(1) Background: Neurologic and musculoskeletal diseases represent a considerable portion of the underlying etiologies responsible for the widely prevalent symptoms of pain, weakens, numbness, and paresthesia. Because of the subjective and often nonspecific nature of these symptoms, different diagnostic modalities have been explored and utilized.; (2) Methods: Literature review; (3) Results: Nerve and muscle biopsy remains the gold standard for diagnosing many of the responsible neurological and musculoskeletal conditions. However, the need for invasive tissue sampling is diminishing as more investigations explore alternative diagnostic modalities. Because of this, it is important to explore the current role of neurosurgical intervention for nerve and muscle biopsies and its current relevance in the diagnostic landscape of neurological and musculoskeletal disorders. With consideration of the role of nerve and muscle biopsy, it is also important to explore innovations and emerging techniques for conducting these procedures. This review explores the indications and emerging techniques for neurological intervention for nerve and muscle biopsies; (4) Conclusions: The role of neurosurgical intervention for nerve and muscle biopsy remains relevant in diagnosing many neurological and musculoskeletal disorders. Biopsy is especially relevant as a supportive point of evidence for diagnosis in atypical cases. Additionally, emerging techniques have been explored to guide diagnostics and biopsy, conduct less invasive biopsies, and reduce risks of worsening neurologic function and other symptoms secondary to biopsy.

Background: Infective endocarditis (IE) continues to be a disease with high mortality despite medical advances. Objective: To investigate the characteristics and prognosis of IE according to the affected valves. Material and methods: The study is retrospective, single-center, cross-sectional and includes 270 patients with diagnosis IE, for the period 2005 – 2021, who received treatment at the University Hospital "St. Georgi" in Plovdiv, Bulgaria. Results: Single-valve IE (SIE) was found in 82.6% (n-222), multivalvular IE (MIE) in 16.66% (n=45) and device IE (CDRIE) in 0.74% (n=2) patients. The most commonly affected valve was the aortic 44.8% (n=121). The predominant multivalvular involvement was aortic-mitral valves (AV-MV) – 13.7% (n=37). The patients with tricuspid valve (TV) IE were significantly younger – 39 (30) years and were more frequently male (80.8%). Mortality was higher in MIE than SIE (31.1% vs 23.8%) and highest in multivalve aortic-tricuspid (AV-TV) IE (75%). Early surgery was done most in AV-MV IE 29.7% (n=11). Charlson comorbidity index was significantly higher in MV 4 (4) and AV 3 (3) than TV IE 1 (5) (p=0.048 and p=0.011, respectively). Septic shock occurred most frequently in AV-TV involvement (75%; p=0.0001). The most common causative agent was Staphylococcus group. Staphylococcus aureus affected more often TV alone 46.2% (n=124) vs. AV 9.9% (n=14); p=0.0001 and vs. MV 22.6% (n=17), p=0.022; Staphylococcus coagulase-negative (CNG) was the prevalent cause of MV IE 22.7% (n=17) vs AV-MV 2.7% (n=1); p=0.007. Streptococci were represented in a low percentage and only in left-sided IE, and more frequently in AV-MV 18.9% (n=7); vs. AV 6.6% (n=8); (p=0.025). Conclusion: Aortic valve is the most frequently affected valve, as single valve IE or multivalve AV-MV, with the predominant causative agents Staphylococcus group. The AV-TV IE has the worst prognosis, with the most common complication of septic shock and the highest in-hospital mortality.

Optical materials with a tunable localized surface plasmon resonance (LSPR) are of a great interest for applications in photonics and optoelectronics. In the present study we explored the potential of generating the LSPR band with an ultra-broad range of over 1000 nm in gold nanoparticles (NPs) precipitated through the thermal treatment in ZnO-Al2O3-SiO2 glass. Using the optical absorption spectroscopy, we demonstrated that the LSPR band's position and shape can be finely controlled by varying the thermal treatment route. Comprehensive methods including Raman spectroscopy, X-ray diffraction and high-resolution transmission electron microscopy were used to study the glass structure, while computational approaches were used for the theoretical description of the absorption spectra. Obtained results allowed us to suggest a scenario responsible for such abnormal LSPR band broadening which includes possible interparticle plasmonic coupling effect taking place during the liquid-liquid phase separation of the heat-treated glass. The formation of gold NPs with an ultra-broad LSPR band in glasses holds promise for sensitizing rare earth ion luminescence for new photonics devices.

{This study investigates the coordinated behaviors and the underlying collective intelligence in biological groups, particularly those led by informed leaders. By establishing new convergence criteria based on real biological group experiments, this research introduces the concept of a volitional term and heterogeneous networks, constructing a coupled force Cucker-Smale model with informed leaders. The inclusion of the informed leader aspect distinctively characterizes the dynamics of leaders and followers, enabling a more accurate representation of biological group behavior. The paper then proposes the Flock Leadership Hierarchy Network (FLH), a model reflecting real biological interactions. By employing time slicing and rolling time windows, the study methodically analyses group behavior stages, using volatility and convergence time as metrics to examine the relationship between group consistency and interactions. Comparative experiments show the FLH network's superior performance. The Kolmogorov-Smirnov test indicates that the FLH network follows a power-law distribution, highlighting the evolutionary intelligence of biological groups. This research offers new perspectives on the evolution of biological groups, contributing to our understanding of both natural and artificial systems, such as animal migration and autonomous drone operations.

Taekwondo has evolved from a traditional martial art into an official Olympic sport. This study introduces a novel action recognition model tailored for Taekwondo unit actions, utilizing joint motion data acquired via wearable inertial measurement unit (IMU) sensors. The utilization of IMU sensor-measured motion data facilitates the capture of the intricate and rapid movements characteristic of Taekwondo techniques. The model, underpinned by a conventional convolutional neural network (CNN)-based image classification framework, synthesizes action images to represent individual Taekwondo unit actions. These action images are generated by mapping joint motion profiles onto the RGB color space, thus encapsulating the motion dynamics of a single unit action within a solitary image. To further refine the representation of rapid movements within these images, a time-warping technique was applied, adjusting motion profiles in relation to the velocity of the action. The effectiveness of the proposed model was assessed using a dataset compiled from 40 Taekwondo experts, yielding remarkable outcomes: an accuracy of 0.998, precision of 0.983, recall of 0.982, and an F1-score of 0.982. These results underscore the time-warping technique's contribution to enhancing feature representation, as well as the proposed method's scalability and effectiveness in recognizing Taekwondo unit actions.

Urban environments face escalating challenges, e.g. due to uncontrolled urbanization, rapid population growth or climate changes, prompting the exploration of sustainable solutions for enhancing urban green spaces (UGS). For this reason, poplars (Populus L.), due to their rapid growth, wide range adaptability to environmental conditions and versatility of use, would have emerged as very promising. This comprehensive review synthesizes current knowledge regarding poplar's application in urban landscapes, emphasizing its multifaceted contributions and benefits. However, challenges arise from the variable lifespans of different poplar cultivars, necessitating strategic management approaches. Selecting cultivars based on growth rates, root system characteristics, and adaptability to urban conditions is pivotal. Adaptive replanting strategies, incorporating species with varying lifespans, offer solutions to maintain continual greenery in urban landscapes. Collaborative efforts between researchers, urban planners, and policymakers are essential for devising comprehensive strategies that maximize benefits while addressing challenges associated with their variable lifespans. In conclusion, harnessing poplar's potential in urban greenery initiatives requires a balanced approach that capitalizes on their benefits while mitigating challenges. Further research and adaptive strategies are crucial for sustained and effective utilization in creating resilient and vibrant urban landscapes.

Knowledge of clinical approaches and barriers in managing childhood myopia is limited. This study explores optometrists' knowledge, attitude, and practice towards childhood myopia. A 26-item survey was circulated online among practising optometrists in India. The questionnaire assessed the demographics, knowledge, self-reported clinical practice behaviour, barriers, source of information guiding their management, and extent of adult caregiver engagement for childhood myopia. Of 393 responses, a significant proportion of respondents (32.6%–92.4%) were unaware of the ocular complications associated with high myopia, with less than half (46.5%) routinely measuring axial length in clinical practice. Despite the improved awareness of emerging myopia management options, the uptake remains generally poor, with single-vision distance full correction spectacles (70.3%) being the most common mode of vision correction. Barriers to adopting emerging evidence are medico-legal concerns and the absence of clinical practice guidelines. Original research articles were the primary source of information supporting clinical practice. Most (>70%) respondents considered involving the adult caregiver in their child's clinical decision-making process. While practitioner knowledge, perspective, and practice are improving, childhood myopia management evidence is constantly evolving and remains inconclusive. Evidence-based practice guidelines and continuing education on myopia control might be helpful for practitioners in improving their clinical decision-making skills.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgAN causes end-stage kidney disease (ESKD) in 20–40% of all cases. The activation of the complement system by pathological circulating IgAs, which is often associated with low serum C3 levels (LowC3), seems to play a crucial role. Previous studies have shown an association between histological evidence of TMA, which is the result of alternative complement activation, and poor outcome. However, it is not known to what extent the decrease in serum C3 levels reflects ongoing TMA injury. Our study aimed at assessing the association of LowC3 and ESKD and whether this association reflects ongoing TMA. We enrolled all patients with biopsy-proven IgAN and followed-up patients until last visit, ESKD or death. Of the 56 patients included in the study, 12 (21%) presented low serum C3 (LowC3) at the time of renal biopsy. TMA was significantly more frequent in the LowC3 group [7/12 (58%) vs 9/44 (20%), p=0.02]. After adjusting for potential confounders, LowC3 was strongly associated with an increased hazard of ESKD (hazard ratio [HR]: 5.84 [95%CI: 1.69,20.15; P=0.005). The association was not affected by adjusting for TMA. The estimated overall proportion of the relation between C3 and ESKD mediated by TMA was low and not statistically significant. Our study provides evidence that C3 hypocomplementemia is associated with an increased risk of ESKD with mechanisms that are largely independent from TMA.

The study concentrated on Myzostomida, which are microscopic polychaetes that live in symbiosis with feather stars, within the coastal waters of Hainan Island. Specimens were collected by researchers using SCUBA diving techniques, leading to the identification of a new species, as well as the documentation of four species that had not been previously recorded in Chinese waters. This discovery stands apart from the seven known Myzostomida species found near Hong Kong and the Dapeng Peninsula in Shenzhen. It underscores significant gaps in our comprehension of marine life in the South China Sea, suggesting the existence of unexplored biodiversity within the region.

