bluuebunny/crossref_metadata_2025 huggingface dataset:
The GPR39 Receptor Plays an Important Role in the Pathogenesis of Overactive Bladder and Corticosterone-Induced Depression
Authors: Wróbel Jan , Iwaniak Paulina , Dobrowolski Piotr , Chwil Mirosława , Sadok Ilona , Kluz Tomasz , Wdowiak Artur , Bojar Iwona , Poleszak Ewa , Misiek Marcin , Zapała Łukasz , Urbańska Ewa M. , Wróbel Andrzej
Published: November 2024

Despite the close and clinically confirmed association between depression and overactive bladder, it remains unclear whether this affective disorder is a factor causing overactive bladder or whether overactive bladder is a specific symptom of psychosomatic disorders. This study examined the effects of repeated corticosterone administration on the occurrence of symptoms associated with depression and overactive bladder. Additionally, we examined whether administering TC-G 1008, an antidepressant that selectively activates the GPR39 receptor, could alleviate corticosterone-induced depression-like behavior and detrusor overactivity-related changes in cystometric measurements. We also explored its potential to reverse alterations in various biomarkers associated with both conditions in the serum, urinary bladder, and brain of female rats. The administration of corticosterone (20 mg/kg/day for 14 days) yielded anticipated results, including an increase in the duration of immobility during the forced swim test, alterations in parameters specific to bladder overactivity, a decrease in neurotrophins, and an elevation in pro-inflammatory cytokine levels. Treatment with TC-G 1008 (15 mg/kg/day) alleviated symptoms of both detrusor overactivity and depression, while also restoring the levels of biochemical and cystometric markers to normal ranges. Additionally, antidepressants based on GPR39 agonists could enhance the levels of kynurenic acid in the neuroprotective pathway. These results indicate that the GPR39 agonist receptor might be a promising future therapeutic approach for treating overactive bladder that occurs alongside depression.
High- and Moderate-Risk Variants Among Breast Cancer Patients and Healthy Donors Enrolled in Multigene Panel Testing in a Population of Central Russia
Authors: Shumilova Syuykum , Danishevich Anastasia , Nikolaev Sergey , Krasnov George , Ikonnikova Anna , Isaeva Darya , Surzhikov Sergei , Zasedatelev Alexander , Bodunova Natalia , Nasedkina Tatiana
Published: November 2024

Assessments of breast cancer (BC) risk in carriers of pathogenic variants identified by gene panel testing in different populations are highly in demand worldwide. We performed target sequencing of 78 genes involved in DNA repair in 860 females with BC and 520 age- and family history-matched controls from Central Russia. Among BC patients, 562/860 (65.3%) were aged 50 years or less at the time of diagnosis. In total, 190/860 (22%) BC patients were carriers of 198 pathogenic/likely pathogenic (P/LP) variants in 30 genes, while among controls, 32/520 (6.2%) carriers of P/LP variants in 17 genes were identified. The odds ratio [95% confidence interval] was 16.3 [4.0–66.7] for BRCA1; 12.0 [2.9–45.9] for BRCA2; and 7.3 [0.9–56.7] for ATM (p < 0.05). Previously undescribed BRCA1/2, ATM, and PALB2 variants, as well as novel recurrent mutations, were identified. The contribution to BC susceptibility of truncating variants in the genes BARD1, RAD50, RAD51C, NBEAL1 (p. E1155*), and XRCC2 (p. P32fs) was evaluated. The BLM, NBN, and MUTYH genes did not demonstrate associations with BC risk. Finding deleterious mutations in BC patients is important for diagnosis and management; in controls, it opens up the possibility of prevention and early diagnostics.
Molecular Modeling of Vasodilatory Activity: Unveiling Novel Candidates Through Density Functional Theory, QSAR, and Molecular Dynamics
Authors: Bernal Anthony , Márquez Edgar A. , Flores-Sumoza Máryury , Cuesta Sebastián A. , Mora José Ramón , Paz José L. , Mendoza-Mendoza Adel , Rodríguez-Macías Juan , Salazar Franklin , Insuasty Daniel , Marrero-Ponce Yovani , Agüero-Chapin Guillermin , Flores-Morales Virginia , Carrascal-Hernández Domingo César
Published: November 2024

Cardiovascular diseases (CVD) pose a significant global health challenge, requiring innovative therapeutic strategies. Vasodilators, which are central to vasodilation and blood pressure reduction, play a crucial role in cardiovascular treatment. This study integrates quantitative structure– (QSAR) modeling and molecular dynamics (MD) simulations to predict the biological activity and interactions of vasodilatory compounds with the aim to repurpose drugs already known and estimateing their potential use as vasodilators. By exploring molecular descriptors, such as electronegativity, softness, and highest occupied molecular orbital (HOMO) energy, this study identifies key structural features influencing vasodilatory effects, as it seems molecules with the same mechanism of actions present similar frontier orbitals pattern. The QSAR model was built using fifty-four Food Drugs Administration-approved (FDA-approved) compounds used in cardiovascular treatment and their activities in rat thoracic aortic rings; several molecular descriptors, such as electronic, thermodynamics, and topographic were used. The best QSAR model was validated through robust training and test dataset split, demonstrating high predictive accuracy in drug design. The validated model was applied on the FDA dataset and molecules in the application domain with high predicted activity were retrieved and filtered. Thirty molecules with the best-predicted pKI50 were further analyzed employing molecular orbital frontiers and classified as angiotensin-I or β1-adrenergic inhibitors; then, the best scoring values obtained from molecular docking were used to perform a molecular dynamics simulation, providing insight into the dynamic interactions between vasodilatory compounds and their targets, elucidating the strength and stability of these interactions over time. According to the binding energies results, this study identifies novel vasodilatory candidates where Dasabuvir and Sertindole seem to have potent and selective activity, offering promising avenues for the development of next-generation cardiovascular therapies. Finally, this research bridges computational modelling with experimental validation, providing valuable insight for the design of optimized vasodilatory agents to address critical unmet needs in cardiovascular medicine.
Transcriptional Analysis and Identification of a Peptidoglycan Hydrolase (PGH) and a Ribosomal Protein with Antimicrobial Activity Produced by Lactiplantibacillus paraplantarum
Authors: Hurtado-Rios Jessica J. , Carrasco-Navarro Ulises , Almanza-Pérez Julio Cesar , Rincón-Guevara Monica A. , Ponce-Alquicira Edith
Published: November 2024

