bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Ozone Exposure, COPD, and Asthma Mortality: A Retrospective Cohort Study in the Republic of Korea
Authors: Kim Min-Seok , Lim Youn-Hee , Oh Jongmin , Myung Jisun , Han Changwoo , Bae Hyun-Joo , Kim Soontae , Hong Yun-Chul , Lee Dong-Wook
Published: November 2024

Ozone concentrations have increased in recent decades, and several studies have reported that long-term exposure to ozone increases the mortality risk induced by respiratory conditions. However, research on cause-specific mortality related to ozone exposure and respiratory diseases remains scarce. We constructed a retrospective cohort of 5,360,032 adults aged ≥ 65 years from the National Health Insurance Service of Republic of Korea, and death certificates were obtained from Statistics Republic of Korea to determine the cause of death between 2010 and 2019. The daily maximum 8 h average levels of ozone during the warm season annually (May–September) and other air pollutants were determined for the residential district. We analyzed the data using a time-varying Cox proportional hazards model with individual- and district-level covariates, incorporating a competing risk framework to address deaths from causes other than chronic obstructive pulmonary disease (COPD) and asthma. In our single-pollutant model with a 3-year moving average, a 1 ppb increase in ozone exposure was associated with a hazard ratio (HR) of 1.011 (95% confidence interval [CI]: 1.008–1.013) for COPD mortality and an HR of 1.016 (95% CI: 1.011–1.022) for asthma mortality. In our model adjusted for the presence of underlying diseases and district-level variables, the HRs were 1.009 (95% CI: 1.008–1.014) for COPD and 1.017 (95% CI: 1.011–1.023) for asthma, respectively. These associations remained robust in our two-pollutant model, except for NO2 and COPD. A linear concentration–response relationship was identified between ozone concentration, COPD, and asthma mortality. In this large nationwide cohort study, long-term exposure to ozone was associated with an increased risk of death from COPD and asthma in older Korean adults.
Genomic Comparisons Revealed the Key Genotypes of Streptomyces sp. CB03234-GS26 to Optimize Its Growth and Relevant Production of Tiancimycins
Authors: Liu Huiming , Lin Jing , Huang Yong , Duan Yanwen , Zhu Xiangcheng
Published: November 2024

Strain robustness and titer improvement are major challenges faced in the industrial development of natural products from Streptomyces. Tiancimycins (TNMs) produced by Streptomyces sp. CB03234 are promising anticancer payloads for antibody-drug conjugates, but further development is severely limited by the low titer of TNMs. Despite many efforts to generate various TNMs overproducers, the mechanisms underlying high TNMs production remain to be explored. Herein, genome resequencing and genomic comparisons of different TNMs overproducers were conducted to explore the unique genotypes in CB03234-GS26. Four target genes were selected for further bioinformatic analyses and genetic validations. The results indicated that the inactivation of histidine ammonia-lyase (HAL) showed the most significant effect by blocking the intracellular degradation of histidine to facilitate relevant enzymatic catalysis and thus improve the production of TNMs. Additionally, the potassium/proton antiporter (P/PA) was crucial for intracellular pH homeostasis, and its deficiency severely impaired the alkaline tolerance of the cells. Subsequent pan-genomic analysis suggested that HAL and P/PA are core enzymes that are highly conserved in Streptomyces. Therefore, HAL and P/PA represented novel targets to regulate secondary metabolism and enhance strain robustness and could become potential synthetic biological modules to facilitate development of natural products and strain improvement in Streptomyces.
Optimized Polyhydroxybutyrate Production by Neobacillus niacini GS1 Utilizing Corn Flour, Wheat Bran, and Peptone: A Sustainable Approach
Authors: Shrimali Gaurav , Gangawane Ajit , Rami Esha , Shah Hardik , Thummar Kashyap , Sahoo Dipak Kumar , Patel Ashish , Schmidt Jens Ejbye
Published: November 2024

Plastic pollution is a pressing environmental challenge, necessitating the development of biodegradable alternatives like polyhydroxybutyrate (PHB). This study focuses on optimizing PHB production by Neobacillus niacini GS1, a bacterium isolated from a municipal dumping site. By utilizing agricultural residues such as corn flour, wheat bran, and peptone as substrates, we aimed to establish an eco-friendly method for biopolymer production, contributing to sustainable agricultural residue management and bioplastic innovation. The bacterium was identified using morphological, biochemical, and molecular techniques. The optimization process involved adjusting variables such as inoculum age, inoculum size, incubation time, agitation rate, incubation temperature, pH of the medium, carbon sources, and nitrogen sources. Response surface methodology (RSM) was employed to identify optimal conditions, with the highest PHB yield of 61.1% achieved under specific conditions: 37 °C, pH 7, and an agitation rate of 150 rpm. These findings underscore the potential of Neobacillus niacini GS1 in converting agro-industrial residues into valuable biopolymers, promoting sustainable bioplastic production, and advancing agricultural residue valorization efforts through the use of eco-friendly materials.
Assessing the Utility of ColabFold and AlphaMissense in Determining Missense Variant Pathogenicity for Congenital Myasthenic Syndromes
Authors: Ryan-Phillips Finlay , Henehan Leighann , Ramdas Sithara , Palace Jacqueline , Beeson David , Dong Yin Yao
Published: November 2024

