bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Association Study to Identify Genetic Factors Linked to HBV Reactivation Following Liver Transplantation in HBV-Infected Patients
Authors: Park Joonhong , Kim Dong Yun , Gee Heon Yung , Yu Hee Chul , Yang Jae Do , Hwang Shin , Choi YoungRok , Lee Jae Geun , Rhu Jinsoo , Choi Donglak , You Young Kyoung , Ryu Je Ho , Nah Yang Won , Kim Bong-Wan , Kim Dong-Sik , Cho Jai Young , Group The Korean Organ Transplantation Registry (KOTRY) Study
Published: December 2024

This study utilized a genome-wide association study (GWAS) to investigate the genetic variations linked to the risk of hepatitis B virus (HBV) reactivation in patients who have undergone liver transplantation (LT), aiming to enhance understanding and improve clinical outcomes. Genotyping performed on a selected patients from the Korean Organ Transplantation Registry (KOTRY) data using high-throughput platforms with the Axiom Korea Biobank array 1.1. The discovery cohort included 21 patients who experienced HBV reactivation (cases) and 888 patients without HBV reactivation (controls) following LT. The replication cohort consisted of 5 patients with HBV reactivation (cases) and 312 patients without HBV reactivation (controls) after LT. Additive logistic regression analysis was conducted using PLINK software ver 1.9, with adjustments for age and gender. The GWAS findings from the discovery cohort were validated using the replication cohort. The GWAS identified several single-nucleotide polymorphisms (SNPs) in the RGL1, CDCA7L, and AQP9 genes that were significantly linked to HBV reactivation after LT, with genome-wide significance thresholds set at p < 10−7. Down-regulation of RGL1 cDNAs was observed in primary duck hepatocytes infected with duck HBV. Overexpression of CDCA7L was found to promote hepatocellular carcinoma cell proliferation and colony formation, whereas knocking down CDCA7L inhibited these processes. Additionally, the absence of AQP9 triggered immune and inflammatory responses, leading to mild and scattered liver cell pyroptosis, accompanied by compensatory liver cell proliferation. This study provides critical insights into the genetic factors influencing HBV reactivation after LT, identifying significant associations with SNPs in RGL1, CDCA7L, and AQP9. These findings hold promise for developing predictive biomarkers and personalized management strategies to improve outcomes for HBV-infected LT recipients.
Effect of Genetic Variants on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Involvement of ABCG2, SLCO1B1 and NAT2
Authors: González-Iglesias Eva , Méndez-Ponce Clara , Ochoa Dolores , Román Manuel , Mejía-Abril Gina , Martín-Vilchez Samuel , de Miguel Alejandro , Gómez-Fernández Antía , Rodríguez-Lopez Andrea , Soria-Chacartegui Paula , Abad-Santos Francisco , Novalbos Jesús
Published: December 2024

Statins are the primary drugs used to prevent cardiovascular disease by inhibiting the HMG-CoA reductase, an enzyme crucial for the synthesis of LDL cholesterol in the liver. A significant number of patients experience adverse drug reactions (ADRs), particularly musculoskeletal problems, which can affect adherence to treatment. Recent clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2022, recommend adjusting rosuvastatin doses based on genetic variations in the ABCG2 and SLCO1B1 genes to minimize ADRs and improve treatment efficacy. Despite these adjustments, some patients still experience ADRs. So, we performed a candidate gene study to better understand the pharmacogenetics of rosuvastatin. This study included 119 healthy volunteers who participated in three bioequivalence trials of rosuvastatin alone or in combination with ezetimibe at the Clinical Trials Unit of the Hospital Universitario de La Princesa (UECHUP). Participants were genotyped using a custom OpenArray from ThermoFisher that assessed 124 variants in 38 genes associated with drug metabolism and transport. No significant differences were observed according to sex or biogeographic origin. A significant increase in t1/2 (pmultivariate(pmv) = 0.013) was observed in the rosuvastatin plus ezetimibe trial compared with the rosuvastatin alone trials. Genetic analysis showed that decreased (DF) and poor function (PF) volunteers for the ABCG2 transporter had higher AUC∞/DW (adjusted dose/weight), AUC72h/DW and Cmax/DW compared to normal function (NF) volunteers (pmv< 0.001). DF and PF volunteers for SLCO1B1 showed an increase in AUC72h/DW (pmv = 0.020) compared to increased (IF) and NF individuals. Results for ABCG2 and SLCO1B1 were consistent with the existing literature. In addition, AUC∞/DW, AUC72h/DW and Cmax/DW were increased in intermediate (IA) and poor (PA) NAT2 acetylators (pmv = 0.001, pmv< 0.001, pmv< 0.001, respectively) compared to rapid acetylators (RA), which could be associated through a secondary pathway that was previously unknown.
The Synergy of Chitosan and Azoxystrobin Against Fusarium graminearum Is Modulated by Selected ABC Transporters
Authors: Poznanski Pawel , Shalmani Abdullah , Poznanski Pascal , Orczyk Waclaw
Published: December 2024

