In this study, we evaluated the physicochemical and microbial qualities of source and stored household waters in some communities in Southwestern Nigeria using standard methods. Compared parameters include physicochemical constituents; Temperature (T), pH, Total Dissolved Solids (TDS), Total Hardness (TH), Biological Oxygen Demand (BOD), Magnesium ion (Mg²⁺) and Calcium ion (Ca²⁺) and microbiological parameters included Total Coliform Counts (TC), Faecal Coliform Counts (FC), Fungal Counts (Fung C), Heterotrophic Plate Counts (HPC). Comparing Stored and Source samples, the mean values of some physicochemical parameters of most of the stored water samples significantly (P<0.05) exceeded that of Sources and ranged in the following order: T (15.3±0.3^oC - 28.3±0.5^oC), pH (6.4±0.1 - 7.6±0.1), TDS (192.1±11.1 ppm - 473.7±27.9 ppm), TH (10.6±1.7 mg/L - 248.6±18.6 mg/L), BOD (0.5±0.0 mg/L - 3.2±0.3 mg/L), Mg²⁺ (6.5±2.4 mg/L - 29.1±3.2 mg/L) and Ca²⁺ (6.5±2.4 mg/L - 51.6±4.4 mg/L). The mean microbial counts obtained from microbial comparison of different points (Stored and Source) of collection showed that most of the stored water had counts significantly exceeding (P<0.05) those of the source water samples (cfu/100 mL) which ranged as follows: TC (3.1±1.5 - 156.8±42.9), FC (0.0±0.0 - 64.3±14.2) and HPC (47.8±12.1 - 266.1±12.2) across all sampled communities. Also, the predominant isolates recovered from the samples were identified as Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Enterobacter aerogenes, Aspergillus spp, Mucor spp, Rhizopus spp and Candida spp. The presence of these pathogenic and potentially pathogenic organisms in the waters and the high counts of the indicator organisms suggest the waters to be a threat to public health.

Crystal structures of simple metals and binary alloy phases based on the face-centered cubic (fcc) structure are analyzed within the model of Fermi sphere – Brillouin zone interactions to understand the stability of original cubic structure and derivative structures with distortions, superlattices and vacancies. Examination of the Brillouin-Jones configuration in relation to the nearly-free electron Fermi sphere for several representative phases reveals significance of the electron energy contribution to the phase stability. Representation of complex structures in the reciprocal space clarifies their relationship to the basic cubic cell.

Propionibacterium acnes and Staphylococcus epidermidis are the major skin bacteria that cause the formation of acne. The present study was conducted to investigate antibacterial activity of ethanolic extract of cinnamon bark, honey and their combination against acne bacteria. The antibacterial activity of extract of cinnamon bark and honey were investigated against P. acnes and S. epidermidis using disc diffusion method. Minimum Inhibitory Concentration (MIC) and minimal bactericidal concentration (MBC) were performed using Clinical and Laboratory Standard Institute (CLSI) methods. The interaction combination between extract of cinnamon bark and honey was determined by using a checkerboards method. The results showed that he MIC of extract of cinnamon bark and honey against P. acne were 256 µg/mL and 50% v/v, respectively, while against S. epidermidis were 1024 µg/mL and 50% v/v, respectively. The MBC of extract of cinnamon against P. acnes and S. epidermidis were more than 2048 µg/mL, whereas the MBC for honey against P. acnes and S. epidermidis were 100%. The combination of cinnamon bark extract and honey against against P. acnes and S. epidermidis, showed additive activity with the FICI value 0.625. Therefore, the combination of extract of cinnamon bark and honey has potential activity against acne causing bacteria.

This study explores the relationship between job satisfaction, employee loyalty and two types of flexible employment arrangements; teleworking and flexi-time. The analysis relies on data derived by the Workplace Employee Relations Survey (WERS) in 2004 and 2011. A propensity score matching and least squares regressions are applied. Furthermore, Bayesian Networks (BN) and Directed Acyclic Graphs (DAGs) are employed in order to confirm the causality between employment types explored and the outcomes of interest. Finally, an instrumental variables (IV) approach based on the BN framework is proposed and applied in this study. The results support that there is a positive causal effect from these employment arrangements on job satisfaction and employee loyalty.

The interplay between wildfires and drought stress has significantly limited forest recovery in the Mediterranean ecosystem of central Chile. Since 2010, the region has faced a prolonged 'Mega Drought,' which intensified into a 'Hyper Drought' in 2019, with record-low precipitation and high temperatures, further constraining forest recovery amidst increasing wildfire frequency. This study evaluates short-term vegetation recovery across drought gradients in three sclerophyllous evergreen forests, analyzing Landsat time series (1987–2022) for 42 wildfires. Using the LandTrendr algorithm, we assessed post-fire forest recovery based on NDVI changes between pre-fire values and subsequent years. The results revealed significant differences in recovery across drought gradients and fire severity interactions. After five years, the xeric forest dominated by Quillaja saponaria and Lithrea caustica showed 89% recovery during the Mega Drought and 34% during the Hyper Drought. In contrast, the mesic forest dominated by Cryptocarya alba and Peumus boldus exhibited 28% recovery during the Mega Drought and 43% during the Hyper Drought. Degraded thorny shrublands showed the lowest recovery, averaging 23% under Hyper Drought and medium fire severity. These findings underscore the critical role of prolonged, severe drought in shaping forest recovery dynamics and highlight the need to understand these patterns to improve future forest resilience under increasingly arid conditions.

Aβ1-42 (amyloid beta) oligomers, the major neurotoxic culprits in Alzheimer's disease, initiate early pathophysiological events, including neuronal hyperactivity, that underlie aberrant network activity and cognitive impairment. Although several synaptotoxic effects have been extensively studied, neuronal hyperexcitability which may also contribute to cognitive deficits is not fully understood. Here, we found several adverse effects of in vivo injection of Aβ1-42 oligomers on contextual memory and intrinsic properties of CA1 pyramidal neurons. Male rats underwent behavioral and electrophysiological studies 1 week after microinjections into the dorsal CA1 region, followed by histological analysis. After 1 week, Aβ1-42 oligomers impaired contextual learning without affecting basic physiological functions and triggered training-induced neuronal excitability. Furthermore, riluzole, a persistent sodium current (INaP) blocker, dose-dependently reduced Aβ1-42 oligomer-induced hyperexcitability. Congo red staining, which detects insoluble amyloid deposits, further identified labeling of CA1 pyramidal neurons while immunohistochemistry with lecanemab, which detects soluble Aβ oligomers, revealed immunoreactivity of both pyramidal and non-pyramidal cells in the target area. Therefore, our study suggests that a single injection of Aβ1-42 oligomers resulted in contextual memory deficits along with concomitant neuronal hyperexcitability and amyloid deposition in the CA1 region after 1 week.

Background/Objectives: Traditional neurosurgical training involves a steep learning curve. The introduction of advanced simulation technologies, such as virtual reality (VR), provides an alternative method for skill acquisition, allowing for repeated practice and objective assessment. This study focuses on evaluating the learning curve associated with lumbar pedicle Kirschner wire insertion using a virtual fluoroscopic simulator among neurosurgical residents. Methods: Eighteen neurosurgery residents and two interns participated in this study. Participants’ initial skill levels were assessed through a questionnaire. Performance metrics, including insertion accuracy, time, and the number of virtual X-ray scans, were recorded across multiple attempts until a “practical learning plateau” was reached. Statistical analyses were conducted to model learning curves, assess the correlation between pre-training experience and performance. Results: The average number of attempts required to stabilize performance was 5.61. Learning rates varied, with some residents showing rapid improvement while others progressed more slowly. Higher accuracy in wire placement correlated with reduced usage on X-rays over time. However, experienced residents did not necessarily learn faster, indicating potential challenges in adapting to new simulation-based methods. Post-training feedback highlighted the simulator’s utility in increasing confidence and skill levels, although some limitations in anatomical accuracy were noted. Conclusions: This study demonstrates the potential of virtual simulation to enhance neurosurgical training by providing a controlled environment for repeated practice and objective feedback. Simulation-based training can effectively complement traditional methods, though individualized approaches may be necessary to accommodate varying learning rates among residents. Further refinement of simulation tools and their integration into standard training curricula are recommended.

The use of natural health products (NHP) is constantly increasing worldwide. Among the most NHP consumed are the resins of Commiphora myrrha (C. myrrha) tree. Consumption of C. myrrha may result in herb-drug interactions that can lead to serious health consequences. This study aims to determine the herb-drug interactions based on the induction of drug-metabolizing enzyme cytochrome P-450 (CYP) 2C9 by a non-toxic boiled aqueous extract of C. myrrha and to unveil the potential involvement of xenobiotic-sensing nuclear receptors such as Pregnane X Receptor (PXR), a well-known CYP 2C9 transcription factor. Tested at low concentrations (0.01-10 g/mL) devoid of anti-proliferative effects, boiled C. myrrha resin aqueous extract upregulated CYP 2C9 gene and protein expressions in a dose-dependent manner, reaching a mean expression level exceeding 3.0-fold change in Hep G2 cells, compared with the basal level expressed in untreated cells. Furthermore, chemical analysis using mass spectrometry and computational molecular docking using in silico studies revealed that few C. myrrha resin-derived metabolites are strongly bound to PXR. In particular, the identified metabolite named diayangambin exhibited a predicted molecular docking score close to that of a native PXR ligand. The use of the nuclear receptor binding assays confirmed the binding between C. myrrha metabolite(s) and PXR, while no binding to the other xenobiotic-sensing nuclear receptor, the constitutive androstane receptor (CAR), was observed, suggesting that C. myrrha metabolite(s) are potential PXR agonists. In conclusion, although in vivo studies are needed, this study cautions patients, healthcare providers, and governmental regulators against the consumption of C. myrrha and diayangambin-rich preparations with a high potential for herb-drug interactions through drug-metabolizing CYP 2C9 enzyme induction, which could affect drug efficacy.