The growing challenge of antibiotic resistance has intensified the search for new antimicrobial agents. Promising alternatives include peptidoglycan hydrolases (PGHs) and certain ribosomal proteins, both of which exhibit antimicrobial activity. This study focuses on a Lactiplantibacillus paraplantarum strain, isolated from fermented meat, capable of inhibiting pathogens such as Listeria innocua, Salmonella Typhimurium, Escherichia coli, Staphylococcus aureus, and Weissella viridescens. The highest growth and antimicrobial activity were observed at a high nitrogen concentration (5.7 g/L). Two antimicrobial proteins were identified: the 50S ribosomal protein L14 (RP uL14) and 6-phospho-N-acetylmuramidase (MupG), a PGH. Partial purification and characterization of these proteins were achieved using SDS-PAGE, zymography, and LC-MS/MS. Transcriptional data (RT-qPCR) showed that higher nitrogen concentrations enhanced MupG expression, while increased carbon concentrations boosted RP uL14 expression. These findings highlight the importance of nutritional sources in maximizing the production of novel antimicrobial proteins, offering a potential path to develop effective alternatives against antibiotic-resistant bacteria.
Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia
Authors: Blokhina Anastasia V. , Ershova Alexandra I. , Kiseleva Anna V. , Sotnikova Evgeniia A. , Zharikova Anastasia A. , Zaicenoka Marija , Vyatkin Yuri V. , Ramensky Vasily E. , Kutsenko Vladimir A. , Garbuzova Elizaveta V. , Divashuk Mikhail G. , Litinskaya Olga A. , Pokrovskaya Maria S. , Shalnova Svetlana A. , Meshkov Alexey N. , Drapkina Oxana M.
Published: November 2024

Familial dysbetalipoproteinemia (FD) is a highly atherogenic, prevalent genetically based lipid disorder. About 10% of FD patients have rare APOE variants associated with autosomal dominant FD. However, there are insufficient data on the relationship between rare APOE variants and FD. Genetic data from 4720 subjects were used to identify rare APOE variants and investigate their pathogenicity for autosomal dominant FD. We observed 24 variants in 86 unrelated probands. Most variants were unique (66.7%). Five identified APOE variants (p.Glu63ArgfsTer15, p.Gly145AlafsTer97, p.Lys164SerfsTer87, p.Arg154Cys, and p.Glu230Lys) are causal for autosomal dominant FD. One of them (p.Lys164SerfsTer87) was described for the first time. When we compared clinical data, it was found that carriers of pathogenic or likely pathogenic APOE variants had significantly higher triglyceride levels (median 5.01 mmol/L) than carriers of benign or likely benign variants (median 1.70 mmol/L, p = 0.034) and variants of uncertain significance (median 1.38 mmol/L, p = 0.036). For the first time, we estimated the expected prevalence of causal variants for autosomal dominant FD in the population sample: 0.27% (one in 619). Investigating the spectrum of APOE variants may advance our understanding of the genetic basis of FD and underscore the importance of APOE gene sequencing in patients with lipid metabolism disorders.
DNA Methylation Changes and Phenotypic Adaptations Induced Repeated Extreme Altitude Exposure at 8848 Meters
Authors: Zhang Shixuan , Yang La , Duoji Zhuoma , Qiangba Danzeng , Hu Xiaoxi , Jiang Zeyu , Hou Dandan , Hu Zixin , Basang Zhuoma
Published: November 2024

Repeated extreme environmental training (RET) enhances adaptability and induces lasting methylation modifications. We recruited 64 participants from a high-altitude region (4700 m), including 32 volunteers with repeated high-altitude exposure, reaching up to 8848 m and as many as 11 exposures. By analyzing 741,489 CpG loci and 39 phenotypes, we identified significant changes in 13 CpG loci (R2 > 0.8, ACC > 0.75) and 15 phenotypes correlated with increasing RET exposures. The phenotypic Bayesian causal network and phenotypic-CpG interaction networks showed greater robustness (node correlation) with more RET exposures, particularly in systolic blood pressure (SP), platelet count (PLT), and neutrophil count (NEUT). Six CpG sites were validated as significantly associated with hypoxia exposure using the GEO public da-taset (AltitudeOmics). Furthermore, dividing the participants into two groups based on the number of RET exposures (n = 9 and 4) revealed six CpG sites significantly corre-lated with PLT and red cell distribution width-standard deviation (RDW.SD). Our findings suggest that increased RET exposures strengthen the interactions between phenotypes and CpG sites, indicating that critical extreme adaptive states may alter methylation patterns, co-evolving with phenotypes such as PLT, RDW.SD, and NEUT.
Gene Expression Dysregulation in Whole Blood of Patients with Clostridioides difficile Infection
Authors: Tsakiroglou Maria , Evans Anthony , Doce-Carracedo Alejandra , Little Margaret , Hornby Rachel , Roberts Paul , Zhang Eunice , Miyajima Fabio , Pirmohamed Munir
Published: November 2024