Background/Objectives: Congenital myasthenic syndromes (CMSs) are caused by variants in >30 genes with increasing numbers of variants of unknown significance (VUS) discovered by next-generation sequencing. Establishing VUS pathogenicity requires in vitro studies that slow diagnosis and treatment initiation. The recently developed protein structure prediction software AlphaFold2/ColabFold has revolutionized structural biology; such predictions have also been leveraged in AlphaMissense, which predicts ClinVar variant pathogenicity with 90% accuracy. Few reports, however, have tested these tools on rigorously characterized clinical data. We therefore assessed ColabFold and AlphaMissense as diagnostic aids for CMSs, using variants of the CHRN genes that encode the nicotinic acetylcholine receptor (nAChR). Methods: Utilizing a dataset of 61 clinically validated CHRN variants, (1) we evaluated the possibility of a ColabFold metric (either predicted structural disruption, prediction confidence, or prediction quality) that distinguishes variant pathogenicity; (2) we assessed AlphaMissense’s ability to differentiate variant pathogenicity; and (3) we compared AlphaMissense to the existing pathogenicity prediction programs AlamutVP and EVE. Results: Analyzing the variant effects on ColabFold CHRN structure prediction, prediction confidence, and prediction quality did not yield any reliable pathogenicity indicative metric. However, AlphaMissense predicted variant pathogenicity with 63.93% accuracy in our dataset—a much greater proportion than AlamutVP (27.87%) and EVE (28.33%). Conclusions: Emerging in silico tools can revolutionize genetic disease diagnosis—however, improvement, refinement, and clinical validation are imperative prior to practical acquisition.
Dysphagia and Body Composition in Cornelia de Lange Syndrome
Authors: Mędza Aleksandra , Cieszko Aleksandra , Gliwa Małgorzata , Brzeziński Michał , Wierzba Jolanta , Szlagatys-Sidorkiewicz Agnieszka , Sznurkowska Katarzyna
Published: November 2024

Background/Objectives: Limited research had investigated nutritional status in patients with Cornelia de Lange Syndrome (CdLS) (OMIM 122470, 300590, 300882, 610759, 620568 and 614701). Body composition assessed via bioelectric impedance (BIA) is a particularly under-explored issue. In this cross-sectional study, we hypothesize that body composition imbalance is frequent in CdLS and may be associated with dysphagia. We aimed to determine dysphagia prevalence in CdLS. Dysphagia may be a sign or a complication of GERD (gastroesophageal reflux disease), which is the most frequent gastroenterological disorder in CdLS patients; Methods: Fourteen Polish patients with a clinical or genetic diagnosis of CdLS were included in the study. We performed body composition analysis via bioelectric impedance taking into account the phase angle (PhA) and Body Cell Mass (BCM) in patients who cooperated and were able to sit still. The patients’ caregivers completed the pediatric version of the Eating Assessment Tool (PEDI-EAT-10). Based on the questionnaire scoring, we divided the patients into dysphagic and non-dysphagic groups. Body compartments of those two groups were compared. Statistical correlations between PhA and the PEDI-EAT-10 score were calculated; Results: Eleven of the fourteen CdLS patients had abnormalities in the BIA analysis in terms of fat mass (FM), fat free mass (FFM) and skeletal muscle mass (SMM). Six patients had excessive FM and four patients were deficient in FM. Two had deficiency in FFM and two had excessive FFM. We noted prevalence of dysphagia at 28.57%, with four patients having an PEDI-EAT-10 score higher or equal to 3, categorized as dysphagic. The dysphagic and non-dysphagic groups were not significantly different in terms of the proportion of patients with FM, FFM, SMM and BCM in the small cohort presented here. A statistically significant inverse correlation was found between the PhA and PEDI-EAT-10 score (rho = −0.72; p = 0.003); Conclusions: CdLS patients require investigation for dysphagia and nutritional status imbalance, as they are both frequent in this syndrome. The most prevalent are abnormalities in FM, both excess and deficit. PhA deviations observed in the bioimpedance study deepen with the severity of dysphagia. These findings require further investigation in a larger cohort.
Actionable Variants of Unknown Significance in Inherited Arrhythmogenic Syndromes: A Further Step Forward in Genetic Diagnosis
Authors: Martínez-Barrios Estefanía , Greco Andrea , Cruzalegui José , Cesar Sergi , Díez-Escuté Nuria , Cerralbo Patricia , Chipa Fredy , Zschaeck Irene , Fogaça-da-Mata Miguel , Díez-López Carles , Arbelo Elena , Grassi Simone , Oliva Antonio , Toro Rocío , Sarquella-Brugada Georgia , Campuzano Oscar
Published: November 2024