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic dis-orders frequently associated with iron accumulation in the basal nuclei of the brain. Among NBIA subtypes, β -propeller protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene WDR45. The aim of this study was to demonstrate autophagic defects and secondary pathological con-sequences in cellular models derived from two patient harboring WDR45 mutations. Both protein and mRNA expression levels of WDR45 were decreased in patient-derived fibro-blasts. In addition, the increase of LC3B upon treatments with autophagy inducers or inhibitors was lower in mutant cells compared to control cells, suggesting decreased autophagosome formation and impaired autophagic flux. Transmission electron microscopy (TEM) analysis showed mitochondrial vacuolization associated with accumulation of lipofuscin-like aggregates containing undegraded material. Autophagy dysregulation was also associated with iron ac-cumulation and lipid peroxidation. In addition, mutant fibroblasts showed altered mitochon-drial bioenergetics. Antioxidants such as pantothenate, vitamin E and α-lipoic prevented lipid peroxidation and iron accumulation. However, antioxidants were not able to correct the ex-pression levels of WDR45 neither the autophagy defect nor cell bioenergetics. Our study demonstrated that WDR45 mutations in BPAN cellular models impaired autophagy, iron metabolism and cell bioenergetics. Antioxidant partially improved cell physiopathology, however autophagy and cell bioenergetics remained affected.

Abstract: Objective: The aim of the study was to identify dietary patterns and its association with socio-economic, dietary and lifestyle practices among adolescents in Malaysia. Methods: A validated food frequency questionnaire was used to assess dietary patterns. Results: Multivariate analyses show that age and physical activity (PA) levels were emerged as positive determinants of healthy-based food pattern in Malay (All, p<0.001), whereas higher consumption of eating-out from home (EatOut) and fast food (All, p<0.05) were negative determinants. High weekly breakfast skipping (p<0.001) and EatOut (p<0.01) were positively associated with a western-based pattern, whereas age (p<0.001) and household income (p<0.05) were negative determinants. Higher frequency of daily snacking (p<0.05) was emerged as positive determinant of local-based food pattern. For Chinese adolescents, age (p<0.001), PA levels (p<0.001) and maternal education level (p<0.05) emerged as positive determinants for the healthy-based pattern, whereas high EatOut and fast food intakes (All, p<0.01) were negative determinants. Higher weekly consumption of EatOut (p<0.01), fast food (p<0.05) and carbonated beverages (p<0.05), and daily snacking practice (p<0.01) were positively associated with higher western-based food pattern, whereas age (p<0.01) was inversely associated. Conclusion: These findings suggest that unhealthy dietary and lifestyle practices could increase the risk of adherence to unhealthy western-based food pattern that is high in fat, sugar and salt contents, and consequently increase the risk of developing obesity and metabolic-related disorders during these critical years of growth.

The StarDICE experiment strives to establish an instrumental metrology chain with a targeted accuracy of 1 mmag in griz bandpasses to meet the calibration requirements of next-generation cosmological surveys. Atmospheric transmission stands out as a significant source of systematic uncertainty. Specifically, gray extinction induces spurious variations of photometric fluxes. We propose a solution relying on an uncooled long-wave infrared thermal camera to evaluate it. This type of camera can provide real-time insights into atmospheric conditions and detect cirrus clouds. However, achieving accurate measurements with thermal imaging systems necessitates prior calibration due to the influence of temperature-induced effects, which compromise their spatial and temporal precision. Moreover, these systems cannot provide scene radiance values in physical units by default. This study introduces a new calibration process utilizing a tailored forward modeling approach. The method is applied to an uncooled FLIR Tau2 thermal camera. It incorporates sensor, housing, flat-field support, and ambient temperatures, along with raw digital response, as input data. Experimental measurements are conducted inside a climatic chamber, with the camera imaging a thermoregulated blackbody source. Results demonstrate the calibration effectiveness, achieving precise radiance measurements with a temporal pixel root-mean-square error (RMSE) of 0.09 W/m2/srand residual spatial noise of 0.03 W/m2/sr.

Background: Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delay leading to worse outcomes and decreased quality of life. Therefore, there is an urgent need for an approach to predict normal mucosa response in patients prior to treatment. Methods: We here describe an assay to detect irradiation response in patient healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated, and cultured for three days. Seven samples were irradiated with X-ray and three additional samples were irradiated with both X-ray and protons. Results: Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample, using standardized automated image analysis. Furthermore, increased levels of inflammation inducing factors - major drivers in mucositis development - could be detected after irradiation. Conclusion: This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Background: Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neuro-degeneration and disease progression. Methods: We evaluated the concentrations of the param-eters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) and the se-lected interleukins (ILs) in serum of 123 relapsing-remitting MS (RRMS) and 88 progressive MS (PMS) patients. Results: The levels of GFAP, S100B and UCHL were higher in the PMS group compared to RRMS as opposed to the levels of NF-H. We observed a positive correlation be-tween the selected pro-inflammatory cytokines and the parameters of brain injury. The Ex-panded Disability Status Scale score (EDSS) increased with GFA and NF-H levels and correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. Conclusions: The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect.

Cameroon introduced the malaria vaccine in its routine immunization programme on 22 January 2024, in the 42 districts out of 200, among the most at risk of malaria. A cross-sectional analysis of data on vaccine key events in the introduction roadmap and vaccine uptake during the first 30 days was conducted. In addition to available gray literature related to the introduction of the malaria vaccine, data on malaria vaccine uptake by vaccination session, collected through a digital platform, were analyzed. A total of 1,893 reports were received from 22 January 2024 to 21 February 2024 from 766 health facilities (85% of overall completeness). Two regions out of 10 recorded less than 80% of completeness. As of 21 February 2024, 13,811 children have received the first dose of the malaria vaccine, including 7,124 girls (51.6%) and 6,687 boys (48.4%). Thirty six percent of children were vaccinated through outreach sessions versus 61.5% through sessions in fixed posts. The overall monthly immunization coverage with the first dose was 37%. Early results have shown positive attitudes towards and acceptance of malaria vaccines. Suboptimal completeness of data reporting and low coverage highlight persistent gaps and challenges in vaccine rollout.

The EASY-NET network program (NET-2016-02364191 - Effectiveness of Audit and Feedback (A&F) strategies to improve health practice and equity in various clinical and organizational set-tings), piloted a new and more structured A&F strategy. This study compared the effectiveness of the new strategy versus the periodic publication of indicators alone in improving the appropri-ateness and timeliness of emergency health interventions in patients with Acute Miocardial In-farction (AMI) and ischemic stroke in the Lazio Region. Efficacy was evaluated according to a prospective quasi-experimental design of pre-post (2021-2022) intervention type with control group. The exposed are hospitals in the Lazio Region where professional teams voluntarily par-ticipated in the intervention. The control group is involved only in the usual reporting activities. Effectiveness analysis was conducted at the patient level. Regional health information systems were used to calculate process and outcome indicators. The effectiveness of the intervention was assessed with Difference In Difference models, comparing pre-post intervention periods between exposures and controls. Estimates were calculated in terms of the difference in percentage points (pp) between absolute risks. Sixteen facilities for the IMA pathway and 13 for the stroke pathway joined the intervention. The intervention reduced the proportion of 30-days readmissions after a hospitalization for ischemic stroke by 0.54 pp in the exposed patients with a significant difference of -3.80 pp (IC95% -6.57; -1.03; 5453 patients, 63.7% cases) in the exposed compared to controls. There were no statistically significant differences attributable to the implemented A&F interven-tion in the other indicators considered. The results show, for the first time in Italy, the impact of A&F interventions in an emergency setting using aggregated data from hospitals involved in the Lazio Region emergency network.

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new antitrypanosomal compounds, we investigated the potential of metabolites from bacteria living in corals and sediments of the Southeastern Brazilian coast. Three corals Tubastraea coccinea, Mussismilia hispida, Madracis decactis and sediments yielded 11 bacterial strains, that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera - Vibrio, Shewanella, Mesoflavibacter, Halomonas, Bacillus and Alteromonas. To conduct this study, EtOAc extracts were prepared and tested against Trypanosoma cruzi. Crude extracts showed IC50 values ranging from 15 to 51 μg/mL against trypomastigotes. The bacterium Mesoflavibacter zeaxanthinifaciens was selected for fractionation, resulting in an active fraction (FII) with IC50 values of 17.7 μg/mL and 23.8 μg/mL against the trypomastigotes and amastigotes, respectively, with neither mammalian cytotoxicity nor hemolytic activity. Using NMR and ESI-HRMS analysis, FII revealed the presence of unsaturated iso-type fatty acids. Its lethal action was investigated, leading to a protein spectral profile of the parasite altered after treatment. FII also induced a rapid permeabilization of the plasma membrane of the parasite, leading to cell death. These findings demonstrate these unsaturated iso-type fatty acids as possible new hits against T. cruzi.

Conclusion: The study highlights the high prevalence of depression among caregivers of geriatric patients in Jeddah and underscores the significant impact of caregiving burden on mental health. These findings emphasize the need for targeted interventions, such as mental health support, respite care programs, and culturally sensitive educational training, to mitigate caregiver burden and enhance the well-being of caregivers.

The emergence of mRNA vaccines for SARS-CoV-2 has opened a new page in vaccine development; nevertheless, concerns of the experts have been expressed about unintentional side effects on the gut microbiota (GM). Previous studies showed that this virus acts as a bacteriophage, which infects and destroys specific bacterial strains in the GM. The present manuscript hypothesizes that the synthetic spike protein could create changes in the composition and the functioning of the GM by entering the intestinal cells after vaccination and impairing the symbiotic relationship between intestinal cells and the GM. An experimental protocol to test the hypothesis is suggested.

In the face of rising global demand and unsustainable production methods, cultivated crustacean meat (CCM) is proposed as an alternative means to produce delicious lobster, shrimp and crab products. Cultivated meat requires starting stem cells that may vary in terms of potency, and propensity to proliferate or differentiate into myogenic (muscle-related) tissues. We suggest that regenerating crustacean limbs harbor a range of stem cells suitable for cultivated meat production and present a humane tissue source because they can be accessed non-lethally. To investigate stem cell activity in this model, we have conducted RNA-Seq analysis across six stages of claw regeneration in the crayfish Cherax quadricarinatus (four pre-molt and two post-molt stages), along with histology and real time quantitative PCR (qPCR). Differential expression analysis revealed expression patterns of significantly up- or down-regulated genes in 14 functional categories. Relative expression of select stem cell target genes (including endocrine, myogenic, cell cycle and pluripotency factors) highlighted two growth peaks during pre-molt regeneration and limited stem cell activity after the molt. Histology and qPCR results support the overall finding that pre-molt limb regeneration stages harbor more stem cell activity, likely making them a more prolific cell source for CCM development.

Background: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). Methods: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 to 2019. The in-hospital mortality rates, length of stay (LoS) and healthcare costs were determined. Results: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p&lt;0.001). The estimated total care cost for all patients with T1DM with CCD was approximately US $326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68-23.79), pulmonary embolism (OR 4.39, 95%CI 2.70-7.13), endocarditis (OR 3.46, 95%CI 1.22-9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92-2.77) and stroke (OR 1.47, 95%CI 1.04-2.09). Conclusions: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.

