bluuebunny/crossref_metadata_2025 huggingface dataset:
Subset of DN Memory B Cells Expressing Low Levels of Inhibitory Receptor BTLA Is Enriched in SLE Patients
Authors: Aubergeon Lucie , Felten Renaud , Gottenberg Jacques-Eric , Dumortier Hélène , Monneaux Fanny
Published: December 2024

The dialogue between T and B cells can be regulated by different mechanisms, such as co-inhibitory receptors, which therefore play a crucial role in preventing autoimmune diseases such as systemic lupus erythematosus (SLE). B and T lymphocyte attenuator (BTLA) is a co-inhibitory receptor expressed on many myeloid and lymphoid cells. Although peripheral B cells express a very high amount of BTLA, previous works in the context of autoimmunity mainly focused on T cells, and whether BTLA expression on B cells plays a role in the lupus pathogenesis is still unclear. In the present study, we examine the expression of BTLA, as well as its ligand HVEM (Herpesvirus Entry Mediator), on various B cell subsets in lupus patients compared to healthy controls (HCs). We evidenced the existence of double-negative (DN; IgD−CD27−) memory B cells expressing very low levels of BTLA, which are enhanced in active lupus patients. An in-depth analysis revealed that these BTLAlow DN cells mainly correspond to the newly reported DN3 B cell subset, originally described in the context of SARS-CoV2 infection. These cells display an activated and antibody-secreting cell phenotype, and we propose that their low BTLA expression may favor their expansion and rapid differentiation into plasmablasts in lupus patients.
Current Insights into the Radiobiology of Boron Neutron Capture Therapy and the Potential for Further Improving Biological Effectiveness
Authors: Punshon Leah D. , Fabbrizi Maria Rita , Phoenix Ben , Green Stuart , Parsons Jason L.
Published: December 2024

Photon (X-ray) radiotherapy is the most common treatment used in cancer therapy. However, the exposure of normal tissues and organs at risk to ionising radiation often results in a significant incidence of low-grade adverse side effects, whilst high-grade toxicities also occur at concerningly high rates. As an alternative, boron neutron capture therapy (BNCT) aims to create densely ionising helium and lithium ions directly within cancer cells, thus sparing the surrounding normal cells and tissues but also leading to significantly more effective tumour control than X-rays. Although very promising for patients with recurring and highly invasive tumours, BNCT does not currently have widespread use worldwide, in part due to limited and reliable neutron sources for clinical use. Another limitation is devising strategies leading to the selective and optimal accumulation of boron within the cancer cells. Boronophenylalanine (BPA) is currently the major compound used in BNCT which takes advantage of the amino acid transporter LAT1 that is overexpressed in a number of human cancers. Additionally, there is a lack of in-depth knowledge regarding the impact of BNCT on cellular DNA, and the molecular mechanisms that are responsive to the treatment, which are important in developing optimal therapeutic strategies using BNCT, are unclear. In this review, we highlight the current knowledge of the radiobiology of BNCT acquired from in vitro and in vivo studies, particularly in the context of DNA damage and repair, but also present evidence of established and new boron-containing compounds aimed at enhancing the specificity and effectiveness of the treatment.
Predictive Value of Flow Cytometry Quantification of BAL Lymphocytes and Neutrophils in ILD
Authors: Novoa-Bolivar Erika M. , Ros José A. , Pérez-Fernández Sonia , Campillo José A. , López-Hernández Ruth , González-López Rosana , Otálora-Alcaraz Almudena , Ortuño-Hernández Cristina , Gimeno Lourdes , Ruiz-Lorente Inmaculada , Ceballos-Francisco Diana , Muro Manuel , Solana Elena , Martinez-Camblor Pablo , Minguela Alfredo
Published: December 2024

Interstitial lung diseases (ILDs) are pathologies affecting the pulmonary interstitium and, less frequently, the alveolar and vascular epithelia. Bronchoalveolar lavage (BAL) is commonly used in ILD evaluation since it allows the sampling of the lower respiratory tract. The prognostic value of BAL cell counts in ILD is unknown. Flow cytometry quantification of lymphocytes and neutrophils in BAL of 1074 real-life consecutive patients were retrospectively correlated with clinical, radiological, anatomopathological, functional/spirometry, and evolutionary data. Cut-offs with predictive value were established at 7% and 5% for lymphocytes and neutrophils, respectively. Three risk stratification groups (Risk-LN) were established: FAVORABLE (lymphocytes > 7% and neutrophils < 5%), INTERMEDIATE (rest of patients), and UNFAVORABLE (lymphocytes < 7% and neutrophils > 5%), showing 75th percentile overall survival (OS) of 10.0 ± 1.4, 5.8 ± 0.6, and 3.0 ± 0.3 years (p < 0.001), respectively. A scoring model combining Risk-LN and the age of the patients with great predictive capacity for OS on fibrotic and non-fibrotic ILDs is proposed. This score is an independent predictive factor (HR = 1.859, p = 0.002) complementary to the fibrosis status (HR = 2.081, p < 0.001) and the type of treatment. Flow cytometry of BAL provides rapid and accurate quantification of lymphocytes and neutrophils, allowing the establishment of a risk score model that is useful in the clinical management of fibrotic and non-fibrotic ILDs from the time of diagnosis.
YBX1: A Multifunctional Protein in Senescence and Immune Regulation
Authors: Zhang Wenze , Liu Ying , Zhao Zhe , Zhang Yizhi , Liang Yujuan , Wang Wanxia
Published: December 2024