Background/Objectives: Inherited arrhythmogenic syndromes comprise a heterogenic group of genetic entities that lead to malignant arrhythmias and sudden cardiac death. Genetic testing has become crucial to understand the disease etiology and allow for the early identification of relatives at risk; however, it requires an accurate interpretation of the data to achieve a clinically actionable outcome. This is particularly challenging for the large number of rare variants obtained by current high-throughput techniques, which are mostly classified as of unknown significance. Methods: In this work, we present a new algorithm for the genetic interpretation of the remaining rare variants in order to shed light on their potential clinical implications and reduce the burden of unknown significance. Results: Our study illustrates the potential utility of our individualized comprehensive stepwise analyses focused on the rare variants associated with IAS, which are currently classified as ambiguous, to further determine their trends towards pathogenicity or benign traits. Conclusions: We advocate for personalized disease-focused population frequency data and family segregation analyses for all rare variants that remain ambiguous to further clarify their role. The current ambiguity should not influence medical decisions, but a potential deleterious role would suggest a closer clinical follow-up and frequent genetic data review for a more personalized clinical approach.
Special Issue “Mechanisms and Novel Therapeutic Approaches for Neurodegenerative Diseases”
Authors: Cardona Fernando
Published: November 2024

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are among the major health problems of the elderly, and represent a major global health challenge due to their increasing prevalence and complex pathophysiological mechanisms [...]
The Demographic and Clinical Characteristics, Prognostic Factors, and Survival Outcomes of Head and Neck Carcinosarcoma: A SEER Database Analysis
Authors: Hou Wanting , Yan Ouying , Zhu Hong
Published: November 2024

Background: Head and neck carcinosarcoma (HNCS) is a rare and highly aggressive malignancy with limited research, resulting in an incomplete understanding of disease progression and a lack of reliable prognostic tools. This study aimed to retrospectively analyze the clinical characteristics and outcomes of HNCS patients using data from the Surveillance, Epidemiology, and End Results (SEER) database and to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS). Methods: Patients diagnosed with HNCS from 1975 to 2020 were identified in the SEER database. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic indicators, with the optimal model selected using the minimal Akaike Information Criterion (AIC). The identified prognostic factors were incorporated into nomograms to predict OS and CSS. Model performance was assessed using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Survival curves were generated using Kaplan–Meier analysis and compared via the log-rank test. Results: A total of 152 HNCS patients were included, with 108 assigned to the training cohort and 44 to the validation cohort in a 7:3 ratio. Prognostic factors including age, primary tumor site, marital status, radiotherapy, chemotherapy, tumor size, pathological grade, and tumor stage were incorporated into the nomogram models. The models demonstrated strong predictive performance, with C-index values for OS and CSS of 0.757 and 0.779 in the training group, and 0.777 and 0.776 in the validation group, respectively. AUC values for predicting 3-, 5-, and 10-year OS were 0.662, 0.713, and 0.761, and for CSS the values were 0.726, 0.703, and 0.693. Kaplan–Meier analysis indicated significantly improved survival for patients with lower risk scores. The 3-, 5-, and 10-year OS rates for the entire cohort were 54.1%, 45.6%, and 35.1%, respectively, and the CSS rates were 62.9%, 57.5%, and 52.2%, respectively. Conclusions: This study provides validated nomograms for predicting OS and CSS in HNCS patients, offering a reliable tool to support clinical decision-making for this challenging malignancy. These nomograms enhance the ability to predict patient prognosis and personalize treatment strategies.
Stability of Blood DNA Methylation Across Two Timepoints in Three Cohorts
Authors: Danielewski Mikołaj , Walkowiak Jarosław , Wielgus Karolina , Nowak Jan Krzysztof
Published: November 2024

Background: DNA methylation mediates the gene–environment interactions, with implications for health and disease. Studies with sampling at more than one timepoint revealed the considerable variability of the blood methylome, but comprehensive resources on genome-wide methylation stability are still lacking. We aimed to identify methylation sites that remain the most stable across two timepoints in human whole blood. Methods: Publicly available blood DNA methylation data from three cohorts were analysed, which included methylation profiles at two timepoints >1 year apart. The cohorts included pre-/post-pubertal children (Illumina 450k array), the elderly (Illumina 450k array), and middle-aged adults with obesity (Illumina EPIC array). Two metrics were used for the stability assessment: the mean absolute difference (MAD) of beta values between two measurements and the intraclass correlation coefficient (ICC). We searched for probes demonstrating high stability (low MAD and high ICC) across the three cohorts. Data from 51 children, 86 elderly adults, and 120 middle-aged participants were re-analysed. Results: The median interquartile range (IQR) of the maximum (from three datasets) MAD was 2.1% (1.5–2.9%), and the median of the minimum ICC agreement coefficient was 0.053 (−0.077–0.304). The Pearson’s correlation coefficient for the ICC vs. maximum MAD was low (r = 0.34, p < 2.2 × 10−16). We found only 239 probes that were highly stable based on both the maximum MAD (<5th percentile, <0.01) and ICC criterion (>95th percentile, >0.74). Conclusions: The whole-blood DNA methylation profile, as measured using microarrays, is dynamic over >1 year, but contains a fraction of stable probes, most of which are related to genomic variation. A resource describing probe stability is made publicly available, with the intention to support biomarker studies and the investigation of early epigenetic programming. The absolute error and correlation are two complementary facets of probe stability that may be considered in further research, especially to determine the stability of probes in health and disease across different tissues and populations.
The Importance of Including Maternal Immune Activation in Animal Models of Hypoxic–Ischemic Encephalopathy
Authors: Collins Bailey , Lemanski Elise A. , Wright-Jin Elizabeth
Published: November 2024

