bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening and Selection of Native Lactic Acid Bacteria Isolated from Chilean Grapes
Authors: Vargas-Luna Carla , Godoy Liliana , Benavides Sergio , Ceppi de Lecco Consuelo , Urtubia Alejandra , Franco Wendy
Published: January 2025

The aim of this study was investigating the biological diversity of lactic acid bacteria isolated from Chilean grapes and identifying potential candidates for use as malolactic fermentation starter cultures. The isolated bacteria underwent a comprehensive six-stage screening process, which was mutually exclusive except for the evaluation of tyramine production and citric acid intake. This process included morphological, metabolic, fermentation yield, and resistance tests to identify promising malolactic strains. Morphological assessments led to the selection of 23 isolates, which were genetically identified as Levilactobacillus brevis (65% abundance) and Leuconostoc mesenteroides (35% abundance). Among these, eight strains exhibited low sugar metabolism rates, while three demonstrated competitive growth and malolactic activity in a synthetic medium containing 10% ethanol, outperforming a commercial strain. Low consumption was observed in the qualitative citric acid intake test, whereas a positive response was noted for tyramine production. At the conclusion of the sequential selection criteria, Levilactobacillus brevis BCV-46 exhibited the most favorable characteristics for potential use as a malolactic starter culture, successfully withstanding the combined stress factors of ethanol, pH, and SO2.
Lipoprotein Lipase: Structure, Function, and Genetic Variation
Authors: Perera Shehan , Wang Jian , McIntyre Adam , Hegele Robert
Published: January 2025

Biallelic rare pathogenic loss-of-function (LOF) variants in lipoprotein lipase (LPL) cause familial chylomicronemia syndrome (FCS). Heterozygosity for these same variants is associated with a highly variable plasma triglyceride (TG) phenotype ranging from normal to severe hypertriglyceridemia (HTG), with longitudinal variation in phenotype severity seen often in a given carrier. Here, we provide an updated overview of genetic variation in LPL in the context of HTG, with a focus on disease-causing and/or disease-associated variants. We provide a curated list of 300 disease-causing variants discovered in LPL, as well as an exon-by-exon breakdown of the LPL gene and protein, highlighting the impact of variants and the various functional residues of domains of the LPL protein. We also provide a curated list of variants of unknown or uncertain significance, many of which may be upgraded to pathogenic/likely pathogenic classification should an additional case and/or segregation data be reported. Finally, we also review the association between benign/likely benign variants in LPL, many of which are common polymorphisms, and the TG phenotype.
The Heterozygous p.A684V Variant in the WFS1 Gene Is a Mutational Hotspot Causing a Severe Hearing Loss Phenotype
Authors: Otsuka Shintaro , Morimoto Chihiro , Nishio Shin-ya , Morita Shinya , Kikuchi Daisuke , Takahashi Masahiro , Kumakawa Kozo , Arai Yasuhiro , Sano Hajime , Yoshimura Hidekane , Yamamoto Norio , Kondo Shunsuke , Hasegawa Mari , Nishi Tomo , Kitahara Tadashi , Usami Shin-ichi
Published: January 2025

Background/Objectives: A heterozygous mutation in the WFS1 gene is responsible for autosomal dominant non-syndromic hearing loss (DFNA6/14/38) and Wolfram-like syndrome, which is characterized by bilateral sensorineural hearing loss with optic atrophy and/or diabetes mellitus. However, detailed clinical features for the patients with the heterozygous p.A684V variant remain unknown. Methods: We report the clinical details of 14 cases with a heterozygous p.A684V variant in the WFS1 gene identified from target resequencing analysis of 63 previously reported deafness genes by next-generation sequencing of 15,684 hearing loss patients (mean age 27.5 ± 23.1 years old, 6574 male, 8612 female and 498 for whom information was unavailable). Results: Among the 14 patients from 13 families with the p.A684V variant, nine were sporadic cases. In addition, we confirmed de novo occurrence of this variant in seven families. This result strongly supports the notion that this variant was located on a mutational hotspot. When comparing previously reported cases of autosomal dominant WFS1 gene-associated hearing loss, most of the patients in this study showed severe-to-profound bilateral sensorineural hearing loss (genotype–phenotype correlation). Two patients had optic atrophy, while the others did not have any other complications. Conclusions: The identified heterozygous p.A684V variant appears to be a hotspot mutation and likely to cause severe-to-profound hearing loss in early childhood. Cochlear implantation is considered favorable in cases of hearing impairment due to this variant.
Depositional Environments and Soft Sediment Deformation in the Early Jurassic Ammonitico Rosso Formation of Western Greece
Authors: Golfinopoulos Vasilis , Piper David J. W. , Zelilidis Avraam , Pe-Piper Georgia , Papadopoulou Penelope , Bourli Nicolina , Iliopoulos George
Published: January 2025

