Indian tobacco farm laborers are primarily women and children working for very low wages. The aim of this study was to explore occupational and reproductive health challenges faced by women tobacco farm labors in Mysore District, India. We conducted interview and six focus group discussions among 41 women tobacco farm laborers. Codes and themes were generated based on deductive and inductive approaches using the socio-ecological model. Participants reported symptoms of green tobacco sickness including headaches, back pain, gastric problems, weakness, and allergies during menstruation, pre-natal, and post-natal periods. Participants had poor awareness about the health effects of tobacco farming and there were gender inequalities in wages and use of personal protective equipment. Participants received support from family and commu-nity health workers during their pregnancy and post-natal period. Women reported wanting ma-ternity benefits from the tobacco board, monetary support, and nutritional supplements. There is a need for health education about the environmental dangers of tobacco among farm laborers, and more supportive policies for women farmworkers during pregnancy and post-natal periods.

The Earth's fresh water resources predominantly is groundwater that is pumped out due to rapid urbanization and aggravated by climate change. Groundwater modeling is a crucial tool for understanding aquifer systems, employing 1D, 2D, and 3D numerical models with distinct applications. One-dimensional models focus on vertical dynamics, examining aquifer properties and simulating vertical contaminant transport. Two-dimensional models extend to regional scales, considering horizontal variations and assessing groundwater-surface water interactions, making them valuable for watershed-scale studies. Three-dimensional models provide a comprehensive representation of hydrogeological systems, capturing intricate flow patterns and aiding site-specific assessments. Comparative analysis reveals model strengths and limitations, emphasizing the importance of calibration for reliable results. Case studies showcase practical applications, such as 1D models in flooding analysis and 2D models for simulating debris flows. Three-dimensional modeling proves essential for understanding complex river-aquifer exchange fluxes. Future directions call for a global groundwater platform to address data variability and technical challenges. Despite substantial investments required, the anticipated returns in scientific advancements, societal benefits, and economic gains are expected to outweigh the initial costs. This review aims in highlighting the significance of advancing all three-dimension groundwater modeling for sustainable water resource management and environmental protection.

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration trough animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, in a one health perspective. This review offers a hands-on vision about the non-invasive and conservative approaches on peripheral nerve injury, focusing the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities, such as low-level laser therapy and ultrasounds. In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoiding situations of permanent monoplegic limbs that could lead to amputation.

Purpose: Inflammation and neutrophils play a central role in both Covid-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on Covid-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations. Methods: We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during Covid-19 infection. Additionally, a unicenter prospective cohort provided data for an exploratory analysis, assessing the immunophenotype of circulating neutrophils and inflammatory cytokines. The primary endpoints were 30-day mortality and severity of Covid-19 disease. Results: Prior to Covid-19, 25% of patients with cancer exhibited elevated dNLR, which increase to 55% at the time of Covid-19 diagnosis. We developed the FLARE score, incorporating both tumor and infection-induced inflammation, which categorized patients into four prognostic groups. The poor prognostic group had a 30-day mortality rate of 68%, significantly higher than the 23% in the favorable group (p<0.0001). The score proved to be an independent predictor of early mortality. The prospective analysis revealed a shift towards immature forms of neutrophils and higher IL-6 levels in patients with cancer and severe Covid-19 infection. Conclusions: A pre-existing tumor-induced pro-inflammatory state significantly impacts Covid-19 outcomes in patients with cancer. The FLARE score serves as an easy-to-use and worldwide accessible effective tool to predict outcomes in this population, while circulating neutrophil subpopulations might provide additional information and could help refine outcome prediction.

Background: Pre-pregnancy overweight and obesity of women of childbearing ages, has alarmingly a growing trend in developed countries. This study aimed to evaluate potential associations between maternal pre-pregnancy excess body weight and childhood demographic and anthropometric characteristics, as well as perinatal and postnatal outcomes. Methods: This is a cross-sectional study conducted on 5198 pre-school children aged 2-5 years old and their matched mothers that were enrolled from nine different Greek regions. Maternal and childhood anthropometric and demographic data, perinatal and postnatal outcomes were collected from medical history records or validated questionnaires. Results: A prevalence of 24.4% and 30.6% of overweight/obesity was recorded for the enrolled children and their mothers 2-5 years postpartum. In multivariate analysis, childhood overweight and obesity was significantly more frequently observed when maternal pre-pregnancy BMI status was overweight or obese [OR: 2.11 (1.80-2.42) p=0.0001]. A high prevalence of caesarean section delivery and childhood diabetes type I was also significantly associated with maternal pre-pregnancy overweight/obesity [OR:1.71 (1.33-2.19) p=0.0175) and OR: 1.27 (1.04-1.53) p=0.0014, respectively]. Conclusions: Maternal pre-pregnancy overweight and obesity rates were related with increased childhood weight status at birth and 2-5 years postpartum, highlighting the necessity of encouraging healthy lifestyle promotion, including healthier nutritional habits, and focusing on obesity population policies and nutritional interventions among women of reproducible age.

Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are highly prevalent and a significant cause of morbidity. Image-guided su-perficial radiation therapy (IGSRT) uses integrated high-resolution dermal ultrasound to improve lesion visualization, but it is unknown whether efficacy varies by histology. This large retro-spective cohort study was conducted to determine the effect of tumor histology on freedom from recurrence in 20,069 biopsy-proven NMSC lesions treated with IGSRT, including 9,928 BCC (49.5%), 5,294 SCC (26.4%), 4,648 SCCIS (23.2%), and 199 lesions with ≥2 NMSCs (1.0%). Freedom from recurrence at 2, 4, and 6 years was 99.60%, 99.45%, and 99.45% in BCC; 99.58%, 99.49%, and 99.49% in SCC; and 99.96%, 99.80%, and 99.80% in SCCIS. Freedom from recurrence at 2, 4, and 6 years following IGSRT did not differ significantly comparing BCC vs. non-BCC or SCC vs. non-SCC but were slightly lower among SCCIS vs. non-SCCIS (p = 0.002). There were no significant differences in freedom from recurrence when stratifying lesions by histologic subtype. This study demonstrates that there is no significant effect of histology on freedom from recurrence in IGSRT-treated NMSC except in SSCIS. These findings support IGSRT as a first-line therapeutic option for NMSC regardless of histology.

Water treatment is one of the most research-challenging areas, and continuously requires the development of efficient sustainable materials for catalytic total mineralization of organic compounds. Herein, Moringa oleifera biomass was converted to "black gold" biochar loaded with ZnO nanoparticles (MOFB@ZnO) by slow pyrolysis, at 500 °C under an inert atmosphere, (MOFB@ZnO). This composite catalyst was used for the total degradation of Congo Red, a model organic pollutant. SEM confirmed the uniform distribution of ZnO nanoparticles, while XPS and XRD indicated the presence of ZnO, primarily in the wurtzite crystalline structure. Optimization was conducted using the central composite design (CCD) method and STATISTICA 12.0 software. The composite catalyst was applied in the electrochemical degradation of Congo Red dye, using a platinum anode and a carbon felt cathode to generate H2O2 from O2 reduction. The ZnO-decorated Moringa oleifera biochar catalyst permitted to achieve of 98% removal of total organic carbon in less than 6h. It is 10-fold more efficient than pristine biochar and can be recycled up to 4 times without any significant loss. The process is highly efficient producing sustainable low-cost catalysts for water purification from organics, and contributes to sustainable chemical processes therefore addressing SDGs 6, 9, and 13.

The failure of immunotherapies in cancer patients is being widely studied due to the complexities present in the tumor microenvironment (TME), where regulatory T cells (Treg) appear to actively participate in providing an immune escape mechanism for tumors. Therefore, therapies to specifically inhibit tumor-infiltrating Treg represent a challenge because Treg are distributed throughout the body and provide physiological immune homeostasis to prevent autoimmune diseases. Characterization of immunological and functional profiles could help to identify the mechanisms that need to be inhibited or activated to ensure Treg modulation in the tumor. To address this, quantitative in-silico approaches based on mechanistic mathematical models integrating multi-scale information from immune and tumor cells and the effect of different therapies have allowed the building of computational frameworks to simulate different hypotheses, some of which have subsequently been experimentally validated. Therefore, this review presents a list of diverse computational mathematical models that examine the role of Treg as a crucial immune resistance mechanism contributing to the failure of immunotherapy. In addition, this review highlights the relevance of certain molecules expressed in Treg that are associated with the TME immunosuppression, which could be incorporated into the mathematical model for a better understanding of the contribution of Treg modulation. Finally, different pre-clinical and clinical combinations of molecules are also included to show the trend of new therapies targeting Treg.

Patient symptoms play a critical role in disease progression and diagnosis, yet they are most often captured in unstructured clinical notes. This study explores use of large language models (LLMs) for extracting patient symptoms from clinical notes, comparing their performance against rule-based information extraction (IE) systems, like BioMedICUS. By fine-tuning an LLM on diverse corpora from multiple healthcare institutions, we aimed to improve symptom extraction accuracy and efficiency with symptoms related to acute and post-acute sequelae of SARS-CoV-2. We also conducted prevalence analysis to highlight significant differences in symptom prevalence across corpora and performed fairness analysis to assess the model's equity across race and gender. Our findings indicate that while LLMs can match the effectiveness of rule-based IE methods, they face significant challenges related to demographic bias and generalizability due to variability in training corpora. This evaluation revealed overfitting and insufficient generalization, especially when models were trained predominantly on limited datasets with single annotator bias. This study also revealed that LLMs offer substantial advantages in efficiency, adaptability, and scalability for biomedical IE, marking a transformative shift in clinical data extraction processes. These results provide real-world evidence of the necessity for diverse, high-quality training datasets and robust annotation processes to enhance LLM’s performance and reliability in clinical applications.

Polypharmacy, the use of multiple medications, is a prevalent issue globally that contributes to increased healthcare costs and places additional burdens on patients' organs. This study aims to reduce the incidence of polypharmacy in the emergency department. We conducted a retrospective review of randomly selected medical records from the Internal Medicine Department of Taipei MacKay Emergency Department, spanning from August 1, 2023, to October 31, 2023. For cases identified as involving polypharmacy, pharmacists provided medication education using the TRM Polypharmacy Interview Guide, while social workers contacted patients via phone to recommend follow-up visits for deprescribing. Patients experiencing polypharmacy were significantly older than those on appropriate medication regimens (79.8 vs. 67.3 years, p=0.002). After deprescribing interventions, the average number of medications for polypharmacy patients was 5.9 higher than for those receiving appropriate prescriptions (9.2 vs. 3.3, p=0.001). The most common conditions associated with polypharmacy were diabetes mellitus, hypertension, and arrhythmia. Polypharmacy poses a significant medication management challenge, with affected patients taking an average of 6.9 more medications than those on appropriate treatment regimens. Our team’s resource management module successfully reduced the incidence of polypharmacy by 8.4% in the emergency department.

Plastic pollution is a pressing environmental challenge, necessitating the development of biodegradable alternatives like polyhydroxybutyrate (PHB). This study focuses on optimizing PHB production by Neobacillus niacinii GS1, a bacterium isolated from a municipal dumping site. By utilizing agricultural residues such as corn flour, wheat bran, and peptone as substrates, we aimed to establish an eco-friendly method for biopolymer production, contributing to sustainable waste management and bioplastic innovation. The bacterium was identified using morphological, biochemical, and molecular techniques. The optimization process involved adjusting variables such as inoculum age, inoculum size, incubation time, agitation rate, incubation temperature, pH of the medium, carbon sources and nitrogen sources. Response surface methodology (RSM) was employed to identify optimal conditions, with the highest PHB yield of 61.1% achieved under specific conditions: 37°C, pH 7, and an agitation rate of 150 rpm. These findings underscore the potential of Neobacillus niacinii GS1 in converting agro-industrial residues into valuable biopolymers, promoting sustainable bioplastic production, and advancing waste valorization efforts through the use of eco-friendly materials.

There have been multiple technological advancements that promise to gradually enable devices to measure and record signals with high resolution and accuracy in the domain of Brain Computer Interfaces (BCI). Multi-modal BCIs have been able to gain significant traction given the potential to enhance signal processing by integrating different recording modalities. In this review, we explore the integration of multiple neuroimaging and neurophysiological modalities including Electroencephalography (EEG), Magnetoencephalography (MEG), Functional Magnetic Resonance Imaging (fMRI), Electrocorticography (ECoG), and Single-Unit Activity (SUA). This multimodal approach leverages the high temporal resolution of EEG and MEG with the spatial precision of fMRI, the invasive yet precise nature of ECoG, and the single-neuron specificity provided by SUA. The paper highlights the advantages of integrating multiple modalities, such as increased accuracy and reliability, and discusses the challenges and limitations of multimodal integration. Furthermore, we explain the data acquisition approaches for each of these modalities. We also demonstrate various software programs that help in extracting, cleaning, and refining the data. We conclude this paper with discussion on the available literature highlighting recent advances, challenges, and future directions for each of these modalities.