Hypoxic–ischemic encephalopathy (HIE) is a perinatal brain injury that is the leading cause of cerebral palsy, developmental delay, and poor cognitive outcomes in children born at term, occurring in about 1.5 out of 1000 births. The only proven therapy for HIE is therapeutic hypothermia. However, despite this treatment, many children ultimately suffer disability, brain injury, and even death. Barriers to implementation including late diagnosis and lack of resources also lead to poorer outcomes. This demonstrates a critical need for additional treatments for HIE, and to facilitate this, we need translational models that accurately reflect risk factors and interactions present in HIE. Maternal or amniotic infection is a significant risk factor and possible cause of HIE in humans. Maternal immune activation (MIA) is a well-established model of maternal infection and inflammation that has significant developmental consequences largely characterized within the context of neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. MIA can also lead to long-lasting changes within the neuroimmune system, which lead to compounding negative outcomes following a second insult. This supports the importance of understanding the interaction of maternal inflammation and hypoxic–ischemic outcomes. Animal models have been invaluable to understanding the pathophysiology of this injury and to the development of therapeutic hypothermia. However, each model system has its own limitations. Large animal models such as pigs may more accurately represent the brain and organ development and complexity in humans, while rodent models are more cost-effective and offer more possible molecular techniques. Recent studies have utilized MIA or direct inflammation prior to HIE insult. Investigators should thoughtfully consider the risk factors they wish to include in their HIE animal models. In the incorporation of MIA, investigators should consider the type, timing, and dose of the inflammatory stimulus, as well as the timing, severity, and type of hypoxic insult. Using a variety of animal models that incorporate the maternal–placental–fetal system of inflammation will most likely lead to a more robust understanding of the mechanisms of this injury that can guide future clinical decisions and therapies.
Current Review of Heart Failure-Related Risk and Prognostic Factors
Authors: Wilk Michał Maksymilian , Wilk Jakub , Urban Szymon , Gajewski Piotr
Published: November 2024

Heart failure (HF) is a complex clinical syndrome characterized by the heart’s inability to maintain sufficient circulation, leading to inadequate organ perfusion and fluid buildup. A thorough understanding of the molecular, biochemical, and hemodynamic interactions that underlie this condition is essential for improving its management and enhancing patient outcomes. Recent advancements in cardiovascular research have emphasized the critical role of microRNAs (miRNAs) as post-transcriptional regulators of gene expression, playing an important part in the development and progression of HF. This review aims to explore the contributions of miRNAs, systemic congestion markers, and traditional biomarkers to the pathophysiology of heart failure, with the objective of clarifying their prognostic value and potential clinical applications. Among the miRNAs studied, miR-30d, miR-126-3p, and miR-483-3p have been identified as key players in processes such as left ventricular remodeling, regulation of pulmonary artery pressure, and adaptation of the right ventricle. These findings underscore the importance of miRNAs in modulating the structural and functional changes seen in HF. Beyond the heart, HF affects multiple organ systems, including the kidneys and liver, with markers of dysfunction in these organs—such as worsening renal function and liver stiffness—being closely linked to increased morbidity and mortality. This highlights the interdependence of the heart and other organs, where systemic congestion, indicated by elevated venous pressures, exacerbates organ dysfunction. In this context, traditional biomarkers like natriuretic peptides and cardiac troponins remain vital tools in the diagnosis and management of HF. Natriuretic peptides reflect ventricular strain, while troponins are indicators of myocardial injury, both of which are critical for risk stratification and monitoring disease progression. Emerging diagnostic techniques, such as lung ultrasonography and advanced echocardiographic methods, offer new ways to assess hemodynamic status, further aiding therapeutic decision-making. These techniques, alongside established biomarkers, provide a more comprehensive approach to understanding the complexities of heart failure and managing its impact on patients. In conclusion, miRNAs, systemic congestion markers, and traditional biomarkers are indispensable for understanding HF pathophysiology and determining patient prognosis. The integration of novel diagnostic tools with existing biomarkers holds the promise of improved strategies for the management of heart failure. However, further research is needed to validate their prognostic value and refine their role in optimizing treatment outcomes.
A Pathological Diagnostic Method for Traditional Brick-Masonry Dwellings: A Case Study in Guangfu Ancient City
Authors: Li Qinghong , Zhang Tiejian , Fang Yingming , Lin Fengzeng
Published: November 2024