The Y-box binding protein 1 (YBX1) is a multifunctional protein with a wide range of roles in cell biology. It plays a crucial role in immune modulation, senescence, and disease progression. This review presents a comprehensive analysis of the specific functions and mechanisms of YBX1 in these areas. Initially, YBX1 is shown to be closely associated with cellular senescence and impacts significant biological processes, including cell proliferation, damage repair, and metabolism. This suggests potential applications in the prevention and treatment of senescence-related diseases. Additionally, YBX1 regulates the immune response by controlling the function of immune cells and the expression of immune molecules. It is essential in maintaining immune system homeostasis and impacts the pathological process of various diseases, including tumors. Lastly, the diverse functions of the YBX1 protein make it a promising candidate for the development of innovative therapeutic strategies for diseases. Comprehensive research on its mechanisms could provide novel insights and approaches for the prevention, diagnosis, and treatment of related diseases.
HLA Class I (A and B) Allele Polymorphism in a Moroccan Population Infected with Hepatitis C Virus
Authors: Machraoui Safa , Hakmaoui Abdelmalek , Errafii Khaoula , Knidiri Mehdi , Essaadouni Lamiaa , Krati Khadija , Admou Brahim
Published: December 2024

Hepatitis C virus (HCV) infection is one of the major health burdens worldwide. Its course depends on the virus itself and the host’s immune responses. The latter are conditioned by immunogenetic factors, in particular human leukocyte antigens (HLAs), whose role in determining the outcome of infection varies according to populations and ethnic groups. The current study attempted to investigate the possible relationship between HLA-A and HLA-B allele polymorphism and its impacts on the clinical outcome of HCV for a better understanding of disease susceptibility and clearance. A cross-sectional and comparative study was carried out on 40 patients with hepatitis C and 100 ethnically matched healthy control subjects originating from southern Morocco. HLA class I alleles were typed using the high-resolution PCR-SSO method. The prevalence of certain HLA class I alleles differed significantly between HCV-infected individuals and healthy controls. In particular, HLA-A*02:01 was less prevalent in chronic HCV infection (p = 0.002), indicating a potential protective effect, while the higher prevalence of HLA-A*68:02, A*66:01 B*15:03, B*41:02, B*44:03, and B*50:01 in patients could indicate a predisposing factor. These findings support the association of these immunogenetic markers with HCV infection, indicating their possible role in determining clinical and genotype forms as well as the outcome of HCV infection. Thus, an in-depth analysis of these alleles could lead to a better understanding of HCV pathogenesis and potential targeted interventions.
Effect of Compact Density of MoO2 Powders on Densification Kinetics and Grain Growth During Sintering Processes
Authors: Lee Jongbeom , Jung Jaehoon , Lee Hyowon , Park Jaesoung , Jeong Haguk
Published: December 2024

MoO2 powders compacted under different uniaxial pressures ranging from 100 to 800 MPa, corresponding to the compact densities ranging from 55% to 65%, respectively, were sintered at targeted temperatures within 650–1050 °C for 1 h in an N2 atmosphere. Then, their densification kinetics and grain growth were investigated. With regard to the densification of MoO2 powders at room temperature, a linear relationship was observed between the compact density and log pressure in the uniaxial pressure range without fracture and local deformation. The relative densities of the sintered MoO2 samples increased with increasing compact density and sintering temperature. At a given sintering temperature, the sample with the highest compact density exhibited the best densification rate. The grain size in the sintered samples was proportional to the relative density, and the grain growth obeyed the Arrhenius equation. The sintered samples with 55%, 60%, and 65% densities during the sintering process have different activation energies values depending on the sintering temperature. At low sintering temperatures, the activation energies for 55%, 60%, and 65% compact densities were 50.8, 39.6, and 26.1 kJ/mol, respectively, and at higher sintering temperatures, the corresponding values were 19.8, 21.5, and 25.4 kJ/mol.
Recent Advances in Lead-Free All-Inorganic Perovskite CsCdCl3 Crystals for Anti-Counterfeiting Applications
Authors: Wang Nankai , Zhu Zhaojie , Li Jianfu , Tu Chaoyang , Chen Weidong , Wang Yan
Published: December 2024

This study reviews the advanced anti-counterfeiting applications of CsCdCl3, a lead-free all-inorganic perovskite crystal exhibiting dynamic luminescent properties responsive to temperature and UV light. Using synthesis methods such as Bridgman and hydrothermal techniques and incorporating dopants like bromine and tellurium, this research achieves improved luminescent stability, spectral diversity, and afterglow characteristics in CsCdCl3. The crystal demonstrates extended afterglow, photochromic shifts, and temperature-sensitive luminescence, enabling applications in 4D encoding for secure data encryption and in cold-chain temperature monitoring for pharmaceuticals. Despite these promising attributes, the challenges related to photostability, batch consistency, and environmental resilience persist, necessitating further exploration into the optimized synthesis and doping strategies to enhance material stability. These findings underscore the potential of CsCdCl3 for high-security information storage, pharmaceutical anti-counterfeiting, and real-time environmental sensing, positioning it as a valuable material for the next generation of secure, intelligent packaging solutions.
Corrosion and Cavitation Performance of Flame-Sprayed NiCrBSi Composite Coatings Reinforced with Hard Particles
Authors: Frunzaverde Doina , Marginean Gabriela , Ciubotariu Costel Relu
Published: December 2024