Organosilicate glass (OSG) films are a vital component in modern electronic devices, with their electrical properties playing a crucial role in device performance. This comprehensive review systematically examines the influence of chemical composition, vacuum ultraviolet (VUV) irradiation, and plasma treatment on the electrical properties of OSG films. Through an extensive survey of literature and experimental findings, we elucidate the intricate interplay between these factors and the resultant alterations in electrical conductivity, dielectric constant, and breakdown strength of OSG films. Key focus areas include the impact of diverse organic moieties incorporated into the silica matrix, the effects of VUV irradiation on film properties, and the modifications induced by various plasma treatment techniques. Furthermore, we discuss the underlying mechanisms governing these phenomena, shedding light on the intricate molecular interactions and structural rearrangements occurring within OSG films under different environmental conditions. This review not only consolidates existing knowledge but also identifies gaps in understanding and suggests avenues for future research, thereby advancing our comprehension of OSG film behavior and paving the way for enhanced performance in next-generation electronic and photonic devices.

Secondary prevention after SCA (acute coronary syndrome) is of paramount importance to reduce the incidence of MACE and improve prognosis in follow-up. The control of avoidable risk factors, lifestyle modifications, but especially careful control of cholesterolemia (with a target of LDL-C

A comparative analysis between Bidirectional Evolutionary Structural Optimization (BESO) and Smoothing-ESO (SESO), simultaneously considering Reliability-Based Topology Optimization (RBTO) and the structure's self-weight in the case of three-dimensional elasticity, is presented in this study. Due to the important role of the existence of uncertainties in making the structural design more realistic, geometry, volumetric fraction, modulus of elasticity, compliance, and loading are considered random variables with normal probability distribution. When adopting the First Order Reliability Method (FORM), the failure probability is calculated based on the reliability index. Furthermore, considering the influence of self-weight in problems involving large structures in civil engineering, especially in the case of bridges, makes the optimal configuration more reliable for design. A series of examples are covered to validate the methods presented, showing their efficiency and robustness.

Thanks to several Vitis vinifera backcrosses with an initial V. vinifera L. × V. rotundifolia (previously Muscadinia rotundifolia) interspecific cross, the MrRUN1/MrRPV1 locus (resistance to downy and powdery mildews) was introgressed in genotypes phenotypically close to V. vinifera varieties. To check the consequences of introgressing parts of the V. rotundifolia genome on gene expression during fruit development, we conducted a comparative RNA-seq study on single berries from different V. vinifera cultivars and V. vinifera × V. rotundifolia hybrids, including ‘G5’ and two derivative microvine lines, ‘MV102’ (resistant) and ‘MV32’ (susceptible) segregating for the MrRUN1/RPV1 locus. RNA-Seq profiles were analyzed on a comprehensive set of single berries from the end of the herbaceous plateau to the ripe stage. Pair-end reads were aligned both on V. vinifera PN40024.v4 reference genome, V. rotundifolia cv ‘Trayshed’ and cv ‘Carlos’, and to the few resistance genes from the original V. rotundifolia cv ‘52’ parent available at NCBI. Weighted Gene Co-expression Network Analysis (WGCNA) led to classifying the differentially expressed genes into 15 modules either preferentially correlated with resistance or berry phenology and composition. Resistance positively correlated transcripts predominantly mapped on the 4-5 Mb distal region of V. rotundifolia chromosome 12 beginning with the MrRUN1/MrRPV1 locus, while the negatively correlated ones mapped on the orthologous V. vinifera region, showing this large extremity of LG12 remained recalcitrant to internal recombination during the successive backcrosses. Some constitutively expressed V. rotundifolia genes were also observed at lower density outside this region. Genes overexpressed in developing berries from resistant accessions, either introgressed from V. rotundifolia, or triggered by these in the vinifera genome, spanned various functional groups, encompassing calcium signal transduction, hormone signaling, transcription factors, plant–pathogen-associated interactions, disease resistance proteins, ROS and phenylpropanoid biosynthesis. This transcriptomic insight provides a foundation for understanding the disease resistance inherent in these hybrid cultivars and suggests a constitutive expression of NIR NBS LRR triggering calcium signaling. Moreover, these results illustrate the magnitude of transcriptomic changes caused by the introgressed V. rotundifolia background in backcrossed hybrids, on a large number of functions largely exceeding the ones constitutively expressed in single resistant gene transformants.

The benthic matrix acts as a key natural archive where the memory of long-term timescale environmental changes is recorded. Some ecological and chemical features of fjord sediments were explored during the AREX cruise carried out in the Svalbard archipelago in summer 2021. The activity rates of the enzymes leucine aminopeptidase (LAP), beta-glucosidase (GLU) and alkaline phosphatase (AP) and community-level physiological profiles (CLPP) were studied with the aim of determining the functional diversity of the benthic microbial community, while bacterial isolates were screened for their susceptibility to antibiotic molecules in order to explore the role of these extreme environments as potential reservoirs of antibiotic resistance. Enzyme activity rates were obtained by fluorogenic substrates, CLPP by Biolog Ecoplates; antibiotic susceptibility assays were performed through the standard disk diffusion method. Spatial trends observed in the functional profiles of the microbial community suggested the variability in the microbial community composition, presumably related to the patchy distribution of organic substrates. Complex Carbon sources, carbohydrates and amino acids were the organic polymers preferentially metabolized by the microbial community. Multiple resistance to ampicillin, clindamycin and gentamycin was detected in all the sampled sediments, excepting in the southern Hornsund area, stressing the role of sediments as a potential reservoir of chemical wastes ascribable to antibiotic residuals. This study provides new insights on the health status of fjord sediments of West Spitsbergen applying a dual ecological and biochemical approach. Microbial communities in the fjord sediments showed globally a good functional diversity, suggesting their versatility to rapidly react to changing conditions.

The crosstalk between tumor progression and ferroptosis is largely unknown. Here, we identify malate dehydrogenase 2 (MDH2) as a key regulator of ferroptosis. MDH2 deficiency inhibits hepatocellular carcinoma (HCC) cell growth and promotes sensitivity of HCC cells to RSL3-induced ferroptosis. MDH2 knockdown enhances RSL3-induced intracellular reactive oxygen species (ROS), free iron ions and lipid peroxides levels, leading to HCC ferroptotic cell death which is rescued by Ferrostatin-1 and iron chelator Deferiprone. Importantly, inhibition of HCC cell growth caused by MDH2 deficiency is partially rescued by ferroptosis blockade. Mechanistically, MDH2 resists RSL3-induced ferroptosis sensitivity by dependence on GPX4, which is stabilized by MDH2 in HCC. The protein expression of MDH2 and GPX4 is positively correlated with each other in HCC cell lines. Furthermore, through UALCAN website analysis, we find that MDH2 and GPX4 are highly expressed in HCC samples. These findings reveal a critical mechanism by which HCC evades ferroptosis via MDH2-mediated stabilization of GPX4 to promote tumor progression and underscore the potential of MDH2 inhibition in combination with ferroptosis inducers for the treatment of HCC.

Background: Alzheimer's Disease (AD) is a progressive and incurable condition that prompts the exploration of interventions to slow its advancement and enhance the quality of life. The cortical brain waves could have a role in the process of executive function deterioration, increasing dementia symptoms. Objective: To interrogate the effects of physical exercise, and non-invasive brain stimulation, both in electrophysiological behavior of the brain, the executive functions, and dementia symptoms in older adults with AD. Methods: One hundred and sixteen older adults were grouped (n=22 each): GAE (AD, PMED+NIBS), GCP (AD, PMED), GCN (AD, NIBS), GCS (control, no intervention). Binaural beats were used as a non-invasive brain stimulation, physical exercise, or both, were applied during 16 weeks. Pre/post measurements included Alpha Band, and SMR Rhythms, executive functions, and dementia symptoms. Results: GCS showed no significant changes (p>0.05). GCN and GCS slightly enhanced inhibitory control (p>0.05) and working memory (p>0.05). In contrast, GCP and GAE improved executive function (p

Despite the high quality of soybean protein, raw soybeans and soybean meal cannot be directly included into animal feed mixtures due to the presence of Kunitz (KTi) and Bowman Birk protease inhibitors (BBi) which reduces animal performance. Heat treatment can substantially inactivate trypsin and chymotrypsin inhibitors (BBi) but such treatment is energy intensive, adds expense, and negatively impact the quality of seed proteins. As an alternative approach we have employed CRISPR/Cas9 gene editing to create mutations in BBi genes to drastically lower the protease inhibitor content in soybean seed. Agrobacterium-mediated transformation was used to generate several stable transgenic soybean events. These independent CRISPR/Cas9 events were examined in comparison to wild type plants using Sanger sequencing, proteomic analysis, trypsin/chymotrypsin inhibitor activity assays and q15RT-PCR. Collectively, our results demonstrate the creation of an allelic series of loss of function mutations affecting the major BBi gene in soybean. Mutations in two of the highly expressed seed specific BBi genes lead to substantial reductions in both trypsin and chymotrypsin inhibitor activities.

Thioethers are critical in the fields of pharmaceuticals and organic synthesis, but most of the methods for synthesizing alkyl thioethers employ foul-smelling thiols as starting materials or generate them as by-products. Additionally, most thiols are air-sensitive and are easily oxidized to produce disulfides under atmospheric conditions; thus, a novel method for synthesizing thioethers is necessary. This paper reports a simple, effective, green method for synthesizing dialkyl or alkyl aryl thioether derivatives using odorless, stable, low-cost ROCS2K as a thiol surrogate. This transformation offers a broad substrate scope and good functional group tolerance with excellent selectivity. The reaction likely proceeds via xanthate intermediates, which can be readily generated via the nucleophilic substitution of alkyl halides or aryl halides with ROCS2K under transition-metal-free and base-free conditions.

Composite membranes formed by sulfonated poly(ether ether ketone) (SPEEK) with embedded carbon quantum dots (CQDs) were used for detection and removal of heavy metal ions, such as lead and cadmium, from water. SPEEK is responsible for the capture of heavy metals based on the cation exchange mechanism, while CQDs detect their contamination by exhibiting changes in fluorescence. Water-insoluble “red” carbon quantum dots (rCQDs) were synthesized from p-phenylenediamine so that their photoluminescence was shifted from that of the polymer matrix. CQDs and the composites were characterized by several techniques: FTIR, Raman, UV/VIS, photoluminescence, XPS spectroscopies and AFM microscopy. The heavy metal ion concentration was analyzed by inductively coupled plasma–optical emission spectroscopy (ICP-OES). The concentration ranges were 10.8 - 0.1 mM for Pb2+ and 10.0 - 0.27 mM for Cd2+. The composite achieved 100% removal efficiency for lead and cadmium if the concentration was below a half of the ion exchange capacity of SPEEK. The regeneration of membranes in 1 M NaCl was also studied. SPEEK/rCQDs showed a turn-off effect more pronounced for lead. A second order law was effective to describe the kinetics of the process.

Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the GEO database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sino-nasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, shows the position of our sample within 1.02 standard deviation of the other IDH-mutant SNUCs. Molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.

