDE5is), which represent potent vasoactive drugs used as a first-line treatment for erectile dysfunction (ED), display important anti-inflammatory effects through cyclic guanosine monophosphate (cGMP) level stabilization. Since PDE5 hydrolyzes cGMP, several studies positioned PDE5 as a therapeutic target, and more specifically, PDE5is as potential alternative strategies for the treatment of a variety of neurological disorders. Indeed, PDE5is can limit neuroinflammation and enhance synaptic plasticity, with beneficial effects on cognitive function and memory. The aim of this review is to provide an overview of some of the main processes underlying neuroinflammation and neurodegeneration which may be potential targets for PDE5is, focusing on sildenafil, the most extensively studied. Current strategies using PDEis for the treatment of neurodegenerative diseases will be summarized.