bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical Study on the Impact of Nonlinear Foundation Stiffness on Pavement Dynamic Response under Vehicle Action
Authors: Ouyang Lijun , Xiang Zhuoying , Zhen Bin , Yuan Weixin
Published: September 2024

This paper presents an analytical study of the dynamic responses in the vehicle–pavement–foundation system, where the vehicle is simplified to a two-degree-of-freedom system, the pavement is modeled using both Euler–Bernoulli (E-B) beam and Timoshenko beam with consideration of pavement roughness, and the subgrade is simulated with a Winkler foundation model featuring cubic nonlinear stiffness. The focus is on using approximate analytical solutions of pavement response to discuss the impact of nonlinear stiffness under various parameter conditions. In previous analytical studies of vehicle–pavement–foundation systems, vehicles were typically simplified to a constant moving force, leading to the conclusion that when the applied force is small, the impact of nonlinear stiffness on the pavement’s dynamic response is minimal; whereas when the force is large, the pavement response increases with the increase in nonlinear stiffness. In this study, the force exerted by the vehicle on the pavement is harmonic, and the impact of nonlinear stiffness on the pavement response is different and much more complex. The research finds that there is a critical value for nonlinear stiffness under the given vehicle parameter conditions: when the nonlinear stiffness is less than the critical value, it has almost no effect on the pavement response; when it exceeds the critical value, the pavement’s response first decreases and then increases with the increase in nonlinear stiffness. The critical value of nonlinear stiffness is not fixed and increases as the vehicle velocity and foundation damping. Moreover, an increase in nonlinear stiffness also causes an increase in the offset between the wheel position and the position of maximum pavement deformation. Under the same parameter conditions, the offset in the E-B beam is significantly greater than that in the Timoshenko beam. Our study’s results enhance the understanding of the nonlinear dynamics within the vehicle–pavement interaction.
Analysis of the Spanish Auditory Test of Speech in Noise (PAHRE) in a Population with Hearing Loss
Authors: Rodríguez-Ferreiro Marlene , Durán-Bouza Montserrat , Marrero-Aguiar Victoria
Published: September 2024

Background: Speech recognition in noise is one of the difficulties faced by people with hearing loss that increases with age. The recently developed Spanish Auditory Test of Speech in Noise (Prueba Auditiva de Habla en Ruido en Español, PAHRE) allows for the identification of these intelligibility difficulties in noise. The aim of this study was to assess speech recognition in noise in people with hearing loss and to test the benefits of the Lombard effect. Methods: The participants were 104 people with hearing difficulties, ranging in age from 37 to 98 years. The variables age, degree of hearing loss, presence of high-frequency dropout, and years of formal education were assessed. Results: Psychometric curves were obtained as a function of signal-to-noise ratio as well as threshold values of speech reception as a function of age group for mild and moderate hearing loss. The results indicated that the speech reception threshold increased with both age and the degree of hearing loss, becoming particularly significant after the age of 70. Furthermore, it was found that the combined factors of age, degree of hearing loss, and educational level predicted a high percentage of the variability in the speech reception threshold. Conclusions: Therefore, the Spanish Auditory Test of Speech in Noise could be a useful clinical tool for diagnosis, monitoring, auditory rehabilitation planning, and hearing aid fitting.
The Bundle of Tensor Densities and Its Covariant Derivatives
Authors: Grandes Umbert Joan , Mestdag Tom
Published: September 2024

We construct the smooth vector bundle of tensor densities of arbitrary weight in a coordinate-independent way. We prove the general existence of a globally smooth tensor density field, as well as the existence of a globally smooth metric density for a pseudo-Riemannian manifold, specifically. We study the coordinate description of a covariant derivative over densities, and define a natural extension of affine connections to densities. We provide an equivalent characterization, in the case of a pseudo-Riemannian manifold.
Contemporary Update on Clinical and Experimental Prostate Cancer Biomarkers: A Multi-Omics-Focused Approach to Detection and Risk Stratification
Authors: Hachem Sana , Yehya Amani , El Masri Jad , Mavingire Nicole , Johnson Jabril R. , Dwead Abdulrahman M. , Kattour Naim , Bouchi Yazan , Kobeissy Firas , Rais-Bahrami Soroush , Mechref Yehia , Abou-Kheir Wassim , Woods-Burnham Leanne
Published: September 2024

Prostate cancer remains a significant health challenge, being the most prevalent non-cutaneous cancer in men worldwide. This review discusses the critical advancements in biomarker discovery using single-omics and multi-omics approaches. Multi-omics, integrating genomic, transcriptomic, proteomic, metabolomic, and epigenomic data, offers a comprehensive understanding of the molecular heterogeneity of prostate cancer, leading to the identification of novel biomarkers and therapeutic targets. This holistic approach not only enhances the specificity and sensitivity of prostate cancer detection but also supports the development of personalized treatment strategies. Key studies highlighted include the identification of novel genes, genetic mutations, peptides, metabolites, and potential biomarkers through multi-omics analyses, which have shown promise in improving prostate cancer management. The integration of multi-omics in clinical practice can potentially revolutionize prostate cancer prognosis and treatment, paving the way for precision medicine. This review underscores the importance of continued research and the application of multi-omics to overcome current challenges in prostate cancer diagnosis and therapy.
T Cell Peptide Prediction, Immune Response, and Host–Pathogen Relationship in Vaccinated and Recovered from Mild COVID-19 Subjects
Authors: Macchia Iole , La Sorsa Valentina , Ciervo Alessandra , Ruspantini Irene , Negri Donatella , Borghi Martina , De Angelis Maria Laura , Luciani Francesca , Martina Antonio , Taglieri Silvia , Durastanti Valentina , Altavista Maria Concetta , Urbani Francesca , Mancini Fabiola
Published: September 2024