The selection of the best allogeneic donor for each specific patient is crucial for the success of allogeneic hematopoietic stem cell transplantation (HSCT). Besides the well-known patient’s characteristics, donor-related variables such as patient-donor histocompatibility and donor age are of utmost importance for the outcome after HSCT. However, there is still debate on the definition of the best stem cell donor when multiple suitable donors exist. By using own data from two transplant centers, we here developed a calculator able to provide the 2-year patients’ overall survival (OS) associated to each of the potential donor options during the selection process. Data on n=737 HSCTs performed from January 2010 to July 2022 have been retrospectively obtained. Donor types were HLA-identical siblings, unrelated or related haploidentical. Cox regression and parametric model indicates patients’ age, disease, comorbidity index and donor type as significant variables (p<0.05) able to predict 2-year OS with robustness (concordance index: 0.677). Estimates are provided with the three donor options for each single, specific patient. Of note, estimates express real data of the transplant centers and reflect their actual experience. In conclusion, we here present the prototype of a new tool for the calculation of patients’ outcome according to the stem cell donor type, guiding transplant physicians during the process of donor selection before HSCT. The novelty of this approach relies on the use of real data from the investigating centers, reflecting the local clinical experience. Improvements are planned by filling additional information and pooling data from more centers.

In mammals, fatty acid transport protein 1 (FATP1) is involved in cellular long-chain fatty acid (LCFA) uptake and activation, especially in processes of transportation, oxidation and triglyceride synthesis. However, the role of Fatp1 in invertebrates, especially decapod crustaceans, is still poorly understood. In this study, the cDNA of a fatp1 gene of a decapod crustacean, mud crab Scylla paramamosain, was cloned and functionally characterized. The fatp1 gene encoded a polypeptide of 643 amino acids that possessed all the typical features of the Fatp family, and shared high homology with the other Fatp orthologs of crustaceans. The relative expression levels of fatp1 were higher in metabolically active tissues such as hepatopancreas, stomach and gill than the other parts of crabs. Knockdown of the fatp1 gene in vivo reduced triglyceride and total lipid levels in the hepatopancreas, and increased the tissue expression levels of genes related to fatty acid transportation, allocation and hydrolysis including long-chain acyl-CoA synthetase 3/4 (acsl3/4) and carnitine palmitoyl transferase 1 (cpt1), and decreased expression levels of genes related to fatty acid synthesis such as acetyl-CoA carboxylase (acc) and fatty acid synthase (fas). Increased dietary n-3 LC-PUFA levels resulted in the up-regulation of fatp1 gene expression in the hepatopancreas, and the increase in LC-PUFA content, especially EPA and DHA, in both polar and nonpolar lipids in hepatopancreas and muscles of crabs. The data collectively suggested that the fatp1 gene, identified in S. paramamosain, might play important roles in regulating fatty acid absorption, utilization and allocation in crustaceans.

Necroptosis is a regulated form of cell death implicated in several pathological conditions, in-cluding viral infections. In this study, we investigated the expression and correlation of necroptosis markers, MLKL, RIP1 and RIP3, in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). Liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture. The cases un-derwent histopathological analysis, followed by tissue immunostaining with the immuno-histochemical method of streptavidin-biotin peroxidase. Using the in situ method, we evaluated the centrilobular (Z3), midzonal (Z2), periportal zone and portal tract (PT) zones of human liver parenchyma with markers for necroptosis, RIPK1, RIPK3 and MLKL. Quantitative analysis re-vealed significantly higher expression of MLKL, RIP1 and RIP3 in the liver parenchyma of YF cases compared to controls in different zones (Z3, Z2, Z1) and portal tracts (PT) of the liver, especially in zone 2. Immunostaining confirmed the localization of MLKL, RIP1 and RIP3 in hepatocytes and inflammatory infiltrates, highlighting their involvement in the pathogenesis of YF. Pearson's correlation analysis demonstrated significant correlations between necroptosis markers which indicate their coordinated regulation during YF-induced liver injury.

Background: Despite procedural advancements in the management of univentricular heart patients palliated with a Fontan-type circulation, their exercise capacity and quality of life remain limited. Postoperative exercise training programs offer potential benefits, yet practical implementation and adherence to guidelines are often inadequate. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Method: A systematic search was conducted on August 24, 2023, using PubMed, Scopus, Web of Science, and Cochrane Library. Studies were screened via Rayyan QCRI based on pre-set exclusion criteria, and their quality was assessed using the Cochrane RoB Tool 2 and the STROBE checklist. A meta-analysis employed a continuous random-effects model to assess the efficacy of cardiac rehabilitation interventions. Results: The study included twenty-six studies (7 RCTs, 19 cohorts) representing 22 individual cohorts. The key findings were that aerobic exercise, lower-extremity resistance training, and inspiratory muscle training significantly improved VO2, enhancing exercise capacity in Fontan patients. Conclusion: While the results are promising, it's crucial to remember that training programs varied widely. Exercise training shows promise for postoperative management, potentially improving exercise capacity, cardiac biomarkers, lung function, and lower limb strength. However, further research is not just a suggestion, but a necessity. It's necessary to refine protocols, assess long-term impacts, and investigate underlying mechanisms, especially for Fontan patients with severe clinical conditions. This emphasizes the importance and urgency of further research in this area.

Autism spectrum disorder (ASD) involves social communication difficulties and repetitive behaviors, with a growing prevalence worldwide. Symptoms include cognitive impairments, gastrointestinal (GI) issues, feeding difficulties, and psychological problems. A significant concern in ASD is food selectivity, leading to nutrient deficiencies. Common GI issues in ASD, such as constipation and irritable bowel syndrome, stem from abnormal gut flora and immune system dysregulation. Sensory sensitivities and behavioral challenges exacerbate these problems, correlating with neurological symptom severity. Children with ASD also exhibit higher oxidative stress due to low antioxidant levels like glutathione. Therapeutic diets, including ketogenic, high-antioxidant, gluten-free, and casein-free, show potential in managing ASD symptoms like behavior, communication, GI issues, and oxidative stress, though the evidence is limited. Various studies have focused on different populations, but there is increasing concern about the impact on children. This review examines the effect of food selectivity, GI problems, and antioxidant deficiencies in ASD and revises the effectiveness of various therapeutic diets, highlighting the need for further research to confirm their long-term benefits.

Developing short-term forecasting model for global atmospheric temperature and wind in the near space is crucial for understanding atmospheric dynamics and supporting human activities in this region. While numerical models have been extensively developed, deep learning techniques have recently shown promise in improving atmospheric forecasting accuracy. In this study, convolutional long short-term memory (ConvLSTM) and convolutional gated recurrent unit (ConvGRU) neural networks were applied to build for short-term global-scale forecasting model of atmospheric temperature and wind in the `near space based on the MERRA-2 reanalysis dataset from 2010-2022. The model results showed that the ConvGRU model outperforms the ConvLSTM model in the short-term forecast results. The ConvGRU model achieved a root mean square error in the first three hours of approximately 1.8 K for temperature predictions, and errors of 4.2 m/s and 3.8 m/s for eastward and northward wind predictions, respectively.

Papillomaviruses (PVs) are oncogenic and infect the skin and mucosa of various host species. Considering the recent advances in research on PVs using rolling circle amplification (RCA) followed by high-throughput sequencing (HTS), in this study, we aimed to investigate the bovine papillomavirus (BPV) types associated with proliferative lesions in the upper alimentary tract of an affected bull and characterize the viral strains through complete genome sequencing using this strategy. We analyzed the PV strains associated with two hyperplastic esophageal lesions through PCR using degenerate primer pairs and RCA, followed by HTS. HTS of the libraries generated using RCA products provided the whole genome sequence of BPV4 present in squamous papilloma, whereas, the complete genome sequence of BPV2 and subgenomic fragments of BPV4 were identified in carcinoma in situ (CIS). We, for the first time, have sequenced BPV2 identified from the CIS of the bovine upper alimentary canal. Additionally, RCA followed by HTS allowed characterization of the mixed infection by BPV2 and BPV4 in this lesion. These data reveal that BPV4 is not the only BPV type present in CIS of the esophageal mucous membrane; moreover, a mixed infection caused by BPV2 and BPV4 at the tested anatomical site was demonstrated.

Many studies have demonstrated hydrogen's therapeutic and preventive effects on various diseases. Its selective antioxidant properties against hydroxyl radicals, which are responsible for the indirect effects of ionizing radiation, may make it worthy of attention as a new radio-protector. We recently developed new hydrogen water that is more stable and has higher antioxidant activity by using ultra-fine bubbles. In this study, female C57BL/6J mice given ad libitum access to ultra-fine bubble hydrogen water (UBHW) were subjected to whole-body irradiation (WBI) with X-rays, and the radio-protective effect of UBHW was evaluated. Sub-lethal WBI resulted in a 30-day survival rate of 100% in UBHW-fed mice, compared with 37% in control mice. In the case of lethal WBI, while the control mice died out in about 3 weeks, the 30-day survival rate improved to 40% by UBHW due to the high scavenging activity of hydroxy radicals. Twenty-six serum proteins involved in inflammatory and immune responses were significantly identified in UBHW-fed mice by proteomics, and UBHW may enhance and regulate these functions, resulting in reduced damage in mice exposed to WBI. We conclude that UBHW has good potential in radio-protection, with evidence that warrants further research efforts in this field.

Much evidence now indicates a direct crosstalk between thyroid hormones (THs) and the immune system. We previously showed that THs behave as anti-inflammatory agents in human leukemic THP-1 monocytes, but a potential neuroprotective effect of THs in microglia have been under-investigated. Microglia, the primary innate immune cells of the brain, play a pivotal role in the regulation of neuroinflammation and nongenomic integrin αvβ3-mediated action of THs appear to be involved. Integrin αvβ3 was highly expressed in activated BV-2 cells, while it was decreased by THs. In addition, THs facilitated wound healing in BV-2 murine microglia cells activated by lipopolysaccharide (LPS), through integrin αvβ3 and reactive oxygen species (ROS), with tetrac (a metabolite of TH) potentiated the inhibition of migration. Nitric oxide (NO) played a role with different mechanisms in the presence of either T3 or T4. Our data showed the capability of TH and analogues to modulate the M1-to-M2 microglial transition and suggest a new spectrum of actions in the central nervous system (CNS).

