bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon Monoxide Release from Aryl-Propargyl Dicobalt(0)Hexacarbonyl Derivatives: A Computational and Experimental Study
Authors: Paciotti Roberto , Coletti Cecilia , Berrino Emanuela , Arrighi Francesca , Maccelli Alessandro , Lasalvia Alba , Crestoni Maria Elisa , Secci Daniela , Carradori Simone , Supuran Claudiu T. , Carta Fabrizio
Published: October 2024

In the present study, we focus on dinuclear cobalt-based CO-RMs with the aim of elucidating their CO release mechanism, as well as to understand how structural changes targeted to modify the electronic properties of these compounds can modulate CO delivery. To this end, we specifically synthesized a set of phenyl-propargyl-based CO-RMs bearing –NO2, –H, and –OCH3 as para-substituents (R) with varying mesomeric influence (M) and different heteroatoms (X = NH, O, or S) linking the propargyl tail and the aromatic ring. The effects of R and X in modulating CO release were assessed by using several experimental and computational techniques to obtain a coherent picture and to shed light on the stability and release properties of Co-based CO-RMs.
Microplastic and the Enteric Nervous System: Effect of PET Microparticles on Selected Neurotransmitters and Cytokines in the Porcine Ileum
Authors: Gałęcka Ismena , Całka Jarosław
Published: October 2024

Microplastic is an environmental hazard to which both animals and humans are exposed. Current reports show that it can cause inflammation, including in the gastrointestinal tract. To examine the impact on the ileum, 15 eight-week-old gilts (five individuals/group) were exposed to PET microplastics (7.6 µm–416.9 µm) at a dose of 0.1 g/day or 1 g/day for 28 days. The collected ileum fragments were investigated for the cytokine concentrations (IL-1β, IL-6, IL-8, IL-10, and TNF-α; ELISA test), neuron populations (cocaine and amphetamine-regulated transcript, galanin, neuronal nitric oxide synthase, substance P, vesicular acetylcholine transporter, and vasoactive intestinal peptide; immunofluorescence staining), and morphometric parameters (histological analysis). Under the influence of MP-PET, there was a reduction in the populations of CART- and GAL-positive neurons in the submucosal plexuses and of nNOS-, VAChT-, and VIP-positive neurons in all the plexuses. In contrast, there was an increase in GAL-positive neurons in the myenteric plexus and SP-positive neurons in all the plexuses. The concentrations of IL-1β, IL-6, IL-8, IL-10, and TNF-α did not undergo statistically significant changes under the influence of the low or high dose of MP-PET. The changes in the histological structure exclusively concerned the thinning of the mucosa and the muscularis externa. The results support the thesis that MP-PET is not neutral to the ileal cells.
Study on the Function of Leptin Nutrient Acquisition and Energy Metabolism of Zebrafish (Danio rerio)
Authors: Wu Jiaqi , Zhuang Wuyuan , Lu Ke , Zhang Lixin , Wang Yuye , Chai Farui , Liang Xu-Fang
Published: October 2024

Leptin plays an indispensable role in energy homeostasis, and its involvement in metabolic activities has been extensively explored in fish. We generated mutant lines of leptina (−5 bp) and leptinb (+8 bp) in zebrafish using CRISPR/Cas9 technology to explore the metabolic characteristics of lepa and lepb mutant zebrafish in response to high glucose nutritional stress induced by high levels of carbohydrates. The results were as follows: the body weight and food intake of adult zebrafish of the two mutant species were increased; the visceral fat accumulation, whole-body crude lipid, and crude protein contents of lepb−/− were increased; and the visceral fat accumulation and crude lipid in lepa−/− zebrafish were decreased. The blood glucose levels of the two mutant zebrafish were increased, the mRNA expression levels of glycolytic genes pk and gck were decreased in the two mutant zebrafish, and there were differences between lepa−/− and lepb−/− zebrafish. The expressions of glycogen synthesis and decomposition genes were inhibited and promoted, respectively. The expression of adipose synthesis genes in the liver and muscle was stimulated in lepb−/− zebrafish but suppressed in lepa−/− zebrafish. Lipolysis and oxidation genes were also stimulated in lepa−/− zebrafish livers, while the livers of lepb−/− zebrafish were stimulated but muscle was inhibited. In conclusion, the results indicate that lepa plays a major role in glucose metabolism, which is conducive to promoting glucose utilization and lipogenesis, while lepb mainly promotes lipolysis and oxidation, regulates protein generation, and plays a minor role in glucose metabolism.
Linking Protein Stability to Pathogenicity: Predicting Clinical Significance of Single-Missense Mutations in Ocular Proteins Using Machine Learning
Authors: Majid Iyad , Sergeev Yuri V.
Published: October 2024