This study investigates the depositional environments and soft sediment deformation within the Early Jurassic Ammonitico Rosso Formation in the External Ionian Basin (Western Greece), focusing on its biostratigraphy, sedimentology, and tectonic activity. This research provides new insights into the depositional environment of the Ammonitico Rosso Formation and its transitions with the underlying and overlying formations. Syn-rift tectonics at the time of deposition formed half-grabens, which influenced sedimentary processes and created conditions for seabed slumping. Detailed field mapping and microfacies analysis revealed two distinct depositional environments: deep-water to open-shelf settings and platform-margin reefs. The entire Ammonitico Rosso Formation is allochthonous, deposited as repetitive slices of little-disturbed stratified sediments capped by debrites near the toe of a complex submarine landslide. The presence of well-preserved fossils, such as planktonic and benthic foraminifera, Radiolaria (both Spumellaria and Nassellaria), and ammonites, allowed precise age determinations, suggesting that the first appearance of Globuligerina might predate previous records, occurring first in the Pliensbachian rather than the Toarcian. These findings contribute to the ongoing debate on the depth and conditions of Ammonitico Rosso deposition, supporting the hypothesis of a relatively deep, open-shelf environment influenced by slope instability.
Impacts of Land Use on Soil Erosion: RUSLE Analysis in a Sub-Basin of the Peruvian Amazon (2016–2022)
Authors: Ascencio-Sanchez Moises , Padilla-Castro Cesar , Riveros-Lizana Christian , Hermoza-Espezúa Rosa María , Atalluz-Ganoza Dayan , Solórzano-Acosta Richard
Published: January 2025

The Peruvian Amazon faces an increasing threat of soil erosion, driven by unsustainable agricultural practices and accelerated deforestation. In Neshuya (Ucayali region), agricultural activity has intensified since 2014, but the effect on soil erosion is unknown. The present study aimed to evaluate the increase in erosion levels, at a sub-basin of the central–eastern Amazon of Peru, in a Geographic Information System (GIS) environment. The revised universal soil loss equation (RUSLE) model was used for assessing the effect of vegetation cover change from 2016 to 2022. In the Neshuya sub-basin (973.4 km2), the average erosion increased from 3.87 to 4.55 t ha−1 year−1, on average. In addition, there is great spatial variability in the values. In addition, 7.65% of the study area (74.52 km2) exceeds the soil loss tolerance limit (15 t ha−1 year−1). The deforestation rate was 17.99 km2 year−1 and by 2022 the forested area reached 237.65 km2. In conclusion, the transition from forest to farmland was related to the most critical erosion values. Unsustainable soil management practices can be the underlying explanation of changes in soil chemical and physical properties. Also, social dynamic changes and differences in landscape patterns play a role.
Synchronous Home-Based Telerehabilitation of the Upper Extremity Following Stroke—A Pyramid Review
Authors: Stangenberg-Gliss Kirsten , Kopkow Christian , Borgetto Bernhard
Published: January 2025

Background: Stroke is a leading cause of long-term disability, often resulting in upper extremity impairment. Telerehabilitation offers a promising approach to deliver therapy in home settings. This review aimed to evaluate the effects of home-based telerehabilitation interventions delivered to address upper extremity function in stroke patients. Methods: A systematic review was conducted following the Pyramid Review methodology. Quantitative and qualitative studies examining home-based telerehabilitation for upper extremity function in stroke patients were included. Data were synthesized using meta-analysis where possible and narrative synthesis. Results: Thirty studies (24 quantitative, four qualitative, and two mixed-methods studies) were included. Telerehabilitation interventions demonstrated improvements in upper extremity function for both subacute and chronic stroke patients, with varying effect sizes across intervention types. Constraint-induced movement therapy adaptations and some sensor-based approaches showed consistently positive results. Qualitative findings revealed generally positive effects, with convenience, gamification, and social support as key motivators for adherence. Conclusions: Home-based telerehabilitation shows promise for improving upper extremity function in stroke patients. However, heterogeneity in intervention designs and outcomes limits definitive conclusions. Future research should focus on larger trials, observational studies, standardized outcome measures, and long-term follow-up as well as qualitative studies with focus on perceived effectiveness to optimize telerehabilitation approaches for stroke recovery.
Unveiling the Original Polychromy of Archaic Architecture: The Gigantomachy on the West Pediment of the Temple of Apollo at Delphi (6th c. B.C.)
Authors: Frantzi Giasemi , Mastrotheodoros Georgios , Theoulakis Panayiotis , Kogou Sotiria , Psalti Athanasia , Brecoulaki Hariclia
Published: January 2025

The Gigantomachy depicted on the west pediment of the Late Archaic temple of Apollo at Delphi marks a significant milestone in early Greek architectural sculpture. Crafted from porous stone and enhanced with plaster and paint, the surviving fragments differ markedly from the marble figures of the east pediment of the same temple. Among the preserved figures of the Gigantomachy are a standing male figure, possibly representing Apollo or Dionysos, a warrior female identified as Athena, and a recumbent male, likely symbolizing the Giant Enkelados. This study aims to investigate the polychromy of the west pediment through a thorough investigation of the remnants of the original decoration. The adopted methodology includes exclusively non-destructive techniques and advanced imaging methods, such as portable X-ray fluorescence spectrometry, visible-induced luminescence (VIL), and 3D microscope observation. Analytical results confirmed the presence of extensive traces of once-vibrant colors on the plaster’s surface, which were often invisible to the naked eye. Specifically, our data support the employment of pigments like Egyptian blue, cinnabar, ochre-based reds and yellows, as well as copper-based green. Notably, these pigments were applied over a white calcium-rich layer, which served as a primer for the porous stone. Ongoing research on the Gigantomachy promises to deepen our understanding of color usage and painting techniques in Archaic Greek art.
Identification and Pathogenicity of Causal Agents of Apple Canker Disease in Kazakhstan
Authors: Tulegenova Zhanar , Amanbayeva Ulbike , Shalabayeva Aida M. , Yelyubayeva Dina , Zhaxylykov Alikhan , Uakhit Rabiga , Smagulova Ainura , Kiyan Vladimir , Dyussembayev Kazbek , Mukiyanova Gulzhamal
Published: January 2025

