bluuebunny/crossref_metadata_2025 huggingface dataset:
Site Matters: Differences in Gene Expression Profiles Along the Bovine Rumen Papilla During Subacute Rumen Acidosis
Authors: Sener-Aydemir Arife , Dengler Franziska , Larsberg Filip , Rivera-Chacon Raul , Castillo-Lopez Ezequias , Zebeli Qendrim , Kreuzer-Redmer Susanne
Published: November 2024

Subacute rumen acidosis (SARA) is a significant concern in dairy cattle fed grain-rich diets. To elucidate the underlying pathophysiological mechanisms, ruminal papilla biopsies are often used. This study aimed to assess how the sampling site along the ruminal papilla influences gene expression profiles in rumen epithelium during SARA. Rumen biopsies from five ruminal-cannulated non-lactating Holstein cows were collected during feeding of a forage diet (FD) and seven (wk1) and 21 days (wk3) after transition to high-grain (HG) feeding. Gene expression in apical (AP), basal (BP), and total length (TP) papillae were compared using RT-qPCR. Significant diet-induced effects were observed in AP for DSG1 (wk3, p = 0.0317), ZO1 (wk1 and wk3, p = 0.0159), GLUT3 (wk3, p = 0.0159), TLR4 (wk3, p = 0.0635), and NFKB (wk1, p = 0.0159), but hardly in BP or TP. Within wk1, TP showed higher transcript levels of ZO1 and TLR4 (p = 0.0079) and SGLT1 (p = 0.0317) compared to AP and BP independently from diet effects. These findings suggest that the apical parts of rumen papillae biopsies are most suitable for gene expression analyses to investigate diet-induced effects on rumen physiology and underscore the importance of considering the sampling site for accurate gene expression studies in rumen epithelium during SARA, providing valuable insights for future research and diagnostic approaches in managing rumen health in dairy cattle.
Network Analysis of miRNA and Cytokine Landscape in Human Hematopoiesis
Authors: Vici Alessandro , Castelli Germana , Francescangeli Federica , Cerio Annamaria , Pelosi Elvira , Screnci Maria , Rossi Stefania , Morsilli Ornella , Felli Nadia , Pasquini Luca , Truglio Giuseppina Ivana , De Angelis Maria Laura , D’Andrea Vito , Rossi Rachele , Verachi Paola , Vila Frenki , Marziali Giovanna , Giuliani Alessandro , Zeuner Ann
Published: November 2024

The differentiation/maturation trajectories of different blood cell types stemming from a CD34+ common ancestor takes place in different biologically relevant multidimensional spaces. Here, we generated microRNA and cytokine profiles from highly purified populations of hematopoietic progenitors/precursors derived from cord blood hematopoietic stem/progenitor cells. MicroRNA and cytokine landscapes were then analyzed to find their mutual relationships under the hypothesis that the highly variable miRNome corresponds to the ‘force field’ driving the goal of a stable phenotype (here corresponding to the cytokine abundance pattern) typical of each cell kind. The high dimensionality and lack of linearity of the hematopoietic process pushed us to adopt a distance–geometry approach to compare different trajectories, while a complex network analysis was instrumental in revealing the fine structure of microRNA–cytokine relations. Importantly, the approach enabled us to identify a limited number of factors (represented either by microRNAs or cytokines) corresponding to crucial nodes responsible for connecting distinct interaction modules. Subtle changes in ‘master nodes’, keeping the connections between different regulatory networks, may therefore be crucial in influencing hematopoietic differentiation. These findings highlight the extremely interconnected network structures underlying hematopoiesis regulation and identify key factors in the microRNA/cytokine landscape that may be potentially crucial for influencing network stability.
Identification of Functional Immune Biomarkers in Breast Cancer Patients
Authors: Derakhshandeh Roshanak , Zhu Yuyi , Li Junxin , Hester Danubia , Younis Rania , Koka Rima , Jones Laundette P. , Sun Wenji , Goloubeva Olga , Tkaczuk Katherine , Bates Joshua , Reader Jocelyn , Webb Tonya J.
Published: November 2024

Cancer immunotherapy has emerged as an effective, personalized treatment for certain patients, particularly for those with hematological malignancies. However, its efficacy in breast cancer has been marginal—perhaps due to cold, immune-excluded, or immune-desert tumors. Natural killer T (NKT) cells play a critical role in cancer immune surveillance and are reduced in cancer patients. Thus, we hypothesized that NKT cells could serve as a surrogate marker for immune function. In order to assess which breast cancer patients would likely benefit from immune cell-based therapies, we have developed a quantitative method to rapidly assess NKT function using stimulation with artificial antigen presenting cells followed by quantitative real-time PCR for IFN-γ. We observed a significant reduction in the percentage of circulating NKT cells in breast cancer patients, compared to healthy donors; however, the majority of patients had functional NKT cells. When we compared BC patients with highly functional NKT cells, as indicated by high IFN-γ induction, to those with little to no induction, following stimulation of NKT cells, there was no significant difference in NKT cell number between the groups, suggesting functional loss has more impact than physical loss of this subpopulation of T cells. In addition, we assessed the percentage of tumor-infiltrating lymphocytes and PD-L1 expression within the tumor microenvironment in the low and high responders. Further characterization of immune gene signatures in these groups identified a concomitant decrease in the induction of TNFα, LAG3, and LIGHT in the low responders. We next investigated the mechanisms by which breast cancers suppress NKT-mediated anti-tumor immune responses. We found that breast cancers secrete immunosuppressive lipids, and treatment with commonly prescribed medications that modulate lipid metabolism, can reduce tumor growth and restore NKT cell responses.
Prenatal Exposure to a Human Relevant Mixture of Endocrine-Disrupting Chemicals Affects Mandibular Development in Mice
Authors: Rinotas Vagelis , Stamatakis Antonios , Stergiopoulos Athanasios , Bornehag Carl-Gustaf , Rüegg Joëlle , Armaka Marietta , Kitraki Efthymia
Published: November 2024