The development of innovative and effective strategies to combat fungal pathogens is critical to sustainable crop protection. Fungicides have been used for over two centuries, with traditional copper- and sulfur-based formulations still in use due to their broad-spectrum, multisite mode of action, which minimizes the risk of pathogen resistance. In contrast, modern systemic fungicides, though potent, often target a single site of action, leading to the accelerated emergence of resistant fungal strains. This study explores synergistic interactions between chitosan (CS) and selected fungicides, focusing on their antifungal activity against Fusarium graminearum. Among the fungicides tested, azoxystrobin (Amistar) exhibited the highest 44.88 synergy score when combined with CS (30 kDa, degree of deacetylation ≥ 90), resulting in significantly improved antifungal efficacy. Furthermore, the combination of CS and Amistar with double-stranded RNA (dsRNA) targeting selected ABC transporter genes further amplified antifungal activity by silencing genes critical for fungal tolerance to treatment. This dual synergy highlights the potential of RNA interference (RNAi) as both a functional tool to investigate fungal physiology and an effective antifungal strategy. These findings reveal a promising and environmentally friendly approach to mitigate resistance while improving fungal control. Furthermore, the remarkable synergy between azoxystrobin and CS presents a novel mechanism with significant potential for sustainable agricultural applications, which warrants further investigation to elucidate its molecular basis.
Transgenic Cotton Expressing dsAgCYP6CY3 Significantly Delays the Growth and Development of Aphis gossypii by Inhibiting Its Glycolysis and TCA Cycle
Authors: Kong Wenting , Li Tingting , Li Yuan , Zhang Lianjun , Xie Jingang , Liu Xiaoning
Published: December 2024

In our previous research, we found that CYP6CY3 not only participates in the detoxification metabolism of neonicotinoid insecticides in cotton aphid but also affects their growth and development. However, how does transgenic cotton expressing dsAgCYP6CY3 affect the growth and development of cotton aphid? In this study, we combined transcriptome and metabolome to analyze how to inhibit the growth and development of cotton aphid treated with transgenic cotton expressing dsAgCYP6CY3-P1 (TG cotton). The results suggested that a total of 509 differentially expressed genes (DEGs) were identified based on the DESeq method, and a total of 431 differential metabolites (DAMs) were discovered using UPLC-MS in the metabolic analysis. Additionally, multiple DEGs and DAMs of glycolytic and The tricarboxylic acid (TCA) cycle pathways were significantly down-regulated. Pyruvate carboxylase (PC), citrate synthase (CS), malate dehydrogenase (MDH) enzyme activities and pyruvate content were reduced in cotton aphid treated with TG cotton. In addition, TG cotton could significantly decrease the total sugar content from the body and honeydew in cotton aphid. The above results indicated that TG cotton inhibited glycolysis and the TCA cycle, and this inhibition is consistent with previous studies showing that cotton aphid fed on TG cotton showed significantly reduced body length and weight as well as delayed molting. These findings provide a new strategy for reducing the transmission of viruses by cotton aphid honeydew, preventing fungal growth, mitigating impacts on normal photosynthesis and improving cotton quality.
Generation of Bona Fide Human Induced Trophoblast Stem Cells by Direct Reprogramming of Term Umbilical Cord Cells
Authors: van Voorden A. Jantine , Boussata Souad , Keijser Remco , Vermij Marloes , Wagner Muriel K. , Ganzevoort Wessel , Afink Gijs B.
Published: December 2024

Placentation disorders, including severe preeclampsia and fetal growth restriction, have their origins in early pregnancy, whereas symptoms typically present later on. To investigate the pathogenesis of these diseases, there is a need for a reliable in vitro model system of early placenta development with known pregnancy outcomes. Therefore, we optimized the generation of human induced trophoblast stem cells (iTSCs) from term umbilical cord, enabling non-invasive collection of patient-derived material immediately after birth. Using a direct reprogramming approach previously described for dermal fibroblasts, we investigated the effects of three supplements (A-485, BMP4, and EPZ-6438) to assess their potential to enhance iTSC induction. The generated iTSCs fulfilled the criteria for bona fide first-trimester trophoblasts and exhibited key functional capacities, including long-term self-renewal, differentiation into hormone-producing syncytiotrophoblasts and invasive extravillous trophoblasts, and the formation of organoids. Furthermore, transcriptomic analysis revealed high similarity between the generated iTSCs and trophoblast stem cells derived from first-trimester placental tissue. The supplements did not improve the generation of iTSCs. In conclusion, we successfully generated bona fide iTSCs from term umbilical cord using a direct reprogramming approach, providing a robust and clinically relevant model to study early placentation mechanisms in patient-derived trophoblasts.
Elucidation of Factors Affecting the Age-Dependent Cancer Occurrence Rates
Authors: Xiao Jun , Cao Yangkun , Li Xuan , Xu Long , Wang Zhihang , Huang Zhenyu , Mu Xuechen , Qu Yinwei , Xu Ying
Published: December 2024

Cancer occurrence rates exhibit diverse age-related patterns, and understanding them may shed new and important light on the drivers of cancer evolution. This study systematically analyzes the age-dependent occurrence rates of 23 carcinoma types, focusing on their age-dependent distribution patterns, the determinants of peak occurrence ages, and the significant difference between the two genders. According to the SEER reports, these cancer types have two types of age-dependent occurrence rate (ADOR) distributions, with most having a unimodal distribution and a few having a bimodal distribution. Our modeling analyses have revealed that (1) the first type can be naturally and simply explained using two age-dependent parameters: the total number of stem cell divisions in an organ from birth to the current age and the availability levels of bloodborne growth factors specifically needed by the cancer (sub)type, and (2) for the second type, the first peak is due to viral infection, while the second peak can be explained as in (1) for each cancer type. Further analyses indicate that (i) the iron level in an organ makes the difference between the male and female cancer occurrence rates, and (ii) the levels of sex hormones are the key determinants in the onset age of multiple cancer types. This analysis deepens our understanding of the dynamics of cancer evolution shared by diverse cancer types and provides new insights that are useful for cancer prevention and therapeutic strategies, thereby addressing critical gaps in the current paradigm of oncological research.
Abscisic Acid, Microtubules and Phospholipase D-Solving a Cellular Bermuda Triangle
Authors: Liu Xuan , Riemann Michael , Nick Peter
Published: December 2024