To enhance the operational life of hydraulic machinery, protective coatings against wear, particularly cavitation erosion, and corrosion might be applied on the surfaces of components. The experiments conducted in this study aimed to assess the suitability of 80/20 NiCrBSi/WC-Co composite coatings for this purpose. A coating of NiCrBSi self-fluxing alloy, which served as the reference material, was deposited alongside a NiCrBSi coating reinforced with 20% WC-Co, both applied by flame spraying onto X3CrNiMo13-4 substrates, the martensitic stainless steel type frequently utilized in turbine blade manufacturing. The improved density of the coatings and adhesion to the substrate was achieved by remelting with an oxyacetylene flame. The cavitation and corrosion performance of both the reference and composite coating were evaluated through cavitation tests and electrochemical measurements conducted in the laboratory. The results demonstrate that the addition of 20% WC-Co significantly enhances the cavitation resistance of the composite material, as evidenced by the reduction to 3.76 times of the cumulative erosion (CE), while the stabilization rate remained at half the value observed for the reference self-fluxing alloy coating. Conversely, the addition of WC-Co into the NiCrBSi coating resulted in a slight decrease in the corrosion resistance of the self-fluxing alloy. Nevertheless, the corrosion rate of the composite coating (124.80 µm/year) did not significantly exceed the upper limit for excellent corrosion resistance (100 µm/year).
Adaptation and Psychometric Analysis of the Scale of Attitudes Towards People with Disabilities (EAPCD) in Work Contexts in Chile
Authors: Chávez-Castillo Yasna , Pérez-Salas Claudia , Zañartu Isidora , Nazar Gabriela , Cigarroa Igor , Zapata-Lamana Rafael
Published: December 2024

Workers’ attitudes towards people with disabilities can influence labor inclusion. Despite the relevance of learning about these attitudes, in Chile, there are no reliable and validated instruments to measure them in workers. An instrumental study was carried out to adapt and psychometrically analyze the Spanish version of the Scale of Attitudes towards People with Disabilities (EAPCD) in the Chilean population. By means of a non-probabilistic convenience sampling, 310 people between 19 and 76 years of age (M = 39.4; SD = 11.2) from different regions of Chile participated in the study. The linguistic adaptation included the change in Spanish idioms and expressions to the Chilean context, whose relevance was validated with cognitive interviews. Descriptive analysis, internal consistency analysis, and CFA (confirmatory factor analysis) were performed. The CFA indicated an adequate fit to the three-factor model proposed in the original scale (χ2(431) = 808.070, p < 0.01; RMSEA = 0.053; CFI = 0.93; TLI = 0.93). The Social Relations and Normalization dimensions were reliable; however, it is recommended that the items of the Intervention Programs dimension be revised or eliminated, since they could be confusing in the local context. It is concluded that the scale is reliable and valid to evaluate attitudes towards the inclusion of people with disabilities in Chile in the work context.
Joint Communication and Channel Discrimination
Authors: Wu Han , Joudeh Hamdi
Published: December 2024

We consider a basic joint communication and sensing setup comprising a transmitter, a receiver and a sensor. The transmitter sends a codeword to the receiver through a discrete memoryless channel, and the receiver is interested in decoding the transmitted codeword. At the same time, the sensor picks up a noisy version of the transmitted codeword through one of two possible discrete memoryless channels. The sensor knows the codeword and wishes to discriminate between the two possible channels, i.e., to identify the channel that has generated the output given the input. We study the trade-off between communication and sensing in the asymptotic regime, captured in terms of the channel coding rate against the two types of discrimination error exponents. We characterize the optimal trade-off between the rate and the exponents for general discrete memoryless channels with an input cost constraint.
Numerical Study and Optimization-Based Sensitivity Analysis of a Vertical-Axis Wind Turbine
Authors: El Maani Rabii , Radi Bouchaib , El Hami Abdelkhalak
Published: December 2024

This study aims to introduce a new optimization method for designing a vertical-axis wind turbine (VAWT) that dynamically morphs its blades as a function of the tip-speed ratio (TSR) and azimuthal angle. For this purpose, the Darrieus turbine is the subject of a dynamic study under transient aerodynamic loads. By resolving the two-dimensional unsteady incompressible Navier–Stokes equation, the aerodynamic torque is obtained with the k-ϵ realizable turbulence model. A comparison between rotor operation at optimal and lower  Cp values is possible according to the investigation of flow-field characteristics for a variety of tip-speed ratio values, with experimental results so that a better understanding of the vertical-axis wind turbine’s basic physics is obtained. Then, a multi-objective optimization technique is coupled with ANSYS Workbench to increase the energy generation of VAWT blades by reducing the drag coefficient and maximizing the power coefficient. The input variables were evaluated through a sensitivity analysis, and the most important one was chosen. The analysis results of the best compromise showed that the design methodology’s output is feasible for manufacturing.
An Economic Analysis of Mid- to Long-Term Prospects for Deep-Sea Offshore Wind-Power-to-Ammonia: A Case Study of Fujian Province
Authors: Zheng Xiaoying , Liu Pei
Published: December 2024