Understanding the effect of single-missense mutations on protein stability is crucial for clinical decision-making and therapeutic development. The impact of these mutations on protein stability and 3D structure remains underexplored. Here, we developed a program to investigate the relationship between pathogenic mutations with protein unfolding and compared seven machine learning (ML) models to predict the clinical significance of single-missense mutations with unknown impacts, based on protein stability parameters. We analyzed seven proteins associated with ocular disease-causing genes. The program revealed an R-squared value of 0.846 using Decision Tree Regression between pathogenic mutations and decreased protein stability, with 96.20% of pathogenic mutations in RPE65 leading to protein instability. Among the ML models, Random Forest achieved the highest AUC (0.922) and PR AUC (0.879) in predicting the clinical significance of mutations with unknown effects. Our findings indicate that most pathogenic mutations affecting protein stability occur in alpha-helices, beta-pleated sheets, and active sites. This study suggests that protein stability can serve as a valuable parameter for interpreting the clinical significance of single-missense mutations in ocular proteins.
The Structural Role of RPN10 in the 26S Proteasome and an RPN2-Binding Residue on RPN13 Are Functionally Important in Arabidopsis
Authors: Lin Shih-Yun , Lin Ya-Ling , Usharani Raju , Radjacommare Ramalingam , Fu Hongyong
Published: October 2024

The ubiquitin receptors RPN10 and RPN13 harbor multiple activities including ubiquitin binding; however, solid evidence connecting a particular activity to specific in vivo functions is scarce. Through complementation, the ubiquitin-binding site-truncated Arabidopsis RPN10 (N215) rescued the growth defects of rpn10-2, supporting the idea that the ubiquitin-binding ability of RPN10 is dispensable and N215, which harbors a vWA domain, is fully functional. Instead, a structural role played by RPN10 in the 26S proteasomes is likely vital in vivo. A site-specific variant, RPN10-11A, that likely has a destabilized vWA domain could partially rescue the rpn10-2 growth defects and is not integrated into 26S proteasomes. Native polyacrylamide gel electrophoresis and mass spectrometry with rpn10-2 26S proteasomes showed that the loss of RPN10 reduced the abundance of double-capped proteasomes, induced the integration of specific subunit paralogues, and increased the association of ECM29, a well-known factor critical for quality checkpoints by binding and inhibiting aberrant proteasomes. Extensive Y2H and GST-pulldown analyses identified RPN2-binding residues on RPN13 that overlapped with ubiquitin-binding and UCH2-binding sites in the RPN13 C-terminus (246–254). Interestingly, an analysis of homozygous rpn10-2 segregation in a rpn13-1 background harboring RPN13 variants defective for ubiquitin binding and/or RPN2 binding supports the criticality of the RPN13–RPN2 association in vivo.
Current Insights into the Role of UV Radiation-Induced Oxidative Stress in Melanoma Pathogenesis
Authors: Gieniusz Ernest , Skrzydlewska Elżbieta , Łuczaj Wojciech
Published: October 2024

Cutaneous melanoma accounts for the majority of skin cancer-related deaths, and its incidence increases each year. The growing number of melanoma cases, especially in advanced stages, poses a significant socio-medical challenge throughout the world. Extensive research on melanoma pathogenesis identifies UV radiation as the most important factor in melanocytic transformation. Oxidative effects of UV irradiation exert their influence on melanoma pathogenesis primarily through modification of nucleic acids, proteins, and lipids, further disrupting cellular signaling and cell cycle regulation. Its effects extend beyond melanocytes, leading to immunosuppression in the exposed skin tissue, which consequently creates conditions for immune surveillance evasion and further progression. In this review, we focus on the specific molecular changes observed in the UV-dependent oxidative stress environment and their biological consequences in the course of the disease, which have not been considered in previous reviews on melanoma. Nonetheless, data show that the exact role of oxidative stress in melanoma initiation and progression remains unclear, as it affects cancerous cells differently depending on the specific context. A better understanding of the pathophysiological basis of melanoma development holds promise for identifying potential targets, which could lead to effective melanoma prevention strategies.
The Senolytic Effect of Indole-3-Carbinol (I3C) on Mouse Embryonic (MEF) and Human Fibroblast Cell Lines
Authors: Sax Scott L. , Centomo Maria Laura , Centofanti Federica , Rizzacasa Barbara , Cox Sierra , Cox Chelsea , Latini Andrea , D’Apice Maria Rosaria , Mannucci Liliana , Novelli Giuseppe , Pandolfi Pier Paolo
Published: October 2024

Senescence and apoptosis are two fundamental cellular processes that play crucial roles in various physiological and pathological conditions. Senescence refers to the irreversible growth arrest that cells undergo in response to various stimuli, including telomeric alterations, stress, and oncogenic signaling. Pharmacological and/or genetic removal of senescent cells, also referred to as senolysis, triggers organ rejuvenation and tissue regeneration. Indole-3-carbinol (I3C) is a natural compound contained in Brassicaceae plants and identified in multiple in vitro and in vivo studies as a well-tolerated and effective compound in cancer prevention and therapy. Its anti-cancer properties have been attributed at least in part to its inhibitory activity of proto-oncogenic HECT E3-ubiquitin ligases such as NEDD4 and WWP1. While the tumor suppressive effects of I3C in cancer cell lines have been reported in multiple studies, little is known regarding the biological effects of I3C in primary normal cells, which attain spontaneous cellular senesce over serial passaging. To this end, we used two model systems: mouse embryonic fibroblasts (MEFs) and human primary dermal fibroblasts. Here, we surprisingly show that I3C does increase cellular senescence at early passages, while dramatically reducing the number of senescent cells through the induction of apoptosis in both mouse and human primary cells. Thus, our findings support the notion that I3C acts as a senolytic compound with important therapeutic implications for the prevention and treatment of aging manifestations. The notion can be readily tested in future clinical trials in humans also in view of the high tolerability and safety previously displayed by I3C in preclinical and clinical studies.
Bioactive Compounds in Osteoarthritis: Molecular Mechanisms and Therapeutic Roles
Authors: Maouche Ahmed , Boumediene Karim , Baugé Catherine
Published: October 2024