COVID-19 remains a significant threat, particularly to vulnerable populations. The emergence of new variants necessitates the development of treatments and vaccines that induce both humoral and cellular immunity. This study aimed to identify potentially immunogenic SARS-CoV-2 peptides and to explore the intricate host–pathogen interactions involving peripheral immune responses, memory profiles, and various demographic, clinical, and lifestyle factors. Using in silico and experimental methods, we identified several CD8-restricted SARS-CoV-2 peptides that are either poorly studied or have previously unreported immunogenicity: fifteen from the Spike and three each from non-structural proteins Nsp1-2-3-16. A Spike peptide, LA-9, demonstrated a 57% response rate in ELISpot assays using PBMCs from 14 HLA-A*02:01 positive, vaccinated, and mild-COVID-19 recovered subjects, indicating its potential for diagnostics, research, and multi-epitope vaccine platforms. We also found that younger individuals, with fewer vaccine doses and longer intervals since infection, showed lower anti-Spike (ELISA) and anti-Wuhan neutralizing antibodies (pseudovirus assay), higher naïve T cells, and lower central memory, effector memory, and CD4hiCD8low T cells (flow cytometry) compared to older subjects. In our cohort, a higher prevalence of Vδ2-γδ and DN T cells, and fewer naïve CD8 T cells, seemed to correlate with strong cellular and lower anti-NP antibody responses and to associate with Omicron infection, absence of confusional state, and habitual sporting activity.
COVID-19 and Human Touch, Two Sides of the Same Coin: An Opinion Article about Touch Deprivation and Future Directions
Authors: Grandi Laura Clara , Bruni Stefania
Published: September 2024

Background. The COVID-19 pandemic introduced unprecedented social distancing measures, resulting in significant deprivation of physical contact. Objective. This opinion article explores the implications of this tactile deprivation on psychological well-being, emphasizing its impact on emotional and cognitive development. Physical contact, particularly social touch mediated by C-tactile fibers, is essential for emotional stability and social bonding. Methods. Drawing on evidence from studies on orphaned children and primates, this opinion article argues for the critical importance of reintroducing physical contact to support mental health. Results. The pandemic’s reduction in physical touch has been associated with increased anxiety, depression, and stress, with notable declines in mood and heightened loneliness. Conclusions. While alternative methods such as virtual reality offer temporary solutions, the article stresses the need for safe, physical interactions as restrictions ease. Future discourse should focus on the long-term effects of touch deprivation and explore effective strategies for mitigating its impacts in similar scenarios.
The Kynurenine Pathway, Aryl Hydrocarbon Receptor, and Alzheimer’s Disease
Authors: Cortés Malagón Enoc Mariano , López Ornelas Adolfo , Olvera Gómez Irlanda , Bonilla Delgado José
Published: September 2024

Alzheimer’s disease (AD) is the leading cause of dementia, mainly affecting elderly individuals. AD is characterized by β-amyloid plaques, abnormal tau tangles, neuronal loss, and metabolic disruptions. Recent studies have revealed the involvement of the kynurenine (KP) pathway and the aryl hydrocarbon receptor (AhR) in AD development. The KP pathway metabolizes tryptophan to produce neuroactive substances like kynurenine, kynurenic acid, and quinolinic acid. In AD, high levels of kynurenine and the neurotoxic quinolinic acid are associated with increased neuroinflammation and excitotoxicity; conversely, reduced levels of kynurenic acid, which acts as a glutamate receptor antagonist, compromise neuroprotection. Research has indicated elevated KP metabolites and enzymes in the hippocampus of AD patients and other tissues such as blood, cerebrospinal fluid, and urine. However, the finding that KP metabolites are AD biomarkers in blood, cerebrospinal fluid, and urine has been controversial. This controversy, stemming from the lack of consideration of the specific stage of AD, details of the patient’s treatment, cognitive deficits, and psychiatric comorbidities, underscores the need for more comprehensive research. AhR, a ligand-activated transcription factor, regulates immune response, oxidative stress, and xenobiotic metabolism. Various ligands, including tryptophan metabolites, can activate it. Some studies suggest that AhR activation contributes to AD, while others propose that it provides neuroprotection. This discrepancy may be explained by the specific ligands that activate AhR, highlighting the complex relationship between the KP pathway, AhR activation, and AD, where the same pathway can produce both neuroprotective and harmful effects.
Subcortical Change and Neurohabilitation Treatment Adherence Effects in Extremely Preterm Children
Authors: Castro-Chavira Susana A. , Gutiérrez-Hernández Claudia C. , Carrillo-Prado Cristina , Harmony Thalía
Published: September 2024

