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Nadav Goldental, Raz Gross, Daniela Amital, Eiran V. Harel, Talma Hendler, Aron Tendler, Liora Levi, Dmitri Lavro, Tal Harmelech, Shulamit Grinapol, Nitsa Nacasch and Eyal Fruchter
Background: Post-traumatic stress disorder (PTSD) manifests through distinct symptom clusters that can respond differently to treatments. Neurofeedback guided by the Amygdala-derived-EEG-fMRI-Pattern (Amyg-EFP-NF) has been utilized to train PTSD patients to regulate amygdala-related activity and decrease symptoms. Methods: We conducted a combined analysis of
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Background: Post-traumatic stress disorder (PTSD) manifests through distinct symptom clusters that can respond differently to treatments. Neurofeedback guided by the Amygdala-derived-EEG-fMRI-Pattern (Amyg-EFP-NF) has been utilized to train PTSD patients to regulate amygdala-related activity and decrease symptoms. Methods: We conducted a combined analysis of 128 PTSD patients from three clinical trials of Amyg-EFP-NF to evaluate effects across symptom clusters (as assessed by CAPS-5 subscales) and on emotion regulation processing (evaluated by the ERQ). Results: Amyg-EFP-NF significantly reduced severity across all PTSD symptom clusters immediately post-treatment, with improvements maintained at three-month follow-up. The arousal and reactivity cluster showed continued significant improvement during follow-up. Combined effect sizes were large (η2p = 0.23–0.35) across all symptom clusters. Regression analysis revealed that emotion regulation processes significantly explained 17% of the variance in symptom improvement during the follow-up period. Conclusions: Reduction of PTSD symptoms following Amyg-EFP-NF occurs across all symptom clusters, with emotional regulation processes potentially serving as an underlying mechanism of action. These results support Amyg-EFP-NF as a comprehensive treatment approach for PTSD that continues to show benefits after treatment completion.
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This paper focuses on the development and experimental validation of a single-phase modular multilevel converter (MMC) based on a battery energy storage system (BESS) for residential uninterruptible power supply (UPS) with two-level active SoC balancing control. The configuration and mathematical modeling of the
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This paper focuses on the development and experimental validation of a single-phase modular multilevel converter (MMC) based on a battery energy storage system (BESS) for residential uninterruptible power supply (UPS) with two-level active SoC balancing control. The configuration and mathematical modeling of the single-phase MMC-BESS are first presented, followed by the details of the control strategies, including dual-loop output voltage and current control in islanded mode, grid-connected control, circulating current control, and two-level active state-of-charge (SoC) balancing control. The design and optimization of the quasi-proportional-resonant (QPR) controllers were investigated by using particle swarm optimization (PSO). Simulation models were built to explore the operating characteristics of the UPS under islanded mode with an RL load and grid-connected mode and assess the control performance. A 500 W experimental prototype was developed and is herein presented, including results under different operating conditions of the MMC-BESS. The experimental results show that for both RL load and grid-connected tests, balancing was achieved. The response time to track the reference value was two grid periods (0.04 s). In the islanded mode test, the THD was 1.37% and 4.59% for the voltage and current, respectively, while in the grid-connected mode test, these values were 1.72% and 4.24% for voltage and current, respectively.
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Layered Ruddlesden–Popper titanates HLnTiO4 and H2Ln2Ti3O10 (Ln = La, Nd) have been exfoliated into nanosheets in aqueous tetrabutylammonium hydroxide and systematically investigated as hydrogen evolution photocatalysts. The nanosheets were tested both in as-prepared pristine form
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Layered Ruddlesden–Popper titanates HLnTiO4 and H2Ln2Ti3O10 (Ln = La, Nd) have been exfoliated into nanosheets in aqueous tetrabutylammonium hydroxide and systematically investigated as hydrogen evolution photocatalysts. The nanosheets were tested both in as-prepared pristine form and after reassembly by two methods (simple filtration and precipitation by hydrochloric acid). The nanosheet-based samples demonstrated by up to 88 times greater photocatalytic performance in comparison with the bulk precursors and, after modification with a Pt cocatalyst, provided apparent quantum efficiency of hydrogen generation up to 14.2% in 1 mol.% aqueous methanol and 3.15% in pure water. It was established that the form in which the nanosheets are used strongly affects the hydrogen production efficiency: the latter typically decreases when moving from the pristine nanosheets to filtered ones and then to those restacked by hydrochloric acid, which is determined by the difference in their physical–chemical characteristics being influenced by the reassembly approach.
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Background and Objectives: Telerehabilitation (TR) offers an innovative approach to overcome accessibility challenges in managing multiple sclerosis (MS). This exploratory study evaluated the efficacy of integrating respiratory exercises into TR programs for improving respiratory function, fatigue, and quality of life. Materials and [...] Read more.