Deep-sea offshore wind power is crucial for reducing emissions in certain regions’ energy transitions. However, its development has been largely overlooked due to its high investment costs and fluctuation. Ammonia production offers a significant opportunity to enhance economic feasibility and facilitate energy consumption. This study, using a bottom-up model and based on the energy system of Fujian Province, China, examines the technical pathways for offshore wind-to-ammonia production. Through extensive scenario calculations, the study analyzes economic factors affecting the development of DOWD. The results show that when ammonia prices range from USD 0.52 to USD 0.6/kg, the deep-sea offshore wind with ammonia production (DOWD+AP) mode demonstrates its advantages, while the price of a single DOWD unit must fall below USD 1.73/W to show superiority. It is recommended that the installation of DOWD in Fujian province should not begin before 2040, with potential ammonia production capacity reaching 24 Mt/year. If ammonia production is unrestricted, the DOWD+AP mode could introduce a new method for flexible regulation, primarily compensating for gaps in solar- and wind-power generation during the summer months.
Changes and Trade-Offs of Ecological Service Functions of Public Welfare Forests (2000–2019) in Southwest Zhejiang Province, China
Authors: Liu Ziqiang , Han Deguo , Ye Limin , Xu Yuanke , Zhang Yong
Published: December 2024

Studying the factors influencing ecosystem regulation services in southwestern Zhejiang is of great significance for formulating reasonable pricing strategies for forest ecosystem regulation services and optimizing ecological security. This study constructed a theoretical framework for analyzing forest ecosystem regulation services and assessed the spatiotemporal evolution and influencing factors of forest ecosystem regulation services using InVEST model calculations and spatial autocorrelation analysis. The results showed that all ecosystem services of forests in the study improved from 2000 to 2019, with the exception of soil conservation. The water conservation function increased significantly from 2000 to 2019, with an overall increase of 3.53%. The biodiversity conservation function in 2019 also increased significantly, with an average increase of 2.16% compared with 2000. The synergies mainly occurred between water source regulation and soil conservation, soil conservation and biodiversity, and forest recreation and carbon storage. Forest Reserve was precipitation, canopy closure, elevation, and soil texture, and their driving forces differed at different time scales. The trade-offs mainly occurred between soil conservation and forest recreation, forest recreation and biodiversity, and carbon storage and biodiversity. The research results provide a reference for achieving ecological protection and high-quality development in the southwestern region of Zhejiang.
Tree Species Classification for Shelterbelt Forest Based on Multi-Source Remote Sensing Data Fusion from Unmanned Aerial Vehicles
Authors: Jiang Kai , Zhao Qingzhan , Wang Xuewen , Sheng Yuhao , Tian Wenzhong
Published: December 2024

Accurately understanding the stand composition of shelter forests is essential for the construction and benefit evaluation of shelter forest projects. This study explores classification methods for dominant tree species in shelter forests using UAV-derived RGB, hyperspectral, and LiDAR data. It also investigates the impact of individual tree crown (ITC) delineation accuracy, crown morphological parameters, and various data sources and classifiers. First, as a result of the overlap and complex structure of tree crowns in shelterbelt forests, existing ITC delineation methods often lead to over-segmentation or segmentation errors. To address this challenge, we propose a watershed and multi-feature-controlled spectral clustering (WMF-SCS) algorithm for ITC delineation based on UAV RGB and LiDAR data, which offers clearer and more reliable classification objects, features, and training data for tree species classification. Second, spectral, texture, structural, and crown morphological parameters were extracted using UAV hyperspectral and LiDAR data combined with ITC delineation results. Twenty-one classification images were constructed using RF, SVM, MLP, and SAMME for tree species classification. The results show that (1) the proposed WMF-SCS algorithm demonstrates significant performance in ITC delineation in complex mixed forest scenarios (Precision = 0.88, Recall = 0.87, F1-Score = 0.87), resulting in a 1.85% increase in overall classification accuracy; (2) the inclusion of crown morphological parameters derived from LiDAR data improves the overall accuracy of the random forest classifier by 5.82%; (3) compared to using LiDAR or hyperspectral data alone, the classification accuracy using multi-source data improves by an average of 7.94% and 7.52%, respectively; (4) the random forest classifier combined with multi-source data achieves the highest classification accuracy and consistency (OA = 90.70%, Kappa = 0.8747).
A Study of Short-Chain Fatty Acids During the Canalicular and Early Saccular Phases of Fetal Lung Development and Childhood Asthma
Authors: Lin Huang , Perkins Neil J. , Nkoy Flory , Stanford Joseph B. , Schliep Karen C. , Peddada Shyamal D.
Published: December 2024