Rice plants are important food crops that are sensitive to cold stress. Microtubules (MTs) are highly associated with plant response to cold stress. The exogenous application of abscisic acid (ABA) can transiently induce the cold stability of microtubules. These phenotypes were accompanied by the transient increase in Phospholipase D (PLD) enzyme activity. The analysis of detyrosinated/tyrosinated α-tubulin by Western blot in the NtTUA3 line or in the NtTUA3+OsTTL line gave us such a conclusion that the effect of ABA on detyrosinated α-tubulin not only was regulated by ABA but also was dependent on the TTLL12 protein. The dual ABA and 1% n-butanol treatments had shown that ABA-induced detyrosinated α-tubulin in a manner distinct from the n-butanol pathway. Detecting the detyrosinated α-tubulin level after pre-treatment with pertussis toxin (PTX), a G-protein inhibitor, followed by ABA, as well as mastoparan (Mas7) treatment suggested that the effect of ABA on detyrosinated α-tubulin was dependent on PLD activity.
Analyses of the MYBL1 Gene in Triple Negative Breast Cancer: Evidence of Regulation of the VCPIP1 Gene and Identification of a Specific Exon Overexpressed in Tumor Cell Lines
Authors: Nganya Chidinma , Bryant Sahia , Alnakhalah Ayah , Allen-Boswell Taylor , Cunningham Sierra , Kanu Samuel , Williams Ashton , Philio Deshai , Dang Kathy , Butler Emmanuel , Player Audrey
Published: December 2024

Previous data show that the knockdown of the MYBL1 gene in the MDA-MB-231 cell line leads to the downregulation of VCPIP1 gene expression. In addition, MYBL1 and VCPIP1 genes are co-expressed and dysregulated in some of the same triple negative breast cancer patient samples. We propose that the co-expression of the two genes is attributed to the MYBL1 transcription factor regulation of the VCPIP1 gene. We identify the MYBL1 transcription factor binding site upstream of the VCPIP1 start site and show that the MYBL1 protein can bind to the sequence identified in the VCPIP1 promoter region. Combined with the results from the knockdown study, these data support the ability of MYBL1 to regulate the VCPIP1 gene. The VCPIP1 gene functions as a deubiquitinating enzyme involved in DNA repair, protein positioning, and the assembly of the Golgi apparatus during mitotic signaling. The transcriptional regulation of VCPIP1 by the MYBL1 gene could implicate MYBL1 in these processes, which might contribute to tumor processes in TNBC. Although both genes are involved in cell cycle regulatory mechanisms, converging signaling mechanisms have not been identified. In a separate study, we performed sequence alignment of the MYBL1 transcript variants and identified an exon unique to the canonical variant. Probes that specifically target the unique MYBL1 exon show that the exon is overexpressed in tumor cell lines compared to non-tumor breast cells. We are classifying this unique MYBL1 exon as a tumor-associated exon.
Head-to-Head Comparison of Aptamer- and Antibody-Based Proteomic Platforms in Human Cerebrospinal Fluid Samples from a Real-World Memory Clinic Cohort
Authors: Puerta Raquel , Cano Amanda , García-González Pablo , García-Gutiérrez Fernando , Capdevila Maria , de Rojas Itziar , Olivé Clàudia , Blázquez-Folch Josep , Sotolongo-Grau Oscar , Miguel Andrea , Montrreal Laura , Martino-Adami Pamela , Khan Asif , Orellana Adelina , Sung Yun Ju , Frikke-Schmidt Ruth , Marchant Natalie , Lambert Jean Charles , Rosende-Roca Maitée , Alegret Montserrat , Fernández Maria Victoria , Marquié Marta , Valero Sergi , Tárraga Lluís , Cruchaga Carlos , Ramírez Alfredo , Boada Mercè , Smets Bart , Cabrera-Socorro Alfredo , Ruiz Agustín
Published: December 2024

High-throughput proteomic platforms are crucial to identify novel Alzheimer’s disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan® assays analyzing the same samples, and between SomaScan® and Olink® results. Association analyses were performed between proteomic measures, CSF biological traits, sample demographics, and AD endophenotypes. Our 12-category metric of reproducibility combining correlation analyses identified 2428 highly reproducible SomaScan CSF measures, with over 600 proteins well reproduced on another proteomic platform. The association analyses among AD clinical phenotypes revealed that the significant associations mainly involved reproducible proteins. The validation of reproducibility in these novel proteomics platforms, measured using this scarce biomaterial, is essential for accurate analysis and proper interpretation of innovative results. This classification metric could enhance confidence in multiplexed proteomic platforms and improve the design of future panels.
Cyclic Imines and Their Salts as Universal Precursors in the Synthesis of Nitrogen-Containing Alkaloids
Authors: Smolobochkin Andrey , Gazizov Almir , Sidlyaruk Nikita , Akylbekov Nurgali , Zhapparbergenov Rakhmetulla , Burilov Alexander
Published: December 2024