Clostridioides difficile (C. difficile) is a global threat and has significant implications for individuals and health care systems. Little is known about host molecular mechanisms and transcriptional changes in peripheral immune cells. This is the first gene expression study in whole blood from patients with C. difficile infection. We took blood and stool samples from patients with toxigenic C. difficile infection (CDI), non-toxigenic C. difficile infection (GDH), inflammatory bowel disease (IBD), diarrhea from other causes (DC), and healthy controls (HC). We performed transcriptome-wide RNA profiling on peripheral blood to identify diarrhea common and CDI unique gene sets. Diarrhea groups upregulated innate immune responses with neutrophils at the epicenter. The common signature associated with diarrhea was non-specific and shared by various other inflammatory conditions. CDI had a unique 45 gene set reflecting the downregulation of humoral and T cell memory functions. Dysregulation of immunometabolic genes was also abundant and linked to immune cell fate during differentiation. Whole transcriptome analysis of white cells in blood from patients with toxigenic C. difficile infection showed that there is an impairment of adaptive immunity and immunometabolism.
The Remarkable Diversity of Vertebrate Bitter Taste Receptors: Recent Advances in Genomic and Functional Studies
Authors: Itoigawa Akihiro , Nakagita Tomoya , Toda Yasuka
Published: November 2024

Bitter taste perception is crucial for animal survival. By detecting potentially harmful substances, such as plant secondary metabolites, as bitter, animals can avoid ingesting toxic compounds. In vertebrates, this function is mediated by taste receptors type 2 (T2Rs), a family of G protein-coupled receptors (GPCRs) expressed on taste buds. Given their vital roles, T2Rs have undergone significant selective pressures throughout vertebrate evolution, leading to frequent gene duplications and deletions, functional changes, and intrapopulation differentiation across various lineages. Recent advancements in genomic and functional research have uncovered the repertoires and functions of bitter taste receptors in a wide range of vertebrate species, shedding light on their evolution in relation to dietary habits and other ecological factors. This review summarizes recent research on bitter taste receptors and explores the mechanisms driving the diversity of these receptors from the perspective of vertebrate ecology and evolution.
Chemical, In Cellulo, and In Silico Characterization of the Aminocholine Analogs of VG
Authors: Kostoudi Stavroula , Iatridis Nikolaos , Hadjipavlou-Litina Dimitra , Pontiki Eleni , Pampalakis Georgios
Published: November 2024

V-type nerve agents are exceedingly toxic chemical warfare agents that irreversibly inhibit acetylcholinesterase (AChE), leading to acetylcholine accumulation in synapses and the disruption of neurotransmission. VG or O.O-diethyl S-(diethylamino)ethyl phosphorothiolate was the first compound of this class that was synthesized. The selenocholines (-Se-), cholines (-O-), and methylene-cholines (-CH2-) analogs of V-agents have been synthesized and their anti-AChE activities reported. Nevertheless, the aminocholine derivatives have not been pursued. Here, we have designed and synthesized a series of phosphorylated aminocholines analogs of VG that were characterized by NMR spectroscopy (H1, C13, P31, and TOCSY). Their pharmacological properties were analyzed in silico, while their toxicological properties were in vitro investigated using the SH-SY5Y cellular model. Despite the drug likeness of the new compounds, these fail to inhibit AChE in vitro and in cellulo. This may be partially explained by the fact that aminocholine is not a good leaving group compared to thiocholine. Remarkably, one of the compounds (P4) was found to even increase the activity of AChE. These compounds may serve as new nerve agent mimics that are safer alternatives for testing countermeasures. Importantly, P4 may act as a lead compound for developing a new class of alternative nerve agent pretreatments that are safer from pyridostigmine.
Characterization and Safety Evaluation of Autoclaved Gut Commensal Parabacteroides goldsteinii RV-01
Authors: Lin Tzu-Lung , Chen Wan-Jiun , Hung Chien-Min , Wong Yea-Lin , Lu Chia-Chen , Lai Hsin-Chih
Published: November 2024

Gut commensals play important roles in maintaining the homeostasis of human health. Previous studies indicated that the abundance of P. goldsteinii in animal hosts was increased by the administration of prebiotics such as polysaccharides purified from iconic oriental medicinal fungi. Subsequently, P. goldsteinii was found to exert beneficial effects on the amelioration of multiple chronic inflammation-associated diseases. Even so, during the process of the development of P. goldsteinii as a next-generation probiotic (NGP), care has to be taken when it is used as a functional food ingredient. In this study, we isolated a novel P. goldsteinii strain, RV-01, from the feces of a healthy adult and carried out comprehensive analyses of its genomic and phenotypic characteristics. Bioinformatic analysis of P. goldsteinii RV-01 revealed the absence of potential virulence genes, as well as the presence of genes and traits potentially beneficial to human health, such as the production of short-chain fatty acids, anti-inflammatory lipopolysaccharides, and zwitterionic capsular polysaccharides, as well as immune regulatory proteins. To circumvent any potential side effects, the P. goldsteinii RV-01 was autoclaved before proceeding to the nonclinical safety assessment. The autoclaved P. goldsteinii RV-01 retained its anti-inflammatory effect in human colon epithelial cells. In addition to the three genotoxicity assays, 28-day subacute and 90-day subchronic animal toxicity studies (the highest dose tested was equivalent to 8.109 × 1010P. goldsteinii RV-01 cells/kg body weight/day) were also implemented. The results of all studies were negative for toxicity. These results support the conclusion that autoclaved P. goldsteinii RV-01 is safe for use as a food ingredient.
Test–Retest Reliability of Deep Learning Analysis of Brain Volumes in Adolescent Brain
Authors: Kasparbauer Anna-Maria , Wunram Heidrun Lioba , Abuhsin Fabian , Körber Friederike , Schönau Eckhard , Bender Stephan , Duran Ibrahim
Published: November 2024