Background: Emerging literature indicates that the microbiome and its byproducts, such as short-chain fatty acids (SCFAs), play an important role in childhood diseases such as allergies and asthma. Specifically, there is evidence suggesting that SCFAs play a critical role in fetal immunoprogramming during the late saccular phase of fetal lung development. An increase in acetate during the late saccular phase is known to play a critical role in inhibiting histone deacetylases (HDACs), resulting in a cascade of events, including Treg immune regulation, involved in fetal immunoprogramming, and reduction in the asthma phenotype. However, it is not known whether changes in SCFA levels, especially acetate, occurred during the canalicular or early saccular phase among pregnant women whose children did not develop asthma. Methods: In this research, we investigated this question using plasma samples obtained from mothers during the 20th and 28th weeks of pregnancy. Mothers whose children developed asthma were categorized as cases, while those whose children did not were categorized as controls. The specimens were assayed for a panel of SCFAs consisting of acetate, propionate, butyrate, valerate, isobutyrate, and isovalerate. Results: The resulting data indicated no significant differences between the cases and controls, either at week 20 or week 28, in any of the SCFAs measured, despite the vascularization during these phases. Conclusions: We did not find differences in measured SCFAs at week 20 or at week 28. A larger prospective study covering multiple time points is necessary to confirm the findings of this preliminary study. Such a study, together with the published literature regarding later time points, may help discover critical windows during pregnancy when simple manipulation of diet will result in healthier outcomes for infants.
Wnt Signaling Pathway in Tumor Biology
Authors: Iluta Sabina , Nistor Madalina , Buruiana Sanda , Dima Delia
Published: December 2024

Relapse and metastasis are the major challenges that stand in the way of cancer healing and survival, mainly attributed to cancer stem cells (CSCs). Their capabilities of self-renewal and tumorigenic potential leads to treatment resistance development. CSCs function through signaling pathways such as the Wnt/β-catenin cascade. While commonly involved in embryogenesis and adult tissues homeostasis, the dysregulation of the Wnt pathway has direct correlations with tumorigenesis, metastasis, and drug resistance. The development of therapies that target CSCs and bulk tumors is both crucial and urgent. However, the extensive crosstalk present between Wnt and other signaling networks (Hedgehog and Notch) complicates the development of efficient long-term therapies with minimal side-effects on normal tissues. Despite the obstacles, the emergence of Wnt inhibitors and subsequent modulation of the signaling pathways would provide dynamic therapeutic approaches to impairing CSCs and reversing resistance mechanisms.
Incidence, Risk Factors, and Outcomes of Thrombocytopenia in Older Medical Inpatients: A Prospective Cohort Study
Authors: Papakitsou Ioanna , Papazachariou Andria , Filippatos Theodosios D , Ioannou Petros
Published: December 2024

Background: Thrombocytopenia, defined as a platelet count of less than 150 × 109/L, is a frequent condition among hospitalized patients and presents unique challenges in diagnosis and management. Despite its commonality, data on incidence and related risk factors in medical inpatients remain limited, especially in older people. Methods: A 2-year prospective cohort study with a 3-year follow-up was conducted on inpatients aged ≥65 years admitted to a medical ward. Clinical data were collected, including demographics, comorbidities, laboratory results, and outcomes. Multivariate logistic regression analysis assessed risk factors associated with non-resolution of thrombocytopenia and mortality. Results: The study included 961 older inpatients with a mean age of 82 years. Thrombocytopenia occurred in 22.6% of the study population. The most common causes were infections (57.4%) and drug-induced thrombocytopenia (25.3%). The non-resolution of thrombocytopenia was noted in 59% of patients. In-hospital and 3-year mortality was significantly higher in this subgroup compared to the rest (24.5% vs. 12.7%, p = 0.015) and (72.4% vs. 59.8%, p = 0.04, respectively). In multivariate analysis, nadir platelet count and hematologic disease were independent factors associated with the non-resolution of thrombocytopenia. Furthermore, in individuals with thrombocytopenia, the administration of norepinephrine (p < 0.001) and a higher clinical frailty score (p < 0.001) were observed as independent mortality predictors. Conclusions: Thrombocytopenia in older medical inpatients is associated with poor prognosis, particularly in those with non-resolution thrombocytopenia. Early identification and targeted management may improve outcomes.
Awareness and Knowledge of Lead Poisoning: A Street Survey in Three Municipalities of Georgia
Authors: Kekelidze Dali , Malazonia Mari , Tsereteli David , Kalandadze Iagor
Published: December 2024

Lead poisoning is a serious public health problem, especially for children. Despite screening programs to reduce lead exposure, there is still a lack of knowledge about its harmful impact. The study aimed to analyze how aware people in Georgia are about lead poisoning and its health effects. In this street survey, 384 adults from three municipalities, Batumi, Ozurgeti, and Zugdidi, were interviewed from March to June 2024. We used descriptive statistics and Pearson’s chi-square test for data analysis. The majority of respondents noted that children are at high risk of lead poisoning. In all selected municipalities, people know that lead can be found in toys, but they do not know it can be found in jewelry and cosmetics, especially in Ozurgeti. Many respondents are not aware that lead poisoning can cause cardiovascular disease, anemia, and kidney failure. More educational campaigns are needed to highlight lead poisoning sources and their effects on health to protect the population.
Testing a Family Conflict Intervention for Parents and Typically Developing Adolescent Siblings of Individuals with Intellectual and/or Developmental Disabilities
Authors: Yang Vevette J. H. , Bergman Kathleen N. , Cummings E. Mark
Published: December 2024

