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28 pages, 4005 KB  
Article
Dual-Tier Cyberattack Detection for Distributed Energy Resource Aggregators
by Celina Wilkerson, Qiuhua Huang, Burhan Hyder and Rohit Jinsiwale
Energies 2026, 19(19), 4661; https://doi.org/10.3390/en19194661 (registering DOI) - 1 Oct 2026
Abstract
As distributed energy resources (DERs) and DER aggregators are integrated into distribution systems, the attack surface of critical power infrastructure expands. Built-in cryptography is effective against some false data injection (FDI) attacks, man-in-the-middle attacks, and tampered data from unauthenticated sources but cannot detect [...] Read more.
As distributed energy resources (DERs) and DER aggregators are integrated into distribution systems, the attack surface of critical power infrastructure expands. Built-in cryptography is effective against some false data injection (FDI) attacks, man-in-the-middle attacks, and tampered data from unauthenticated sources but cannot detect denial of service (DoS) attacks or FDI attacks originating from already-authenticated devices. This paper proposes a Dual-Tier Cyberattack Detection (DTCD) algorithm implemented within a DER aggregator that detects cyberattacks within the cyber and physical layers of a DER-integrated distribution system. The first tier, or cyber filter (CF), applies rule-based cyber checks to detect protocol-level DoS attacks, including TCP floods, SYN floods, and port scan attacks, and timestamp-based FDI anomalies. The second tier, or voltage anomaly detector (VAD), applies a physics-based Gradient Boosting Machine (GBM) dual-fusion model to detect event-driven FDI attacks by evaluating whether observed bus voltage deviations can be explained by expected load or photovoltaic (PV) changes. The algorithm is validated in real-time hardware-in-the-loop (HIL) testing on the PNNL powerNET cyberphysical testbed using an IEEE 123 bus model with DNP3 communication. CF detects all four tested attack signatures under partially mitigated traffic conditions with sub-50 ms detection times. VAD achieves a pooled F1-score of 0.875 and a receiver operating characteristic area under the curve (ROC AUC) of 0.802 across six attack scenarios at three operating conditions and four test days. VAD completes analysis in 2363 ms on average, within the sub-SCADA timeline. A two-tier comparison study shows that DTCD’s cyber check and physics-based tiers outperform cryptographic and signature-based intrusion detection approaches in the first tier and a standalone-GBM approach in the second tier. The two tiers operate in parallel and provide complementary coverage of DoS and FDI attacks. Replacing CF misses timestamp anomalies, and replacing VAD lowers the FDI F1-score. Results demonstrate that the proposed algorithm effectively complements cryptographic prevention as a detection layer, can provide cybersecurity coverage for legacy devices through aggregator-level packet screening, and completes its analysis within the sub-SCADA operational window. Full article
(This article belongs to the Topic Power System Technologies and Applications)
11 pages, 232 KB  
Article
The Christocentric School of Rohia Monastery Around Father Nicolae Steinhardt (1912–1989) and the School of Păltiniș
by Florin-Toader Tomoioagă
Religions 2026, 17(10), 1141; https://doi.org/10.3390/rel17101141 - 29 Sep 2026
Abstract
The aim of the present study is to bring forward two cultural and spiritual phenomena that shaped the intellectual and religious landscapes of Romania at the end of the 20th Century and continue to influence them until nowadays. More precisely, the topic focuses [...] Read more.
The aim of the present study is to bring forward two cultural and spiritual phenomena that shaped the intellectual and religious landscapes of Romania at the end of the 20th Century and continue to influence them until nowadays. More precisely, the topic focuses on the School of Rohia Monastery gathered around the personality of the monk and man of letters Nicolae Steinhardt and the School of Păltiniș, led by the philosopher Constantin Noica. The option to treat the two phenomena in the same frame is imposed by the cultural and personal connections of the two leaders and by the similarities of the informal schools they created around them. Therefore, the research methods used in this study in order to offer a precise image of the two informal schools are the descriptive method and the comparative method. The comparative method will be used to highlight not only the similarities but, as well, the differences between the two schools and between their leaders. As this will become evident in the following lines, during the repressive regime of Ceaușescu, in the ’70s and ’80s, Steinhardt and Noica opted for a very different form of resistance: the first one chose a total refusal of adaptation and collaboration with it, while the second one accepted a formal association with it. However, both of them, in different ways, served the great ideal of culture, Father Nicolae Steinhardt from a Christian monastic setting and perspective, while the philosopher Constantin Noica from an ahistorical and purely intellectual perspective. Full article
(This article belongs to the Special Issue Religious Phenomena in Romania in the 20th and Early 21st Centuries)
20 pages, 3177 KB  
Case Report
The Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis Spectrum: A Report of Two Contrasting Cases Managed in a Burn Unit
by Mihai-Codrin Constantinescu, Dan-Cristian Moraru, Vladimir Poroch, Stefana Avadanei-Luca, Andrei-Nicolae Gologan, Alexandru-Hristo Amarandei, Awad Dmour, Dragos-Florin Gheuca-Solovastru, Bianca-Ana Dmour, Delia-Gabriela Ciobanu-Apostol and Mihaela Pertea
Diseases 2026, 14(10), 355; https://doi.org/10.3390/diseases14100355 - 25 Sep 2026
Viewed by 121
Abstract
Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, potentially life-threatening mucocutaneous reactions classified based on body surface area (BSA) involvement: SJS affects less than 10% BSA, SJS/TEN overlap affects 10–30% BSA, and TEN affects more than 30% BSA. The mortality [...] Read more.
Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, potentially life-threatening mucocutaneous reactions classified based on body surface area (BSA) involvement: SJS affects less than 10% BSA, SJS/TEN overlap affects 10–30% BSA, and TEN affects more than 30% BSA. The mortality rates range from 4.8–9% for SJS to 14.8–48% for TEN. Treatment remains controversial, with corticosteroids and intravenous immunoglobulin (IVIg) being the most debated therapeutic options. While some studies suggest IVIg may block Fas-mediated keratinocyte apoptosis, meta-analyses have shown conflicting results regarding mortality benefit. Case presentation: We describe two patients from opposite ends of the SJS/TEN spectrum, managed in a burn unit with different therapeutic approaches. The first patient, a 47-year-old man with systemic lupus erythematosus, developed TEN with approximately 35% body surface area involvement, complicated by sepsis and rhabdomyolysis; he was treated with systemic corticosteroids and intravenous immunoglobulin (IVIg, 0.4 g/kg/day for 3 days). The second patient, a 66-year-old woman, developed SJS attributed to amoxicillin–clavulanic acid and was treated with systemic corticosteroids alone. Both patients achieved complete re-epithelialization without major sequelae. Conclusions: These two cases illustrate the clinical heterogeneity of the SJS/TEN spectrum and the central role of early recognition, prompt withdrawal of the culprit drug, transfer to a specialized unit, and multidisciplinary supportive care. Given the substantial differences between the two patients in age, sex, comorbidities, culprit drugs, and disease severity, no comparative or causal inference regarding the relative efficacy of the two treatment strategies can be drawn; no efficacy claim is made for either therapeutic approach; this report is descriptive, and the two cases are presented as contrasting rather than comparable. Full article
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9 pages, 2291 KB  
Case Report
Mechanical Circulatory Support with iVAC2L During High-Risk Percutaneous Coronary Intervention: A Case Report
by Gerda Sibirkstyte, Mindaugas Barauskas, Martynas Jurenas, Ramunas Unikas, Marcelo B. Bastos and Chrisna de Wet Breukelen
J. Clin. Med. 2026, 15(18), 7322; https://doi.org/10.3390/jcm15187322 - 21 Sep 2026
Viewed by 169
Abstract
Background: High-risk percutaneous coronary intervention (HR-PCI) in patients with severe left ventricular (LV) systolic dysfunction and complex coronary artery disease may be complicated by abrupt intraprocedural hemodynamic deterioration. Temporary mechanical circulatory support may be considered after individualized Heart Team assessment; however, clinical experience [...] Read more.
Background: High-risk percutaneous coronary intervention (HR-PCI) in patients with severe left ventricular (LV) systolic dysfunction and complex coronary artery disease may be complicated by abrupt intraprocedural hemodynamic deterioration. Temporary mechanical circulatory support may be considered after individualized Heart Team assessment; however, clinical experience with the pulsatile iVAC2L device remains limited. Case Presentation: An 84-year-old man presented with inferior ST-segment-elevation myocardial infarction, acute decompensated heart failure, pulmonary edema, and an LV ejection fraction of 10–15%. Coronary angiography (CAG) showed a presumed chronic total occlusion of the right coronary artery (RCA) and critical disease of the left main (LMCA), left anterior descending (LAD), and left circumflex (LCx) arteries. Preparation for coronary artery bypass grafting was initiated, but clinical deterioration prompted PCI. The first attempt was aborted after cardiac arrest during coronary wiring. Following stabilization and repeat Heart Team assessment, iVAC2L-supported HR-PCI was performed. During 60 min of active pump support, five stents were implanted in the LMCA, LAD, and LCx. The patient remained conscious and hemodynamically stable without vasopressors. LV ejection fraction was approximately 20% at discharge after six hospital days, and the patient was transferred to inpatient rehabilitation. Conclusions: In this selected patient, iVAC2L-supported HR-PCI was technically feasible and was associated with maintained intraprocedural hemodynamic stability. A single case cannot establish comparative safety or efficacy; prospective studies are required to define patient selection, procedural protocols, and clinically meaningful outcomes. Full article
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21 pages, 10535 KB  
Review
Rescue Transcatheter Aortic Valve Implantation for Severe Native Aortic Regurgitation in a Young Patient with Hypertrophic Obstructive Cardiomyopathy and Cardiogenic Shock: Review of the Literature and Case Presentation
by Catalina Andreea Parasca, Dan Deleanu, Pavel Platon, Crina Ioana Radulescu, Mihai Stefan, Ruxandra Oana Jurcut, Daniela Carmen Filipescu and Vlad Anton Iliescu
Life 2026, 16(9), 1503; https://doi.org/10.3390/life16091503 - 9 Sep 2026
Viewed by 260
Abstract
Transcatheter aortic valve implantation (TAVI) for pure native aortic regurgitation (AR) remains technically challenging, primarily because absent annular calcification limits prosthesis anchoring. We reviewed contemporary evidence on TAVI for native AR, focusing on devices, procedural performance, complications, and outcomes. A comprehensive PubMed search [...] Read more.