Many regions of the world have traditional dwellings, which not only represent the main form of residential architecture, but also carry the local vernacular culture, display the region’s unique architectural style, materials and technology, and have important historical and cultural value. Due to environmental factors, traditional dwellings often suffer from architectural damage that threatens the stability of their structure and affects their esthetics value, resulting in a significant number of abandoned and demolished houses. In order to scientifically and effectively solve the damage problems of traditional dwellings, based on the theory of architectural pathology, the following diagnostic method for damage manifestation and the characteristics of traditional houses is proposed: “Architectural Pathology Appraisal–Pathological Environment Analysis–Mechanical Properties Testings”. The traditional dwellings in the ancient city of Guangfu were used as a case study for the practical application of the methodology for analyzing the main types and causes of the damage of the dwellings by examining the damage information of the dwellings, collecting the environmental data of the damaged walls, and testing the mechanical properties of the damaged walls. The results show that the main damage type in the ancient city dwellings of Guangfu is dampness damage, with corrosion deterioration, wall alkali flooding, and the moisture infiltration phenomenon as the manifested symptoms, and the damage is mainly concentrated in the lower part of the wall. In addition, the humidity and moisture content in the lower part of the wall is higher than that in the upper part of the wall, and the compressive strength of the damaged part of the wall is lower than that of the undamaged part. The humid environment of the old town contributed significantly to the destruction of the dwellings, and water intrusion led to a reduction in the strength of the dwellings’ bricks. Through the diagnostic method of building pathology, the causes of Guangfu dwellings’ damage are identified, and scientific and targeted damage intervention suggestions are made. This is expected to provide guidance for the treatment and prevention of building pathology in the ancient city of Guangfu and serve as a reference for the diagnosis and treatment of pathology in traditional dwellings in other areas.
Cell Death by Metals: Diversity of Phenomena vs. Distinctive Categories
Authors: Shtil Alexander A. , Chernov Kirill V. , Tsymbal Sergey A.
Published: November 2024

Dear Editor: [...]
Tumor-Associated Edema in Children with Kaposi Sarcoma: 14 Years’ Experience at Kamuzu Central Hospital, Lilongwe, Malawi
Authors: Manase Fatsani Rose , Silverstein Allison , Kamiyango William , Villiera Jimmy , Dziwe Clement , Wallrauch Claudia , Heller Tom , Zobeck Mark , Tomoka Tamiwe , Scheurer Michael E. , Allen Carl E. , Ozuah Nmazuo , Mzikamanda Rizine , El-Mallawany Nader Kim , McAtee Casey L.
Published: November 2024

Background/Objectives: Kaposi sarcoma (KS) is a common lymphatic endothelial cancer among children with and without HIV in central and eastern Africa. Despite its clinical heterogeneity, its various clinical phenotypes are often grouped together in staging and treatment algorithms. Patients with KS tumor-associated edema, referring to hard, non-pitting lesions which often lead to chronic disability, represent a unique, understudied subgroup of children with KS. To continue our work defining the distinct phenotypes of pediatric KS, this study aimed to assess the clinical progression and outcomes of KS edema in children. Methods: A retrospective cohort study was conducted at Kamuzu Central Hospital in Lilongwe, Malawi, focusing on children diagnosed with KS edema between 2010 and 2023. Results: We identified 52 children with KS edema, representing 27% of all patients with KS. Initial chemotherapy resulted in a clinical response in 92% of patients, but 46% experienced relapse or disease progression with a median time to first relapse of 12 months. Multiple progressions were common, with 31% of patients experiencing two or more events. Event-free survival at two years was 32%, dropping to 24% at five years, while overall survival was 73% at two years and 57% at five years. Relapse was more common among patients with KS edema versus those without it (relative risk = 2.1; 95%CI, 1.4–3.2; p < 0.001). Eight patients (15%) relapsed with visceral disease, five of whom originally presented with KS edema alone. Conclusions: Patients with KS edema have a unique, relapsing-remitting pattern of disease with a high risk of relapse relative to other forms of KS with subsequent long-term mortality, even after initial positive treatment responses. Late relapse and mortality with visceral disease are possible even among children presenting initially with KS edema alone. Children with KS edema require long-term follow-up, and novel treatment approaches tailored towards preventing frequent relapse are needed.
Physical Literacy and Physical Activity in Early Years Education: What’s Known, What’s Done, and What’s Needed?
Authors: Weir Natalie , Pringle Andy , Roscoe Clare M. P.
Published: November 2024

Background: Physical literacy (PL) is increasingly recognised as essential for fostering lifelong engagement in physical activity (PA), particularly when nurtured in early childhood. Yet there remains limited understanding of how stakeholders in early years (EY) education perceive, value, and implement a PL-informed approach. This study aims to explore knowledge and beliefs regarding PL and PA in relation to 3–5-year-olds, investigating key questions around perceived importance, current practices, and barriers to implementation. Methods: A concurrent mixed-methods approach was used, incorporating semi-structured expert interviews (n = 11), focus groups (n = 22), and a survey (n = 210). Thematic analysis was used to identify key themes from qualitative data, and survey data were analysed to complement and triangulate the qualitative findings. Results: The findings revealed variation in stakeholders’ awareness of PA recommendations and confusion over terminology. Whilst stakeholders acknowledged the importance of PL, there remains uncertainty about the connection between theory and practical application. Identified barriers included resource limitations, conflicting priorities, and insufficient training and policy support. Feedback on an educational PL-EY model was generally positive, suggesting strong potential as a tool to support PL understanding and application in early childhood contexts. Conclusions: Given the pivotal role of EY education in shaping children’s behaviours, health, and wellbeing, this study highlights the necessity of a holistic approach to interventions, strong stakeholder involvement, and evidence-based practices to foster PL in EY children. The PL-EY model presents a promising direction for future resources and education and raises critical questions about what effective interventions to develop PL in this age group should consider and look like.
Intraosseous Delivery of Mesenchymal Stem Cells for the Treatment of Bone and Hematological Diseases
Authors: Artamonov Mikhail Yu. , Sokov Evgeniy L.
Published: November 2024