Parents and typically developing (TD) youth siblings of individuals with intellectual and/or developmental disabilities (IDD) often experience greater caregiving burden, stress, and hardships in family functioning. They are at increased risk of family conflict and youth adjustment problems when TD siblings are adolescents since they need to balance caregiving responsibilities and various changes that naturally occur during adolescence. However, there is a lack of intervention research on parents and TD adolescent siblings that focuses on family conflict and family-wide participation. This study analyzed whether participating in a brief family intervention could improve families’ knowledge of marital and family-wide conflict and TD adolescents’ adjustment problems. We found that mothers and fathers significantly improved their knowledge of marital conflict and that TD adolescents significantly improved their knowledge of family-wide conflict. We also found that fathers reported significant reductions in internalizing and externalizing problems in TD adolescents. The findings support the impact of even brief evidence-based interventions targeting family-level improvements for families with both TD adolescent siblings and individuals with IDD. The findings also accentuate the significance of involving both mothers and fathers in family intervention research, suggesting that different caregivers may experience both shared and unique benefits from participating.
Should Artificial Intelligence Play a Durable Role in Biomedical Research and Practice?
Authors: Bongrand Pierre
Published: December 2024

During the last decade, artificial intelligence (AI) was applied to nearly all domains of human activity, including scientific research. It is thus warranted to ask whether AI thinking should be durably involved in biomedical research. This problem was addressed by examining three complementary questions (i) What are the major barriers currently met by biomedical investigators? It is suggested that during the last 2 decades there was a shift towards a growing need to elucidate complex systems, and that this was not sufficiently fulfilled by previously successful methods such as theoretical modeling or computer simulation (ii) What is the potential of AI to meet the aforementioned need? it is suggested that recent AI methods are well-suited to perform classification and prediction tasks on multivariate systems, and possibly help in data interpretation, provided their efficiency is properly validated. (iii) Recent representative results obtained with machine learning suggest that AI efficiency may be comparable to that displayed by human operators. It is concluded that AI should durably play an important role in biomedical practice. Also, as already suggested in other scientific domains such as physics, combining AI with conventional methods might generate further progress and new applications, involving heuristic and data interpretation.
Integrated Analysis of Transcriptome and Metabolome in the Brain After Cold Stress of Red Tilapia During Overwintering
Authors: Zhu Chenxi , Yang Haoran , Zhu Wenbin , Jiang Qichen , Dong Zaijie , Wang Lanmei
Published: December 2024

Cold stress during overwintering is considered a bottleneck problem limiting the development of the red tilapia (Oreochromis spp.) industry, and the regulation mechanism is currently not well understood. In this study, the fish (initial weight: 72.71 ± 1.32 g) were divided into the cold stress group (cold) and the control (normal) group. In the control group, the water temperature was maintained at 20 °C, which is basically consistent with the overwintering water temperature in greenhouses of local areas. In the cold group, the water temperature decreased from 20 °C to 8 °C by 2 °C per day during the experiment. At the end of the experiment, the levels of fish serum urea nitrogen, glucose, norepinephrine, alkaline phosphatase, total bilirubin, and total cholesterol in the cold group changed significantly compared with that in the control group (P < 0.05). Then transcriptome sequencing and LC–MS metabolome of brain tissue were further employed to obtain the mRNA and metabolite datasets. We found that the FoxO signaling pathway and ABC transporters played an important role by transcriptome–metabolome association analysis. In the FoxO signaling pathway, the differentially expressed genes were related to cell cycle regulation, apoptosis and immune-regulation, and oxidative stress resistance and DNA repair. In the ABC transporters pathway, the ATP-binding cassette (ABC) subfamily abca, abcb, and abcc gene expression levels, and the deoxycytidine, L-lysine, L-glutamic acid, L-threonine, ornithine, and uridine metabolite contents changed. Our results suggested that the cold stress may promote apoptosis through regulation of the FoxO signaling pathway. The ABC transporters may respond to cold stress by regulating amino acid metabolism. The results provided a comprehensive understanding of fish cold stress during overwintering, which will facilitate the breeding of new cold-resistant varieties of red tilapia in the future.
Beyond the “Dominant” and “Recessive” Patterns of Inheritance
Authors: Chatzikyriakidou Anthoula
Published: December 2024