Background: Low back pain (LBP) is a major cause of disability globally, and the diagnosis of LBP is challenging for clinicians. Objective: This study aimed to assess the accuracy level of arti-ficial intelligence as a Clinical Decision Support System (CDSS) called Therapa compared to MRI in predicting lumbar disc herniated patients. Methods: One hundred low back pain patients aged ≥18 years old were included in the study. The study was conducted in 3 stages, at first, a case se-ries was conducted by matching MRI and Therapha diagnosis for 10 patients. Subsequently, Delphi methodology was employed to establish a clinical consensus. Lastly, to determine the ac-curacy of the newly developed software, a cross-sectional study was undertaken, involving 100 patients. Results: The software showed a significant diagnostic accuracy with the area under the curve in the ROC analysis determined as 0.84 with a sensitivity of 88% and a specificity of 80%. Conclusion: The study’s findings revealed that CDSS using Therapha has a reasonable level of ef-ficacy, and this can be utilized clinically to acquire faster and more accurate screening of patients with lumbar disc herniation.

Green peppers (Capsicum annuum L.) is a fruit vegetable with great culinary versatility, and present important nutritional properties for human health. Water deficit negatively affects nutritional quality of green peppers fruits. This study aimed to investigate the influence of zinc oxide nanoparticles (ZnONPs), associated with plant growth-promoting bacteria (PGPB), on the post-harvest quality nutritional of green peppers subjected to water deficit. In an open-field ex-periment, two irrigation levels (50 and 100% of crop evapotranspiration - Etc), four treatments composed by combination of ZnONPs, zinc sulfate (ZnSO4) and PGPB (T1 = ZnSO4, T2 = foliar ZnONPs, T3 = foliar ZnONPs + PGPB, T4 = ZnSO4 via soil + PGPB via soil) and a control treatment (Check) were tested. Water deficit or water deficit mitigation treatments did not interfere with the physical-chemical parameters (except vitamin C content) and physical color parameters (except L*) of green pepper. The water deficit reduced the levels of Ca, Mg, P, K, Mn, Fe, B, and Zn in the fruits. The foliar application of ZnONPs in association with PGPB provided better nutritional quality of green pepper in terms of vitamin C and mineral nutrients. Under water deficit, ZnONPs or ZnSO4 via foliar, associated or not with PGPB, increased the levels of Ca, P, Mg, and Fe in the fruits. Applying Zn via foliar as ZnONPs or ZnSO4 mitigated the negative effects of water deficit on the quality of pepper fruits that was enhanced by the Bacillus subtilis and B. amyloliquefaciens inoculation.

Overweight/obesity and cardiovascular diseases are associated with high rates of mobility and mortality. We investigated inflammatory lesions and ionic transporters in the left ventricle of male rats chronically fed a high-fat diet (HL). They developed moderate overweight with early expansion of visceral adiposity. The inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-), Na+-transporting ATPases, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles, and the left ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). HL rats doubled IL-6 and TNF-, which returned to normal levels when signaling coupled to Angiotensin II type 2 receptors (AT2R) was supraregulated by Ang-(3–4) administration. The decreased glucose tolerance was accompanied by significantly reduced plasma triglycerides due to intense hepatic steatosis (Crisóstomo et al. Metabolism Open. 2022, 14, 100176). AT2R (and AT1R) abundance did not change. (Na++K+)ATPase and ouabain-resistant Na+-ATPase were downregulated and upregulated, respectively, normalized with Ang-(3–4). SERCA2a lost its most critical regulatory property, inhibition by excess substrate. The ultrasound showed no changes in FS and EF. We conclude that very moderate overweight can cause silent initial molecular tissue damage in heart, which can evolve to cause systolic dysfunction.

The IMbrave150 trial established atezolizumab with bevacizumab (A+B) as standard care for hepatocellular carcinoma (HCC), recommending an esophagogastroduodenoscopy (EGD) within 6 months of treatment initiation to prevent bleeding from esophagogastric varices. The necessity of mandatory EGD for all patients remains unclear. We retrospectively analyzed 112 HCC patients treated with A+B at five Canadian cancer centers from July 1, 2020, to August 31, 2022. A+B was the first-line therapy for 90% of patients, with median overall survival at 20.3 months and progression-free survival at 9.6 months. There was no survival difference between patients with bleeding and those without. Before A+B, 71%(79) of patients underwent an EGD within 6 months, revealing varices in 41%(32) and requiring intervention in 19%(15). The overall bleeding rate was 15%(17), with GI-specific bleeding occurring in 83%(5) of the EGD group and 17%(1) of the non-EGD group (p=0.24). Non-GI bleeding was observed in 10%(11) of patients. Outcomes for HCC patients treated with A+B in Canada were comparable to IMbrave150. Our study showed twice the rate of varices detection and treatment compared to IMbrave150, reflecting real-world treatment of high-risk populations. There was no increased GI bleeding in patients without pre-treatment EGD, supporting a selective EGD approach.

Background: The Risk of Paradoxical Embolism (RoPE) score was developed to identify stroke-related patent foramen ovale (PFO) in patients with cryptogenic stroke. Methods: We conducted a retrospective analysis of the 2016 to 2020 National Inpatient Sample to determine the performance of modified RoPE score for PFO presence in patients with acute ischemic stroke (AIS). Results: A total of 3,338,805 hospital admissions for AIS were analysed and 3.0% had PFO. Patients with PFO were younger compared to those without PFO (median 63 years vs. 71 years, p&lt;0.001) and fewer were female (46.1% vs. 49.7%, p&lt;0.001). The patients with PFO had greater mean modified RoPE score (4.0 vs. 3.3, p&lt;0.001). The area under the curve for the RoPE score in predicting PFO was 0.625 (95%CI 0.620-0.629). The best diagnostic power of the RoPE score was achieved with a cut point of ≥4 where the sensitivity was 55% and the specificity was 64.2%. A cut point of ≥5 increased specificity (83.1%) at the expense of sensitivity (35.8%). The strongest predictor of PFO was deep vein thrombosis (OR 3.97, 95%CI 3.76-4.20). Conclusions: The modified RoPE score had modest predictive value in identifying patients with PFO among patients admitted with AIS.

Rutin, a flavonoid compound found in various plants, has gained attention for its potential applications in the cosmetic industry due to its antioxidant, anti-inflammatory, and potential photoprotective properties. Our review explored the use of rutin (rutoside, 3-O-rutinoside-quercetin) in cosmetics/dermocosmetics, focusing on its physicochemical properties and stability, cutaneous permeability, and efficacy in sunscreen systems, involving in vitro tests and the current state of clinical trials. Rutin's ability to scavenge free radicals, prevent peroxidation, and reduce vascular fragility makes this flavonoid a promising ingredient for photoprotection. Studies have shown that rutin can enhance the sun protection factor (SPF) of sunscreen formulations, especially when combined with organic UV filters. The encapsulation of rutin in nanostructures has also been investigated to improve its applicability. Overall, rutin shows potential as a safe and effective ingredient in cosmetic/dermocosmetic formulations, offering protection against the harmful effects of UV radiation and oxidative stress on the skin.

Image-guided radiotherapy supported by surface guidance can help track lower lung lesion respiratory motion while reducing a patient’s exposure to ionizing radiation. However, it is not always clear how skin respiratory motion magnitudes and correlations with lung lesion respiratory motion vary between different skin regions of interest (ROI). Four-dimensional Computed Tomography (4DCT) images provide information on both skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. Analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing lower lung lobe lesion, as well as respiratory motion correlations between nine ROIs and TS. The effects of gender and adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between ROIs in both respiratory motion magnitudes and correlations to TS have been detected. An overall negative correlation between ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. Respiratory magnitudes in regions without rib support tended to be larger for men than for women, but no differences in ROI-to-TS correlation between sexes have been detected. Described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

1) Background: carbapenem-resistant Acinetobacter baumannii (CRAB) is an opportunistic Gram-negative pathogen that has a significant role in healthcare-associated infections. Unlike several studies on the antibiotic-resistant epidemiology of A. baumanni, virulence molecular epidemiology was less studied. This study aimed to investigate CRAB virulence genes and their ability to form biofilms, and to correlate their biofilm formation ability with both; biofilm-encoding virulence genes and carbapenemase-encoding resistance genes. 2) Methods: 107 CRAB clinical isolates were collected from two hospitals in Jordan between 2018 and 2019 and were screened for virulence genes using PCR. In addition, biofilm formation ability was assessed using the microtiter plate method. 3) Results: the frequencies of the bap, OmpA, surA, PLD, paaE, basD, and traT virulence genes were 99.10%, 98.20%, 98.20%, 95.50%, 89.10%, 86.40%, and 8.20%, respectively. Overall, 86.4% of the tested isolates were biofilm formers with varying degrees; weak (28.2%), moderate (36.4%) and strong (21.8%). A significant relationship was found between the carbapenemase-encoding gene (OXA-23 gene) and biofilm production. 4) Conclusion: to the best of our knowledge, this is the first study in Jordan that inspected CRAB virulence genes and highlighted the importance of improving infection control measures to avoid CRAB outbreaks.

This work addresses the challenge of EEG visual multiclass classification into 40 classes for Brain-Computer interface applications, by using deep learning architectures. The visual multiclass classification approach offers BCI applications a significant advantage, since it allows the supervision of more than one BCI interaction, considering that each class label supervises a BCI task. However, because of the nonlinearity and nonstationarity of EEG signals, performing multiclassifiers based on EEG features remains a significant challenge for BCI systems. In the present work, mutual information-based discriminant channel selection and Minimum-Norm Estimate algorithms are implemented to select discriminant channels and enhance EEG data. Hence, deep EEGNet and Convolutional-recurrent neural networks are implemented separately to classify EEG data of image visualization into 40 labels. By using the k-fold cross-validation approach, average classification accuracies of 94.8% and 89.8% were obtained by implementing the aforementioned network architectures, respectively. Satisfactory results obtained with this method offer a new implementation opportunity for multi-task BCI applications by utilizing a reduced number of channels (&lt;50%), compared to those presented in the related literature where the whole set of channels is used.