Mandible is a bony structure of neuroectodermal origin with unique characteristics that support dentition and jaw movements. In the present study, we investigated the effects of gestational exposure to a mixture of endocrine-disrupting chemicals (EDCs) on mandibular growth in mice. The mixture under study (Mixture N1) has been associated with neurodevelopmental effects in both a human cohort and animal studies. Pregnant mice were exposed throughout gestation to 0.5× (times of pregnant women’s exposure levels), 10×, 100× and 500× of Mixture N1, or the vehicle, and the mandibles of the male offspring were studied in adulthood. Micro-CT analysis showed non-monotonic effects of Mixture N1 in the distances between specific mandibular landmarks and in the crown width of M1 molar, as well as changes in the mandibular bone characteristics. The alveolar bone volume was reduced, and the trabecular separation was increased in the 500× exposed mice. Bone volume in the condyle head was increased in all treated groups. Τhe Safranin-O-stained area of mature hypertrophic chondrocytes and the width of their zones were reduced in 0.5×, 10× and 100× exposed groups. This is the first indication that prenatal exposure to an epidemiologically defined EDC mixture, associated with neurodevelopmental impacts, can also affect mandibular growth in mammals.
Mineralocorticoid Receptor and Sleep Quality in Chronic Kidney Disease
Authors: de la Puente-Aldea Juan , Lopez-Llanos Oscar , Horrillo Daniel , Marcos-Sanchez Hortensia , Sanz-Ballesteros Sandra , Franco Raquel , Jaisser Frederic , Senovilla Laura , Palacios-Ramirez Roberto
Published: November 2024

The classical function of the mineralocorticoid receptor (MR) is to maintain electrolytic homeostasis and control extracellular volume and blood pressure. The MR is expressed in the central nervous system (CNS) and is involved in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis as well as sleep physiology, playing a role in the non-rapid eye movement (NREM) phase of sleep. Some patients with psychiatric disorders have very poor sleep quality, and a relationship between MR dysregulation and this disorder has been found in them. In addition, the MR is involved in the regulation of the renal peripheral clock. One of the most common comorbidities observed in patients with chronic kidney disease (CKD) is poor sleep quality. Patients with CKD experience sleep disturbances, including reduced sleep duration, sleep fragmentation, and insomnia. To date, no studies have specifically investigated the relationship between MR activation and CKD-associated sleep disturbances. However, in this review, we analyzed the environment that occurs in CKD and proposed two MR-related mechanisms that may be responsible for these sleep disturbances: the circadian clock disruption and the high levels of MR agonist observed in CKD.
The Role of Gut Microbiota in the Onset and Progression of Obesity and Associated Comorbidities
Authors: Enache Robert-Mihai , Profir Monica , Roşu Oana Alexandra , Creţoiu Sanda Maria , Gaspar Bogdan Severus
Published: November 2024

Obesity, a global public health problem, is constantly increasing, so the concerns in preventing and combating it are increasingly focused on the intestinal microbiota. It was found that the microbiota is different in lean people compared to obese individuals, but the exact mechanisms by which energy homeostasis is influenced are still incompletely known. Numerous studies show the involvement of certain bacterial species in promoting obesity and associated diseases such as diabetes, hypertension, cancer, etc. Our aim is to summarize the main findings regarding the influence of several factors such as lifestyle changes, including diet and bariatric surgery, on the diversity of the gut microbiota in obese individuals. The second purpose of this paper is to investigate the potential effect of various microbiota modulation techniques on ameliorating obesity and its comorbidities. A literature search was conducted using the PubMed database, identifying articles published between 2019 and 2024. Most studies identified suggest that obesity is generally associated with alterations of the gut microbiome such as decreased microbial diversity, an increased Firmicutes-to-Bacteroidetes ratio, and increased SCFAs levels. Our findings also indicate that gut microbiota modulation techniques could represent a novel strategy in treating obesity and related metabolic diseases. Although some mechanisms (e.g., inflammation or hormonal regulation) are already considered a powerful connection between gut microbiota and obesity development, further research is needed to enhance the knowledge on this particular topic.
Stereoview Images of Hydrogen-Bonded Quinoxalines with a Helical Axis; Pyrimidines and a Pyridazine That Form Extended Tapes
Authors: Plater Michael John , Harrison William T. A.
Published: November 2024