Extremely preterm birth entails an increased risk for multimorbidity and the prevalence of developmental deficits because this risk is negatively correlated to the number of gestation weeks. This work evaluated subcortical volume changes in children born extremely preterm who received Katona neurohabilitation, as well as the effects of subcortical volume and treatment adherence on their three-year-old neurodevelopment outcomes. Fifteen extremely preterm-born participants were treated from two months to two years old and followed up until past three years of age. The participants received Katona neurohabilitation, which provides vestibular and proprioceptive stimulation and promotes movement integration through the early, intensive practice of human-specific elementary movements. Subcortical brain volumes from magnetic resonance images were obtained at the beginning and after treatment. Also, treatment adherence to Katona neurohabilitation and neurodevelopment outcomes were measured. The results showed that absolute subcortical volumes increased after treatment; however, when adjusted by intracranial volume, these volumes decreased. Subcortical function inhibition allows cortical control and increased connectivity, which may explain decreased adjusted volume. Regression analyses showed that after-treatment hippocampal volumes had a discrete predictive value. However, treatment adherence showed a clear effect on mental and psychomotor neurodevelopment. Thus, the effectiveness of Katona neurohabilitation is constrained by treatment adherence.
Correction: Tiwari et al. Neuroprotective Effect of α-Mangostin in Ameliorating Propionic Acid-Induced Experimental Model of Autism in Wistar Rats. Brain Sci. 2021, 11, 288
Authors: Tiwari Aarti , Khera Rishabh , Rahi Saloni , Mehan Sidharth , Makeen Hafiz Antar , Khormi Yahya H. , Rehman Muneeb U , Khan Andleeb
Published: September 2024

Missing Supplementary Materials: [...]
Double-Edged Effects of Social Strategies on the Well-Being of Autistic People: Impact of Self-Perceived Effort and Efficacy
Authors: Funawatari Ren , Sumiya Motofumi , Iwabuchi Toshiki , Senju Atsushi
Published: September 2024

Background/Objectives: Autistic people employ various social strategies to form and maintain interpersonal relationships in their daily environments. These strategies can help autistic people with social interactions (leading to self-perceived efficacy of using social strategies), but can also lead to cognitive fatigue (self-perceived effort of using social strategies). However, previous studies have focused primarily on self-perceived effort, overlooking the self-perceived efficacy of using social strategies, and the balance between self-perceived effort and efficacy. To address this gap, this study examined the impact of autistic people’s use of social strategies on their well-being, focusing on self-perceived effort, self-perceived efficacy, and their interaction effect. Methods: An online survey was conducted among self-reported autistic people in Japan aged 18–65 years, using a modified Compensation Checklist. Data from 104 self-reported autistic participants were analyzed using linear regression. Results: High self-perceived effort in using social strategies was negatively associated with well-being, whereas high self-perceived efficacy was positively associated with well-being. The interaction effect between effort and efficacy was not significant. These results were supported even when loneliness was used as an index of social well-being. Additionally, the number of strategies used by an autistic person was positively associated with well-being. Conclusions: This study highlights the double-edged effect of autistic people using social strategies, and that using a broader repertoire of social strategies may improve the well-being of autistic people. These findings call for a nuanced approach by researchers and clinicians considering both the positive and negative aspects of using social strategies.
The Impact of Diglossia on Executive Functions and on Reading in Arabic
Authors: Ibrahim Raphiq
Published: September 2024

Background: In contrast to most other languages, where the spoken and written words are similar, children that have mastered Spoken Arabic (SA) learn to read a new written form of Arabic usually called Literary Arabic (LA). This phenomenon is called “diglossia”. Methods: Based on a series of studies comparing monolingual Arabic speaking and bilingual children, it has been suggested that Arabic speaking individuals develop metacognitive abilities that are considered bilinguals de facto. Some of the cognitive functions that would seem to benefit from fluency in more than one language are metalinguistic and metacognitive awareness. Results: This review article summarizes the results of studies on the relationship between bilingualism, diglossia and executive functions (EFs) which involve metacognitive awareness, selective attention, control of inhibition and cognitive flexibility as well as working memory (phonemic manipulation and metalingual performances). Conclusions: The findings are in line with research results that have shown that bilingualism has a positive effect on the functioning of an individual’s attentional system across the lifespan. The neural basis of diglossia in Arabic, as well as the conclusions and implications drawn from the impact of diglossia on EF and on reading in Arabic, are discussed.
Social Media Use and Academic Performance in Chinese Children and Adolescents: A Moderated Chain Mediation Model
Authors: Hou Yu , Qin Chuting , Xu Peng
Published: September 2024

Based on data from the 2022 Chinese Minors’ Digital Life and Online Protection Survey, this study investigated the status quo of social media use and its influencing mechanism on academic performance among Chinese children and adolescents. The statistical results indicate that the average level of Chinese students’ social media use was generally low, with their academic performance varying across socio-demographic and schooling characteristics. After controlling for other variables, it was found that the frequency of social media use could exert a significant positive impact on students’ academic performance. Moreover, the mechanism analysis revealed that online learning behavior and prosocial behavior served as chain mediators linking social media use to academic performance. Specifically, students could transfer their social media behavioral patterns to the internet-based learning context, and then effectively utilize remote learning resources. Meanwhile, engagement with social media would cultivate individuals’ prosocial personality, thereby stimulating intrinsic motivation for learning and ultimately enhancing academic performance. The heterogeneity analysis further confirmed that the impact of social media use on students’ academic performance was stronger in lower-class families, underscoring the moderating role of family socioeconomic status in the relationship between social media use and academic performance. The findings suggest that if academic performance is regarded as an integral part of individual capacity development, then the rational utilization of social media resources might be a pivotal approach to alleviate the predicament of developmental inequality faced by students from low socioeconomic backgrounds.
A Novel Data Analytics Methodology for Analyzing Real Estate Brokerage Markets with Case Study of Dubai
Authors: Al Abdulsalam Ahmed Saif , Al Hashemi Maged Mohammed Al-Baiti , Aleissaee Mohammed Zayed Sulaiman , Almansoori Abdelaziz Saleh Husain , Ertek Gurdal , Labben Thouraya Gherissi
Published: September 2024

