bluuebunny/crossref_metadata_2025 huggingface dataset:
Emotional and Psychological Safety in Healthcare Digitalization: A Design Ethnographic Study
Authors: Vöcking Mara , Karrenbrock Anne , Beckmann Andreas , Vondeberg Carmen , Obert Laura , Hemming Bernhard , Minartz Peter , Bleck Christian , Cürlis Diana , Kuske Silke
Published: September 2024

Objectives

Emotional and psychological safety is important during the use of digital technologies in healthcare. We aimed to gain comprehensive insight into needs, influencing factors and outcomes in the context of perceived safety and digital technologies in healthcare.

Methods

We employed a participatory, design ethnographic research approach with 16 participants in 10 use cases. The methods included in an iterative process were, think-aloud, guideline-based interviews, process mapping, storyboard creation, and photo documentation. A qualitative, primarily inductive data analysis and synthesis was performed.

Results

Perceived safety is influenced by various factors and unmet needs. Increased perceived safety can positively support the use of digital technologies, whereas low perceived safety can limit or even hinder its use.

Conclusion

The needs of the different target groups should be considered throughout the entire process of digital technology development and healthcare provision to support their implementation. These findings support further research by providing specific aspects of emotional and psychological safety regarding target groups, settings, and ages and those with different levels of affinity for digital technologies.
Artificial Intelligence—What to Expect From Machine Learning and Deep Learning in Hernia Surgery
Authors: Vogel Robert , Mück Björn
Published: September 2024

This mini-review explores the integration of Artificial Intelligence (AI) within hernia surgery, highlighting the role of Machine Learning (ML) and Deep Learning (DL). The term AI incorporates various technologies including ML, Neural Networks (NN), and DL. Classical ML algorithms depend on structured, labeled data for predictions, requiring significant human oversight. In contrast, DL, a subset of ML, generally leverages unlabeled, raw data such as images and videos to autonomously identify patterns and make intricate deductions. This process is enabled by neural networks used in DL, where hidden layers between the input and output capture complex data patterns. These layers’ configuration and weighting are pivotal in developing effective models for various applications, such as image and speech recognition, natural language processing, and more specifically, surgical procedures and outcomes in hernia surgery. Significant advancements have been achieved with DL models in surgical settings, particularly in predicting the complexity of abdominal wall reconstruction (AWR) and other postoperative outcomes, which are elaborated in detail within the context of this mini-review. The review method involved analyzing relevant literature from databases such as PubMed and Google Scholar, focusing on studies related to preoperative planning, intraoperative techniques, and postoperative management within hernia surgery. Only recent, peer-reviewed publications in English that directly relate to the topic were included, highlighting the latest advancements in the field to depict potential benefits and current limitations of AI technologies in hernia surgery, advocating for further research and application in this evolving field.
May Small Airways Dysfunction (SAD) Play a Role in the Idiopathic Pulmonary Fibrosis (IPF) and May SAD Be a Therapeutic Target?
Authors: Ziora Dariusz
Published: September 2024

Small airway dysfunction (SAD) is a pathological process that affects the bronchioles and non-cartilaginous airways below 2 mm in diameter. This short review presents a link between SAD and IPF. Pathomorphological changes of small airways in fibrotic lungs are discussed. Additionally, functional abnormalities related to SAD measured by spirometry and oscillometry are presented. The problem of early detection and treatment of SAD as a procedure potentially capable of mitigating fibrosis is mentioned.
A Deep Reinforcement Learning Optimization Method Considering Network Node Failures
Authors: Ding Xueying , Liao Xiao , Cui Wei , Meng Xiangliang , Liu Ruosong , Ye Qingshan , Li Donghe
Published: September 2024

Nowadays, the microgrid system is characterized by a diversification of power factors and a complex network structure. Existing studies on microgrid fault diagnosis and troubleshooting mostly focus on the fault detection and operation optimization of a single power device. However, for increasingly complex microgrid systems, it becomes increasingly challenging to effectively contain faults within a specific spatiotemporal range. This can lead to the spread of power faults, posing great harm to the safety of the microgrid. The topology optimization of the microgrid based on deep reinforcement learning proposed in this paper starts from the overall power grid and aims to minimize the overall failure rate of the microgrid by optimizing the topology of the power grid. This approach can limit internal faults within a small range, greatly improving the safety and reliability of microgrid operation. The method proposed in this paper can optimize the network topology for the single node fault and multi-node fault, reducing the influence range of the node fault by 21% and 58%, respectively.
Recent Advances in Numerical Simulation of Ejector Pumps for Vacuum Generation—A Review
Authors: Sadeghiseraji Jaber , Garcia-Vilchez Mercè , Castilla Robert , Raush Gustavo
Published: September 2024

This review paper provides an overview of recent advances in computational fluid dynamics (CFD) simulations of ejector pumps for vacuum generation. It examines various turbulence models, multiphase flow approaches, and numerical techniques employed to capture complex flow phenomena like shock waves, mixing, phase transitions, and heat/mass transfer. Emphasis is placed on the comprehensive assessment of flow characteristics within ejectors, including condensation effects such as nucleation, droplet growth, and non-equilibrium conditions. This review highlights efforts in optimizing ejector geometries and operating parameters to enhance the entrainment ratio, a crucial performance metric for ejectors. The studies reviewed encompass diverse working fluids, flow regimes, and geometric configurations, underscoring the significance of ejector technology across various industries. While substantial progress has been made in developing advanced simulation techniques, several challenges persist, including accurate modeling of real gas behavior, phase change kinetics, and coupled heat/mass transfer phenomena. Future research efforts should focus on developing robust multiphase models, implementing advanced turbulence modeling techniques, integrating machine learning-based optimization methods, and exploring novel ejector configurations for emerging applications.
Consensus-Based Model Predictive Control for Active Power and Voltage Regulation in Active Distribution Networks
Authors: Antonelli Gianluca , Fusco Giuseppe , Russo Mario
Published: September 2024