Background and Objectives: Telerehabilitation (TR) offers an innovative approach to overcome accessibility challenges in managing multiple sclerosis (MS). This exploratory study evaluated the efficacy of integrating respiratory exercises into TR programs for improving respiratory function, fatigue, and quality of life. Materials and Methods: A randomized controlled trial involving 48 MS patients randomized into TR and control groups was conducted. Both groups performed respiratory exercises over eight weeks. Pulmonary function, fatigue severity (FSS), quality of life (MSQOL-54), and functional capacity (6MWT) were assessed before and after the intervention. Results: Both groups demonstrated significant within-group improvements in FEV1 (L), PEF (L), FEF%25–75 (L), FSS, MSQOL-54 physical and mental subscales, and the 6MWT distance (p < 0.05). The TR group exhibited unique improvements in FEV1 (%) and slightly greater reductions in fatigue, although the intergroup differences were not statistically significant. Conclusions: Telerehabilitation incorporating respiratory exercises effectively enhances the respiratory function, fatigue, and quality of life of MS patients, suggesting a viable alternative to conventional rehabilitation. Future studies should focus on advanced-stage MS, long-term sustainability, and technological integration to optimize the potential of TR.
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The enhancement of proppant conductivity in shale gas fracturing can be effectively achieved through the implementation of coated proppants. After soaking, non-curable viscous resin-coated proppants exhibit progressive viscosity development and spontaneous agglomeration during the transportation phase. Furthermore, upon fracture closure, the formed proppant
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The enhancement of proppant conductivity in shale gas fracturing can be effectively achieved through the implementation of coated proppants. After soaking, non-curable viscous resin-coated proppants exhibit progressive viscosity development and spontaneous agglomeration during the transportation phase. Furthermore, upon fracture closure, the formed proppant agglomerates demonstrate significant stability and do not flow back with the fracturing fluid through the wellbore. While contemporary research has mostly focused on proppant coating methodologies, the transportation process of these proppants remains insufficiently investigated. To fill this knowledge gap, a sophisticated migration two-phase flow coupling model was developed utilizing the computational fluid dynamics–discrete element method (CFD-DEM) approach. This model incorporates the bond contact forces between film-coated proppant particles, accounting for their distinctive cementing characteristics during transport. Through comprehensive numerical simulations, the transport properties of film-coated proppants were systematically analyzed. Field application indicated that compared with conventional continuous sand fracturing, the amount of proppant after treatment with viscous resin film was reduced by 35% and the production was increased by about 25–30%. Additionally, the optimization of the field-scale coated proppant transport processes was achieved through the implementation of a lower fracturing displacement combined with staged sand addition.
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(1) Background: It is controversial if Merkel cell carcinomas (MCCs) spread to lymph nodes or distant metastases (LNM/DM) first. (2) Methods: A total of 303 patients from six institutions (March 1982–February 2015) were combined with individual patient data from a PubMed search, totaling
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(1) Background: It is controversial if Merkel cell carcinomas (MCCs) spread to lymph nodes or distant metastases (LNM/DM) first. (2) Methods: A total of 303 patients from six institutions (March 1982–February 2015) were combined with individual patient data from a PubMed search, totaling 949 patients. The primary outcome was recurrence patterns. (3) Results: (a) More patients presented with lymph node metastases (LNMs) than DMs at diagnosis: 17.9% (166 among the 929 patients with known staging) vs. 1.9% (18/929); (b) 310/929 (33.4%) developed lifetime DM, of whom 220/310 also developed LNM. The majority (133 patients) of patients were documented to have developed LNM before DM. (c) A shorter median time of 1.5 months (range: 0–47.0) from initial diagnosis to LNM, versus 8 months (range: 0–107.8) to DM, was also found. Another observation was that 2.4% (23/949) of patients with primary tumors ≤1 cm developed lifetime DM, with the smallest being 0.2 cm. (4) Conclusions: Three observations support the idea that prior LNM gives rise to subsequent DM as the main pathway of dissemination in MCC. This implies that patients with nodal metastases should be considered for adjuvant systemic therapy studies as an enriched population. Participation in clinical trials is strongly encouraged.
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The influence of pH on silicon dioxide direct bonding is studied, unveiling its role in bonding energy enhancement. We show that the deposition of basic salt or molecules consistently increases the silicon dioxide adherence energy. The underlying mechanisms, including silica hydrolysis and catalysis
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The influence of pH on silicon dioxide direct bonding is studied, unveiling its role in bonding energy enhancement. We show that the deposition of basic salt or molecules consistently increases the silicon dioxide adherence energy. The underlying mechanisms, including silica hydrolysis and catalysis of siloxane bond formation, are explored. The results offer valuable insights into optimized direct bonding processes for microelectronics and related applications.