Different supramolecular motifs are formed by the crystallisation of amino-substituted derivatives of quinoxaline, pyrimidine and pyridazine. These were made from the corresponding mono- or dichlorinated heterocycles by a nucleophilic displacement reaction. The pyridine-type nitrogen atoms activate the chlorine atoms because they can stabilise a negative charge, which forms when the amine attacks the ring. One amino group can be attached under mild conditions in hot ethanol or acetonitrile, but the first then deactivates the ring so the second requires more forceful conditions using a pressure vessel at 150 °C. Butylamine is frequently used because it reduces the polarity of the product, making it easier to purify and isolate. The extended structure of the quinoxaline derivatives 16–18 show a common ‘pincer’ hydrogen-bond motif, with a quinoxaline nitrogen atom accepting two N–H···N hydrogen bonds, giving a spiral or helical axis. The chain symmetries are 41, 21 and 31, respectively, depending on the substituents. A stereoview of each is shown. The pyrimidine derivatives 19, 12, 20, 14 and 21 form hydrogen-bonded tapes and compound 20 forms inversion dimers.
Evaluation of Short-Term Stability of Different Nitazenes Psychoactive Opioids in Dried Blood Spots by Liquid Chromatography-High-Resolution Mass Spectrometry
Authors: Vitrano Alessandro , Di Giorgi Alessandro , Abbate Vincenzo , Basile Giuseppe , La Maida Nunzia , Pichini Simona , Di Trana Annagiulia
Published: November 2024

Nitazenes represent a new synthetic opioids sub-class belonging to new psychoactive substances (NPSs). Their high pharmacological potency has led to numerous intoxications and fatalities, even at minimum doses. The aim of this study was to assess the stability of four nitazenes (etazene, flunitazene, isotonitazene and protonitazene) in dried blood spot (DBS) samples at different storage temperatures (room temperature and 4 °C) and determine the optimal storage conditions. Moreover, we developed and validated a new and fast liquid chromatography–high-resolution mass spectrometry method by the optimization of chromatographic conditions with the use of a different chromatographic column and mobile phases. Two concentrations, 1 and 5 ng/mL, were chosen based on the available data on nitazenes-related intoxications and their stability was evaluated at days 0 (control), 1, 7 and 30. The results showed that all analytes at 1 ng/mL were not detectable after 30 days at room temperature; a similar pattern was observed for 1 ng/mL etazene and isotonitazene samples when stored at 4 °C, whereas flunitazene and protonitazene decreased to a mean of 66% and 69% initial concentrations, respectively, at day 30. Differently, all analytes at 5 ng/mL were quantified above 44% and 41% initial concentrations at room temperature and 4 °C, respectively, showing a higher stability. The study of nitazenes stability in DBSs represents an important tool to determine the optimal sample storage conditions, such as temperature and time between sample collection and analysis. In contrast to another study, our study showed distinct stability behaviors for every investigated analyte, which also depended on the concentration. Therefore, it is difficult to define an optimal storage condition acceptable for all nitazenes. Room temperature proved to be the best medium- and long-term storage conditions for the highest concentrations, but the stability of low levels of flunitazene and protonitazene improved at 4 °C.
Exploring Toxicity of Per- and Polyfluoroalkyl Substances (PFAS) Mixture Through ADMET and Toxicogenomic In Silico Analysis: Molecular Insights
Authors: Baralić Katarina , Petkovski Teodora , Piletić Nađa , Marić Đurđica , Buha Djordjevic Aleksandra , Antonijević Biljana , Đukić-Ćosić Danijela
Published: November 2024

This study aimed to explore the health impacts, mechanisms of toxicity, and key gene biomarkers of a mixture of the most prominent perfluoroalkyl/polyfluoroalkyl substances (PFAS) through in silico ADMET and toxicogenomic analysis. The following databases and tools were used: AdmetSAR (2.0), ADMETlab (2.0), Comparative Toxicogenomic Database, ToppGene Suite portal, Metascape (3.5), GeneMANIA server, and CytoHubba and CytoNCA Cytoscape (3.10.3) plug-ins. ADMET analysis showed that PFAS compounds pose risks of organ-specific toxicity, prolonged retention, and metabolic disruptions. Forty mutual genes were identified for all the tested PFAS. The mutual gene set was linked to disruption of lipid metabolism, particularly through nuclear receptors. The most important gene clusters identified were nuclear receptor signaling and PPAR signaling pathways, with kidney and liver diseases, diabetes, and obesity as the most significant related diseases. Phenotype data showed that PFAS compounds impact cell death, growth, inflammation, steroid biosynthesis, and thyroid hormone metabolism. Gene network analysis revealed that 52% of the 40 mutual genes showed co-expression, with co-localization as the next major interaction (18.23%). Eight key genes were extracted from the network: EHHADH, APOA2, MBL2, SULT2A1, FABP1, PPARA, PCK2, and PLIN2. These results highlight the need for further research to fully understand the health risks of PFAS mixtures.
Similarity Analysis of Computer-Generated and Commercial Libraries for Targeted Biocompatible Coded Amino Acid Replacement
Authors: Meringer Markus , Casanola-Martin Gerardo M. , Rasulev Bakhtiyor , Cleaves H. James
Published: November 2024