In this paper, a consensus-based model predictive control (Cb-MPC) scheme is proposed to control the active power and voltage at all nodes in grid-connected active distribution networks (ADNs) with multiple distributed energy resources (DERs). The proposed design methodology is based on a multiple-input multiple-output (MIMO) model of an ADN which accounts for both the internal and external interactions among the control loops of the DERs. To achieve the control objective, each DER unit is equipped with a controller–observer system. In particular, the observer implements the consensus algorithm to estimate the collective system state by exchanging data only with its neighbors. The scope of the controller is to solve the MPC optimal problem based on its collective state estimate, and, due to the presence of an integral term in the control action, it is robust against any unknown scenarios of the ADN, which are represented by uncertainty in the model parameters. The results of numerical simulations validate the effectiveness of the proposed method in the presence of unknown changes in the operating conditions of the ADN and of communication using a sample and hold function.
Comprehensive Investigation of the Thermal Performance of an Electrically Heated Double-Glazed Window: A Theoretical and Experimental Approach
Authors: Basok Borys , Pavlenko Anatoliy , Novikov Volodymyr , Koshlak Hanna , Ciosek Anita , Moroz Maryna
Published: September 2024

The thermal performance of windows is an important area of research to reduce the energy consumption of buildings and improve indoor comfort. The application of innovative glazing technologies can improve the energy performance of windows and transparent facades, resulting in significant energy savings. This paper presents research results on the energy performance of electrically heated windows. A comprehensive CFD and experimental analysis of the heat transfer processes in a window space depending on the size, power, and location of an electric heater was performed. The convective gas flows in the gas gaps and in the boundary layer were also analysed, and it is shown that a window with an electric heater can reduce the energy consumption of a room by 10–12%. This study is a pilot study to assess the feasibility and cost-effectiveness of electric local heating of a window or facade to minimise heat loss before full-scale implementation. The results of numerical modelling and experimental studies confirm the potential of the new technologies.
The Ubiquitination of Arrestin3 within the Nucleus Triggers the Nuclear Export of Mdm2, Which, in Turn, Mediates the Ubiquitination of GRK2 in the Cytosol
Authors: Kundu Dooti , Min Xiao , Zhang Xiaohan , Tian Xinru , Wang Shujie , Kim Kyeong-Man
Published: September 2024

GRK2 and arrestin3, key players in the functional regulation of G protein-coupled receptors (GPCRs), are ubiquitinated by Mdm2, a nuclear protein. The agonist-induced increase in arrestin3 ubiquitination occurs in the nucleus, underscoring the crucial role of its nuclear translocation in this process. The ubiquitination of arrestin3 occurs in the nucleus, highlighting the pivotal role of its nuclear translocation in this process. In contrast, GRK2 cannot translocate into the nucleus; thus, facilitation of the cytosolic translocation of nuclear Mdm2 is required to ubiquitinate GRK2 in the cytosol. Among the explored cellular components and processes, arrestin, Gβγ, clathrin, and receptor phosphorylation were found to be required for the nuclear import of arrestin3, the ubiquitination of arrestin3 in the nucleus, nuclear export of Mdm2, and the ubiquitination of GRK2 in the cytosol. In conclusion, our findings demonstrate that agonist-induced ubiquitination of arrestin3 in the nucleus is interconnected with cytosolic GRK2 ubiquitination.
Peptides Evaluated In Silico, In Vitro, and In Vivo as Therapeutic Tools for Obesity: A Systematic Review
Authors: Aguiar Ana Júlia Felipe Camelo , de Medeiros Wendjilla Fortunato , da Silva-Maia Juliana Kelly , Bezerra Ingrid Wilza Leal , Piuvezam Grasiela , Morais Ana Heloneida de Araújo
Published: September 2024

Bioinformatics has emerged as a valuable tool for screening drugs and understanding their effects. This systematic review aimed to evaluate whether in silico studies using anti-obesity peptides targeting therapeutic pathways for obesity, when subsequently evaluated in vitro and in vivo, demonstrated effects consistent with those predicted in the computational analysis. The review was framed by the question: “What peptides or proteins have been used to treat obesity in in silico studies?” and structured according to the acronym PECo. The systematic review protocol was developed and registered in PROSPERO (CRD42022355540) in accordance with the PRISMA-P, and all stages of the review adhered to these guidelines. Studies were sourced from the following databases: PubMed, ScienceDirect, Scopus, Web of Science, Virtual Heath Library, and EMBASE. The search strategies resulted in 1015 articles, of which, based on the exclusion and inclusion criteria, 7 were included in this systematic review. The anti-obesity peptides identified originated from various sources including bovine alpha-lactalbumin from cocoa seed (Theobroma cacao L.), chia seed (Salvia hispanica L.), rice bran (Oryza sativa), sesame (Sesamum indicum L.), sea buckthorn seed flour (Hippophae rhamnoides), and adzuki beans (Vigna angularis). All articles underwent in vitro and in vivo reassessment and used molecular docking methodology in their in silico studies. Among the studies included in the review, 46.15% were classified as having an “uncertain risk of bias” in six of the thirteen criteria evaluated. The primary target investigated was pancreatic lipase (n = 5), with all peptides targeting this enzyme demonstrating inhibition, a finding supported both in vitro and in vivo. Additionally, other peptides were identified as PPARγ and PPARα agonists (n = 2). Notably, all peptides exhibited different mechanisms of action in lipid metabolism and adipogenesis. The findings of this systematic review underscore the effectiveness of computational simulation as a screening tool, providing crucial insights and guiding in vitro and in vivo investigations for the discovery of novel anti-obesity peptides.
Cardiotoxicity of Iron and Zinc and Their Association with the Mitochondrial Unfolded Protein Response in Humans
Authors: Mirosevic Vid , Svagusa Tomo , Matic Natalija , Maldini Kresimir , Siljeg Mario , Milicic Davor , Gasparovic Hrvoje , Rudez Igor , Sepac Ana , Gojmerac Lucija , Kulic Ana , Bakovic Petra , Sedlic Filip
Published: September 2024

