bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival analysis of PLWHA undergoing combined antiretroviral therapy: exploring long-term prognosis and influencing factors
Authors: Pu Jun-fan , Wu Jing
Published: February 2024

Introduction

The survival time of human immunodeficiency virus (HIV)–infected individuals or patients with acquired immunodeficiency syndrome (AIDS) is influenced by multiple factors. Studying survival and influential factors after antiretroviral therapy (ART) contributes to improving treatment protocols, management strategies, and prognosis for people living with HIV/AIDS (PLWHA).

Methods

This retrospective cohort study collected case data and follow-up records of PLWHA who received ART in Dazu District, Chongqing City, between 2007 and 2022. Cumulative survival rates were calculated using life tables. Survival curves were plotted using the Kaplan–Meier method. Uni-variable and multivariable Cox proportional hazards models analyzed factors influencing survival.

Results

The study included 5,237 PLWHA receiving ART. Within the first year of ART initiation, 146 AIDS-related deaths occurred, accounting for 29.49% (146/495) of total deaths. Cumulative survival rates at 1, 5, 10, and 15 years were 0.97, 0.90, 0.85, and 0.79, respectively. During the observation period, male patients who received ART had a 1.89 times higher risk of death compared to females (aHR, 1.89; 95%; CI, 1.50–2.37). Patients aged ≥60 years had a 3.44-fold higher risk of death than those aged <30 years (aHR, 3.44; 95% CI, 1.22–9.67). Injection drug users (aHR, 4.95; 95% CI, 2.00–12.24) had a higher risk of death than those with heterosexual (aHR, 1.60; 95% CI, 0.69–3.72) and homosexual transmission. Patients with a baseline CD4+ T lymphocyte count <200 cells/μL (aHR, 8.02; 95% CI, 4.74–13.57) and between 200 and 349 cells/μL (aHR, 2.14; 95% CI, 1.26–3.64) had a higher risk of death than those with ≥350 cells/μL. Patients with ART initiation at WHO clinical stage IV had a 2.48-fold higher risk of death than those at stage I (aHR, 2.48; 95% CI, 1.17–5.23).

Conclusion

The first year following ART initiation is critical in HIV/AIDS treatment, emphasizing the need for intensified follow-up and monitoring to facilitate successful immune system reconstruction. Older age, male sex, injection drug use, baseline CD4+ T lymphocyte count <200 cells/μL, and WHO clinical stage IV are associated with an increased risk of death. Tailored treatment and management strategies should be implemented for patient populations at higher risk of mortality and with a poorer prognosis.
Importance of Community Health Workers for Maternal Health Care Management
Authors: Gupta Archana , Khan Saba
Published: February 2024

Objectives: Community Health Workers (CHWs) are important healthcare professionals and key members of team. The purpose of this research is to identify the roles and responsibilities of CHWs in developed and developing countries who provide healthcare assistance to pregnant and lactating women.

Methods: For this particular study, a comparison was conducted between CHWs role in seven developed countries, seven South Asian developing countries, and India, with special emphasis on improving maternal health status.

Results: CHW programs are essential in communities, institutional health programs, and outreach delivery systems. Without active community involvement, CHWs cannot reach their full potential. Developed countries have frameworks for CHWs, such as the Swasthya Shebika Program, Village Health Worker Cadret, Lady Health Worker Programme, and Accredited Social Health Activist program. CHWs are well-paid in developed nations and work with marginalized groups to spread health messages. However, up to 60% of community health workers in low- and lower-middle-income countries do not receive remuneration.

Conclusion: Health systems must support CHWs in choosing technical interventions and providing necessary training, supervision, and logistical support.
Citrus Carotenoid Extracts Promote ROS Accumulation and Induce Oxidative Stress to Exert Anti-Proliferative and Pro-Apoptotic Effects in MDA-MB-231 Cells
Authors: Wei Juanjuan , Ye Zimao , Li Yurong , Li Yi , Zhou Zhiqin
Published: February 2024

Citrus fruits are economically significant crops worldwide, as they contain various bioactive compounds that possess health-promoting properties. Carotenoids, as the most important component in citrus, exhibit notable pharmacological activities, such as antioxidation and anticancer, which make carotenoids valuable in the prevention and treatment of breast cancer. In this study, after treatment with carotenoid extracts from XiYou (XY) and ZaoHongQiCheng (ZH), we evaluated the cytotoxicity, apoptosis, antioxidant system, and oxidative stress induced by ROS overproduction and MMP damage in MDA-MB-231 cells. The analysis confirmed that cell proliferation was inhibited in a concentration-dependent manner, accompanied by G0/G1 arrest and cell apoptosis. XY and ZH promoted the accumulation of ROS, decreased MMP, increased malondialdehyde (MDA) levels, consumed glutathione (GSH), and reduced the activity of antioxidant enzymes (peroxidase (POD), catalase (CAT), glutathione reductase (GR), and superoxide dismutase (SOD)). Meanwhile, XY and ZH induced apoptosis through the mitochondrial pathway by significantly upregulated P53, BAX, caspase-3, caspase-7, and caspase-9 gene expression levels and downregulated Bcl-2. Carotenoid-rich extracts were found to cause oxidative stress by enhancing ROS production through their pro-oxidative potential, and the aggravation of oxidative processes promotes apoptosis in MDA-MB-231 cells. These results indicate that citrus carotenoids can be used as potential pro-oxidants and have the potential to be developed into products for the prevention or treatment of breast cancer.
Understanding the Factors That Influence the Antioxidant Activity of Manganosalen Complexes with Neuroprotective Effects
Authors: Rouco Lara , Alvariño Rebeca , Alfonso Amparo , Fernández-Fariña Sandra , González-Noya Ana M. , Martínez-Calvo Miguel , Pedrido Rosa , Rodríguez-Silva Laura , Maneiro Marcelino
Published: February 2024