Transcatheter aortic valve implantation (TAVI) for pure native aortic regurgitation (AR) remains technically challenging, primarily because absent annular calcification limits prosthesis anchoring. We reviewed contemporary evidence on TAVI for native AR, focusing on devices, procedural performance, complications, and outcomes. A comprehensive PubMed search identified 371 articles, of which 28 studies comprising 3282 patients met the inclusion criteria; notably, 64.3% were published from 2023 onward, reflecting the rapidly expanding evidence in this field. Conventional off-label devices were evaluated in 60.7% of studies and dedicated AR devices in 35.7%, while 3.6% directly compared both strategies. Technical/device success ranged from 72% to 100%, generally exceeding 85–90% in contemporary series, while 30-day mortality ranged from 0% to 23%. To illustrate the technical challenges and expand this evidence, we present a 24-year-old man with MYH7-associated hypertrophic obstructive cardiomyopathy and severe post-myectomy AR complicated by biventricular failure, cardiogenic shock, and multiorgan dysfunction. Given prohibitive surgical risk, rescue transfemoral TAVI was performed. Despite embolization of the first balloon-expandable prosthesis, a second valve was successfully implanted using an individualized anchoring strategy. At 1 year, the patient was in NYHA class I with biventricular recovery. TAVI represents an evolving alternative for carefully selected patients with severe native AR and prohibitive surgical risk. Full article
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19 pages, 1653 KB  
Article
Associations of OPRM1, COMT, and ABCB1 Variants with Opioid Analgesic Response in Acute Renal Colic: A Candidate-Gene Study
by Sıtkı Ün, Ramazan Sabırlı, İbrahim Türkçüer, Gergana Lengerova, Martina Bozhkova, Steliyan Petrov and Aylin Köseler
Pharmaceuticals 2026, 19(9), 1343; https://doi.org/10.3390/ph19091343 - 24 Aug 2026
Viewed by 613
Abstract
Background: Acute renal colic is a common urological emergency characterized by substantial interindividual variability in analgesic response. Pharmacogenetic variation in OPRM1, COMT, and ABCB1 may contribute to differences in opioid efficacy and pain control. This study primarily evaluated the associations [...] Read more.
Background: Acute renal colic is a common urological emergency characterized by substantial interindividual variability in analgesic response. Pharmacogenetic variation in OPRM1, COMT, and ABCB1 may contribute to differences in opioid efficacy and pain control. This study primarily evaluated the associations of OPRM1 A118G (rs1799971), COMT Val158Met (rs4680), and ABCB1 C3435T (rs1045642) polymorphisms with opioid analgesic response in patients with acute renal colic. As a secondary exploratory analysis, genotype and allele frequencies were compared between patients and healthy controls. Methods: This prospective case–control study included 150 patients with acute renal colic and 100 healthy controls. Genotyping was performed using TaqMan SNP Genotyping Assays based on real-time polymerase chain reaction. Genotype frequencies were compared between groups using dominant and recessive genetic models, and Hardy–Weinberg equilibrium was assessed. In addition, genotype–phenotype associations were evaluated using pain severity, early analgesic response, initial opioid dose, rescue analgesic requirement, and multivariable logistic regression analyses. Results: In the secondary exploratory case–control analysis, no statistically significant differences in genotype or allele frequencies of OPRM1 rs1799971, COMT rs4680, or ABCB1 rs1045642 were observed between patients with acute renal colic and healthy controls. Within the patient cohort, however, genotype–phenotype analyses identified differences in early analgesic outcomes. Baseline-adjusted 30 min VAS differed according to OPRM1, COMT, and ABCB1 genotype, with the most pronounced difference observed for ABCB1 rs1045642. Patients with the ABCB1 TT genotype had higher adjusted 30 min VAS scores and showed a pattern of greater opioid requirement and more frequent rescue analgesia. In exploratory multivariable analysis, the ABCB1 TT genotype was associated with higher odds of inadequate early analgesic response (adjusted OR = 2.74, 95% CI 1.18–6.37; p = 0.019). Given the limited number of outcome events, this adjusted association should be considered preliminary and hypothesis-generating. Conclusions: No significant differences in the distributions of the polymorphisms investigated were observed between patients with acute renal colic and healthy controls. Within the patient group, ABCB1 genetic variation was associated with early opioid analgesic response, although this finding should be considered preliminary and requires confirmation in larger prospective pharmacogenetic studies before clinical implementation. Any potential future pharmacogenetic application should be considered as an adjunct to established first-line renal–colic management and specifically in patients for whom opioid therapy is clinically indicated. Full article
(This article belongs to the Section Pharmacology)
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19 pages, 1072 KB  
Article
Population-Specific Genetic Markers of Prostate Cancer Risk in Kazakh Men: Association Analysis of 102 SNPs and Risk Prediction Modeling
by Kairat Kazbekov, Yerbol Zhapparov, Nasrulla Shanazarov, Valery Benberin, Sergey Zinchenko and Ainagul Kazbekova
Genes 2026, 17(8), 956; https://doi.org/10.3390/genes17080956 - 14 Aug 2026
Viewed by 338
Abstract
Background/Objectives: GWASs have identified more than 250 prostate cancer (PCa) predisposition loci, predominantly in European and partly Asian cohorts. The Kazakh population is markedly under-represented in international genetic studies, limiting existing risk models. This study aimed to analyze the distribution of 102 PCa-associated [...] Read more.