In this paper we explore the known connection among sustainability, resilience, and well-being within the framework of active inference. Initially, we revisit how the notions of well-being and resilience intersect within active inference before defining sustainability. We adopt a holistic concept of sustainability denoting the enduring capacity to meet needs over time without depleting crucial resources. It extends beyond material wealth to encompass community networks, labor, and knowledge. Using the Free Energy Principle, we can emphasize the role of fostering resource renewal, harmonious system-entity exchanges, and practices that encourage self-organization and resilience as pathways to achieving sustainability, both in an agent and in collectives. We start by connecting Active Inference with well-being, building on exsiting work. We then attempt to link resilience with sustainability, asserting that resilience alone is insufficient for sustainable outcomes. While crucial for absorbing shocks and stresses, resilience must be intrinsically linked with sustainability to ensure that adaptive capacities do not merely perpetuate existing vulnerabilities. Rather, it should facilitate transformative processes that address the root causes of unsustainability. Sustainability, therefore, must manifest across extended timescales and all system strata, from individual components to the broader system, to uphold ecological integrity, economic stability, and social well-being. We explain how sustainability manifests at the level of an agent, and then at the level of collectives and systems. To model and quantify the interdependencies between resources and their impact on overall system sustainability, we introduce the application of network theory and dynamical systems theory. We emphasize the optimization of precision or learning rates through the active inference framework, advocating for an approach that fosters the elastic and plastic resilience necessary for long-term sustainability and abundance.

Background: Tachycardia-induced cardiomyopathy (TIC) is caused by prolonged tachycardia leading to left ventricular dilatation and systolic dysfunction with heart failure. Although TIC is more common in adult, it is rare in early infant. Methods: Clinical testing was performed as part of medical evaluation and management. Next gene se-quencing (NGS) was performed for a patient with TIC. Literature review about TIC was con-ducted. Results: The case was a 5-month-old infant referred the hospital due to symptoms with heart failure at least lasting two months. Heart rate was 200 beats per minute, left ventricular ejection fraction fell below 14%, and electrocardiograms showed atrial flutter, suggesting TIC. After cardiover-sion, there was no recurrence of atrial flutter, and cardiac function was improved at 98 days after tachycardia arrest. There were no pathogenic variants identified according to NGS. Literature review identified 8 early infantile cases with TIC reported. However, there were no previous re-ports such as our case with longer duration of TIC. Conclusions: Improvement of cardiac function depends on the duration of TIC. TIC should be considered in all patients with a dilated cardiomyopathy of uncertain origin and who have tachycardias such as atrial flutter.

Background: Modulator therapies improve weight and body mass index (BMI) in cystic fibrosis (CF) patients. We aimed to compare the nutritional risk index (NRI) in adult CF patients receiving modulator (MT) or only non-modulator (conventional) therapies (non-MT). Methods: A single-center prospective cohort study was conducted between June-December 2023. The NRI based on weight gain and albumin was calculated at beginning and end of a 12 weeks period in both groups. This design was pragmatic, since based on individual patient access to MT for 12 weeks. Results: 107 patients were included [mean (SD) age: 23.85 (4.98) years, 54.7% male, 46.7% MT]. In the MT group, mean (SD) weight (kg) and albumin (g/dL) increased significantly [changes: +3.09 (2.74) and +0.17 (0.37); p

VITEK MS PRIME (bioMerieux), a newly developed Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, alongside VITEK PICKME Pen (PICKME), offers easy sample preparation for bacteria and yeast. VITEK MS PRIME also offers two software platforms for filamentous fungi: the IVD database and the RUO database. Our study evaluated its identification agreement on 320 clinical isolates of bacteria and yeasts, comparing PICKME and traditional wooden toothpick sampling techniques against ASTA Mi-croIDSys Elite results. Additionally, we assessed the IVD (v3.2) and SARAMIS (v4.16) RUO data-bases on 289 filamentous fungi against molecular sequencing. The concordant rates for spe-cies-level identification of bacteria and yeasts were about 89.4% (286/320) between the PICKME and wooden toothpick, about 83.4-85.3% between VITEK MS PRIME and ASTA MicroIDSys Elite. Retesting with PICKME improved concordance to 91.9%. For filamentous fungi, species-level identification reached 71.3% with the IVD database and 85.8% with RUO, which significantly enhanced basidiomycetes' identification from 35.3% to 100%. Some strains in the IVD database, like Aspergillus vesicolor, Exophiala xenobiotica, and Nannizzia gypsea failed to be identified. VITEK MS PRIME with PICKME offers reliable and efficient microorganism identification. For fila-mentous fungi, combining the use of the RUO database can be beneficial, especially for basidi-omycetes.

Abstract: Alzheimer's Disease (AD) is a progressive uncurable neurodegenerative disease affect-ing millions worldwide. Various methods, including drug therapies and light emission diode (LED) irradiation, are promising alternatives for preventing and reducing the rapid progression of neurodegenerative diseases, also stimulating the reconstructing of neural tissue structures. In this study, we evaluated the neuroprotective and restorative effects of taurine combined with LED on human neuroblastoma cells (SH-SY5Y), under oxidative stress condition, a considerable modulator in AD. We evaluated LED at the wavelength of 660 nm and taurine under different concentrations before and after exposing SH-SY5Y cells to different concentrations of hydrogen peroxide (H2O2), assessing mitochondrial activity by the MTT colorimetric test and labeling live cell mitochondria by fluorescence using MitoTracker Orange. Cell viability was also evaluated by the trypan blue exclusion assay, and we verified cellular morphological structures by scan-ning electron microscopy (SEM). It was observed that neuroprotective effects are achieved by both LED and taurine when cells are exposed to them and later are stressed with H2O2. Compar-ing both agents, LED irradiation is sufficient to stimulate cell proliferation, representing an af-fordable candidate to contribute against neurodegeneration.

This study aims to enhance multimodal transportation systems by mitigating CO2 emissions and enhancing operational efficiency. It introduces a novel centralized cargo concentration approach tailored for regions facing geographical challenges. The method proposes for direct transportation of cargo from its loading origin to export ports, bypassing intermediate hubs. The mathematical model determines the most efficient means of transport for each route, factoring in variables like distance, volume, and cargo type. Research results indicate that, in scenarios with a high concentration of cargo, multiple hubs may not be necessary, which could streamline transportation and logistics operations. Modal preferences vary based on regional dynamics and cargo characteristics, with rail and sea transport emerging as preferable options under specific circumstances, surpassing the efficacy of road transport. The proposed model showcases reductions in both logistics costs and CO2 emissions compared to road-centric scenarios. It underscores the strategic integration of diverse transportation modes as pivotal for enhancing efficiency and sustainability. This study furnishes a framework adaptable to optimizing multimodal transportation systems in regions sharing similar geographical and logistical attributes.

African scientific research faces formidable challenges, particularly with limited access to state-of-the-art measurement instruments. The high cost associated with these devices presents a significant barrier for regional research laboratories, impeding their ability to conduct sophisticated experiments and gather precise data. This predicament not only hampers the individual laboratories but also has broader implications for the African scientific community and the advancement of knowledge in developing nations—the financial cost barrier considerably impacts the research quality of these laboratories. Reflection on technical and economical solutions needs to be quickly found to help these countries advance their research. In civil Engineering, the thermal conductivity property is the most important measurement for characterising heat transfer in construction materials. Existing devices (i.e., conductometers) in a laboratory are expensive (approximately 30,000 euros) and unavailable for some African laboratories. The study proposes a new and affordable device to evaluate thermal conductivity in construction materials. The method involves establishing a thermal flux between a heat source ( from the Joule effect provided by steel wool where a current is circulating) and a cold source (generated by ice cube) under steady-state conditions. The development of the cylindrical prototype is based on the comparative flux-meter method outlined in the measuring protocol of the ASTM E1225 standard document. Experiments were conducted on four distinct materials (polystyrene, wood, agglomerated wood, and rigid foam). The results indicate a correct correlation between the experimental values obtained from the newly developed prototype and the reference values found in the literature. For example, concerning the experimental polystyrene study, the detailed case analysis reveals a good correlation, with a deviation of only 4%. The percent error found falls within the acceptable range indicated by the standards recommendations of the ASTM E1225 standard, i.e., within 5% acceptable error.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

Waste biogenic materials from seafood exploitation are valuable resources of new compounds exploitation within the blue bioeconomy concept. Here, we describe the effectiveness of Raman technology implementation as an in-line tool for demineralization process control of crustaceans or gastropods. We produced transparent chitin polymer foils from three waste crustacean shells (C. sapidus, S. mantis and M. squinado) using a slow, green chemical approach employing acetic acid, and showed the progressive process of biogenic carbonate dissolution and increasing the Raman characteristic signal of chitin, in a time dependence manner. It turned that chitin foils obtaining is species-specific, and the demineralization bath of waste shell mixture can be effectively tracked by Raman spectroscopy, for solvent control and the recovery of the calcium acetate as valuable by-product. Comparatively, calcium acetate drug, a compound widely used in kidney failure diseases, or as additive in nutraceuticals and food industry, has been obtained here, following a green demineralization path of the sea snail Rapana venosa intact shell, assisted by Raman tech-nology, using 9% acetic acid (vinegar) solution for 14 days. To validate the final products identity and quality, The process of waste shells demineralization and the final products of the treatment were investigated using various Raman techniques and technologies, cross-validating the results with FT-IR, XRD and SEM-EDX techniques. NIR Raman spectroscopy revealed chitin bands in a time-dependent manner, while Resonance Raman spectroscopy showed the preservation of ca-rotenoids after two weeks of acetic acid treatment. A hand-held flexible TacticID Raman system with a 1064 nm excitation demonstrated its effectiveness as a rapid, in-line decision making tool during process control and revealed excellent reproducibility of the lab-based instrument signal, suitable for in situ evaluation of the demineralization status and solvent saturation control. The calcium acetate recovered from residual treatment solutions was assessed regarding its hydration status, purity, and suitability as recrystallized material for further use as pharmaceutical product or ingredient in complex formulations.

Saliva, as a diagnostic medium, offers a promising alternative to blood by virtue of its non-invasive collection, which enhances patient compliance, especially in paediatric and geriatric populations. In this study, we assessed the utility of saliva as a non-invasive medium for measuring V. cholerae-specific serum antibodies in naturally infected individuals. We tested paired serum and saliva samples obtained from a total of 63 cholera patients enrolled in a cohort study. Vibriocidal antibodies assay (IgM/IgG) as markers for accurate determination was used to determine cholera specific antibody levels. Using receiver operating characteristics (ROC) curve, we found that the best cut-off that maximizes (sensitivity + specificity) is 10 titers. At this saliva titer, the sensitivity is 76.9% (95%CI: 60.9%, 87.7%) and specificity is 80.0% (95%CI: 56.6%, 92.5%). Using Spearman’s correlation coefficient, we also found evidence of a positive correlation between Vibrio Cholerae saliva and serum antibodies (rho=0.66, p&lt;0.001). In conclusion, saliva-based diagnostic cholera tests has high diagnostic accuracy, and would be advantageous, cheaper, and quicker for early diagnosis of severe cholera outcomes.