This study was designed to examine the association between myocardial concentrations of the trace elements Cu, Fe, Mn, Mo, and Zn and the expression of mitochondrial unfolded protein response (UPRmt) elements and the age of patients who received heart transplantation or a left-ventricular assist device (ageHTx/LVAD). Inductively coupled plasma mass spectrometry was used to determine the concentration of Cu, Fe, Mn, Mo, and Zn in the myocardium of control subjects and patients undergoing heart transplantation or left-ventricular assist device (LVAD) implantation. We used ELISA to quantify the expression of UPRmt proteins and 4-Hydroxynonenal (4-HNE), which served as a marker of oxidative-stress-induced lipid peroxidation. Concentrations of Cu, Mn, Mo, and Zn were similar in the control and heart failure (HF) myocardium, while Fe showed a significant decrease in the HF group compared to the control. A higher cumulative concentration of Fe and Zn in the myocardium was associated with reduced ageHTx/LVAD, which was not observed for other combinations of trace elements or their individual effects. The trace elements Cu, Mn, and Zn showed positive correlations with several UPRmt proteins, while Fe had a negative correlation with UPRmt effector protease YME1L. None of the trace elements correlated with 4-HNE in the myocardium. The concentrations of the trace elements Mn and Zn were significantly higher in the myocardium of patients with dilated cardiomyopathy than in patients with ischemic cardiomyopathy. A higher cumulative concentration of Fe and Zn in the myocardium was associated with a younger age at which patients received heart transplantation or LVAD, potentially suggesting an acceleration of HF. A positive correlation between myocardial Cu, Mn, and Zn and the expression of UPRmt proteins and a negative correlation between myocardial Fe and YME1L expression suggest that these trace elements exerted their actions on the human heart by interacting with the UPRmt. An altered generation of oxidative stress was not an underlying mechanism of the observed changes.
C-C Chemokine Receptor 7 Promotes T-Cell Acute Lymphoblastic Leukemia Invasion of the Central Nervous System via β2-Integrins
Authors: Cardona Cesar I. , Rodriguez Alondra , Torres Vivian C. , Sanchez Anahi , Torres Angel , Vazquez Aaron E. , Wagler Amy E. , Brissette Michael A. , Bill Colin A. , Vines Charlotte M.
Published: September 2024

C-C Chemokine Receptor 7 (CCR7) mediates T-cell acute lymphoblastic leukemia (T-ALL) invasion of the central nervous system (CNS) mediated by chemotactic migration to C-C chemokine ligand 19 (CCL19). To determine if a CCL19 antagonist, CCL198-83, could inhibit CCR7-induced chemotaxis and signaling via CCL19 but not CCL21, we used transwell migration and Ca2+ mobilization signaling assays. We found that in response to CCL19, human T-ALL cells employ β2 integrins to invade human brain microvascular endothelial cell monolayers. In vivo, using an inducible mouse model of T-ALL, we found that we were able to increase the survival of the mice treated with CCL198-83 when compared to non-treated controls. Overall, our results describe a targetable cell surface receptor, CCR7, which can be inhibited to prevent β2-integrin-mediated T-ALL invasion of the CNS and potentially provides a platform for the pharmacological inhibition of T-ALL cell entry into the CNS.
Correlation of Solvent Interaction Analysis Signatures with Thermodynamic Properties and In Silico Calculations of the Structural Effects of Point Mutations in Two Proteins
Authors: Titus Amber R. , Madeira Pedro P. , Uversky Vladimir N. , Zaslavsky Boris Y.
Published: September 2024

The partition behavior of single and double-point mutants of bacteriophage T4 lysozyme (T4 lysozyme) and staphylococcal nuclease A was examined in different aqueous two-phase systems (ATPSs) and studied by Solvent Interaction Analysis (SIA). Additionally, the solvent accessible surface area (SASA) of modeled mutants of both proteins was calculated. The in silico calculations and the in vitro analyses of the staphylococcal nuclease and T4 lysozyme mutants correlate, indicating that the partition analysis in ATPSs provides a valid descriptor (SIA signature) covering various protein features, such as structure, structural dynamics, and conformational stability.
From iPSCs to Pancreatic β Cells: Unveiling Molecular Pathways and Enhancements with Vitamin C and Retinoic Acid in Diabetes Research
Authors: Arroyave Felipe , Uscátegui Yomaira , Lizcano Fernando
Published: September 2024