Despite the vast economic impact of real estate markets worldwide, research on real estate brokerage markets remains limited. Specifically, there are few studies that provide a systematic, integrated, and replicable analytical methodology to analyze and benchmark a given real estate brokerage market. To this end, this paper introduces a data analytics methodology for analyzing real estate brokerage markets, integrating various statistical and analytical methods to extract insights from market data, supporting real estate investment decisions. The applicability of the methodology is demonstrated with a case study analyzing data from the top 50 real estate brokerage firms in Dubai, UAE. As shown in the case study, applying this methodology to brokerage market data enables the visual benchmarking of firms, identification of similarities between them, profiling and comparison of clusters of firms, and exploration of the impacts of various categorical and numerical attributes on performance. A notable finding for the Dubai real estate brokerage market is that it takes a minimum of 700 days for a brokerage firm to mature and advance to the next level of business success.
Analyzing the Impact of Deep Excavation on Retaining Structure Deformation Based on Element Tracking
Authors: Tan Wen , Lei Zhenyu , Wang Yanhong , Liu Jinsong , Lai Pengbang , Mei Yuan , Liu Wenzhan , Zhou Dongbo
Published: September 2024

In the simulation of foundation pit excavation, the traditional element birth–death method commonly used tends to encounter issues such as uncoordinated deformation and changes in the constitutive model, affecting the accuracy of the prediction results. To address these issues, this study proposes the use of element tracking. By duplicating elements for temporary supports or structures requiring changes in material properties and appropriately activating or deactivating them at the right moments, the simulation of the foundation pit excavation process can be achieved more precisely. Using the construction process of the Tangxi Passenger Transport Station’s comprehensive transportation hub foundation pit as an example, this study applied the proposed simulation method and compared the results with actual measurements, demonstrating its effectiveness. This research offers a more accurate approach for simulating foundation pit excavation and provides a reference for similar numerical simulation problems.
Evaluating the Flexural Performance of Sintered Sludge Ash-Modified Cement Paste Using Surface Cracks and Fracture Toughness
Authors: He Zhengfeng , Wu Zhuofan , Liu Jian , Wang Qi , Zhuang Liling , Wang Shumin , Zhao Qingxin
Published: September 2024

Sintered sludge ash (SSA) represents a promising alternative to traditional cement, offering a potential pathway for reducing carbon emissions. This study examined the flexural performance of SSA-modified cement paste (SSC paste) at varying SSA proportions (S0 (0%), S1 (5%), S2 (15%), and S3 (25%)) and employed innovative digital image correlation (DIC) technology to track the evolution of surface cracks during flexural strength testing. Furthermore, Griffith’s theory of fracture toughness was employed to evaluate the fracture performance of SSC paste. The observations of flexural strength at 3, 7, and 28 days indicated that the content of SSA had an adverse effect on flexural performance. Furthermore, the monitoring of cracks confirmed the practicality of DIC in evaluating flexural properties. The analysis of maximum strain and crack propagation via DIC revealed a distinct trend: the presence of 5% SSA inhibited crack propagation and enhanced flexural ductility, whereas the presence of 25% SSA produced the opposite effect. This was corroborated by fracture toughness calculations based on Griffith’s theory. It is noteworthy that 15% SSA represented a critical threshold that delineated variations in flexural strength, ductility, and fracture toughness, which may be linked to the Ca/Si and Ca/Al ratios in the composite matrix. This study demonstrates the innovative application of digital image correlation (DIC) in the monitoring of crack behavior and offers new insights into the crucial proportion of SSA that affects the mechanical properties of SSC paste.
Interface Fatigue Test of Hybrid-Bonded Fiber-Reinforced Plastic-Reinforced Concrete Specimen
Authors: Zhou Kun , Wei Qian , Wang Jiabin , Gao Lei , Dong Chao , Zhang Zejun , Fu Kunhao , Cheng Ziqin
Published: September 2024