Osteoarthritis (OA) is the most common and debilitating form of arthritis. Current therapies focus on pain relief and efforts to slow disease progression through a combination of drug and non-drug treatments. Bioactive compounds derived from plants show significant promise due to their anti-inflammatory, antioxidant, and tissue-protective properties. These natural compounds can help regulate the inflammatory processes and metabolic pathways involved in OA, thereby alleviating symptoms and potentially slowing disease progression. Investigating the efficacy of these natural agents in treating osteoarthritis addresses a growing demand for natural health solutions and creates new opportunities for managing this increasingly prevalent age-related condition. The aim of this review is to provide an overview of the use of some bioactive compounds from plants in modulating the progression of osteoarthritis and alleviating associated pain.
Epigenetic Explorations of Neurological Disorders, the Identification Methods, and Therapeutic Avenues
Authors: Firdaus Zeba , Li Xiaogang
Published: October 2024

Neurodegenerative disorders are major health concerns globally, especially in aging societies. The exploration of brain epigenomes, which consist of multiple forms of DNA methylation and covalent histone modifications, offers new and unanticipated perspective into the mechanisms of aging and neurodegenerative diseases. Initially, chromatin defects in the brain were thought to be static abnormalities from early development associated with rare genetic syndromes. However, it is now evident that mutations and the dysregulation of the epigenetic machinery extend across a broader spectrum, encompassing adult-onset neurodegenerative diseases. Hence, it is crucial to develop methodologies that can enhance epigenetic research. Several approaches have been created to investigate alterations in epigenetics on a spectrum of scales—ranging from low to high—with a particular focus on detecting DNA methylation and histone modifications. This article explores the burgeoning realm of neuroepigenetics, emphasizing its role in enhancing our mechanistic comprehension of neurodegenerative disorders and elucidating the predominant techniques employed for detecting modifications in the epigenome. Additionally, we ponder the potential influence of these advancements on shaping future therapeutic approaches.
Identification of Genes Associated with Familial Focal Segmental Glomerulosclerosis Through Transcriptomics and In Silico Analysis, Including RPL27, TUBB6, and PFDN5
Authors: Mahmoud Anfal Hussain , Alhamidi Reem Sami , Ilce Burcu Yener , Hamad Alaa Mohamed , Ali Nival , Mahasneh Amjad , Talaat Iman M. , Tlili Abdelaziz , Hamoudi Rifat
Published: October 2024

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and often leads to progressive kidney failure. Its varying clinical presentation suggests potential genetic diversity, requiring further molecular investigation. This study aims to elucidate some of the genetic and molecular mechanisms underlying FSGS. The study focuses on the use of bioinformatic analysis of gene expression data to identify genes associated with familial FSGS. A comprehensive in silico analysis was performed using the GSE99340 data set from Gene Expression Omnibus (GEO) comparing gene expression in glomerular and tubulointerstitial tissues from FSGS patients (n = 10) and Minimal Change Disease (MCD) patients (n = 8). These findings were validated using transcriptomics data obtained using RNA sequencing from FSGS (n = 3) and control samples (n = 3) from the UAE. Further validation was conducted using qRT-PCR on an independent FFPE cohort (FSGS, n = 6; MCD, n = 7) and saliva samples (FSGS, n = 3; Control, n = 7) from the UAE. Three genes (TUBB6, RPL27, and PFDN5) showed significant differential expression (p < 0.01) when comparing FSGS and MCD with healthy controls. These genes are associated with cell junction organization and synaptic pathways of the neuron, supporting the link between FSGS and the neural system. These genes can potentially be useful as diagnostic biomarkers for FSGS and to develop new treatment options.
Phenotypic Biomarkers of Aqueous Extracellular Vesicles from Retinoblastoma Eyes
Authors: Amacker Anne , Peng Chen-Ching , Jiang Nan , Sirivolu Shreya , Higa Nikki , Stachelek Kevin , Reiser Bibiana , Kuhn Peter , Cobrinik David , Neviani Paolo , Berry Jesse L. , Jovanovic-Talisman Tijana , Xu Liya
Published: October 2024

Recent advancements in aqueous humor (AH) cell-free DNA (cfDNA) genomics have opened new avenues for ex vivo molecular profiling of retinoblastoma (RB), the most common pediatric intraocular malignancy, where biopsy is typically prohibited. While these insights offer a genetic blueprint of the tumor, they lack multi-omic molecular phenotyping, which is essential for understanding the functional state. Extracellular vesicles (EVs), naturally present in AH, are promising by offering time-resolved phenotypic information. We employed multiplex bead-based flow cytometry and Single Extracellular Vesicle Nanoscopy (SEVEN) to analyze EV phenotypes in AH from a cohort of five RB, with three uveal melanoma (UM) and two age-matched glaucoma (GLC) samples serving as controls. The studies identified CD133-enriched EVs uniquely in RB AH, absent in both GLC and UM AH. This was corroborated by further analysis of five RB cell lines, including two commercial (Y79, Weri) and three in-house developed lines, confirming CD133 enrichment and supporting its role as an RB-specific EV marker. Single-vesicle analysis demonstrated a strong association of CD133 with CD81 and CD63, with minimal CD9 presence. These results, validated through complementary techniques, position CD133 as a critical marker in RB-derived EVs, paving the way for enhanced multi-omic RB characterization and potential advancements in clinical diagnostics.
CK and LRRK2 Involvement in Neurodegenerative Diseases
Authors: Bova Valentina , Mannino Deborah , Capra Anna Paola , Lanza Marika , Palermo Nicoletta , Filippone Alessia , Esposito Emanuela
Published: October 2024