Introduction: Inflammation is a significant contributor to cardiovascular disease (CVD) in people with HIV (PWH), who face twice the risk of CVD compared to the general population. The presence of co-existing rheumatic disease (RD) may further exacerbate inflammation and increase the incidence of CVD events in this population. Methods: We conducted a retrospective study using electronic health record (EHR) data from the Veterans Affairs Medical Center in Atlanta, covering the period from 2000 to 2019. The study included 3,930 veterans with HIV, and assessed the impact of rheumatic disease therapies (RDT) on CVD outcomes. The primary outcome was the first occurrence of a CVD event. Results: Rheumatic disease was significantly associated with an increased risk of CVD events (OR = 2.67; p < 0.001). Additionally, exposure to multiple RDTs (aHR = 2.121, p = 0.047), NSAIDs (aHR = 1.694, p = 0.003), glucocorticoids (aHR = 2.332, p < 0.0001), and hypouricemic agents and colchicine (aHR = 3.445, p < 0.0001) were all significantly associated with increased CVD events. Conclusion: The co-existence of HIV infection and rheumatic disease, along with the use of RDTs, may amplify the risk of CVD events in PWH. These findings underscore the need for further investigation into the relationship between RD, RDTs, and CVD risk in larger, controlled studies, given the potential implications for treatment decisions in this patient population.

Background: Studying patients carrying identical by descent (IBD) pathogenic gene variants allows to control for the disease-causing genetic background and to more accurately document the impact of modifiers. Familial hypercholesterolemia (FH) is characterized by elevated LDL-c levels, premature atherosclerosis and is often caused by defects in the LDLR gene. There is a high prevalence of FH in French Canada carry IBD FH-causing due to a founder effect from France in the 17th Century. Several FH patients currently living in French Canada (founder population) and in France (colonizing population) carry IBD FH-causing variants. The expression of FH is affected by environmental and genetic modifiers and patients with IBD variants may present different characteristics. Methods: In this study, we compared FH clinical expression patients carrying IBD LDLR pathogenic variants living in France or Canada. Four IBD variants, namely c.259T>G p.(Trp87Gly); c.2000G>A p.(Cys667Tyr); c.682G>A p.(Glu228Lys); and c.1048C>T p.(Arg350*) were selected. Untreated plasma lipid profiles, APOE genotype, cardiovascular risk factors and occurrence of symptomatic ASCVD were compared in 105 adult carriers (30 from France and 75 from French Canada). Results: All parameters were similar between the two populations, except for untreated total cholesterol (10.14 ± 1.89 mmol/L vs 8.65 ± 1.84 mmol/L, p=0.0006) and LDL-c concentrations (7.94 ± 1.86 mmol/L vs 6.93 ± 1.78 mmol/L, p=0.016) that were significantly higher in FH patients living in France, a trend that was observed in all studied LDLR variants. Conclusion: This study illustrates that FH patients sharing IBD pathogenic LDLR variants that have evolved in different geographic, cultural and socio-economic environments for hundreds of years, differ in term of cholesterol levels highlighting the importance of better understanding the interplay between genetic and environmental modulators of FH expression.

Water quality control employs techniques mostly targeting individual analytes; group detection is also practiced, but the choice of group methods is limited, which supports interest in developing such methods. We have examined an interaction of hypochlorite with a chlorine-containing heptamethine carbocyanine dye in the presence of 30 organic and inorganic model analytes that were found to induce diverse color changes in the system. The main supposed mechanisms are retardation of the dye oxidation with hypochlorite (presumably by scavenging chlorine radicals) and substitution of chlorine atom in the dye by the most nucleophilic analytes (amines, amino acids, proteins, DNA, phenol). The grass-green substitution product is more contrastingly visible against the dark-purple hypochlorite oxidation product of the dye than against the original emerald-green dye. The indicator reaction is monitored photographically for 10–40 min and the images are processed using principal component analysis (PCA) or linear discriminant analysis (LDA), allowing for data convolution for the complex color transitions. Nitrogen compounds are discriminated from the others, and more reactive analytes (tryptophan, cysteine, bovine serum albumin, and DNA) are detected in the presence of less reactive ones in natural water. The system is promising for the development of group assays for dissolved organic matter and discrimination of water samples.

The combination of nanoemulgel and phytochemistry has resulted in several recent discoveries in the field of the topical delivery systems. The present study aimed to prepare turmeric (Curcuma longa) and neem (Azadirachta indica) based nanoemulgel against microbial infection as topical drug delivery. Olive oil (oil phase), Tween 80 (surfactant), and PEG600 (co-surfactant) were used for the preparation of nanoemulsion. Carbopol 934 was used as gelling agent to convert the nanoemulsion to nanoemulgel and promote to control the release of biological properties of turmeric and neem. The nanoemulsion were characterized based on particle size distribution, PDI values and compatibility using FTIR analysis. In contrast, the nanoemulgel was evaluated based on pH, viscosity, spreadability, plant extract and excipients compatibility or physical state, in-vitro study, ex-vivo mucoadhesive study, antimicrobial properties and stability. The resulting nanoemulsion was homogeneous, stable during the centrifugation process, with the smallest droplets and low PDI values. FTIR analysis also confirmed good compatibility and absence of phase separation between the oil substance, surfactant, co-surfactant with both plant extracts. The improved nanoemulgel also demonstrated a smooth texture, good consistency, pH, desired viscosity, ex-vivo mucoadhesive strength with highest spreadability, and an 18-hour in-vitro drug release study. Additionally, it exhibited better antimicrobial properties against different microbial strain. Stability studies also revealed that the product had good rheological properties and physicochemical state for a period of over 3 months. The present study has affirmed that turmeric and neem based nanoemulgel as a promising alternative for microbial infection particularly associated by microorganisms via topical application.

The Greater Amanzule Peatland (GAP) in Ghana represents an important ecosystem facing dynamic land cover changes as a result of both natural and anthropogenic factors. This study integrates multispectral and radar remote sensing data from Landsat-7 and -8, L-band SAR, and SRTM to conduct a machine learning-based analysis of these changes from 2010 to 2020 and to predict future scenarios up to 2040. Findings reveal a 12% expansion in peatland cover, equivalent to approximately 6,570 ± 308.59 hectares, despite declines in specific peatland types. Concurrently, anthropogenic land uses have increased, evidenced by an 85% rise in rubber plantations (from 30,530 ± 110.96 hectares to 56,617 ± 220.90 hectares) and a 6% reduction in natural forest cover (5,965 ± 353.72 hectares). Sparse vegetation, including smallholder farms, decreased by 35% from 45,064 ± 163.79 hectares to 29,424 ± 114.81 hectares. Projections for 2030 and 2040 indicate minimal changes based on current trends; however, these do not consider potential impacts from climate change, large-scale development projects, and demographic shifts, necessitating cautious interpretation. The results highlight areas of stability and vulnerability within the GAP and offer critical insights for the development of targeted conservation strategies. Additionally, the methodological framework presented provides a robust approach for accurate and detailed landscape-scale monitoring of tropical peatlands, applicable to other regions facing similar environmental challenges.

The optimal surgical approach for thymoma resection is still an object of debate. The increasing experience in robotic-assisted thoracic surgery (RATS) has led to the progressive affirmation of this technique as a valid alternative to Video-Assisted Thoracic Surgery (VATS), sternotomy and thoracotomy in this setting. The present study aims to compare the post-operative and short-term results of RATS Thymectomy for thymoma with those of other main surgical approaches (sternotomy, thoracotomy, and VATS) from a high-volume single center.Between May 2021 - September 2023, 40 consecutive patients underwent RATS Thymectomy for I to limited-stage III thymoma in our center. Three homogenous groups of consecutive patients who received thymic surgery by main alternative approaches (sternotomy, thoracotomy, VATS) over the last 5 years, were identified in order to perform a comparative analysis. Data of operative technique, time of surgery, associated resections, conversion rate, overall morbidity, tumor size, radicality, postoperative pain, length of hospital stay, and cosmetic results were recorded and compared between each control group and the RATS group. Tumor size was higher in the sternotomy group, but not significantly. The mean operative time of RATS interventions was significantly lower than that of sternotomy and VATS. It was significantly shorter compared to thoracotomy if excluding docking-undocking time. Higher rate of associated adjacent structures resection was reported in the sternotomy group (p=0.005). Conversion rate was significantly higher in VATS group (p= 0.026) compared to RATS. Postoperative pain at 24 and 48 hours was significantly lower in RATS group compared to the others. Improved cosmetics results were reported after RATS compared to sternotomy (p= 0.0001) and thoracotomy (p= 0.001) groups, with a trend towards better results compared to VATS (p=0.05). Length of hospital stay was shorter in the RATS group with a significant difference vs. the sternotomy group (p<0.001). These results from a single center confirm the safety and effectiveness of RATS for the treatment of limited stage thymoma. Advantage in terms of operative outcomes, post-operative pain, cosmetic results, and hospital stay was observed if compared to the alternative approaches. Short-term oncologic outcome was excellent based on the high complete excision rate of the tumor.

Polyetheretherketone is a promising material for implants due to its good mechanical properties and excellent biocompatibility. Its accessibility to a wide range of applications is facilitated by the ability to process it with an easy-to-use manufacturing process such as Fused Filament Fabrication. The elimination of disadvantages associated with the manufacturing process, such as a poor surface quality, is a main challenge to deal with. As part of the mass finishing process, centrifugal disc finishing has demonstrated good results in surface optimization, making it a promising candidate for post-processing of additively manufactured parts. The objective of this study is to identify the key parameters of the centrifugal disc finishing process on the waviness of additively manufactured PEEK specimen, which has not been investigated yet. Waviness of the specimen was investigated by means of confocal laser scanning microscopy (CLSM), while weight loss was additionally tracked. Six parameters were investigated: type, amount and speed of media, use of compound, amount of water and time. Type of media, time and speed were found to significantly influence waviness reduction and weight loss. Surface electron microscopy images demonstrated the additional effects of deburring and corner rounding. Results on previous studies with specimens made of metal showed similar results. Further investigation is required to optimise waviness reduction and polish parts in a second post-processing step.

The fracture strength was compared in a scratch test of coatings based on the ZrN system with the introduction of Ti, Nb and Hf, which were deposited on a titanium alloy substrate. The coatings were deposited using Controlled Accelerated Arc (CAA-PVD) technology. The comparison was carried out according to two parameters: adhesion strength to the substrate and overall coating strength. The (Zr,Hf)N coating showed better resistance to destruction, but had worse adhesion to the substrate. As a result, although the coating is retained directly in the scribing groove, a large area of delamination and destruction is formed around the groove. The (Ti,Zr,Nb)N coating, with its somewhat lower strength, has high adhesion to the substrate; no noticeable delamination is observed along the groove boundary.

In vitro cancer cell cytotoxicity (IC50 values) of (E)-3-(4’-methylbenzylidene)-4-chromanone (IIIb) showed &gt;50.0 decreases in comparison to those of the respective tetralone derivative (IIIc). On the other hand, such a decrease was not observed in the analogous 4-OCH3 (IIc and IIIc) derivatives. Since the compounds can be considered cyclic chalcone analogs, kinetics and diastereoselectivity of non-enzyme catalyzed reactions with reduced glutathione (GSH) and N-acetylcysteine (NAC) of IIIb and IIIc were investigated to assess the possible role of thiol-reactivity in the increased cytotoxicity of IIIb. Reactivity of the compounds and stereochemical outcome of the reactions were evaluated using high-pressure liquid chromatography-mass spectrometry (HPLC-MS). Molecular modeling calculations were performed to rationalize the observed differences in the thiol-reactivities of the chromanones (III) and the previously investigated tetralones (II). The results indicated possible role of spontaneous thiol-reactivity of compounds III in their recorded biological effects.

K+ channels do play a role in cell shape changes observed during cell proliferation and apoptosis. Research suggested that the dynamics of aggregation of Aquaporin-4 (AQP4) into AQP4-OAPs isoforms can trigger cell shape changes in malignant glioma cells. Here, we investigated the relationship between AQP4 and some K+ channels in the malignant glioma U87 line. The U87 cells transfected with the human M1-AQP4 and M23-AQP4 isoforms were investigated for morphology, gene expression of KCNJ8, KCNJ11, ABCC8, ABCC9, KCNMA1, and Cyclin genes by RT-PCR, recording the whole-cell K+ ions currents by patch-clamp experiments. AQP4 aggregation into OAPs increases the plasma membrane functional expression of the Kir6.2 and SUR2 subunits of the KATP channels, and of the KCNMA1 of the BK channels in U87 cells leading to a large increase in inward and outward K+ ion currents. These changes were associated with changes in morphology with a decrease in cell volume in the U87 cells and an increase in the ER density. These U87 cells accumulate in the mitotic and G2 cell cycle. The KATP channel blocker zoledronic acid reduced cell proliferation in either M23 AQP4-OAPs and M1 AQP4-tetramers transfected cells leading to early and late apoptosis, respectively. BK channel sustains the efflux of K+ ions associated with the M23 AQP4-OAPs expression in the U87 cells, but it is downregulated in the M1 AQP4-tetramers cells; KATP channels are effective in the M1 AQP4-tetramers and M23 AQP4-OAPs cells. Zoledronic acid can be effective in targeting pathogenic M1 AQP4-tetramers cell phenotype inhibiting KATP channels and inducing early apoptosis.