Apples are widely consumed by people all over the world due to their taste and nutritional value. However, apple trees are prone to various environmental stresses, including fungal diseases. Among them, Cytospora canker (or Valsa canker) can cause dieback of branches and twigs. Although Kazakhstan is well known as an origin of apples, very little is known about canker diseases that spread across all commercial orchards. Therefore, an accurate identification of the causal agents of those diseases is needed for further application of informed disease management strategies. In this study, eleven isolates belonging to four Cytospora species were isolated from multiple cultivars, grown in six different orchards within the Almaty region, Kazakhstan. As a result of a multilocus phylogenetic analysis using ITS, LSU and tef1-α marker genes and morphological characterization, these isolates were described as Cytospora parasitica, Cytospora sorbina, Cytospora pruinopsis and Cytospora chrysosperma. Moreover, a pathogenicity test was conducted on detached twigs, and it demonstrated that two of these fungi were highly virulent. Overall, this paper is a first report of the causal agents of apple canker disease in Kazakhstan and could be a trigger for conducting future studies to better understand the disease epidemiology, as well as build management strategies.
Exploring Staff Perceptions of the Management of Clinical Trials and Its Impact on Enhancing Health Service Delivery
Authors: Sappor Emmanuel Ekundayo , Chakraborty Rhyddhi
Published: January 2025

The role of clinical trials cannot be ignored due to its contribution to innovative treatment, therapies, and drug development in promoting quality service delivery. We investigated and explored the management aspect of clinical trials and its impact on healthcare service delivery within the NHS. A qualitative methodology with an interpretivism approach was adopted to collect data from nine participants using a purposive sampling method in the management of clinical trials at the NHS. A semi-structured interview with open-ended questions and probing techniques conducted via Microsoft Teams was used as a data collection tool. The collected data were thematically analysed with the support of NVivo 14 software. The staffs’ perceptions were somewhat effective and highlights required improvement for better performance regarding clinical trial management at the NHS setting. The findings represent improved patient outcomes, increasing evidence-based decision making, and the development of innovative therapies and research infrastructure could be some positive impacts of the effective management of clinical trials. However, the findings show that improvement in stakeholder collaboration and communication is vital to combat the existing challenges such as regulatory hurdles and issues in participant recruitment, retention, and communication. The findings provide practical values and insight into the staff working in the management of clinical trial processes and the audiences relevant to this field. A comprehensive understanding of the proactive measures and factors that are essential for the improvement of clinical trial management has been interpreted. In the hospital’s settings, supervision and improvement of clinical trials are necessary to promote innovative therapies, research infrastructure, and quality patient care and service delivery.
“It Would Ruin My Life”: Pacific Islander Male Adolescents’ Perceptions of Mental Health Help-Seeking—An Interpretative Phenomenological Analysis Focus Group Study
Authors: Garrett Melia Fonoimoana , Cutrer-Párraga Elizabeth A. , Allen G. E. Kawika , Young Ellie L. , Urbina Kristofer J. , Hull Isabel Medina
Published: January 2025

Given rising mental health concerns among Pacific Islander (PI) adolescents, this population remains underserved by available mental health resources. This interpretative phenomenological analysis with focus groups (IPA-FG) examined the lived experiences and perceptions of 19 male PI adolescents (ages 14–16) from Native Hawaiian, Maori, Samoan, and Tongan backgrounds regarding mental health help-seeking behaviors. Four overarching themes emerged: stigma and judgment, cultural misalignment in professional services, impact of disclosure and perceived punitive consequences, and a complex ecosystem of trusted relationships as mental health support. Notably, participants expressed belief that disclosing mental health challenges would “ruin their lives” and held misconceptions about adults’ ability to address mental health concerns. These findings are particularly significant given high suicidality rates among PI adolescents. This study provides insights for developing culturally responsive mental health interventions and highlights the urgent need to address mental health stigma within PI communities. Implications for practice are discussed.
Space Efficiency of Transit-Oriented Station Areas: A Case Study from a Complex Adaptive System Perspective
Authors: Fan Jinwen , Shi Zhenwu , Liu Jie , Wang Jinru
Published: January 2025

Transit-oriented development (TOD) has been widely adopted in urban planning to alleviate traffic congestion, urban sprawl, and other problems. The TOD metro station area, as a dynamic and open spatial system, presents typical complex features. To improve urban planning by understanding the complex features of metro station areas, this study proposes a comprehensive evaluation method using complex adaptive system theory (CAS) to assess space efficiency and the use of an evaluation method like COWA (continuous ordered weighted averaging) operator and cloud model to show efficiency. Factors include external relevance, internal coordination, and environmental adaptation. This study uses Museum Station of Harbin Railway Transportation as the case study, and the results show that the space efficiency of Harbin’s TOD metro station areas are lacking in internal coordination and environmental adaptation. The proposed evaluation method not only identifies areas of space inefficiencies in urban rail transit station areas but also provides valuable insights for informed decision-making and future urban development initiatives.
Redosing with Intralymphatic GAD-Alum in the Treatment of Type 1 Diabetes: The DIAGNODE-B Pilot Trial
Authors: Casas Rosaura , Tompa Andrea , Åkesson Karin , Teixeira Pedro F. , Lindqvist Anton , Ludvigsson Johnny
Published: January 2025