This research produced five hybrid-bonded fiber-reinforced plastic (HB-FRP)-reinforced beam specimens, and different fatigue load amplitudes were used as parameter variables for the fatigue performance tests of the FRP–concrete interface. The results show that FRP sliding with the number of cycles can be roughly divided into fatigue initiation stage, fatigue development stage, and fatigue damage stage, and finally, because the load is too large and friction, pin, and bonding cannot provide a greater inhibition effect, FRP adhesive length is not enough to withstand the stripping load and failure. FRP slip increases with increasing fatigue load amplitude for the same number of fatigue cycles; for the specimens with fatigue damage, the interfacial stiffness of FRP–concrete decreases with the increase in the number of cyclic, and the rate of stiffness damage at the FRP–concrete interface accelerates with increasing fatigue load amplitude. For fatigue load magnitudes higher than 0.6, the slopes of fatigue bond–slip curves decrease with the increase in the number of cycles. When the fatigue load magnitude is lower than 0.4, the slope of the fatigue bond–slip curve increases with the number of cycles and is close to the slope of the monotonically loaded curve. Due to the difference in load class, the bond strength of HB-F-1 continues to decrease with the increase in fatigue times, decreasing by 26% after 100 fatigue cycles and decreasing to 7.33 MPa after 5000 fatigue cycles. The bond strength of the sample HB-F-2 first increased and then decreased with the increase in fatigue times. After 10,000 fatigue cycles, the bond strength decreased by 8%, and at 11,133,300 fatigue breaks, the bond strength of the sample HB-F-3 continued to increase with the increase in fatigue times. At 2 million fatigue load cycles, the bond strength increased to 7 MPa, far from reaching the peak strength. The empirical formulas for the fatigue life curve of HB-FRP-reinforced specimens under single steel fasteners are proposed.
Analysis of Factors Influencing the Low-Temperature Behavior of Recycled Asphalt Mixtures in Seasonal Freeze-Thaw Regions
Authors: Wang Shujian , Wu Chuanshan , Zhao Yongli , Su Zhikai , Su Gang , Tang Dong , Yang Tao
Published: September 2024

The use of recycled asphalt mixtures in regions with seasonal freeze-thaw cycles is becoming more popular. However, strict requirements for low-temperature cracking resistance limit their widespread application. This study designed thirteen types of recycled asphalt mixtures to explore factors affecting low-temperature performance in seasonal freeze-thaw regions and potential optimization methods. The three-point bending test assessed the low-temperature cracking performance of mixtures with varying recycled asphalt pavement (RAP) content, asphalt-aggregate ratios, asphalt types, and gradations under both conventional and freeze-thaw conditions. Results show that destructive strain and fracture energy decrease with higher RAP content, but increase with higher asphalt-aggregate ratios and 4.75 mm sieve passing rates. Adding rubber powder significantly enhances both destructive strain and fracture energy. Furthermore, the destructive strain remains insensitive to factors under both and freeze-thaw conditions, while fracture energy effectively distinguishes differences in low-temperature crack resistance. Analysis of variance reveals that RAP content, asphalt-aggregate ratio, asphalt type, and gradation significantly affect fracture energy after freeze-thaw cycles. Optimizing gradation is recommended to improve low-temperature performance of recycled asphalt mixtures in freeze-thaw regions.
Research on Summer Hourly Climate-Influencing Factors in Suburban Areas of Cities in CFA Zone—Taking Chengdu, China as an Example
Authors: Sima Lei , Liu Yisha , Zhang Jian , Shang Xiaowei
Published: September 2024

Elevated temperatures in urban centers have become a common problem in cities around the world. However, the climate problems in suburban areas are equally severe; there is an urgent need to find zero-carbon ways to mitigate this problem. Recent studies have revealed the thermal performance of vegetation, buildings, and water surfaces. They functioned differently regarding the climate at different periods of the day. Accordingly, this study synthesizes remote sensing technology and meteorology station observation data to deeply explore the differences in the role of each climate-influencing factor in the suburban areas of Chengdu. The land surface temperature (LST) and air temperature (Ta) were used as thermal environmental indicators, while the normalized difference vegetation index (NDVI), normalized difference water index (NDWI), normalized difference built-up index (NDBI), and altitude were used as environmental factors. The results showed that the relevant influences of the environmental factors on the climate in the sample areas were significantly affected by the time of the day. The NDVI (R2 = 0.5884), NDBI (R2 = 0.3012), and altitude (R2 = 0.5638) all showed strong correlations with Ta during the night (20:00–7:00), which gradually weakened after sunrise, yet the NDWI showed a poorer cooling effect during the night, which gradually strengthened after sunrise, reaching a maximum at 15:00 (R2 = 0.5012). One reason for this phenomenon was the daily weather changes. These findings facilitate the advancement of the understanding of the climate in suburban areas and provide clear directions for further thermal services targeted towards people in different urban areas.
Menopausal Hormone Therapy in Breast Cancer Survivors
Authors: Culhane Rose , Zaborowski Alexandra M. , Hill Arnold D. K.
Published: September 2024

Menopausal symptoms negatively impact quality of life in breast cancer survivors. The paucity of data on the impact of Menopausal Hormone Therapy (MHT) on oncological outcomes in these patients limits informed clinical discussion. Defining the risk of cancer recurrence with MHT is central to the appraisal of risk/benefit, particularly with low-risk disease (based on genomic profile). The aim of this review is to summarize the current data evaluating MHT in breast cancer patients. A systematic review of the literature was performed to evaluate the impact of MHT on oncological outcomes in breast cancer survivors. Three major databases (PubMed, EMBASE and Medline) were searched. The review included all prospective studies published in English. Four randomized control trials and four non-randomized prospective studies were identified. An increase in breast cancer recurrence with MHT was observed in the early randomized trials whilst no increased risk of recurrence was reported in the observational studies. There remains a need to quantify MHT-related recurrence risk in patients with molecularly favorable disease.
Autophagy Blockage Up-Regulates HLA-Class-I Molecule Expression in Lung Cancer and Enhances Anti-PD-L1 Immunotherapy Efficacy
Authors: Xanthopoulou Erasmia , Lamprou Ioannis , Mitrakas Achilleas G. , Michos Georgios D. , Zois Christos E. , Giatromanolaki Alexandra , Harris Adrian L. , Koukourakis Michael I.
Published: September 2024