Many non-natural amino acids can be incorporated by biological systems into coded functional peptides and proteins. For such incorporations to be effective, they must not only be compatible with the desired function but also evade various biochemical error-checking mechanisms. The underlying molecular mechanisms are complex, and this problem has been approached previously largely by expert perception of isomer compatibility, followed by empirical study. However, the number of amino acids that might be incorporable by the biological coding machinery may be too large to survey efficiently using such an intuitive approach. We introduce here a workflow for searching real and computed non-natural amino acid libraries for biosimilar amino acids which may be incorporable into coded proteins with minimal unintended disturbance of function. This workflow was also applied to molecules which have been previously benchmarked for their compatibility with the biological translation apparatus, as well as commercial catalogs. We report the results of scoring their contents based on fingerprint similarity via Tanimoto coefficients. These similarity scoring methods reveal candidate amino acids which could be substitutable into modern proteins. Our analysis discovers some already-implemented substitutions, but also suggests many novel ones.
Control of HSV-1 Infection: Directions for the Development of CRISPR/Cas-Based Therapeutics and Diagnostics
Authors: Sosnovtseva Anastasiia O. , Demidova Natalia A. , Klimova Regina R. , Kovalev Maxim A. , Kushch Alla A. , Starodubova Elizaveta S. , Latanova Anastasia A. , Karpov Dmitry S.
Published: November 2024

It is estimated that nearly all individuals have been infected with herpesviruses, with herpes simplex virus type 1 (HSV-1) representing the most prevalent virus. In most cases, HSV-1 causes non-life-threatening skin damage in adults. However, in patients with compromised immune systems, it can cause serious diseases, including death. The situation is further complicated by the emergence of strains that are resistant to both traditional and novel antiviral drugs. It is, therefore, imperative that new methods of combating HSV-1 and other herpesviruses be developed without delay. CRISPR/Cas systems may prove an effective means of controlling herpesvirus infections. This review presents the current understanding of the underlying molecular mechanisms of HSV-1 infection and discusses four potential applications of CRISPR/Cas systems in the fight against HSV-1 infections. These include the search for viral and cellular genes that may serve as effective targets, the optimization of anti-HSV-1 activity of CRISPR/Cas systems in vivo, the development of CRISPR/Cas-based HSV-1 diagnostics, and the validation of HSV-1 drug resistance mutations.
PRITrans: A Transformer-Based Approach for the Prediction of the Effects of Missense Mutation on Protein–RNA Interactions
Authors: Ge Fang , Li Cui-Feng , Zhang Chao-Ming , Zhang Ming , Yu Dong-Jun
Published: November 2024

Protein–RNA interactions are essential to many cellular functions, and missense mutations in RNA-binding proteins can disrupt these interactions, often leading to disease. To address this, we developed PRITrans, a specialized computational method aimed at predicting the effects of missense mutations on protein–RNA interactions, which is vital for understanding disease mechanisms and advancing molecular biology research. PRITrans is a novel deep learning model designed to predict the effects of missense mutations on protein–RNA interactions, which employs a Transformer architecture enhanced with multiscale convolution modules for comprehensive feature extraction. Its primary innovation lies in integrating protein language model embeddings with a deep feature fusion strategy, effectively handling high-dimensional feature representations. By utilizing multi-layer self-attention mechanisms, PRITrans captures nuanced, high-level sequence information, while multiscale convolutions extract features across various depths, thereby enhancing predictive accuracy. Consequently, this architecture enables significant improvements in ΔΔG prediction compared to traditional approaches. We validated PRITrans using three different cross-validation strategies on two newly reconstructed mutation datasets, S315 and S630 (containing 315 forward and 315 reverse mutations). The results consistently demonstrated PRITrans’s strong performance on both datasets. PRITrans demonstrated strong predictive capability, achieving a Pearson correlation coefficient of 0.741 and a root mean square error (RMSE) of 1.168 kcal/mol on the S630 dataset. Moreover, its robust performance extended to independent test sets, achieving a Pearson correlation of 0.699 and an RMSE of 1.592 kcal/mol. These results underscore PRITrans’s potential as a powerful tool for protein-RNA interaction studies. Moreover, when tested against existing prediction methods on an independent dataset, PRITrans showed improved predictive accuracy and robustness.
Tau Isoform-Regulated Schwann Cell Proliferation and Migration Improve Peripheral Nerve Regeneration After Injury
Authors: Li Shiying , Zhang Fuqian , Wang Guifang , Liu Qianyan , Wang Xinghui , Chen Qianqian , Chu Dandan
Published: November 2024

Tau is a microtubule-associated protein that plays a vital role in the mammalian nervous system. Alternative splicing of the MAPT gene leads to the formation of tau isoforms with varying N-terminal inserts and microtubule-binding repeats. Dysregulation of tau alternative splicing has been linked to diseases in the central nervous system, but the roles of tau isoforms in the peripheral nervous system remain unclear. Here, we investigated the alternative splicing of tau exons 4A and 10 in the sciatic nerve and Schwann cells during development and following injury. We discovered that low-molecular-weight (LMW) tau, resulting from the exclusion of exon 4A, and 3R tau, generated by the exclusion of exon 10, diminishes with aging in rat sciatic nerve and Schwann cells. High-molecular-weight (HMW) tau and 3R tau increase in the adult sciatic nerve post-injury. We constructed viruses that expressed HMW−4R, LMW−4R, HMW−3R, and LMW−3R and introduced them into cultured cells or the distal part of the injured sciatic nerve to assess their effects on Schwann cell migration and proliferation. We also examined the effects of the four isoforms on axon growth and debris clearance after sciatic nerve injury. Our results demonstrated that tau isoforms inhibit Schwann cell proliferation while promoting Schwann cell migration and sciatic nerve regeneration. Specifically, the 3R−tau isoforms were more effective than the 4R−tau isoforms in promoting nerve regeneration. In conclusion, our study reveals the roles of tau isoforms in the peripheral nervous system and provides insights into the development of new therapeutic strategies for peripheral nerve injuries.
Two Novel Membranes Based on Collagen and Polyphenols for Enhanced Wound Healing
Authors: Shubina Victoria S. , Kobyakova Margarita I. , Penkov Nikita V. , Mitenko Gennady V. , Udaltsov Sergey N. , Shatalin Yuri V.
Published: November 2024