Immunotherapies aimed at preserving residual beta cell function in type 1 diabetes have been successful, although the effect has been limited, or raised safety concerns. Transient effects often observed may necessitate redosing to prolong the effect, although this is not always feasible or safe. Treatment with intralymphatic GAD-alum has been shown to be tolerable and safe in persons with type 1 diabetes and has shown significant efficacy to preserve C-peptide with associated clinical benefit in individuals with the human leukocyte antigen DR3DQ2 haplotype. To further explore the feasibility and advantages of redosing with intralymphatic GAD-alum, six participants who had previously received active treatment with intralymphatic GAD-alum and carried HLA DR3-DQ2 received one additional intralymphatic dose of 4 μg GAD-alum in the pilot trial DIAGNODE-B. The participants also received 2000 U/day vitamin D (Calciferol) supplementation for two months, starting one month prior to the GAD-alum injection. During the 12-month follow-up, residual beta cell function was estimated with Mixed-Meal Tolerance Tests, and clinical and immune responses were observed. C-peptide decreased minimally, and most patients showed stable HbA1c and IDAA1c. The mean % TIR increased while the mean daily insulin dose decreased at month 12 compared to the baseline. Redosing with GAD-alum seems to be safe and tolerable, and may prolong the disease modification elicited by the original GAD-alum treatment.
Lactoferrin Attenuates Pro-Inflammatory Response and Promotes the Conversion into Neuronal Lineages in the Astrocytes
Authors: Ruggiero Melania , Cianciulli Antonia , Calvello Rosa , Lofrumento Dario Domenico , Saponaro Concetta , Filannino Francesca Martina , Porro Chiara , Panaro Maria Antonietta
Published: January 2025

Neurodegenerative diseases are characterized by progressive loss of neurons and persistent inflammation. Neurons are terminally differentiated cells, and lost neurons cannot be replaced since neurogenesis is restricted to only two neurogenic niches in the adult brain, whose neurogenic potential decreases with age. In this regard, the astrocytes reprogramming into neurons may represent a promising strategy for restoring the lost neurons and rebuilding neural circuits. To date, many anti-inflammatory agents have been shown to reduce neuroinflammation; however, their potential to restore neuronal loss was poorly investigated. This study investigates the anti-inflammatory effects of lactoferrin on DI-TNC1 astrocyte cell line and its ability to induce astrocyte reprogramming in a context of sustained inflammation. For this purpose, astrocytes were pre-treated with lactoferrin (4 μg/mL) for 24 h, then with lipopolysaccharide (LPS) (400 ng/mL), and examined 2, 9 and 16 days from treatment. The results demonstrate that lactoferrin attenuates astrocyte reactivity by reducing Toll-like receptor 4 (TLR4), Glial fibrillary acidic protein (GFAP) and IL-6 expression, as well as by upregulating Interleukin-10 (IL-10) cytokine and NRF2 expression. Moreover, lactoferrin promotes the reprogramming of reactive astrocytes into proliferative neuroblasts by inducing the overexpression of the Sex determining region Y/SRY-box 2 (SOX2) reprogramming transcription factor. Overall, this study highlights the potential effects of lactoferrin to attenuate neuroinflammation and improve neurogenesis, suggesting a future strategy for the treatment of neurodegenerative disorders.
Chronic Gastrointestinal Disorders and miRNA-Associated Disease: An Up-to-Date
Authors: Giammona Alessandro , Galuzzi Bruno Giovanni , Imperia Elena , Gervasoni Clarissa , Remedia Sofia , Restaneo Laura , Nespoli Martina , De Gara Laura , Tani Flaminia , Cicala Michele , Guarino Michele Pier Luca , Porro Danilo , Cerasa Antonio , Lo Dico Alessia , Altomare Annamaria , Bertoli Gloria
Published: January 2025

Chronic gastrointestinal disorders such as inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS) impose significant health burdens globally. IBDs, encompassing Crohn’s disease and ulcerative colitis, are multifactorial disorders characterized by chronic inflammation of the gastrointestinal tract. On the other hand, IBS is one of the principal gastrointestinal tract functional disorders and is characterized by abdominal pain and altered bowel habits. Although the precise etiopathogenesis of these disorders remains unclear, mounting evidence suggests that non-coding RNA molecules play crucial roles in regulating gene expression associated with inflammation, apoptosis, oxidative stress, and tissue permeability, thus influencing disease progression. miRNAs have emerged as possible reliable biomarkers, as they can be analyzed in the biological fluids of patients at a low cost. This review explores the roles of miRNAs in IBDs and IBS, focusing on their involvement in the control of disease hallmarks. By an extensive literature review and employing bioinformatics tools, we identified the miRNAs frequently studied concerning these diseases. Ultimately, specific miRNAs could be proposed as diagnostic biomarkers for IBDs and IBS. Their ability to be secreted into biofluids makes them promising candidates for non-invasive diagnostic tools. Therefore, understanding molecular mechanisms through the ways in which they regulate gastrointestinal inflammation and immune responses could provide new insights into the pathogenesis of IBDs and IBS and open avenues for miRNA-based therapeutic interventions.
Sea Anemone Kunitz Peptide HCIQ2c1 Reduces Histamine-, Lipopolysaccharide-, and Carrageenan-Induced Inflammation via the Suppression of Pro-Inflammatory Mediators
Authors: Kvetkina Aleksandra N. , Klimovich Anna A. , Deriavko Yulia V. , Pislyagin Evgeniy A. , Menchinskaya Ekaterina S. , Bystritskaya Evgenia P. , Isaeva Marina P. , Lyukmanova Ekaterina N. , Shenkarev Zakhar O. , Aminin Dmitriy L. , Leychenko Elena V.
Published: January 2025