Neurodegenerative diseases (NDDs) are currently the most widespread neuronal pathologies in the world. Among these, the most widespread are Alzheimer’s disease (AD), dementia, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD)—all characterized by a progressive loss of neurons in specific regions of the brain leading to varied clinical symptoms. At the basis of neurodegenerative diseases, an emerging role is played by genetic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene that cause increased LRRK2 activity with consequent alteration of neuronal autophagy pathways. LRRK2 kinase activity requires GTPase activity which functions independently of kinase activity and is required for neurotoxicity and to potentiate neuronal death. Important in the neurodegeneration process is the upregulation of casein kinase (CK), which causes the alteration of the AMPK pathway by enhancing the phosphorylation of α-synuclein and huntingtin proteins, known to be involved in PD and HD, and increasing the accumulation of the amyloid-β protein (Aβ) for AD. Recent research has identified CK of the kinases upstream of LRRK2 as a regulator of the stability of the LRRK2 protein. Based on this evidence, this review aims to understand the direct involvement of individual kinases in NDDs and how their crosstalk may impact the pathogenesis and early onset of neurodegenerative diseases.
Proximity Elongation Assay and ELISA for the Identification of Serum Diagnostic Biomarkers in Parkinson’s Disease and Progressive Supranuclear Palsy
Authors: Cristiani Costanza Maria , Calomino Camilla , Scaramuzzino Luana , Murfuni Maria Stella , Parrotta Elvira Immacolata , Bianco Maria Giovanna , Cuda Giovanni , Quattrone Aldo , Quattrone Andrea
Published: October 2024

Clinical differentiation of progressive supranuclear palsy (PSP) from Parkinson’s disease (PD) is challenging due to overlapping phenotypes and late onset of PSP specific symptoms, highlighting the need for easily assessable biomarkers. We used proximity elongation assay (PEA) to analyze 460 proteins in serum samples from 46 PD, 30 PSP patients, and 24 healthy controls. ANCOVA was used to identify the most promising proteins and machine learning (ML) XGBoost and random forest algorithms to assess their classification performance. Promising proteins were also quantified by ELISA. Moreover, correlations between serum biomarkers and biological and clinical features were investigated. We identified five proteins (TFF3, CPB1, OPG, CNTN1, TIMP4) showing different levels between PSP and PD, which achieved good performance (AUC: 0.892) when combined by ML. On the other hand, when the three most significant biomarkers (TFF3, CPB1 and OPG) were analyzed by ELISA, there was no difference between groups. Serum levels of TFF3 positively correlated with age in all subjects’ groups, while for OPG and CPB1 such a correlation occurred in PSP patients only. Moreover, CPB1 positively correlated with disease severity in PD, while no correlations were observed in the PSP group. Overall, we identified CPB1 correlating with PD severity, which may support clinical staging of PD. In addition, our results showing discrepancy between PEA and ELISA technology suggest that caution should be used when translating proteomic findings into clinical practice.
Chitin Translocation Is Functionally Coupled with Synthesis in Chitin Synthase
Authors: Niu Suhao , Qi Lei , Zhang Xiaoyue , He Dongfang , Li Pengwei , Wang Hao , Bi Yunchen
Published: October 2024

Chitin, an extracellular polysaccharide, is synthesized by membrane-embedded chitin synthase (CHS) utilizing intracellular substrates. The mechanism of the translocation of synthesized chitin across the membrane to extracellular locations remains unresolved. We prove that the chitin synthase from Phytophthora sojae (PsCHS) is a processive glycosyltransferase, which can rapidly produce and tightly bind with the highly polymerized chitin. We further demonstrate that PsCHS is a bifunctional enzyme, which is necessary and sufficient to translocate the synthesized chitin. PsCHS was purified and then reconstituted into proteoliposomes (PLs). The nascent chitin is generated and protected from chitinase degradation unless detergent solubilizes the PLs, showing that PsCHS translocates the newly produced chitin into the lumen of the PLs. We also attempted to resolve the PsCHS structure of the synthesized chitin-bound state, although it was not successful; the obtained high-resolution structure of the UDP/Mn2+-bound state could still assist in describing the characterization of the PsCHS’s transmembrane channel. Consistently, we demonstrate that PsCHS is indispensable and capable of translocating chitin in a process that is tightly coupled to chitin synthesis.
Systematic Analysis of Cinnamyl Alcohol Dehydrogenase Family in Cassava and Validation of MeCAD13 and MeCAD28 in Lignin Synthesis and Postharvest Physiological Deterioration
Authors: An Feifei , Chen Ting , Zhu Wenli , Xiao Xinhui , Xue Jingjing , Luo Xiuqin , Wei Zhuowen , Li Kaimian , Chen Songbi , Cai Jie
Published: October 2024