Two novel membranes based on collagen and two polyphenols, taxifolin pentaglutarate (TfG5) and a conjugate of taxifolin with glyoxylic acid (DfTf), were prepared. Fourier transform infrared spectroscopy examination confirmed the preservation of the triple helical structure of collagen. A scanning electron microscopy study showed that both materials had a porous structure. The incorporation of DfTf into the freeze-dried collagen matrix increased the aggregation of collagen fibers to a higher extent than the incorporation of TfG5, resulting in a more compact structure of the material containing DfTf. It was found that NIH/3T3 mouse fibroblasts were attached to, and relatively evenly spread out on, the surface of both newly obtained membranes. In addition, it was shown that the membranes enhanced skin wound healing in rats with a chemical burn induced by acetic acid. The treatment with the materials led to a faster reepithelization and granulation tissue formation compared with the use of other agents (collagen without polyphenols and buffer saline). It was also found that, in the wound tissue, the level of thiobarbituric acid reactive substances (TBARS) was significantly higher and the level of low-molecular-weight SH-containing compounds (RSH) was significantly lower than those in healthy skin, indicating a rise in oxidative stress at the site of injury. The treatment with collagen membranes containing polyphenols significantly decreased the TBARS level and increased the RSH level, suggesting the antioxidant/anti-inflammatory effect of the materials. The membrane containing TfG5 was more effective than other ones (the collagen membrane containing DfTf and collagen without polyphenols). On the whole, the data obtained indicate that collagen materials containing DfTf and TfG5 have potential as powerful therapeutic agents for the treatment of burn wounds.
The Influence of Environmental Exposure to Xenoestrogens on the Risk of Cancer Development
Authors: Gachowska Martyna , Dąbrowska Alicja , Wilczyński Bartosz , Kuźnicki Jacek , Sauer Natalia , Szlasa Wojciech , Kobierzycki Christopher , Łapińska Zofia , Kulbacka Julita
Published: November 2024

Xenoestrogens (XEs) are a group of exogenous substances that may interfere with the functioning of the endocrine system. They may mimic the function of estrogens, and their sources are plants, water or dust, plastic, chemical agents, and some drugs. Thus, people are highly exposed to their actions. Together with the development of industry, the number of XEs in our environment increases. They interact directly with estrogen receptors, disrupting the transmission of cellular signals. It is proven that XEs exhibit clinical application in e.g., menopause hormone therapy, but some studies observed that intense exposure to XEs leads to the progression of various cancers. Moreover, these substances exhibit the ability to cross the placental barrier, therefore, prenatal exposure may disturb fetus development. Due to the wide range of effects resulting from the biological activity of these substances, there is a need for this knowledge to be systematized. This review aims to comprehensively assess the environmental sources of XEs and their role in increasing cancer risk, focusing on current evidence of their biological and pathological impacts.
Automaticity of the Pulmonary Vein Myocardium and the Effect of Class I Antiarrhythmic Drugs
Authors: Namekata Iyuki , Seki Maika , Saito Taro , Odaka Ryosuke , Hamaguchi Shogo , Tanaka Hikaru
Published: November 2024

The pulmonary vein wall contains a myocardial layer whose ectopic automaticity is the major cause of atrial fibrillation. This review summarizes the results obtained in isolated pulmonary vein myocardium from small experimental animals, focusing on the studies with the guinea pig. The diversity in the action potential waveform reflects the difference in the repolarizing potassium channel currents involved. The diastolic depolarization, the trigger of automatic action potentials, is caused by multiple membrane currents, including the Na+-Ca2+ exchanger current and late INa. The action potential waveform and automaticity are affected differentially by α- and β-adrenoceptor stimulation. Class I antiarrhythmic drugs block the propagation of ectopic electrical activity of the pulmonary vein myocardium through blockade of the peak INa. Some of the class I antiarrhythmic drugs block the late INa and inhibit pulmonary vein automaticity. The negative inotropic and chronotropic effects of class I antiarrhythmic drugs could be largely attributed to their blocking effect on the Ca2+ channel rather than the Na+ channel. Such a comprehensive understanding of pulmonary vein automaticity and class I antiarrhythmic drugs would lead to an improvement in pharmacotherapy and the development of novel therapeutic agents for atrial fibrillation.
Organic Sunscreens and Their Products of Degradation in Biotic and Abiotic Conditions—In Silico Studies of Drug-Likeness and Human Placental Transport
Authors: Sobańska Anna W. , Banerjee Arkaprava , Roy Kunal
Published: November 2024