Background/Objectives: Immune checkpoint inhibitors have an established role in non-small cell lung cancer (NSCLC) therapy. The loss of HLA-class-I expression allows cancer cell evasion from immune surveillance, disease progression, and failure of immunotherapy. The restoration of HLA-class-I expression may prove to be a game-changer in current immunotherapy strategies. Autophagic activity has been recently postulated to repress HLA-class-I expression in cancer cells. Methods: NSCLC cell lines (A549 and H1299) underwent late-stage (chloroquine and bafilomycin) and early-stage autophagy blockage (ULK1 inhibitors and MAP1LC3A silencing). The HLA-class-I expression was assessed with flow cytometry, a Western blot, and RT-PCR. NSCLC tissues were examined for MAP1LC3A and HLA-class-I expression using double immunohistochemistry. CD8+ T-cell cytotoxicity was examined in cancer cells pre-incubated with chloroquine and anti-PD-L1 monoclonal antibodies (Moabs); Results: A striking increase in HLA-class-I expression following incubation with chloroquine, bafilomycin, and IFNγ was noted in A549 and H1299 cancer cells, respectively. This effect was further confirmed in CD133+ cancer stem cells. HLA-class-I, β2-microglobulin, and TAP1 mRNA levels remained stable. Prolonged exposure to chloroquine further enhanced HLA-class-I expression. Similar results were noted following exposure to a ULK1 and a PIKfyve inhibitor. Permanent silencing of the MAP1LC3A gene resulted in enhanced HLA-class-I expression. In immunohistochemistry experiments, double LC3A+/HLA-class-I expression was seldom. Pre-incubation of H1299 cancer cells with chloroquine and anti-PD-L1 MoAbs increased the mean % of apoptotic/necrotic cells from 2.5% to 18.4%; Conclusions: Autophagy blockers acting either at late or early stages of the autophagic process may restore HLA-class-I-mediated antigen presentation, eventually leading to enhanced immunotherapy efficacy.
Barriers to T Cell Functionality in the Glioblastoma Microenvironment
Authors: Nader Noor E. , Frederico Stephen C. , Miller Tracy , Huq Sakibul , Zhang Xiaoran , Kohanbash Gary , Hadjipanayis Constantinos G.
Published: September 2024

Glioblastoma (GBM) is an aggressive primary brain tumor depicted by a cold tumor microenvironment, low immunogenicity, and limited effective therapeutic interventions. Its location in the brain, a highly immune-selective organ, acts as a barrier, limiting immune access and promoting GBM dissemination, despite therapeutic interventions. Currently, chemotherapy and radiation combined with surgical resection are the standard of care for GBM treatment. Although immune checkpoint blockade has revolutionized the treatment of solid tumors, its observed success in extracranial tumors has not translated into a significant survival benefit for GBM patients. To develop effective immunotherapies for GBM, it is vital to tailor treatments to overcome the numerous immunosuppressive barriers that inhibit T cell responses to these tumors. In this review, we address the unique physical and immunological barriers that make GBM challenging to treat. Additionally, we explore potential therapeutic mechanisms, studied in central nervous system (CNS) and non-CNS cancers, that may overcome these barriers. Furthermore, we examine current and promising immunotherapy clinical trials and immunotherapeutic interventions for GBM. By highlighting the array of challenges T cell-based therapies face in GBM, we hope this review can guide investigators as they develop future immunotherapies for this highly aggressive malignancy.
Investigation of the Performances of TiO2 and Pd@TiO2 in Photocatalytic Hydrogen Evolution and Hydrogenation of Acetylenic Compounds for Application in Photocatalytic Transfer Hydrogenation
Authors: Talgatov Eldar T. , Naizabayev Akzhol A. , Kenzheyeva Alima M. , Myltykbayeva Zhannur K. , Koca Atıf , Bukharbayeva Farida U. , Akhmetova Sandugash N. , Yersaiyn Raiymbek , Auyezkhanova Assemgul S.
Published: September 2024