Background/Objectives: GWASs have identified more than 250 prostate cancer (PCa) predisposition loci, predominantly in European and partly Asian cohorts. The Kazakh population is markedly under-represented in international genetic studies, limiting existing risk models. This study aimed to analyze the distribution of 102 PCa-associated single-nucleotide polymorphism (SNP) genotypes and alleles and to identify reliable population-specific associations with PCa risk in Kazakh men. Methods: This retrospective case–control study included 941 Kazakh men (476 with histologically confirmed PCa and 465 cancer-free controls). Genomic DNA extracted from peripheral blood was genotyped with TaqMan® OpenArray® technology on a QuantStudio 12K Flex system. Associations were assessed by Pearson’s χ2 test and logistic regression, with genotypic and allelic odds ratios (OR) and 95% confidence intervals (CI). Two-step multiple-testing correction (Bonferroni and Benjamini–Hochberg false-discovery rate, FDR) was applied. Predictive models were built using classification and regression trees (CART) and stepwise logistic regression. Results: Of 102 SNPs, 39 showed nominally significant genotypic differences; 12 remained significant after Bonferroni correction and 2 after FDR (14 in total). Several of the corrected loci were significant at both the genotypic and allelic level. Allelic ORs ranged from 0.37 (protective rs10187424 T allele) to 4.81 (rs1545985). A parsimonious seven-SNP autosomal logistic-regression model achieved an apparent AuROC of 0.84 (10-fold cross-validated 0.82); adding age as a covariate raised discrimination to 0.87. Ten of the fourteen significant loci remained significant after age adjustment, and six of these formed a core signal robust to both age imbalance and genotyping-quality concerns. Conclusions: This first large-scale SNP-association study in Kazakh men shows allele-frequency profiles resembling East Asian rather than European populations, confirming the need for population-specific genetic risk-assessment tools. The seven-SNP model showed high discriminatory power in the training set and requires external validation before clinical application. Full article
(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases 2026)
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12 pages, 2023 KB  
Case Report
Pulmonary Embolism Complicating Active Pulmonary Tuberculosis: Two Case Reports of Tuberculosis-Associated Hypercoagulability
by Denisa Maria Mitroi, Ramona Cioboata, Mihai Olteanu, Oana Maria Catana, Anca Lelia Riza and Viorel Biciusca
Diagnostics 2026, 16(14), 2140; https://doi.org/10.3390/diagnostics16142140 - 8 Jul 2026
Viewed by 1581
Abstract
Background: Active tuberculosis (TB) is increasingly recognized as a systemic thrombo-inflammatory condition capable of inducing a clinically relevant hypercoagulable state and increasing the risk of venous thromboembolism, including pulmonary embolism (PE). However, this association remains underrecognized in clinical practice, and its biological and [...] Read more.