This article aimed to evaluate, using statistical tools, the generation and composition of urban solid waste (MSW) in the city of Belém, Pará, from nine urban collection sectors in the municipality, and the average nominal income of the population. Approximately 900kg of urban solid waste were col-lected from the municipality in the period from 2021 to 2022. Statistical tests were carried out on hypotheses with 5% significance in comparative evaluations, and their respective average nominal incomes. The results indicated that the organic fraction corresponds to 55.57% of the waste generated in the municipality, 14.26% is inert waste (potentially contaminating) and 0.67% is miscellaneous waste. It was observed that the waste generated by families with high purchasing power tends to contain higher percentages of recyclables, while in families with lower purchasing power the highest percentages tend to be organic. Knowledge of the generation of MSW is fundamental for the choice and dimensioning of operations and processes involved in the management chain at the municipal level. The decentralization of services offered based on solid waste management would enable greater success in serving the population.

In clinical practice, patient assessments rely on established scales. Integrating data from these scales into the International Classification of Functioning, Disability, and Health (ICF) framework has been suggested; however, a standardized approach is lacking. Herein, we tested a new approach to develop a conversion table translating clinical scale scores into ICF Qualifiers based on a clinician survey. The survey queried rehabilitation professionals about which functional independence measure (FIM) item scores (1-7) corresponded to the ICF qualifiers (0-4). A total of 458 rehabilitation professionals participated. The survey findings indicated a general consensus on the equivalence of FIM scores with ICF qualifiers. The median value for each item remained consistent across all item groups. Specifically, FIM 1 had a median value of 4; FIM 2 and 3 had median values of 3; FIM 4 and 5 had median values of 2; FIM 6 had a median value of 1; and FIM 7 had a median value of 0. Despite limitations due to the irreconcilable differences between the frameworks of existing scales and the ICF, these results underline the ICF's potential to serve as a central hub for integrating clinical data from various scales.

This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU) grew within a colloidal suspension of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers MA and ME, respectively). This method, applied for the first time in Semi Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality, since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a twenty-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst-solvent combinations. ME-based PHU exhibited higher (M_w ) ̅ than MA-based PHU (34,100 Da and 16,400 Da, respectively). Applying the enhanced methodology to prepare ten multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating ME enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when MA was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.

The clinical practice implies a research translation that helps the use of scientific data and thera-peutic evidence for patient benefits. This review critically summarizes the potential impact of cannabinoids in concomitance with other drugs in the following chronic diseases as Epilepsy, Au-tism Spectrum Disorders (ASD), Oncology, Multiple Sclerosis, and Chronic Pain. The potential in-teractions can change the predicted clinical outcomes of therapeutic protocols and need to be evaluated. Some of the effects would be additive, synergistic or antagonistic, but can also enroll changes in absorption, distribution, metabolism, particularly via cytochrome P450 (CYP) isoen-zymes (e.g CYP2C9 and CYP3A4) and excretion. For instance, the combination of canna-bis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases plasma concentration of Δ-9-tetrahydrocannabinol (THC) and CBD (CBD). Opposable, rifampic-in, a CYP3A4 inducer, stands out for the approximately 20-40% reduction in plasma THC levels and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Indeed, pharmacokinetic interactions have been also reported with antiseizure drugs. Moreover, pharmacodynamic interactions between cannabinoids and drugs with sympathomimetic effects (eg tachycardia, hypertension), central nervous system depressants (eg drowsiness, ataxia), and anticholinergics (eg tachycardia and drowsiness) are also expected. Even though pending further studies, there is currently clinical evidence supporting drug interaction with cannabinoids, demanding doctors evaluate the risk of drug combinations with cannabinoids. The tables herein provided were designed to facilitate the identification of bi-orelevant interactions that may compromise therapeutic efficacy and toxicity.

It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

A sustainable green one pot procedure for the synthesis of dihydropyrimidinones (DHPMs) derivatives by a three-component reaction of β-ketoester derivatives, aldehyde and urea or thiourea over the alkali-treated H-ZSM-5 zeolite under ball-milling has been developed. The product was isolated by simple washing of the crude reaction residue with ethyl acetate followed by evaporation of solvent. The hierachical zeolite catalyst (MFI27_6) showed high yield (86–96%) of dihydropyrimidinones (DHPMs), in very short time (10-30 min). The catalyst is recycled for subsequent reactions in four runs without appreciable loss of activity and high yields of products provide efficient protocol for Biginelli reactions.

Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is the limitation in self-repair ability of cartilage. Therefore, developing the strategies for cartilage repair is very important. Here, we reported a new manufacturing process of water-based polyurethane based photosensitive materials with hyaluronic acid and applied the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton's jelly mesenchymal stem cells (hWJMSCs) and the cells showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and facilitate the development of cartilage tissue engineering.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

Amyloid self-assembled from amyloid peptides βΑ40 or βΑ42 is notorious for its neurotoxic effects in plaque and neurofibrillary tangle formations leading to neuron dysfunction and diseases of cognitive decline (e.g. Alzheimer’s, Parkinson’s and Huntington's disease). This contrasts with so-called functional amyloids which are non-toxic ordered template structures amenable to applications in tissue engineering. Amyloid fibrils of variable morphology including long and hollow fibres and flattened tube and spiral ribbon-like structures have been used in engineering applications in nano-biology. Protein assemblies based on amyloid core structures display diverse biological functionalities could be applied in futuristic self-assembling biomaterials in nano-electronics. These possibilities have revolutionized the development of next generation computers and biosensors, ultracapacitors, memristors, actuators, molecular switches and could also be used to develop artificial synapses. Amyloid fibril assemblies have also been used in photoelectric and photon capture light harvesting technologies and been applied in innovative nano-photoelectronics and photovoltaics. Hybrid Aβ(16–22)-α-synuclein amyloid fibrils also exhibit light-harvesting and electron-transfer properties. Engineered amyloid assemblies are thus facilitating innovative futuristic advances in nano-technology. Furthermore, with a better understanding of amyloid fibril assembly processes it may be possible to develop therapeutic methods that prevent the toxic build up of this polymer in brain tissues that leads to diseases of cognitive decline. With the ever-expanding prevalence of these diseases in the ageing general global population, there certainly is a clear and present need to find a remedy for these debilitating conditions.

This work continues the review and illustrative application to energy systems of the “Fourth-Order Best-Estimate Results with Reduced Uncertainties Predictive Modeling” (4th-BERRU-PM) methodology. The 4th-BERRU-PM methodology uses the Maximum Entropy (MaxEnt) principle to incorporate fourth-order experimental and computational information, in-cluding fourth (and higher) order sensitivities of computed model responses with respect to model parameters. The 4th-BERRU-PM methodology yields the fourth-order MaxEnt posterior distribution of experimentally measured and computed model responses and parameters, in the combined phase-space of model responses and parameters. The 4th-BERRU-PM methodology encompasses fourth-order sensitivity analysis (SA) and uncertainty quantification (UQ), which were reviewed in the accompanying work (Part 1), as well as fourth-order data assimilation (DA) and model calibration (MC) capabilities, which will be reviewed and illustrated in this work (Part 2). The applicability of the 4th-BERRU-PM methodology to energy systems is illustrated by using the Polyethylene-Reflected Plutonium (acronym: PERP) OECD/NEA reactor physics benchmark, which is modeled using the linear neutron transport Boltzmann equation, involving 21976 im-precisely known parameters. This benchmark is representative of “large-scale computations” such as those involved in the modeling of energy systems. The result (“response”) of interest for the PERP benchmark is the leakage of neutrons through the outer surface of this spherical benchmark, which can be computed numerically and measured experimentally. The impact of the high-order sensitivities of the response with respect to the PERP model parameters is quantified for “high-precision” parameters (2% standard deviations) and “medium-precision” parameters (5% standard deviations). Analyzing the best-estimate results with reduced uncertainties for the 1st- through 4th-order moments (mean values, covariance, skewness, and kurtosis) produced by the 4th-BERRU-PM methodology for the PERP benchmark indicates that, even for systems mod-eled by linear equations (e.g., the PERP benchmark), retaining only first-order sensitivities is insufficient for reliable predictive modeling (including SA, UQ, DA, MC). At least second-order sensitivities should be retained in order to obtain reliable predictions.

The Simulation analogy presented in this work enhances the accessibility of abstract quantum theories, specifically the stochastic hydrodyanimc model (SQHM), by relating them to our daily experiences. The SQHM incorporates the influence of fluctuating gravitational background, resembling dark energy, into quantum equations. This model successfully addresses key aspects of Objective-Collapse Theories, including resolving the 'tails' problem through the definition of quantum potential length in addition to the De Broglie length, beyond which coherent Schrödinger quantum behavior and wavefunction tails cannot be maintained. The SQHM emphasizes that an external environment is unnecessary, asserting that the quantum stochastic behavior leading to wave-function collapse can be an inherent property of a system in a spacetime with fluctuating metrics. Embedded in relativistic quantum mechanics, the theory establishes a coherent link between the uncertainty principle and the constancy of light speed, aligning seamlessly with finite information transmission speed. Within a fluctuating quantum system, the SQHM derives the indeterminacy relation between energy and time, offering insights into measurement processes impossible within a finite time interval in a truly quantum global system. Experimental validation is found in confirming the Lindemann constant for solid lattice melting points and the transition from fluid to superfluid states. The SQHM's self-consistency lies in its ability to describe wavefunction collapse and the measure process. Additionally, the theory resolves the Pre-existing Reality problem by showing that large-scale systems naturally decay into decoherent states stable in time. Continuing, the paper demonstrates that the physical dynamics of SQHM can be analogized to a computer simulation employing optimization procedures for realization. This perspective elucidates the concept of time in contemporary reality and enriches our comprehension of free will. The overall framework introduces an irreversible process impacting the manifestation of macroscopic reality at the present time, asserting that the multiverse exists solely in future states, with the past comprising the formed universe after the current moment. Decoherence at the present time functions as a reduction of the multiverse to a single universe. The macroscopic reality, characterized by fractal consistency where microscopic domains with quantum properties coexist, provides insights into how our consciousness apprehends dynamic reality, the spontaneous emergence of gravity in discrete spacetime evolution, and the attainment of the classical General Relativity limit in Quantum Loop Gravity and Causal Dynamical Triangulation. The Simulation Analogy highlights a strategy focused on minimizing information processing, facilitating the universal simulation in solving its predetermined problem. From within, reality becomes the manifestation of specific physical laws emerging from the inherent structure of the simulation devised to address its particular issue. In this context, the reality simulation appears to employ an entropic optimization strategy, minimizing information loss while efficiently compressing data in line with the simulation's intended purpose.