Diabetes mellitus, a chronic and non-transmissible disease, triggers a wide range of micro- and macrovascular complications. The differentiation of pancreatic β-like cells (PβLCs) from induced pluripotent stem cells (iPSCs) offers a promising avenue for regenerative medicine aimed at treating diabetes. Current differentiation protocols strive to emulate pancreatic embryonic development by utilizing cytokines and small molecules at specific doses to activate and inhibit distinct molecular signaling pathways, directing the differentiation of iPSCs into pancreatic β cells. Despite significant progress and improved protocols, the full spectrum of molecular signaling pathways governing pancreatic development and the physiological characteristics of the differentiated cells are not yet fully understood. Here, we report a specific combination of cofactors and small molecules that successfully differentiate iPSCs into PβLCs. Our protocol has shown to be effective, with the resulting cells exhibiting key functional properties of pancreatic β cells, including the expression of crucial molecular markers (pdx1, nkx6.1, ngn3) and the capability to secrete insulin in response to glucose. Furthermore, the addition of vitamin C and retinoic acid in the final stages of differentiation led to the overexpression of specific β cell genes.
Clerodendranthus spicatus (Thunb.) Water Extracts Reduce Lipid Accumulation and Oxidative Stress in the Caenorhabditis elegans
Authors: Xiao Xian , Wu Fanhua , Wang Bing , Cai Zeping , Wang Lanying , Zhang Yunfei , Yu Xudong , Luo Yanping
Published: September 2024

Clerodendranthus spicatus (Thunb.) (Kidney tea) is a very distinctive ethnic herbal medicine in China. Its leaves are widely used as a healthy tea. Many previous studies have demonstrated its various longevity-promoting effects; however, the safety and specific health-promoting effects of Clerodendranthus spicatus (C. spicatus) as a dietary supplement remain unclear. In order to understand the effect of C. spicatus on the longevity of Caenorhabditis elegans (C. elegans), we evaluated its role in C. elegans; C. spicatus water extracts (CSw) were analyzed for the major components and the effects on C. elegans were investigated from physiological and biochemical to molecular levels; CSw contain significant phenolic components (primarily rosmarinic acid and eugenolinic acid) and flavonoids (primarily quercetin and isorhamnetin) and can increase the lifespan of C. elegans. Further investigations showed that CSw modulate stress resistance and lipid metabolism through influencing DAF-16/FoxO (DAF-16), Heat shock factor 1 (HSF-1), and Nuclear Hormone Receptor-49 (NHR-49) signalling pathways; CSw can improve the antioxidant and hypolipidemic activity of C. elegans and prolong the lifespan of C. elegans (with the best effect at low concentrations). Therefore, the recommended daily use of C. spicatus should be considered when consuming it as a healthy tea on a daily basis.
VCD Analysis of Axial Chirality in Synthetic Stereoisomeric Biaryl-Type bis-Isochroman Heterodimers with Isolated Blocks of Central and Axial Chirality
Authors: Czenke Zoltán , Mándi Attila , Király Sándor Balázs , Kiss-Szikszai Attila , Kónya-Ábrahám Anita , Kurucz-Szabados Anna , Cserepes Krisztián , Bényei Attila , Zhang Changsheng , Kicsák Máté , Kurtán Tibor
Published: September 2024

Optically active heterodimeric 5,5′-linked bis-isochromans, containing a stereogenic ortho-trisubstituted biaryl axis and up to four chirality centers, were synthesized stereoselectively by using a Suzuki–Miyaura biaryl coupling reaction of optically active isochroman and 1-arylpropan-2-ol derivatives, providing the first access to synthetic biaryl-type isochroman dimers. Enantiomeric pairs and stereoisomers up to seven derivatives were prepared with four different substitution patterns, which enabled us to test how OR, ECD, and VCD measurements and DFT calculations can be used to determine parallel central and axial chirality elements in three isolated blocks of chirality. In contrast to natural penicisteckins A–D and related biaryls, the ECD spectra and OR data of (aS) and (aR) atropodiastereomers did not reflect the opposite axial chirality, but they were characteristic of the central chirality. The atropodiastereomers showed consistently near-mirror-image VCD curves, allowing the determination of axial chirality with the aid of DFT calculation or by comparison of characteristic VCD transitions.
Exploring the Rhizospheric Microbial Communities under Long-Term Precipitation Regime in Norway Spruce Seed Orchard
Authors: Zádrapová Dagmar , Chakraborty Amrita , Žáček Petr , Korecký Jiří , Bhar Anirban , Roy Amit
Published: September 2024