This study aimed to investigate whether genes with different modes of inheritance differ in the presence of promoter-enriched CGI loci. For each autosomal chromosome, the author searched for variations in the total number of diseases’ phenotypes with autosomal dominant (AD) and recessive (AR) inheritance for a list of promoter-poor CGI (CGI−) and promoter-enriched CGI (CGI+) genes using the OMIM database. Then, the CGI− and CGI+ genes displaying random allelic or bi-allelic expression were examined. The author evaluated whether there was a distinct distribution of AD and AR diseases in the groups of chromosomes based on their SNP hotspot density. The same analysis was conducted for the X chromosome. The SPSS statistical package was utilized. The distribution of AD and AR diseases between CGI− and CGI+ bi-allelic genes significantly differed in autosomal chromosomes 6 and 17, which show intermediate SNP hotspot density. Additionally, a statistically significant difference was observed in AD and AR diseases in the remaining autosomal chromosomes with low SNP hotspots between their randomly allelic expressed CGI− and CGI+ genes. Specifically, AD diseases were related to CGI− genes, while AR diseases were associated with CGI+ genes. In the X chromosome, X-linked dominant (XLD) diseases were mainly found in CGI+ genes, and X-linked recessive (XLR) diseases were found in CGI− genes, regardless of the X-inactivation process. It is essential to study inheritance and classify genetic variants in a more stochastic way than the terms “Dominant” and “Recessive,” and their derivatives, such as “Codominant” and “Incomplete Dominant,” are applied in Mendelian and non-Mendelian inheritance. This concept may further explain the “Reduced Penetrance” and “Variable Expressivity” in certain human diseases. All the above suggests a need to reassess how genetic and epigenetic data are studied and utilized for genetic counseling or precision medicine.
Cellular and Molecular Effects of the Bruck Syndrome-Associated Mutation in the PLOD2 Gene
Authors: Bolshakova Olga I. , Latypova Evgenia M. , Komissarov Artem E. , Slobodina Alexandra D. , Ryabova Elena V. , Varfolomeeva Elena Yu. , Agranovich Olga E. , Batkin Sergey F. , Sarantseva Svetlana V.
Published: December 2024

Bruck syndrome is a rare autosomal recessive disorder characterized by increased bone fragility and joint contractures similar to those in arthrogryposis and is known to be associated with mutations in the FKBP10 (FKBP prolyl isomerase 10) and PLOD2 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2) genes. These genes encode endoplasmic reticulum proteins that play an important role in the biosynthesis of type I collagen, which in turn affects the structure and strength of connective tissues and bones in the body. Mutations are associated with disturbances in both the primary collagen chain and its post-translational formation, but the mechanism by which mutations lead to Bruck syndrome phenotypes has not been determined, not only because of the small number of patients who come to the attention of researchers but also because of the lack of disease models. In our work, we investigated the cellular effects of two forms of the wild-type PLOD2 gene, as well as the PLOD2 gene with homozygous mutation c.1885A>G (p.Thr629Ala). The synthesized genetic constructs were transfected into HEK293 cell line and human skin fibroblasts (DF2 line). The localization of PLOD2 protein in cells and the effects caused by the expression of different isoforms—long, short, and long with mutation—were analyzed. In addition, the results of the transcriptome analysis of a patient with Bruck syndrome, in whom this mutation was detected, are presented.
Modeling Fibroblast–Cardiomyocyte Interactions: Unveiling the Role of Ion Currents in Action Potential Modulation
Authors: Dong Yuqing , Liu Fusheng
Published: December 2024

Fibrotic cardiomyopathy represents a significant pathological condition characterized by the interaction between cardiomyocytes and fibroblasts in the heart, and it currently lacks an effective cure. In vitro platforms, such as engineered heart tissue (EHT) developed through the co-culturing of cardiomyocytes and fibroblasts, are under investigation to elucidate and manipulate these cellular interactions. We present the first integration of mathematical electrophysiological models that encapsulate fibroblast–cardiomyocyte interactions with experimental EHT studies to identify and modulate the ion channels governing these dynamics. Our findings resolve a long-standing debate regarding the effect of fibroblast coupling on cardiomyocyte action potential duration (APD). We demonstrate that these seemingly contradictory outcomes are contingent upon the specific properties of the cardiomyocyte to which the fibroblast is coupled, particularly the relative magnitudes of the fast Na+ and transient outward K+ currents within the cardiomyocyte. Our results emphasize the critical importance of detailed ionic current representation in cardiomyocytes for accurately predicting the interactions between cardiomyocytes and fibroblasts in EHT. Surprisingly, complex ion channel-based models of fibroblast electrophysiology did not outperform simplified resistance–capacitance models in this analysis. Collectively, our findings highlight the promising potential of synergizing in vitro and in silico approaches to identify therapeutic targets for cardiomyopathies.
Evaluation of Cell-Free DNA Long Fragments in the Triage of FIT+ Patients Enrolled in a Colorectal Cancer Screening Program: An Italian Prospective, Cross-Sectional Study
Authors: Scimia Mauro , Pepe Francesco , Russo Gianluca , Malapelle Umberto , Scimia Simone , Alfieri Annalaura , Olivieri Valentina , Chuang Rachel , Tanaka Hiromi , Sha Michael , Chen David , Scimone Claudia , Palumbo Lucia , Shen Shuo , Gavrilov Yulia , Edelstein Stav , Bianco Maria Antonia , Troncone Giancarlo
Published: December 2024