Magnetic resonance imaging (MRI) is essential for studying brain development and psychiatric disorders in adolescents. However, the imaging consistency remains challenging, highlighting the need for advanced methodologies to improve the diagnostic and research reliability in this unique developmental period. Adolescence is marked by significant neuroanatomical changes, distinguishing adolescent brains from those of adults and making age-specific imaging research crucial for understanding the neuropsychiatric conditions in youth. This study examines the test–retest reliability of anatomical brain MRI scans in adolescents diagnosed with depressive disorders, emphasizing a developmental perspective on neuropsychiatric disorders. Using a sample of 42 adolescents, we assessed the consistency of structural imaging metrics across 95 brain regions with deep learning-based neuroimaging analysis pipelines. The results demonstrated moderate to excellent reliability, with the intraclass correlation coefficients (ICC) ranging from 0.57 to 0.99 across regions. Notably, regions such as the pallidum, amygdala, entorhinal cortex, and white matter hypointensities showed moderate reliability, likely reflecting the challenges in the segmentation or inherent anatomical variability unique to this age group. This study highlights the necessity of integrating advanced imaging technologies to enhance the accuracy and reliability of the neuroimaging data specific to adolescents. Addressing the regional variability and strengthening the methodological rigor are essential for advancing the understanding of brain development and psychiatric disorders in this distinct developmental stage. Future research should focus on larger, more diverse samples, multi-site studies, and emerging imaging techniques to further validate the neuroimaging biomarkers. Such advancements could improve the clinical outcomes and deepen our understanding of the neuropsychiatric conditions unique to adolescence.
Multiple Instance Bagging and Risk Histogram for Survival Time Analysis Based on Whole Slide Images of Brain Cancer Patients
Authors: Chang Yu Ping , Yang Ya-Chun , Yu Sung-Nien
Published: November 2024

This study tackles the challenges in computer-aided prognosis for glioblastoma multiforme, a highly aggressive brain cancer, using only whole slide images (WSIs) as input. Unlike traditional methods that rely on random selection or region-of-interest (ROI) extraction to choose meaningful subsets of patches representing the whole slide, we propose a multiple instance bagging approach. This method utilizes all patches extracted from the whole slide, employing different subsets in each training epoch, thereby leveraging information from the entire slide while keeping the training computationally feasible. Additionally, we developed a two-stage framework based on the ResNet-CBAM model which estimates not just the usual survival risk, but also predicts the actual survival time. Using risk scores of patches estimated from the risk estimation stage, a risk histogram can be constructed and used as input to train a survival time prediction model. A censor hinge loss based on root mean square error was also developed to handle censored data when training the regression model. Tests using the Cancer Genome Atlas Program’s glioblastoma public database yielded a concordance index of 73.16±2.15%, surpassing existing models. Log-rank testing on predicted high- and low-risk groups using the Kaplan–Meier method revealed a p-value of 3.88×10−9, well below the usual threshold of 0.005, indicating the model’s ability to significantly differentiate between the two groups. We also implemented a heatmap visualization method that provides interpretable risk assessments at the patch level, potentially aiding clinicians in identifying high-risk regions within WSIs. Notably, these results were achieved using 98% fewer parameters compared to state-of-the-art models.
Hard Carbon as Anodes for Potassium-Ion Batteries: Developments and Prospects
Authors: Qiu Peng , Chen Haohong , Zhang Hanzhi , Wang Han , Wang Lianhao , Guo Yingying , Qi Ji , Yi Yong , Zhang Guobin
Published: November 2024

Potassium-ion batteries (PIBs) are regarded as a potential substitute for LIBs owing to the benefits of potassium’s abundance, low cost, and high safety. Nonetheless, the practical implementation of potassium-ion batteries still encounters numerous challenges, with the selection and design of anode materials standing out as a key factor impeding their progress. Hard carbon, characterized by its amorphous structure, high specific surface area, and well-developed pore structure, facilitates the insertion/extraction of potassium ions, demonstrating excellent rate performance and cycling stability. This review synthesizes the recent advancements in hard carbon materials utilized in PIB anodes, with a particular focus on the potassium storage mechanism, electrochemical properties, and modification strategies of hard carbon. Ultimately, we present a summary of the current challenges and future development directions of hard carbon materials, with the objective of providing a reference for the design and optimization of hard carbon materials for PIBs.
Emerging Carbon-Based Catalysts for the Oxygen Reduction Reaction: Insights into Mechanisms and Applications
Authors: Guo Jing , Yao Yuqi , Yan Xin , Meng Xue , Wang Qing , Zhang Yahui , Yan Shengxue , Zhao Xue , Luo Shaohua
Published: November 2024