Background: Active tuberculosis (TB) is increasingly recognized as a systemic thrombo-inflammatory condition capable of inducing a clinically relevant hypercoagulable state and increasing the risk of venous thromboembolism, including pulmonary embolism (PE). However, this association remains underrecognized in clinical practice, and its biological and therapeutic implications are not yet fully defined. We report two cases of active pulmonary tuberculosis complicated by PE and review the literature to highlight the temporal patterns, laboratory features, and clinical relevance of TB-associated hypercoagulability. Case Presentation: The first case involved a 65-year-old man with stage II chronic obstructive pulmonary disease in whom PE was identified concurrently with the diagnosis of active pulmonary TB. The second case concerned a 43-year-old man with severe pulmonary tuberculosis and subsequent intestinal involvement, in whom bilateral PE developed during the early intensive phase of antituberculous therapy. In both patients, laboratory evaluation demonstrated a consistent prothrombotic profile characterized by reactive thrombocytosis, elevated inflammatory markers, increased fibrinogen and D-dimer levels, and reduced protein C and protein S activity. Both patients received standard antituberculous therapy combined with therapeutic anticoagulation, with favorable clinical, laboratory, and radiological outcomes. Discussion: These cases are consistent with emerging evidence that active tuberculosis may induce a reversible infection-related hypercoagulable state through systemic inflammation, endothelial dysfunction, platelet activation, impaired fibrinolysis, and transient depletion of natural anticoagulants. They illustrate two clinically relevant temporal patterns described in the literature, namely PE detected at diagnosis and PE developing during early treatment despite appropriate therapy. The normalization of coagulation abnormalities after treatment further supports an acquired TB-related thrombo-inflammatory mechanism. Conclusions: Active tuberculosis may be complicated by pulmonary embolism both at presentation and during the early phase of treatment. Reactive thrombocytosis, elevated inflammatory markers, increased D-dimer levels, and reduced protein C and protein S activity may serve as useful indicators of TB-associated hypercoagulability. Pulmonary embolism should be considered in patients with severe tuberculosis who show unexplained deterioration or delayed recovery. Larger prospective studies are needed to clarify the role of coagulation profiling and biomarker-guided management in this setting. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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18 pages, 6479 KB  
Article
Targeting the hsa-miR-155-5p–BACH1–MMP-9 Signaling Hub in Lung Cancer: A Novel Anticancer Mechanism of Thymoquinone
by Yusuf Saleem Khan, Aisha Farhana, Alfatih Mohamed Ahmed Alnajib, Azharuddin Sajid Syed Khaja, Hatim Adam Nagi, Tarig Ginawi, Abuzar Abdulwahab Osman, Ayman Ali Mohammed Alameen, Emad Manni and Zafar Rasheed
Biomolecules 2026, 16(7), 955; https://doi.org/10.3390/biom16070955 - 27 Jun 2026
Viewed by 742
Abstract
Objective: Lung cancer (LC) remains a leading cause of cancer mortality worldwide. Thymoquinone (TQ), a bioactive compound derived from Nigella sativa, possesses anti-inflammatory and antioxidant properties, but its precise mechanisms concerning miRNA regulation in LC are poorly defined. This study investigates the [...] Read more.
Objective: Lung cancer (LC) remains a leading cause of cancer mortality worldwide. Thymoquinone (TQ), a bioactive compound derived from Nigella sativa, possesses anti-inflammatory and antioxidant properties, but its precise mechanisms concerning miRNA regulation in LC are poorly defined. This study investigates the anti-cancer potential of TQ through modulation of microRNA signaling in LC. Methods: We employed an integrated approach combining bioinformatic predictions with rigorous experimental validation in A549 lung adenocarcinoma cells and SHP-77 human small-cell lung carcinoma (SCLC) cells. Bioinformatic analyses predicted miRNA targets, and experimental techniques included dual-luciferase reporter assays, miRNA inhibition, TaqMan RT-qPCR, cell-based ELISA, and Western blotting to dissect the molecular pathway. Results: We identified the transcription factor BACH1 as a direct and novel target of hsa-miR-155-5p. TQ potently suppressed interferon-γ-induced expression of both hsa-miR-155-5p and its target, BACH1. This TQ-mediated suppression led to subsequent downregulation of the key metastasis-promoter Matrix Metalloproteinase-9 (MMP-9). Genetic inhibition of miR-155-5p or direct BACH1 inhibition phenocopied the effects of TQ, confirming the functional significance of this axis. Thus, we define a novel oncogenic signaling cascade—the hsa-miR-155-5p/BACH1/MMP-9 axis that is effectively disrupted by TQ. Conclusions: This represents the first evidence that TQ exerts its anti-cancer effects in LC through the modulation of the critical signaling cascade (hsa-miR-155-5p → BACH1 → MMP-9). Our findings establish TQ as a multi-targeted agent capable of simultaneously inhibiting miRNA-mediated oncogenic signaling and protein-level effectors. The dual therapeutic action of TQ represents a novel therapeutic strategy and underscores its potential for synergistic combination therapies. Full article
(This article belongs to the Special Issue Signal Transduction and Pathway Regulation in Cancer)
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28 pages, 7113 KB  
Article
Optimization of Human–Machine Interface Layout for Mechanical Support Position of Manned Submersibles Based on a Task-Information Network Approach
by Xiyue Wang, Liping Pang, Xiaodong Cao, Yuejie Fan, Bingxu Zhao, Xin Wang and Wentao Wu
J. Mar. Sci. Eng. 2026, 14(13), 1176; https://doi.org/10.3390/jmse14131176 - 26 Jun 2026
Viewed by 330
Abstract
The human–machine interface (HMI) of the mechanical support (MS) position (MS-HMIs) of manned submersibles features multiple screens, information-rich displays, and complex operational logic, which can reduce operator efficiency, increase cognitive load, and lead to human errors. The layout determines the perception of information [...] Read more.