Intrauterine growth restriction (IUGR) pigs are characterized by long-term growth failure, metabolic disorders, and intestinal microbiota imbalance. The characteristics of the negative effects of IUGR at different swine growth stages are still unclear. Therefore, this study explored whether intrauterine growth restriction (IUGR) model damaged the intestinal barrier function and altered the colonization and metabolic profiles of the colonic microbiota in growing-finishing pigs by the multi-omics method. Seventy-two piglets (36 IUGR and 36 NBW) were selected for this trial to analyze physiological and plasma biochemical parameters, oxidative damage, and inflammatory response in the colon. Moreover, the colonic microbial communities were examined using 16s rRNA sequencing and metabolomics to reveal the intestinal characteristics of pigs at different growth stages (25, 50, and 100 kg). IUGR altered the plasma concentrations of glucose, total protein triglyceride, and cholesterol. Colonic tight junction proteins were markedly inhibited by IUGR. IUGR decreased plasma T-AOC, SOD, and GSH levels, and colonic SOD-1, SOD-2, and GPX4 expressions by restraining the Nrf2/Keap1 signaling pathway. Moreover, IUGR increased the colonic IL-1β and TNF-α levels while reducing IL-10, possibly activating the TLR4-NF-κB/ERK pathways. Notably, IUGR pigs had lower colonic Streptococcus abundance and Firmicutes-to-Bacteroidetes ratio at the 25 kg BW stage while having higher Firmicutes abundance at the 100 kg BW stage; moreover, IUGR pigs had lower SCFAs concentrations. Metabolomics analysis showed that IUGR increased colonic lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic concentrations and enriched three differential metabolic pathways, including linoleic acid, sphingolipid, and purine metabolisms throughout the trial. Collectively, IUGR altered the nutrient metabolism, redox status, and colonic microbial community and metabolite profiles of pigs and continued to disrupt colonic barrier function by reducing antioxidant capacity via the Nrf2/Keap1 pathway and activating inflammation via the TLR4-NF-κB/ERK pathway during the growing-finishing stage. Colonic Firmicutes and Streptococcus could be potential regulatory targets for modulating the metabolism and health of IUGR pigs.

Oxidoreductase (OXR) enzymes are in high demand for biocatalytic applications in food industry and cosmetics: glucose oxidase (GOx), cellobiose dehydrogenase (CBDH), bioremediation: horseradish peroxidase (HRP), laccase (LAC), and medicine for biosensors and miniature biofuel cells (GOx, CBDH, LAC, HRP). They can be used in a soluble form and/or within the yeast cell walls expressed as chimeras on the surface of yeast cells (YSD), such as P. pastoris and S. cerevisiae. However, most of the current studies suffer from either low yield for soluble enzyme expression or low enzyme activity when expressed as chimeric proteins using YSD. This is always the case in studies dealing with heterologous expression of oxidoreductase enzymes, since there is requirement not only for multiple OXR genes integrations into the yeast genome (super transformations), and codon optimization, but also very careful design of fermentation media composition, and fermentation conditions during expression due to need for adding transition metals (copper, iron), and metabolic precursors of FAD and heme. Therefore, scientists are still trying to find optimal formula using above mentioned approaches, and most recently also using protein engineering and directed evolution for additional increase in the yield of recombinant enzyme production. In this review article we will cover all the current state of the art technologies and most recent advances in the field that yielded high expression level for some of these enzymes in specially designed expression/fermentation systems. We will also tackle and discuss new possibilities for further increase in fermentation yield by the cutting-edge technologies such are directed evolution, protein and strain engineering, high-throughput screening methods based on in vitro compartmentalization, flow cytometry and microfluidics.

Additive Manufacturing (AM) has been proving suitable to support or even replace traditional manufacturing in several industries, offering many advantages such as delivery time and reduction in terms of material waste, energy consumption and greenhouse gas (GHG) emissions. This study aimed to carry out a comparative assessment of the life cycle, from gate to gate, in the production of a low alloy carbon steel flange part using ER-90 wire. The methods utilized were Wire and Arc Additive Manufacturing (WAAM) and conventional manufacturing (CM) by forging, and comparative factors were energy demands, GHG emissions and generated solid waste. The total energy consumption in WAAM was 10,239.40 MJ, total carbon footprint in CO2 equivalent (CO2e) was 714.1 kgCO2e kg-1, and generated solid waste was 68.6 kg, respectively, 90%, 95% and 76% lower than consumption calculated in conventional manufacturing.

Nowadays, brain signal processing is performed rapidly in various brain-computer interface (BCI) applications. Most researchers focus on developing new methods for the future or improving the basic implemented models to identify the optimum standalone feature set. Our research focuses on four ideas. One of them introduces future communication models, and the others are for improving old models or methods. These are: 1) new communication imagery model instead of speech imager using the mental task: Due to speech imagery is very difficult, and it is impossible to imagine sound for all of the characters in all of the languages. Our research introduces a new mental task model for all languages that call Lip-sync imagery. This model can use for all characters in all languages. This paper implemented two lip-sync for two sounds, characters or letters. 2) New combination Signals: Selecting an inopportune frequency domain can lead to inefficient feature extraction. Therefore, domain selection is so important for processing. This combination of limited frequency ranges proposes a preliminary for creating Fragmentary Continuous frequency. For the first model, two s intervals of 4 Hz as filter banks were examined and tested. The primary purpose is to identify the combination of filter banks with 4Hz (scale of each filter bank) from the 4Hz to 40Hz frequency domain as new combination signals (8Hz) to obtain well and efficient features using increasing distinctive patterns and decreasing similar patterns of brain activities.3) new supplement bond graph classifier for SVM classifier: When SVM linear uses in very noisy, the performance is decreased. But we introduce a new bond graph linear classifier to supplement SVM linear in noisy data. 4) a deep formula recognition model: it converts the data of the first layer into a formula model (formula extraction model). The main goal is to reduce the noise in the subsequent layers for the coefficients of the formulas. The output of the last layer is the coefficients selected by different functions in different layers. Finally, the classifier extracts the root interval of the formulas, and the diagnosis does based on the root interval. For all of the ideas achieved the results of implementing methods. The results are between 55% to 98%. Less result is 55% for the deep detection formula, and the highest result is 98% for new combination signals.

Disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause epilepsy. Our study aims at revealing therapeutic potential of vitamins B1 and B6 in epilepsy by estimating effects of their combined administration on a seizure and its consequences in rats subjected to pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to Racine’s scale along with delayed physiological and biochemical consequences next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than male rats. Next day after a seizure, gender differences in behavior and brain biochemistry arise. The induced gender differences in anxiety, exploratory and locomotor activity correspond to disappearance of gender differences in the brain GABA, aspartate, alanine and serine, with appearance of those in glutamate, glutamine and tyrosine. PTZ decreases the brain malate dehydrogenase activity, glutamine and urea in the males, and phenylalanine in the females. Administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5-2 h) between the vitamins and PTZ administration. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. Delayed effects of vitamins and/or PTZ are mostly gender-specific and interacting. Our findings on the gender differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

A new cocrystal salt of metformin, an antidiabetic drug, and N,N’-(1,4-phenylene)dioxalamic acid, was synthesized by mechanochemical synthesis, purified by crystallization from solution and characterized by single X-ray crystallography. The structure revealed a salt-type cocrystal composed of one dicationic metformin unit, two monoanionic units of the acid and four water molecules namely H2Mf(HpOXA)2∙4H2O. X-ray powder, IR, 13C-CPMAS, thermal and BET adsorption-desorption analyses were performed to elucidate the structure of the molecular and supramolecurar structure of the anhydrous microcrystalline mesoporous solid H2Mf(HpOXA)2. The results suggest that their structures, conformation and hydrogen bonding schemes are very similar between them. To the best of our knowledge, the selective formation of the monoanion HpOXA⁻, as well as its structure in the solid, is herein reported for the first time. Regular O(-)∙∙∙C(), O(-)∙∙∙N+ and bifacial O(-)∙∙∙C()∙∙∙O(-) of n→* charge-assisted interactions are herein described in H2MfA cocrystal salts which could be responsible of the interactions of metformin in biologic systems. The results, support the participation of n→* charge-assisted interactions independently, and not just as a short contact imposed by the geometric constraint due to the hydrogen bonding patterns.