The oxygen reduction reaction (ORR), as a key electrode process in fuel cells and metal-air batteries, plays a pivotal role in advancing clean energy technologies. However, the slow kinetics and high overpotential of the ORR significantly limit the efficiency of these energy devices. Therefore, the development of efficient, stable, and cost-effective ORR catalysts has become a central focus of current research. Carbon-based catalysts, with their excellent conductivity, chemical stability, and tunable structural features, have emerged as promising alternatives to traditional precious metal catalysts. Nevertheless, challenges remain in the design of active sites, the tuning of electronic structures, and the large-scale synthesis of carbon-based catalysts. This review systematically introduces the fundamental mechanisms and key factors influencing the ORR, providing an analysis of the critical variables that affect catalyst performance. Furthermore, it summarizes several common methods for synthesizing carbon-based catalysts, including pyrolysis, deposition, and ball milling. Following this, the review categorizes and discusses the latest advancements in metal-free carbon-based catalysts, single-atom and dual-atom catalysts, as well as metal-based nanoparticle catalysts, with a particular focus on their mechanisms for enhancing the ORR performance. Finally, the current state of research on carbon-based ORR catalysts is summarized, and future development directions are proposed, emphasizing the optimization of active sites, improvements in catalyst stability, and potential strategies for large-scale applications.
Influence of Temperature and Photoperiod on Survival and Development of Eoreuma loftini (Lepidoptera: Crambidae)
Authors: Villegas James M. , Diaz Rodrigo , Stout Michael J. , Papitchaya Fin , Wilson Blake E.
Published: November 2024

The Mexican rice borer, Eoreuma loftini (Lepidoptera: Crambidae) is an economically important pest of sugarcane, rice, and corn in Louisiana, Texas, and Mexico. This pest is considered invasive in the US and is expanding its range northward. Due to its subtropical origin, E. loftini’s northern distribution might be limited by cold tolerance. A series of assays determined the influence of temperature and photoperiod on E. loftini life table parameters. Adult oviposition was reduced at temperatures > 30 °C. Egg viability was reduced at 20 and 36 °C relative to intermediate temperatures. Egg development time was greatest at 18 °C. Larvae did not develop to the pupal stage at temperatures ≤ 20 °C. Larval duration decreased with increasing temperature from 22 to 36 °C. Adult longevity decreased with increasing temperature from 18 °C (15 d) to 34 °C (7 d). Exposure to a short-day photoperiod decreased larval mortality at −5 °C. Larval survival of >80% up to 5 days at −5 °C suggests E. loftini cold tolerance is sufficient to minimize the influence of hard freezes on overwintering populations. Larval survival for 5 d at 40 °C was 75%. Exposure to 45 °C for periods > 1 d caused 100% mortality. These results suggest that E. loftini exhibits considerable thermal plasticity and cold tolerance, which may facilitate its range expansion in the United States.
End of the Season Blues: Senescence and Reproductive Trade-Offs in Male Scorpions
Authors: Vrech David E. , Oviedo-Diego Mariela A. , Olivero Paola A. , Peretti Alfredo V.
Published: November 2024

Seasonal reproductive dynamics and senescence have profound impacts on male fertility, yet these processes remain understudied in scorpions. This study investigates how reproductive parameters—such as testicular mass, sperm quantity, and viability—change over the course of the reproductive season in Urophonius achalensis males. We found that early-season males exhibited higher sperm quality and testicular mass compared to their older counterparts, suggesting that senescence, rather than reproductive effort, drives the decline in sperm viability. Interestingly, isolated males accumulated more sperm without a reduction in viability, highlighting potential mechanisms that preserve sperm quality despite senescence. Body condition also played a key role, with males in better condition showing higher sperm counts but facing a sharper decline in sperm viability as the season progressed, suggesting trade-offs between early reproductive success and later-life reproductive costs. Our findings offer novel insights into the reproductive strategies of scorpions, emphasizing the interplay between senescence, environmental stressors, and reproductive investment. This work provides new insights into the reproductive biology of scorpions, with broader implications for understanding the role of senescence and mating systems in shaping reproductive strategies.
The Changes in Cross-Resistance, Fitness, and Feeding Behavior in Aphis gossypii as Their Resistance to Sulfoxaflor Declines
Authors: Lv Mingyuan , Wang Wei , Fang Fengyun , Fu Xiaowei , Liang Gemei
Published: November 2024