The human–machine interface (HMI) of the mechanical support (MS) position (MS-HMIs) of manned submersibles features multiple screens, information-rich displays, and complex operational logic, which can reduce operator efficiency, increase cognitive load, and lead to human errors. The layout determines the perception of information density, complexity, and logic, making the optimization of the HMI layout highly significant. To address this issue, a layout optimization approach is proposed based on a task-information network integrating multi-objective optimization. First, the basic MS-HMI elements are decomposed, and Hierarchical Task Analysis (HTA) is used to construct task sequences and element usage sequences. The Space-P and Space-L methods are applied to build the task–information network, based on which element grouping and importance are determined through network topology analysis. Incorporating ergonomic layout principles, a multi-objective optimization model is formulated and solved using the NSGA-II algorithm to generate feasible optimized layouts. Experimental verification results demonstrate that the optimized interfaces significantly outperform the original design in terms of operational performance, eye-tracking metrics, and subjective evaluations. Operation duration and task completion time decreased by over 6%, average saccade speed was reduced by up to 17.1%, and subjective ratings improved substantially. By integrating complex network analysis, typical submersible task sequences, and ergonomic principles, this study presents a systematic, evidence-based, effective, and task-compliant method for optimizing HMI layouts. Full article
(This article belongs to the Section Ocean Engineering)
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16 pages, 1962 KB  
Article
Vigorous Physical Activity Mitigates Susceptibility to Obesity Associated with Risk Genotypes of FTO and MC4R, and SREBF1 Is Hypermethylated: A Cross-Sectional Pilot Study
by Jenni Chambers, Mary Erazo Bastidas, Clare M. P. Roscoe, Corinna Chidley, Aaisha Makkar and Aparna Duggirala
Epigenomes 2026, 10(2), 42; https://doi.org/10.3390/epigenomes10020042 - 21 Jun 2026
Viewed by 993
Abstract
Aim: The aim of this study was to correlate single-nucleotide polymorphisms (SNPs) in the FTO and MC4R genes with body composition (BC) in populations with various levels of physical activity, and to investigate associations of SREBF1 methylation with the level of physical [...] Read more.
Aim: The aim of this study was to correlate single-nucleotide polymorphisms (SNPs) in the FTO and MC4R genes with body composition (BC) in populations with various levels of physical activity, and to investigate associations of SREBF1 methylation with the level of physical activity (PA) and BC. Methods: Fifty-six participants aged 18–65 years old with no underlying medical conditions were included in the study and were classified into sedentary/light PA (SLPA), moderate PA (MPA) and vigorous PA (VPA) groups using the International PA questionnaire (IPAQ). Anthropometric measures such as age, gender, body mass index (BMI) and body fat percentage (BFP) were recorded at the time of recruitment. Venous blood samples were collected during participant recruitment and DNA was extracted. Genotyping assays were performed for SNPs in FTO (rs9939609) and MC4R (rs17782313) using Taqman® RT qPCR and TaqMan Genotyper software 1.7.1. Methylation analysis assay for CpG sites in the SREBF1 gene was performed on 56 samples using PyroMark® Q48 Autoprep (Qiagen, Venlo, The Netherlands). The results were statistically analysed to identify any associations between FTO/MC4R genotypes and the level of PA, and between SREBF1 methylation status and the level of PA. This is the first study to investigate links between PA and quantitative methylation of SREBF1. Results: According to IPAQ guidance, the 56 participants were classified into SLPA n = 14, MPA n = 11 and VPA n = 31. The correlation analysis revealed that the FTO rs9939609 ‘A’ risk allele had a significant negative association with BFP in the VPA group (p = 0.0387); the MC4R rs17782313 ‘C’ risk allele had a significant positive association with BMI in the VPA group (p = 0.0256). In the SREBF1 pyrosequencing analysis, higher levels of methylation were observed in the VPA group (p = 0.07). Conclusions: We concluded that SNPs associated with obesity identified in FTO rs9939609 and MC4R rs17782313 could help to predict the molecular effects of PA. A high frequency of FTO risk variants in the cohort was observed and the VPA group could help maintain a healthy BFP. Full article
(This article belongs to the Special Issue Epigenetic Signatures in Metabolic Health and Cancer)
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16 pages, 339 KB  
Article
IL12B rs3213094 as a Predictor of Early Response to Biologic Therapy in Psoriasis: A Real-World Study in a Romanian Cohort
by Alessandra-Madalina Matei-Man, Ildiko-Orsolya Gaal, Andreea Catana, Stefan Vesa, Simona Senila, Elisabeta Candrea, Meda Orasan, Alexandra Puskas, Ana Calina Man and Teodora Mocan
Medicina 2026, 62(6), 1041; https://doi.org/10.3390/medicina62061041 - 28 May 2026
Viewed by 548
Abstract
Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease characterized by heterogeneous clinical presentation and variable response to biologic therapy. Genetic variation within the IL-23/Th17 inflammatory pathway may influence treatment outcomes. This study evaluated the association between IL12B rs3213094 and IL23R [...] Read more.
Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease characterized by heterogeneous clinical presentation and variable response to biologic therapy. Genetic variation within the IL-23/Th17 inflammatory pathway may influence treatment outcomes. This study evaluated the association between IL12B rs3213094 and IL23R rs11209026 single-nucleotide polymorphisms (SNPs) and response to biologic therapy in patients with moderate-to-severe psoriasis. Materials and Methods: We conducted a multicenter observational study including 92 Romanian patients with moderate-to-severe psoriasis vulgaris receiving their first biologic therapy (anti-TNF, anti-IL-17, or anti-IL-23 monoclonal antibodies). Clinical response was assessed using the Psoriasis Area and Severity Index (PASI) at baseline and weeks 12, 24, 36, and 48. Early response was defined as achieving PASI75 at week 12. Patient-reported disease impact was assessed using the Dermatology Life Quality Index (DLQI) at the same time points. Genotyping of IL12B rs3213094 and IL23R rs11209026 was performed using TaqMan assays. Longitudinal PASI dynamics were analyzed using repeated-measures ANOVA, while multivariable logistic regression was used to identify independent predictors of PASI75 at week 12. Results: A significant reduction in PASI scores over time was observed (p < 0.001). The IL12B rs3213094 genotype was associated with differences in early response kinetics, with T-allele carriers showing significantly greater PASI improvement at week 12 compared with CC homozygotes (90.0% vs. 65.7%, p = 0.003). This effect was limited to early treatment and attenuated at later time points. In multivariable analysis, the IL12B rs3213094 CT + TT genotype was independently associated with PASI75 achievement at week 12 (OR = 4.285, 95% CI 1.500–12.239, p = 0.007). Treatment with anti-IL-17 agents was also an independent predictor of early response (OR = 3.946, 95% CI 1.416–10.998, p = 0.009). No significant association was observed between IL23R rs11209026 and treatment response. DLQI scores improved significantly over time (p < 0.001), without genotype-dependent differences. Conclusions: IL12B rs3213094 SNP is significantly associated with early biologic treatment response in psoriasis, supporting its potential role as a pharmacogenetic biomarker of treatment responsiveness. These findings may inform the integration of genetic markers into personalized therapeutic strategies, particularly in underrepresented populations such as those from Eastern Europe. Further studies in larger cohorts are warranted to validate these results. Full article
12 pages, 1264 KB  
Case Report
Drug-Resistant Tuberculous Spondylitis Treated with Bedaquiline-Containing Regimens in South Korea: Two Case Reports
by Keon Young Lee, Miri Hyun, Ji Yeon Lee and Hyun ah Kim
Antibiotics 2026, 15(5), 493; https://doi.org/10.3390/antibiotics15050493 - 14 May 2026
Viewed by 905
Abstract
Background: South Korea continues to report a considerable burden of drug-resistant tuberculosis (TB). Bedaquiline-containing regimens are recommended for multidrug-resistant pulmonary TB, but evidence regarding the optimal treatment for extrapulmonary manifestations such as spinal TB remains limited. Case presentation: Herein, we report two cases [...] Read more.
Background: South Korea continues to report a considerable burden of drug-resistant tuberculosis (TB). Bedaquiline-containing regimens are recommended for multidrug-resistant pulmonary TB, but evidence regarding the optimal treatment for extrapulmonary manifestations such as spinal TB remains limited. Case presentation: Herein, we report two cases of drug-resistant tuberculous spondylitis that were successfully managed using bedaquiline-containing regimens. Case 1 involved a 67-year-old man who was receiving chemotherapy for lymphoma and had a history of spinal TB treated 20 years earlier. The patient presented with dysphagia and upper limb weakness. Cervical magnetic resonance imaging revealed C4–5 spondylitis with an epidural abscess. He underwent surgical treatment, and Mycobacterium tuberculosis resistant to rifampin was isolated from cultured intraoperatively obtained tissue specimens. The patient received an antibiotic regimen consisting of bedaquiline, levofloxacin, linezolid, cycloserine, and clofazimine. Clinical and radiological improvements were achieved after 12 months of this treatment; bedaquiline was included in the regimen for the first 6 months, while the other agents were continued for the entire course. Case 2 involved a 71-year-old man with T12–L2 spondylitis and a left psoas abscess. Tissue culture confirmed Mycobacterium tuberculosis resistant to isoniazid, rifampin, and ethambutol. The patient was started on the same bedaquiline-containing regimen. Clinical and radiological improvements were observed after 18 months of this therapy, including 6 months of bedaquiline. Conclusions: Our clinical experiences suggest that bedaquiline-containing regimens represent a feasible and effective therapeutic option for drug-resistant tuberculous spondylitis. Larger studies are warranted to establish the optimal management strategies for extrapulmonary drug-resistant TB infections. Full article
(This article belongs to the Special Issue Diagnostics and Antimicrobial Treatment of Tuberculosis)
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22 pages, 315 KB  
Article
Salivary Prevalence of Four Oral Pathogens in Postpartum Women in Northeast Romania: An Exploratory Cross-Sectional Study
by Giorgio Nichitean, Elena Teona Cosovanu, Oana Bejan, Silvia Ionescu, Doina Ivanov, Costin Damian, Demetra Socolov, Mihaela Grigore, Cristina Daniela Dimitriu, Cezar Foia, Ionut Luchian, Diana Tatarciuc, Irina Draga Caruntu, Luminita Smaranda Iancu and Ramona Gabriela Ursu
Pathogens 2026, 15(5), 507; https://doi.org/10.3390/pathogens15050507 - 8 May 2026
Viewed by 681
Abstract
Background: Oral dysbiosis during pregnancy has been associated with adverse outcomes, including preterm birth, premature rupture of membranes (PROM), and low birth weight, yet oral health remains an underappreciated component of routine prenatal care. Dental caries and gingival bleeding are frequently reported during [...] Read more.