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The optimization of overhead hoist transport (OHT) systems in semiconductor manufacturing plays a crucial role in improving production efficiency. In this study, the development of a discrete event simulation model to analyze the physical and control characteristics of an OHT system is presented,
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The optimization of overhead hoist transport (OHT) systems in semiconductor manufacturing plays a crucial role in improving production efficiency. In this study, the development of a discrete event simulation model to analyze the physical and control characteristics of an OHT system is presented, focusing on building a modular simulation framework for evaluating operational strategies by applying various optimization techniques. Additionally, a step-by-step analysis is introduced to optimize OHT operation using the developed model. The simulation model is broadly divided into three parts according to their purposes. The physical system encompasses the physical entities such as the equipment and vehicles. The experimental frame comprises a generator, which triggers experiments, and a result analyzer. Finally, the system controller is structured hierarchically and consists of an upper layer, known as the manufacturing control system, and subordinate layers. The subordinate layers are modularly divided according to their roles and encompass a main controller responsible for OHT control and a scheduling agent manager for dispatching and routing based on SEMI commands. The proposed simulation model adopts a structure based on the discrete event systems specification (DEVS). Since the hierarchical system controller may face challenges such as computational overhead and adaptability issues in real-world implementation, the modular design based on DEVS is utilized to maintain independence between layers while ensuring a flexible system configuration. Through an exploratory analysis using the simulation model, we adopt a step-by-step approach to optimize the OHT operation. The optimal operation is achieved by identifying the optimal number of OHT units and pieces of equipment per manufacturing zone. The results of the exploratory analysis for the three scenarios validate the effectiveness of the proposed framework. Increasing the number of OHT units beyond 17 resulted in only a 0.08% reduction in lead time, confirming that 17 units is the optimal number. Additionally, by adjusting the amount of equipment based on their utilization rates, we found that reducing the amount of equipment from 12 to five in process E-1 and from seven to three in the OUT process did not degrade performance. The proposed simulation framework was thus validated as being effective in evaluating OHT operational efficiency and useful for analyzing key performance indicators such as OHT utilization rates. The proposed model and analysis method effectively model and optimize OHT systems in semiconductor manufacturing, contributing to improved production efficiency and reduced operational costs. Furthermore, this work can bridge the gap between theoretical modeling and practical complexities in semiconductor logistics.
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Background: Acute lower respiratory tract conditions are highly prevalent in paediatrics. Many of these conditions present as consolidations on imaging studies. One of the most common causes is bacterial pneumonia (BP), which requires an accurate diagnosis to implement the best treatment plan. Despite
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Background: Acute lower respiratory tract conditions are highly prevalent in paediatrics. Many of these conditions present as consolidations on imaging studies. One of the most common causes is bacterial pneumonia (BP), which requires an accurate diagnosis to implement the best treatment plan. Despite the fact that major guidelines constrain the use of invasive tests, chest X-ray (CXR) or blood tests are still routinely used for the diagnosis. In this regard, the introduction of lung ultrasound (LUS) signified an advancement in reducing the invasiveness of diagnosis. However, there are still situations where distinguishing between different aetiologies remains challenging, especially in the case of atelectasis. Methods: This is a prospective cohort study to assess the diagnostic accuracy of new non-invasive, quantifiable, and reproducible imaging biomarkers (lung elastance and microvascularization ratio) for differentiating BP from another major entity that causes the appearance of consolidation in imaging tests, atelectasis. It will be conducted at Sant Joan de Déu Hospital in Spain from June 2025 to June 2027. Firstly, imaging biomarkers will be measured in well-aerated lung tissue without consolidation to establish their values in healthy lung tissue, according to a predefined imaging acquisition protocol. Subsequently, the imaging biomarkers will be assessed in patients with confirmed lung consolidation by LUS (Group 1: BP; Group 2: atelectasis). Results: The study aims to determine whether there are statistically significant differences in the biomarker values in relation to the normal values and between the different etiological groups. Conclusions: The demonstration of the reliable diagnostic accuracy of these biomarkers could significantly reduce the need for invasive techniques and improve the therapeutic management of many patients with BP and other pulmonary conditions presenting with consolidation in imaging tests.
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Extracts from 58 species of corticioid fungi (phylum Basidiomycota), mainly belonging to the orders Hymenochaetales, Polyporales and Russulales, were tested for their inhibitory activity against five species of bacteria: Corynebacterium striatum, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus [...] Read more.