Mango industry played important roles in the economy of tropical and subtropical regions in China. Embryo abortion, flesh rotten, pericarp stain and so on always result in heavy loss. Transgenic breeding is a potential way for solving these problems. However, dependable protocol for mango transgene has not been reported until now. In this research, we found that after mango embryogenic callus were infected by Agrobacterium, most callus necrotized and died. No seedling was differentiated from the survived callus. Contents of 106 compounds in mango callus infected by Agrobacterium were found significantly different from those in control. The top 7 up-regulated compounds were gallic acid, phosphoenolpyruvic acid, dihydrotricetin, ubiquinone, dihydrokaempferol, D-erythrose-4-phosphate and cyanidin. The expressions of ROS-related genes, gallic acid synthesis genes, and defense related genes in callus infected by Agrobacterium were significantly higher than those in control. The growth of Agrobacterium on culturing plate pipetting gallic acid was inhibited. Mango callus infected by Agrobacterium transformed with type III secretion system gene cluster (T3SS) and effector gene AvrPto isolated from Pseudomonas syringae pv. tomato strain DC3000 brown and necrotize slower than those infected by Agrobacterium transformed with net vector (NV). The contents of ROS in callus in-fected by Agrobacterium (T3SS-AvrPto) were less than those in callus infected by Agrobacterium (NV). The expressions of genes participated in immune responses in mango callus infected by Agrobacterium (T3SS-AvrPto) were also less than those in mango callus infected by Agrobacterium (NV). The transformation rate of mango callus infected with Agrobacterium (T3SS-AvrPto-gfp) was 1.6 %. No callus infected with Agrobacterium (NV-gfp) was transformed successfully. The efficiency of mango transformation can be improved by constructing Agrobacterium strains harboring type III secretion system gene cluster and its effector gene.

Basophils are initiators of the Th2 response related to the progression of canine visceral leishmaniasis (CanL). Miltefosine has been presented as an alternative in treatment due to its leishmanicide and immunomodulatory effects. Many blood cells have been used as predictive biomarkers, but none of them focused on the immunomodulatory action of miltefosine in the different stages of the disease. Identifying the predictive hematological biomarkers in dogs with visceral leishmaniasis treated with miltefosine. The animals were divided into three groups: sick dogs; infected dogs, dogs exposed. The animals were submitted to differential blood cell count and CanL diagnosis, through DPP, ELISA and qPCR. The groups were monitored from the time zero (T0) before treatment, and the times twenty (T20) and thirty (T30) days after the beginning of treatment using miltefosine at a dose of 1mL/10kg per day for 28 days. Basophils showed an exponential increase in the infected and sick group with an increase of IgG, suggesting a Th2 response. In the exposed group there was reduction of basophils with increase in monocytes and IgG reduction, suggesting a Th1 response. We suggest basophils as a predictive biomarker of immunomodulation in the treatment of CanL with miltefosine.

Background This study aimed to examine the acute effects of different pre-ST strategies on muscular performance and blood pressure (BP) responses in recreationally strength-trained women. Methods: Twelve overweight women with normal-to-elevated BP were recruited and performed six exper-imental protocols in a randomized order: 1) control protocol (CC) – BP assessed without exercises performed, 2) strength training (ST), 3) foam rolling warm-up followed by strength training (FR+ST), 4) specific warm-up followed by strength training (SW+ST), 5) aerobic exercise followed by strength training (AE+ST), and 6) stretching exercises followed by strength training (SE+ST). Strength training consisted of three sets at 80% of 10RM with a self-suggested rest interval between sets for bench press, back squat, bench press 45º, front squat, lat pull-down, leg press, shoulder press, and leg extension. Results: All experimental protocol had a lower total training volume, fa-tigue index, and repetitions performance in relation to ST (p

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain per-iodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tis-sue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL-cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotions of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as il-lustrated by the production of the antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the perio-dontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.

Mucus plugging of the respiratory tract occurs in airway diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis. It can cause blockage of airways, leading to breathlessness and lung failure. Here, we demonstrate the effect of BromAc® in dissolving mucus plugs in an novel ex-vivo ovine obstructive lung model using a ventilatory setup. Mucus simulant was filled into the trachea of freshly slaughtered ovine lungs and ventilated via an endotracheal tube (ETT) using Continuous Mandatory Ventilation. Predetermined single or repeated doses of Bromelain, Acetylcysteine (Ac), BromAc® and saline control were administered via an Aerogen® vibrating nebuliser and ventilated for 30 or 60 minutes. Ventilatory recording of resistance, compliance, tidal volume was conducted and rheology pre and post treatment were measured. A significant decline in airway resistance (p&lt;0.0001) compared to saline control was observed when treated with Bromelain, Ac and BromAc®, with the latter showing a stronger mucolytic effect than single agents. The decline in resistance was also effective in shorter timepoint (p&lt;0.05) at lower doses of the drugs. Changes in compliance, peak pressure and tidal volume was not observed post-administration of the drugs. Rheology measurements revealed that BromAc®™ significantly reduced the viscosity of the mucin at the end of 30-minute and 60-minute time points (p&lt;0.001) compared to the saline control. BromAc® showed complete dissolution of the respiratory mucus simulant and improved ventilatory airflow parameters in the ex-vivo ovine model.

The study was conducted at El-Sabahia Research Station (latitude 31°12'N, longitude 29°58'E), Alexandria, Egypt, to evaluate the effect of Spirulina platensis algae extract on the growth, yield, and juice quality of four sugarcane genotypes during the 2020/2021 and 2021/2022 seasons. The sugarcane genotypes tested (G.T. 54-9, G. 2003-47, G. 84-47, and G. 2004-27) were treated with four concentrations (0, 0.1, 0.2, and 0.3%) of Spirulina algae extract (SE) during their development as plant cane and first ratoon crops. At harvest, the growth, physiological, and juice quality characteristics were documented, while chlorophyll content was measured 210 days after sowing. Spraying canes with 0.2% of SE was the most effective treatment in enhancing all of the evaluated characteristics compared to those left without SE. Cane yield was more closely correlated with stalk weight (r = 0.88), followed by leaf area index (r = 0.82), chlorophyll content (r = 0.82), stalk length (r = 0.76), and number of tillers (r = 0.73), while recoverable sugar yield was closely correlated (P < 0.01) with sugar content% (r = 0.76).

Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3-5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in triple-negative MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMEC) at 2.5% w/v, and it was found that MH reduced proliferation of MCF-7 cells but not that of HMEC. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, effects of MH induced activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.

Agaricus bisporus is one of the most popular mushroom species in the world; however, mushrooms are highly susceptible to browning due to the absence of a protective cuticle layer and high respiration rate. The molecular mechanism underlying the process of mushroom browningneeds to be explored. Here, we analyzed the transcriptomic and metabolomic data from A. bisporusat ambient temperature. Specifically, a total of 263 significantly changed metabolites and 4492 differentially expressed genes were identified. Lipid metabolites associated with cell membrane degradation were predominantly up-regulated during ambient storage. Transcriptomic data further revealed the alterations of the expression of membrane lipid metabolism-related enzymes. Additionally, energy metabolic processes and products such as glycolysis and linoleic acid changed significantly during ambient storage, indicating their potential roles in the quality deterioration of A. bisporus. These findings provide new insights into the underlyingl ipidmetabolic mechanism of A. bisporus during postharvest ambient storage and will provide values for mushroom preservation techniques.

The inclusion of exogenous phytase in broiler P and Ca deficient diets in response to heightened concerns over excessive P excretion into the environment over the years has remarkably been documented. However, responses among these studies have been inconsistent because of the several factors affecting P utilization. For this reason, a systematic review with meta-analysis of results from forty-one studies published from 2000 to February 2024 was evaluated to: 1) quantitatively summarize the size of phytase effect on growth performance, bone strength, and mineralization in broilers fed P and Ca deficient basal diets and 2) estimate and explore the heterogeneity of the effect sizes of outcomes using sub-group and meta-regression analyses. The quality of the included studies was assessed using the Cochrane Collaboration’s SYRCLE Risk of Bias checklists for animal studies. Additionally, applying the random-effects models, Hedges’ g effect size of supplementation with phytase was calculated using the R software to determine the standardized mean difference (SMD) at a 95% confidence interval. Sub-group analysis and meta-regression further explored heterogeneity (P_SMD ≤ 0.05, I² > 50%, n ≥ 10). The meta-analysis showed that supplemental phytase increases ADFI and BWG and reduces FCR at each time point of growth (< 0.0001). Additionally, phytase supplementation consistently increased tibia ash, P and Ca, and bone strength (< 0.0001) of broilers fed P and Ca deficient diets. Results of the subgroup and meta-regression analyses showed that age and strain of broiler, dietary P source, and duration of phytase exposure significantly influence the effect size of phytase on growth and bone parameters. In conclusion, phytase can attenuate the effect of reducing dietary available phosphorus and calcium and improve ADFI, BWG, and reduced FCR, especially when added to starter diets. It further enhances bone ash, bone mineralization, and bone-breaking strength of broilers, even though the effects of bone ash and strength can be maximized in the starter phase of growth. However, the effect sizes of phytase were related to the age and strain of the broiler, dietary P source, and duration of phytase exposure rather than the dosage.

This work presents a methodology for the generation and classification of phase resolved partial discharges (PRPD) patterns based on the use of a printed UHF monopole antenna and signal con-ditioning circuit to reduce hardware requirements. For this purpose, envelope detection technique was applied. In addition, test objects such as a hydrogenerator bar, dielectric disks with internal cavities in an oil cell, potential transformer, and tip-tip electrodes immersed in oil were used to generate partial discharge (PD) signals. To detect and classify partial discharges, the standard IEC 60270 (2000) method was used as reference. After acquisition of conditioned UHF signals, digital signal filtering threshold technique was used, and peaks of partial discharges envelopes pulses were extracted. Feature selection techniques were used to classify the discharges and choose the best features to train machine learning algorithms, such as multilayer perceptron, support vector ma-chine and decision tree. Accuracies greater than 84% were met, revealing the classification potential of the methodology proposed in this work.

Beans are the most widely used protein source in the world and their productivity is directly linked to nitrogen (N). The short crop cycle imposes the need for fast methodologies for N quantification. In this work, we evaluated the performance of four machine learning algorithms in nitrogen prediction using NIR spectroscopy. Increasing doses of nitrogen were applied to the plants and leaf reflectance was collected. Weka software was used to test the algorithms. The selection of the most effective spectral zones was made with the VIP. Considering predictions with the whole NIR, the best results were achieved with RF (R2 = 0,84 and RMSE = 2,69 g kg-1) and KNN (R2 = 0,77 and RMSE = 3,86 g kg-1). The intervals of 700-740 nm and 983-995 nm were considered the most important for the study of N. More efficient predictions were verified when only spectral regions screened by VIP were included, increasing the accuracy of the RF, KNN and M5 models by 6%, 4% and 8%, respectively. The efficiency of N prediction based on NIR reflectance combined with machine learning was verified. This approach can optimize the management of nitrogen fertilization, serving as an important tool in precision agriculture.

Based on a constant volume combustion chamber, the initial ambient pressure effect on combustion performance and flame propagation of the active and passive pre-chamber ignition systems were studied. Compared with the passive pre-chamber, the active pre-chamber can significantly expand the lean combustion limit, enhance the ignition and combustion performance, and speed up the combustion of the main combustion chamber. At slightly lean combustion conditions, the heat release performance has a positive correlation with the initial ambient pressure. As the premixed λ increases, the heat release performance and the initial ambient pressure begin to become negatively correlated. Ignition delay can be minimized by controlling the excess air coefficient in the pre-chamber close to the stoichiometric ratio. The high ambient pressure in the constant volume chamber greatly reduces the mixture entrainment ability of the jet flame at lean combustion conditions, thereby reducing the combustion speed and peak heat release rate.

This study investigates the application of frequency augmentation techniques to improve condition-based maintenance (CBM+) systems for airborne weapon systems, focusing on the predictive accuracy of velocity and acceleration parameters. Utilizing MIL-STD-1553B MUX data from 138 sorties of fixed-wing aircraft, we explored six augmentation methods, including traditional interpolations (linear, quadratic, cubic spline) and advanced machine learning models (K-Nearest Neighbor, LSTM, and Bi-LSTM). Our findings indicate that while traditional methods like linear interpolation are more effective for velocity parameters, advanced ML techniques, particularly Bi-LSTM, provide better results for acceleration parameters, which exhibit more complex and rapid variability. The study underscores the necessity of tailoring augmentation approaches to specific parameter characteristics and highlights the potential of ML models in capturing intricate patterns within time-series data. These insights are critical for advancing CBM+ systems in military avionics, enhancing reliability and operational efficiency through improved data processing strategies. Future work should explore more performant augmentation techniques, such as by integrating multi-dimensional datasets, and explore ways to develop automated tools for a more powerful predictive maintenance framework.

Background: With the rapid improvement of the healthcare technologies, security and privacy of the most sensitive data, health data is at risk. Protecting patient privacy has many components, even though the data are in electronic format. Although patient privacy is thoroughly discussed in the literature, there is no study presenting all components of patient privacy protection. Methods: In this study, a complete evaluation framework is presented, as an evaluation tool, an inventory is developed, reliability and validity of the inventory is examined. Study is conducted in three phases: Conceptual framework development, inventory development and an evaluation case study. In the evaluation, fuzzy conjoint analysis is employed to handle the subjectivity and am-biguity. As the result of the evaluation, the institution is given a patient privacy protection ma-turity grade, between 1 and 5, where 1 is the worst and 5 is the best grade. Results: In the case study, XXX’s biggest hospital, employing 800 nurses, is evaluated. Half of the nurses, 400, have partici-pated in the study. Literature tells healthcare institutions do not invest enough to protect patient privacy, and the study results support this finding. Institution’s maturity grade resulted as level 2, which is bad. Conclusion: The study measures he privacy maturity with many evaluation com-ponents. Result of the evaluation explains to the patients and the public if their data is safe or not. With this maturity grade, patients have an idea about which institution to choose, public can conclude the institutions’ reliability in terms of patient privacy.