Alkaloids are predominantly nitrogen-containing heterocyclic compounds that are usually isolated from plants, and sometimes from insects or animals. Alkaloids are one of the most important types of natural products due to their diverse biological activities and potential applications in modern medicine. Cyclic imines were chosen as starting compounds for the synthesis of alkaloids due to their high synthetic potential. Thus, this review summarizes the achievements in the synthesis of various alkaloids from cyclic imines, paying special attention to stereoselective methods used for their preparation. Information on the biological activity of some alkaloids, their application and occurrence in natural objects is presented. Synthesis methods are classified based on the type of alkaloid obtained.
Standardization to Characterize the Complexity of Vessel Network Using the Aortic Ring Model
Authors: Wolint Petra , Hofmann Silvan , von Atzigen Julia , Böni Roland , Miescher Iris , Giovanoli Pietro , Calcagni Maurizio , Emmert Maximilian Y. , Buschmann Johanna
Published: December 2024

Regeneration after ischemia requires to be promoted by (re)perfusion of the affected tissue, and, to date, there is no therapy that covers all needs. In treatment with mesenchymal stem cells (MSC), the secretome acts via paracrine mechanisms and has a positive influence on vascular regeneration via proangiogenic factors. A lack of standardization and the high complexity of vascular structures make it difficult to compare angiogenic readouts from different studies. This emphasizes the need for improved approaches and the introduction of an index in the preclinical setting. A characterization of human MSC secretomes obtained from one of the three formats—single cells, small, and large spheroids—was performed using the chicken aortic ring assay in combination with a modified angiogenic activity index (AAI) and an angiogenic profile. While the secretome of the small spheroid group showed an inhibitory effect on angiogenesis, the large spheroid group impressed with a fully pro-angiogenic response, and a higher AAI compared to the single cell group, underlying the suitability of these three-stem cell-derived secretomes with their distinct angiogenic properties to validate the AAI and the novel angiogenic profile established here.
Small Extracellular Vesicles Derived from Lipopolysaccharide-Treated Stem Cells from the Apical Papilla Modulate Macrophage Phenotypes and Inflammatory Interactions in Pulpal and Periodontal Tissues
Authors: Tessier Solène , Halgand Boris , Aubeux Davy , Véziers Joëlle , Galvani Angélique , Jamoneau Juliette , Pérez Fabienne , Geoffroy Valérie , Gaudin Alexis
Published: December 2024

Inflammation significantly influences cellular communication in the oral environment, impacting tissue repair and regeneration. This study explores the role of small extracellular vesicles (sEVs) derived from lipopolysaccharide (LPS)-treated stem cells from the apical papilla (SCAP) in modulating macrophage polarization and osteoblast differentiation. SCAPs were treated with LPS for 24 h, and sEVs from untreated (SCAP-sEVs) and LPS-treated SCAP (LPS-SCAP-sEVs) were isolated via ultracentrifugation and characterized using transmission electron microscopy, Western blot, and Tunable Resistive Pulse Sensing. LPS-SCAP-sEVs exhibited characteristic exosome morphology (~100 nm diameter) and expressed vesicular markers (CD9, CD63, CD81, and HSP70). Functional analysis revealed that LPS-SCAP-sEVs promoted M1 macrophage polarization, as evidenced by the increased pro-inflammatory cytokines (IL-6 and IL-1β) and the reduced anti-inflammatory markers (IL-10 and CD206), while impairing the M2 phenotype. Additionally, LPS-SCAP-sEVs had a minimal impact on SCAP metabolic activity or osteogenic gene expression but significantly reduced mineralization capacity in osteogenic conditions. These findings suggest that sEVs mediate the inflammatory interplay between SCAP and macrophages, skewing macrophage polarization toward a pro-inflammatory state and hindering osteoblast differentiation. Understanding this sEV-driven communication axis provides novel insights into the cellular mechanisms underlying inflammation in oral tissues and highlights potential therapeutic targets for modulating extracellular vesicle activity during acute inflammatory episodes.
Association of Baseline Lipopolysaccharide-Binding Protein with Expanded Disability Status Score Dynamics in Patients with Relapsing–Remitting Multiple Sclerosis: A Pilot Study
Authors: Vilmane Anda , Kolesova Oksana , Nora-Krukle Zaiga , Kolesovs Aleksandrs , Pastare Daina , Jaunozolina Liga , Kande Linda , Egle Jelena , Kromane Daniela , Micule Madara , Liepina Sintija , Zeltina Estere , Gravelsina Sabine , Rasa-Dzelzkaleja Santa , Viksna Ludmila , Karelis Guntis
Published: December 2024

Forecasting the progression of the disease in the early inflammatory stage of the most prevalent type of multiple sclerosis (MS), referred to as relapsing–remitting multiple sclerosis (RRMS), is essential for making prompt treatment modifications, aimed to reduce clinical relapses and disability. In total, 58 patients with RRMS, having an Expanded Disability Status Scale (EDSS) score less than 4, were included in this study. Baseline magnetic resonance imaging (MRI) was performed, and brain and spinal cord lesions were evaluated. The disability of the patients was evaluated using EDSS at baseline and follow-up; enzyme-linked immunosorbent assays (ELISAs) were also used to determine the level of blood-based inflammation markers in plasma at baseline. The main results demonstrated that the baseline level of LBP was correlated with an increase in EDSS in a short (8–10 months) follow-up period. Furthermore, the prognostic significance of LBP was only observed in patients who received disease-modifying treatment (DMT) before the study. Our results suggest that the baseline level of LBP may be among the predictors of disability progression in RRMS over short follow-up periods, particularly in those receiving treatment. It highlights the effect of endotoxins in the pathogenesis of RRMS.
Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability
Authors: Veldman Abigail , Sikkema-Raddatz Birgit , Derks Terry G. J. , van Karnebeek Clara D. M. , Kiewiet M. B. Gea , Mulder Margaretha F. , Nelen Marcel R. , Rubio-Gozalbo M. Estela , Sinke Richard J. , de Sain-van der Velden Monique G. , Visser Gepke , de Vries Maaike C. , Westra Dineke , Williams Monique , Wevers Ron A. , Heiner-Fokkema M. Rebecca , van Spronsen Francjan J.
Published: December 2024