Manganosalen complexes are a class of catalytic antioxidants with beneficial effects against different neurological disorders according to various in vitro and in vivo studies. The interest in the factors that determine their antioxidant activity is based on the fact that they are key to achieving more efficient models. In this work, we report a set of new manganosalen complexes, thoroughly characterized in the solid state and in solution by different techniques. The chelating Schiff base ligands used were prepared from condensation of different substituted hydroxybenzaldehydes with 1,2-diaminoethane and 1,3-diaminopropane. The antioxidant activity of the new models was tested through superoxide dismutase and catalase probes in conjunction with the studies about their neuroprotective effects in human SH-SY5Y neuroblastoma cells in an oxidative stress model. The ability to scavenge excess reactive oxygen species (ROS) varied depending on the manganosalen models, which also yielded different improvements in cell survival. An assessment of the different factors that affect the oxidant activity for these complexes, and others previously reported, revealed the major influence of the structural factors versus the redox properties of the manganosalen complexes.
Cellular Pre-Adaptation to the High O2 Concentration Used in Standard Cell Culture Confers Resistance to Subsequent H2O2-Induced Cell Death
Authors: Jordan Jack B. , Smallwood Miranda J. , Smerdon Gary R. , Winyard Paul G.
Published: February 2024

The addition of hydrogen peroxide (H2O2) to cultured cells is widely used as a method to modulate redox-regulated cellular pathways, including the induction of programmed cell death in cell culture experiments and the testing of pro- and antioxidant compounds. Here, we assessed the effect on the cellular response to H2O2 of pre-adapting squamous cell carcinoma cells (A431) to the standard cell culture oxygenation of 18.6% O2, compared to cells pre-adapted to a physiological skin O2 concentration (3.0% O2). We showed that cells pre-adapted to 18.6% O2 resisted H2O2-induced cell death compared to cells pre-adapted to 3.0% O2 for 96 h prior to treatment with H2O2. Moreover, the enzymatic activities of catalase and glutathione reductase, as well as the protein expression levels of catalase, were higher in cells pre-adapted to 18.6% O2 compared to cells pre-adapted to 3.0% O2. H2O2-resistant cells, pre-adapted to 18.6% O2, exhibited increased nuclear Nrf-2 levels. It is concluded that A431 cells pre-adapted to standard cell culture oxygenation conditions resist H2O2-induced cell death. This effect may be related to their heightened activation of Nrf-2.
Nutrigenomics of Natural Antioxidants in Broilers
Authors: Kouvedaki Ioanna , Pappas Athanasios C. , Surai Peter F. , Zoidis Evangelos
Published: February 2024

The broiler industry supplies high-quality animal protein to the world. The ban of antibiotics as growth promoters has opened the way for plenty of phytochemicals and antioxidants to be explored. This study summarizes the use of natural antioxidants in a broiler diet as a way through which to deal with stressors, as well as their effects on the expression of various genes. The transcriptional factors and genes involved in the regulation of redox homeostasis are described and emphasis is placed on nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B. Sources such as fruits, vegetables, spices, mushrooms, and algae contain numerous natural antioxidant compounds. The antioxidant activity of these compounds has also been confirmed at the genome level. This study focuses on the regulation of oxidative stress-related genes, as well as on genes that regulate the inflammatory response, apoptosis, response to heat stress, lipid metabolism, and the intestinal barrier status. The natural compounds presented include, but are not limited to, the following: rutin, lycopene, magnolol, genistein, hesperidin, naringin, quercetin, curcumin, bisdemethoxycurcumin, resveratrol, astaxanthin, squalene, pterostilbene, protocatechuic acid, taraxasterol, myricetin, and proanthocyanidins. Several studies have revealed a dose-dependent action. Future studies should focus on the role of phytogenic compounds as antibiotic alternatives in relation to gut microbiota and their role in eubiosis.
Semantic Segmentation of 3D Point Clouds in Outdoor Environments Based on Local Dual-Enhancement
Authors: Zhang Kai , An Yi , Cui Yunhao , Dong Hongxiang
Published: February 2024