Extracts from 58 species of corticioid fungi (phylum Basidiomycota), mainly belonging to the orders Hymenochaetales, Polyporales and Russulales, were tested for their inhibitory activity against five species of bacteria: Corynebacterium striatum, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Twenty-four of the species we analyzed in this study were tested for antibacterial activity for the first time. The fruiting bodies of the fungi were collected from dead wood in the forests of north-eastern Poland, and macerated in methanol. Dried extracts were redissolved in dimethyl sulfoxide and applied to broth cultures of the bacteria, which were then inoculated on agar plates. Noblesia crocea demonstrated moderate inhibitory activity against all five tested bacteria; Amylocorticium subincarnatum, Laxitextum bicolor, Peniophora laeta, P. rufomarginata, Phanerochaete sordida, and Xylobolus frustulatus inhibited four bacterial species. The extracts from 14 fungal species tested were moderately active against only two bacteria, P. aeruginosa and C. striatum; 17 species were active against C. striatum only. The full inhibition was observed with concentrations of extract 25 or 50 mg/mL.
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Rip currents are fast-moving, narrow channels of water that flow seaward from the shoreline, typically forming within the surf zone and extending beyond the wave-breaking region. These currents pose significant hazards to swimmers, contributing to numerous drowning incidents, especially with the increasing popularity
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Rip currents are fast-moving, narrow channels of water that flow seaward from the shoreline, typically forming within the surf zone and extending beyond the wave-breaking region. These currents pose significant hazards to swimmers, contributing to numerous drowning incidents, especially with the increasing popularity of ocean recreation. Despite their prevalence, rip currents remain difficult to detect visually, and no universally reliable method exists for their identification by beachgoers. To address this challenge, this study presents a novel approach for detecting rip currents in optical images using wavelet-based edge detection and image convolution techniques. Five identification criteria were established based on previous literature and expert observations. The proposed program incorporates image augmentation, averaging, and frame aggregation to enhance generalization and accuracy. Experimental analysis involving four iterations and four wavelet bases demonstrated that using two iterations with the Daubechies wavelet yielded the highest interpretation accuracy (88.3%). Performance evaluation using a confusion matrix further confirmed an accuracy rate of 83.0%. The results indicate that the proposed method identifies rip currents in images, offering a valuable tool for researchers studying rip current patterns. This approach lays the groundwork for future advancements in rip current detection and related research.
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This study aimed to evaluate the practicality and feasibility of using intracavitary electrocardiography to confirm the proper placement of a central venous catheter for hemodialysis. Central venous catheters are typically placed using an echo-guided technique based on anatomical landmarks, followed by X-ray confirmation.
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This study aimed to evaluate the practicality and feasibility of using intracavitary electrocardiography to confirm the proper placement of a central venous catheter for hemodialysis. Central venous catheters are typically placed using an echo-guided technique based on anatomical landmarks, followed by X-ray confirmation. Anesthesiology guidelines recommend evaluating the intracavitary electrocardiogram during the procedure to verify the correct CVC placement. This study involved 11 patients without rhythm disturbances, in whom a central venous catheter was placed in the right internal jugular vein at our institute in 2024. The patient’s electrocardiogram was analyzed using the MAGELLANO® (Italy) device to identify changes in the P wave or QRS complex, which confirmed the CVC’s correct placement at the right cavoatrial junction. Thoracic ultrasound was used to identify the right internal jugular vein and exclude iatrogenic pneumothorax. A subsequent chest X-ray was performed to further confirm the correct placement. In addition, a non-systematic review of the most recent literature on this topic was conducted using the Database PubMed—United States National Library of Medicine. Chest X-ray consistently verified the correct placements identified by ECG-IC, with no post-procedure complications. ECG-IC is a straightforward, viable, and cost-effective technique with high sensitivity when administered by properly trained professionals. This approach, combining ultrasound-guided CVC placement in the right internal jugular vein and intracavitary ECG monitoring, can omit X-ray control in more than 90% of cases.
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Athletic individuals may intentionally aim to gain weight, primarily as lean body mass, to improve athletic performance or to better match opponents’ size. This study aimed to investigate the self-reported nutrition- and exercise-related behaviors of athletic individuals aiming to gain weight. Cross-sectional data
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Athletic individuals may intentionally aim to gain weight, primarily as lean body mass, to improve athletic performance or to better match opponents’ size. This study aimed to investigate the self-reported nutrition- and exercise-related behaviors of athletic individuals aiming to gain weight. Cross-sectional data were drawn from an online survey of athletic adults recruited locally, nationally, and internationally. In total, 168 athletic participants (24 ± 5 years; 29% female, 71% male) completed the survey and were actively attempting or had attempted weight gain in the last 12 months to gain muscle mass (87.5%), for aesthetic reasons (66.1%), or to improve athletic performance (63.7%). The most prevalent dietary strategies reported to increase weight gain were consuming more energy than usual (88.0%) from mainly protein foods (83.9%) and using protein powders (67.3%). In total, 9.6% of participants reported using anabolic hormones. The main exercise change was increased resistance training (81.5%). Our results confirm that both male and female athletic individuals intentionally attempt to gain weight. Nutrition and exercise professionals may use the findings to be aware of these common dietary and exercise strategies and to better educate their athletic clients on appropriate methods that are evidence-based and not detrimental to health.