The biomarker-based Dutch Newborn Screening (NBS) panel (as of 2024) comprises 19 inherited metabolic disorders (IMDs). With the use of next-generation sequencing (NGS) as a first-tier screen, NBS could expand to include IMDs that lack a reliable biochemical footprint in dried blood spots, while also reducing secondary findings. To be eligible for inclusion in NBS, an IMD needs to fulfill the Wilson and Jungner criteria, with treatability being one of the most important criteria. In this study, we aimed to identify IMDs eligible for DNA-first NBS when considering only treatability in the context of NBS as a prerequisite. First, three independent reviewers performed a systematic literature review of the 1459 genotypic IMDs and their causative gene(s), as described in the International Classification of Inherited Metabolic Disorders (dated 1 February 2021), applying 16 criteria to exclude non-treatable disorders. Eligible disorders were then discussed in three online meetings with a project group of clinical laboratory geneticists, medical laboratory specialists specialized in IMD, and pediatricians with expertise in IMDs. Based on treatability, we identified 100 genes, causing 95 IMDs, as eligible for NBS, including 42 causal genes for the IMDs in the current biomarker-based NBS. The other 58 genes are primarily associated with treatable defects in amino acid metabolism and fatty acid oxidation. Other IMDs were excluded, most often because of insufficient literature. As the evaluation of treatability was not straightforward, we recommend the development of standardized treatability scores for the inclusion of IMDs in NBS.
Consolidated Newborn Bloodspot Screening Efforts in Developing Countries in the Asia Pacific—2024
Authors: Therrell Bradford L. , Padilla Carmencita D. , Abadingo Michelle E. , Adhikari Shree Prasad , Aung Thuza , Aye Thet Thet , Dey Sanjoy Kumer , Faizi Muhammad , Ganbaatar Erdenetuya , Giang Tran Thi Huong , Hang Hoang Thu , Heng Rathmony , Kapoor Seema , Nyamdavaa Khurelbaatar , Paudel Prajwal , Phou Kimyi , Pulungan Aman B. , Sayyavong Chittaphone , Walani Salimah R. , Zafar Tariq
Published: December 2024

Approximately half of all births globally occur in the Asia Pacific Region. Concerted efforts to support local activities aimed at developing national newborn screening (NBS) have been ongoing for almost 30 years, first by the International Atomic Energy Agency (IAEA) and then through volunteer efforts. Sustainable newborn bloodspot screening (NBS) continues to be initiated and develop in many of the countries with developing economies in the region. Since the discontinuation of IAEA funding in 2007, a working group of the Asia Pacific Society of Human Genetics (APSHG) consisting of interested representatives from countries in the region with less than 50% NBS coverage has participated in periodic workshops to exchange information, set goals, and provide peer support. Facilitated by international NBS experts, interested corporate sponsors, and the APSHG, the 7th workshop of representatives from 10 East Asian countries with developing NBS systems was recently held in Kathmandu, Nepal. This report summarizes the NBS activities in these countries and describes the continuing efforts to move NBS ahead in the region.
Impact of Sofosbuvir Plus Daclatasvir Therapy on the Frequency of CD200R+ Dendritic Cells in Chronic Hepatitis C Virus Infection
Authors: Hetta Helal F. , Mekky Mohamed A. , Sayed Hani I. , Soliman Mahran Ahmed AbdElkader , Salama Eman H. , Sayed Douaa , Abdallah Mariam E. , Mohamed Doaa Safwat , El-Badawy Omnia , El-Mokhtar Mohamed A.
Published: December 2024

Dendritic cells (DCs) play a crucial role in controlling viral infections. Little is known about the changes in frequencies of the DC subsets in patients with chronic hepatitis C (CHC), particularly in the era of interferon-free regimens. We aimed to evaluate the impact of sofosbuvir/daclatasvir on the frequency of different peripheral DC subsets, the expression of the inhibitory CD200R and its ligand CD200 on DC, and their relation to the treatment outcome. A total of 1000 patients with CHC were enrolled and treated with a fixed oral dose of 400 mg of sofosbuvir and 60 mg of daclatasvir for 12 weeks. A total of 940 patients achieved sustained virologic response (SVR), and only 60 patients were non-responders (NRs). The frequencies of the peripheral plasmacytoid (pDC) and myeloid (mDCs) subsets and their surface expressions of CD200R and CD200 molecules were analyzed using flow cytometry. This analysis included 60 non-responders (NR group), 60 randomly selected sustained virologic responders (SVR group) at baseline, and at the end of treatment, and 60 healthy controls. HCV infection was associated with a down-regulation in the frequency of mDC, compared to healthy controls. In addition, mDC in HCV-infected patients showed lower levels of CD200R. However, neither the pDC frequency nor their CD200R expression was significantly altered. Interestingly, by the end of therapy, the frequencies of circulating mDCs and CD200R+mDC increased significantly in the SVR group and were even comparable to healthy controls. The levels of these cells were not normalized in the NR group. Percentages of mDCs and CD200R+mDC subsets showed good prognostic accuracy for predicting virologic response to therapy. Our results showed that HCV infection was associated with modulation of the mDC frequency and their surface expression of CD200R. Successful daclatasvir and sofosbuvir combined therapy was associated with the normalization of the percentages of mDC and CD200R+mDC.
Image Augmentation Using Both Background Extraction and the SAHI Approach in the Context of Vision-Based Insect Localization and Counting
Authors: Saradopoulos Ioannis , Potamitis Ilyas , Rigakis Iraklis , Konstantaras Antonios , Barbounakis Ioannis S.
Published: December 2024