The rhizosphere is the hotspot for microbial enzyme activities and contributes to carbon cycling. Precipitation is an important component of global climate change that can profoundly alter belowground microbial communities. However, the impact of precipitation on conifer rhizospheric microbial populations has not been investigated in detail. In the present study, using high-throughput amplicon sequencing, we investigated the impact of precipitation on the rhizospheric soil microbial communities in two Norway Spruce clonal seed orchards, Lipová Lhota (L-site) and Prenet (P-site). P-site has received nearly double the precipitation than L-site for the last three decades. P-site documented higher soil water content with a significantly higher abundance of Aluminium (Al), Iron (Fe), Phosphorous (P), and Sulphur (S) than L-site. Rhizospheric soil metabolite profiling revealed an increased abundance of acids, carbohydrates, fatty acids, and alcohols in P-site. There was variance in the relative abundance of distinct microbiomes between the sites. A higher abundance of Proteobacteria, Acidobacteriota, Ascomycota, and Mortiellomycota was observed in P-site receiving high precipitation, while Bacteroidota, Actinobacteria, Chloroflexi, Firmicutes, Gemmatimonadota, and Basidiomycota were prevalent in L-site. The higher clustering coefficient of the microbial network in P-site suggested that the microbial community structure is highly interconnected and tends to cluster closely. The current study unveils the impact of precipitation variations on the spruce rhizospheric microbial association and opens new avenues for understanding the impact of global change on conifer rizospheric microbial associations.
Identification and Analysis of Aluminum-Activated Malate Transporter Gene Family Reveals Functional Diversification in Orchidaceae and the Expression Patterns of Dendrobium catenatum Aluminum-Activated Malate Transporters
Authors: Peng Fu-Cheng , Yuan Meng , Zhou Lin , Zheng Bao-Qiang , Wang Yan
Published: September 2024

Aluminum-activated malate transporter (ALMT) genes play an important role in aluminum ion (Al3+) tolerance, fruit acidity, and stomatal movement. Although decades of research have been carried out in many plants, there is little knowledge about the roles of ALMT in Orchidaceae. In this study, 34 ALMT genes were identified in the genomes of four orchid species. Specifically, ten ALMT genes were found in Dendrobium chrysotoxum and D. catenatum, and seven were found in Apostasia shenzhenica and Phalaenopsis equestris. These ALMT genes were further categorized into four clades (clades 1–4) based on phylogenetic relationships. Sequence alignment and conserved motif analysis revealed that most orchid ALMT proteins contain conserved regions (TM1, GABA binding motif, and WEP motif). We also discovered a unique motif (19) belonging to clade 1, which can serve as a specifically identified characteristic. Comparison with the gene structure of AtALMT genes (Arabidopsis thaliana) showed that the gene structure of ALMT was conserved across species, but the introns were longer in orchids. The promoters of orchid ALMT genes contain many light-responsive and hormone-responsive elements, suggesting that their expression may be regulated by light and phytohormones. Chromosomal localization and collinear analysis of D. chrysotoxum indicated that tandem duplication (TD) is the main reason for the difference in the number of ALMT genes in these orchids. D. catenatum was chosen for the RT-qPCR experiment, and the results showed that the DcaALMT gene expression pattern varied in different tissues. The expression of DcaALMT1-9 was significantly changed after ABA treatment. Combining the circadian CO2 uptake rate, titratable total acid, and RT-qPCR data analysis, most DcaALMT genes were highly expressed at night and around dawn. The result revealed that DcaALMT genes might be involved in photosynthate accumulation. The above study provides more comprehensive information for the ALMT gene family in Orchidaceae and a basis for subsequent functional analysis.
Association between Serum Glycated Hemoglobin Levels and Female Infertility: A Cross-Sectional Survey and Genetic Approach
Authors: Liao Chung-Chih , Lee Chun-I , Liao Ke-Ru , Li Jung-Miao
Published: September 2024

Female infertility affects a significant portion of the population, and recent studies suggest a potential link between glycemic control and reproductive health. This study investigates the association between serum glycated hemoglobin (HbA1c) levels and female infertility, utilizing data from the NHANES 2017–2020 and Mendelian randomization (MR) analysis. A cross-sectional study was conducted with 1578 women aged 20–45 who attempted pregnancy for at least one year. Serum HbA1c levels were analyzed in relation to infertility status, with multivariable logistic regression models adjusting for covariates such as age, body mass index, race/ethnicity, education, marital status, hypertension, and hyperlipidemia. Higher HbA1c levels were significantly associated with increased infertility risk. Each 1% increase in HbA1c was linked to higher odds of infertility (adjusted OR: 1.40, 95% CI: 1.15–1.69, p = 0.003). HbA1c levels ≥ 6.5% showed the strongest association. MR analysis employed single-nucleotide polymorphisms as instrumental variables to assess the causal relationship between HbA1c and infertility, confirming a causal relationship between higher genetically predicted HbA1c levels and infertility (OR: 1.82, 95% CI: 1.33–2.49, p = 0.00018). Sensitivity analyses supported the robustness of these findings. Elevated HbA1c levels are associated with an increased risk of female infertility, suggesting the importance of glycemic control in reproductive health management.
Docetaxel-Induced Cell Death Is Regulated by a Fatty Acid-Binding Protein 12-Slug-Survivin Pathway in Prostate Cancer Cells
Authors: Liu Rong-Zong , Garg Mansi , Yang Xiao-Hong , Godbout Roseline
Published: September 2024