Despite significant prevention efforts, the numbers of physically inactive individuals, chronic illnesses, exhaustion syndromes and sick leaves are increasing. A still unresolved problem with exercise promotion is the low participation of sedentary persons. This collective term covers heterogeneous subgroups. Their engagement with movement campaigns and resistance to change are influenced by numerous factors. Our aim was to analyse survey data on health, performance, lifestyle habits and the approachability to physical activity campaigns obtained from the Germany-wide ActIv survey. From 2,888 study participants aged 50-60 years, 668 persons were categorised into the subgroups "never-athletes", "sports-dropouts", "always-athletes" and "sports-beginners". Large and significant group differences were found for BMI, assessment of quality of life, health and fitness, risk factors and health problems. 42.5% of "never-athletes" and 32.5% of "sports-dropouts" did not state any barriers to sport. There are substantial disparities between the non-athlete groups in terms of their motivation to exercise. In contrast, there are comparatively minor differences in motivation between "sports-dropouts" and "sports-beginners", whose health and fitness are the primary motivators for sport. Our analyses suggest that (i) negative health and performance trends cannot be compensated by appeals for voluntary participation in exercise programmes and (ii) powerful incentive systems are required.

Seeing atomic configuration of single organic nanoparticles at sub-Å spatial resolution by transmission electron microscopy has been so far prevented by the high sensitivity of soft matter to radiation damage. The difficulty is related to the need to irradiate the particle with a total dose of few electrons/Å2, not compatible with the electron beam density necessary to search the low-contrast nanoparticle, to control its drift, to finely adjust the electro-optical conditions and particle orientation, and to finally acquire an effective atomic resolution image. On the other hand, the capability to study individual pristine nanoparticles, such as proteins, active pharmaceutical ingredients, and polymers, with peculiar sensitivity to the variation of the local structure, defects, and strain, would provide advancements in many fields, including materials science, medicine, biology, and pharmacology. Here we report direct sub-ångström resolution imaging at room temperature of pristine unstained crystalline polymer-based nanoparticles. This result is obtained by combining low-dose in-line electron holography and phase-contrast imaging on state-of-the-art equipment, providing an effective tool for the quantitative sub-angstrom imaging of soft matter.

In the article, the results of research on a NiTi alloy with a high nickel content (51.7 at.%), produced using the additive technology SLM method and subjected to isothermal aging after so-lution annealing, are presented. The study involved the determination of the sequence of phase transformations occurring using differential scanning calorimetry (DSC), and the determination of the temperature range of these transformations. In parallel, the phase composition was determined using the XRD method; hardness and the Young’s modulus were also determined. The analysis of the DSC results obtained indicates the following characteristic features of the NiTi alloy, which change with ageing time: (1) during cooling (from +1500C to -500C), the type of transformation changes from a one-step transformation after solution annealing to a two-step transformation after the ageing process over 1, 20 and 100 hours at 500°C; (2) during heating (from -500C to +1500C) for all the samples, regardless of the ageing time, only a one-step transformation from martensite M(B19’) to austenite A(B2) is observed; (3) the temperature at which the transformation starts increases with the ageing time, (4) the width of the total temperature range of the transformation M(B19’)  A(B2) during heating changes from large (∆T=49,7°C), after solution annealing, to narrow (∆T=19.3°C and ∆T=17.9°C after 20 h and 100 h of ageing) and, most importantly, (5) a comparison with literature data shows that, irrespective of the composition of the NiTi alloy and the manufacturing technology of the alloy samples (regardless of the fact whether this was traditional or additive technology), a sufficiently long ageing process period leads to the occurrence of the martensite  austenite transformation in the same temperature range.

Due to bacterial contamination, natural medicinal preservatives may be an alternative to enhance the quality of milk. Besides, thorough biocompatibility testing is deemed essential before integrating natural extracts into food products. To address this matter, our research focused on evaluating the antimicrobial potential of Plectranthus amboinicus, Flueggea leucopyrus, Cymbopogon citratus, and Bacopa monnieri against prevalent foodborne pathogens, including Staphylococcus aureus, Escherichia coli, Salmonella spp, and Pseudomonas aeruginosa and investigating the efficacy of plant extracts as natural preservatives along with biocompatibility and toxicity assessments. The methanolic extracts of plant materials were used for measuring antimicrobial activity using the agar well diffusion method, Minimum Inhibitory Concentration (MIC) and Minimum bactericidal concentration (MBC) assays. The preservative activity was tested by isolating pathogenic organisms in a sterilized milk medium and toxicity and biocompatibility was assessed using zebrafish embryo and brine shrimp lethality assays. At a concentration of 400 mg/ml, all plant extracts demonstrated notable activity against bacterial strains. B. monnieri at 400 mg/ml exhibited particularly significant effects on S. aureus (30.3 mm ± 0.6), surpassing the positive control, gentamicin (28.3 mm ± 0.6), while also displaying pronounced activity against E. coli. F. leucopyrus, at the same concentration, showed antimicrobial activity comparable to the positive control against both S. aureus (28.0 mm ± 1.0) and E. coli (27.0 mm ± 1.0). However, as there’s weak-mild toxicity in these herbs, prior to consumption, careful consideration of their toxicity and biocompatibility is imperative for ensuring their safe use.

Background/Aim: Baricitinib (BAR) is the first oral selective Janus kinase inhibitor approved in Europe for rheumatoid arthritis (RA). Real-world data are still needed to clarify its long-term benefit/risk profile. This study aimed to evaluate the effectiveness, persistence, adherence, and safety of BAR in a real-world setting. Methods: An ambispective study was conducted between October 2017 and December 2021 in RA patients starting BAR. Effectiveness was evaluated by change from baseline in the Disease Activity Score using 28-joint counts-C reactive protein (DAS28CRP), and achievement of low disease activity/remission. Drug persistence was evaluated by Kaplan-Meier analysis. Adherence was estimated by medication possession ratio (MPR) and the 5-item Compliance Questionnaire for Rheumatology. Safety was assessed by global incidence proportion and adjusted incidence rates of adverse events. Results: 61/64 recruited patients were finally analyzed, 83.6% female, 78.7% seropositive, mean age of 58.1 (15.4) years, and disease duration of 13.9 (8.3) years. 32.8% were naïve to biologics and 16.4% received BAR on monotherapy. After a median exposure to BAR of 12.4 (6.6-31.2) months (range 3.1-51.4), a significant change in DAS28CRP was observed (difference -1.2, p=0.000). A total of 70.5% and 60.7% patients achieved low disease activity or remission, respectively and 50.8% (31/61) patients remained on BAR during follow-up with a median persistence of 31.2 (9.3-53.1) months. The average MPR was 0.96 (0.08) and all patients were “good adherents” by questionnaire. 21.3% patients discontinued baricitinib due to toxicity. Conclusion: In our real-world practice, BAR demonstrated effectiveness, large persistence, high adherence to treatment and acceptable safety profile.

The conserved cyanobacterial protein PipX is part of a complex interaction network with regulators involved in essential processes that include metabolic homeostasis or ribosome assembly. Because PipX interactions depend on the relative levels of their different partners and of the effector molecules binding to them, in vivo studies are required to understand the physiological significance and contribution of environmental factors to regulation of PipX complexes. Here we have used the NanoBiT complementation system to analyse regulation of complex formation in Synechococcus elongatus between PipX and each of its two best characterized partners, PII and NtcA. Our results confirm previous in vitro analysis on regulation of PipX-PII and PipX-NtcA complexes by 2-oxoglutarate and on regulation of PipX-PII by the ATP/ADP ratio, showing the disruption of PipX-NtcA complexes by increased levels of ADP-bound PII in Synechococcus elongatus. The demonstration of a positive role of PII on PipX-NtcA complexes under the initial response to nitrogen starvation or the impact of a PipX point mutation on the activity of PipX-PII and PipX-NtcA reporters are further indications of the sensitivity of the system. This study reveals additional regulatory complexities in the PipX interaction network, opening the way to future research in cyanobacteria.

The BRAFV600E mutation, found in approximately 50% of melanoma cases, is associated with aggressive tumor behavior and poor prognosis. This study aimed to assess its impact on immunogenic cell death (ICD), a pivotal cytotoxic process triggering anti-tumor immune responses. Through comprehensive in silico analysis of The Cancer Genome Atlas data, we explored the association between the BRAFV600E mutation, immune subtype dynamics, and tumor mutation burden (TMB). Our findings revealed that the mutation correlated with a lower TMB, indicating a reduced generation of immunogenic neoantigens. Investigation into immune subtypes reveals an exacerbation of immunosuppression mechanisms in BRAFV600E-mutated tumors. To assess the response to ICD inducers, including doxorubicin and Me-ALA-based photodynamic therapy (PDT), compared to the non-ICD inducer cisplatin, we used distinct melanoma cell lines with wild-type BRAF (SK-MEL-2) and BRAFV600E mutation (SK-MEL-28, A375). We demonstrated a differential response to PDT between the WT and BRAFV600E cell lines. Further transcriptomic analysis revealed upregulation of IFNAR1, IFNAR2, and CXCL10 genes associated with the BRAFV600E mutation, suggesting their involvement in ICD. Using a gene reporter assay, we showed that PDT robustly activated the IFN-1 pathway through cGAS-STING signaling. Collectively, our results underscore the complex interplay between the BRAFV600E mutation and immune responses, emphasizing a putative correlation between tumors carrying the mutation and their responsiveness to therapies inducing the IFN-1 pathway, such as the ICD inducer PDT, possibly mediated by the elevated expression of IFNAR1/2 receptors.

Abstract: Background: epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early-onset, and unfavorable developmental outcome. We describe a cohort of pediatric patients with EE who underwent intravenous methylprednisolone (IVMP) pulse therapy to examine its efficacy/tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were: ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction >50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of Life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: Twenty-one patients were included. The responding rate was 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Genetic etiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy (p=0.0475). The fourth month of therapy was the minimum time point to establish the effectiveness of the treatment. All patients showed improvements in QoL, EEG tracing and postural-motor development. No relevant adverse events were observed. Conclusions: Our study confirms the efficacy and tolerability of pulse IVMP treatment in pediatric patients with EE, especially with genetic etiology and ESES. The fourth month of therapy was the minimum time point to establish its effectiveness. QoL, EEG and postural-motor development also showed improvement.

Autonomous vehicle technology, employing image sensors for road marking recognition, is largely dependent on the Lane Departure Warning System (LDWS) to prevent vehicular deviations from driving lanes. The effectiveness of image-based lane recognition, however, is susceptible to environmental influences like weather conditions and the surrounding road environment. This study investigates the impact of road marking retro-reflectivity on LDWS under varied environmental conditions. Conducted at the Yeoncheon SOC Demonstration Research Center, the experiments encompassed a spectrum of weather scenarios, incorporating rainfall and shifts between day and night lighting. Controlled wear was applied to white, yellow, and blue road markings, followed by measuring their retro-reflectivity at different stages of degradation. The LDWS's performance was evaluated by assessing the recognition rates of these markings under these diverse environmental settings. The study reveals that enhanced retro-reflectivity significantly boosts LDWS detection, especially in challenging weather conditions. Furthermore, the research led to the development of a simulation framework to analyze the cost-effectiveness of road marking maintenance, aligning it with the safety needs of autonomous vehicles. This framework suggests the necessity for updated road marking guidelines that cater to the advanced needs of driver assistance systems and autonomous vehicle technology.

Objective: In this work, we evaluated the chemical composition by chromatography coupled to mass spectrometry, antimicrobial and insecticidal activity of essential oils (TrEO) and nanoeffu-sion (NTrEO) of oil from Tetradenia riparia leaves. We also evaluated the acute toxicity in Mus musculus. The results showed that S. aureus showed greater susceptibility to TrEO, with a minimum inhibitory concentration (MIC) of 125 µg.mL-1, when compared to P. aeruginosa, E. coli, which presented a MIC of 250 µg.mL-1. There was a greater toxic effect on TrEO (LC50 = 630.29 µg.mL-1) and NTrEO (LC50 = 713.68 µg.mL-1) larvae, effect on pupae (LC50 = 630.29 µg.mL-1) and NTrEO (LC50 = 713.68 µg.mL-1) and ovicide (LC50 = 631.184 µg.mL-1) and NTrEO (LC50 = 146.701 µg.mL-1) of Ae. aegypti after 24 h of exposure, when compared to other exposure periods. Chemical analysis re-vealed 20 components, aromadendrene oxide (23.47%) being the main component. Female and male mice were used to assess toxicity and oral administration of NTrEO to mice did not result in acute toxicity. Thus, the essential oil of T. riparia and its nanoemulsion have insecticidal and an-timicrobial potential for Ae. aegypti, S. aureus, E. coli, P. aeruginosa, and has a high toxicological safety threshold at the concentrations evaluated in this study.