Insects play essential roles in ecosystems, providing services such as pollination and pest regulation. However, global insect populations are in decline due to factors like habitat loss and climate change, raising concerns about ecosystem stability. Traditional insect monitoring methods are limited in scope, but advancements in AI and machine learning enable automated, non-invasive monitoring with camera traps. In this study, we leverage the new Diopsis dataset that contains images from field operations to explore an approach that emphasizes both background extraction from images and the SAHI approach. By creating augmented backgrounds from extracting insects from training images and using these backgrounds as canvases to artificially relocate insects, we can improve detection accuracy, reaching mAP50 72.7% with YOLO10nano, and reduce variability when counting insects on different backgrounds and image sizes, supporting efficient insect monitoring on low-power devices such as Raspberry Pi Zero W 2.
An Exploratory Investigation of Chatbot Applications in Anxiety Management: A Focus on Personalized Interventions
Authors: Manole Alexia , Cârciumaru Răzvan , Brînzaș Rodica , Manole Felicia
Published: December 2024

Anxiety disorders are among the most prevalent mental health conditions globally, causing significant personal and societal burdens. Traditional therapies, while effective, often face barriers such as limited accessibility, high costs, and the stigma associated with seeking mental health care. The emergence of artificial intelligence (AI) chatbots offers a novel solution by providing accessible, cost-effective, and immediate support for individuals experiencing anxiety. This comprehensive review examines the evolution, efficacy, advantages, limitations, challenges, and future perspectives of AI chatbots in the treatment of anxiety disorders. A methodologically rigorous literature search was conducted across multiple databases, focusing on publications from 2010 to 2024 that evaluated AI chatbot interventions targeting anxiety symptoms. Empirical studies demonstrate that AI chatbots can effectively reduce anxiety symptoms by delivering therapeutic interventions like cognitive-behavioral therapy through interactive and personalized dialogues. The advantages include increased accessibility without geographical or temporal limitations, reduced costs, and an anonymity that encourages openness and reduces stigma. However, limitations persist, such as the lack of human empathy, ethical and privacy concerns related to data security, and technical challenges in understanding complex human emotions. The key challenges identified involve enhancing the emotional intelligence of chatbots, integrating them with traditional therapy, and establishing robust ethical frameworks to ensure user safety and data protection. Future research should focus on improving AI capabilities, personalization, cultural adaptation, and user engagement. In conclusion, AI chatbots represent a promising adjunct in treating anxiety disorders, offering scalable interventions that can complement traditional mental health services. Balancing technological innovation with ethical responsibility is crucial to maximize their potential benefits.
The Use of Voice Control in 3D Medical Data Visualization Implementation, Legal, and Ethical Issues
Authors: Vincze Miklos , Molnar Bela , Kozlovszky Miklos
Published: December 2024

Voice-controlled devices are becoming increasingly common in our everyday lives as well as in medicine. Whether it is our smartphones, with voice assistants that make it easier to access functions, or IoT (Internet of Things) devices that let us control certain areas of our home with voice commands using sensors and different communication networks, or even medical robots that can be controlled by a doctor with voice instructions. Over the last decade, systems using voice control have made great progress, both in terms of accuracy of voice processing and usability. The topic of voice control is intertwined with the application of artificial intelligence (AI), as the mapping of spoken commands into written text and their understanding is mostly conducted by some kind of trained AI model. Our research had two objectives. The first was to design and develop a system that enables doctors to evaluate medical data in 3D using voice control. The second was to describe the legal and ethical issues involved in using AI-based solutions for voice control. During our research, we created a voice control module for an existing software called PathoVR, using a model taught by Google to interpret the voice commands given by the user. Our research, presented in this paper, can be divided into two parts. In the first, we have designed and developed a system that allows the user to evaluate 3D pathological medical serial sections using voice commands. In contrast, in the second part of our research, we investigated the legal and ethical issues that may arise when using voice control in the medical field. In our research, we have identified legal and ethical barriers to the use of artificial intelligence in voice control, which need to be answered in order to make this technology part of everyday medicine.
A Symbolic Algorithm for Checking the Identifiability of a Time-Series Model
Authors: Mélard  Guy
Published: December 2024

Several authors have attempted to compute the asymptotic Fisher information matrix for a univariate or multivariate time-series model to check for its identifiability. This has the form of a contour integral of a matrix of rational functions. A recent paper has proposed a short Wolfram Mathematica notebook for VARMAX models that makes use of symbolic integration. It cannot be used in open-source symbolic computation software like GNU Octave and GNU Maxima. It was based on symbolic integration but the integrand lacked symmetry characteristics in the appearance of polynomial roots smaller or greater than 1 in modulus. A more symmetric form of the integrand is proposed for VARMA models that first allows a simpler approach to symbolic integration. Second, the computation of the integral through Cauchy residues is also possible. Third, an old numerical algorithm by Söderström is used symbolically. These three approaches are investigated and compared on a pair of examples, not only for the Wolfram Language in Mathematica but also for GNU Octave and GNU Maxima. As a consequence, there are now sufficient conditions for exact model identifiability with fast procedures.
Deep Learning-Based Analysis of Ocular Anterior Segment Diseases from Patient-Self-Captured Smartphone Images
Authors: Gu Byoungyoung , Christopher Mark , Lim Su-Ho , Baxter Sally L.
Published: December 2024