Chemotherapy is an important treatment option for advanced prostate cancer, especially for metastatic prostate cancer (PCa). Resistance to first-line chemotherapeutic drugs such as docetaxel often accompanies prostate cancer progression. Attempts to overcome resistance to docetaxel by combining docetaxel with other biological agents have been mostly unsuccessful. A better understanding of the mechanisms underlying docetaxel resistance may provide new avenues for the treatment of advanced PCa. We have previously found that the fatty acid-binding protein 12 (FABP12)-PPARγ pathway modulates lipid-related bioenergetics and PCa metastatic transformation through induction of Slug, a master driver of epithelial-to-mesenchymal transition (EMT). Here, we report that the FABP12-Slug axis also underlies chemoresistance in PCa cells. Cell sensitivity to docetaxel is markedly suppressed in FABP12-expressing cells, along with induction of Survivin, a typical apoptosis inhibitor, and inhibition of cleaved PARP, a hallmark of programmed cell death. Importantly, Slug depletion down-regulates Survivin and restores cell sensitivity to docetaxel in FABP12-expressing cells. Finally, we also show that high levels of Survivin are associated with poor prognosis in PCa patients, with FABP12 status determining its prognostic significance. Our research identifies a FABP12-Slug-Survivin pathway driving docetaxel resistance in PCa cells, suggesting that targeting FABP12 may be a precision approach to improve chemodrug efficacy and curb metastatic progression in PCa.
The Influence of Retinol Ointment on Rabbit Skin (Oryctolagus cuniculus) Ion Transport—An In Vitro Study
Authors: Dłubała Klaudia , Wasiek Sandra , Pilarska Patrycja , Szewczyk-Golec Karolina , Mila-Kierzenkowska Celestyna , Łączkowski Krzysztof Z. , Sobiesiak Marta , Gackowski Marcin , Tylkowski Bartosz , Hołyńska-Iwan Iga
Published: September 2024

Retinoids are known to improve the condition of the skin. Transepithelial transport of sodium and chloride ions is important for proper skin function. So far, the effect of applying vitamin A preparations to the skin on ion transport has not been evaluated. In the study, electrophysiological parameters, including transepithelial electric potential (PD) and transepithelial resistance (R), of rabbit skin specimens after 24 h exposure to retinol ointment (800 mass units/g) were measured in a modified Ussing chamber. The R of the fragments incubated with retinol was significantly different than that of the control skin samples incubated in iso-osmotic Ringer solution. For the controls, the PD values were negative, whereas the retinol-treated specimens revealed positive PD values. Mechanical–chemical stimulation with the use of inhibitors of the transport of sodium (amiloride) or chloride (bumetanide) ions revealed specific changes in the maximal and minimal PD values measured for the retinol-treated samples. Retinol was shown to slightly modify the transport pathways of sodium and chloride ions. In particular, an intensification of the chloride ion secretion from keratinocytes was observed. The proposed action may contribute to deep hydration and increase skin tightness, limiting the action of other substances on its surface.
WormCNN-Assisted Establishment and Analysis of Glycation Stress Models in C. elegans: Insights into Disease and Healthy Aging
Authors: Pan Yan , Huang Zhihang , Cai Hongxia , Li Zhiru , Zhu Jingyuan , Wu Dan , Xu Wentao , Qiu Hexiang , Zhang Nan , Li Guojun , Gao Shan , Xian Bo
Published: September 2024

Glycation Stress (GS), induced by advanced glycation end-products (AGEs), significantly impacts aging processes. This study introduces a new model of GS of Caenorhabditis elegans by feeding them Escherichia coli OP50 cultured in a glucose-enriched medium, which better simulates human dietary glycation compared to previous single protein–glucose cross-linking methods. Utilizing WormCNN, a deep learning model, we assessed the health status and calculated the Healthy Aging Index (HAI) of worms with or without GS. Our results demonstrated accelerated aging in the GS group, evidenced by increased autofluorescence and altered gene expression of key aging regulators, daf-2 and daf-16. Additionally, we observed elevated pharyngeal pumping rates in AGEs-fed worms, suggesting an addictive response similar to human dietary patterns. This study highlights the profound effects of GS on worm aging and underscores the critical role of computer vision in accurately assessing health status and aiding in the establishment of disease models. The findings provide insights into glycation-induced aging and offer a comprehensive approach to studying the effects of dietary glycation on aging processes.
A Novel Rare PSEN2 Val226Ala in PSEN2 in a Korean Patient with Atypical Alzheimer’s Disease, and the Importance of PSEN2 5th Transmembrane Domain (TM5) in AD Pathogenesis
Authors: Yang YoungSoon , Bagyinszky Eva , An Seong Soo A.
Published: September 2024

In this manuscript, a novel presenilin-2 (PSEN2) mutation, Val226Ala, was found in a 59-year-old Korean patient who exhibited rapid progressive memory dysfunction and hallucinations six months prior to her first visit to the hospital. Her Magnetic Resonance Imaging (MRI) showed brain atrophy, and both amyloid positron emission tomography (PET) and multimer detection system-oligomeric amyloid-beta (Aβ) results were positive. The patient was diagnosed with early onset Alzheimer’s disease. The whole-exome analysis revealed a new PSEN2 Val226Ala mutation with heterozygosity in the 5th transmembrane domain of the PSEN2 protein near the lumen region. Analyses of the structural prediction suggested structural changes in the helix, specifically a loss of a hydrogen bond between Val226 and Gln229, which may lead to elevated helix motion. Multiple PSEN2 mutations were reported in PSEN2 transmembrane-5 (TM5), such as Tyr231Cys, Ile235Phe, Ala237Val, Leu238Phe, Leu238Pro, and Met239Thr, highlighting the dynamic importance of the 5th transmembrane domain of PSEN2. Mutations in TM5 may alter the access tunnel of the Aβ substrate in the membrane to the gamma-secretase active site, indicating a possible influence on enzyme function that increases Aβ production. Interestingly, the current patient with the Val226Ala mutation presented with a combination of hallucinations and memory dysfunction. Although the causal mechanisms of hallucinations in AD remain unclear, it is possible that PSEN2 interacts with other disease risk factors, including Notch Receptor 3 (NOTCH3) or Glucosylceramidase Beta-1 (GBA) variants, enhancing the occurrence of hallucinations. In conclusion, the direct or indirect role of PSEN2 Val226Ala in AD onset cannot be ruled out.
Insights from Structure-Based Simulations into the Persulfidation of Uridine Diphosphate-Glycosyltransferase71c5 Facilitating the Reversible Inactivation of Abscisic Acid
Authors: Li Miaomiao , Xiao Lihui , Sun Ke , Qiu Taotao , Lai Sisong , Chen Guojing , Geng Lingxi , Huang Siqi , Xie Yanjie
Published: September 2024