Reactive oxygen species (ROS) play a pivotal role in cellular function, and their overproduction contributes to oxidative stress, fatigue, aging, and diseases. To counteract these effects, incorpo-rating antioxidant-rich nutrients is recommended. Functional waters, including electrolyzed hydrogen water (EHW), are gaining attention for potential antioxidant effects through daily in-take. This study employs aquaphotomics and near-infrared spectroscopy (NIRS) to elucidate the molecular mechanisms behind the antioxidant activity of EHW. Previous investigation reported a 100% loss in antioxidant functionality through autoclaving, and a 40% decrease with hydrogen gas removal, prompting the current investigation into the mechanisms of antioxidant effects and especially the role of water molecular structure in it. Aquaphotomics analysis of near infrared (NIR) spectral data revealed that the primary characteristic of EHW associated with anti-radical function is presence of water solvation shells. Autoclaving and degassing led to loss of these water molecular species and a significant increase in free water molecules. The study suggests that water shells (solvation shells) in EHW play a crucial role in neutralizing ROS, although the specific ions or nanoparticles responsible for creating these shells remain unidentified. This concept aligns well with existing proposals of the crucial role of water solvation shells in ROS neutralization.

Cognitive impairment affects 34-65% of People with Multiple Sclerosis (PwMS), significantly impacting their quality of life. Clinicians routinely address cognitive deficits with in-clinic neuro-behavioural interventions, but accessibility issues exist. Telerehabilitation is a promising solution that utilises digital tools for home-based cognitive remediation. This narrative review assessed the feasibility and efficacy of cognitive telerehabilitation in PwMS, identifying 13 relevant studies. Regarding the feasibility of cognitive telerehabilitation, evidence shows adherence rates are generally good, although, surprisingly, not all studies reported a measure of compliance with the cognitive training explored. Considering the efficacy of different rehabilitative techniques on cognitive performance of PwMS, findings are generally inconsistent, with only one study reporting consistently positive results. A range of methodological limitations are reported as potential factors contributing to the variability of results. Overcoming some of these issues will be key. Upcoming research is necessary to determine optimal intervention approaches, long-term effects of rehabilitation, and how to best integrate the use of telerehabilitation into routine clinical practice. By exploiting digital tools in the best way and addressing methodological concerns, home-based rehabilitation holds the potential for improving cognitive functions and enhancing the quality of life in PwMS.

The discovery by the Large Area Telescope on board Fermi of variable gamma-ray emission from radio-loud narrow-line Seyfert 1 (NLSy1) galaxies revealed the presence of a possible third class of AGN with relativistic jets in addition to blazars and radio galaxies. Considering that NLSy1 are usually hosted in spiral galaxies, this finding poses intriguing questions about the nature of these objects and the formation of relativistic jets. We report on a systematic investigation of the gamma-ray properties of a sample of radio-loud NLSy1, including the detection of new objects, using 7 years of Fermi-LAT data with the new Pass 8 event-level analysis. In addition we discuss the radio-to-very-high-energy properties of the gamma-ray emitting NLSy1, their host galaxy, and black hole mass in the context of the blazar scenario and the unification of relativistic jets at different scales.

This paper aims to establish a current relationship between pharmaceutical sciences and the development of perfumes and fragrances, which bring significant economic benefits and whose added value is among other professionals, the one made by professionals in Pharmacy. For this purpose, historical data are used as a starting point and galenic, chemical and botanical aspects are discussed in a transversal way. In this sense, it must be taken into account that in the case of Spanish pharmacy, it is closely linked to the knowledge and use of plants. Sources such as Web of Science (WOS) and databases such as Scopus, monographs and various web pages (where scientific-technical documents appear) have been used. The results and discussion are based on the selection of the 50 plant species most commonly used in high quality fragrances. Therefore, this publication should be considered as an approach to this subject based on an analysis of a representative sample of data. Some characteristics of perfumes (classification according to the concentration of essential oils and combination of plant extracts) are presented beforehand. They also briefly compile the traditional and modern ways in the treatment of these extracts. The main focus of this work is the botanical and chemical analysis of these described plants, pointing out their common name, correct botanical name, geographical place of origin, used part of the plant and main molecules. The 50 botanical species belong to 27 families of angiosperms and are represented in a large part of the phylogenetic tree of botanical systematics. The most significant families are aromatic: Rutaceae (16.7%), Lamiaceae (16.7%) and Apiaceae (6.5%). The most represented genus is Citrus (with seven species or hybrids). However, it should be noted that natural extracts of good quality natural fragrances may be supplemented with chemically synthesized molecules. Of the 50 botanical species selected, 84% of the extracts have their origin in Tropical Asia, the Middle East and the Mediterranean region. This figure generally coincides with the percentage of medicinal plants (or their extracts) admitted by the European Pharmacopoeia. All parts of a plant (depending on which one it is) can be a source of molecules for the elaboration of these products. The most commonly used parts to obtain extracts are flowers (34%) and leaves (30%), a biological circumstance that is explained in this work. On the opposite side are the resins (10%), rhizomes and roots (8%). In this work, 110 molecules have been found that are part of the essences of perfumes and fragrances, the most frequent are: linalool, limonene, 1,8-cineole, eugenol and derivatives, geraniol, vanillin and derivatives, β-cariophyllene, p-cmene and farnesene and derivatives (3.64%). However, in order to elaborate a quality perfume, many other molecules must be taken into account, according to the creative experience of the perfumer, which is subject to confidentiality and chemical analysis according to current legislation, which would avoid fraud, allergy and dermatitis problems.

Rich biodiversity is one of the Philippines’ greatest assets. Unfortunately, there is a continuous decline in the diversity of flora and fauna across the world. This calls for the need to educate people, especially younger generations, to value and protect biodiversity and natural resources. The study aimed to assess the students’ extent of knowledge and identify their perspectives towards biodiversity and its protection and conservation. A total of 268 randomly selected students at Aurora State College of Technology Zabali Campus were involved in the study. Survey questionnaires were used to obtain data and information which were subjected to statistical tests. The students had a moderate knowledge level on biodiversity with a mean score of 6.65 out of 10 items (SD = 1.50). Their perspective on biodiversity was leaning toward its protection and conservation, with a mean score of 7.2 out of 10 items (SD = 1.29). Factors affecting the students’ knowledge were gender (p = .003) and academic department (p = 0.003). Females and those associated with the Department of Forestry and Environmental Sciences and Department of Industrial technology were found to have more knowledge than the others. Males, on the other hand, were found to have a more positive perspective towards biodiversity. Knowledge and perspective had a weak correlation with r = 0.39. Students were not well-aware, but were in support of the Philippines’ biodiversity-related laws, which could help shape their mindset and actions towards biodiversity conservation and protection. As an implication, the college administration must revisit the curricula of all degree programs and ensure that students from each degree program are environmentally educated, emphasizing biodiversity conservation.

This preprint is focused in the presence of plastics and microplastics in food. We will discuss how many we eat, and how they arrive to the food, and why. We will treat many other things, such as the waste treatment in Europe and in Spain, with updated data; how much plastic waste is generated; what are microplastics and how they are analyzed, I will tell about the experience we have at the University of Alicante (UA); how they can be removed and we will estimate how many we eat over the course of a year.

First, we examine how spin is treated in special relativity and the necessity of introducing spin supplementary conditions (SSC) and how they are related to the choice of a center-of-mass of a spinning particle. Next, we discuss quantum electrodynamics and the Foldy-Wouthuysen transformation which we note is a position operator identical to the Pryce-Newton-Wigner position operator. The classical version of the operators are shown to be essential for the treatment of classical relativistic particles in general relativity, of special interest being the case of binary systems (black holes/neutron stars) which emit gravitational radiation.

Background and Objectives: Clinical trials are a critical step in the development of new medicines and medical devices, testing the efficacy and safety of new treatment regimens. However, if the results of clinical trials are not made public, the evidence base on interventions is incomplete and possibly distorted, which lead to suboptimal treatment choices and negatively affect public health. This study analyses and contrasts the laws and regulations governing clinical trial registration and reporting in China and the United States. Methods: We used desk research to compile, assess and compare current laws, regulations, compliance patterns, and enforcement mechanisms and actions in China and the United States (U.S.). Policy documents were downloaded from Chinese and U.S. government websites. A spreadsheet analysis was utilized for direct comparison. Results: Both China and the U.S. have laws and regulations governing clinical trial registration and reporting. Chinese legislation covers a broader range of trials. In the U.S. trial results must be disclosed to both the national regulator and the public, while Chinese law mandates disclosure to the regulator alone. Cross-country comparisons of regulatory compliance by trial sponsors are impossible due to the opacity of the Chinese data platform. Neither country effectively ensures that all clinical trial results are made public as required by the Declaration of Helsinki and recommended by the WHO. Interpretation: While neither country is perfect, both may be able to learn from each other. There is a major gap in the literature regarding the extent of non-publication of clinical trial results by sponsors operating in China.

Artificial Intelligence (AI) has emerged as a disruptive technology in various areas, and medicine is no exception. In the last decade, there has been rapid progress in the application of AI in healthcare, from diagnosing and prognosticating diseases to improving operational efficiency in hospitals. This literature review explores the advances of artificial intelligence in the field of medicine, discusses its benefits, and discusses the ethical and regulatory challenges that need to be addressed to maximize its potential.

From the formalism of the thermodynamics of irreversible processes and the theory of complex systems, characterization of longevity and aging and its relationship with the emergence and evolution of cancer was carried out. It was found that: 1. The rate of entropy production can be used as an index of robustness, plasticity, the aggressiveness of cancer, and as a measure of biological age; 2. The aging process, as well as the evolution of cancer, goes through what we have called “biological phase transition”; 3. The process of metastasis, which occurs through epithelial-mesenchymal transition (EMT), appears as a phase transition far from thermodynamic equilibrium and exhibits Shilnikov chaos-like dynamic behavior. This dynamic guarantees the robustness of the process and, in turn, its unpredictability; 4. It was shown that as the ferroptosis process is strengthened, the complexity of the dynamics associated with the emergence and evolution of cancer decreases. The theoretical framework developed contributes to a better understanding of the biophysical-chemical phenomena of longevity and aging and their relationship with cancer.

We live in the time of profound transformations commonly labelled with the word “globalization”. The rise of one ecological-technological-social system encompassing our whole planet is an important element of these processes. Solving big global problems demands knowledge of two complementary sorts: on the one hand – going “in depth”, on the other – going “in breadth”. The present paper assumes the second (in a sense: philosophical) perspective. It tries to analyze some relations between the development of technology (IT) and the development of democracy. The notion of democracy, its various forms and axiological reasons for it are considered first. In the subsequent chapter different consequences (both positive and negative) the IT development has for contemporary democracy are discussed. In the next chapter the evolutionary nature of the technological development is debated as well as the question of (democratic) control of this process. The development of Artificial General Intelligence is presented as a challenge for democracy

The internationals guidelines about food intolerances, allergy and immunity provide for rigorous steps in which ultrasonography is not provided. However there is evidence in literature about an ancillar role of ultrasonography in these conditions. In this report we analyze the main pathologies with allergic or immune pathogenesis

Culture, gender and religion are closely linked each other’s, profoundly affect the role of each person within the Society, and also affect the ability to access to the health resources. We are now living a worldwide crisis due to the SARS-CoV-2 pandemic. In order to appropriately tackle it, an alliance between science, politics and citizens is needed. In this article, we summarize current evidences of how religions can represent, on one hand, a risk moment for spreading the virus (in relation with overcrowded events), on the other, a precious opportunity to engage people, and in particular minorities, in fighting the pandemic. To win this fight, we need a multicultural approach that takes into account every aspect of human life, and among these religion, which influences so much culture, everyday life and well-being.

The market of natural and organic cosmetics has been growing in last decades. The increase in interest in this type of product is a consequence of the concern that consumers have been presenting in relation to the environment and health. In addition to the appreciation the use of sustainable ingredients in cosmetic formulations, the consumers are also concerned about pollution caused by the use of plastics, which leads industries to reinvent themselves and rethink about the composition of packaging. The factor that most drives the purchase of natural and organic cosmetics is the fact that the consumer, in addition to contributing to the preservation of the environment, is also using a sustainable product. The growing demand for natural and organic cosmetics results in a concern of the brands with the organic issue, with the decreased use of animal derived ingredients and with the updating the parameters required for certification of a cosmetic as natural or organic. Due to the few studies available in this area, the importance of clarifying the definitions and concepts of natural and organic cosmetics is evident, in order to contribute with accurate information for the cosmetic sector.

Boundary behavior of a given important function or its limit values are essential in the whole spectrum of mathematics and science. We consider some tractable cases of limit values in which either a difference of two ingredients or a difference equation is used coupled with the relevant functional equations to give rise to unexpected results. This involves the expression for the Laurent coefficients including the residue, the Kronecker limit formulas and higher order coefficients as well as the difference formed to cancel the inaccessible part, typically the Clausen functions. We also state Abelian results which yield asymptotic formulas for weighted summatory function from that for the original summatory function

Microbiota plays a key role in various body’s functions, physiological, metabolic and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Several evidences indicate that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that resides on the mucosal surface or within the mucus layer participate in interactions with the host immune system, and a healthy gut microbiota is essential for the development of mucosal immunity. The immunomodulatory activity of probiotics has been proposed in several bowel disorders or in aging-related dysfunctions. In HIV infected patients, the intestinal immune system is affected and inflammation persists during ART therapy too. Several studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition and microbial translocation in HIV infection. This mini-review aims to suggest how the use of probiotics is beneficial not only in maintaining a healthy status but also to improve conditions in HIV subjects.