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Sustainable leisure, shared among grandparents and grandchildren, provides multiple benefits, as it enhances contexts and bonds that foster personal, familiar, social and emotional development. In addition to this, it directly contributes to the achievement of the sustainable development goals, established in Agenda 2030.
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Sustainable leisure, shared among grandparents and grandchildren, provides multiple benefits, as it enhances contexts and bonds that foster personal, familiar, social and emotional development. In addition to this, it directly contributes to the achievement of the sustainable development goals, established in Agenda 2030. The objective was to examine, from the grandparents’ perspective, and taking into account their educational level, the links that exist among co-learning processes and the practice of sustainable intergenerational leisure and its evolution throughout the pandemic era. This project sought to combine quantitative (N = 350) and qualitative (N = 18) methodologies, using an ad hoc questionnaire and a discussion group, in different moments, before and after the pandemic. The SPSS 23.0 statistical program was used for quantitative analysis and the NVivo Release 1.6 software for the qualitative study. The results show that intergenerational co-learning is a motive and a relevant stimulus that encourages both generations to share these experiences in natural spaces, which brings them together and facilitates lifelong learning. It has been proven that, before the lockdown, sustainable leisure practices showed significant differences depending on the level of education of the older generation. This had an impact on participation in activities associated with different types of leisure, with a tendency to increase the practice as the level of education rises. Nevertheless, after the pandemic, a greater reduction has been observed in the practice of shared leisure activities among those with a higher educational level.
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This study investigated the effects of iron supplementation and inflammatory disease on cortisol, white blood cell (WBC) count, total protein (TP), lactate, interleukin 1 β (IL1β), interleukin 6 (IL6), substance P (SP), hepcidin, haptoglobin, and ferric-reducing ability of plasma (FRAP) in calves. Correlation
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This study investigated the effects of iron supplementation and inflammatory disease on cortisol, white blood cell (WBC) count, total protein (TP), lactate, interleukin 1 β (IL1β), interleukin 6 (IL6), substance P (SP), hepcidin, haptoglobin, and ferric-reducing ability of plasma (FRAP) in calves. Correlation analyses for the aforementioned parameters with serum iron and ferritin were performed in 40 neonatal calves over the first 10 days of life. Neither iron supplementation, disease status, nor sex had statistically significant effects on the areas under the curve of ferritin, WBC, TP, IL1β, IL6, SP, hepcidin, haptoglobin, or FRAP. However, cortisol concentrations were influenced by disease development. Cortisol concentrations were higher at birth (44.1 ± 1.95 ng/mL) than on day 2 (38.8 ± 1.87 ng/mL) (p = 0.0477), and healthy animals exhibited lower cortisol concentrations than diseased calves (p = 0.0028). Correlation analyses indicated weak positive correlations between ferritin and IL1β (p = 0.0015; ρ = 0.49) and IL6 (p = 0.0011; ρ = 0.50), respectively. The clinical significance of these findings and resulting therapeutic consequences, especially with respect to iron supplementation, should be further investigated in calves and adult cattle.
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Ultra-wideband (UWB) technology is widely used for high-precision indoor positioning due to its adaptability to various environments. However, in long linear areas, such as tunnels or corridors, the near-linear deployment of base stations caused by structural constraints significantly degrades UWB localization accuracy, rendering
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Ultra-wideband (UWB) technology is widely used for high-precision indoor positioning due to its adaptability to various environments. However, in long linear areas, such as tunnels or corridors, the near-linear deployment of base stations caused by structural constraints significantly degrades UWB localization accuracy, rendering conventional algorithms ineffective. To address this issue, this study proposes a high-precision UWB+TOA-R positioning algorithm that incorporates Ridge estimation as a constraint condition. The algorithm introduces equivalent weights to refine the iterative computation of Ridge estimation, establishing an iteratively computed TOA-RR solution model. Experiments were conducted in a long linear corridor to compare the performance of three UWB localization models: the TOA-Least Squares (TOA-LS) model, the TOA-Ridge estimation (TOA-R) model, and the proposed TOA-Ridge estimation iterative (TOA-RR) model. The results indicate that the TOA-LS model suffers from significant coordinate distortions due to abnormalities in the inverse matrix of the coefficient matrix, regardless of the initial tag coordinates. The TOA-R model demonstrates improved accuracy and stability, particularly in cases of significant initial deviations, but still exhibits residual errors. In contrast, the TOA-RR model achieves enhanced stability and accuracy, with a positioning error of approximately 0.5 m. This study resolves the challenge of inaccurate UWB localization in long linear areas, providing a robust solution for such environments.