Semantic segmentation of 3D point clouds in drivable areas is very important for unmanned vehicles. Due to the imbalance between the size of various outdoor scene objects and the sample size, the object boundaries are not clear, and small sample features cannot be extracted. As a result, the semantic segmentation accuracy of 3D point clouds in outdoor environment is not high. To solve these problems, we propose a local dual-enhancement network (LDE-Net) for semantic segmentation of 3D point clouds in outdoor environments for unmanned vehicles. The network is composed of local-global feature extraction modules, and a local feature aggregation classifier. The local-global feature extraction module captures both local and global features, which can improve the accuracy and robustness of semantic segmentation. The local feature aggregation classifier considers the feature information of neighboring points to ensure clarity of object boundaries and the high overall accuracy of semantic segmentation. Experimental results show that provides clearer boundaries between various objects, and has higher identification accuracy for small sample objects. The LDE-Net has good performance for semantic segmentation of 3D point clouds in outdoor environments.
Solidification of Radioactive Wastes Using Recycled Cement Originating from Decommissioned Nuclear-Energy Facilities
Authors: Jeon Ji-Hun , Lee Jong-Hwan , Lee Woo-Chun , Lee Sang-Woo , Kim Soon-Oh
Published: February 2024

Hundreds of thousands of tons of waste are generated from decommissioned nuclear- power facilities, and it has become a critical global issue to secure technology for reducing and recycling this waste. Concrete waste (CW) is estimated to comprise 60–80% of the total waste, and concrete-waste powder (CWP) includes enough inorganic substances used as effective materials for waste treatment. Accordingly, it can be used to produce recycled cement (RC). This study aimed to evaluate the performance of a solidification agent manufactured using recycled cement (SRC) for the safe packing of radioactive wastes, such as coarse aggregates of CW, waste soil, and metal wastes originating from decommissioned nuclear facilities. The experimental results indicated that the most relevant incineration temperature of CWP for RC was 700 °C. The optimum water-to-binder ratio was determined to be 0.4, and the most relevant substitution ratio of ground granulated blast furnace slag for CWP was determined to be 15%. In addition, calcium silicate hydrate is the most effective hydration product for improving the compressive strength of SRC. The maximum packing capacities of the SRC for coarse aggregates, waste soil, and metal waste, which were simulated as radioactive wastes, were determined to be 30, 5, and 7 wt%, respectively. The results of leaching tests using SRC containing radioactive wastes contaminated with Co, Cs, and Sr indicated that their leachability indices met the acceptance level for disposal. Consequently, the RC composed of CWP can be used as a solidifying agent to safely dispose of radioactive wastes, such as coarse aggregates, waste soil, and metal waste.
Experimental Study on Dispersion Stability and Polishing Performance of Polishing Solution Based on Micro-Abrasive Water Jet Polishing
Authors: Lin Lin , Jiang Dongcen , Zhang Yunpeng , You Hui
Published: February 2024

In micro-abrasive water jet polishing (MAWJP) technology, where abrasive particles serve as polishing tools, particles tend to form large clusters, leading to increased nozzle wear and diminished material polishing quality. Achieving a polishing solution with good dispersion stability is crucial for enhancing polishing accuracy and minimizing nozzle wear. Therefore, this study employed three dispersants with distinct dispersion mechanisms to examine the impact of each dispersant’s concentration on the dispersion stability of the polishing solution across various abrasive concentrations. Through experimentation, the optimal dispersant type and concentration ratio of abrasive to dispersant were determined, and the effect of the selected dispersant on jet polishing performance was validated. The results of the dispersion stability experiment indicated that, in comparison to Na(PO3)6 and polyethylene glycol (PEG), the polishing solution containing 1.0–2.0 wt% phosphoric ester compounds exhibited a more stable dispersion effect (zeta potential < −50 mV) and superior dispersibility, characterized by a smaller average particle size. Furthermore, K9 optical glass was subjected to fixed-point and local polishing using phosphoric ester compounds as the dispersant. The fixed-point polishing experiment revealed that, at a dispersant concentration of 1.0 wt% and an abrasive concentration of 20 wt%, a smooth and symmetrical material removal profile could be achieved. In the local polishing experiment, the reduction rate of the root mean square of the surface roughness (RMS) increased from 54.33% to 82.24%, and the reduction rate of peak-to-valley height difference in surface (PV) increased from 38.84% to 68.97%. In conclusion, the incorporation of a dispersant proves effective in enhancing the dispersion stability of the polishing solution and dispersibility of the abrasive particles, thereby improving the surface quality of the materials in MAWJP.
Usability Testing of Mobile Applications: A Methodological Framework
Authors: Weichbroth Paweł
Published: February 2024

Less than five percent of all mobile applications have become successful throughout 2023. The success of a new mobile application depends on a variety of factors ranging from business understanding, customer value, and perceived quality of use. In this sense, the topic of usability testing of mobile applications is relevant from the point of view of user satisfaction and acceptance. However, the current knowledge seems to be fragmented, scattered across many papers and reports, and sometimes poorly documented. This paper attempts to fill this gap by investigating the current state of knowledge by reviewing the previous literature relevant to the research topic and developing a unified view. In particular, the methodological framework is outlined and discussed, including the discourse on settings for laboratory and field studies, data collection techniques, experimental designs for mobile usability testing, and a generic research framework. Therefore, the paper contributes to both the theory and practice of human–computer interaction by providing methodological foundations for usability testing of mobile applications, paving the way for further studies in this area. Moreover, the paper provides a better understanding of the related topics, in particular shedding light on methodological foundations, key concepts, challenges, and issues, equipping readers with a comprehensive knowledge base to navigate and contribute to the advancement of the field of mobile usability.
Reinforcement Learning of Bipedal Walking Using a Simple Reference Motion
Authors: Itahashi Naoya , Itoh Hideaki , Fukumoto Hisao , Wakuya Hiroshi
Published: February 2024