Introduction: Colorectal cancer screening programs are effective in reducing incidence and mortality. In Europe, every FIT+ patient is referred to colonoscopy. The available data show that ~75.0% of these patients are negative. It is desirable to select patients at a greater risk of having a positive colonoscopy. Materials and Methods: 711 subjects, aged 50–74, attending the screening program of ASL-NA-3-SUD (Naples, Italy), were enrolled in a cross-sectional study to evaluate the performance of the QuantiDNA™ test and the non-inferiority of an alternative approach (AAP). This evaluation is based on FIT+ and QuantiDNA™+ patients referred to colonoscopy, compared to Standard of Care (SOC) colonoscopy following a FIT+ test alone. A non-inferiority margin (NIM) for colorectal neoplasia (CN) and advanced adenomas (AA) was set at −10% and at −3.8% for CRC. Results: The odds ratio was 1.76 (p-value = 0.009). The detection rate of AAP was 15.9% for colorectal neoplasia, 13.0% for advanced adenoma, and 3.0% for CRC. The risk difference between AAP and SOC was −5.07% (95% C.I. −9.23, −0.90) for colorectal neoplasia, −4.02% (95% C.I. −7.89, −0.16) for advanced adenomas, and −1.04% (95% C.I. −3.16, 1.07) for CRC. This data suggests that AAP is non-inferior to SOC for detecting CN, AA, and CRC. The expected decrease in colonoscopies is 33.4%. Conclusions: The QuantiDNA™ test is straightforward, non-invasive, and well-tolerated. Data from this study indicate that it is effective in the reduction of the need for colonoscopy examinations (−33.4%) and is non-inferior to SOC in the detection of significant colorectal lesions.
Non-Traditional Natural Stabilizers in Drug Nanosuspensions
Authors: Ozsoysal Simay , Bilgili Ecevit
Published: December 2024

Poor solubility of many drugs, with ensuing low bioavailability, is a big challenge in pharmaceutical development. Nanosuspensions have emerged as a platform approach for long-acting injectables and solid dosages that enhance drug bioavailability. Despite improvements in nanosuspension preparation methods, ensuring nanosuspension stability remains a critical issue. Conventionally, synthetic and semi-synthetic polymers and surfactants are used in nanosuspension formulations. However, no polymer or surfactant group is universally applicable to all drugs. This fact, as well as their toxicity and side effects, especially if used in excess, have sparked the interest of researchers in the search for novel, natural stabilizers. The objective of this paper is to provide a comprehensive analysis of non-traditional natural stabilizers reported in the literature published over the last decade. First, physical stability and stabilization mechanisms are briefly reviewed. Then, various classes of non-traditional natural stabilizers are introduced, with particular emphasis on their stabilization potential, safety, and pharmaceutical acceptability. Wherever data were available, their performance was compared with the traditional stabilizers. Furthermore, the benefits and limitations of using these stabilizers are examined, concluding with future prospects. This review is expected to serve as a valuable guide for researchers and formulators, offering insights into non-traditional natural stabilizers in drug nanosuspension formulations.
Anomalies in Long-Crack Propagation at Low ΔK in Some Engineering Alloys
Authors: Kujawski Daniel , Vasudevan Asuri K.
Published: December 2024

In this article, we discuss an unusual pattern in long-crack behavior at low stress intensity factor ranges ΔK (below ΔKth), characterized by an initial dip, followed by a plateau, and then an acceleration in fatigue crack growth (FCG) rate. This unanticipated FCG behavior was first observed experimentally in the IMI 834 alloy and reported by Marci in 1996. Such an anomaly is only reported from experimental observation but cannot be understood or explained using the plasticity, roughness, or oxide-induced crack closure assumptions. It also has not been fully explained through either metallurgical analysis or failure mode investigation. The established application of fracture mechanics to the FCG rate (da/dN) assumes that the FCG rate decreases with decreasing ΔK towards the threshold of ΔKth with (da/dN) ≤ 10−7 mm/cycle. Yet, some materials exhibit a lack of ΔK threshold dependence for long cracks when tested using constant-Kmax or constant-R-ratio testing. An understanding of this anomaly and the related physics poses a scientific challenge. It is also relevant to predict the safe service life of structures subjected to high-frequency and low-amplitude vibrating loads. Here, we provide our interpretation and discuss the significant implications of this phenomenon in the context of damage-tolerant design.
Study on the Effect of Laser Power on the Microstructure and Properties of Cladding Stellite 12 Coatings on H13 Steel
Authors: Wang Qianjie , Shu Xuedao , Xu Haijie , Xu Sheng , Zhang Song
Published: December 2024

To address the issue of cracking in aluminum extrusion dies during operation, this study employs laser cladding technology to modify the surface of these dies. This modification aims to enhance their hardness and friction resistance. Laser cladding technology was utilized to coat the surface of H13 steel with Stellite 12, a cobalt-based alloy, at varying laser power levels. The surface formation quality, microstructural organization, phase composition, microhardness, and wear resistance of the coatings were investigated using optical microscopy, scanning electron microscopy, energy-dispersive spectroscopy, X-ray diffraction (XRD), microhardness testing, and confocal microscopy. The results indicated that as the laser power increased, the surface formation quality of the coating gradually improved, while the dilution rate of the coating increased. Changes in the phase composition and microstructure were not significant, and both microhardness and wear resistance initially increased before decreasing. Optimal process parameters for achieving good surface formation quality, high microhardness, and strong wear resistance were found to be a laser output power of 2200 W, scanning speed of 10 mm/s, feeding rate of 1.2 r/min, and overlap rate of 40%. The results indicate that the coating applied to the surface of H13 steel using Stellite 12 enhances the performance of aluminum extrusion dies.