This article presents a concise survey of basic discrete and semi-discrete nonlinear models which produce two- and three-dimensional (2D and 3D) solitons, and a summary of main theoretical and experimental results obtained for such solitons. The models are based on the discrete nonlinear Schrödinger (DNLS) equations and their generalizations, such as a system of discrete Gross-Pitaevskii (GP) equations with the Lee-Huang-Yang corrections, the 2D Salerno model (SM), DNLS equations with long-range dipole-dipole and quadrupole-quadrupole interactions, a system of coupled discrete equations for the second-harmonic generation with the quadratic (χ⁽²⁾) nonlinearity, a 2D DNLS equation with a superlattice modulation opening mini-gaps, a discretized NLS equation with rotation, a DNLS coupler and its PT-symmetric version, a system of DNLS equations for the spin-orbit-coupled (SOC) binary Bose-Einstein condensate, and others. The article presents a review of basic species of multidimensional discrete modes, including fundamental and vortex solitons, their bound states, gap solitons populating mini-gaps, symmetric and asymmetric solitons in the conservative and PT-symmetric couplers, cuspons in the 2D SM, discrete SOC solitons of the semi-vortex and mixed-mode types, 3D discrete skyrmions, and some others.

Tao and Ming (name) or Tao and Yan (language or speech) is an inseparable pair of important concepts in traditional Chinese language philosophy. In LaoTze’s opinion, Tao could not be spoken out, and language or speech could not reach Tao’s essence. Yan and Tao are separated from each other, and they are paradoxical. All the confusion derives from Yan regardless of how delicate they are. Tao can be expressed in words, but it will never be expressed through common languages. In this article, Tao is regarded as a human being’s thoughts or intentions and is even considered to be the origin of the real world. Language can express people’s thought, although it has some limitations. There exist some contradictions between the real word and the world expressed in words. To enable people to better understand the existence of the real world from multiple perspectives at the language or linguistic level without being constrained by words, this article studies LaoTze’s linguistic philosophy reflected in his opinion on the relationship between Tao and Yan and makes a comparative analysis of modern Western language philosophers’ stand on language (or speech) and existence.

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed, but appears to have tissue-specific roles. Earlier studies have focused on the role of hypothlamic FTO in the regulation of metabolism. However, it appears that FTO plays a role in the regulation of metabolism in a tissue-specific manner. Recent studies suggest that expression of hepatic FTO is regulated by metabolic signals such as nutrients and hormones and altered FTO levels in liver affects glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

Cool-season grasses are the most common forage types in livestock operations and amenities. Several of the cool-season grasses establish mutualistic associations with an endophytic fungus of the Epichloe genus. The grasses and endophytic fungi have evolved over a long period of time to form host-fungus specific relationships that confer protection for the grass against various stressors in exchange for housing and nutrients to the fungus. This review provides an overview of the mechanisms by which Epichloe endophytes and grasses interact, including molecular pathways for secondary metabolite production. It also outlines specific mechanisms by which the endophyte helps protect the plant from various abiotic and biotic stressors. Finally, the review provides information on how Epichloe infection of grass and stress affect the rhizosphere environment of the plant.

Thrombin (factor IIa) and factor Xa (FXa) are key enzymes at the junction of the intrinsic and extrinsic coagulation pathways and are the most attractive pharmacological targets for the development of novel anticoagulants. Twenty non-amidino N²-thiophencarbonyl- and N²-tosyl anthranilamides 1-20 and six amidino N²-thiophencarbonyl- and N²-tosylanthranilamides 21-26 were synthesized and evaluated prothrombin time (PT) and activated partial thromboplastin time (aPTT) using human plasma at concentration 30 μg/mL in vitro. From these results, compounds 5, 9, and 21-23 were selected to study the further antithrombotic activity. The anticoagulant properties of 5, 9, and 21-23 significantly exhibited a concentration-dependent prolongation of in vitro PT and aPTT, in vivo bleeding time, and ex vivo clotting time. These compounds concentration-dependently inhibited the activities of thrombin and FXa and inhibited the generation of thrombin and FXa in human endothelial cells. In addition, data showed that 5, 9, and 21-23 significantly inhibited thrombin catalyzed fibrin polymerization and mouse platelet aggregation and inhibited platelet aggregation induced U46619 in vitro and ex vivo. N-(3'-Amidinophenyl)-2-((thiophen-2''-yl)carbonyl amino)benzamide (21) was most active.

Background: In the aftermath of the ORAL Surveillance trial, real-world studies are needed to elucidate the effectiveness and safety of Janus kinase inhibitors (JAKis) in routine clinical practice. Methods: We performed a multicenter, retrospective cohort study investigating the real-life effectiveness and safety of filgotinib, a novel JAK1 inhibitor, in adult patients with rheumatoid arthritis (RA). Demographic information, disease characteristics, prior treatment history, and comorbid conditions, were retrieved from clinical records at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment. Results: A total of 82 patients (63 women) agreed to participate in the study, of which 39 (47.6%) were older than 65 years. Average RA duration was 13 ± 9 years; 19 patients (23.1%) were current or former smokers and 4 patients (4.9%) had a past history of cardiovascular events. Most patients had previously received at least one biologic disease-modifying antirheumatic drug (range: 1–6+); in addition, 11 patients (13.4%) had been already exposed to another JAKi. During the follow-up, 7 patients discontinued treatment due to primary failure (n = 3) or adverse events (n = 4). Significant reductions in pain and number of tender and swollen joints were observed at T3 and T6. A relevant proportion of patients achieved DAS28-CRP remission at T3 and T6 (46.3% and 66.2%, respectively). Conclusion: Our data provide additional insight into the effectiveness and safety of filgotinib in a real-world setting, even among patients with difficult-to-treat RA and a high prevalence of cardiovascular risk factors.

This work aims to investigate the effect of process temperature and catalyst content by thermochemical degradation of municipal solid waste (MSW) fraction (organic matter + paper + plastic) on the yield of reaction products (bio-oil, biochar, H2O and gas), physi-cochemical properties and chemical composition of bio-oils, as well as on the morphol-ogy and crystalline phases of biochar in laboratory scale. The organic matter, paper and plastic segregated from the gravimetric composition of total waste sample were subject-ed to the pre-treatments of drying, crushing and sieving. Thermal pyrolysis was per-formed at 400, 450 and 475 °C and 1.0 atmosphere, and catalytic pyrolysis at 450°C and 1.0 atmosphere, using 5.0, 10.0 and 15.0% (wt.) of FCC zeolite, bath mode, using a laboratory-scale borosilicate glass reactor. The bio-oil was characterized for acidic val-ue. The chemical functions present in the bio-oil identified by FT-IR and the composi-tion by GC-MS. Biochar was characterized by SEM/EDS and XRD. Thermal pyrolysis of the MSW fraction shows bio-oil yields between 9.44 and 9.24% (wt), aqueous phase yields between 21.93 and 18.78% (wt), solid phase yields between 67.97 and 40.34% (wt) and gas yields between 28.27 and 5.92% (wt). The bio-oil yield decreased with in-creasing process temperature. For the experiments using FCC, the biochar and gas yields slightly increased with increasing FCC content, while that of bio-oil decreased and the H2O phase remained constant. GC-MS of bio-oils identified the presence of hy-drocarbons and oxygenates, as well as nitrogen-containing compounds including am-ides and amines. The acidity of the bio-oil increased with increasing temperature and with the aid of FCC as a catalyst. The presence of hydrocarbons in bio-oil was identified by the addition of FCC catalyst due to the deoxygenation of carboxylic acids, followed by decarboxylation and decarbonylation reactions, producing aliphatic and aromatic hydrocarbons.

Inherited cardiomyopathies are a diverse group of heart muscle diseases caused by genetic mutations that result in structural and functional abnormalities of the myocardium. Understanding genotype-phenotype correlations in these conditions is vital for personalized cardiac medicine, enabling targeted therapeutic strategies and predictive diagnostics. This review explores the major types of inherited cardiomyopathies—hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM)—and provides detailed insights into how different genetic mutations manifest as clinical features. The integration of multi-omics approaches and advanced disease modeling techniques has enhanced our ability to dissect these correlations. The review also discusses the implications of these findings for personalized medicine, including tailored therapeutic strategies, predictive diagnostics, and future research directions.

CD44 regulates cell adhesion, proliferation, survival, and stemness and has been considered a tumor therapy target. CD44 possesses the shortest CD44 standard (CD44s) and a variety of CD44 variant (CD44v) isoforms. Since the expression of CD44v is restricted in epithelial cells and carcinomas compared to CD44s, CD44v has been considered a promising target for monoclonal antibody (mAb) therapy. We previously developed an anti‐CD44v10 mAb, C44Mab-18 (IgM, kappa) to recognize the variant exon 10-encoded region. In the present study, a mouse IgG2a version of C44Mab-18 (C44Mab-18-mG2a) was generated to evaluate the antitumor activities against CD44-positive cells compared with previously established anti-pan CD44 mAb, C44Mab-46-mG2a. C44Mab-18-mG2a exhibited higher reactivity compared with C44Mab-46-mG2a to CD44v3–10-overexpressed CHO-K1 (CHO/CD44v3–10) and oral squamous cell carcinoma cell lines (HSC-2 and SAS) in flow cytometry. C44Mab-18-mG2a exerted a superior antibody‐dependent cellular cytotoxicity (ADCC) against CD44v3–10. In contrast, C44Mab-46-mG2a showed a superior complement‐dependent cytotoxicity (CDC) against CD44v3–10. A similar tendency was observed in ADCC and CDC against HSC-2 and SAS. Furthermore, administering C44Mab-18-mG2a or C44Mab-46-mG2a significantly suppressed CD44v3–10, HSC-2, and SAS xenograft tumor growth compared with the control mouse IgG2a. These results indicate that C44Mab-18-mG2a could be a promising therapeutic regimen for CD44v10-positive tumors.

Glioblastomas (GBMs) are the most malignant and intractable of all cancers, with an unfavourable clinical prognosis for affected patients. The objective was analysis the sensitivity of GBM cells to the antimicrobial peptides (AMPs) cathelicidin (LL-37) and protegrin-1 (PG-1), both alone and in combination with chemotherapy, to predict overall survival (OS) in the patients. The study was conducted on 27 GBM patients treated in the neurosurgical departments of the Almazov Medical Research Centre (Saint-Petersburg, Russia) from 2021 to 2024. The cytotoxic effects of chemo-therapy, AMPs and their combinations on brain tumor cells were assessed by MTT assay using 50%-inhibitory concentration (IC50). In GBM cells from the patients, LL-37 and PG-1 exhibited strong anticancer effects, surpassing those of chemotherapy drugs. These LL-37 and PG-1 anti-cancer effects were associated with a statistically significant increase in life expectancy and OS in GBM patients. These findings were confirmed by the experiments on rats with C6 glioma, where intranasal administration of LL-37 (300 μM) and PG-1 (600 μM) increased the life expectancy of the animals to 69 and 55 days, respectively, compared to 24 days in the control group (HR=4.139, p=0.0005; HR=2.542, p=0.0759). Additionally, the combination of LL-37 and PG-1 with chemo-therapy drugs showed that a high IC50 of LL-37 with cisplatin (cutoff >800 μM) in GBM cells was associated with increased life expectancy (19 vs 5 months, HR=4.708, p=0.0101) and OS in GBM patients. These combinations could be used in future GBM treatments.

Keywords: Chronic Obstructive Pulmonary Disease (COPD), Long Non-Coding RNAs (lncRNAs), Molecular Pathogenesis, Inflammation, Lung Cancer, Diagnostic Biomarkers

This article aims to carry out experiments on water absorption by husked red rice, at constant temperatures of 28, 40 and 50 °C. The description of the absorption kinetics, as well as the analyses of water distribution and volumetric expansion of each grain, at a given instant, was done using a diffusion model. In order for the model to be as close as possible to the real physical situation, the mesh necessary to numerically solve the diffusion equation was generated from the photograph of a grain. Thus, the diffusion equation was written in Boundary-Fitted Coordinates (BFC). The solution of the diffusion equation written in generalized coordinates was then discretized in space and time, using the Finite Volume method, with a fully implicit formulation, considering variable volume and also variable mass diffusivity as a function of local moisture content. Optimizations based on Levenberg-Marquardt algorithm make it possible to determine the parameters of an exponential function relating mass diffusivity and the local moisture content for each temperature. Statistical indicators (chi-square, determination coefficient and Student’s t-test) allowed concluding that the model proposed was very satisfactory for all temperatures, making it possible to simulate water absorption, water distribution and volumetric expansion of the grain over time.