Inflammation is a physiological response of the immune system to infectious agents or tissue injury, which involves a cascade of vascular and cellular events and the activation of biochemical pathways depending on the type of harmful agent and the stimulus generated. The Kunitz peptide HCIQ2c1 of sea anemone Heteractis magnifica is a strong protease inhibitor and exhibits neuroprotective and analgesic activities. In this study, we investigated the anti-inflammatory potential of HCIQ2c1 in histamine- and lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as well as in LPS-induced systemic inflammation and carrageenan-induced paw edema models in CD-1 mice. We found that 10 μM HCIQ2c1 dramatically decreases histamine-induced intracellular Ca2+ release and LPS-induced reactive oxygen species (ROS) production in RAW 264.7 macrophages. Moreover, HCIQ2c1 significantly inhibited the production of LPS-induced tumor necrosis factor α (TNF-α), inducible NO-synthase (iNOS), and 5-lipoxygenase (5-LO) but slightly influenced the IL-1β and cyclooxygenase-2 (COX-2) expression level in macrophages. Furthermore, intravenous administration by HCIQ2c1 at 0.1 mg/kg dose reduced LPS-induced TNF-α, IL-1β, COX-2, and iNOS gene expression in CD-1 mice. The subplantar administration of HCIQ2c1 at 0.1 mg/kg dose to mice significantly reduced carrageenan-induced paw edema by a factor of two, which is comparable to the effect of diclofenac at 1 mg/kg dose. Thus, peptide HCIQ2c1 has a strong anti-inflammatory potential by the attenuation of systemic and local inflammatory effects through the inhibition of intracellular Ca2+ release, the production of ROS and pro-inflammatory cytokines, and enzymes involved in arachidonic acid metabolism.
Characterization of the N6-Methyladenosine Gene Family in Peanuts and Its Role in Abiotic Stress
Authors: Wang Wei , Bian Jianxin , Liu Xiaoyu , Liu Xiaoqin
Published: January 2025

Members of the m6A gene family are involved in key biological processes such as plant growth, development, stress responses, and light signal transduction. However, the function of m6A genes in peanuts has been understudied. Our analysis identified 61 m6A family members in the peanut genome, including 21 writer genes, 22 eraser genes, and 18 reader genes, distributed across 20 chromosomes. Phylogenetic analysis revealed that ALKBH proteins are categorized into six subfamilies, while YTH family proteins form nine subfamilies. Promoter cis-element analysis indicated that m6A gene promoters contain light-responsive, hormone-responsive, growth-related, low-temperature defense, and other stress-related elements. Expression studies of AhALKBH8Ba and AhALKBH8Bb in various peanut tissues suggest that these genes play vital roles in peanut fruit needle development. Furthermore, AhETC1a and AhETC1b were significantly upregulated following the loss of mechanical pressure in peanut pods. This study identifies several key genes involved in light and mechanical stress response during peanut pod development.
Adaptive Oversampling via Density Estimation for Online Imbalanced Classification
Authors: Lee Daeun , Kim Hyunjoong
Published: January 2025

Online learning is a framework for processing and learning from sequential data in real time, offering benefits such as promptness and low memory usage. However, it faces critical challenges, including concept drift, where data distributions evolve over time, and class imbalance, which significantly hinders the accurate classification of minority classes. Addressing these issues simultaneously remains a challenging research problem. This study introduces a novel algorithm that integrates adaptive weighted kernel density estimation (awKDE) and a conscious biasing mechanism to efficiently manage memory, while enhancing the classification performance. The proposed method dynamically detects the minority class and employs a biasing strategy to prioritize its representation during training. By generating synthetic minority samples using awKDE, the algorithm adaptively balances class distributions, ensuring robustness in evolving environments. Experimental evaluations across synthetic and real-world datasets demonstrated that the proposed method achieved up to a 13.3 times improvement in classification performance over established oversampling methods and up to a 1.66 times better performance over adaptive rebalancing approaches, while requiring significantly less memory. These results underscore the method’s scalability and practicality for real-time online learning applications.
Triskelion—In Pursuit of Proficiency Through Immersive Gameplay
Authors: Winter Victor
Published: January 2025

As technology advances, interest in video games is extending to broader audiences. This makes gamification as a mechanism for improving educational outcomes increasingly attractive. This article reports on a study in which a 3D third-person video game was used to develop proficiency in spatial reasoning abilities relating to symmetry. The video game, called Triskelion, interleaves elements of traditional gameplay with educational elements. Gameplay includes non-violent shooter elements, parkour, searching, and exploring. Educational elements include points, leaderboards, a theme, clear goals, feedback, and a group challenge in the form of a clan-based match. This composition of elements makes Triskelion unique in the genre of academic educational games. Our study compares one Triskelion match to a longer educational sequence consisting of a “practice test”, followed by engagement with a 3D digital experience called the Kessel Run. Analysis of the results using the Mann–Whitney U test revealed (p = 0.9297) that both pedagogical pathways yielded similar proficiency results. This suggests that Triskelion might create a learning environment more aligned with the characteristics of deliberate practice.
Postharvest Practices and Farmers’ Knowledge in Managing Maize Pests in the Eastern Cape Province, South Africa
Authors: Gumede Bongumusa Charles , Kuria Simon Kamande
Published: January 2025