The goal of this study is to evaluate the Eye Home Clinic app (ver 1.0), which uses deep learning models to assess the quality of self-captured anterior segment images and detect anterior segment diseases using only the patient’s smartphone. Images undergo quality assessment based on the ‘DL-Image Eligibility’ model, and usable images are analyzed by the ‘DL-Diagnosis’ model to detect one of several anterior segment diseases. A dataset of 1006 images was used for training, and a dataset of 520 images was used for validation. The ‘DL-Image Eligibility’ model achieved an AUC of 0.87, with an accuracy of 0.75. The ‘DL-Diagnosis’ model had higher specificity (0.97) but lower sensitivity (0.29), with an AUC of 0.62. While the app shows potential for anterior segment telemedicine, improvements are needed in the DL model’s sensitivity for detecting abnormalities. Oversampling techniques, transfer learning, and dataset expansion should be considered to enhance the performance in future research. Based on data from users in over 100 countries, significant differences in photo quality among user groups were also identified. iOS users, younger users (21–40 years), and users reporting eye symptoms submitted more usable images. This study underscores the importance of user education and technological advancements to optimize smartphone-based ocular diagnostics.
Flexible and Sustainable Incremental Houses: Advancing Semi-Volumetric Systems of Prefabricated Construction for Rapid Urbanization in Indonesia
Authors: Viriezky Viata , Susanto Dalhar , Alkadri Miktha Farid
Published: December 2024

The Indonesian population is projected to increase by 66.65 in 2035 due to the continuous rise in urbanization globally. The growth contributed to the growing housing backlog and limited availability of residential spaces. This led to the evolution of incremental housing construction as an appropriate solution to residents’ needs. However, several factors hinder the implementation of incremental housing, including prolonged construction durations that delay the completion of an entire house, compromised quality of workmanship and materials, as well as poor flexibility. Conventional on-site construction, with concrete serving as the main material, led to prolonged construction time, difficult renovation, and untreatable waste. Preliminary studies have been conducted on incremental housing from urban development and financial perspectives, with none on alternative construction systems. Therefore, this study aimed to develop flexible and sustainable incremental housing with an assembly–disassembly system capable of reducing construction time and waste. This study experimented on the connection systems through digital simulations and prototypes leading to a construction system that combines frames and panels in a semi-volumetric system. It also combined a plug-and-play connection type to achieve the highest assembly–disassembly efficiency value (0.07), the lowest waste (below 25%), and a 30% shorter construction time. The result showed no displacement when tested with a load of up to 3 tons. This study contributed to the growing body of knowledge on alternative incremental house construction techniques, paving the way for more adaptable and environmentally responsible housing solutions in urban settings, particularly in rapidly urbanizing regions like Indonesia.
1,10-Phenanthroline and 4,5-Diazafluorene Ketones and Their Silver(I) and Platinum(II) Complexes: Syntheses and Biological Evaluation as Antiproliferative Agents
Authors: Sandin-Mazzondo Leonardo , Martínez-Ilarduya Jesús M. , Miguel Jesús A. , Bartolomé Camino , Alonso Concepción
Published: December 2024

Using non-classical polyfluorophenyl ligands in Pt(II) complexes and other transition metals such as silver is a promising approach in the search for more effective and safer antitumoral drugs. In this work, a series of chelating N-donor ligands with 1,10-phenanthroline and 4,5-diazafluorene backbones and ketone groups were synthesized (1,10-phenanthroline-5,6-dione, 1; (R/S)-6-hydroxy-6-(2-oxypropyl)-1,10-phenanthroline-5(6H)-one, 2; 4,5-diazafluoren-9-one, 3; 9-hydroxy-9-(2-oxypropyl)-4,5-diazafluorene, 4). The corresponding [Ag(N,N)2]NO3 (1Ag–4Ag) and [Pt(C6F5)2(N,N)] (1Pt–4Pt) complexes were prepared. The stability of these complexes in DMSO solution was studied, showing no dissociation over 48 h for almost all complexes, except 3Pt. The compounds were characterized by NMR (1H, 13C, and 19F), MS, and X-ray diffraction (2, 4, 1Ag, 3Ag, 1Pt, and 3Pt). A study of the cytotoxicity of the compounds in lung carcinoma (A-549) and fetal lung fibroblast (MRC-5) cell lines was performed. Compounds 1, 2, 1Ag, 2Ag, 3Ag, 1Pt, 3Pt, and 4Pt were more active against A-549 cells than cisplatin. Complexes 3Ag and 1Pt showed an acceptable SI and better selectivity than cisplatin, proving that silver(I) complexes and Pt(polyfluorophenyl) complexes are valuable options in searching for new antitumoral drugs.
Fruit Flies (Diptera: Tephritidae) in Minas Gerais, Brazil: Trophic Interactions and New Reports
Authors: Coelho Rosamara Souza , Alvarenga Clarice , Pec Marvin , Rodrigues-Silva Ana Luisa , Peche Pedro Maranha , Alves Emanoel , Marucci Rosangela
Published: December 2024