Background: Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to increased levels of high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). Objective: The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Methods: Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. Results: HMGB1 and DKK1 are significantly higher in T2DM irrespective of hypertension. T2DM was also accompanied by increased atherogenicity indices. HMGB1 and DKK1 are significantly correlated with HbA1c, glucose, indices of insulin resistance, β-cell function, and glucose toxicity, and different atherogenic indices. A large part of the variance in the β-cell index (30.5%) and glucose toxicity (34.8%) was explained by the combined effects of HMGB1 and DKK1 and hypertension. We found that 18.3% of the variance of the atherogenic index of plasma was explained by HMGB1 and DKK1 levels and that 31.2% was explained by glucose toxicity, HMGB1 and body weight. Conclusion: The higher serum HMGB1 and DKK1 levels in T2DM patients and the associations with atherogenicity indicate that low grade inflammation and disorders in the Wnt pathways are associated with T2DM and that both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are new drug targets in the treatment of T2DM.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in Wuhan, Hubei province, China being its epicenter in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11, 2020). COVID-19 has presently spread to more than 195 countries/territories while killing nearly 19,600 humans out of cumulative confirmed cases accounting to more than 430,000 within a short period of just a few weeks. The majority of deaths have been reported in Italy and China. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter COVID-19. The present review presents an overview of COVID-19 and the causative virus SARS-CoV-2, with particular emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread., highlighting in very brief the preventive and control measures along with a few of the recent research developments to counter this pandemic virus/disease.

Rationale: Major depressive disorder (MDD) is characterized by signaling aberrations in interleukin (IL)-6, IL-10, beta-endorphins as well as mu (MOR) and kappa (KOR) opioid receptors. Here we examined whether these biomarkers may aid in the classification of unknown subjects into the target class MDD.Methods: The aforementioned biomarkers were assayed in 60 first-episode, drug-naïve depressed patients and 30 controls. We analyzed the data using joint principal component analysis (PCA) performed on all subjects to check whether subjects cluster by classes; support vector machine (SVM) with 10-fold validation; and linear discriminant analysis (LDA) and SIMCA performed on calibration and validation sets and we computed the figures of merit and learnt from the data. Results: PCA shows that both groups were well separated using the first three PCs, while correlation loadings show that all 5 biomarkers have discriminatory value. SVM and LDA yielded an accuracy of 100% in validation samples. Using SIMCA there was a highly significant discrimination of both groups (model-to-model distance=87.5); all biomarkers showed a significant discrimination and modeling power, while 10% of the patients were identified as outsiders and no aliens could be identified.Discussion: We have delineated that MDD is a distinct class with respect to neuro-immune and opioid biomarkers and that future unknown subjects can be authenticated as having MDD using this SIMCA fingerprint. Precision psychiatry should employ SIMCA a) to authenticate patients as belonging to the claimed target class and identify other subjects as outsiders, members of another class or aliens; and b) to acquire knowledge through learning from the data by constructing a biomarker fingerprint of the target class.

Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory reflex system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in natural regulatory autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative specific epitopes (OSEs), nitroso (NO) and nitro (NO₂) adducts in schizophrenia remain unknown.This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl and NO₂-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls.Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO₂-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2 – 42.2 %) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO₂-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall.These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in lowered IgM responses to MDA and azelaic acid (part of the CIRS) attenuate the negative immune-regulatory feedback on the primary immune response and that this process may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

Background: The patients with head and neck cancer often experience impaired sleep. Moreover, the treatment may negatively affect sleep quality. The aim of this observational study was to evaluate the sleep quality after treatment for head and neck cancer, and its relationship with quality of life and psychological distress. Methods: One hundred fifty-one patients who underwent treatment for head and neck cancer at our department were included in the study. Quality of life, sleep quality, risk of sleep apnea, sleepiness, pain and psychological distress were assessed by means of specific questionnaires. Results: The median follow-up was 30 months. A poor sleep quality was observed in 55.6% of cases. An association between PSQI global sleep quality and EORTC global health status was found. The DT, the HADS anxiety and the HADS depression scores were associated to PSQI global score, sleep quality, sleep latency, sleep disturbances, daytime dysfunction. Conclusions: Sleep disturbances, particularly OSA and insomnia, are frequent in HNC patients, and significantly impact their quality of life and psychological well-being. Given the effect of sleep on overall well-being, addressing sleep disorders should be a priority in the care of HNC patients.

This study aimed to investigate the prevalence of cardiovascular disease (CVD) risk factors among Algerian aircrew, a population exposed to unique environmental and occupational stressors. By comparing these rates to the general population, we sought to identify specific health challenges faced by aircrew. Methods: A cross-sectional study was conducted on 154 Algerian aircrew participants. Prevalence rates for current smoking, hypertension, diabetes, and dyslipidemia were compared between the aircrew and a general population control group. Results: Our findings revealed significantly higher rates of current smoking among aircrew compared to the general population. Additionally, smoking, dyslipidemia, hypertension, and diabetes emerged as the most prevalent risk factors within the aircrew population. Conclusions: Despite the rigorous selection process for aircrew recruitment, our study confirms findings from previous literature, highlighting the high rate of normal qualifying examinations. The substantial sample size and homogeneous nature of the aircrew population enhance the reliability and generalizability of our conclusions. These findings underscore the importance of targeted interventions to mitigate CVD risk factors within this specific population, given the unique environmental and occupational factors associated with aircrew.

We will outline the relationship between luminosity distance and cosmological redshifts, demonstrating that it is consistent with a new cosmological model recently proposed by Haug and Tatum [1], which appears to resolve the Hubble tension within the Rh = ct cosmology.

In today’s business landscape, customer retention has become a critical factor for sustainable growth. Many companies continue to focus on acquisition, which leads to high costs and constant customer turnover. This article highlights the importance of retention, proposing a shift in focus toward loyalty as the key to maximizing customer lifetime value (LTV). Improving retention not only increases LTV but also reduces acquisition costs, enhances virality, and provides financial stability. This paper introduces a scientific approach that allows companies to identify the underlying causes of low retention through observation, hypothesis formulation, and controlled experimentation. Using tools such as data analysis and A/B testing, companies can iteratively optimize their retention strategy, adjusting interventions in real-time based on the results obtained. Continuous experimentation emerges as an indispensable tool for navigating market complexity, enabling organizations to learn and adapt quickly. This data-driven approach not only improves retention but also drives long-term growth by building strong relationships with customers. In an increasingly competitive environment, companies that prioritize retention and experimentation are better positioned to achieve resilient and profitable growth.

The region of Lorraine in France witnessed the collapse of the steel industries in the late twentieth century, causing massive job losses and social devastation. Daewoo Electronics, a division of one of the great Korean conglomerates of the 1980s and 1990s, came to Lorraine in eastern France in 1987. They were lured there by generous French government subsidies and the chance to enter the European market. They opened three factories in consumer electronics and components, and also nearly acquired Thomson Multimédia, a state-owned consumer electronics factory, from the French government “for a single symbolic franc.” The resulting uproar, from political opponents and Thomson and Daewoo employees, ended the deal and soured their relationship with France. Daewoo employed just over a thousand people before they closed in 2003, a result of the collapse of the entire Daewoo Group. This article places this sequence of events, widely covered in the media, in the context of French anxiety about globalization, the loss of industrial substance, and France’s place in a changing world. It is suggested that this episode, occurring at a critical juncture in the transformation of industrial capitalism into a service and digital economy, illustrates the difficulties of this period and the media coverage of factory closings.

Genetic engineering has revolutionized our ability to modify microorganisms for various applications in agriculture, medicine, and industry. This review examines recent advances in genetic engineering techniques for bacteria, fungi, and oomycetes, with a focus on CRISPR-Cas systems. In bacteria, CRISPR-Cas9 has enabled precise genome editing, enhancing applications in antibiotic production and metabolic engineering. For fungi, despite challenges associated with their complex cell structures, CRISPR/Cas9 has advanced the production of enzymes and secondary metabolites. In oomycetes, significant plant pathogens, modified Agrobacterium-mediated transformation and CRISPR/Cas12a have contributed to developing disease-resistant crops. The review provides a comparative analysis of genetic engineering efficiencies across these microorganisms and addresses ethical and regulatory considerations. Future research directions include refining genetic tools to improve efficiency and expand applicability in non-model organisms. This comprehensive overview highlights the transformative potential of genetic engineering in microbiology and its implications for addressing global challenges in agriculture, medicine, and biotechnology.

The circadian clock is an autonomous timekeeping system evolved by organisms to adapt to external changes, regulating a variety of important physiological and behavioral processes. Recent studies have shown that the sirtuin family of histone deacetylases is involved in regulating the expression of clock genes and plays an important role in maintaining the normal rhythm of clock gene expression and behavior. Moreover, sirtuins are regulated directly or indirectly by the circadian clock system. The mutual regulation between the circadian clock and sirtuins is likely involved in a variety of signal transduction and metabolism processes. In this review, we discuss the molecular mechanisms and research progress on the intertwined relationship between the circadian clock and sirtuins, highlighting sirtuins as molecular links between metabolic control and circadian rhythms and offering our perspectives on future developments in the field.

This study examines the relationship between chondroitin sulphate, proteinoids, and computational neuron models, with a specific emphasis on the Izhikevich neuron model. We investigate the effect of chondroitin sulphate-proteinoid complexes on the behaviour and dynamics of simulated neurons. Through the use of computational simulations, we provide evidence that these biomolecular components have the power to regulate the responsiveness of neurons, the patterns of their firing, and the ability of their synapses to change within the Izhikevich architecture. The findings suggest that the interactions between chondroitin sulphate and proteinoid cause notable alterations in the dynamics of membrane potential and the timing of spikes. We detect adjustments in the features of neuronal responses, such as shifts in the thresholds for firing, alterations in spike frequency adaptation, and changes to bursting patterns. The findings indicate that chondroitin sulphate and proteinoids may have a role in precisely adjusting neuronal information processing and network behaviour. This study offers new and valuable information about the complex connection between the many components of the extracellular matrix, protein-based structures, and the functioning of neurons. In addition, our analysis of the proteinoid-chondroitine system using game theory uncovers a significant Prisoner’s Dilemma scenario. The system’s inclination towards defection, due to the appeal of cheating and the significant penalty for cooperation, with a mean voltage of −9.19 mV, indicates that defective behaviors may prevail in the long-term dynamics of these neuronal interactions.