This study aims to establish the pest management approach for pests of stored maize and determine the current control practices. Semi-structured questionnaires were administered to 77 smallholder farmers from 16 villages at King Sabata Dalindyebo local municipality in the Eastern Cape Province of South Africa. The results revealed that about 50% of the farmers had a formal education, the average farm size was 1 hectare, and they were predominantly cultivating yellow maize. Most farmers (57%) cultivated maize for human consumption, income generation, and livestock feeding. The results also showed that metal tanks tended to be the most preferred (81.82%) storage facility for storing maize. Furthermore, the study found that Sitophilus zeamais Motschulsky and Sitotroga cerealella (Olivier) were the major storage insect pests of maize. The storage pests were managed using synthetic pesticides (84.42%), namely aluminium phosphide. This pesticide is a solid formulation for generating gas phosphine for fumigation. The continued indiscriminate use of this pesticide in protecting stored maize in this region could be a health hazard to humans and may result in the development of pest resistance.
Functional Analysis of Genes Encoding Juvenile Hormone Receptor Met and Transcription Factor Kr-h1 in the Reproductive Capacity of Coccinella septempunctata Males
Authors: Cheng Ying , Zhou Yuhang , Li Cao
Published: January 2025

This study focuses on the regulatory effects of genes encoding the juvenile hormone (JH) receptor methoprene-tolerant (Met) and transcription factor krüppel homolog 1 (Kr-h1) on the reproductive capacity of Coccinella septempunctata male adults. Met and Kr-h1 expression levels were analyzed in males fed on artificial diets with and without JH by quantitative real-time PCR, and the effects of Met and Kr-h1 on male reproduction were analyzed by RNA interference technology. Met transcription levels in 5- and 10-day-old males fed with a JH-supplemented diet were lower than those without JH. Kr-h1 expression in 5-day-old adult males was lower in diets lacking JH but was higher in 10-day-old males fed on a diet lacking JH. There were no significant differences in the testes sizes of male ladybugs injected with Met-dsRNA when compared to GFP-dsRNA; however, the testis volume of ladybugs injected with Kr-h1-dsRNA was smaller than those injected with GFP-dsRNA. After males were injected with Met-dsRNA and Kr-h1-dsRNA, the mean egg production by females decreased by 12.75% and 23.10%, respectively, at 20 d postinjection. Our results show that Met and Kr-h1 have important roles in regulating reproduction by directly affecting testes development in males and egg production in females.
Limb Axis Disorder During Leg Length Discrepancy Treatment with Temporary Epiphysiodesis Using Eight-Plate Implants
Authors: Starobrat Grzegorz , Danielewicz Anna , Szponder Tomasz , Wójciak Magdalena , Sowa Ireneusz , Różańska-Boczula Monika , Latalski Michał
Published: January 2025

Background: A common problem in pediatric orthopedics is leg length discrepancy (LLD). In adulthood, this may result in overload and degenerative changes in the lumbar spine, hip, and knee joints of the longer limb, and the fixed equinus position of the foot of the shorter limb. Surgical treatment using temporary epiphysiodesis with eight-plate implants is a minimally invasive, safe, and patient-tolerated procedure in LLD. However, publications mainly describe the effects of treatment in the form of achieved equalization and there is little information about the occurrence of secondary deformations. Our study aimed to determine the effect of temporary growth plate blocking on the final axis after treatment. Methods: The study was based on an analysis of radiographs recorded from 2010 to 2019 and an assessment of parameters such as MAD (mechanical axis deviation), mMPTA (mechanical medial proximal tibial angle), and M/at (mechanical axis of the tibia). Results: Twenty-four girls and thirty-six boys treated with eight-plate implants were included in the investigation. The duration of the treatment was 18 months (group I), 30 months (group II), and 42 months (group III). Our study revealed that the most significant differences were observed in the MAD parameter. MAD changed in a statistically significant manner across all investigated groups, for both girls and boys, regardless of the treatment duration. Conclusions: The treatment of LLD with epiphysiodesis using eight-plate implants influences both the anatomical axis of the bones and the mechanical axis of the limb.
Network Analysis of Legg–Calve–Perthes Disease and Its Comorbidities
Authors: Kim KyeongMi , Ko Kyung Rae , Yoon Siyoung , Chung Jaiwoo , Lee Soonchul
Published: January 2025

Background/Objectives: Legg–Calvé–Perthes disease (LCPD) is characterized by idiopathic avascular necrosis of the femoral head in children. There are several hypotheses regarding the cause of LCPD; however, the exact cause remains unclear. Studies on comorbidities can provide better insight into the disease. We aimed to perform a network analysis to identify the associations between LCPD and comorbidities. Methods: We analyzed patients aged ≤ 12 years with LCPD as defined by ICD-10 codes M91.1, M91.8, and M91.9 registered in the National Health Insurance Service cohort database from 2002 to 2015. A control group was designed using propensity score matching. Comorbidities were identified and network analysis was performed. The identified comorbidities were reclassified into clinical disease groups considering their clinical relevance, and a network map was created using odds ratios. Results: In total, 23 significant disease clusters were identified. Injury-related disease clusters with ICD-10 codes starting with “S” were the most frequent. They were reclassified into 11 disease groups based on clinical relevance. Among these, congenital deformities of hip (Q65) had the highest odds ratio. Congenital deformities of feet (Q66) and other anemia (D64) had a single association with LCPD in the comorbidity network analysis. Conclusions: We confirmed the association between LCPD and comorbidities using a network analysis. The LCPD comorbidity network identified in this study is expected to serve as the basis for future research on LCPD.
The Possible Impact of Zinc-Enriched Multivitamins on Treatment-Naïve Recurrent Aphthous Stomatitis Patients
Authors: Seo Hye Rin , Chung Kyung Bae , Kim Do-Young
Published: January 2025