Cassava (Manihot esculenta Crantz) is used as a biomass energy material and an effective supplement for food and feed. Cinnamyl alcohol dehydrogenase (CAD) catalyzes the final step of lignin biosynthesis and is responsible for various stresses. However, systematic investigations of the CAD gene family in cassava have been poorly understood. In this study, a genome-wide survey and bioinformatics analysis of CAD gene family was performed, transcriptomics, qRT-PCR, gene silencing and stress of yeast cell were used for excavate and validate the candidate MeCADs gene. 36 MeCADs genes unevenly distributed across 12 chromosomes were identified. Through phylogenetic analyses alongside their Arabidopsis counterparts, these MeCADs were divided into four groups, each containing a similar structure and conserved motifs. Interestingly, transcriptome data analysis revealed that 32 MeCAD genes were involved in the postharvest physiological deterioration (PPD) process, whereas 27 MeCAD genes showed significant changes. Additionally, the relative quantitative analysis of 6 MeCAD genes demonstrated that they were sensitive to PPD, suggesting that they may be involved in the regulation of PPD. Silencing MeCAD13 and MeCAD28 further showed that lignin content significantly decreased in the leaves. The wound-stress tolerance of transgenic yeast cells was enhanced after transformation with MeCAD13 and MeCAD28. MeCAD13 and MeCAD28 may play positive roles in lignin biosynthesis and PPD response, respectively. These results provided a systematic functional analysis of MeCADs in cassava and paved a new way to genetically modify lignin biosynthesis and PPD tolerance.
Integrated Transcriptomic and Proteomic Analysis of Nutritional Quality-Related Molecular Mechanisms in “Longjia”, “Yangpao”, and “Niangqing” Walnuts (Juglans sigillata)
Authors: Wang Hailang , Su Yue , Hu Xiang , Wu Boxiao , Liu Yun , Kan Huan , Cao Changwei
Published: October 2024

In this study, “Longjia (LJ)” and “Yangpao (YP)”exhibited higher contents of major nutrients compared to “Niangqing (NQ)” walnuts. The combination of transcriptome and proteome by RNA sequencing and isotope labeling for relative and absolute quantification techniques provides new insights into the molecular mechanisms underlying the nutritional quality of the three walnut species. A total of 4146 genes and 139 proteins showed differential expression levels in the three comparison groups. Combined transcriptome and proteome analyses revealed that these genes and proteins were mainly enriched in signaling pathways such as fatty acid biosynthesis, protein processing in endoplasmic reticulum, and amino acid metabolism, revealing their relationship with the nutritional quality of walnut kernels. This study identified key genes and proteins associated with nutrient metabolism and accumulation in walnut kernels, provided transcriptomic and proteomic information on the molecular mechanisms of nutrient differences in walnut kernels, and contributed to the elucidation of the mechanisms of nutrient differences and the selection and breeding of high-quality walnut seedlings.
Genome-Wide Association-Based Identification of Alleles, Genes and Haplotypes Influencing Yield in Rice (Oryza sativa L.) Under Low-Phosphorus Acidic Lowland Soils
Authors: James M. , Tyagi Wricha , Magudeeswari P. , Neeraja C. N. , Rai Mayank
Published: October 2024

Rice provides poor yields in acidic soils due to several nutrient deficiencies and metal toxicities. The low availability of phosphorus (P) in acidic soils offers a natural condition for screening genotypes for grain yield and phosphorus utilization efficiency (PUE). The objective of this study was to phenotype a subset of indica rice accessions from 3000 Rice Genome Project (3K-RGP) under acidic soils and find associated genes and alleles. A panel of 234 genotypes, along with checks, were grown under low-input acidic soils for two consecutive seasons, followed by a low-P-based hydroponic screening experiment. The heritability of the agro-morphological traits was high across seasons, and Ward’s clustering method identified 46 genotypes that can be used as low-P-tolerant donors in acidic soil conditions. Genotypes ARC10145, RPA5929, and K1559-4, with a higher grain yield than checks, were identified. Over 29 million SNPs were retrieved from the Rice SNP-Seek database, and after quality control, they were utilized for a genome-wide association study (GWAS) with seventeen traits. Ten quantitative trait nucleotides (QTNs) for three yield traits and five QTNs for PUE were identified. A set of 34 candidate genes for yield-related traits was also identified. An association study using this indica panel for an already reported 1.84 Mbp region on chromosome 2 identified genes Os02g09840 and Os02g08420 for yield and PUE, respectively. A haplotype analysis for the candidate genes identified favorable allelic combinations. Donors carrying the superior haplotypic combinations for the identified genes could be exploited in future breeding programs.
Evaluation of β-Actin and Mitochondrial DNA Levels in Determining the Age of Suidae Remains
Authors: Szymankiewicz Krzesimir , Walczak Marek , Podgórska Katarzyna
Published: October 2024

African Swine Fever (ASF) is an infectious disease affecting pigs and wild boars, causing significant economic losses. Epidemiological surveillance plays an important role in minimizing its impact. The aim of this study was to evaluate the usefulness of β-actin DNA and mitochondrial DNA (mtDNA) levels in determining the age of animal remains from the Suidae family, which could be helpful in epidemiological investigations. The study included selected tissues and internal organs of Sus scrofa domesticus, exposed to natural environmental conditions or kept in stable 4 °C conditions, to assess the levels of β-actin and mtDNA over a period of 18 months. The levels of both tested parameters exhibited the expected decreasing trend over time. However, in most tissues, some discrepancies from this general pattern were observed. The results obtained for bone marrow showed a consistent downward trend and a strong correlation between mtDNA and β-actin, with long-term detectability (up to the 13th month of the study). Therefore, bone marrow could be considered a matrix of choice for age assessment. However, due to various influencing factors, further studies are required.
Modeling the Bioenergetics and Life History Traits of Chironomus riparius–Consequences of Food Limitation
Authors: Klagkou Evridiki , Gergs Andre , Baden Christian U. , Lika Konstadia
Published: October 2024