Mesenchymal stem cells are used most in regenerative medicine due to their capacities in differentiation and immune modulation. The intraosseous injection of MSC into the bone has been recommended because of expected outcomes for retention, bioavailability, and enhanced therapeutic efficacy, particularly in conditions involving the bone, such as osteoporosis and osteonecrosis. A review of the intraosseous delivery of mesenchymal stem cells in comparison with intravenous and intra-arterial delivery methods will be subjected to critical examination. This delivery mode fares better regarding paracrine signaling and immunomodulation attributes, which are the cornerstone of tissue regeneration and inflammation reduction. The local complications and technical challenges still apply with this method. This study was more focused on further research soon to be conducted to further elucidate long-term safety and efficacy of intraosseous mesenchymal stem cell therapy. Though much has been achieved with very impressive progress in this field, it is worth noting that more studies need to be put into place so that this technique can be established as a routine approach, especially with further research in biomaterials, gene therapy, and personalized medicine.
Correlation of Eight (8) Polymorphisms and Their Genotypes with the Risk Factors of Cardiovascular Disease in a Black Elderly Population
Authors: Chalwe Joseph Musonda , Grobler Christa Johanna , Oldewage-Theron Wilna Hendrika
Published: November 2024

Single nucleotide polymorphisms (SNPs) have been associated with the development of cardiovascular diseases (CVDs). This study correlated eight SNPs with the risk factors of CVD in a black elderly population. Genotyping was used to detect eight polymorphisms; rs675 (ApoA-IV), rs699 (Angiotensinogen (AGT)), rs247616 and rs1968905 (Cholesteryl ester transfer protein (CETP)), rs1801278 (Insulin receptor substrate 1 (IRS-1)), rs1805087 (Methylenetetrahydrofolate reductase (MTHFR)) and rs28362286 and rs67608943 (Proprotein convertase subtilisin/kexin type 9 (PCSK9)), as well as their genotypes in deoxyribonucleic acid (DNA) extracted from peripheral blood. The cardiovascular risk (CVR) measurements were conducted on a Konelab 20i Thermo Scientific autoanalyzer and an enzyme-linked immunoassay (ELISA) assay. International Business Machines Corporation (IBM)® Statistical Package for the Social Sciences ® (SPSS) version 28 was used for statistical analysis. The heterozygous and homozygous genotypes of the eight polymorphisms were detected with the corresponding CVD risk factors. Subgroup analysis indicated that certain genotype carriers exhibited variations in their concentrations of CVR factors compared to others; however, these differences did not reach statistical significance. For example, carriers of the G genotype of the rs699 polymorphism showed marginally different blood pressure readings compared to the AG genotype carriers. The multiple linear regression analysis indicated that the only significant association was between PCSK9 and the rs28362286 (p = 0.029) polymorphism. The findings of our study show that single nucleotide polymorphisms are disseminated across the human genome. The heterozygous and homozygous genotypes of the SNPs require further investigation as they may have independent and possible collective roles in increasing the risk of CVDs.
Machine Learning-Assisted Hartree–Fock Approach for Energy Level Calculations in the Neutral Ytterbium Atom
Authors: Ma Kaichen , Yang Chen , Zhang Junyao , Li Yunfei , Jiang Gang , Chai Junjie
Published: November 2024

Data-driven machine learning approaches with precise predictive capabilities are proposed to address the long-standing challenges in the calculation of complex many-electron atomic systems, including high computational costs and limited accuracy. In this work, we develop a general workflow for machine learning-assisted atomic structure calculations based on the Cowan code’s Hartree–Fock with relativistic corrections (HFR) theory. The workflow incorporates enhanced ElasticNet and XGBoost algorithms, refined using entropy weight methodology to optimize performance. This semi-empirical framework is applied to calculate and analyze the excited state energy levels of the 4f closed-shell Yb I atom, providing insights into the applicability of different algorithms under various conditions. The reliability and advantages of this innovative approach are demonstrated through comprehensive comparisons with ab initio calculations, experimental data, and other theoretical results.
A Comprehensive Approach to Nearly Zero Energy Buildings and Districts: Analysis of a Region Undergoing Energy Transition
Authors: Martinopoulos Georgios , Tsimpoukis Alexandros , Sougkakis Vasileios , Dallas Petros , Angelakoglou Komninos , Giourka Paraskevi , Nikolopoulos Nikolaos
Published: November 2024