In this paper, a novel reinforcement learning method that enables a humanoid robot to learn bipedal walking using a simple reference motion is proposed. Reinforcement learning has recently emerged as a useful method for robots to learn bipedal walking, but, in many studies, a reference motion is necessary for successful learning, and it is laborious or costly to prepare a reference motion. To overcome this problem, our proposed method uses a simple reference motion consisting of three sine waves and automatically sets the waveform parameters using Bayesian optimization. Thus, the reference motion can easily be prepared with minimal human involvement. Moreover, we introduce two means to facilitate reinforcement learning: (1) we combine reinforcement learning with inverse kinematics (IK), and (2) we use the reference motion as a bias for the action determined via reinforcement learning, rather than as an imitation target. Through numerical experiments, we show that our proposed method enables bipedal walking to be learned based on a small number of samples. Furthermore, we conduct a zero-shot sim-to-real transfer experiment using a domain randomization method and demonstrate that a real humanoid robot, KHR-3HV, can walk with the controller acquired using the proposed method.
Optimization Design of Double Wishbone Front Suspension Parameters for Large Mining Dump Truck and Analysis of Ride Comfort
Authors: Zhao Jianqiao , Ren Xueping , Dong Zhiming , Liu Tongtong
Published: February 2024

With the advancement of technology, mining trucks are gradually becoming larger, imposing higher performance requirements on the front suspension. There is a need to transform the original integral non-independent front axle of mining dump trucks with a payload exceeding 300 tons into an independent front suspension with a double-wishbone suspension. The changing of the front suspension is bound to have an impact on the overall vehicle’s handling stability and ride comfort. Therefore, the following research is conducted to investigate and analyze these effects. Firstly, the paper proposes a method for optimizing the parameters of the double-wishbone front suspension. The double-wishbone front suspension is modeled, and a comparison with a kinematic model is conducted to validate the accuracy of the model. Secondly, unreasonable hardpoint parameters are optimized. Thirdly, a dynamic model of the entire vehicle is established based on the optimized parameters, and an analysis of handling stability and ride comfort for the entire vehicle is performed. Finally, simulation results are compared and analyzed against experimental data. The results indicate that the optimized positioning parameters not only effectively enhance the suspension performance of the mining dump truck but also meet the requirements for handling stability and smoothness. The overall smoothness of the vehicle is significantly improved after the modification. This study not only holds significant engineering value in reducing vibrations in dump trucks and enhancing driver comfort, but also provides theoretical support for subsequent research and development in the industry.
Solving Particle–Antiparticle and Cosmological Constant Problems
Authors: Lev Felix M.
Published: February 2024

We solve the particle-antiparticle and cosmological constant problems proceeding from quantum theory, which postulates that: various states of the system under consideration are elements of a Hilbert space H with a positive definite metric; each physical quantity is defined by a self-adjoint operator in H; symmetry at the quantum level is defined by a representation of a real Lie algebra A in H such that the representation operator of any basis element of A is self-adjoint. These conditions guarantee the probabilistic interpretation of quantum theory. We explain that in the approaches to solving these problems that are described in the literature, not all of these conditions have been met. We argue that fundamental objects in particle theory are not elementary particles and antiparticles but objects described by irreducible representations (IRs) of the de Sitter (dS) algebra. One might ask why, then, experimental data give the impression that particles and antiparticles are fundamental and there are conserved additive quantum numbers (electric charge, baryon quantum number and others). The reason is that, at the present stage of the universe, the contraction parameter R from the dS to the Poincare algebra is very large and, in the formal limit R→∞, one IR of the dS algebra splits into two IRs of the Poincare algebra corresponding to a particle and its antiparticle with the same masses. The problem of why the quantities (c,ℏ,R) are as are does not arise because they are contraction parameters for transitions from more general Lie algebras to less general ones. Then the baryon asymmetry of the universe problem does not arise. At the present stage of the universe, the phenomenon of cosmological acceleration (PCA) is described without uncertainties as an inevitable kinematical consequence of quantum theory in semiclassical approximation. In particular, it is not necessary to involve dark energy the physical meaning of which is a mystery. In our approach, background space and its geometry are not used and R has nothing to do with the radius of dS space. In semiclassical approximation, the results for the PCA are the same as in General Relativity if Λ=3/R2, i.e., Λ>0 and there is no freedom for choosing the value of Λ.
Bayesian Inference for a Hidden Truncated Bivariate Exponential Distribution with Applications
Authors: Ghosh Indranil , Ng Hon Keung Tony , Kim Kipum , Kim Seong W.
Published: February 2024