Chironomids have a number of characteristics that make them a useful group for investigating the impact of environmental and chemical stressors on their life cycle stages. It is crucial to first understand sensitivities to environmental factors and provide a basis for interpreting the results of toxicity tests. We focused on Chironomus riparius–one of the most studied species in aquatic toxicity tests—to understand the changes during the larval stage under conditions of food abundance and limitation. We developed a model based on Dynamic Energy Budget (DEB) theory, a framework to capture the entire life cycle of an individual under varying food and temperature conditions. Available information from this study and the literature pointed out that the first three larval instars are immature and the fourth larval instar is mature, during which the organism saves, in two phases, energy for essential processes occurring during the subsequent non-feeding stages. The model can successfully predict the observed prolonged fourth instar duration under food limitation, the times of life history events (e.g., pupation and emergence), and egg production. This model has the potential to be integrated with toxicokinetic–toxicodynamic models to study the effects of toxicants on a variety of biological traits.
From Data Integration to Precision Medicine: A Value-Based Healthcare Approach for Sarcoma Care
Authors: Fuchs Bruno , Heesen Philip
Published: October 2024

The transformation of healthcare from a fee-for-service model to value-based care is particularly crucial in managing complex and rare diseases like sarcoma, where data fragmentation and variability present significant challenges. This manuscript reviews strategies for structured and harmonized data integration—a critical precursor to precision medicine in sarcoma care. We demonstrate how standardizing data formats, ontologies, and coding systems enable seamless integration of clinical, economic, and patient-reported outcomes across institutions, paving the way for comprehensive predictive analytics. By establishing robust value-based healthcare (VBHC) frameworks through digital transformation and predictive models, including digital twins, we create the foundation for personalized sarcoma treatment and real-world-time clinical decision-making. The manuscript also addresses practical challenges, including the need for system standardization, overcoming regulatory and privacy concerns, and managing high costs. We propose actionable strategies to overcome these barriers and discuss the role of advanced analytics and future research directions that further enhance VBHC and precision medicine. This work outlines the necessary steps to build a cohesive, data-driven approach that supports the transition to precision medicine, fundamentally improving outcomes for sarcoma patients.
Bioimpedance Analysis in CKD and HF Patients: A Critical Review of Benefits, Limitations, and Future Directions
Authors: La Porta Edoardo , Faragli Alessandro , Herrmann Alexander , Lo Muzio Francesco Paolo , Estienne Luca , Nigra Stefano Geniere , Bellasi Antonio , Deferrari Giacomo , Ricevuti Giovanni , Di Somma Salvatore , Alogna Alessio
Published: October 2024

Bioimpedance analysis (BIA) is a validated non-invasive technique already proven to be useful for the diagnosis, prognosis, and management of body fluids in subjects with heart failure (HF) and chronic kidney disease (CKD). Although BIA has been widely employed for research purposes, its clinical application is still not fully widespread. The aim of this review is to provide a comprehensive overview of the state of the art of BIA utilization by analyzing the clinical benefits, limitations, and potential future developments in this clinically unexplored field.
Serum Osmolality as a Predictor of Renal Function Decline: A Retrospective Cohort Study
Authors: Wu Jheng-Jia , Tung Chun-Wu , Lin Chun-Wei , Huang Jui-Chu , Yang Jen-Tsung , Tsai Yuan-Hsiung , Peng Yun-Shing
Published: October 2024

Background and Aims: Dehydration is a prevalent and costly healthcare concern, linked to heightened risks of acute kidney injury and in-hospital mortality. Despite its significance, limited evidence exists regarding its prevalence and correlation with renal function decline in apparently healthy individuals. This retrospective cohort study aimed to investigate the prevalence and association of dehydration with renal function decline and the development or progression of chronic kidney disease (CKD) in the general population. Methods: The medical records of subjects undergoing annual health check-ups from 2016 to 2019 at a single center in Taiwan were analyzed, and those with CKD stage V, insufficient data, or an increased estimated glomerular filtration rate (eGFR) were excluded. Serum osmolality, eGFR, and relevant parameters were measured. Logistic regression and Kaplan–Meier analyses were used to assess associations between osmolality and CKD-related outcomes. Results: Among the 4449 eligible subjects, those in the higher osmolality quartiles had an elevated risk of CKD or CKD progression. Multivariate analyses identified age, systolic blood pressure, serum osmolality, uric acid, proteinuria, and a history of diabetes as independent risk factors, with high-density lipoprotein being protective. Cumulative incidence curves demonstrated a significant increase in the risk of CKD with increasing osmolality levels. Restricted cubic spline analyses confirmed a nonlinear relationship between osmolality and CKD risk. Conclusions: Elevated serum osmolality independently predicted renal function decline and CKD development in apparently healthy individuals, and this effect persisted after adjusting for established risk factors. Our findings underscore the importance of addressing dehydration as a modifiable risk factor for CKD.
Machine Learning Models Leveraging Smartphone-Based Patient Mobility Data Can Accurately Predict Functional Outcomes After Spine Surgery
Authors: Ahmad Hasan S. , Chauhan Daksh , Dagli Mert Marcel , Turlip Ryan W. , Bashti Malek , Hamade Ali , Wang Patrick T. , Ghenbot Yohannes , Yang Andrew I. , Basil Gregory W. , Welch William C. , Yoon Jang Won
Published: October 2024