Background: Oral dysbiosis during pregnancy has been associated with adverse outcomes, including preterm birth, premature rupture of membranes (PROM), and low birth weight, yet oral health remains an underappreciated component of routine prenatal care. Dental caries and gingival bleeding are frequently reported during pregnancy and may remain clinically relevant in the immediate postpartum period, but their relationship with specific oral pathogens in postpartum women has been insufficiently characterised, particularly in Eastern European populations. Methods: This exploratory cross-sectional, single-centre study included 60 postpartum women recruited consecutively at “Cuza-Vodă” Clinical Hospital of Obstetrics and Gynecology, Iași, Romania, between December 2025 and February 2026. All participants completed a structured questionnaire covering obstetric history, demographic characteristics, and oral hygiene behaviours and underwent a standardised clinical oral examination by two calibrated examiners. Before study initiation, the two examiners underwent a joint calibration session based on the predefined visual oral assessment criteria used in this study and agreed on uniform recording procedures for visible dental caries, self-reported gingival bleeding during brushing, tooth mobility, and overall oral status. Saliva samples were collected after delivery. Genomic DNA was extracted using a magnetic-bead protocol and analysed by Real-Time PCR using TaqMan-based assays to detect four oral pathogens: Porphyromonas gingivalis, Streptococcus mutans, Mycoplasma salivarium, and Fusobacterium nucleatum. Results: Most participants were primiparous (55.0%) and delivered at term (≥37 weeks of gestation; 78.3%). The prevalence of pathogen detection was: P. gingivalis 38.3% (23/60), S. mutans 70.0% (42/60), M. salivarium 71.7% (43/60), and F. nucleatum 100% (60/60). Poly-microbial carriage was common: 15.0% of participants carried all three variable pathogens simultaneously (S. mutans, M. salivarium, and P. gingivalis), and the most frequent two-pathogen combination was S. mutans + M. salivarium (30.0%). No statistically significant associations were identified between pathogen detection and clinical or obstetric variables, consistent with limited statistical power in this small convenience sample. Conclusions: This exploratory study provides the first salivary prevalence estimates for these four oral pathogens in postpartum women in Northeast Romania. The high prevalence of poly-microbial carriage, including the novel quantitative estimate for M. salivarium, provides an empirical foundation for power calculations and future confirmatory research integrating standardised periodontal assessment with pregnancy outcome data. Full article
18 pages, 4618 KB  
Article
Establishment of a Quadruplex RT-qPCR Method for the Detection of All Lineages of PPRV
by Jiao Xu, Jiani Li, Qinghua Wang, Jiamin Zhou, Shuang Liu, Yingli Wang, Jiarong Yu, Jingyue Bao and Lin Yang
Animals 2026, 16(9), 1397; https://doi.org/10.3390/ani16091397 - 3 May 2026
Cited by 1 | Viewed by 916
Abstract
Peste des petits ruminants (PPR) is an infectious disease with high morbidity and mortality rates, and four distinct lineages have been discovered in different regions globally. In this study, a quadruplex RT-qPCR method capable of differentiating all four lineages of PPRV was established. [...] Read more.
Peste des petits ruminants (PPR) is an infectious disease with high morbidity and mortality rates, and four distinct lineages have been discovered in different regions globally. In this study, a quadruplex RT-qPCR method capable of differentiating all four lineages of PPRV was established. By screening specific conserved regions across all viral genomes, we designed primers, as well as four TaqMan probes capable of distinguishing all lineages. The established method underwent validation of its relevant characteristics. The sensitivity of the detection method was determined by testing plasmid serial dilutions ranging from 108 to 100 copies/μL; results showed that the method could detect as few as 10 copies per microliter of PPRV. No cross-reactivity was observed among the four probes or with other common pathogens of goats and sheep. The coefficient of variation (CV) values for inter-assay and intra-assay repeatability of each probe were both below 2% (intra-assay: 0.11% to 0.98%; inter-assay: 0.18% to 1.95%), demonstrating excellent repeatability. Testing of 62 clinical samples also confirmed that the method could effectively detect and differentiate clinical samples of different PPR lineages. This method, for the first time, enabled the differentiation of all PPRV lineages in a single reaction, improving the detection efficiency of the PPR virus and providing robust technical support for the global PPR eradication program. Full article
(This article belongs to the Collection Diseases of Small Ruminants)
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