A diverse orchard with fruit fly hosts may provide information about trophic relationships, including new insights into beneficial insects. We evaluated the composition of the fruit fly complex to provide information on tephritid species, parasitoids and multitrophic interactions for the southern region of Minas Gerais, Brazil. Sampling was carried out using traps and by collecting fruits from plants and/or the ground according to availability/the fruiting period. Occurrences of Anastrepha amita Zucchi and A. punctata Hendel were recorded for the first time in the state of Minas Gerais, and new trophic associations were obtained for A. bahiensis Lima, A. bistrigata Bezzi, A. fraterculus (Wiedemann), A. obliqua (Macquart) and Ceratitis capitata (Wiedemann). Ten tephritid species were obtained from trap sampling, with C. capitata, A. fraterculus and A. obliqua being the most abundant. Five species of fruit flies and seven species of parasitoids were obtained from fruits. The braconid Doryctobracon areolatus (Szépligeti) was the most frequently collected among the parasitoid species. Pitanga (Eugenia uniflora L.) and purple guava (Psidium myrtoides O. Berg) fruits were classified as repositories of fruit fly parasitoids.
Dietary Quercetin Regulates Gut Microbiome Diversity and Abundance in Apis cerana (Hymenoptera Apidae)
Authors: Wu Haodong , Ji Conghui , Wang Ruisheng , Gao Lijiao , Luo Wenhua , Liu Jialin
Published: December 2024

Honeybee gut microbiota plays a crucial role in maintaining their health and digestive function. Studies have confirmed that quercetin improves honeybee health by enhancing their pesticide tolerance and survival rates. This study aimed to examine the effects of quercetin on the bee gut microbiome by absolute quantification sequencing. We included 1800 bees from the experimental apiary and exposed them to 151.2, 75.6, and 37.8 mg/L of quercetin. Gut samples were collected on the 5th and 9th days, subjected to a polymerase chain reaction and 16S rRNA sequencing, and analyzed. After 5 days of quercetin treatment, the diversity of the honeybee gut microbiota was altered, and total bacterial copies and Lactobacillus abundance significantly decreased at high quercetin concentrations (151.2 and 75.6 mg/L). On day 9, the gut microbial community had recovered from the adverse effects, and Gilliamella abundance increased in response to 37.8 mg/L quercetin treatment. However, quercetin had no noticeable effects on survival rate, food consumption, and gut structure. Our study confirmed the effect of short-term quercetin intake on the gut microbiota of A. cerana, providing valuable insights into how phytochemicals alter the bee gut microbiome, and their repercussions on host physiology.
Evaluation of the Sterile Insect Technique for the Control of the Melon Fly (Bactrocera cucurbitae) Under Laboratory and Semi-Field Conditions in Sri Lanka
Authors: Nawarathne Muditha , Udayanga Lahiru , Ekanayake Hasini , Alotaib Bader Alhafi , Pathirage Ananda , Siriwardena Nayana , Jayarathne Athula , Ammouneh Hassan , Najim Mohamed M. M. , Traore Abou , Ranathunge Tharaka
Published: December 2024

The melon fly, Bactrocera cucurbitae, poses a severe threat to the country’s agricultural productivity, particularly in the cultivation of cucurbitaceous crops. This study was conducted to determine the ideal irradiation dose to be used to set up a Sterile Insect Technique (SIT)-based strategy to control B. cucurbitae outbreaks in Sri Lanka. A B. cucurbitae colony was established and maintained under standard laboratory conditions. Male pupae (100 pupae per treatment) were exposed to different radiation doses, namely 0 (control), 50, 60, 70, 80, 90, 100, and 110 Gy. The effect of irradiation on selected performance parameters such as survival, flight ability, fecundity, fertility, and adult longevity was evaluated under laboratory conditions. In addition, mating competitiveness was evaluated for irradiated male B. cucurbitae. Significant differences were observed in percentage pupal survival, flight ability, and fertility rates (p < 0.05) at a 95% level of confidence. Further, the 50% and 75% adult longevity periods of irradiated B. cucurbitae males significantly decreased with the increasing irradiation dosage (p < 0.05). B. cucurbitae exposed to 70 Gy radiation reported a mean pupal survival rate of 94.0 ± 1.25, flight ability of 93.3 ± 1.88, and fertility 0.2 ± 0.05%, along with a mean longevity of 38 ± 1.5 days until 50% reduction in the population. The competitiveness of B. cucurbitae exposed to 70 Gy with respect to wild males was 0.56 under laboratory conditions, which reduced up to 0.5 in semi-field settings. The 70 Gy dose could be recommended as the optimal radiation dose for the production of sterile B. cucurbitae males with an acceptable level of fitness and sterility to be used in SIT-based melon fly control programmes in Sri Lanka.
First Report and Phylogenetic Analysis of Mitochondrial Genomes of Chrysomya villeneuvi and Sarcophaga genuforceps
Authors: Yang Fengqin , Xiao Jiao , Zhang Xiangyan , Shang Yanjie , Guo Yadong
Published: December 2024

The mitochondrial genome, highly conserved across species, is crucial for species identification, phylogenetic analysis, and evolutionary research. Chrysomya villeneuvi and Sarcophaga genuforceps, two species with significant forensic value, have been understudied in terms of genetic data. In this study, the complete mitochondrial genomes of C. villeneuvi (15,623 bp) and S. genuforceps (15,729 bp) were sequenced and analyzed. All thirteen protein-coding genes (PCGs) exhibited Ka/Ks ratios below one, indicating purifying selection and supporting their utility as barcoding markers. Phylogenetic analysis and genetic distance calculations based on PCGs showed that C. villeneuvi is closely related to Chrysomya rufifacies and Chrysomya albiceps, and S. genuforceps aligns more closely with Sarcophaga kentejana and Sarcophaga schuetzei. This research is the first to provide mitochondrial genome data for C. villeneuvi and S. genuforceps, expanding the genetic resources available for Calliphoridae and Sarcophagidae and offering a foundation for further forensic and evolutionary studies.