Objective: The development of adjacent segment disease or the progression of spondylosis following the surgical treatment of spinal stenosis and spondylolisthesis is well documented and can lead to subsequent functional decline after a successful index surgery. The early detection of negative inflection points during patients’ functional recovery can improve timely intervention. In this study, we developed machine learning (ML) models to predict the occurrence of post-operative decline in patient mobility. Methods: Patients receiving spine surgery for degenerative spinal stenosis or spondylolisthesis were retroactively consented and enrolled. Activity data (steps-per-day) previously recorded across a 4-year peri-operative were collected alongside relevant clinical and demographic variables. Logistic regression (LR), random forest (RF), and extreme gradient boosting (XGBoost) ML models were constructed and trained on 80% of the dataset and validated using the remaining 20%. The study’s primary endpoint was the models’ ability to predict post-operative decline in patient mobility. Results: A total of 75 patients were included. Following training, RF and XGBoost models achieved accuracy values of 86.7% (sensitivity 80%, specificity 90%) and 80% (sensitivity 60%, specificity 90%), respectively, in predicting post-operative functional decline. The LR model was the least effective with an accuracy of 73.3% (sensitivity 50%, specificity 88.8%). Receiver operating characteristic curves showed an area under the curve of 0.80 for RF, 0.70 for XGBoost, and 0.69 for LR. Conclusions: ML models trained on activity data collected from smartphones successfully forecast functional decline in post-operative activity following spine surgery. These results lay the groundwork for the future integration of ML into the surgeon’s toolbox for prognostication and surgical planning.
Evaluation of Lateral and Medial Parts of the Hamstring Muscle Fatigue Symmetry in Professional Footballers Cleared to Play After ACL Reconstruction
Authors: Oleksy Łukasz , Mika Anna , Sopa Martyna , Stolarczyk Artur , Adamska Olga , Szczudło Miłosz , Kielnar Renata , Hagner-Derengowska Magdalena , Buryta Rafał , Nowak Michał Jakub , Kowal Matylda , Deszczyński Jarosław Michał
Published: October 2024

Objectives: Rupture of the anterior cruciate ligament (ACL) is a severe injury common in sports. It also has a high rate of re-injury. The aim of this work was to assess hamstring muscle fatigue in active football players after ACL reconstruction who were cleared to play and to determine symmetry between the lateral and medial hamstring muscles. Methods: In professional football players post ACL reconstruction (n = 25) and non-injured players (n = 26), the bioelectrical activity of the medial (biceps femoris—BF) and lateral (semimembranosus and semitendinosus—SEM) hamstring muscles was measured during 60 s of isometric contraction. The fatigue variables were calculated using the Continuous Wavelet Transform (CWT) tool. Results: The football players following ACL reconstruction demonstrated significant asymmetry in fatigue of the lateral and medial hamstring muscles, with greater fatigue in the SEM compared to the BF muscle. Moreover, in those after reconstruction, the changes are more pronounced, with higher muscle fatigue in both limbs (they have lower MDF than non-injured players) and more severe SEM muscle insufficiency (noted in both limbs but with greater intensity in the non-operated one). Conclusions: The higher SEM muscle fatigue observed in this study influenced the lateral-to-medial activation ratio within the hamstring muscle, which may be a probable cause of this muscle’s insufficiency in laterally stabilizing the knee in the frontal and transverse plane. Furthermore, the hamstring muscles after reconstruction were more fatigued in both limbs, which may be another risk factor for ACL graft rupture. Therefore, increased fatigue in specific hamstring muscles may indicate the direction in which knee stabilization is compromised due to ACL overload. A muscle that becomes fatigued and inefficient more quickly also becomes ineffective in performing its function sooner, which can lead to increased overloading forces acting on the ACL graft.
Towards Standardized Assessment of Outcomes in Back Pain—Validation of Linking Studies Between Disease-Specific and Generic Patient-Reported Outcome Measures
Authors: Hartmann Claudia , Liegl Gregor , Rose Matthias , Fischer Felix
Published: October 2024

Background: Comparing outcomes across different health measurement tools is essential where various patient-reported outcome measures (PROMs) are used. In spinal surgery, where recent studies show that over 30 different PROMs are applied, this need becomes even more pressing. Although several statistical transformations between the Oswestry Disability Index (ODI) and the PROMIS Profile 29 have been proposed, validation studies on conversion equations and cross-walk tables remain limited. In this study, we examined the agreement between observed ODI scores and those predicted from the PROMIS Profile 29 in a large sample of patients with low back pain, collected from routine clinical care. Methods: We compared the performance of regression and linking models at both the individual and group levels. Using Bland–Altman plots, we assessed the mean difference, 95% limits of agreement, root mean squared error (RMSE), and standardized mean differences (Cohen’s d) between predicted and observed ODI scores. Results: While group-level agreement was satisfactory, with negligible effect sizes, individual prediction accuracy was relatively poor. Additionally, regression models showed inconsistent performance across the ODI score range, though incorporating more domains marginally improved predictions. Conclusions: The equipercentile linking approach demonstrated stable agreement across all ODI scores, making it the preferred method. Future regression models should account for nonlinear relationships between PROMs to enhance prediction accuracy.
Minimally Invasive Aortic Valve Replacement for High-Risk Populations: Transaxillary Access Enhances Survival in Patients with Obesity
Authors: Taghizadeh-Waghefi Ali , Petrov Asen , Arzt Sebastian , Alexiou Konstantin , Matschke Klaus , Kappert Utz , Wilbring Manuel
Published: October 2024