In many real-life scenarios, one variable is observed only if the other concomitant variable or the set of concomitant variables (in the multivariate scenario) is truncated from below, above, or from a two-sided approach. Hidden truncation models have been applied to analyze data when bivariate or multivariate observations are subject to some form of truncation. While the statistical inference for hidden truncation models (truncation from above) under the frequentist and the Bayesian paradigms has been adequately discussed in the literature, the estimation of a two-sided hidden truncation model under the Bayesian framework has not yet been discussed. In this paper, we consider the Bayesian inference for a general two-sided hidden truncation model based on the Arnold–Strauss bivariate exponential distribution. In addition, a Bayesian model selection approach based on the Bayes factor to select between models without truncation, with truncation from below, from above, and two-sided truncation is also explored. An extensive simulation study is carried out for varying parameter choices under the conjugate prior set-up. For illustrative purposes, a real-life dataset is re-analyzed to demonstrate the applicability of the proposed methodology.
The Involvement of YNR069C in Protein Synthesis in the Baker’s Yeast, Saccharomyces cerevisiae
Authors: Takallou Sarah , Hajikarimlou Maryam , Al-gafari Mustafa , Wang Jiashu , Kazmirchuk Thomas David Daniel , Said Kamaledin B. , Samanfar Bahram , Golshani Ashkan
Published: February 2024

Maintaining translation fidelity is a critical step within the process of gene expression. It requires the involvement of numerous regulatory elements to ensure the synthesis of functional proteins. The efficient termination of protein synthesis can play a crucial role in preserving this fidelity. Here, we report on investigating a protein of unknown function, YNR069C (also known as BSC5), for its activity in the process of translation. We observed a significant increase in the bypass of premature stop codons upon the deletion of YNR069C. Interestingly, the genomic arrangement of this ORF suggests a compatible mode of expression reliant on translational readthrough, incorporating the neighboring open reading frame. We also showed that the deletion of YNR069C results in an increase in the rate of translation. Based on our results, we propose that YNR069C may play a role in translation fidelity, impacting the overall quantity and quality of translation. Our genetic interaction analysis supports our hypothesis, associating the role of YNR069C to the regulation of protein synthesis.
Exploring FDA-Approved Frontiers: Insights into Natural and Engineered Peptide Analogues in the GLP-1, GIP, GHRH, CCK, ACTH, and α-MSH Realms
Authors: Al Musaimi Othman
Published: February 2024

Peptides continue to gain significance in the pharmaceutical arena. Since the unveiling of insulin in 1921, the Food and Drug Administration (FDA) has authorised around 100 peptides for various applications. Peptides, although initially derived from endogenous sources, have evolved beyond their natural origins, exhibiting favourable therapeutic effectiveness. Medicinal chemistry has played a pivotal role in synthesising valuable natural peptide analogues, providing synthetic alternatives with therapeutic potential. Furthermore, key chemical modifications have enhanced the stability of peptides and strengthened their interactions with therapeutic targets. For instance, selective modifications have extended their half-life and lessened the frequency of their administration while maintaining the desired therapeutic action. In this review, I analyse the FDA approval of natural peptides, as well as engineered peptides for diabetes treatment, growth-hormone-releasing hormone (GHRH), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), and α-melanocyte stimulating hormone (α-MSH) peptide analogues. Attention will be paid to the structure, mode of action, developmental journey, FDA authorisation, and the adverse effects of these peptides.
Maternal-Foetal/Infant Interactions—Gut Microbiota and Immune Health
Authors: Adamczak Ada Maria , Werblińska Alicja , Jamka Małgorzata , Walkowiak Jarosław
Published: February 2024

In recent years, the number of scientific publications on the role of intestinal microbiota in shaping human health, as well as the occurrence of intestinal dysbiosis in various disease entities, has increased dynamically. However, there is a gap in comprehensively understanding the factors influencing a child’s gut microbiota. This review discusses the establishment of gut microbiota and the immunological mechanisms regulating children’s microbiota, emphasising the importance of prioritising the development of appropriate gut microbiota in a child from the planning stages of pregnancy. The databases PubMed, Web of Sciences, Cochrane, Scopus and Google Scholar were searched to identify relevant articles. A child’s gut microbiota composition is influenced by numerous factors, such as diet during pregnancy, antibiotic therapy, the mother’s vaginal microbiota, delivery method, and, later, feeding method and environmental factors. During pregnancy, the foetus naturally acquires bacterial strains from the mother through the placenta, thereby shaping the newborn’s immune system. Inappropriate maternal vaginal microbiota may increase the risk of preterm birth. Formula-fed infants typically exhibit a more diverse microbiota than their breastfed counterparts. These factors, among others, shape the maturation of the child’s immune system, impacting the production of IgA antibodies that are central to cellular humoral immune defence. Further research should focus on identifying specific microbiota–immune system interactions influencing a child’s immune health and developing personalised treatment strategies for immune-related disorders.
The Gastric Cancer Immune Prognostic Score (GCIPS) Shows Potential in Predicting an Unfavorable Prognosis for Gastric Cancer Patients Undergoing Immune Checkpoint Inhibitor Treatment
Authors: Zuo Yanjiao , Sun Hao , Pan Hongming , Zhao Ruihu , Xue Yingwei , Song Hongjiang
Published: February 2024