The increasing resistance in Aphis gossypii field populations to sulfoxaflor and many different types of insecticides represents a significant challenge in protecting cotton production in China. Although resistant pests were able to regain their susceptibility to insecticides after the reduction in insecticide applications, some of their biological parameters remained different from susceptible strains. The resistance to sulfoxaflor was unstable in A. gossypii after the loss of selective pressure. The strain with declined resistance (Sul-D) (RR = 1.11-fold) restored its susceptibility to sulfoxaflor, acetamiprid, and imidacloprid after the sulfoxaflor-resistant (Sul-R) (RR = 51.57-fold) was maintained without insecticide pressure for 22 generations. Sul-R had a relative fitness of 0.87, and the Sul-D strain still had a relative fitness of 0.84, even if its susceptibility to sulfoxaflor was restored. Compared with the susceptible strain (Sus), the Sul-R and Sul-D strains became more active in searching for appropriate feeding positions because they generated more intercellular apoplastic stylar pathway events (C). However, the phloem-feeding ability was reduced in the Sul-R and Sul-D strains, as shown by the decrease in phloem behavioral parameters, such as phloem salivations (E1), phloem ingestion (E2), and the percentages of E1 and E2. The negative hormesis effect of sulfoxaflor on phloem feeding was observed in susceptible strain but not in Sul-R and Sul-D, as evidenced by the significant decreases in the number of E1, the duration of E1 and E2, and the percentage of E1 and E2 in the Sus strain. Sulfoxaflor resistance was unstable in A. gossypii, and there was still a fitness cost to A. gossypii after recovering susceptibility to sulfoxaflor. The phloem-feeding ability was reduced in the Sul-R and Sul-D strains compared with the Sus strain, but the negative hormesis effect of sulfoxaflor on phloem feeding was only found in the Sus strain. The outcomes of this study could contribute to a comprehensive risk assessment and provide a basis for developing a better strategy to control A. gossypii.
Scanning Electron Microscopy of the Proboscis and Associated Sensilla in Colias erate (Esper, 1805) (Lepidoptera: Pieridae)
Authors: Yuan Jia-Qi , Li Fei-Fei , Zhu Ling , Zhang Wen , Ma Li-Hu , Miao Ying
Published: November 2024

Morphological studies of the proboscis can provide valuable insights into the evolutionary adaptations of Lepidoptera. However, such research is relatively limited for Pieridae, a family that is significant both ecologically and economically. In this study, scanning electron microscopy (SEM) was employed to investigate the proboscis and associated sensilla of adult C. erate, with an emphasis on ultrastructural details and potential sex-specific differences. The proboscis in both sexes exhibits a similar structure, consisting of two elongated maxillary galeae connected by dorsal and ventral legulae. It is divided into three distinct zones based on morphological changes in the dorsal legulae. The outer surface of the proboscis is characterized by spike-like microbumps on transverse ridges, while the inner surface (food canal) is smooth throughout all three zones, with regularly spaced transverse grooves. Three types of sensilla comprising five subtypes were identified: sensilla chaetica (sc), sensilla basiconica (sb1, sb2, and sb3), and sensilla styloconica (ss). The functional implications of these morphological features are also discussed briefly.
Distributed Dispatch of Distribution Network Operators, Distributed Energy Resource Aggregators, and Distributed Energy Resources: A Three-Level Conditional Value-at-Risk Optimization Model
Authors: Huang Qifeng , Cheng Hanmiao , Zhuang Zhong , Duan Meimei , Fang Kaijie , Huang Yixuan , Wang Liyu
Published: November 2024

To enhance the participation enthusiasm of distributed energy resources (DERs) and DER aggregators in their demand response, this paper develops a three-level distributed scheduling model for the distribution network operators (DNO), DER aggregators, and DERs based on the conditional value-at-risk (CVaR) theory. First, a demand response model is established for the DNO, DER aggregators, and DERs. Next, we employ the analytical target cascading (ATC) method to construct a three-level distributed scheduling model, where incentive and compensation prices are shared as consensus variables across the model levels to amplify the influence of DER aggregators on incentive prices and DERs on compensation prices. Then, the photovoltaic output model is restructured using the CVaR theory to effectively measure the risk associated with photovoltaic output uncertainty. Finally, an analysis is conducted using the IEEE 33-node distribution network to validate the effectiveness of the proposed model.
Using Virtual Reality Recreation Therapy to Enhance Social Interaction and Well-Being in Homebound Seniors
Authors: Foo Jonathan J. , Chew Keng Hao , Lim Peggy , Tay June , Ma Carol Hok Ka
Published: November 2024

In view of Singapore’s rapidly ageing population, this study is an exploratory pilot designed to assess the feasibility and potential impact of virtual reality recreation therapy (VRRT) on homebound seniors. A tri-party research partnership was formed between the Singapore University of Social Sciences (SUSS), NTUC Health Home Care, and Vue Reality Labs. The aim was to explore the benefits of VR recreation therapy for homebound seniors, contributing to the goal of ‘aging in place’. Over two years, a 52-week VR curriculum was developed, featuring social, travel, and cultural topics tailored to the seniors. Five care associates from NTUC Health Home Care received facilitator training by Vue Reality Labs. A total of 71 homebound senior participants aged 50 to 102 engaged in over 1600 session hours during the 52-week trial; 62% had varying levels of dementia. A mixed-methods approach was adopted to explore the general impact and feasibility of VR recreation therapy, incorporating quantitative data on participants’ emotional, social, and cognitive conditions and qualitative data from facilitator interviews. The findings revealed that most senior participants enjoyed the VR sessions, perceiving them to positively impact their overall health and well-being. Caregivers reported improvements in cognitive, social, and emotional functioning of the participants. The positive effects extended to caregivers and facilitators, with renewed relationships and enhanced skills, respectively. The insights and observations gathered from this pilot study will serve as a foundation for designing a more robust study for deploying the VR recreation therapy programme in senior care.
Effects of Acute Maximum-Intensity Exercise on Matrix Metalloproteinase-2, -9, and Tissue Inhibitor of Metalloproteinase-1 Levels in Adult Males with Type 1 Diabetes Mellitus Treated with Insulin Pumps
Authors: Kryst Joanna , Matejko Bartłomiej , Czerwińska-Ledwig Olga , Tota Łukasz , Zuziak Roxana , Piotrowska Anna
Published: November 2024