This paper explores the development of positive energy communities using Eordaia, Greece, as a case study. The approach combines building and district-level energy analysis to achieve nearly zero energy performance through retrofitting, district-level storage systems, and renewable energy technologies. A parametric analysis utilizing RETSCREEN Expert and EnergyPlan software determines the optimal mix of technologies based on technical and financial parameters, with Eordaia, a region in energy transition and part of the RESPONSE Horizon project, illustrating the practical benefits. It includes a neighborhood of 105 mixed-use properties and two municipal buildings where a range of renewable energy sources and energy efficiency measures are applied. Insulation, photovoltaic systems, LED lighting, predictive thermostats, and windows coated with nanotechnology are some of the key interventions considered. The findings show considerable reductions in CO2 emissions and energy use, with payback periods ranging from 8.7 to 9.6 years. This study underscores the value of district-level strategies over individual building retrofits, highlighting cost savings and improved energy performance. These findings offer valuable insights for urban planners and policymakers aiming to transform urban areas into sustainable, positive energy districts, supporting the EU’s 2050 net-zero emissions goals.
Adaptive Remaining Capacity Estimator of Lithium-Ion Battery Using Genetic Algorithm-Tuned Random Forest Regressor Under Dynamic Thermal and Operational Environments
Authors: Khan Uzair , Tariq Mohd , Sarwat Arif I.
Published: November 2024

The increasing interests and recent advancements in artificial intelligence and machine learning have significantly accelerated the development of novel techniques for the state estimation of batteries in electrified vehicles’ battery management systems (BMSs). Determining the remaining capacity among the several BMS states is crucial for ensuring the safe and stable functioning of an electric vehicle. This paper proposes an adaptive estimator for the remaining capacity of lithium-ion batteries, leveraging a Genetic Algorithm (GA)-tuned random forest (RF) regressor. The estimator is designed to function effectively under varying thermal conditions. The optimization of critical parameters, namely, the number of estimators (n-estimators) and the minimum number of samples per leaf (min-samples-leaf), is a focal point of this study to enhance model accuracy and robustness. The model effectively captures the battery’s dynamic behavior and inherent non-linearity. The Mean Absolute Error (MAE) and Root Mean Square Error (RMSE) achieved during testing demonstrate promising accuracy and superior prediction. The results demonstrated significant improvements in state of charge (SOC) estimation accuracy. The proposed GA-optimized RF model achieved an MAE of 0.0026 at 25 °C and 0.0102 at −20 °C, showing a 41.37% to 50% reduction in the MAE compared to traditional random forest models without GA optimization. The RMSE was also reduced by 18.57% to 31.01% across the tested temperature range. These improvements highlight the model’s ability to accurately estimate the SOC in varying thermal conditions.
Ensemble Pretrained Convolutional Neural Networks for the Classification of Insulator Surface Conditions
Authors: Serikbay Arailym , Bagheri Mehdi , Zollanvari Amin , Phung B. T.
Published: November 2024

Overhead transmission line insulators are non-conductive materials that separate conductors from grounded transmission towers. Once in operation, they frequently experience environmental pollution and electrical or mechanical stress. Since adverse operational conditions can lead to insulation failure, regular inspections are essential to prevent power outages. To this end, this paper proposes a novel technique based on deep convolutional neural networks (CNNs) to classify high-voltage insulator surface conditions based on their image. Successful applications of CNNs in computer vision have led to several pretrained architectures for image classification. To use these pretrained models, a practitioner typically fine-tunes and selects one final model via a model selection stage and discards all other models. In contrast with many existing studies that use such a “winner-takes-all” approach, here, we identify the best subset of seven popular pretrained CNN architectures that are combined by soft voting to form an ensemble classifier. From a machine learning (ML) perspective, this focus is warranted because the convolutional base of each pretrained architecture operates as a feature extractor and an ensemble of them works as a combination of various feature extraction rules. Our numerical experiments demonstrate the advantage of the identified ensemble model to individual pretrained architectures.
Patterns and Driving Mechanisms of Soil Organic Carbon, Nitrogen, and Phosphorus, and Their Stoichiometry in Limestone Mines of Anhui Province, China
Authors: Long Yiyi , Zhang Dandan , Wu Hongmiao , Li Jinsheng , Xiong Peifeng , Zhao Guohong , Liu Hai , Wu Boren , Zhang Zhen
Published: November 2024

Active vegetation restoration plays an important role in the improvement in soil organic matter (SOM), including the carbon (C), nitrogen (N) and phosphorus (P) sequestration of degraded mining ecosystems. However, there is still a lack of understanding of the key drivers of SOM pool size and dynamics in active vegetation restoration. For this study, soil was collected from five different sites (Xiaoxian, Dingyuan, Chaohu, Tongling and Dongzhi), four habitats (platforms, slopes, steps and native areas) and two soil layers (0–20 cm and 20–40 cm) in limestone mines of Anhui province to quantify the spatial distribution of SOM contents and their stoichiometric characteristics and influential factors. It was found that the top soil in Chaohu had the highest significant C, N and P contents in the ranges of 14.95–17.97, 1.74–2.21 and 0.80–1.24 g/kg, respectively. Comparing the stoichiometric ratios of the different sites revealed significant differences in C:N and N:P ratios, but C:P ratios were relatively consistent. In particular, the C:N and C:P ratios in deep soil were higher than those in top soil, whereas the N:P ratio in deep soil was lower than that in top soil, suggesting that soil N is a major limiting factor in the top soil. The SOM content did not differ significantly between the three reclaimed habitats, but was significantly higher than that in the native habitat, suggesting that mine restoration has significantly enhanced SOM accumulation. Further analysis showed that nutrient availability and enzyme activity are important factors affecting soil C, N and P content in top soil, while the relationship gradually weakens in deep soil. This was attributed to active anthropogenic management and conservation measures during the early stages of reclamation. This study shows that the ecological recovery of the mining area can be enhanced by implementing differentiated vegetation planting strategies and anthropogenic management on different habitats in the mining area.
Enhanced Resistance to Pinewood Nematode Disease in Pinus densiflora Induced by Fungal Elicitor from Penicillium chrysogenum
Authors: Moon Young Bum , Kim Yi Rae , Han Jung Yeon , Choi Yong Eui
Published: November 2024