A total of 16 organic sunscreens and over 160 products of their degradation in biotic and abiotic conditions were investigated in the context of their safety during pregnancy. Drug-likeness and the ability of the studied compounds to be absorbed from the gastrointestinal tract and cross the human placenta were predicted in silico using the SwissADME software (for drug-likeness and oral absorption) and multiple linear regression and “ARKA” models (for placenta permeability expressed as fetus-to-mother blood concentration in the state of equilibrium), with the latter outperforming the MLR models. It was established that most of the studied compounds can be absorbed from the gastrointestinal tract. The drug-likeness of the studied compounds (expressed as a binary descriptor, Lipinski) is closely related to their ability to cross the placenta (most likely by a passive diffusion mechanism). The organic sunscreens and their degradation products are likely to cross the placenta, except for very bulky and highly lipophilic 1,3,5-triazine derivatives; an avobenzone degradation product, 1,2-bis(4-tert-butylphenyl)ethane-1,2-dione; diethylamino hydroxybenzoyl hexyl benzoate; and dimerization products of sunscreens from the 4-methoxycinnamate group.
Poly(3,4-ethylenedioxythiophene) and Poly(3-octylthiophene-2,5-diyl) Molecules as Composite Transducers in Potentiometric Sensors—Synthesis and Application
Authors: Lenar Nikola , Piech Robert , Paczosa-Bator Beata
Published: November 2024

The aim of this paper is to investigate the influence of the molecules of conducting polymers on the properties of potentiometric sensors. Two conducting polymers, poly(3-octylthiophene-2,5-diyl) and poly(3,4-ethylene-1,4-dioxythiophene), were compared in the context of the design of ion-selective electrodes. This study offers a comparison of the most popular conducting polymers in the context of the design of potentiometric sensors. Firstly, the properties of both materials, such as their microstructure, electrical performance, wettability, and thermic properties, were examined. Subsequently, conducting polymers were applied as transducer layers in potassium-selective sensors. The properties of both groups of sensors were evaluated using the potentiometry method. Research has shown that the presence of poly(3-octylthiophene-2,5-diyl) (POT) in the transducer layer makes it superhydrophobic, leading to a long lifetime of sensors. On the other hand, the addition of poly(3,4-ethylene-1,4-dioxythiophene) polystyrene sulfonate (PEDOT:PSS) allows for the enhancement of electrical capacitance parameter values, which beneficially influence the stability of the potentiometric response of sensors. Both examined conducting polymers turned out to be perfect materials for transducer layers in potentiometric sensors, each being responsible for enhancing different properties of electrodes.
The Effects of SGLT2 Inhibitors on Blood Pressure and Other Cardiometabolic Risk Factors
Authors: Katsimardou Alexandra , Theofilis Panagiotis , Vordoni Aikaterini , Doumas Michael , Kalaitzidis Rigas G.
Published: November 2024

Beyond their established hypoglycemic, cardioprotective, and nephroprotective properties, sodium–glucose cotransporters 2 (SGLT2) inhibitors exert other pleiotropic actions on blood pressure levels, body weight, and lipid metabolism. Blood pressure (BP) reduction varies based on the background history, including an effect on systolic, diastolic BP, and 24 h BP measurements. The reduction in body weight between 1 and 2 kg for the first months is caused by a reduction in visceral and subcutaneous fat due to glycosuria and loss of calories. Regarding lipid metabolism, a reduction in triglycerides and an increase in total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) have been reported, although these alterations are small and could provide additional cardiovascular protection. Various pathophysiologic mechanisms have been proposed to explain the above-mentioned pleiotropic actions of SGLT2 inhibitors. Natriuresis, osmotic diuresis, body weight reduction, amelioration of endothelial dysfunction and arterial stiffness, sympathetic tone decrease, and uric acid reduction are among those that have been suggested for BP reduction. Apart from glycosuria and calorie loss, other mechanisms seem to contribute to body weight reduction, such as the beiging of white adipose tissue, while the mechanisms involved in lipid metabolism alterations have not been clearly determined.
Enhancing Predictive Maintenance Through Detection of Unrecorded Track Work
Authors: Schatzl Jan , Gerhold Florian , Loidolt Markus , Marschnig Stefan
Published: November 2024

Predictive maintenance can help infrastructure managers to reduce costs and improve railway availability while ensuring safety. However, its accuracy depends on reliable data from various sources, especially track measurement data. When analysing track data over time, historical maintenance actions must be considered, as otherwise the interpretation of the data would be misleading. This research aims to address inconsistencies in recorded maintenance data by detecting unrecorded track works through track geometry evaluations. The main goal is to provide the foundations for accurate descriptions of track behaviour, supporting the implementation of effective predictive maintenance regimes. As part of the research, three different approaches are analysed and evaluated, whereby two of them are based on cross-sectional analyses and the third one detects track works in longitudinal track dimension. The results show that the CRAB algorithm produces the most statistically significant results. Conversely, the cumulative track geometry-based algorithm provides a homogeneous representation of past maintenance work and a result that is statistically only marginally inferior. Consequently, these two methods are best suited to build the foundation for making accurate cross-sectional conclusions about track geometry behaviour. This allows for the verification and enhancement of existing maintenance databases.
Machine-Based Resistance Training Improves Functional Capacity in Older Adults: A Systematic Review and Meta-Analysis
Authors: Kirk Archie , Steele James , Fisher James P.
Published: November 2024