Knowing the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many places during the first wave of COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain), during “Falles” mass gathering events in March 2020, a cross-sectional study was performed in June 2020 querying public health register. Logistic regression models were used. From a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak by anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), thus an underreporting of 92.3% (95% Confidence Interval [CI] 89.5%-94.6%), 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting were no medical assistance for COVID-19 disease, adjusted odds ratio [aOR] 10.83 (95% CI 2.49-47.11), no chronic illness, aOR=2.81 (95% CI 1.28-6.17), middle and lower social classes, aOR=3.12 (95% CI 1.42-6.85), younger age, aOR=0.97 (95% CI 0.94-0.99), shorter duration of illness, aOR=0.98 (95% CI 0.97-0.99). To improve surveillance, studies of representative population samples are necessary to estimate the magnitude of future epidemics, and novel approaches are recommended.

Hydroalcoholic extracts from Malbec and Torrontés wine pomace (Vitis vinifera L.) originating from the high-altitude vineyards of Argentina's Calchaquí Valleys were characterized. Total phenolics, hydroxycinnamic acids, orthodiphenols, anthocyanins, non-flavonoid phenolics, total flavonoids, flavones/flavonols, flavanones/dihydroflavonols, and tannins were quanti-fied through spectrophotometric methods, with Malbec extract exhibiting higher concentra-tions in most of phytochemical groups when compared to Torrontés. HPLC-DAD identified more than 30 phenolic compounds in both extracts. Malbec displayed superior antiradical ac-tivity (ABTS cation, nitric oxide, and superoxide anion radicals), reduction power (iron, copper and phosphomolybdenum), hypochlorite scavenging, and iron chelating ability, compara-tively to Torrontés. The cytotoxicity assessments revealed that Torrontés affected the viability of HT29-MTX and Caco-2 colon cancer cells by 70% and 50%, respectively, at the highest tested concentration (1 mg/mL). At the same time, both extracts did not demonstrate acute toxicity in Artemia salina or in red blood cell assays at 500 µg/mL. Both extracts inhibited the lipoxygen-ase enzyme, with Malbec also reducing the tyrosinase activity and neither inhibited the xan-thine oxidase. The substantial phenolic content and diverse biological activities in Calchaquí Valleys' pomaces underline their potentialities to be valorized for pharmaceutical, cosmetic, and food industries.

Pancreatic cancer stands out as one of the most lethal forms of malignancies, representing 2% of all cancer cases and contributing to 5% of cancer-related fatalities. Therefore, early detection of pancreatic cancer is crucial for enhancing treatment outcomes. Various hereditary cancer syndromes have been linked to an elevated risk of developing pancreatic cancer, suggesting potential benefits from surveillance strategies for individuals at risk. Presently, precision medicine employs PARP inhibitor therapy for pancreatic cancer patients carrying germline variants in Homologous Recombination Repair (HRR) genes. Our objective was to ascertain the occurrence of germline pathogenic/likely pathogenic variants in genes predisposing to cancer among pancreatic cancer patients. Methodologically, we analyzed 184 pancreatic cancer patients referred to our laboratory for genetic examination. Utilizing a Next-Generation Sequencing (NGS) approach, we scrutinized 52 genes implicated in hereditary cancer predisposition. Our findings revealed that 21% of the patients analyzed harbored germline pathogenic/likely pathogenic variants. Within this subset, 48% exhibited positive results in pancreatic cancer susceptibility genes, namely ATM (17%), BRCA1 (12%), BRCA2 (7%), CDKN2A (7%), and PALB2. Significantly, 64.3% of the pathogenic variants were associated with genes involved in the HRR pathway (ATM, BRCA1, BRCA2, BRIP1, CHEK2, FANCL, MRE11, PALB2, RAD50, RAD51B and RAD51C). In conclusion, our study underscores the significance of multigene genetic testing for pancreatic cancer patients, with 21% of individuals yielding findings linked to pancreatic or other cancer predisposition. Moreover, patients carried pathogenic/likely pathogenic variants in HRR genes, potentially benefiting from targeted therapies such as PARP inhibitors or platinum-based treatments.

An immune-inflammatory response is accompanied by increased nitro-oxidative stress. The aims of this mechanistic review are to review: a) the role of redox sensitive transcription factors and enzymes, ROS/RNS production and the activity of cellular antioxidants on the activation and performance of macrophages, dendritic cells, neutrophils, T cells, B cells and natural killer cells; b) the involvement of high-density lipoprotein (HDL), apolipoprotein (Apo)A1, paraoxonase (PON)-1, and oxidized phospholipids in the regulation of the immune response; and c) the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response. The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor (NF)-κB, HIF1alpha, the mechanistic target of rapamycin (mTor), the phosphatidylinositol 3‑kinase (PI3K) / protein kinase B (AKT) signalling pathway, mitogen-activated protein (MAP) kinases, 5' AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor (PPAR). The performance and survival of individual immune cells is under redox control and sensitive to intracellular and extracellular levels of ROS/RNS and is heavily influenced by cellular anti-oxidants including the glutathione and thioredoxin systems, nuclear factor erythroid 2-related factor 2 (Nrf-2), and the HDL complex. Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems, the tricarboxylic acid cycle, mitochondrial functions, and the metabolism of immune cells. In conclusion, those redox-associated mechanisms modulate metabolic reprogramming of immune cells, macrophage and T helper cell polarization, phagocytosis, production of pro- versus anti-inflammatory cytokines, immune training and tolerance, chemotaxis, pathogen sensing, antiviral and antibacterial effects, Toll-like receptor activity, and endotoxin tolerance.

Listwaenite rocks are widely spread in Fenja area of the Semail ophiolite of Oman and in Islam Abad area of the Neyriz ophiolite of Iran. There are three types of listwaenites found in these regions: silica-, carbonate-, and carbonate-silica (which includes dolomite, calcite, and magnesite. The alteration of host harzburgites started with hydrothermal alteration to serpentinite, followed by carbonation and silicification of serpentinite. Calcite- and magnesite-dolomite- listwaenites are more abundant in the Fenja area of Oman, while dolomite-listwaenites are more abundant in Islam Abad area in Iran. The mineralogy of listwaenites varies in both Iran and Oman; common minerals include quartz, calcite, goethite, magnesite, dolomite, serpentine, hematite, magnetite, Cr-mica, and Cr-spinel The major element chemistry of the different types of listwaenites in both Fenja and Islam Abad area generally comparable, and is largely similar to that of hydrothermally carbonated harzburgites, serpentinite, and listwaenites worldwide, despite spanning extraordinary and highly variable contents in major oxides, such as CaO, SiO2, MgO and LOI. Relict texture and common occurrence of Cr-spinel as well as the high concentrations of Cr, Ni and Co suggest that the protolith of the listwaenites in both regions was serpentinized harzburgites and serpentines. In comparison to the primary mantle and chondrite in spider diagrams, the Neyriz listwaenites have higher trace and REE element abundances than comparable listwaenites in the Fenja region. Harzburgite-normalized patterns of trace elements and REE in serpentinite and listwaenites overlap the average composition of harzburgite. PM-normalized trace element and REE patterns for serpentinized harzburgite and serpentinite show enrichment in Cs, U, Pb and Sr, with no Eu anomaly, comparable to mantle wedge serpentinites. The variable and high abundances of Ca, Mg, Ba, Zr, Sr, Pb, Zn, Mo and W in the carbonate- and silica-carbonate listwaenites, with unique Si enrichment and Mg, Na2O, Zr, Y, Ba, Sr, Rb, Cu, Pb, Sc, Cs, Nb, Mo and W. depletion in silica listwaenites are indicative of large fluctuations in major and trace element mobility. Cr, Ni and Co were immobile during alteration Enrichment in Ca and Si could occur by internal or late outside supply. Ca, Mg and Si are conceivably the foremost mobile major components amid harzburgite and serpentinite carbonation with mobilization confirmed by formation of quartz and Mg-carbonate in silica-carbonate listwaenites and quartz in silica listwaenites. The listwaenites in Islam Abad and Fenja area were formed due to hydrothermal alteration of serpentinite along thrust faults and shear zones which acted as pathway for Ca and/or Si rich fluids. The intensity of deformation in Islamabad listwaenites has been higher than Fenja listwaenites as indicated by higher abundance of trace elements.

The fluorinated organic compounds have superior physicochemical properties than general organic compounds due to the strong C-F single bond, and widely used in medicine, biology, pesticides, and materials science. In order to gain a deeper understanding of the physicochemical properties of fluorinated organic compounds, fluorinated aromatic compounds have been investigated by various spectroscopic techniques. 2-Fluorobenzonitrile and 3-fluorobenzonitrile are important fine chemical intermediates, and their excited state S1 and cationic ground state D0 vibrational features remain unknown. In this paper, we used two-color resonance two photon ionization (2-color REMPI) and mass analyzed threshold ionization (MATI) spectroscopy to study S1 and D0 states vibrational features of 2-fluorobenzonitrile and 3-fluorobenzonitrile. The precise excitation energy (band origin) and adiabatic ionization energy were determined to be 36028 2 cm-1 and 78650 5 cm-1 for 2-fluorobenzonitrile; and 35989 2 cm-1 and 78873 5 cm-1 for 3-fluorobenzonitrile, respectively. The density functional theory (DFT) at the levels of RB3LYP/aug-cc-pvtz, TD-B3LYP/aug-cc-pvtz, and UB3LYP/aug-cc-pvtz were used to calculate the stable structures and vibrational frequencies for the ground states S0, excited state S1, and cationic ground state D0, respectively. Franck-Condon spectral simulations for transitions of S1 S0 and D0 S1 were performed based on above DFT calculations. The theoretical and experimental results are in good agreement. The observed vibrational features in S1 and D0 states are assigned according to the simulated spectra and the comparison with structurally similar molecules. Several experimental findings and molecular features were discussed in detail.

This article explores the Role and Contributions of Small and Medium Enterprises (SMEs) in a globalized and innovative economy, looking specifically at the challenges and opportunities. The establishment and expansion of new firms provides a sizable amount of net new jobs. While high-expectation entrepreneurial enterprises and gazelles are usually found among innovative and technology-based new organizations, it is also essential that there be a sizable supply for them to play a significant part in economic growth. In other words, encouraging all forms of en-trepreneurship is likely to increase the number of innovative, fast-growing enterprises as well as entrepreneurship. In many European countries, entrepreneurship needs to be encouraged. Findings show the crucial role the SME sector plays in the South African economy in tackling sustainable development. About 90% of all official firms in South Africa are thought to be small, medium, or micro-enterprises. The study concluded that one of the major contributions to the South African economy is the SME sector. The SME is not just viewed as a source of new jobs, but also as a sector that absorbs laid-off workers from both the private and public sectors.

The study aimed to estimate the prevalence and correlates of oral hygiene (OH) and hand hygiene (HH) behaviour among school adolescents in three Caribbean countries. In all, 7,476 school adolescents (median age 14 years), from Dominican Republic, Suriname and Trinidad and Tobago responded the cross-sectional “Global School-based Student Health Survey” (GSHS) in 2016-2017. The prevalence poor OH (tooth brushing <2 times/day) was 16.9%, poor HH (not always before meals) was 68.2%, poor HH (not always after toilet) was 28.4% and poor HH (not always with soap) was 52.7%. In adjusted logistic regression analysis, current cannabis use, inadequate fruit and vegetable intake, poor mental health and low parental support increased the odds for poor OH. Rarely or sometimes experiencing hunger, trouble from alcohol use, inadequate fruit and vegetable intake, poor mental health, and low parental support were associated with poor HH (before meals, and/or after toilet, and/or with soap). The survey showed poor OH and HH behaviour practices. Several sociodemographic factors, health risk behaviours, poor mental health and low parental support were found associated with poor OH and/or HH behaviour that can assist with tailoring OH and HH health promotion.

This paper explores strategies for fostering efficient vocal communication and collaboration between human workers and collaborative robots (cobots) in assembly processes. Vocal communication enables division of attention of the worker, as it frees the visual attention, and the worker’s hands, dedicated to the task at hand. Speech generation and speech recognition are pre-requisites for effective vocal communication. The study focuses on cobot assistive tasks, where the human is in charge of the work and performs the main tasks while the cobot assists the worker in various peripheral jobs, such as bringing tools, parts, or materials, and returning them, or disposing them; or screwing or packaging the products. A nuanced understanding is necessary for understanding how human-robot interactions can be optimized to enhance overall productivity and safety. Through a comprehensive review of relevant literature and empirical studies, this manuscript identifies key factors influencing successful vocal communication, and proposes practical strategies for implementation.

This paper summarizes some works exploiting the ate-type addition of electron-withdrawing monomers to hydrogenosiloxane groups so as to generate new silicone materials. Two types of monomers were oligomerized onto silicone backbones, namely unsaturated phosphonate and sulfone monomers. Phosphonated silicones are thermally more resistant than conventional silicones and can be transformed into amphiphilic polymers after selective ester hydrolysis. Sulfoned silicones generate solid supramolecular elastomers thanks to the strong pseudo-ionic interactions in play between sulfone groups. Rheology and modulated DSC show a solid/viscoelastic transition around 175°C, which allows using these thermoplastic materials on a larger scale than conventional silicone urea copolymers. These results open new avenues in the generation of silicone block- and grafted-copolymers with unique functionality and properties.