Background and Purpose: Moyamoya disease is a rare cerebrovascular disorder characterized by stenosis of the carotid arteries and the formation of collateral vessels at the base of the brain. While advances have been made in understanding its genetics, diagnostic criteria, and treatment strategies, further research is needed. The purpose of this literature review is to synthesize current knowledge on Moyamoya disease and identify areas for future study. Materials and Methods: A literature search of databases including PubMed, Embase, and Web of Science was conducted. Search terms included "Moyamoya disease" and related terms. Only English articles were reviewed, with no date restrictions. Relevant data was extracted and synthesized. Results: Key findings indicate that genetic factors such as RNF213 variants play an important role in disease susceptibility. Imaging modalities such as MRI and CT angiography are crucial for diagnosis. Surgical revascularization shows superior outcomes compared to medical management for ischemic and hemorrhagic presentations. However, optimal treatment for asymptomatic cases remains unclear. Neurocognitive and psychiatric sequelae can negatively impact quality of life. Promising research directions include investigating ethnic differences, developing biomarkers, and exploring novel therapeutics targeting molecular pathways. Conclusions: In summary, comprehension of Moyamoya disease has significantly progressed but gaps remain regarding treatment of certain populations and underlying mechanisms. Further research addressing these areas can aid in developing personalized care approaches and new interventions to improve patient outcomes

Background and Objectives: The deltopectoral (DP) flap represents a reconstructive option for head and neck. It is a fasciocutaneous flap raised from the anterior chest wall below the clavicle. Its role partially declined with the arise of free flaps. However, it still remains a valid option in patients that could not undergo a reconstruction with free flaps. The aim of this retrospective study was to evaluate the role of the DP flap in head and neck reconstruction, with a focus on surgical outcomes and complications. Materials and Methods: Thirty-one patients who underwent head and neck reconstruction with DP flap were included in the study. The delayed technique was not used in any procedure to harvest the flap beyond the deltopectoral groove. The patients’ characteristics, the recipient site, the closure of the donor site and the flap-related complications were recorded. Results: The median time to autonomization of DP flap was 23 days. Post-operative complications were observed in 10 subjects (32.3%). A partial necrosis was seen in 5 patients (16.1%), while a complete necrosis developed only in one case (3.2%). The diabetes mellitus was the only parameter associated to post-operative complications. In particular, the percentage of necrosis in subjects with or without diabetes was 66.7% and 8.0%, respectively. Conclusions: The DP has a wide range of applications in head and neck reconstruction and a low complication rate can be observed. The delayed technique does not necessarily need to be applied, and the flap can be extended beyond the deltopectoral groove when necessary. However, patients with diabetes mellitus have a higher risk of postoperative necrosis of the distal portion of the flap.

This article introduces a new interpretation to Socialism that approaches it via a heuristic study of Epochs. It is intended by this study that the intention of socialism (what it politically, socially, et cetera is proclaimed to be) is to be proposed to be indeterminate.The expectation of what Socialism is to be as a future entity is merely an interpretation that is predicated on Marx’s Capitalist Laws that have been since shown to be false. Its argument is suggested significantly by Engels’ discussions of human development and therein places an added focus on a historically based platform.

The implementation of cybersecurity standards and directives in the maritime sector plays a crucial role in protecting critical maritime infrastructures from cyber threats. The level of protection depends heavily on humans. However, the effectiveness of cybersecurity training and compliance programs, an essential component of these standards, is often hindered by challenges related to the sector’s environment, including the established technologies, practices, and norms. This paper aims to identify these challenges through a literature review and set the basis for more effective human risk minimisation, responses, and training. We identify 18 challenges and validate them with an online survey (N=205) capturing real-world perspectives from maritime-related stakeholders. Our findings contribute to enhancing the effectiveness of maritime cybersecurity training and compliance programs, ultimately strengthening the maritime cybersecurity posture.

Whole grain consumption in the US has increased due to the introduction of whole grains initially in breakfast cereals and then in snacks. Most people consider fiber as the health benefit of eating whole grains since it inhibits the absorption of fats and sugar in the GI tract. Polyphenols, the major antioxidants in the US diet, are primarily covalently bound to the fiber matrix of grains that are broken during digestion. Human biomarkers have been found after cereal grain consumption, thus proving bioavailabilty of polyphenols. Savory snacks (n=32) studied included potato chips, tortilla chips, pretzels and crackers. The snacks contained as the first ingredient enriched wheat, whole wheat, corn, potatoes, and beans. We have used both a Folin and ferric reducing antioxidant power (FRAP) colorimetric method with catechin as the standard for the commercial snack assays. Total polyphenols were analyzed after basic hydrolysis. Maximum bio-accessible polyphenols were measured after sample hydrolysis simulating in vivo digestion. FRAP measurements were done on the same samples. FRAP total antioxidant capacity values were significantly higher than Folin total polyphenols but followed the same trends and were highly correlated. Digestion significantly decreased both polyphenols and antioxidant capacity. Whole grain snacks, defined as having &gt; 50% whole grains, had significantly more polyphenols (7 times) than enriched grain snacks. Savory snack Folin polyphenols after in vitro digestion averaged 64% of the total polyphenol value. This indicates polyphenol bio-accessibility might be favorable after snack consumption. Using published data and this work, the order of total polyphenols in all snacks is nuts &gt;&gt; dried fruits &gt; popcorn &gt; pretzels &gt; tortilla chips &gt; crackers &gt; potato chips. Potato chips are the most consumed snack but are lowest in polyphenols antioxidants.

Tropical regions face significant energy challenges due to climatic conditions. This study investigates the interplay between sustainable architecture and building energy regulations in mitigating these challenges. The study aims to assess the effectiveness of existing building energy regulations in promoting sustainable architecture in tropical climates and identify key architectural strategies and regulatory frameworks for optimizing energy efficiency in tropical buildings. A comparative analysis of building regulations and case studies of sustainable buildings in selected tropical regions is conducted. The findings reveal that current regulations often must be revised to address tropical climates' unique energy demands. Incorporating passive design principles, renewable energy systems, and material selection is crucial for energy efficiency. It is recommended that building energy regulations be strengthened to mandate sustainable design strategies and provide incentives to promote the adoption of energy-efficient technologies.

Tropical regions face unique challenges in building sustainability due to high temperatures, humidity, and heavy rainfall. While building energy regulations are essential for promoting energy efficiency, their effectiveness in addressing tropical climate conditions needs to be studied more. This research aims to systematically investigate tropical building sustainability issues and evaluate the impacts of building energy regulations on these challenges. The study will identify gaps in current regulations by analyzing existing research and recommend strategies for developing more comprehensive frameworks that promote sustainable building practices in tropical regions. This research contributes to developing effective policies and strategies for achieving sustainable and energy-efficient built environments in tropical climates.

The design of school environments plays a pivotal role in promoting student wellness, mindfulness, and socio-emotional learning (SEL). This article explores the integration of Environment Behaviour Studies (EBS) concepts into school design to enhance students' overall well-being and academic success. It highlights the importance of indoor environmental quality, ergonomic and flexible learning spaces, and biophilic design in fostering a healthy and engaging learning atmosphere. Additionally, the article delves into the creation of mindfulness spaces, sensory-friendly environments, and the use of colour and aesthetics to support emotional regulation and mental health. By examining case studies of successful implementations, the article underscores best practices for designing schools that promote positive social interactions, ensure safety, and reflect community values. Ultimately, this comprehensive approach to school design aims to nurture holistic development, support socio-emotional learning, and prepare students for lifelong success.

I present a personal account of self-organizing systems. As such, it is necessarily biased and partial. Nevertheless, it should be useful to motivate useful discussions. The relevant contribution is not my attempts at answering questions (maybe all my answers are wrong), but the steps towards framing relevant questions to better understand self-organization, information, complexity, and emergence. With this aim, I start with a notion and examples of self-organizing systems (what?), continue with their properties and related concepts (how?), and close with applications (why?).

Drug repositioning is an efficient strategy to search for new treatment alternatives that is especially valuable for neglected parasitic diseases such as leishmaniasis. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERM) that have shown antileishmanial activity. Clomiphene is a SERM structurally similar to tamoxifen whose antileishmanial potential is unknown. That is why the objective of the present work was to evaluate its antileishmanial activity in vitro and in vivo, in comparison with tamoxifen. The inhibitory effect against promastigotes of L. amazonensis, L. major and L. mexicana was evaluated for both compounds; as well as the cytotoxicity against mouse peritoneal macrophages, the growth inhibitory activity in intracellular amastigotes of L. mexicana, and the in vivo activity in mice experimentally infected with L. mexicana. Clomiphene was about twice as active as tamoxifen against both promastigotes and intracellular amastigotes, with IC50 values of 1.7-3.3 µM for clomiphene and 2.9-6.4 µM for tamoxifen against all three species promastigotes; and 2.8 ± 0.2 µM and 3.7 ± 0.3 µM, respectively, against L. mexicana amastigotes. Clomiphene structurally affected several parasite organelles in a concentration-dependent fashion, leading to the death of both promastigotes and intracellular amastigotes. Interestingly, the macrophage host cell did not appear damaged with any of the clomiphene concentrations tested. By oral administration at 20 mg/kg for 14 days, both compounds showed similar effects in terms of reducing the growth of the lesions, as well as the weight of the lesions and the parasite load at the end of the follow-up period. The results showed the potential of SERM as antileishmanial drugs and support further testing of clomiphene and other compounds of this pharmacological group.

This review discusses approaches and implementations of flowrate sensing and measurement in smart inhalers for effective respiratory disease management. It highlights the importance of compliance with proper inhaling techniques and consistent adherence for managing respiratory conditions. Methods and relevant commercial and prototype research-type devices for sensing and measuring inhalation flowrate in smart inhalers are studied and compared. The study argues that utilisation of acoustic analysis and air pressure sensing is a promising approach to detect and evaluate the inhaling action ultimately allowing to improve the treatment outcomes and life quality of patients with respiratory diseases.