Currently, the textile industry is a poorly automated sector, due in part to problems in the handling of deformable leather and textile parts during production operations. In this work, several problems in the handling process of leather and textile parts are addressed, introducing methods to increase the automation of the process. A pneumatic actuator designed to pick up textile or leather parts avoiding their deformation during transport has been developed. This actuator maximizes the number of gripping points to improve handling, making it more stable and efficient. Additionally, a vision system has been implemented in the part picking task which, in conjunction with the CAD information of the part, sends the modified gripping position of the part to the robot. This allows customized handling of each textile or leather part. Finally, validation tests have been carried out on this development, both in simulations and in laboratory conditions, demonstrating its viability and direct applicability in the production line.

Melasma is a challenging skin condition which involves both structural and functional skin alterations. Despite the availability of various treatment options, the management remains complex. This is the first study to investigate topical application of Rosa Damascena stem cell exosomes when used concomitantly with microneedling in women and men with facial melasma. We recruited 20 subjects with Fitzpatrick skin types I-III, exhibiting melasma of varying severity. The modified Melasma Area and Severity Index (mMASI) and Global Aesthetic Improvement Scale (GAIS) were utilized to evaluate treatment response. The treatment protocol involved microneedling followed by exosome application over four or five sessions, at 4-week intervals. Ninety percent of subjects demonstrated a significant improvement in mMASI scores, while only 10% showed no change. GAIS assessment further supports overall improvement, with just 10% categorized as "not changed". Tolerability was favorable, with mild, transient side effects. Our findings suggest promising outcomes with this combined therapy, underscoring its potential as a safe and effective approach for treating melasma, particularly in severe and moderate cases. However, further research with larger sample sizes and control arms is warranted to validate these findings and explore long-term efficacy.

Micro nano bubbles (MNBs) can generate ·OH in situ, which provides a new idea for the safe and efficient removal of pollutants in water supply systems. However, the difficulty in obtaining stable MNBs causes the low efficiency of ·OH generation, which makes the inability to guarantee the removal efficiency of pollutants. This paper reviews the application research of MNBs technology in water security from three aspects: the generation process of MNBs in water, the generation rule of ·OH during MNBs collapse, and the control mechanism of MNBs on pollutants and biofilms. We found that MNBs generation methods are divided into chemical and mechanical (about 10 kinds) categories, and the instability of bubble size restricts the application of MNBs technology. The generation of ·OH by MNBs is affected by pH, gas source, bubble size, temperature, external stimulation. And pH and external stimulus have more influence on ·OH generation in situ than other factors. Adjusting pH to alkaline or acidic conditions and selecting ozone or oxygen as the gas source can promote the ·OH generation. MNBs’ collapse also releases a large amount of energy, which the temperature and pressure can reach 3000K and 5Gpa respectively, making it efficient to remove ≈90 % of pollutants (i.e., trichloroethylene, benzene, and chlorobenzene). The biofilm can also be removed by physical, chemical, and thermal effect. MNBs technology also has great application potential in drinking water, which can be applied to improve water quality, optimize household water purifiers, and enhance the taste of bottled water. Under the premise of safety, let people of different ages taste, finding that compared with ordinary drinking water, 85.7 % of people think MNBs water is softer, 73.3 % of people think MNBs water is sweeter. This further proves that MNBs water has a great prospect in the drinking water application. This review provides innovative theoretical support for solving the problem of drinking water safety.

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with a distinct set of facial features, growth limitations, and limb anomalies. Its clinical spectrum is broad and presents significant challenges in pediatric diagnosis and management. The variable presentation of the disorder, due to cohesin complex mutations, requires extensive research to refine care and improve outcomes. This article provides a case series review of pediatric CdLS patients, alongside a comprehensive literature review, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. It also discusses the evolution of diagnostic and therapeutic techniques, with an emphasis on innovations in genetic testing, including the detection of mosaicism and novel genetic variations. The aim is to synthesise case studies with current research to advance our understanding of CdLS and the effectiveness of management strategies in pediatric healthcare. This work highlights the need for an integrated, evidence-based approach to diagnosis and treatment, and aims to fill existing research gaps and advocate for holistic care protocols and tailored treatment plans for CdLS patients, ultimately improving their quality of life.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

The inhibition of alpha-glucosidase and alpha-amylase is one of clinic strategies for remedy the type II diabetes. Herbal medicines are reported to alleviate hyperglycemia. However, the constituents from those sources whether are targeted to the alpha-glucosidase and alpha-amylase still unexplored. This study attempted to select the compounds for efficacy of hypoglycemia via cellular and mouse levels. The results illustrated that the cytotoxicity in all tested compounds at various concentrations except the concentration of 16-hydroxy-cleroda-3,13-dine-16,15-olide (HCD) at 30 µM were not significant difference (p > 0.05) when compared with the untreated control. Acarbose (reference drug), Antroquinonol, Catechin, Quercetin, Actinodaphnine, Curcumin, HCD, Docosanol, Tetracosanol, Berberine, and Rutin could effectively inhibit the alpha-glucosidase activity of Caco-2 cells when compared with the control (maltose). The compounds (Curcumin, HCD, Tetracosanol, Antroquinonol, Berberine, Catechin, Actinodaphnine, and Rutin) could reduce blood sugar level at 30 min in tested mice. The effects of tested compounds on area under curve (AUC) were significant (p < 0.05) among Acarbose, Tetracosanol, Antroquinonol, Catechin, Actinodaphnine, and Rutin along with Berberine and Quercetin. In in vitro (alpha-glucosidase) with in vivo (alpha-amylase) experiments suggest that bioactive compounds can be a potential inhibitor candidate of alpha-glucosidase and alpha-amylase for the alleviation of type II diabetes.

The accurate wellbore pressure control not only prevents from lost circulation/blowout and fracturing formation by managing density of drilling fluid, but also improves productivity by mitigating reservoir damage. The geothermal pressure calculated by constant parameters for geothermal well would bring big error easily, as the changes of physical, rheological and thermal properties of drilling fluids with temperature were neglected. This paper researches the wellbore pressure coupling by calculating the temperature distribution with existed model, fitting the rule of density of drilling fluid with temperature and establishing mathematical models to stimulate the wellbore pressures, which is expressed as the variation of Equivalent Circulating Density (ECD) under different conditions. With this method, temperature and ECDs in the wellbore of the first medium-deep geothermal well ZK212 Yangyi Geothermal Field in Tibet were determined, and the sensitivity analysis was simulated by assumed parameters, i.e. circulating time, flow rate, geothermal gradient, diameters of wellbore, rheological models and regimes, the results indicated the geothermal gradient and flow rate were the most influence parameters on the temperature and ECD distribution, and additives added in drilling fluid should be careful which would change the properties of drilling fluid and induce the temperature redistribution. To make sure the safe drilling, velocity of pipes tripping into the hole, depth and diameter of wellbore are considered to control the surge pressure.

Aims and Background: People living with mental disorders experience a disproportionately higher burden of tobacco-related disease than the general population. Long-term substitution with less harmful nicotine products could reduce the tobacco-related harm among this population. This study investigated the views and preferences of people with mental health disorders about different nicotine products and their use as long-term substitutes for cigarettes. Methods: Semi-structured focus group discussion followed by a brief questionnaire. The discussion transcripts were analysed for content and themes and quantitative data summarised with descriptive statistics. Results: Twenty-nine participants took part in four focus groups. Vaping devices were the most acceptable nicotine products discussed, however preferences for nicotine products were idiosyncratic and varied along aesthetic, pragmatic, sensory and symbolic dimensions. The concept of tobacco harm reduction was unfamiliar to participants, however they generally agreed with the logic of replacing cigarettes with less harmful nicotine products. Barriers to activating tobacco harm reduction included the symbolism of smoking and quitting; the importance placed on health; the consumer appeal of alternatives; and cost implications. Discussion and Conclusion: Engaging this population in tobacco harm reduction options will require communication that challenges black and white thinking (a conceptual framework in which smoking cigarettes or quitting all nicotine are the only legitimate options) as in practice this serves to support the continuance of smoking. Consumers should be encouraged to trial a range of nicotine products to find the most acceptable alternative to smoking that reduces health harms. Providing incentives to switch to nicotine products could help overcome barriers to using less harmful nicotine products among mental health consumers.

Duchenne muscular dystrophy (DMD) is the most prevalent progressive muscular dystrophy, and the guidelines recommend the regular assessment of respiratory muscle function. This study aimed to assess the relationship between maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) and sniff nasal inspiratory pressure (SNIP) measurements and upright-supine spirometry parameters in children with DMD, predictability of upright-supine spirometry in terms of diaphragm involvement, and impact of nutrition on muscle strength. This prospective cross-sectional study examined patients with DMD by comparing upright and supine FVC, MIP, MEP, and SNIP measurements. Forty-four patients were included in the study. The mean patient age was 10.8±2.9 years. Twenty-five patients were ambulatory. A significant decrease in FVC, FEV1, and FEF25-75 values was detected in the supine position in both ambulatory and nonambulatory patients (p&lt;0.05). All patients had low MIP, MEP, and SNIP measurements (less than 60 cm H2O). MIP, MEP, and SNIP values were significantly lower in patients with malnutrition than in those without (p&lt;0.05). To accurately assess respiratory muscle strength, supine FVC should be combined with upright FVC, MIP, MEP, and SNIP measurements. It is crucial to regularly screen patients for malnutrition, as this can significantly affect respiratory muscle function during pulmonology follow-up.

Background: The monocyte-phagocyte system (MPS), including monocytes/macrophages and dendritic cells (DCs), plays a key role in anti-viral immunity. We aimed to analyze the prognostic value of the MPS components on in-hospital mortality in a cohort of 58 patients (M/F ; mean ageSD years) with COVID-19 pneumonia and 22 age- and sex-matched healthy controls. Methods: We measured frequencies and absolute numbers of peripheral blood CD169+ monocytes, conventional CD1c+ and CD141+ (namely cDC2 and cDC1), and plasmacytoid CD303+ DCs by means of multi-parametric flow cytometry. A gene profile analysis of 770 immune-inflammatory related human genes and 20 SARS-CoV-2 genes was also performed. Results: Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls (p 0.04 and p 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients (p

Idiopathic pulmonary fibrosis [IPF] is a chronic progressive disease characterised by the accumulation of scar tissue in the lung parenchyma. It primarily occurs in middle-aged and elderly adults and results in significant morbidity and mortality worldwide. The disease occurs due to repetitive lung epithelial injury, subsequent fibroblast activation and myofibroblast differentiation, resulting in excessive extracellular matrix deposition. This leads to scar formation and subsequent loss of lung function. Current treatment options for patients with IPF include the two anti-fibrotic drugs, pirfenidone and nintedanib, which can slow disease progression; however, there are currently no known cures for the disease. As such, novel methods and drug targets are warranted. In this review, we provide an up-to-date account of the importance of specific cytokines and the potential role of regulatory immune cells. We discuss their role in the pathogenesis of IPF and address some of the key gaps in knowledge.