Background/Objectives: Recurrent aphthous stomatitis is a common oral mucosal disorder characterized by painful ulcerations and frequent recurrences, which can significantly impair quality of life. This study explores the efficacy of zinc-enriched multivitamin supplementation (ZnVita, containing 22.5 mg of elemental zinc) for the treatment of recurrent aphthous stomatitis in treatment-naïve patients, aiming to diminish the reliance on immunomodulatory drugs. Methods: Conducted as a retrospective observational study at a tertiary referral hospital from 2013 to 2023, we analyzed 201 patients who received ZnVita daily for a minimum duration of one month as their initial management. Patients who were using systemic immunomodulating agents or met the diagnostic criteria for Behçet’s disease were excluded. Results: Of the 201 patients, 95 presented with an oral ulcer alone and 106 exhibited additional symptoms associated with Behçet’s disease. Efficacy analysis was conducted on 155 patients due to follow-up loss or incomplete data. Among them, 58.7% (91/155) showed partial or significant responses. Patients with BD-related symptoms were significantly more prevalent among non-responders (64.1%, 41/64) compared to responders (42.9%, 39/91), with a statistically significant difference (p = 0.009). Treatment was well-tolerated, with mild gastrointestinal adverse events reported in only 2.5% of cases. Conclusions: These results suggest that zinc-enriched multivitamin supplementation offers a beneficial and safe initial treatment alternative for a considerable proportion of treatment-naïve recurrent aphthous stomatitis patients, especially those without concurrent symptoms of Behçet’s disease, showcasing its potential in reducing the future need for immunomodulatory treatments.
Non-Classical Complications of Adult-Onset Still’s Disease: A Multicenter Spanish Study
Authors: Narváez Javier , Palacios-Olid Judith , García de Yebenes María Jesús , Holgado Susana , Olivé Alejandro , Casafont-Solé Ivette , Castañeda Santos , Valero-Martínez Cristina , Martín-López María , Carreira Patricia E. , Mora-Limiñana Maribel , Nuño-Nuño Laura , Robles-Marhuenda Angel , Bernabeu Pilar , Campos José , Graña Jenaro , Ortiz-Santamaria Vera , Camacho-Lovillo Marisol , Vargas Carmen , Sanchez-Manubens Judith , Anton Jordi
Published: January 2025

Objective: To investigate the prevalence and clinical spectrum of atypical or non-classical complications in adult-onset Still’s disease (AOSD) beyond macrophage activation syndrome (MAS) and to identify factors linked to their occurrence. Methods: Multicenter cross-sectional study of AODS cases included in the Spanish registry on Still’s disease. Results: This study included 107 patients (67% women), of whom 64 (59.8%) developed non-classical complications. These include macrophage activation syndrome in 9.5%, atypical skin manifestations in 38.8%, cardiac involvement in 22.7% (comprising pericarditis, myocarditis, pulmonary arterial hypertension, and noninfectious endocarditis), pleuritis in 28.9%, transient pulmonary infiltrates in 4%, significant headache in 14.1%, lower abdominal pain with evidence of peritonitis in 8.4%, and secondary amyloidosis in 0.9%. In the multivariate logistic regression analysis, lymphadenopathy (OR 2.85, 95% CI 1.03–7.91, p = 0.044) and the systemic score system (SSC) index (OR 1.86, 95% CI 1.29–2.69, p = 0.001) were independently associated with the development of non-classical clinical manifestations. In contrast, typical exanthema was associated with a reduced risk of these complications (OR 0.32, 95% CI 0.11–0.95, p = 0.041). Conclusions: In addition to the typical clinical manifestations and MAS, a significant proportion of patients with AOSD develop uncommon complications, some of which can be potentially life-threatening. These should be considered in the evaluation and follow-up of patients. Early recognition and prompt management are crucial to significantly reduce morbidity and mortality.
Machine Learning Approach for Prediction and Reliability Analysis of Failure Strength of U-Shaped Concrete Samples Joined with UHPC and PUC Composites
Authors: Haruna Sadi I. , Ibrahim Yasser E. , Umar Ibrahim Khalil
Published: January 2025