Preterm birth (PTB), a multi-causal syndrome, is one of the global epidemics. Maternal nutrition, but also neonatal and placental telomere length (TL), are among the factors affecting PTB risk. However, the exact relationship between these factors and the PTB outcome, remains obscure. The aim of this review, was to investigate the association between PTB, maternal nutrition and placental-infant TL. Observational studies were sought, with the keywords: maternal nutrition, placenta TL, newborn, TL, and PTB. No study was found that included all keywords simultaneously, and thus, the keywords, were searched in dyads, to reach assumptive conclusions. The findings show that maternal nutrition affects PTB risk, through its influence on maternal TL. On the other hand, maternal TL independently affects PTB risk, and at the same time PTB is a major determinant of offspring TL regulation. The strength of the associations and the extent of the influence from covariates, remains to be elucidated in future research. Furthermore, the question of whether maternal TL, is simply a biomarker of maternal nutritional status and PTB risk, or a causative factor of PTB, to date, remains to be answered.

The offshore oil and gas working environment is an inherently dangerous one, with risks posed to physical safety on a daily basis. One neglected field of research is the added psychosocial stressors present in this environment. This research examined the experiences of offshore oil and gas workers through one-on-one online interviews which were recorded and transcribed. Transcripts were analysed through qualitative software NVivo, which generated themes and patterns for the responses given to questions which were developed through a focus group. The results of the analysis showed that multiple psychosocial stressors are present for this population, such as fear of speaking up, unsatisfactory company-provided facilities, work-life interference, work status, micromanaging, gender harassment and bullying. In addition, interviews identified that production and time pressures along with fatigue can influence accidents and mistakes. Climate factors also cause discomfort, however these are managed according to best practice by organisations. Due to the timing of the study, COVID-19 was a significant stressor for some, but not all, employees. In conclusion, offshore oil and gas workers face multiple stressors in a dangerous environment that may lead to devastating consequences.

The objective of this study is to examine different types of bias present in assessment tools and techniques, identify and eliminate any forms of favoritism, and suggest effective approaches for advancing equity and objectivity in assessment procedures. The research utilizes a qualitative methodology, incorporating surveys and focus group discussions with educators and students to collect data. Thematic analysis is a method employed for the purpose of analyzing qualitative data. The results suggest that students hailing from diverse cultural backgrounds perceive partiality in the language and cultural context of evaluations, leading to diminished scores. According to academic professionals, standardized tests are subject to bias, and offering accommodations that cater to linguistic and cultural diversity may improve the academic achievement of students from diverse cultural backgrounds. The findings of this research are of great importance to professionals in the domains of education, policy development, and academia who seek to improve assessment practices and promote equitable educational opportunities for all learners.

The aim of the article is to present a snapshot in time, of the current state in cryptocurrencies, the values and risks associated to blockchains. With emergence of over 20,000 crypto projects, the first objective of this article is to present the stage as it is in 2023, with historical overview since Satoshi presented the first paper on decentralised blockchains, until today. Second objective of the article is to review the values and risks associated to cryptocurrencies, and to clarify the differences between cryptocurrencies from blockchain technologies. The research questions that drive this article are related determining if the blockchain technology an innovation or its already obsolete technology? Are there any significant risks from cryptocurrencies? And are the potential values to society and economy worth pursuing? Would developed or developing countries benefit more from these technologies? And which blockchain projects will survive in the long run? In other words, where is the money and is there money or just hype. The review discusses the high probability that some crypto projects will fail, and given the vast number of cryptos, the article acknowledges that many of these projects are nothing more than ponzies. These are discussed and acknowledged, then the focus is shifted to the real-world use cases of blockchain projects.

Visually impaired people encounter many impediments and challenges in their lives such as related to their mobility, education, communication, use of technology, and others. This paper reports the results of an online survey to understand the requirements and challenges blind and visually impaired people face in their daily lives regarding the availability and use of digital devices. The survey was conducted among the blind and visually impaired in Saudi Arabia using digital forms. A total of 164 people responded to the survey most of them using the VoiceOver function. People were asked about the use of smart devices, special devices, operating systems, object recognition apps, indoor and outdoor navigation apps, virtual digital assistive apps, the purpose (navigation, education, etc.) of and difficulty in using these apps, the type of assistance needed, the reliance on others in using the assistive technologies, and the level of satisfaction from the existing assistive technologies. The majority of the participants were 18 – 65 years old with 13% under 18 and 3% above 65. Sixty-five percent of the participants were graduates or postgraduates and the rest only had secondary education. White Cane, mobile phones, Apple iOS, Envision, Seeing AI, VoiceOver, and Google Maps were the most used devices, technologies, and apps used by the participants. Navigation at 39.6% was the most reported purpose of the special devices followed by education (34.1%) and office jobs (12.8%). The information from this survey along with a detailed literature review of academic and commercial technologies for the visually impaired was used to establish the research gap, design requirements, and a comprehensive understanding of the relevant landscape, which in turn was used to design smart glasses called LidSonic for visually impaired.

Information can be considered as the most fundamental, philosophical, physical and mathematical concept originating from the totality by means of physical and mathematical transcendentalism (the counterpart of philosophical transcendentalism). Classical and quantum information, particularly by their units, bit and qubit, correspond and unify the finite and infinite. As classical information is relevant to finite series and sets, as quantum information, to infinite ones. A fundamental joint relativity of the finite and infinite, of the external and internal is to be investigated. The corresponding invariance is able to define physical action and its quantity only on the basis of information and especially: on the relativity of classical and quantum information. The concept of transcendental time, an epoché in relation to the direction of time arrow can be defined. Its correlate is that information invariant to the finite and infinite, therefore unifying both classical and quantum information.

In this article, the usual factorials and binomial coefficients have been generalized and extended to the negative integers. Basing on this generalization and extension, a new kind of polynomials has been proposed, which led directly to the non-classical hypergeometric orthogonal polynomials and the non-classical second-order hypergeometric linear DEs. The resulting polynomials can be used in non-relativistic and relativistic QM, particularly, in the case of the Schrödinger equation, and Dirac equations for an electron in a Coulomb potential field.

Various crystallite size estimation methods were used to analyze X-ray diffractograms of spherical cerium dioxide and donut-like titanium dioxide anatase nanoparticles aiming to evaluate their reliability and limitations. The microstructural parameters were estimated from Scherrer, Monshi, Williamson-Hall, and their variants: i) uniform deformation model, ii) uniform strain deformation model, and iii) uniform deformation energy density model, and also size-strain plot, and Halder-Wagner method. For that, and improved systematic Matlab code was developed to estimate the crystallite sizes and strain, and the linear regression analysis was used to compare all the models based on the coefficient of determination, where the Halder Wagner method gave the highest value (close to 1). Therefore, being the best candidate to fit the X-ray Diffraction data of metal-oxide nanoparticles. Advanced Rietveld was introduced for comparison purposes. Refined microstructural parameters were obtained from a nanostructured 40.5 nm Lanthanum hexaboride nanoparticles and correlated with the above estimation methods and transmission electron microscopy images. In addition, electron density modelling was also studied for final refined nanostructures, and μ-Raman spectra were recorded for each material estimating the mean crystallite size and comparing by means of a phonon confinement model.

Oligodendrocytes are myelinating cells of the central nervous system, which are generated by progenitor oligodendrocytes as a result of maturation processes. The main function of mature oligodendrocytes is to produce myelin, a lipid-rich multi-lamellar membrane that wraps tightly around neuronal axons, isolating them and facilitating nerve conduction through saltatory propagation. The myelination process requires the consumption of a lot of energy and a high metabolic turnover. Mitochondria are essential organelles which regulate many cellular functions including the energy production through oxidative phosphorylation. Any mitochondrial dysfunction impacts cellular metabolism and negatively affects the health of the organism. If the functioning of the mitochondria is unbalanced the myelination process is impaired. At the end of myelination, oligodendrocytes synthesize about 40% of the total lipids present in the brain. Since lipid synthesis occurs in the cellular endoplasmic reticulum, the alteration of this organelle can lead to partial or deficient myelination, triggering numerous neurodegenerative diseases. In this review the main dysfunctions of oligodendrocytes caused by exogenous or endogenous stimuli will be investigated. Furthermore, the oligodendrocyte reactions to excessive mitochondrial oxidative stress and an altered regulation of the functioning of the endoplasmic reticulum will be discussed.

Metabolic syndrome, diabetes and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise, and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. Also, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.

The manufacturing method influences the properties of the produced components. This work investigates the influence of manufacturing methods such as fused filament fabrication (3D printing) and injection molding on water absorption, mechanical and thermal properties of the specimens produced from neat biobased poly(lactic acid) (PLA) polymer and poly(lactic acid)/wood composites. Acrylonitrile butadiene styrene (ABS) acts as the reference material due to its low water absorption and good functional properties. The printing layer thickness is one of the factors that affects the properties of a 3D printed specimen. The investigation includes two different layer thicknesses (0.2 mm and 0.3 mm) while maintaining uniform overall thickness of the specimens across two manufacturing methods. 3D printed specimens absorb significantly higher amounts of water than the injection molded specimens, and the increase in the layer thickness of the 3D printed specimens contributes to further increased water absorption. However, the swelling due to water absorption in 3D printed specimens decreases on increased layer thickness. Tensile, flexural and impact properties of all the specimens decrease after water absorption while the properties improve on decreasing the layer thickness. Higher porosity on increasing the layer thickness is the predominant factor. The results from dynamic mechanical analysis and microscopy validate the outcomes.

Various autoimmune diseases, including autoimmune hypothyroidism (AHT), are associated with a higher risk of developing mood disorders throughout life. Depression is accompanied by the changes in the levels of inflammatory and trophic factors, including interleukines (IL-1beta, IL-2, IL-6), interferon alpha (IFN-alpha), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) and brain derived neurotrophic factor (BDNF). Similar disturbances in the cytokine profile are seen in AHT patients and their relatives. Disclosure of the relationship between the co-existence of depression and autoimmune subclinical thyroiditis indicates that the pathomecha-nism of depression may be related to the changes in the immune system, it is possible that both conditions may be caused by the same immune processes. The above hypothesis is indirectly sup-ported by the observations that the treatment with both antidepressants and levothyroxine leads to a decrease in the levels of proinflammatory cytokines with an increase in BDNF concentrations, simultaneously correlating with an improvement in the clinical parameters. However, so far there are no long-term studies determining the causal relationship between depression, thyroid auto-antibodies, and cytokine profile, which could bring us closer to understanding the interrelation-ships between them and facilitate the use of an adequate pharmacotherapy, not necessarily psy-chiatric. We consider the above issues insufficiently investigated but of great importance. This ar-ticle is an overview of the available literature as well as an introduction to our research project.

This article explores how Artificial Intelligence (AI) is drastically changing the logistics industry by transforming operations and significantly improving customer satisfaction. Through meticulous analysis of real-life cases and extensive examination of numerical data, this comprehensive research thoroughly investigates the profound impact of AI on supply chain management. The findings clearly reveal the multifaceted role of AI in significantly reducing costs, greatly improving delivery accuracy, and significantly enhancing inventory control. AI is not just an incremental advancement, but rather a revolutionary leap forward for the future logistics industry, firmly paving the way for unparalleled automation, digital transformation, and operational effectiveness

The dawn of quasispecies theory revolutionized our understanding of viral evolution and pathogenesis. This theory conceptualises viruses as dynamic populations of closely related but genetically diverse variants that constantly mutate and adapt to environmental pressures. Quasispecies dynamics govern key aspects of virus-host interactions, such as adaptive evolution, immune evasion, drug resistance, and host tropism. In this article, we discuss the fundamental role of quasispecies theory in elucidating viral fitness landscapes, shaping antiviral strategies, and predicting viral emergence and evolution. We provide a concise overview of the original quasispecies model and its latest advancements, which enable the study of the connection between viral dynamics and the significant genetic diversity exhibited by viruses. We then point out some key features of virus dynamics that need to be incorporated into quasispecies theory. We continue with examples of convergence between theory and real viruses by discussing theoretical results supported by RNA virus data and vice versa. Next, we discuss the need to extend the concept of sequence space beyond the classical hypercube towards more complex, multidimensional connected sequence spaces that we have called ultracubes. Finally, we highlight the necessity of developing multi-scale models to understand how viral evolutionary dynamics within a host can affect epidemiological patterns. We also examine the limitations of quasispecies theory in predicting virus evolution and emergence.

Blockchain technology has emerged as a necessity for the decentralization of payment methods and transactions, but it has brought with it many properties of distributed systems that have made it a crucial technology for overcoming some of society's challenges, especially in the context of decentralizing services, transparency of information, availability, and security. Its architecture and communication methods, although possessing some complex nuances to understand, particularly for the lay audience in the field of distributed systems, protocols, and computer networks. In this article, we will explore some topics of distributed systems related to blockchain technology.

This review focuses on the synthesis and biological activity of flavones and their related flavonoidic compounds: flavonols and aurones. Among the biological activities of flavones and aurones, the anticancer, antioxidant and antimicrobial properties are highlighted and detailed in this review. The most applied method for the synthesis of flavones and aurones is based on the oxidative cyclisation of o-hydroxychalcones. Depending on the reaction conditions and the structure of the precursor, in some cases several cyclization products result simultaneously: flavones, flavanones, flavonols and aurones. Based on the literature data and the results obtained in our research group, our aim is to highlight the most promising methods for the synthesis of flavones, as well as the synthetic routes for the other structurally related cyclization products, hydroxyflavones and aurones, considering that in practice it is difficult to predict which is the main or exclusive cyclisation product of o-hydroxychalcones under certain reaction conditions.