Background/Objectives: Resistance training (RT) can improve the functional performance of older adults, maintaining independence and quality of life. It has been proposed that training interventions should implement exercises associated with the movements needed in everyday life. However, this strength training philosophy presents challenges, specifically to older adults, and the use of resistance machines might present an efficacious alternative. The aim of this systematic review and meta-analysis was to explore the impact of machine-based RT on strength and functional capacity in older adults. Methods: The inclusion criteria were for strength training interventions to be a minimum of 6 weeks, using only resistance machines, with pre- and post-intervention measurements of functional capacity of either a timed up-and-go and/or a sit-to-stand test, and including healthy older adults (>60 years). Results: Following the screening, 17 articles met the inclusion criteria for the systematic review, 15 of which were included in the meta-analysis for functional outcomes (n = 614 participants), and 11 of which were included in the meta-analysis for strength outcomes (n = 511 participants). Analyses revealed significant standardized mean change in favor of machine-based RT for functional outcomes (0.72, 95% CIs 0.39 to 1.07) and strength outcomes (0.71, 95% CIs 0.34 to 1.08) compared to control conditions (functional = 0.09, 95% CIs − 0.1 to 0.28, strength = 0.1, 95% CIs − 0.05 to 0.24). Substantial heterogeneity was noted in the manipulation of RT variables and the magnitude of effects between studies. Conclusions: The data presented support the idea that significant strength and functional performance outcomes are attainable using uncomplicated, machine-based RT.
Spatially Localized Visual Perception Estimation by Means of Prosthetic Vision Simulation
Authors: Villarreal Diego Luján , Krautschneider Wolfgang
Published: November 2024

Retinal prosthetic devices aim to repair some vision in visually impaired patients by electrically stimulating neural cells in the visual system. Although there have been several notable advancements in the creation of electrically stimulated small dot-like perceptions, a deeper comprehension of the physical properties of phosphenes is still necessary. This study analyzes the influence of two independent electrode array topologies to achieve single-localized stimulation while the retina is electrically stimulated: a two-dimensional (2D) hexagon-shaped array reported in clinical studies and a patented three-dimensional (3D) linear electrode carrier. For both, cell stimulation is verified in COMSOL Multiphysics by developing a lifelike 3D computational model that includes the relevant retinal interface elements and dynamics of the voltage-gated ionic channels. The evoked percepts previously described in clinical studies using the 2D array are strongly associated with our simulation-based findings, allowing for the development of analytical models of the evoked percepts. Moreover, our findings identify differences between visual sensations induced by the arrays. The 2D array showed drawbacks during stimulation; similarly, the state-of-the-art 2D visual prostheses provide only dot-like visual sensations in close proximity to the electrode. The 3D design could offer a technique for improving cell selectivity because it requires low-intensity threshold activation which results in volumes of stimulation similar to the volume surrounded by a solitary RGC. Our research establishes a proof-of-concept technique for determining the utility of the 3D electrode array for selectively activating individual RGCs at the highest density via small-sized electrodes while maintaining electrochemical safety.
Understanding Consumption Reduction Through the TPB: Moderating Effects of the Need for Evaluation and Self-Referencing Individual Differences
Authors: Ghorban Nejad Shiva , Skeiseid Heidi Victoria , Derdowski Lukasz Andrzej
Published: November 2024

Limited research has focused on consumption reduction as one potential pathway to meet sustainable development goals. This paper investigates consumers’ intentions to undertake consumption reduction through the lens of an extended theory of planned behavior (TPB), where selected individual differences, namely the need for evaluation (NE) and self-referencing (SR), are given considerable attention. In total, 226 respondents participated in this web-based survey study. The results from structural equation modeling analysis confirm that the extended theory of planned behavior effectively explains consumers’ intentions to undertake consumption reduction. Notably, the individual differences of the NE and SR each uniquely moderate the relationships within the TPB model. This study provides a theoretical contribution by integrating the selected moderators (i.e., the NE and SR) into the TPB framework, increases the TPB’s predictive power, and further provides a novel understanding of the underlying influences of individual differences on consumers’ intentions to undertake consumption reduction for the benefit of the environment. Moreover, the findings offer practical implications for policymakers and social marketers in designing tailor-made interventions and consumption reduction strategies by considering the important role of individual differences.
Numerical Study of the Nonlinear Soil–Pile–Structure Interaction Effects on the Lateral Response of Marine Jetties
Authors: Koronides Marios , Michailides Constantine , Stylianidis Panagiotis , Onoufriou Toula
Published: November 2024

This study presents three-dimensional finite element analyses of two marine structures subjected to lateral loading to approximate environmental forces (e.g., wind, waves, currents, earthquakes). The first structure is a marine jetty supported by twenty-four piles, representative of an existing structure in Cyprus, while the second is a simplified four-pile marine structure. Soil–pile interaction is modelled using nonlinear p-y, τ-z, and q-z springs that are distributed along the piles, while steel plasticity is also considered. This study examines the relationship between failure modes, deformation modes, and plastic hinge locations with soil behaviour and soil reaction forces. It also aims at investigating the behaviour of the above structures in lateral loading and quantifying the consequences of unrealistic assumptions such as soil and steel linearity or tension-resistant q-z springs. The results indicate that such assumptions can lead to the wrong prediction of failure modes, plastic hinges, and critical elements while emphasising the crucial role of soil nonlinearity and axial pile–soil behaviour on the structural response. It is demonstrated that the dominant nonlinear sources relevant to this study, whether soil nonlinearity, plastic hinge formation, or a combination of the two, are primarily influenced by the axial capacity of soil–pile foundation systems, particularly their tensile component.
Cross-Granularity Infrared Image Segmentation Network for Nighttime Marine Observations
Authors: Xu Hu , Yu Yang , Zhang Xiaomin , He Ju
Published: November 2024