Background/Objectives: Minimally invasive cardiac surgery is often avoided in patients with obesity due to exposure and surgical access concerns. Nonetheless, these patients have elevated periprocedural risks. Minimally invasive transaxillary aortic valve surgery offers a sternum-sparing “nearly no visible scar” alternative to the traditional full sternotomy. This study evaluated the clinical outcomes of patients with obesity compared to a propensity score-matched full sternotomy cohort. Methods: This retrospective cohort study included 1086 patients with obesity (body mass index [BMI] of >30 kg/m2) undergoing isolated aortic valve replacement from 2014 to 2023. Two hundred consecutive patients who received transaxillary minimally invasive cardiac lateral surgery (MICLAT-S) served as a treatment group, while a control group was generated via 1:1 propensity score matching from 886 patients who underwent full sternotomy. The final sample comprised 400 patients in both groups. Outcomes included major adverse cardio-cerebral events, mortality, and postoperative complications. Results: After matching, the clinical baselines were comparable. The mean BMI was 34.4 ± 4.0 kg/m2 (median: 33.9, range: 31.0–64.0). Despite the significantly longer skin-to-skin time (135.0 ± 37.7 vs. 119.0 ± 33.8 min; p ≤ 0.001), cardiopulmonary bypass time (69.1 ± 19.1 vs. 56.1 ± 21.4 min; p ≤ 0.001), and aortic cross-clamp time (44.0 ± 13.4 vs. 41.9 ± 13.3 min; p = 0.044), the MICLAT-S group showed a shorter hospital stay (9.71 ± 6.19 vs. 12.4 ± 7.13 days; p ≤ 0.001), lower transfusion requirements (0.54 ± 1.67 vs. 5.17 ± 9.38 units; p ≤ 0.001), reduced postoperative wound healing issues (5.0% vs. 12.0%; p = 0.012), and a lower 30-day mortality rate (1.5% vs. 6.0%; p = 0.031). Conclusions: MICLAT-S is safe and effective. Compared to traditional sternotomy in patients with obesity, MICLAT-S improves survival, reduces postoperative morbidity, and shortens hospital stays.
Attitude Practical Stabilization of Underactuated Autonomous Underwater Vehicles in Vertical Plane
Authors: Wang Yuliang , Bao Han , Li Yiping , Zhang Hongbin
Published: October 2024

Due to the singularity of Euler angles and the ambiguity of quaternions, to further expand the attitude reachable range of underactuated AUVs in the vertical plane, SO(3) is used to represent the attitude change of underactuated AUVs. The transverse function of the attitude on SO(3) is designed, and the exponential mapping method is used to construct the attitude kinematic controller of underactuated AUVs. Considering the changes in the model and ocean current during motion, interval type II fuzzy systems (IT2-FLSs) are used to estimate these changes. The backstepping method and the small gain theorem are adopted to design dynamic controllers to ensure the stability and robustness of the system. A novel saturation auxiliary system is designed to compensate for the influence of actuator saturation characteristics. Finally, the simulation results verify the effectiveness of the proposed controller and ensure the practical stabilization of the underactuated AUV attitude.
Effector-Mediated Suppression of Programmed Cell Death by Phytophthora palmivora in Oil Palm
Authors: Rodríguez-Cruz María Camila , Montoya Carmenza , Ayala-Diaz Iván , Araque Leonardo , Romero Hernán Mauricio
Published: October 2024

Phytophthora palmivora is the pathogen causing bud rot in oil palm (Elaeis guineensis). This pathogen secretes effector proteins that manipulate host defenses, contributing to disease progression. In this study, we systematically investigated the role of specific effector proteins in suppressing programmed cell death (PCD) in oil palm leaflets. Our approach included using genomic and transcriptomic data from a Colombian P. palmivora isolate alongside the coexpression network of a substantial effector dataset. From this analysis, ten candidate effectors were selected, characterized, and evaluated for their ability to suppress PCD in oil palm leaflets through transient expression via biolistics. Several effectors exhibited significant anti-PCD activity in susceptible and less susceptible oil palm genotypes. Notably, the effectors Avr3F (689), RxLR (1540), and RxLR (1546) demonstrated suppression of PCD in both genotypes, while the other effectors played variable roles in PCD regulation. Phylogenetic analysis further identified distinct clades among the effectors, possibly associated with their functional activities. Additionally, specific motifs, such as RXLR-dEER, K, and Y, appeared to correlate with PCD suppression. This research enhances our understanding of the molecular mechanisms underlying the interaction between P. palmivora effectors and oil palm host responses, highlighting these proteins’ genotype-specific regulation of PCD. The findings contribute valuable insights into plant–pathogen interactions and offer potential avenues for targeted disease control strategies in the oil palm industry.