The emergence of drug resistance inducing mutations in Hepatitis C virus (HCV) coupled with genotypic heterogeneity has made targeting NS3/4A serine protease difficult. In this work, we investigated the mutagenic variations in the binding pocket of Genotype 3 (G3) HCV NS3/4A and evaluated ligands for efficacious inhibition. We report mutations at 14 positions within the ligand-binding residues of HCV NS3/4A including H57R and S139P within the catalytic triad. We then modeled each mutational variant for pharmacophore-based virtual screening (PBVS) followed by covalent docking towards identifying a potential covalent inhibitor, i.e. cpd-217. The binding stability of cpd-217 was then supported by molecular dynamic simulation followed by MM/GBSA binding free energy calculation. The free energy decomposition analysis indicated that the resistant mutants alter the HCV NS3/4A-ligand interaction, resulting in an unbalanced energy distribution within the binding site leading to drug resistance. cpd-217 was identified to interact with all NS3/4A G3 variants with significant covalent docking scores. In conclusion, cpd-217 emerges as a potential inhibitor of HCV NS3/4A G3 variants that warrants further in vitro and in vivo studies. The study will pave the way for drug design and development of HCV G3 NS3/4A.

The potential of generalized machine learning models developed for crop water estimation was examined in the current study. Extreme Gradient Boosting (XGBoost), Gradient Boosting Machine (GBM), and Random Forest (RF) are three ensembled machine learning models that were developed using all of the data from a single location from 1976 to 2017 and then immediately applied at eleven different locations without the need for any local calibration. For the test period of January 2018 to June 2020, the model's capacity to estimate the numerical values of crop water requirement (Pen-man-Monteith (PM) ETo values) was assessed. In comparison to the GBM and RF models, the XGBoost model outperformed them both marginally and significantly. The estimate's weighted standard error was smaller than 0.85 mm/day, and the model's effectiveness varied from 96% to 99% across various locations. The model's strong performance was indicated by the decreased noise-to-signal ratio. A real-time water management system at the regional level can be seamlessly linked with this type of model due to its accuracy in estimating crop water requirements and its capacity to generalize.

Urbanization is a dynamic process. At different stages of urbanization, polices of managing car-bon emissions should be adjusted. In this paper, two types of nighttime light data and statistical data of 68 cities in China from 2002 to 2021 are used to establish an urban development evalua-tion system comprising population, economy, construction, and society subsystems. Then, cities were categorized into expanding, contracting, and stable types to understand the uncertainty of urbanization's impact on carbon emissions. The main conclusions are as follows: (1) Integrated nighttime light data is used to extract built-up area boundaries, achieving an overall accuracy ranging from 68.75% to 98.4%, with kappa coefficients ranging between 0.60 and 0.94. (2) Ex-panding cities were concentrated in the eastern coastal regions, while contracting cities were mainly located in inland cities with traditional industries. Urban agglomerations in the Beijing-Tianjin-Hebei region, Yangtze River Delta region, and Chengdu-Chongqing metropolitan demonstrate synchronized characteristic of urbanization development. (3)Economy and con-struction have a greater impact on carbon emissions than population and society. For expanding cities, the focus of carbon emission governance should prioritize rational land use planning. Conversely, for contracting cities, emphasis should be placed on adjusting economic structures.

Neutrophil extracellular trap formation has been identified as a new cell death mediator, termed NETosis, which is distinct from apoptosis and necrosis. NETs capture foreign substances, such as bacteria, by releasing DNA into the extracellular environment, and have been associated with inflammatory diseases and altered immune responses. Short-chain fatty acids, such as acetate, are produced by the gut microbiota and reportedly enhance innate immune responses; however, the underlying molecular mechanisms remain unclear. Here, we investigated the effects of sodium acetate, which has the highest SCFA concentration in the blood and gastrointestinal tract, on NETosis by focusing on the mechanisms associated with histone acetylation in neutrophil-like HL-60 cells. Sodium acetate enhanced NETosis as shown by fluorescence staining with SYTOX green, and the effect was directly proportional to the treatment duration (16–24 h). Moreover, the addition of sodium acetate significantly enhanced the acetylation of Ace-H3, H3K9ace, H3K14ace, and H3K27ace. Sodium acetate-induced histone acetylation rapidly decreased upon stimulation with the calcium ionophore A23187, whereas histone citrullination markedly increased. These results demonstrate that sodium acetate induces NETosis via histone acetylation in neutrophil-like HL-60 cells, providing new insights into the therapeutic effects based on the innate immunity-enhancing effect of dietary fiber.

: Rasmussen’s encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherectomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Further-more, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expres-sion of cell cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest potential involvement of cell cycle regulators in the progression of RE.

Exploring the growth and physiological response mechanisms of rice under continuous drought stress circumstances can provide a significant scientific foundation and technological assistance for meeting drought difficulties, improving drought resistance and rice (Oryza sativa L.) output, and ensuring food security. In this study, a rice field experiment was conducted under a rain shelter with five different treatments set up: P1 (drought stress from tillering stage), P2 (drought stress from jointing-booting stage), P3 (drought stress from heading-flowering stage), P4 (drought stress from grain filling stage), and CK (adequate water management throughout the growth stage). Continuous drought stress from different growth stages with four levels (mild, medium, serious, and extreme). The results showed that the effects of different drought stress treatments on rice growth varied significantly. Compared with the CK treatment, plant height was reduced by 12.10%, 8.14%, 3.83%, and 1.06% in the P1, P2, P3, and P4 treatments, respectively; and the number of tillers was reduced by 23.83%, 18.91%, 13.47%, and 8.68%, respectively. With the increase in drought stress levels, SPAD values and Rubisco activity of rice leaf continued to decrease; SOD activity showed a decreasing trend, but the decreasing trend of POD and CAT activities was not significant, while MDA content showed an increasing trend. For yield components, continuous drought stress significantly reduced spike length, effective number of spikes, thousand grain weight, grain number per spike, and fruiting rate of rice compared to CK treatments during the growth period. In general, continuous drought stress during the early growth period affected the effective spike number and the grain number per spike. Continuous drought stress after the grain filling stage had the least effect on yield and water use efficiency was much higher than other treatments. The results of these studies reveal the response of rice growth and physiology to continuous drought stress, which is important for agricultural practices.

Abstract: To obtain bovine oocytes in high quality, effects of vitamin C (VC) on in vitro maturation (IVM) of bovine oocytes and early embryo development were investigated. The results showed that: 1) The IVM medium containing 50 µg/mL VC improved the oocyte maturation rate, while no effects on the development of parthenogenetic embryos; 2) The in vitro culture (IVC) medium containing 20 µg/mL VC increased the cleavage rate of the in vitro fertilized (IVF) embryos, enhanced the mRNA levels of pluripotency gene Oct4, Sox2, Cdx2 and Nanog in the blastocysts, but no effect on the blastocyst rate; 3) Combing supplemention of 50 µg/mL in IVM medium + 20 µg/ml VC in IVC medium (VC 50/20) increased the cleavage rate of IVF embryos and enhanced the mRNA levels of Oct4, Sox2, Cdx2 and Nanog in the blastocysts; 4) Combination of VC 0/20 and VC 50/20 enhanced the expression of anti-apoptotic gene Bcl-2 and VC 50/0 weakened the expression of pro-apoptotic gene Bax, while VC 0/40 and VC 0/60 increased Bax expression and decreased the Bcl-2/Bax ratio in blastocysts. Together, VC supplementation at tuned concentration as well its combination in IVM and IVC media improves the developmental rates of bovine oocytes and embryos.

Syndemics theory has been applied to study interactions between biomedical and social factors leading to clustering of diseases. Because syndemics theory focuses on interactions that enhance risk, the concept of vulnerability is central to this approach. We conducted a scoping review to better understand how syndemics theory helped to define, operationalize, and tackle issues of vulnerability during the COVID-19 pandemic. Original research, review, and opinion pieces elaborating on syndemics, vulnerability and COVID-19, published between December 2019 and October 2022 and available in PubMed, were eligible. We analysed 40 records and identified three framings of syndemics operating during this period: (1) interactions between COVID-19, diseases/health conditions and specific social factors; (2) interactions between COVID-19 and social determinants of health; and (3) impacts of COVID-19 on specific populations. Emerging conceptualizations described vulnerability to COVID-19 as a systemic issue; explained the impact of COVID-19 control measures on increased vulnerability; and presented COVID-19 as a syndemic on its own. However, this theory's potential for deepening our understanding of vulnerability during this pandemic was constrained by superficial explorations of the interactions between biomedical and social spheres, and insufficient theoretical and methodological support from the social sciences.

Studies and opinion articles present unequal conclusions concerning empathy and morality, mainly because a somewhat heterogeneous and foggy conceptual approach prevails. This scoping review aims to analyse the relationship between empathy and morality and to present a novel conceptual model of empathy applied to moral decisions.A search in PsycINFO, Scopus and PubMed identified articles addressing the relationship between empathy and morality.Thirty-two articles were included. We find an absence of a consensual definition of empathy. It is commonly defined as a predominant emotional process and a factor of bias and prejudice in moral decisions.According to our conceptual model, empathy is a distinct, complex human neuropsychological capacity that mobilises and is dependent on the proper functioning of several brain areas and balances the scales on which are Emotion and Reason, enabling the most thoughtful moral decisions possible in diverse circumstances and contexts.

There are various approaches to managing polyethylene terephthalate waste, including methods for recycling PET. However, at present, only the cleanest wastes that can already be efficiently recycled using known methods are considered in the scientific literature. The study aims to look at other forms of polyethylene terephthalate waste that pose a challenge: low quality PET flakes, polyester tire cord, PET dust and prepolymer waste. The waste was characterized by FTIR spectroscopy, viscosimetry, differential scanning calorimetry, laser diffraction and sieve analysis. The findings describe the composition and properties of various forms of polyethylene terephthalate waste. Low quality PET flake waste and polyethylene terephthalate dust have been shown to be suitable for all chemical recycling methods. When recycling waste polyester tire cord, it is difficult to completely separate the rubber, so its presence in the final product must be taken into account. The most promising way to process a prepolymer is its depolymerization by hydrolysis, alcoholysis or glycolysis to produce monomers for the synthesis of PET, similar in properties to the primary one.

This comparative study aims to investigate environmental awareness, knowledge, and safety among students in Montenegro and North Macedonia, considering the unique socio-cultural and environmental contexts of both countries. A mixed-methods approach involving surveys and interviews was employed to gather data from students in educational institutions across Montenegro and North Macedonia. The study assessed various factors, including students' awareness of environmental issues, their perceived level of knowledge, and their attitudes towards safety measures. A comprehensive series of 400 face-to-face interviews was carried out and these interviews encompassed 200 students from Montenegro and an equal number from North Macedonia, taking place at two esteemed academic institutions: The University of Montenegro in Podgorica and The University of St. Clement of Ohrid, Bitola, Republic of North Macedonia. Our hypothetical conceptual framework proposes that a combination of variables, including gender (H1), age (H2), year of study (H3), and rate of study (H4), significantly influences the attitudes of students from Montenegro and North Macedonia towards environmental awareness, safety, and knowledge. Research findings indicate significant variations in environmental awareness and knowledge perception among students in the two countries. While both Montenegro and North Macedonia face environmental challenges, differences in educational systems and socio-economic factors contribute to distinct attitudes and behaviors towards environmental issues and safety practices. This study sheds light on the importance of understanding regional differences in environmental awareness and knowledge perception among students. By identifying areas of strength and areas needing improvement, policymakers and educators can develop targeted interventions to enhance environmental education and foster a culture of sustainability in both Montenegro and North Macedonia.