The action of abscisic acid (ABA) is closely related to its level in plant tissues. Uridine diphosphate-glycosyltransferase71c5 (UGT71C5) was characterized as a major UGT enzyme to catalyze the formation of the ABA-glucose ester (ABA-GE), a reversible inactive form of free ABA in Arabidopsis thaliana (thale cress). UGTs function in a mode where the catalytic base deprotonates an acceptor to allow a nucleophilic attack at the anomeric center of the donor, achieving the transfer of a glucose moiety. The proteomic data revealed that UGT71C5 can be persulfidated. Herein, an experimental method was employed to detect the persulfidation site of UGT71C5, and the computational methods were further used to identify the yet unknown molecular basis of ABA glycosylation as well as the regulatory role of persulfidation in this process. Our results suggest that the linker and the U-shaped loop are regulatory structural elements: the linker is associated with the binding of uridine diphosphate glucose (UPG) and the U-shaped loop is involved in binding both UPG and ABA.It was also found that it is through tuning the dynamics of the U-shaped loop that is accompanied by the movement of tyrosine (Y388) that the persulfidation of cysteine (C311) leads to the catalytic residue histidine (H16) being in place, preparing for the deprotonation of ABA, and then reorientates UPG and deprotonated ABA closer to the ‘Michaelis’ complex, facilitating the transfer of a glucose moiety. Ultimately, the persulfidation of UGT71C5 is in favor of ABA glycosylation. Our results provide insights into the molecular details of UGT71C5 recognizing substrates and insights concerning persulfidation as a possible mechanism for hydrogen sulfide (H2S) to modulate the content of ABA, which helps us understand how modulating ABA level strengthens plant tolerance.
The Unexplored Role of Mitochondria-Related Oxidative Stress in Diverticular Disease
Authors: Cappelletti Martina , Pallotta Lucia , Vona Rosa , Tinari Antonella , Pisano Annalinda , Casella Giovanni , Crocetti Daniele , Carlomagno Dominga , Tattoli Ivan , Giordano Carla , Matarrese Paola , Severi Carola
Published: September 2024

The pathophysiology of diverticular disease (DD) is not well outlined. Recent studies performed on the DD human ex vivo model have shown the presence of a predominant transmural oxidative imbalance whose origin remains unknown. Considering the central role of mitochondria in oxidative stress, the present study evaluates their involvement in the alterations of DD clinical phenotypes. Colonic surgical samples of patients with asymptomatic diverticulosis, complicated DD, and controls were analyzed. Electron microscopy, protein expression, and cytofluorimetric analyses were performed to assess the contribution of mitochondrial oxidative stress. Functional muscle activity was tested on cells in response to contractile and relaxant agents. To assess the possibility of reverting oxidative damages, N-acetylcysteine was tested on an in vitro model. Compared with the controls, DD tissues showed a marketed increase in mitochondrial number and fusion accompanied by the altered mitochondrial electron transport chain complexes. In SMCs, the mitochondrial mass increase was accompanied by altered mitochondrial metabolic activity supported by a membrane potential decrease. Ulteriorly, a decrease in antioxidant content and altered contraction–relaxation dynamics reverted by N-acetylcysteine were observed. Therefore, the oxidative stress-driven alterations resulted in mitochondrial impairment. The beneficial effects of antioxidant treatments open new possibilities for tailored therapeutic strategies that have not been tested for this disease.
Selected Papers from the pHealth 2022 Conference, Oslo, Norway, 8–10 November 2022
Authors: Blobel Bernd
Published: September 2024

This Special Issue of the Journal of Personalized Medicine presents extended versions of selected contributions to pHealth 2022, the 19th International Conference on Wearable Micro and Nano Technologies for Personalized Health, held on 8–10 November 2022 in Oslo, Norway [...]
Laser Powder Bed Fusion of Copper–Tungsten Powders Manufactured by Milling or Co-Injection Atomization Process
Authors: Rauh Simon , Prabhu Shashank Deepak , Wolf Gerhard , Fischer Lioba , Hempel Nico , Mayr Peter
Published: September 2024