(1) Background: This study aims to explore the predictive capability of the Gastric Cancer Immune Prognostic Score (GCIPS) for an unfavorable prognosis in gastric cancer patients undergoing immune checkpoint inhibitor (ICI) treatment. (2) Methods: This study included 302 gastric cancer patients who underwent treatment with ICIs at our institution from January 2017 to December 2022. The patients were randomly divided into a test set (201 cases) and a validation set (101 cases) using a random number table. Kaplan–Meier survival analysis and the log-rank test were used to investigate survival differences. Cox regression analysis and Lasso regression analysis were employed to establish the GCIPS and identify independent prognostic indicators. ROC curves, time–ROC curves, and nomograms were utilized to further explore the predictive performance of GCIPS. (3) Results: The test set and validation set showed no statistical differences in clinical and pathological features, as well as blood parameters (all p > 0.05). Cox regression analysis revealed that white blood cells (WBC), lymphocytes (LYM), and the international normalized ratio (INR) emerged as independent prognostic blood indicators after eliminating collinearity through Lasso analysis. The GCIPS was established using β coefficients with the following formula: GCIPS = WBC (109/L) × 0.071 − LYM (109/L) × 0.375 + INR × 2.986. ROC curves based on death and time–ROC curves demonstrated that the GCIPS had higher AUCs than other classical markers at most time points. Survival analyses of all subgroups also revealed a significant correlation between the GCIPS and patients’ progression-free survival (PFS) and overall survival (OS) (all p < 0.05). Furthermore, the GCIPS was identified as an independent prognostic factor for both PFS and OS. Analyses in the validation set further confirmed the reliability and stability of the GCIPS in predicting patient prognosis. Finally, nomograms incorporating the GCIPS exhibited high accuracy in both the test and validation sets. Additionally, the nomograms revealed that the GCIPS had a higher prognostic value than any other factor, including the TNM stage. (4) Conclusions: The GCIPS demonstrated its ability to predict adverse outcomes in gastric cancer patients undergoing ICIs treatment and had a high prognostic value. As a readily accessible and simple novel biomarker, it effectively identified high-risk patients.
Phillygenin Suppresses Glutamate Exocytosis in Rat Cerebrocortical Nerve Terminals (Synaptosomes) through the Inhibition of Cav2.2 Calcium Channels
Authors: Lee Ming-Yi , Lin Tzu-Yu , Chang Ya-Ying , Chiu Kuan-Ming , Wang Su-Jane
Published: February 2024

Glutamate is a major excitatory neurotransmitter that mediates neuronal damage in acute and chronic brain disorders. The effect and mechanism of phillygenin, a natural compound with neuroprotective potential, on glutamate release in isolated nerve terminals (synaptosomes) prepared from the rat cerebral cortex were examined. In this study, 4-aminopyridine (4-AP), a potassium channel blocker, was utilized to induce the release of glutamate, which was subsequently quantified via a fluorometric assay. Our findings revealed that phillygenin reduced 4-AP-induced glutamate release, and this inhibitory effect was reversed by removing extracellular Ca2+ or inhibiting vesicular transport with bafilomycin A1. However, exposure to the glutamate transporter inhibitor dl-threo-beta-benzyl-oxyaspartate (dl-TOBA) did not influence the inhibitory effect. Moreover, phillygenin did not change the synaptosomal membrane potential but lowered the 4-AP-triggered increase in intrasynaptosomal Ca2+ concentration ([Ca2+]i). Antagonizing Cav2.2 (N-type) calcium channels blocked the inhibition of glutamate release by phillygenin, whereas pretreatment with the mitochondrial Na+/Ca2+ exchanger inhibitor, CGP37157 or the ryanodine receptor inhibitor, dantrolene, both of which block intracellular Ca2+ release, had no effect. The effect of phillygenin on glutamate release triggered by 4-AP was completely abolished when MAPK/ERK inhibitors were applied. Furthermore, phillygenin attenuated the phosphorylation of ERK1/2 and its major presynaptic target, synapsin I, a protein associated with synaptic vesicles. These data collectively suggest that phillygenin mediates the inhibition of evoked glutamate release from synaptosomes primarily by reducing the influx of Ca2+ through Cav2.2 calcium channels, thereby subsequently suppressing the MAPK/ERK/synapsin I signaling cascade.
Procedural Memory Deficits in Preschool Children with Developmental Language Disorder in a Spanish-Speaking Population
Authors: Sanhueza Soraya , Urrutia Mabel , Marrero Hipólito
Published: February 2024

This study aimed to compare procedural learning skills between Spanish-speaking preschool children (ages 4 years to 4 years, 11 months) with developmental language disorder (DLD) and their chronologically matched typically developing (TD) peers. Using the serial reaction time (SRT) task, participants (30 children with DLD and 30 TD children) responded to visual stimuli in a sequenced manner over four blocks, followed by a random order block. The task assessed reaction time (RT) and accuracy. The results showed a significant interaction between group and block for RT and accuracy, with children with DLD exhibiting longer RTs and accuracy deficits across blocks. In contrast, the TD group showed higher RT efficiency and accuracy in the sequential blocks and, as expected, decreased performance in the random block according to the experimental manipulation. Overall, the results of this investigation suggest that there was no implicit learning in the DLD group, as indicated by the SRT task paradigms of procedural memory. These findings align with some aspects of the procedural deficit hypothesis (PDH), which suggests that linguistic deficits in the DLD population may derive from a deficit in sequential learning from the procedural memory system domain in the Spanish context.
Sex Differences in Conversion Risk from Mild Cognitive Impairment to Alzheimer’s Disease: An Explainable Machine Learning Study with Random Survival Forests and SHAP
Authors: Sarica Alessia , Pelagi Assunta , Aracri Federica , Arcuri Fulvia , Quattrone Aldo , Quattrone Andrea ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2024