The aim of this study was to evaluate whether alterations in food availability compromise the metabolic homeostasis of honey bees exposed to three fungicides alone or together. Ten honey bee colonies were utilized, with half receiving energy-protein supplementation for 15 weeks while another five colonies had their protein supply reduced with pollen traps. Subsequently, forager bees were collected and exposed by contact to 1 or 7 µg of bixafen, prothioconazole, and trifloxystrobin, either individually or in combination. After 48 hours, abdomens without the intestine was used for the analysis of expression of antioxidant genes (SOD-1, CAT, and GPX-1), detoxification genes (GST-1 and CYP306A1), the storage protein gene vitellogenin, and immune system antimicrobial peptide genes (Defensin-1, Abaecin, Hymenoptaecin, and Apidaecin), through real-time PCR. All pesticide treatments induced changes in gene expression, with bixafen showing the most prominent upregulation. Exposure to 1 µg of each of the three pesticides resulted in upregulation of genes associated with detoxification and nutrition processes, and downregulation of immune system genes. When the three pesticides were combined at a dose of 7 µg each, there was a pronounced downregulation of all genes. Dietary supplementation led to a slight reduction in gene expression alterations provoked by the fungicides.

Many neurodegenerative diseases are directly related to the formation of toxic protein aggregates, such as Parkinson’s and Alzheimer’s diseases, which are associated with the aggregation of alpha-synuclein (α-syn) and beta-amyloid (Aβ ), respectively. In this context, protein fibrils are the hallmark of these neurodegenerative diseases. In this sense, planning or designing compounds that are capable of preventing or reducing the formation of protein aggregation in the brain can be of fundamental importance for the curative treatment of these diseases. This work presents an in silico and experimental study to investigate the inhibitory potential of the ligands Octovespin (bioinspired by the wasp venom Polybia Occidentalis) and Fraternine-10 (bioinspired by the wasp venom Parachartergus fraternus wasp) against the aggregation of fibrils of the peptides Aβ(17-42) and α-syn, respectively. Using molecular docking and molecular dynamics simulations with 100 ns, the disaggregation capacity of these ligands was studied. The results obtained indicate that Octovespin and Fraternine-10 interact with the Aβ and α-syn protein fibrils throughout the simulation time. The RMSD values and the interactions with amino acids responsible for fibril aggregation demonstrate that both Octovespin and Fraternine-10 have a significant disaggregation potential, which corroborates the observations in vitro and in vivo. Furthermore, experimental results of Fraternine-10 demonstrate an anti-aggregation effect, indicating that it can promote the disaggregation of fibrils and prevent them from aggregating again to form oligomers. These discoveries qualify these molecules as potential candidates to become medicines against Parkinson’s and Alzheimer’s diseases.

Background: breastfeeding is the optimal nourishment for infants and recommends that children commence breastfeeding within the first hour of birth and be exclusively breastfed for the initial 6 months of life. Our objective was to determine which factors related to mothers could influence the degree of exclusive breastfeeding during hospitalization, as well as to assess breastfeeding mothers' attitudes towards breastfeeding. Methods: A multicenter cross-sectional study was undertaken in the healthcare area of Santiago de Compostela, Spain. The reduced Iowa Infant Feeding Attitude Scale (IIFAS-s) was employed to gauge maternal attitudes toward feeding their baby. Results: 64 women were studied. The overall score of IIFAS-s (mean ± standard deviation) was 36.95 ± 5.17. No use of pacifier by the newborn was associated with a positive attitude for breastfeeding. Having previous children (ORa=6,40; IC95% 1,26 – 32,51) and previous experience with breastfeeding (ORa=6,70; IC95% 1,31 – 34,27) increase the likelihood of exclusive breastfeeding during admission. Conclusions: It is important to identify the factors that contribute to increasing the probability that mothers choose exclusive breastfeeding. We must guide our training efforts to these factors.

Abstract Background Fatigue Syndrome (FS) is described as extreme exhaustion following ordinary activities. Sleep deprivation, the use of antidepressants, autoimmune illnesses, and anemia are also risk factors for FS. Symptoms of FS include headache, dizziness, and dyspnea, among others. Objective: This study focused on assessing the prevalence of fatigue syndrome (FS) and its association with depression and anxiety, among the medical students in Saudi Arabia. Methodology In this cross-sectional investigation conducted in 2023, 740 medical students participated. Data were gathered using an online survey, which encompassed four key sections: Sociodemographic details, the 11-item Chalder Fatigue Questionnaire (CFQ), the 9-item Primary Health Questionnaire (PHQ) assessing depression, and the Generalized Anxiety Disorder 7-item (GAD-7) scale. Analyses were performed by the use of SPSS version 25. Results A total of 740 students were surveyed, 417 (56.4%) satisfied the diagnostic requirements for fatigue syndrome (FS), with most of them being females. Furthermore, 234 (31.2%) and 296 (40.8%) of the participants reported having significant anxiety symptoms and depressive symptoms, respectively. FS was positively correlated with symptoms of anxiety and depression (P

A 68-year-old man with malignant metastatic melanoma in complete remission after Pembrolizumab treatment, developed 10 months after Pembrolizumab cessation due a grade 3 diarrhea, confusion, altered mental status, progressive memory loss, gait disturbance. He was admitted to the neurologic department and comprehensive neurological workup, brain magnetic resonance imaging, cerebral fluid analysis, EEG, blood test allowed the diagnosis of autoimmune encephalitis. The patient was treated with plasmapheresis, high dose of intravenous steroids and intravenous immunoglobulins. The patient improved and he is now well with a performance status 1. This case is interesting since the AE developed approximately 10 months after the cessation of immunotherapy, the underlying cancer was in complete remission and the AE showed a good response to the treatment done.

Several epidemiological studies and intervention trials have demonstrated that flavanols present in grapes and blueberries can lower the risk of cardiovascular disease. However, the mechanisms of action of these compounds remain unclear due to their low bioavailability. A polyphenol-rich grape and blueberry extract (PEGB) contained about 16% flavanol, of which 11% was monomer and 4% was dimer. A sensory test investigated the oral perception of a PEGB. At concentrations where quercetin had almost no detectable taste, PEGB exhibited significant astringency. Furthermore, in comparing the redox properties against O2･- using a luminescence method, PEGB acted as a prooxidant at low concentrations, promoting O2･-production and scavenging O2･-at high concentrations under pH conditions similar to oral cavity and intestine. In contrast, quercetin showed antioxidant activity at any concentration. A single oral administration of PEGB to rats showed a significant increase in skeletal muscle arteriolar blood flow. According to these results, PEGB containing flavanols displays a potent astringent flavor, increases O2･-production at low concentrations in a neutral pH environment as well as oral and intestine, and considerably enhances blood flow to skeletal muscles after a single dose in rats. The results of this study indicate a need to investigate the causal relationship between oral perception, redox properties, and bioactivity of polyphenols.

Gold nanoparticles (AuNPs) exhibit improved optical and spectral properties compared to bulk materials, making them suitable for detection of DNA, RNA, antigens, and antibodies. Here, we describe a simple, selective, and rapid non-cross linking detection assay, using approx. 35 nm spherical Au nanoprobes, for a common mutation occurring in exon 19 of the epidermal growth factor receptor (EGFR), associated with non-small cell lung cancer cells. AuNPs were synthesized based on the seed-mediated growth method and functionalized with a specific 16 bp thiolated oligonucleotide using a pH-assisted method. Both AuNPs and Au nanoprobes proved to be highly stable and monodisperse by ultraviolet-visible spectrophotometry, dynamic light scattering (DLS) and electrophoretic light scattering (ELS). Our results indicate a detection limit of 1.5 µg mL−1 using a 0.15 nmol dm−3 Au nanoprobe concentration. In conclusion, this work is an effective possibility for a straight-forward, fast, and inexpensive alternative for the detection of DNA sequences related to lung cancer, leading to a potential platform for an early diagnosis of lung cancer patients.

The satellite Earth observation (EO) sector is burgeoning with hundreds of commercial satellites being launched each year, delivering a rich source of data that could be exploited for societal benefit. Data streams from the growing constellation of commercial satellites are of variable quality, limiting the potential for their combined use in science applications that need long time-series data from multiple sources. The quality of calibration performed on optical sensors onboard many satellite systems is highly variable due to calibration methods, sensor design, mission objective, budget, or other operational constraints. A small number of currently operating well-characterised satellite systems with onboard calibration, such as Landsat-8/9, Sentinel-2, and planned future missions like the NASA Climate Absolute Radiance and Refractivity Observatory (CLARREO) Pathfinder, the European Space Agency (ESA) Traceable Radiometry Underpinning Terrestrial and Helio Studies (TRUTHS), and LIBRA from China, are considered benchmarks for optical data quality due to their traceability to international measurement standards. This paper describes the concept of a space-based transfer calibration radiometer called the Satellite Cross-Calibration Radiometer (SCR) that would enable the calibration parameters from satellites such as Landsat-8/9, Sentinel-2, or other benchmark systems to be transferred to a range of commercial optical EO satellite systems while in orbit. A description of the key characteristics of the SCR to successfully operate in orbit and transfer calibration from Reference systems to Client systems is presented. A system like the SCR in orbit could complement SI-Traceable satellites (SITSats) to improve data quality and consistency and facilitate the interoperable use of data from multiple optical sensor systems for delivering higher returns on the global investment in EO.

Mesenchymal stem cells (MSCs), whose main function is tissue repair, use collagen to restore the structural integrity of damaged tissue, maintaining its organization through concomitant remodelling. The non-enzymatic glycation of collagen is likely to compromise its communication with MSC, which indeed underlies various pathological conditions such as late complications of diabetes and aging. However, data on the effect of more early stages of collagen glycation on the MSC interaction are lacking. This study focused on the fate of in vitro glycated rat tail collagen (RTC) in contact with MSCs after its pre-exposure to glucose for 1 or 5 days. Using human adipose tissue-derived MSCs (ADMSCs), we showed that their interaction with glycated collagen is significantly altered, manifested morphologically by reduced cell spreading, less formation of focal adhesions, and weaker development of the actin cytoskeleton, further confirmed by ImageJ morphometric analysis. This suggests a poorer recognition of early glycated collagen by integrin receptors, possibly due to steric hindrance of their binding sites. These morphological events were also accompanied by greatly reduced fibril-like reorganization of adsorbed FITC-collagen (a sign of impaired remodeling), complemented by reduced sensitivity to proteases. The latter was confirmed in two ways: measuring directly FITC-collagen degradation by the attached cells and quantifying the proteolysis reduction upon exogenous addition of collagenase in a cell-free system. The mechanism of the observed effects is unclear, although differential scanning calorimetry confirmed the presence of weak structural changes in glycated collagen. All this led us to conclude that the reason for the morphological changes of ADMSCs is the impaired interaction with early-glycated collagen due to the hindrance of complementary sequences for integrins, which certainly also affects the mechanical remodeling of collagen. However, the impaired collagenolytic activity, together with the observed small changes in the thermal transition profile, undoubtedly indicate some internal changes in the structural organization of the collagen molecule occurring even at this early stage of glycation, which in turn contributes further to the impaired MSC remodeling activity.