Background: Dysregulation of matrix metalloproteinases (MMPs) activity is considered one of the potential causes of vascular complications in diabetic patients. Since training volume may influence MMPs levels in varying ways, the aim of our study was to evaluate changes in MMPs levels following acute maximum-intensity exercise in male patients with type 1 diabetes mellitus (T1DM). Methods: This study included 24 male T1DM patients and 10 healthy controls. Aerobic capacity was evaluated with a treadmill test. Levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured both before the aerobic capacity test and 60 min after its completion utilizing enzyme-linked immunosorbent assay (ELISA) system kits. Results: Before the aerobic capacity test only, MMP-9 serum levels were significantly elevated in the T1DM group compared to the controls. Following maximum-intensity exercise, the levels of MMP-2, MMP-9, and TIMP-1 were significantly higher in T1DM patients than in the control group. Between-group comparisons revealed that maximum-intensity exercise induced a statistically significant increase in MMP-2 serum levels from baseline in T1DM patients compared to controls. Conclusions: Our findings suggest that high-intensity exercise in T1DM patients leads to dysregulation of MMPs, as manifested by a significant increase in MMP-2 levels. This dysregulation may play a role in the development of vascular complications in diabetic patients.
Evaluating Psychological Effects of Amputation Through Virtual Reality Embodiment: A Study on Anxiety and Body Appreciation
Authors: Manzano-Torra Aina , Porras-Garcia Bruno , Gutiérrez-Maldonado José
Published: November 2024

Background/Objectives: A high number of patients who suffer the amputation of a lower limb will present psychological problems such as anxiety, depression, and post-traumatic stress disorder after surgery. This study embodies participants in a self-avatar with a right lower-limb amputation in a virtual reality environment. The aim was to determine if this experience increases anxiety levels compared to embodiment in a normal avatar. The study also examines whether body appreciation is related to anxiety levels. Methods: Subjects completed the Body Appreciation Scale (BAS) questionnaire before being immersed in the virtual environment, the Visual Analogue Scale for Anxiety (VAS-A) after each condition, and the Embodiment Questionnaire at the end of the experiment. Results: Univariate analysis showed that participants reported significantly higher levels of anxiety when exposed to the virtual avatar with an amputation compared to the full virtual body avatar. These results indicate that lower levels of body appreciation were associated with higher levels of anxiety across conditions, suggesting that participants with lower body appreciation experienced greater psychological maladjustment (measured by anxiety) in response to the virtual scenarios. Conclusions: The results suggest that the virtual avatar with a lower-limb amputation elicited significantly greater anxiety, and that body appreciation plays a key role in moderating this psychological response. Future research could focus on developing virtual exposure-based therapy for amputees using virtual reality to help reduce the anxiety experienced by patients during this process.
Incidence of Diabetic Retinopathy in Individuals with Type 2 Diabetes: A Study Using Real-World Data
Authors: Hernández-Teixidó Carlos , Barrot de la Puente Joan , Miravet Jiménez Sònia , Fernández-Camins Berta , Mauricio Didac , Romero Aroca Pedro , Vlacho Bogdan , Franch-Nadal Josep
Published: November 2024

Background/Objectives: This study aimed to assess the incidence of diabetic retinopathy (DR) in patients with type 2 diabetes (T2DM) treated in primary-care settings in Catalonia, Spain, and identify key risk factors associated with DR development. Methods: A retrospective cohort study was conducted using the SIDIAP (System for Research and Development in Primary Care) database. Patients aged 30–90 with T2DM who underwent retinal screening between 2010 and 2015 were included. Multivariable Cox regression analysis was used to assess the impact of clinical variables, including HbA1c levels, diabetes duration, and comorbidities, on DR incidence. Results: This study included 146,506 patients, with a mean follow-up time of 6.96 years. During this period, 4.7% of the patients developed DR, resulting in an incidence rate of 6.99 per 1000 person-years. Higher HbA1c levels were strongly associated with an increased DR risk, with patients with HbA1c > 10% having more than four times the risk compared to those with HbA1c levels < 7% (hazard ratio: 4.23; 95% CI: 3.90–4.58). Other significant risk factors for DR included greater diabetes duration, male sex, ex-smoker status, macrovascular disease, and chronic kidney disease. In contrast, obesity appeared to be a protective factor against DR, with an HR of 0.93 (95% CI: 0.89–0.98). Conclusions: In our real-world setting, the incidence rate of DR was 6.99 per 1000 person-years. Poor glycemic control, especially HbA1c > 10%, and prolonged diabetes duration were key risk factors. Effective management of these factors is crucial in preventing DR progression. Regular retinal screenings in primary care play a vital role in early detection and reducing the DR burden for T2DM patients.
Does the Intensity of Therapy Correspond to the Severity of Acute Respiratory Distress Syndrome (ARDS)?
Authors: Nocera Domenico , Giovanazzi Stefano , Pozzi Tommaso , Ghidoni Valentina , Donati Beatrice , Catozzi Giulia , D’Albo Rosanna , Caronna Martina , Grava Ilaria , Gazzè Gaetano , Collino Francesca , Coppola Silvia , Gattarello Simone , Busana Mattia , Romitti Federica , Moerer Onnen , Quintel Michael , Camporota Luigi , Gattinoni Luciano
Published: November 2024