The development of effective bifunctional catalysts demonstrating high performance in both photocatalytic hydrogen evolution and selective hydrogenation of unsaturated compounds is of great interest for photocatalytic transfer hydrogenation. In this work, TiO2 and Pd@TiO2 catalysts were studied in two separate processes: photocatalytic H2 evolution and conventional hydrogenation reactions. Photocatalytic properties of titanium dioxide synthesized by a simple precipitation method were compared with those of commercial ones. Commercial anatase with a lower agglomeration degree showed better activity in H2 evolution. Further modification of the commercial anatase with Pd resulted in increasing its activity, achieving an H2 evolution rate of 760 μmol/h gcat. The Pd catalysts supported on different TiO2 samples were tested in hydrogenation of acetylenic compounds. The activity of the Pd@TiO2 catalysts was found to be dependent on the photocatalytic properties of TiO2 supports. XPS studies of Pd catalysts indicated that commercial anatase with better photocatalytic properties provided easier reduction of Pd2+ to active Pd0 particles. The Pd catalyst supported on commercial anatase demonstrated the highest activity in the hydrogenation process. The WC≡C rate achieved 2.6 × 10−6, 9.0 × 10−6 and 35.7 × 10−6 mol/s for hydrogenation of 2-hexyne-1-ol, 5-hexyne-1-ol and 2-hexyne, respectively. The selectivity of the catalyst to target olefinic compounds was 94–96%. In addition, the hydrogenation rate was found to be significantly affected by reaction conditions such as hydrogen concentration and solvent composition. The WC≡C rate decreased linearly with decreasing hydrogen concentration in a H2:He gas mixture (30–100 vol%). Performing the reaction in 0.10 M NaOH ethanolic solution resulted in increasing the WC≡C rate and selectivity of the process. The Pd catalyst was reused in an alkali medium (NaOH in ethanol) for 35 runs without significant degradation in its catalytic activity. Thus, the results obtained in this work can be useful in photocatalytic transfer hydrogenation.
Therapeutic Effect of Boron Neutron Capture Therapy on Boronophenylalanine Administration via Cerebrospinal Fluid Circulation in Glioma Rat Models
Authors: Kusaka Sachie , Voulgaris Nikolaos , Onishi Kazuki , Ueda Junpei , Saito Shigeyoshi , Tamaki Shingo , Murata Isao , Takata Takushi , Suzuki Minoru
Published: September 2024

In recent years, various drug delivery systems circumventing the blood–brain barrier have emerged for treating brain tumors. This study aimed to improve the efficacy of brain tumor treatment in boron neutron capture therapy (BNCT) using cerebrospinal fluid (CSF) circulation to deliver boronophenylalanine (BPA) to targeted tumors. Previous experiments have demonstrated that boron accumulation in the brain cells of normal rats remains comparable to that after intravenous (IV) administration, despite BPA being administered via CSF at significantly lower doses (approximately 1/90 of IV doses). Based on these findings, BNCT was conducted on glioma model rats at the Kyoto University Research Reactor Institute (KUR), with BPA administered via CSF. This method involved implanting C6 cells into the brains of 8-week-old Wistar rats, followed by administering BPA and neutron irradiation after a 10-day period. In this study, the rats were divided into four groups: one receiving CSF administration, another receiving IV administration, and two control groups without BPA administration, with one subjected to neutron irradiation and the other not. In the CSF administration group, BPA was infused from the cisterna magna at 8 mg/kg/h for 2 h, while in the IV administration group, BPA was intravenously administered at 350 mg/kg via the tail vein over 1.5 h. Thermal neutron irradiation (5 MW) for 20 min, with an average fluence of 3.8 × 1012/cm2, was conducted at KUR’s heavy water neutron irradiation facility. Subsequently, all of the rats were monitored under identical conditions for 7 days, with pre- and post-irradiation tumor size assessed through MRI and pathological examination. The results indicate a remarkable therapeutic efficacy in both BPA-administered groups (CSF and IV). Notably, the rats treated with CSF administration exhibited diminished BPA accumulation in normal tissue compared to those treated with IV administration, alongside maintaining excellent overall health. Thus, CSF-based BPA administration holds promise as a novel drug delivery mechanism in BNCT.
Investigation of Whitening Mechanism on Cultural Relic Surfaces Treated with Paraloid B72
Authors: Zhao Xing , Li Xia , Zhang Siyu , Niu Qing , Li Zongmin , Xue Cheng
Published: September 2024

In the conservation of cultural relics, the application of Paraloid B72 in humid environments frequently results in the surface whitening of artifacts, which impairs their appearance and conceals important details. This study investigates the mechanisms underlying this phenomenon by examining the effect of ambient humidity, Paraloid B72 mass concentration, solution addition volume, and solvent type. To evaluate the microstructure, transmittance, and composition of the films, a range of analytical techniques were employed, including optical microscopy, scanning electron microscopy, a UV-Visible Spectrophotometer, and Fourier transform infrared spectroscopy. The findings indicate that higher ambient humidity, lower Paraloid B72 mass concentration, smaller solution addition volume, and solvents with higher volatility and water miscibility increase water content during curing, intensifying the whitening effect. These factors modify the interaction between water and solvent, altering the surface structure of Paraloid B72. The whitening mechanism is linked to the cooling effect of solvent volatility, which lowers the dew point temperature at the air–solution interface, causing moisture condensation. Moisture forms droplets that leave irregular pores upon volatility, resulting in surface roughness, optical heterogeneity, and a reduced refractive index, resulting in whitening. This study provides a theoretical basis for understanding and preventing the whitening of Paraloid B72.
An Ecomorphological Description of Amblyraja radiata (Rajiformes: Rajidae) in Waters of Eastern Canada
Authors: Kulka David W. , Miri Carolyn M. , Atchison Sheila , Simpson Mark R.
Published: September 2024