Alzheimer’s disease (AD) exhibits sex-linked variations, with women having a higher prevalence, and little is known about the sexual dimorphism in progressing from Mild Cognitive Impairment (MCI) to AD. The main aim of our study was to shed light on the sex-specific conversion-to-AD risk factors using Random Survival Forests (RSF), a Machine Learning survival approach, and Shapley Additive Explanations (SHAP) on dementia biomarkers in stable (sMCI) and progressive (pMCI) patients. With this purpose, we built two separate models for male (M-RSF) and female (F-RSF) cohorts to assess whether global explanations differ between the sexes. Similarly, SHAP local explanations were obtained to investigate changes across sexes in feature contributions to individual risk predictions. The M-RSF achieved higher performance on the test set (0.87) than the F-RSF (0.79), and global explanations of male and female models had limited similarity (<71.1%). Common influential variables across the sexes included brain glucose metabolism and CSF biomarkers. Conversely, the M-RSF had a notable contribution from hippocampus, which had a lower impact on the F-RSF, while verbal memory and executive function were key contributors only in F-RSF. Our findings confirmed that females had a higher risk of progressing to dementia; moreover, we highlighted distinct sex-driven patterns of variable importance, uncovering different feature contribution risks across sexes that decrease/increase the conversion-to-AD risk.
Exploring Methodological Issues in Mental Practice for Upper-Extremity Function Following Stroke-Related Paralysis: A Scoping Review
Authors: Nakashima Akira , Okamura Ryohei , Moriuchi Takefumi , Fujiwara Kengo , Higashi Toshio , Tomori Kounosuke
Published: February 2024

In this scoping review, we aimed to comprehensively clarify the methodology of Mental practice (MP) by systematically mapping studies documenting the application of MP to post-stroke paralytic upper-extremity function. Specifically, when is an MP intervention most commonly applied after stroke onset? What is the corresponding MP load (intervention time, number of intervention days, and intervention period)? What are the most common methods of Motor Imagery (MI) recall and MI tasks used during the application of MP? Is MP often used in conjunction with individual rehabilitation? What are the paralyzed side’s upper-limb and cognitive function levels at the start of an MP intervention? The research questions were identified according to PRISMA-ScR. The PubMed, Scopus, Medline, and Cochrane Library databases were used to screen articles published until 19 July 2022. In total, 694 English-language articles were identified, of which 61 were finally included. Most of the studies were conducted in the chronic phase after stroke onset, with limited interventions in the acute or subacute phase. The most common intervention time was ≤30 min and intervention frequency was 5 times/week in MP. An audio guide was most commonly used to recall MI during MP, and 50 studies examined the effects of MP in combination with individual rehabilitation. The Fugl-Meyer Assessment mean for the 38 studies, determined using the Fugl-Meyer Assessment, was 30.3 ± 11.5. Additional research with the aim of unifying the widely varying MP methodologies identified herein is warranted.
Oxytocin Enhances Time-Dependent Responses in the Aggressive Zebrafish (Danio rerio)
Authors: Robea Madalina-Andreea , Oprea Georgiana , Plavan Gabriel , Nicoara Mircea Nicusor , Mavroudis Ioannis , Burlui Vasile , Ciobica Alin
Published: February 2024

Autism spectrum disorder (ASD) has become one of the most well-known disorders encountered since early childhood among people. Nowadays, the main concerns are its high prevalence and the lack of proper therapeutic interventions. In this way, the necessity of using animal models that can mimic some of the spectrum symptoms, besides deepening the mechanisms of occurrence, is undeniable. Oxytocin (OT) is often mentioned and linked to producing social domain improvements. The goal of the present study was to determine if different time exposures to OT can trigger distinct behavioral responses in zebrafish, potentially offering insights into autism therapy. To accomplish this goal, zebrafish were exposed to the same dose of OT (33.2 ng/mL OT) for one week but with different time frames, such as: continuous exposure for seven days, fifteen minutes per day for seven days, and every two days for the same amount of time. The behavior of the fish was recorded using the EthoVision XT 11.5 software, and each trial lasted four minutes. Specific parameters for locomotor activity and aggressive behavior were measured. Overall, zebrafish exposure to OT generated several improvements in locomotor activity and aggressive behavior. Moreover, the differences in the exposure period indicated that time is an important factor, showing that continuous exposure to OT was linked with better performance than exposure to the hormone every two days. At the same time, the most variable results were observed in the case of fish exposed every day to OT. Exposure to OT could lead to certain improvements in zebrafish behavior that can be time-sensitive. Nevertheless, further work is needed in order to investigate the mechanisms of action of OT in an ASD context.
CFD Analysis for a New Trombe Wall Concept
Authors: Bulmez Alexandru , Brezeanu Alin , Dragomir George , Fratu Mariana , Iordan Nicolae , Bolocan Sorin , Rozorea Lucian , Popa Eugen , Năstase Gabriel
Published: February 2024