To meet the increasing demand for resilient infrastructure in seismic and high-impact areas, accurate prediction and reliability analysis of the performance of composite structures under impact loads is essential. Conventional techniques, including experimental testing and high-quality finite element simulation, require considerable time and resources. To address these issues, this study investigated individual and hybrid models including support vector regression (SVR), Gaussian process regression (GPR), and improved eliminate particle swamp optimization hybridized artificial neural network (IEPANN) models for predicting the failure strength of composite concrete developed by combining normal concrete (NC) with ultra-high performance concrete (UHPC) and polyurethane-based polymer concrete (PUC), considering different surface treatments and subjected to various static and impact loads. An experimental dataset was utilized to train the ML models and perform the reliability analysis on the impact dataset. Key parameters included compressive strength (Cfc), flexural load of the U-shaped specimens (P), density (ρ), first crack strength (N1), and splitting tensile strength (ft). Results revealed that all the developed models had high prediction accuracy, achieving NSE values above acceptable thresholds greater than 90% across all the datasets. Statistical errors such as RMSE, MAE, and PBIAS were calculated to fall within acceptable limits. Hybrid IEPANN appeared to be the most effective model, demonstrating the highest NSE value of 0.999 and the lowest RMSE, PBIAS, and MAE values of 0.0013, 0.0018, and 0.001, respectively. The reliability analysis revealed that impact times (N1 and N2) reduced as the survival probability increased.
An Evaluation of the Biocompatibility and Chemical Properties of Two Bioceramic Root Canal Sealers in a Sealer Extrusion Model of Rat Molars
Authors: Takahara Shintaro , Edanami Naoki , Ibn Belal Razi Saifullah , Yoshiba Kunihiko , Takenaka Shoji , Ohkura Naoto , Yoshiba Nagako , Gomez-Kasimoto Susan , Noiri Yuichiro
Published: January 2025

This study assessed the biocompatibility and chemical properties of two bioceramic root canal sealers, EndoSequence BC Sealer (EBC) and Nishika Canal Sealer BG (NBG), using a sealer extrusion model. Eight-week-old male Wistar rats were used. The mesial root canals of the upper first molars were pulpectomized and overfilled with EBC, NBG, or, as reference, epoxy resin-based AH Plus (AHP). After 28 days, periapical tissue reactions were assessed using microcomputed tomography and histological staining. The elemental composition and chemical composition of the extruded EBC and NBG were analyzed at Day 1 and 28 using an electron probe microanalyzer and micro-Raman spectroscopy. No periapical lesions were observed with the sealer extrusion. Additionally, inflammation around the extruded EBC and NBG was minimal to mild on Day 28, whereas moderate inflammation was found around the extruded AHP. Silicon concentration in the extruded EBC and NBG decreased significantly from Day 1 to 28, with almost no silicon present on Day 28. Furthermore, the extruded EBC and NBG became calcium- and phosphorus-rich, showing a Raman band for hydroxyapatite on Day 28. In conclusion, EBC and NBG demonstrated favorable biocompatibility and the ability to release silicon elements and produce hydroxyapatite when extruded into the periapical tissues. AHP showed moderate periapical tissue irritancy.
A New Deep Learning-Based Method for Automated Identification of Thoracic Lymph Node Stations in Endobronchial Ultrasound (EBUS): A Proof-of-Concept Study
Authors: Ervik Øyvind , Rødde Mia , Hofstad Erlend Fagertun , Tveten Ingrid , Langø Thomas , Leira Håkon O. , Amundsen Tore , Sorger Hanne
Published: January 2025

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a cornerstone in minimally invasive thoracic lymph node sampling. In lung cancer staging, precise assessment of lymph node position is crucial for clinical decision-making. This study aimed to demonstrate a new deep learning method to classify thoracic lymph nodes based on their anatomical location using EBUS images. Bronchoscopists labeled lymph node stations in real-time according to the Mountain Dressler nomenclature. EBUS images were then used to train and test a deep neural network (DNN) model, with intraoperative labels as ground truth. In total, 28,134 EBUS images were acquired from 56 patients. The model achieved an overall classification accuracy of 59.5 ± 5.2%. The highest precision, sensitivity, and F1 score were observed in station 4L, 77.6 ± 13.1%, 77.6 ± 15.4%, and 77.6 ± 15.4%, respectively. The lowest precision, sensitivity, and F1 score were observed in station 10L. The average processing and prediction time for a sequence of ten images was 0.65 ± 0.04 s, demonstrating the feasibility of real-time applications. In conclusion, the new DNN-based model could be used to classify lymph node stations from EBUS images. The method performance was promising with a potential for clinical use.
Application of Generative Artificial Intelligence Models for Accurate Prescription Label Identification and Information Retrieval for the Elderly in Northern East of Thailand
Authors: Thetbanthad Parinya , Sathanarugsawait Benjaporn , Praneetpolgrang Prasong
Published: January 2025

This study introduces a novel AI-driven approach to support elderly patients in Thailand with medication management, focusing on accurate drug label interpretation. Two model architectures were explored: a Two-Stage Optical Character Recognition (OCR) and Large Language Model (LLM) pipeline combining EasyOCR with Qwen2-72b-instruct and a Uni-Stage Visual Question Answering (VQA) model using Qwen2-72b-VL. Both models operated in a zero-shot capacity, utilizing Retrieval-Augmented Generation (RAG) with DrugBank references to ensure contextual relevance and accuracy. Performance was evaluated on a dataset of 100 diverse prescription labels from Thai healthcare facilities, using RAG Assessment (RAGAs) metrics to assess Context Recall, Factual Correctness, Faithfulness, and Semantic Similarity. The Two-Stage model achieved high accuracy (94%) and strong RAGAs scores, particularly in Context Recall (0.88) and Semantic Similarity (0.91), making it well-suited for complex medication instructions. In contrast, the Uni-Stage model delivered faster response times, making it practical for high-volume environments such as pharmacies. This study demonstrates the potential of zero-shot AI models in addressing medication management challenges for the elderly by providing clear, accurate, and contextually relevant label interpretations. The findings underscore the adaptability of AI in healthcare, balancing accuracy and efficiency to meet various real-world needs.