The processing of pure copper (Cu) has been a challenge for laser-based additive manufacturing for many years since copper powders have a high reflectivity of up to 83% of electromagnetic radiation at a wavelength of 1070 nm. In this study, Cu particles were coated with sub-micrometer tungsten (W) particles to increase the laser beam absorptivity. The coated powders were processed by powder bed fusion-laser beam for metals (PBF-LB/M) with a conventional laser system of <300 watts laser power and a wavelength of 1070 nm. Two different powder manufacturing routes were developed. The first manufacturing route was gas atomization combined with a milling process by a planetary mill. The second manufacturing method was gas atomization with particle co-injection, where a separate W particle jet was sprayed into the atomized Cu jet. As part of the investigations, an extensive characterization of powder and additively manufactured test specimens was carried out. The specimens of Cu/W powders manufactured by the milling process have shown superior results. The laser absorptivity of the Cu/W powder was increased from 22.5% (pure Cu powder) to up to 71.6% for powders with 3 vol% W. In addition, a relative density of test specimens up to 98.2% (optically) and 95.6% (Archimedes) was reached. Furthermore, thermal conductivity was measured by laser flash analysis (LFA) and thermo-optical measurement (TOM). By using eddy current measurement, the electrical conductivity was analyzed. In comparison to the Cu reference, a thermal conductivity of 88.9% and an electrical conductivity of 85.8% were determined. Moreover, the Vickers hardness was measured. The effect of porosity on conductivity properties and hardness was investigated and showed a linear correlation. Finally, a demonstrator was built in which a wall thickness of down to 200 µm was achieved. This demonstrates that the Cu/W composite can be used for heat exchangers, heat sinks, and coils.
Mechanical Properties of P91 Steel (X10CrMoVNb9-1) during Simulated Operation in a Hydrogen-Containing Environment
Authors: Junak Grzegorz , Adamiec Janusz , Łyczkowska Katarzyna
Published: September 2024

P91 steel (X10CrMoVNb9-1) is widely used in the energy industry. It is characterized by good mechanical properties, creep resistance, corrosion resistance, impact toughness, and resistance to thermal fatigue. Due to their operating conditions and martensitic structure, components made from P91 steel are often subject to damage related to the presence of hydrogen. This article compares the results of the mechanical properties evaluation for P91 steel in an aggressive solution charged under load and without load. Based on the research, it was found that the hydrogen environment significantly affects the mechanical properties of P91 steel, reducing strength and yield strength, and decreasing ductility. It was revealed that in samples tested after 72 h without preloading, the tensile strength decreased by 1.5%, and the elongation decreased by about 29% for the sample, compared to the delivered condition sample. Under loaded conditions, the difference in tensile strength increased by approximately 8%, while elongation increased by nearly 50%
Investigating Flow-Induced Corrosion of Magnesium in Ophthalmological Milieu
Authors: Ferroni Marco , De Gaetano Francesco , Gastaldi Dario , Cereda Matteo Giuseppe , Boschetti Federica
Published: September 2024

Although the impact of local fluid dynamics in the biodegradation of magnesium is well known, currently no studies in the literature address the degradation effects of ocular vitreous on bioresorbable devices made of magnesium, which could be developed as drug delivery carriers. The aim of this study was to investigate the flow-induced corrosion mechanism of magnesium in an ophthalmological environment for future applications in ophthalmic drug delivery. To achieve this, experimental and computational methods were combined. Specifically, a CFD model was employed to design experimental conditions that replicate the ocular flow-induced shear stress (FISS) on manufactured magnesium samples. Pure Mg samples were tested in a bioreactor system capable of imposing the ocular CFD calculated values of FISS on the Mg samples’ surface by varying the pump flow rate. Optimal flow rates for a range of different FISS values specific to the ophthalmological fluid dynamics affecting the device were indeed determined before running the experiments. After conducting customized corrosion tests, morphological observations and profilometric maps of the eroded surfaces of Mg samples were obtained using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). These maps were then post-processed for the parametric evaluation of corrosion rates. Pre-existing localized superficial defects did affect the final corrosion pattern. SEM images and CLSM data confirmed a uniform corrosion mechanism, with corrosion rates of 1.9, 2.7, and 3.4 μm/day under different shear stress conditions (0, 0.01, and 0.032 Pa, respectively). More generally, uniform corrosion on pure Mg samples increased with higher FISS values, and at higher shear stress values (FISS = 0.032 Pa), a notable washing-out effect of the corrosion products was observed. The removal of corrosion products at higher shear stresses suggests that the dynamic ocular environment, influenced by saccadic movements, plays a significant role in the corrosion mechanism of pure magnesium. The corrosion rates determined in this study, in conjunction with clinical drug release requirements, are crucial for designing potential drug-release devices for ocular applications.
Exploring the Diversity and Specificity of Secondary Biosynthetic Potential in Rhodococcus
Authors: Hu Gang-Ao , Song Yue , Liu Shi-Yi , Yu Wen-Chao , Yu Yan-Lei , Chen Jian-Wei , Wang Hong , Wei Bin
Published: September 2024

The actinomycete genus Rhodococcus is known for its diverse biosynthetic enzymes, with potential in pollutant degradation, chemical biocatalysis, and natural product exploration. Comparative genomics have analyzed the distribution patterns of non-ribosomal peptide synthetases (NRPSs) in Rhodococcus. The diversity and specificity of its secondary metabolism offer valuable insights for exploring natural products, yet remain understudied. In the present study, we analyzed the distribution patterns of biosynthetic gene clusters (BGCs) in the most comprehensive Rhodococcus genome data to date. The results show that 86.5% of the gene cluster families (GCFs) are only distributed in a specific phylogenomic-clade of Rhodococcus, with the most predominant types of gene clusters being NRPS and ribosomally synthesized and post-translationally modified peptides (RiPPs). In-depth mining of RiPP gene clusters revealed that Rhodococcus encodes many clade-specific novel RiPPs, with thirteen core peptides showing antibacterial potential. High-throughput elicitor screening (HiTES) and non-targeted metabolomics revealed that a marine-derived Rhodococcus strain produces a large number of new aurachin-like compounds when exposed to specific elicitors. The present study highlights the diversity and specificity of secondary biosynthetic potential in Rhodococcus, and provides valuable information for the targeted exploration of novel natural products from Rhodococcus, especially for phylogenomic-clade-specific metabolites.