The envelope (façade) of a building is the first barrier between the exterior and the interior of the building and withstands the highest variation in temperature and solar radiation. Trombe walls are used to take advantage of that and contribute to the heating of interior air, helping the heating system. In this study, a new Trombe wall design is presented to contribute significantly to the indoor ventilation of residential buildings. For this, an exterior wall equipped with a proposed Trombe system was studied in a numerical simulation analysis. The proposed systems consist of two important sections, an exterior one and an interior one. The air cavities on the exterior of the wall, covered with silica glass, are the first heat-transfer layer. The secondary layer used for heat transfer, on the interior, is comprised of a MPCLB wall of 115 mm. The air circulation from the exterior to the interior was established as forced convection with a ventilator. The air circulates through the first heating layer on the exterior air cavities and then passes through the second heating layer on the interior MPCLBs. Two cities in Romania were considered to represent the coldest and hottest climates in Romania. Brașov represents the cold climate and Constanța represents the hot climate. In the investigation, both the presence and absence of solar radiation were taken into account. In total, four cases were established. For all four cases, monthly research was made using monthly mean temperatures, and direct and diffuse solar radiation. The results are promising and illustrate that the system works best during the transitional seasons of spring and autumn. The lower the outdoor temperature, the higher the temperature can be increased. Overall, solar radiation accounted for an average 2 °C increase. The temperature increase varied between 3.4 °C and 15.99 °C for Brașov and between 6.42 °C and 12.07 °C in Constanța. This study presents an alternative way to use the Trombe wall for indoor ventilation purposes throughout the year, compared to traditional uses for the Trombe wall for indoor heating.
Effects of Lip Length and Inside Radius-to-Thickness Ratio on Buckling Behavior of Cold-Formed Steel C-Sections
Authors: Hussein Ardalan B. , Hussein Diyari B.
Published: February 2024

Cold-formed steel (CFS) sections constructed with high-strength steel have gained prominence in construction owing to their advantages, including a high strength-to-weight ratio, shape flexibility, availability in long spans, portability, cost-effectiveness, and design versatility. However, the thin thickness of CFS members makes them susceptible to various forms of buckling. This study focuses on addressing and mitigating different types of buckling in columns and beams by manipulating the lip length (d) and the ratio of inside radius to thickness (Ri/t) in CFS C-sections. To achieve this objective, a comprehensive analysis involving 176 models was conducted through the Finite Element Method (FEM). The findings reveal that an increase in lip length leads to a corresponding increase in critical elastic buckling load and moment (Pcrl, Pcrd, Pcre, Mcrl, Mcrd, and Mcre). It is recommended to utilize a lip length greater than or equal to 15 mm for both columns and beams to mitigate various buckling types effectively. Conversely, an increase in the ratio of inside radius to thickness (Ri/t) results in an increase in critical elastic local buckling load (Pcrl) and moment (Mcrl). Thus, lip length (d) significantly influences column and beam buckling, whereas Ri/t exhibits a relatively impactful effect. Subsequently, the experimental test results were used to verify finite element models. These insights contribute significant knowledge for optimizing the design and performance of CFS C-sections in structural applications.
The Correlation between Morpho-Dynamic Contrast-Enhanced Mammography (CEM) Features and Prognostic Factors in Breast Cancer: A Single-Center Retrospective Analysis
Authors: Piccolo Claudia Lucia , Celli Ilenia , Bandini Claudio , Tommasiello Manuela , Sammarra Matteo , Faggioni Lorenzo , Cioni Dania , Beomonte Zobel Bruno , Neri Emanuele
Published: February 2024

Breast cancer, a major contributor to female mortality globally, presents challenges in detection, prompting exploration beyond digital mammography. Contrast-Enhanced Mammography (CEM), integrating morphological and functional information, emerges as a promising alternative, offering advantages in cost-effectiveness and reduced anxiety compared to MRI. This study investigates CEM’s correlation with breast cancer prognostic factors, encompassing histology, grade, and molecular markers. In a retrospective analysis involving 114 women, CEM revealed diverse lesion characteristics. Statistical analyses identified correlations between specific CEM features, such as spiculated margins and irregular shape, and prognostic factors like tumor grade and molecular markers. Notably, spiculated margins predicted lower grade and HER2 status, while irregular shape correlated with PgR and Ki-67 status. The study emphasizes CEM’s potential in predicting breast cancer prognosis, shedding light on tumor behavior. Despite the limitations, including sample size and single-observer analysis, the findings advocate for CEM’s role in stratifying breast cancers based on biological characteristics. CEM features, particularly spiculated margins, irregular shape, and enhancement dynamics, may serve as valuable indicators for personalized treatment decisions. Further research is crucial to validate these correlations and enhance CEM’s clinical utility in breast cancer assessment.
Special Issue Entitled “10th Anniversary of Catalysts: Recent Advances in the Use of Catalysts for Pharmaceuticals”
Authors: Alcántara Andrés R.
Published: February 2024

The worldwide market for active pharmaceutical ingredients (APIs) is currently in a favourable condition [...]