Pine wilt disease, caused by the pine wood nematode (Bursaphelenchus xylophilus), poses a serious threat to forests in Korea. In this study, we investigated the resistance of Pinus densiflora to B. xylophilus following treatment with a fungal elicitor derived from Penicillium chrysogenum through trunk injection and soil drenching. Soil drenching with the fungal elicitor led to increased accumulation of two key defensive compounds: pinosylvin monomethyl ether (PME) and dihydropinosylvin monomethyl ether (DPME) in the needles. In untreated control plants inoculated with B. xylophilus, 67.9% died within five months, whereas only 33.3% of plants pretreated with the elicitor succumbed. Trunk injection of the fungal elicitor also significantly enhanced PME production. The PME concentration in the needles peaked at 155.4 µg/g dry weight (DW) four weeks post-elicitor injection. To assess the impact of elicitor treatment on nematode resistance, we monitored the downward movement of B. xylophilus in plants two months post-injection of fungal elicitor. Nematodes were introduced at the upper internodal segments of branches, and their mobility to the lower segments was measured. In elicitor-treated trees, the movement and population of B. xylophilus were significantly reduced, highlighting the effectiveness of the treatment. These results demonstrate that fungal elicitor treatments, through soil drenching or trunk injection, can enhance the resistance of P. densiflora to B. xylophilus. This eco-friendly approach offers a promising strategy for managing pine wilt disease in susceptible pine species.
Targeted Screening of Lactiplantibacillus plantarum Strains Isolated from Tomatoes and Its Application in Tomato Fermented Juice
Authors: Tuerhong Nuersiman , Wang Liang , Cui Jie , Shataer Dilireba , Yan Huizhen , Dong Xiaoxiao , Gao Ziqi , Zhang Minwei , Qin Yanan , Lu Jing
Published: November 2024

This study explores the functional attributes of Lactiplantibacillus plantarum (L. plantarum) strains isolated from fermented tomato juice, focusing on their physiological, biochemical, and probiotic characteristics. The identified 66 gram-positive strains included 36 L. plantarum ones, which exhibited robust growth in acidic environments (pH 2.0–5.0) and utilization of various carbohydrates. Notably, seven strains outperformed a commercial strain in extreme acidic conditions. Antioxidant activity varied, with strain A24 showing the highest hydroxyl radical scavenging ability, while strains with high surface hydrophobicity had lower DPPH scavenging activity, indicating no direct correlation between these properties. Strains also showed strain-specific differences in carbohydrate utilization and antibiotic resistance, with some resistant to gentamicin and ciprofloxacin. Survival rates under simulated gastrointestinal conditions were strain-specific, with some strains demonstrating high survival rates, indicating their potential as probiotics. Furthermore, 13 strains used as fermentation starters in tomato juice significantly enhanced antioxidant activity and reduced pH and total soluble solids, indicating efficient sugar utilization and lactic acid production. These findings suggest that L. plantarum strains are well-suited for functional food fermentation and probiotic applications, with strain-specific traits offering versatility for use in acidic food products and probiotic formulations.
Lymphocytic Esophagitis—A Novel Clinicopathologic Variant of Chronic Esophagitis: A Review Paper
Authors: Wojas Oksana , Krzych-Fałta Edyta , Żybul Paulina , Samoliński Bolesław , Przybyłkowski Adam
Published: November 2024

Background/Objectives: Lymphocytic esophagitis is a rare inflammatory disease of the esophagus, first described in 2006. Since that time, interest in this disease entity has steadily increased, yet specific data on the etiology of the disease are still lacking. Lymphocytic esophagitis co-occurs with esophageal motility disorders, Crohn’s disease, hypersensitivity (allergy, asthma), the use of certain medications, or immune disorders. Risk factors include smoking and alcohol abuse. The disease is more prevalent in women, developing predominantly within the sixth decade of life. The most important symptom is dysphagia, with odynophagia, epigastric, and chest pain or heartburn being less common. No particular endoscopic presentation is pathognomonic for lymphocytic esophagitis, the findings not infrequently resembling those of eosinophilic esophagitis. Conclusions: There is great need for an international consensus defining strict histopathological criteria for the diagnosis of lymphocytic esophagitis as well as relevant diagnostic and therapeutic management. This review paper presents the current state of knowledge on lymphocytic esophagitis.
Year in Review 2023: Gout Clinical Research
Authors: Challener Greg , Yokose Chio
Published: November 2024

Gout is the most common inflammatory arthritis, with a growing global disease burden. This conference report summarizes nine impactful publications dating from 11/2022 to 10/2023 to inform and improve clinical care in gout. The articles we present here collectively address diverse facets of gout research, including gout epidemiology, predictive biomarkers, the occurrence of complications relating to gout flares, and gout management strategies.