At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in male and female patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33×10^-8 calculated with the Yates-corrected Chi-square test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWAS of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network. This study indicates that a number of genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The results also suggest the genetic basis of sex-specific psychiatric comorbidities of AD.

Although mammography has been the gold standard for early detection of breast cancer, if a woman has dense breast tissue, a false negative diagnosis may occur. Breast ultrasound, whether hand-held or automated, is a useful adjunct to mammography but adds extra time and cost. The primary aim was to demonstrate that our second-generation Aceso system, which combines full-field digital mammography (FFDM) and automated breast ultrasound (ABUS) in a single platform, is able to produce improved quality images that provide clinically meaningful results. Aceso was first tested using two industry standards: a CDMAM phantom to assess the FFDM images; and the CIRS 054GS phantom to evaluate the ABUS images. In addition, 25 women participated in a clinical trial: 14 were healthy volunteers while 11 were patients referred by the breast clinic at Groote Schuur Hospital. The CDMAM phantom results showed the FFDM results were better than EUREF’s standard of “acceptable” and were approaching “achievable”. The ABUS results showed lateral and axial spatial resolution of 0.5 mm and adequate depth penetration of 80 mm. Our second-generation Aceso system, with its improved quality of clinical FFDM and ABUS images, has demonstrated its potential for early detection of breast cancer in a busy clinic.

Albedo is a key variable in the response of glaciers to climate. In Iceland, large albedo variations in the ice caps may be caused by the deposition of volcanic ash (tephra). Sparse in situ field measurements are insufficient to characterize the spatial variation of albedo over the ice caps. Here we evaluate the latest MCD43 MODIS albedo product (collection 6) to monitor albedo over the Icelandic ice caps using albedo from ten automatic weather stations in Vatnajökull and Langjökull as ground truth. We examine the influence of the albedo variability within MODIS pixels by comparing the results with a collection of Landsat scenes. The results indicate a good ability of the MODIS product to characterize the seasonal and interannual albedo changes with correlation coefficients ranging from 0.47 to 0.90 (median 0.84) and a small bias ranging from -0.07 to 0.09. The root-mean square errors (RMSE) ranging from 0.08 and 0.21, is larger than that from previous studies, but we did not discard the retrievals flagged as bad quality to maximize the amount of observations given the frequent cloud obstruction in Iceland. We find a positive but non-significant relationship between the RMSE and the subpixel variability as indicated by the standard deviation of the Landsat albedo within the MODIS pixel (R=0.48). The summer albedo maps and time series computed from the MODIS product show that the albedo decreased significantly after the Eyjafjallajökull and Grímsvötn eruptions in 2010 and 2011 in all the main ice caps (except the northernmost Drangajökull), with albedo reduction up to 0.6 over large regions of the accumulation areas. Following this validation, these data will be assimilated in an energy and mass balance model of to better understand the relative influence of the volcanic and climate forcing to the ongoing mass losses of Icelandic ice caps.

Reference evapotranspiration (ET0) plays an irreplaceable role in regional dry/wet conditions under the background of climate change. Based on the FAO Penman-Monteith method and daily climate variables, ET0 was calculated for 22 stations in and around Songnen Grassland, northeast China, during 1960-2014. The temporal and spatial variations of ET0 and precipitation (P) were comprehensively analyzed at different time scales by using the Mann-Kendall test, Sen’s slope estimator, and linear regression coupling with break trend analysis. Sensitivity analysis was used to detect the key climate parameter attributed to ET0 change. Then, the role of ET0 in regional dry/wet conditions was discussed by analyzing the relationship between ET0, P and aridity index (AI). Results shown a higher ET0 in the southwest and a lower in the northeast, but P was opposite to that of ET0. Evidently decreasing trend of ET0 at different time scales was detected in almost the entire region, and the significant trend mainly distributed in the eastern, northeastern and central. For the whole region, sensitivity analysis indicated decreasing trend of ET0 was primarily attributed to relative humidity and maximum air temperature. The positive contribution of increasing temperature rising to ET0 was offset by the effect of significantly decreasing relative humidity, wind speed and sunshine duration. In addition, the value of ET0 shown higher in drought years and lower in wet years.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

Mistreatment can adversely affect students’ academic performance and mental health. This study aimed to investigate the prevalence of mistreatment and its association with academic motivation among Thai medical students in clinical years. A cross-sectional study was conducted among medical students throughout Thailand using the Composite Questionnaire of Mistreatment and Academic Motivation Scale (AMS). Descriptive statistics, chi-square tests, correlations, and regression analyses were conducted. A p-value &lt; 0.05 was considered statistically significant. The sample included 399 students, with mean age of 23 ± 1.29 years old, and 61.5% were female. A total of 81% of participants experienced mistreatment. Twenty-nine percents of students thought that mistreatment occurred because the maltreaters did not consider mistreatment as inappropriate or serious. Students who experienced mistreatment exhibited lower AMS (B = -9.16, 95% CI: -15.37 to -2.95, p-value = 0.004) than those who did not. Moreover, students who experienced academic mistreatment exhibited a higher amotivation score (B = 1.50, 95% CI: 0.16 to 2.85, p-value = 0.029) than those who did not. The prevalence of mistreatment was unexpectedly high, and it associated with students' motivation to study. Educational institutions should prioritize addressing this issue and developing strategies to provide assistance, including the enhancement of reporting systems.

Epilepsy is a non-communicable neurological disease characterized by abnormal brain activity with conceivable peripheral implications. Few studies examine the role of peripheral and brain inflammation in the relationship between seizure predisposition and nonalcoholic fatty liver disease. Severe early-life infections leading to sepsis results in increased inflammation that can aggravate epilepsy and hepatic damage progression both associated with increased odds for hospital admissions in epileptic patients. Here, we examined the effect of early LPS challenge (1 mg/kg, i.p. at post-natal day3, PND3) in inducing hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45), evaluating the intra- and inter-gender differences on systemic and liver inflammation, hepatic lipid dysmetabolism and oxidative damage associated to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Early LPS challenge induced a major inflammatory and immune response in male epileptic rats than females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-insulted females showed a marked alteration in hepatic metabolic and lipid profile and the reduction in mitochondrial fatty acid oxidation. The two different gender-related mechanisms of LPS-induced liver injury converge in mitochondrial oxidative damage with intensified ROS production in both sexes, that notably induced a compensatory increase in antioxidant defense only in females. Our study with a translational potential points out that early postnatal infections predispose epileptic rats to develop or worsen hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

Abstract: (1) Background: We determined the prevalence of hepatitis B virus (HBV) amongst people without human immunodeficiency virus (HIV) in rural and peri-urban areas in Botswana. (2) Methods: We screened hepatitis B surface antigen (HBsAg) from archived plasma samples of people without HIV (n=2135) randomly selected from the Botswana Combination Prevention Program (BCPP) (2013–2018). We sequenced 415 bp of the surface region using BigDye sequencing chemistry. (3) Results: The median age of participants was 31 (IQR: 24–46) and 64% (1360/2135) were female. HBsAg prevalence was 4.0% (86/2135) [95% CI: 3.3 – 4.9]) and ranged between 0%–9.2%. Older participants (>35 years) had increased odds of HBsAg positivity (OR: 1.94; 95% CI: [1.32–2.86]; p = 0.001. Thirteen samples were sequenced and 7 (53.8%) were genotype A, 3 (23.1%) were genotype D and genotype E each. Clinically significant mutations were identified in the surface region, but no classic drug resistance mutations were identified. (4) Conclusions: We report an HBV prevalence of 4.0% (95% CI 3.3 – 4.9) among people without HIV in rural and pe-ri-urban communities in Botswana with varying rates in different communities. A comprehen-sive national HBV program is required in Botswana to guide HBV prevention, testing and management.

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.

Aims. Bone metastases have an incidence of up to 75% in metastatic breast cancer, thanks to the evolution of imaging we can identify them in the oligometastatic phase. With the introduction of target therapies and increasingly effective conjugated antibodies, it is increasingly common to treat patients with radiotherapy although asymptomatic (if single or ≤5 bone lesions). Volumes and doses in this setting do not yet have a clear guidelines. In this study, the aim is to administer to the macroscopically evident disease an ablative dose that favors the local control of disease. Aim of this retrospective analysis is to evaluate the outcome of pts receiving SIB for treatment of bone metastases. Material and Methods. A retrospective analysis including mBC patients (pts) undergone RT on bone metastases was conducted for pts treated between January 2014 and January 2022. Primary endpoint was freedom from local progression (FFLP). Rate of disease progression after radiotherapy (DP-AR) and overall survival (OS) were secondary endpoints. Subgroup analysis (age, immunophenotype, line of therapy) were performed. Results. Among 954 mBC who underwent radiotherapy for metastases, 85 pts underwent SIB-IMRT with a boost on macroscopic lesion of 8-6 Gy in 5 fr. Mean follow up was 41 months (6-61.5 m). Nineteen pts had single bone metastase (22.4%), 20 pts were oligometastatic (23,5%), 46 pts were plurimetastatic (54,1%). FFLP was 17 months (95% CI 3.2-61.5 m). Only 6 pts (7%) had local relapse on SIB-IMRT site during follow up. DP-AR was 13,2 m (95% CI 3.1-56.9 m). OS was 82,7 m (95% CI 10.6-343 m). Local-relapse was not associated with age, immunophenotype or sistemic line ongoing. Among secondary outcomes, DP-AR resulted associated to immunophenotype (p 0.002). DP-AR and OS were not significantly associated with local relapse (respectively p 0.148 and p 0.4). Conclusions. Pts with breast tumor can be treated with SIB-IMRT on bone metastases with a 93% of local control at 17 months from radiotherapy. Further data are needed to individuate pts who can benefit of dose-escalation and also sinergic effect with systemic therapies to possibly increase DP-AR.

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.

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.

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). This review paper provides a comprehensive overview of fNIRS, EEG, and fMRI, including their principles, advantages, limitations, and integration with other modalities for advanced BCIs. The paper highlights the advantages of integrating multiple modalities, such as increased accuracy and reliability, and discusses the challenges and limitations of multimodal integration. Applications of advanced BCIs in clinical, assistive, gaming, and entertainment domains are also discussed. 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 on data acquisition approaches and a comparison of the ease of use for each of the modalities.

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.

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.

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.