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Peripheral nerve injury (PNI) remains a significant clinical challenge, often leading to long-term functional impairment. Despite advances in therapies, current repair strategies offer unsatisfactory clinical outcomes. Exosomes derived from induced pluripotent stem cells (iPSC-Exos) have emerged as a promising therapeutic approach in regenerative
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Peripheral nerve injury (PNI) remains a significant clinical challenge, often leading to long-term functional impairment. Despite advances in therapies, current repair strategies offer unsatisfactory clinical outcomes. Exosomes derived from induced pluripotent stem cells (iPSC-Exos) have emerged as a promising therapeutic approach in regenerative medicine. This study assesses the efficacy and safety of iPSC-Exos in a rat model of sciatic nerve crush injury. Briefly, iPSCs were generated from peripheral blood mononuclear cells (PBMCs) of healthy donors using Sendai virus vectors and validated for pluripotency. iPSC-Exos were characterized and injected at the injury site. Functional recovery was assessed through gait analysis, grip strength, and pain response. Histological and molecular analyses were used to examine axonal regeneration, myelination, Schwann cell (SC) activation, angiogenesis, and changes in gene expression. iPSC-Exos were efficiently internalized by SC, promoting their proliferation. No adverse effects were observed between groups on body weight, organ histology, or hematological parameters. iPSC-Exos injection significantly enhanced nerve regeneration, muscle preservation, and vascularization, with RNA sequencing revealing activation of PI3K-AKT and focal adhesion pathways. These findings support iPSC-Exos as a safe and effective non-cell-based therapy for PNIs, highlighting their potential for clinical applications in regenerative medicine.
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Growth differentiation factor 6 (GDF6), a member of the TGF-β superfamily, plays multifaceted roles in tumorigenesis, yet its molecular mechanisms and cancer-type-specific regulatory networks remain poorly defined. This study investigates GDF6’s context-dependent functions through pan-cancer multi-omics integration and functional validation. Transcriptomic data from
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Growth differentiation factor 6 (GDF6), a member of the TGF-β superfamily, plays multifaceted roles in tumorigenesis, yet its molecular mechanisms and cancer-type-specific regulatory networks remain poorly defined. This study investigates GDF6’s context-dependent functions through pan-cancer multi-omics integration and functional validation. Transcriptomic data from TCGA (33 cancers, n = 10,535) and GTEx were analyzed to assess GDF6 dysregulation. Co-expression networks, pathway enrichment (KEGG/GO), and epigenetic interactions (m6A, m5C, m1A) were explored. Functional assays included siRNA knockdown, wound healing, and validation in immunotherapy cohorts. GDF6 exhibited bidirectional expression patterns, with downregulation in 23 cancers (e.g., GBM, BRCA) and upregulation in 7 malignancies (e.g., KIRC, PAAD). Mechanistically, GDF6 activated the PI3K-Akt/VEGF pathways, thereby promoting angiogenesis and metastasis. It modulated epigenetic regulation through interactions with m6A readers and erasers. Additionally, GDF6 reshaped the immune microenvironment by recruiting myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts. Notably, GDF6’s dual role extended to immunotherapy: it suppressed anti-PD1 efficacy but enhanced anti-PD-L1 sensitivity, linked to differential MHC-II and hypoxia-response regulation. This study deciphers GDF6’s context-dependent molecular networks, revealing its dual roles in metastasis and immune evasion. These findings highlight GDF6 as a central node in TGF-β-mediated oncogenic signaling and a potential therapeutic target for precision intervention.
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de Grijs and Bono (ApJS 2020, 246, 3) compiled a list of distances to M87 from the literature published in the last 100 years. They reported the arithmetic mean of the three most stable tracers (Cepheids, tip of the red giant branch, and
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de Grijs and Bono (ApJS 2020, 246, 3) compiled a list of distances to M87 from the literature published in the last 100 years. They reported the arithmetic mean of the three most stable tracers (Cepheids, tip of the red giant branch, and surface brightness fluctuations). The arithmetic mean is one of the measures of central tendency of a distribution; others are the median and mode. The three do not align for asymmetric distributions, which is the case for the distance moduli to M87. I construct a kernel density distribution of the set of and estimate the recommended distance to M87 as its mode, obtaining mag, corresponding to Mpc, which yields uncertainties smaller than those associated with the mean and median.