We examine the distribution, habitat association, morphometrics, meristics, and reproductive attributes of Amblyraja radiata over much of its Canadian range, Grand Banks to Arctic waters. It is distributed widely on the shelf and upper slope between 30 and 1288 m, reaching highest density in 100–400 m and occupying most available temperatures, between −1.0 and 8.8 °C, but concentrating in 1.6–3.5 °C. The maximum (and average) size decreases with increasing latitude in a continuum from 102 cm (55 cm) in the south, to 45 cm (20 cm) in the north. The proportion of mature fish increases with depth (40% at 0–50 m to 80% at 1150–1200 m) and temperature (35% at <0 °C to 55% at 5+ °C). The size at maturity decreases south to north; size at onset of maturity in males—43 (south) to 19 (north) cm, in females—49 to 23 cm; length at 50% maturity in males—74 to 44 cm, in females—66 to 40 cm. A. radiata maturity is also reflected in the rapid increase in the size of secondary sexual characteristics. Some meristics were consistent over the entire study area (spines near the spiracles and shoulders) while others varied with latitude (teeth rows, midline spines, spines near the eyes, % dorsal fins joined, spines between dorsal fins) or by fish length/maturity; the tail length/total length as a proportion of total length decreased during Stage 1 then increased at onset of maturity.
A Comprehensive Approach to the Diagnosis of Leigh Syndrome Spectrum
Authors: Baldo Manuela Schubert , Azevedo Luísa , Coelho Margarida Paiva , Martins Esmeralda , Vilarinho Laura
Published: September 2024

Background: Leigh syndrome spectrum (LSS) is a novel nomenclature that encompasses both classical Leigh syndrome and Leigh-like phenotypes. Given the heterogeneity of disease presentation, a new consensus published recently addressed the main issues and proposed general guidelines towards diagnosis. Based on these recommendations, we developed a simple pipeline that can be useful in the diagnosis of LSS. Methods: We combined previously published criteria with our own experience to achieve a diagnostic framework that can provide faster satisfactory results with fewer resources. Results: We suggest adding basic biochemical tests for amino acids, acylcarnitine, and urinary organic acids as parallel investigations, as these results can be obtained in a short time. This approach characterized 80% of our cohort and promoted specific intervention in 10% of confirmed cases. Conclusions: Genetic studies are crucial in the diagnosis of LSS, but they are time-consuming and might delay tailored interventions. Therefore, we suggest adding more affordable and less complex biochemical studies as primary tests when investigating treatable causes of LSS.
Diagnosis Based on Population Data versus Personalized Data: The Evolving Paradigm in Laboratory Medicine
Authors: Coskun Abdurrahman
Published: September 2024

The diagnosis of diseases is a complex process involving the integration of multiple parameters obtained from various sources, including laboratory findings. The interpretation of laboratory data is inherently comparative, necessitating reliable references for accurate assessment. Different types of references, such as reference intervals, decision limits, action limits, and reference change values, are essential tools in the interpretation of laboratory data. Although these references are used to interpret individual laboratory data, they are typically derived from population data, which raises concerns about their reliability and consequently the accuracy of interpretation of individuals’ laboratory data. The accuracy of diagnosis is critical to all subsequent steps in medical practice, making the estimate of reliable references a priority. For more precise interpretation, references should ideally be derived from an individual’s own data rather than from population averages. This manuscript summarizes the current sources of references used in laboratory data interpretation, examines the references themselves, and discusses the transition from population-based laboratory medicine to personalized laboratory medicine.
Integrating Genetic Alterations and Histopathological Features for Enhanced Risk Stratification in Non-Muscle-Invasive Bladder Cancer
Authors: Lillesand Melinda , Kvikstad Vebjørn , Gudlaugsson Einar , Skaland Ivar , Slewa Johannessen Aida , Nigatu Tesfahun Almaz , Sperstad Sigmund Vegard , Janssen Emiel A. M. , Austdal Marie
Published: September 2024

Background: Urothelial carcinoma presents as non-muscle-invasive bladder cancer (NMIBC) in ~75% of primary cases. Addressing the limitations of the TNM and WHO04/16 classification systems, this study investigates genetic alterations, the mitotic activity index (MAI), and immunohistochemistry (IHC) markers CK20, p53, and CD25 as better prognostic biomarkers in NMIBC. Methods: Using the Oncomine™ Focus Assay for targeted next-generation sequencing (NGS), 409 single-nucleotide variations (SNVs) and 193 copy number variations (CNVs) were identified across 287 patients with TaT1 tumors. Results: FGFR3 and PIK3CA alterations were significantly more prevalent in Ta tumors, while T1 tumors had significant ERBB2 alterations. Low-grade (LG) tumors were enriched with FGFR3 alterations, while high-grade (HG) tumors were significantly associated with ERBB2 alterations, as well as FGFR1 and CCND1 amplifications. FGFR3 alterations were linked to shorter recurrence-free survival (RFS; p = 0.033) but improved progression-free survival (PFS; p < 0.001). Conversely, ERBB2 alterations (p < 0.001), ERBB3 mutations (p = 0.044), and both MYC (p < 0.001) and MYCN (p = 0.011) amplifications were associated with shorter PFS. Survival analysis of gene sets revealed inverse associations between PIK3CA and ERBB2 (p = 0.003), as well as PIK3CA and MYC (p = 0.005), with PFS. Conclusions: In multivariate Cox regression, MAI was the strongest predictor for PFS. Integrating genetic alterations and histopathological features may improve risk stratification in NMIBC.