Objectives: The intensity of respiratory treatment in acute respiratory distress syndrome (ARDS) is traditionally adjusted based on oxygenation severity, as defined by the mild, moderate, and severe Berlin classifications. However, ventilator-induced lung injury (VILI) is primarily determined by ventilator settings, namely tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP). All these variables, along with respiratory elastance, are included in the concept of mechanical power. The aim of this study is to investigate whether applied mechanical power is proportional to oxygenation severity. Methods: We analyzed 291 ARDS patients (71 mild, 155 moderate, and 65 severe). We defined low, middle, and high mechanical power by dividing the entire population into tertiles with a similar number of patients. In each oxygenation class, we measured computed tomography (CT) anatomy, gas exchange, respiratory mechanics, mechanical power, and mortality rate. Results: ARDS severity was proportional to lung anatomy impairment, as defined by quantitative CT scans (i.e., lung volume and well-aerated tissue decreased across the ARDS classes, while respiratory elastance increased, as did mortality). Mechanical power, however, was similarly distributed across the severity classes, as the decrease in tidal volume in severe ARDS was offset by an increase in respiratory rate. Within each ARDS class, mortality increased from low to high mechanical power (roughly 1% for each J/min increase). Conclusions: Both lung severity and mechanical power independently impact mortality rates. It is tempting to speculate that ARDS severity primarily reflects the natural course of the disease, while mechanical power primarily reflects the risk of VILI.
Unlocking the Secrets of Acute Coronary Syndromes Using Intravascular Imaging: From Pathophysiology to Improving Outcomes
Authors: Apostolos Anastasios , Karanasos Antonios , Ktenopoulos Nikolaos , Tsalamandris Sotirios , Vlachakis Panayotis K. , Kachrimanidis Ioannis , Skalidis Ioannis , Sagris Marios , Koliastasis Leonidas , Drakopoulou Maria , Synetos Andreas , Tsioufis Konstantinos , Toutouzas Konstantinos
Published: November 2024

Acute coronary syndrome (ACS) represents the most severe manifestation of coronary artery disease. Intravascular imaging, both intravascular ultrasound (IVUS) and optical coherence tomography (OCT), have played crucial roles for the impressive reduction in mortality of ACS. Intravascular imaging is useful for the detection of atherosclerotic mechanism (plaque rupture, calcified nodules, or plaque erosions) and for the evaluation of nonatherosclerotic and nonobstructive types of ACS. In addition, IVUS and OCT play a crucial role in the optimization of the PCI. The aim of the current review is to present the role of intravascular imaging in identifying the mechanisms of ACS and its prognostic role in future events, to review the current guidelines suggesting intravascular imaging use in ACS, to summarize its role in PCI in patients with ACS, and to compare IVUS and OCT.
Leading Causes of US Deaths in the 2022
Authors: Mattiuzzi Camilla , Lippi Giuseppe
Published: November 2024

Background and Objective: Obtaining reliable and up-to-date information on mortality causes is essential for the planning and implementation of effective preventive interventions. We present here an analysis of the leading causes of death in the US in 2022. Material and Methods: We conducted an electronic search of the US Centers for Control and Prevention (CDC) Web-based Injury Statistics Query and Reporting System (WISQARS) and Wide-Ranging, Online Data for Epidemiologic Research (WONDER) to obtain information on the leading causes of death in the US for the most recent searchable year with definitive data (i.e., 2022), stratified by age and sex. Results: Overall, heart disease was the leading cause of death (26.2% of all deaths), followed by malignant neoplasms (22.7%), unintentional injuries (8.5%) and coronavirus disease 2019 (COVID-19; 6.9%). Although heart disease and malignant neoplasms remained the leading causes of death in both sexes, unintentional injuries were the third cause for men (10.5%), while strokes were the third cause in women (7.5%). COVID-19 remained the fourth most common cause of death in both sexes (7.1% in men and 6.8% in women). The ten most common causes of death showed an increasing mortality tendency in parallel with the aging of population, with similar trends for both sexes. The only exception was unintentional injury, which was the most common cause of death in both sexes between the ages of 15-44 years, then reached a plateau, before increasing again in people aged 65 years or older. Conclusions: Greater efforts should be put into prevention and education, as heart disease, cancer, and even unintentional injuries are preventable diseases.
The Importance of Genetic Background and Neurotransmission in the Pathogenesis of the Co-Occurrence of Sleep Bruxism and Sleep-Disordered Breathing—Review of a New Perspective
Authors: Smardz Joanna , Jenca Andrej , Orzeszek Sylwia
Published: November 2024

Sleep bruxism (SB) and sleep-disordered breathing (SDB) are two prevalent conditions that significantly impact overall health. Studies suggest that up to 49.7% of individuals with SDB also exhibit symptoms of SB. This review aims to provide a comprehensive analysis of the role of genetic background and neurotransmission in the pathogenesis of the co-occurrence of SB and SDB. It seeks to synthesize current knowledge, highlight gaps in the existing literature, and propose a new perspective that integrates genetic and neurobiological factors. This review shows that both SB and SDB may be influenced by a combination of genetic, neurochemical, and environmental factors that contribute to their shared pathophysiology. The key neurotransmitters—dopamine, serotonin, and GABA—may play a significant role in their co-occurrence by regulating motor activity, sleep architecture, and respiratory control. Understanding genetic and neurochemical mechanisms may allow for more precise diagnostic tools and more personalized treatment approaches regarding SB and SDB. Clinically, there is a need for interdisciplinary collaboration between sleep specialists, dentists, neurologists, and geneticists. There is also a need to conduct large-scale genetic studies, coupled with neuroimaging and neurophysiological research, uncovering additional insights into the shared mechanisms of SB and SDB.