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The high input/output demands of memory packages require precise trace width and spacing, posing challenges for contemporary package design. Substrate copper trace cracks are a major reliability issue during temperature cycling tests (TCTs). This study offers a detailed analysis of copper trace crack
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The high input/output demands of memory packages require precise trace width and spacing, posing challenges for contemporary package design. Substrate copper trace cracks are a major reliability issue during temperature cycling tests (TCTs). This study offers a detailed analysis of copper trace crack mechanisms through experimental observations, material characterization, and numerical simulations. Common failure modes of trace cracks are identified from experimental data, pinpointing initiation sites and propagation paths. Young’s modulus of copper foil samples is assessed using four testing methods, revealing consistent trends across samples from different substrate suppliers. Sample A with higher E/H values tested via nanoindentation correlated with lower failure rates in the experiment. Stress–strain testing on copper foil was successfully performed at the lower TCT temperature limit of −65 °C, providing vital input for finite element (FE) models. The simulations show strong alignment with trace crack locations under different failure modes. The impact of copper trace width and material properties is illustrated in numerical models by comparing variations in plastic strain responses, which show differences of up to 40% and 30%, respectively. The simulation design of the experiments (DOE) indicates that high-strength solder resist (SR) can significantly enhance temperature cycling performance by reducing SR and copper trace stress and strain by up to 75%. The accumulation of plastic strain in copper traces is predicted to increase up to four times when SR breaks at the crack location, underscoring the importance of SR in copper trace reliability.
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Luis Pacheco, Fernando Oliveira Tavares, Makhabbat Ramazanova, Jorge Fuentes Ávila, Helena Albuquerque, Fátima Matos Silva, Jorge Marques, Mario Guillo, Beatriz Barrera Zuleta and Silvia Marín Guzmán
Research outputs in higher education institutions (HEIs) are crucially dependent on the research management process. Departing from a SWOT analysis, the main objective of this paper is to analyze the perceptions of stakeholders (researchers, teachers, and senior research managers) regarding the main strengths
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Research outputs in higher education institutions (HEIs) are crucially dependent on the research management process. Departing from a SWOT analysis, the main objective of this paper is to analyze the perceptions of stakeholders (researchers, teachers, and senior research managers) regarding the main strengths and weaknesses of HEIs, as well as assess the potential opportunities and threats present in the external environment. It analyzed a total of 462 responses from seven HEIs and two ministries participating in the INNOVA project in Bolivia and Paraguay. The results from the statistical analysis indicate that the respondents tend to identify the traditional obstacles and facilitators to research development, namely, the scarcity and instability of public policies, which permeate the institutions, diminishing the consistency of internal research policies and creating difficulties in access to funding and career development opportunities. Building on the substantial progress made in recent years, the unvirtuous cycle may be halted with political stability and committed action between all the concerned parties.
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In an increasingly interconnected world, businesses may face the challenge of managing crises, whether they are economic downturns, natural disasters, or global pandemics. During such times, building strong and sustainable marketing resilience becomes crucial for businesses aiming to survive and thrive. Digital technologies—particularly
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In an increasingly interconnected world, businesses may face the challenge of managing crises, whether they are economic downturns, natural disasters, or global pandemics. During such times, building strong and sustainable marketing resilience becomes crucial for businesses aiming to survive and thrive. Digital technologies—particularly social media platforms and artificial intelligence (AI)—can play a vital role in enhancing marketing resilience. This research seeks to answer the core question: “How can social media and AI technologies help businesses build marketing resilience during crises”? Drawing from a literature review, this study analyzes a wide range of relevant research. The findings indicate that AI and social media together contribute to enhancing marketing resilience during crises by enabling real-time engagement, data-driven decision-making, and personalized communication. However, these technologies also present challenges, such as privacy concerns, algorithmic bias, and potential risks to brand reputation. This research contributes to the field by analyzing how AI and social media technologies enable companies to remain agile, reduce the impact of crises, and maintain sustainability objectives in their marketing practices.