Infrared image segmentation in marine environments is crucial for enhancing nighttime observations and ensuring maritime safety. While recent advancements in deep learning have significantly improved segmentation accuracy, challenges remain due to nighttime marine scenes including low contrast and noise backgrounds. This paper introduces a cross-granularity infrared image segmentation network CGSegNet designed to address these challenges specifically for infrared images. The proposed method designs a hybrid feature framework with cross-granularity to enhance segmentation performance in complex water surface scenarios. To suppress feature semantic disparity against different feature granularity, we propose an adaptive multi-scale fusion module (AMF) that combines local granularity extraction with global context granularity. Additionally, incorporating a handcrafted histogram of oriented gradients (HOG) features, we designed a novel HOG feature fusion module to improve edge detection accuracy under low-contrast conditions. Comprehensive experiments conducted on the public infrared segmentation dataset demonstrate that our method outperforms state-of-the-art techniques, achieving superior segmentation results compared to professional infrared image segmentation methods. The results highlight the potential of our approach in facilitating accurate infrared image segmentation for nighttime marine observation, with implications for maritime safety and environmental monitoring.
Limits in the Perception of Facial Symmetry—A Prospective Study
Authors: Eißing Friederike Lisa , Dirksen Dieter , Runte Christoph , Jung Susanne
Published: November 2024

Objectives: It is generally accepted that the symmetry of the face plays a significant role in the visual perception of its attractiveness. Therefore, its objective assessment could be useful for individual therapy planning. However, there is an ongoing debate about whether completely symmetrical faces are less attractive than those with minor deviations. The aim of this study is to find thresholds of symmetry perception among faces with an increased spectrum of asymmetry values. Methods: The faces of 50 persons (25 men, 25 women) were digitized using a 3D scanner based on the fringe projection technique, and asymmetry values were calculated. In order to achieve a larger spectrum of asymmetry values, some of the surfaces were symmetrized or the symmetry was reduced. Afterward, an independent second group of 50 persons (13 medical professionals, 37 laypersons) rated “symmetry”, “attractiveness” and “health” using a visual analog scale (VAS). Results: Symmetry ratings and asymmetry value had a strong and monotonically decreasing association (rho = −0.78, p ˂ 0.001). Manipulated or naturally asymmetrical faces (n = 12) could not be well distinguished with regard to their symmetry (rho = −0.14, p = 0.67). The same applies to very symmetrical or symmetrized faces (n = 10, rho = −0.14, p = 0.67). Medical professionals rated the symmetry (p ˂ 0.001) and attractiveness (p ˂ 0.001) significantly higher than laypersons, while there was no significant difference in the health assessment (p = 0.24). Conclusions: It could be shown that there are indications of threshold values in the perception of facial symmetries, both in the direction of very symmetrical faces and in the direction of asymmetrical faces. There is no evidence that completely symmetrical faces are perceived as less attractive. Thus, in maxillofacial surgery, treatment should aim for the highest symmetry possible, although small deviations are not detrimental.
Planting Ages Inhibited Soil Respiration and CO2-C Emissions Attribute to Soil Degradation in Gravel-Mulched Land in Arid Areas
Authors: Wang Bingyao , Li Yunfei , Liu Zhixian , Wang Peiyuan , Wang Zhanjun , Wu Xudong , Gao Yongping , Liu Lichao , Yang Haotian
Published: November 2024

Gravel mulching is a widely employed strategy for water conservation in arid agricultural regions, with potential implications for soil carbon (C) sequestration and greenhouse gas emissions. However, soil respiration and CO2-C emissions remain uncertain owing to less consideration of the influence of precipitation patterns and planting age. In this study, we investigated the soil respiration rate (Rsoil) and cumulative CO2-C emission (Ccum), both measured over a period of 72 h, along with soil properties and enzyme activities under different precipitation conditions based on gravel mulching with different planting ages. We analyzed the effects of planting ages on Rsoil and Ccum and revealed the underlying mechanisms driving changes in environmental factors on Rsoil and Ccum. The results demonstrated that the Rsoil reached the maximum value at about 1 h, 0.5 h, and 0.25 h after rewetting in 1, 10, and 20 years of gravel mulching under the condition with 1 mm, 5 mm, and 10 mm of precipitation, respectively, whereas the Rsoil exhibited its maximum at about 8 h after soil rewetting under precipitation of 30 mm. The Ccum induced by precipitation pulses tends to decrease with increasing years of gravel mulching. The Ccum was 0.0061 t ha−1 in the 20-year gravel-mulched soil, representing a 53.79% reduction compared to the 1-year gravel-mulched soil. Soil organic matter (SOM), planting ages, and alkaline phosphatase (ALP) were the primary factors influencing the Rsoil and Ccum in 0–20 cm, while SOM, planting ages, and soil porosity (AirP) were the key factors affecting the Rsoil and Ccum in 20–40 cm. The Rsoil and Ccum in the 0–20 cm soil were regulated by soil enzyme activities, while those of 20–40 cm soil were controlled by soil properties. This indicates that the decrease in Rsoil and Ccum is caused by soil degradation, characterized by a decrease in SOM and ALP. This study offers a novel insight into the long-term environmental impact of gravel mulching measures in arid areas, which is helpful in providing a theoretical basis for dryland agricultural management. It is imperative to consider the duration of gravel mulching when predicting the potential for C sequestration in arid agricultural areas.