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Mike Nundwe, Joseph Yamweka Chizimu, John Mwaba, Misheck Shawa, Rodrick S. Katete, Mable Mwale Mutengo, Ruth Nakazwe, Namwiinga R. Mulunda, Cephas Sialubanje, Mox Malama Kalumbi, Yamba Kaunda, Rapheal Chanda, Herman Chambaro, Harvey K. Kamboyi, Thoko Kapalamula, Steward Mudenda, Freeman W. Chabala, Bernard M. Hang’ombe, Roma Chilengi, Chie Nakajima and Yasuhiko Suzukiadd
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Background: Shigella species are the leading cause of human shigellosis. In Zambia, more than 30% of children experiencing diarrhea are infected with Shigella species. The increasing resistance of Shigella species to the recommended therapy is of great concern. Therefore, this study investigated the
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Background: Shigella species are the leading cause of human shigellosis. In Zambia, more than 30% of children experiencing diarrhea are infected with Shigella species. The increasing resistance of Shigella species to the recommended therapy is of great concern. Therefore, this study investigated the antibiotic resistance profiles and phenotypic and genotypic characteristics of Shigella isolates at the largest referral hospital in Zambia. Methodology: Of the forty-eight archived presumptive Shigella isolates, thirty-two were serologically confirmed and subjected to antimicrobial susceptibility testing using the Kirby Bauer disk diffusion method. Thereafter, polymerase chain reaction was performed to detect the bla genes. Results: Most isolates were Shigella flexneri (16/32, 50%) and Shigella sonnei (14/32, 44%), while Shigella boydii and Shigella dysenteriae were rare. High resistance rates were noted for sulfamethoxazole/trimethoprim (78%) and tetracycline (75%), while 15.6% of the isolates showed resistance to ciprofloxacin and/or azithromycin. The blaTEM gene encoding beta-lactamase was detected in 7/32 (22%) of isolates. Conclusions: In this study, a significant number of multidrug-resistant isolates were identified. Additionally, Shigella species resistant to the World Health Organization-recommended drugs call for strengthened laboratory diagnosis and close monitoring of these pathogens to guide the clinical management of shigellosis.
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Background: Few studies have compared the risk of reoperation by timing in breast reconstruction surgery after mastectomy. We evaluated the first and total number of reoperations by reconstruction timing in women with breast cancer undergoing primary mastectomy. Methods: A cohort study of 23,301
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Background: Few studies have compared the risk of reoperation by timing in breast reconstruction surgery after mastectomy. We evaluated the first and total number of reoperations by reconstruction timing in women with breast cancer undergoing primary mastectomy. Methods: A cohort study of 23,301 primary mastectomies in women with breast cancer undergoing either immediate breast reconstruction (IBR) or delayed reconstruction was carried out within Kaiser Permanente between 2010 and 2022. The first reoperation rate was calculated using cause-specific Cox Proportional Hazards Models, while Multiplicative Cox Proportional Hazards Models were used to account for mortality and timing in reoperation. Patients were continuously monitored for death, outcome of interest, loss to follow-up through healthcare membership termination, or study end date (31 December 2022). Results: In total, 78.4% (n = 18,276) of the cohort underwent IBR. The average follow-up time was 5.9 years (±3.8). The following covariates were imbalanced (standardized mean difference [SMD] ≥ 0.20) between IBR and delayed groups: BMI, smoking status, year of mastectomy, bilateral procedures, and reconstruction type. The crude incidence of first reoperation was 33.04% vs. 31.72% in IBR vs. delayed patients and the risk of reoperation was 18% higher in IBR patients (HR = 1.18, 95% CI = 1.12–1.25). There was no difference in the risk of reoperation by timing (p > 0.05) when assessing multiple reoperations. The reoperation risk was the highest for IBR patients who did not complete reconstruction or single-stage reconstruction. In addition, the first reoperation rate of IBR patients was higher in those who underwent expander–implant-based reconstruction. Conclusions: The first reoperation rate was higher in IBR patients compared to those who delayed reconstruction, although we failed to detect a difference for multiple returns to surgery, except in certain subgroups. Assessing reoperation risk by timing among different reconstruction modalities can aid patients in making informed decisions about the type of breast reconstruction to undergo.
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This communication examines the interplay between linguistic mediation and knowledge conversion in cyber-sociotechnical systems (CSTSs) via the WAx framework, which outlines various work representations and eight key conversion activities. Grounded in enactivist principles, we argue that language is a dynamic mechanism that shapes,
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This communication examines the interplay between linguistic mediation and knowledge conversion in cyber-sociotechnical systems (CSTSs) via the WAx framework, which outlines various work representations and eight key conversion activities. Grounded in enactivist principles, we argue that language is a dynamic mechanism that shapes, and is shaped by, human–machine interactions, enhancing system resilience and adaptability. By integrating the concepts of simplexity, complixity, and complexity compression, we illustrate how complex cognitive and operational processes can be selectively condensed into efficient outcomes. A case study of a chatbot-based customer support system demonstrates how the phases of socialization, introspection, externalization, combination, internalization, conceptualization, reification, and influence collaboratively drive the evolution of resilient CSTS designs. Our findings indicate that natural language serves as a bridging tool for effective sense-making, adaptive coordination, and continuous learning, offering novel insights into designing technologically advanced, socially grounded, and evolving sociotechnical systems.
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