Functional neurological disorder, or FND, is widely misunderstood, particularly when considering recent research that suggests that the illness has a biological rather than a psychiatric basis. Nonetheless, the long-held view that FND is a purely psychiatric disorder without biological basis, or even a contrived (malingered) illness, remains pervasive both in modern medical care and general society. This is because FND involves an intermittent course of involuntary disability that rapidly alternates with improved neurological control. This has in turn caused shaming, low self-efficacy, and social isolation of the patients. Little research has examined the numerous biomarkers that are shared between FND and canonical neurological disorders and the encouraging outcomes that can follow conventional neurological rehabilitation, modified for this disorder. This review summarizes current research on FND biomarkers and physical rehabilitation results. General healthcare providers would benefit their care for their patients through their improved understanding the illness and recourses for support and treatment that are provided in this review.

Conjunctival melanoma (Co-M) is an aggressive, invasive eye and eyelid cancer. Its global inci-dence of ~1 in a million is increasing at a rate ratio of ~1.4, but this rises sharply in over 65-year-olds. Although rare, Co-M has a devastating impact on the lives of those who develop it. Co-M is often misdiagnosed or overlooked leading to vision loss either from destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. Due to its rarity, there is limited evidence for diagnosis and management; hence, there is no standardised treatment and not all cases are referred to a specialised ocular oncology centre. Recent progress in cancer immunology and genetics have revolutionised treatment of cutaneous melanoma, which share some similarities to Co-M. A better understanding of Co-M and its precursor lesions is urgently needed to lead the development of novel targeted and immuno-therapies both for local tumour control and disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge of Co-M, its epidemiology, pathogenesis, presentation, diagnosis, management, and recent advances in novel biological therapies for personalised treatment of this disease.

This paper presents an explicit method for constructing tangential and anisotropic bases in quadratic spaces. We will also provide three theorems that allow us to explicitly calculate vectors that are orthogonal or tangent to given vectors or that provide necessary and sufficient conditions for the existence of such vectors. A classical theorem on quadratic space states that every finite-dimensional quadratic space has an orthogonal basis. A result that seems to be unanswered is under what conditions a finite-dimensional quadratic space has a basis consisting of isotropic vectors. A second problem is whether or not every finite-dimensional quadratic space has a basis consisting of mutually tangent vectors, where two vectors v,w are tangent if (u·v)2=(u·u)(v·v). In this paper, we attack these two problems.

This paper presents an enhanced Fully Connected Neural Network (FCNN) framework that incorporates manifold learning and Renormalization Group (RG) methods. By integrating Christoffel symbols, the model adapts to the curvature and topology of the data manifold, improving learning from geometrically complex data. Additionally, RG methods enable effective multi-scale data processing. We demonstrate the enhanced model’s performance on synthetic and real-world datasets, showing improved accuracy compared to standard FCNNs, particularly in complex systems simulation.

In this paper, we present a multi-task model that predicts disparities and confidence levels in deep stereo matching simultaneously. We do this by combining its successful model for each separate task and obtaining a multitask model that can be trained with a proposed loss function. We show the advantages of this model compared to training and predicting disparity and confidence sequentially. This method enables an improvement of 15% to 30% in the area under the curve (AUC) metric when trained parallel rather than sequential. In addition, the effect of weighting the components in the loss function on the stereo and confidence performance is investigated. By improving the confidence estimate, the practicality of stereo estimators for creating distance images is increased.

The complexity of plastic polymers and even more so of additives has increased enormously in recent years. This makes the high-quality recycling of mixed plastic waste considerably more difficult. Some additives have now been strictly regulated or even completely banned for good reasons ('legacy additives'). Material or mechanical recycling generally utilises old plastics that still contain these substances. Consequently, products that are manufactured using such recyclates are contaminated with these harmful substances. We therefore recommend avoiding the use of these recyclates for products with intensive contact with consumers until further notice. We also show that the climate policy challenges for the plastics (and chemical) industry necessitate a defossilisation ('feedstock change'). This turnaround can only succeed if solely high-quality recycling takes place in future; recyclates should primarily replace virgin plastics. This can only work if used plastics with a high degree of homogeneity and known formulation are collected separately, as is already the case today with PET bottles. In this context, we would like to point out inconsistencies in the current legislation on the European emissions trading system.

Glycerol conversion to valuable biomolecules has been a research avenue that has attracted a significant interest in recent years due to its increasing over production, with possibilities for chemical transformation for eco-friendly processes and distinct compounds with biological activities. Also, in the current climate change in which a major emphasis is being placed on the design of green processes, solvents are key factors from both an economic and environmental point of view. In this context, due to its abundance and low-price, glycerol represents an innovative solvent coming from biomass and produce in high amount. On the other hand, Epichlorydrin, Glycidol and Solketal have become useful intermediates in chemical transformations when using glycerol as a raw material. This review focuses on glycerol as a green solvent in the synthesis of complex molecules, Epichlorydrin, Glycidol, Solketal and Tosyl solketal as an efficient recycling process for glycerol, as well as building blocks in the synthesis of glycerol derivatives, which are undeniable new source of potentials drugs.

Severe deficiency of ADAMTS13 (<10 iu/dL) is diagnostic of thrombotic thrombocytopenic purpura (TTP) and leads to accumulation of ultra-large VWF multimers, platelet aggregation and widespread microthrombi, which can be life-threatening. However, the clinical implications of a low ADAMTS13 activity level are not only important in an acute episode of TTP. In this article, we discuss the effects of a low ADAMTS13 activity in congenital and immune-mediated TTP patients not only at presentation, but once in a clinical remission. Evidence is emerging of the clinical effects of a low ADAMTS13 activity in other disease areas outside of TTP and here we explore the wider impact of low ADAMTS13 activity on the vascular endothelium and the potential for recombinant ADAMTS13 therapy in other thrombotic disease states.

O estudo apresenta uma afirmação e explicação de que ocorrem progressões numéricas maiores e menores que dependem da representação contida no espaço físico. Em casos gerais, números maiores são múltiplos e números menores são simples, porque vários números contêm mais números em muitos espaços físicos do que números simples. Em casos específicos, dependem da afirmação do que é a representação específica, podendo ocorrer realidades diferentes de casos gerais. Além disso, a teoria explica a mudança no número de números primos.

Interoperable multilayer networks are pivotal and transformative in public digital health. They not only enhance the delivery of healthcare services but also contribute significantly to improving public health outcomes. Through better accessibility, efficiency, and data-driven decision-making, these networks are revolutionizing how we approach public health. The seamless data exchange and integration they facilitate across different healthcare systems and providers can lead to substantial cost savings for public healthcare systems. These networks pave the way for a more efficient and effective healthcare system by reducing redundancies, optimizing resource allocation, and minimizing unnecessary procedures. This study combines the pressing issues of public digital health with the innovative interpretation of multilayer network theory, proposing practical solutions that inspire academics and practitioners alike.Public digital health is not just about improving care access and patient engagement. It is also about ensuring the financial sustainability of our healthcare systems. Innovative multilayer network analysis is critical in this game, improving interoperability and reducing spatial and temporal constraints. These networks streamline processes and improve efficiency by easing complex interactions within healthcare systems. This process, in turn, allows healthcare providers to deliver high-quality care at a lower cost, transforming, whenever possible, in-patients and out-patients into home-patients. Networks are a cornerstone and a beacon of hope for transforming public digital health. They are increasing the Value for Money and enhancing a patient-centric approach, making us optimistic about the future of healthcare.This study shows that revolutionizing digital healthcare methodologies has a profound impact on crucial elements like resilience, interoperability, and patient well-being within public health. The enhancement of interoperability facilitates the smooth flow of data exchange across various platforms and healthcare providers, fostering improved collaboration and decision-making processes and elevating the safety of patients.

Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population above 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (Syn)-rich Lewy bodies both manifesting with classical motor signs. Syn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considerate prevalent among individuals before PD diagnosis and persisting throughout the patient’s life. NMS mainly include loss of taste and smell, constipation, psychiatric disorders, dementia, rapid eye movement (REM) sleep behavior impairment, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings showing the impact of Syn deposits on several prodromal NMS and emphasizes the importance of early detection of Syn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

Azolla is the only plant with a co-evolving nitrogen-fixing (diazotrophic) cyanobacterial symbiont (cyanobiont), Nostoc azollae, resulting from Whole Genome Duplication (WGD) 80 million years ago in Azolla’s ancestor. Additional genes from the WGD resulted in genetic, biochemical and morphological changes in the plant that enabled transmission of the cyanobiont to successive generations via its megaspores. The resulting permanent symbiosis and co-evolution led to loss, downregulation or conversion of non-essential genes to pseudogenes in the cyanobiont, changing it from a free-living organism to an obligate symbiont. Upregulation of other genes in the cyanobiont increased its atmospheric dinitrogen fixation and provision of nitrogen-based products to the plant. As a result, Azolla can double its biomass in less than two days free-floating on fresh water and sequester large amounts of atmospheric CO2, giving it the potential to mitigate anthropogenic climate change through Carbon Capture and Storage. Azolla’s biomass can also provide local, low-cost food, biofertiliser, feed and biofuel that are urgently needed as our population increases by a billion every twelve years. This paper integrates data from biology, genetics, geology and paleontology to identify the location, timing and mechanism for the acquisition of a co-evolving diazotrophic cyanobiont by Azolla’s ancestor in the Late Cretaceous (Campanian) of North America.

This document introduces methods and algorithms to characterize a series of values as patterns of repeating symbols or sequences selected with the criterion to maximize the information retrieved. The method converts a series of real-number values into texts. Then, it interprets the text from a point of view specified by several parameters. Located patterns are linked nested, with shorter sequences within longer ones. Texts are then synthesized and organized in a tree-like structure, substantially reducing entropy. The characterization of processes serves as the basis for constructing models to estimate likely projected values. Alternative ways to assess the multiscale complexity of unidimensional processes are applications of the results obtained here.

Alzheimer's disease still holds many mysteries that are yet to be revealed. Exploring the reasons behind the increase in suicidal behavior in patients undergoing promising treatments for Alzheimer's disease is a scientific endeavor. Research practices must be built upon strong theoretical frameworks that can guide the investigation. Throughout decades of professional experience in caring for suicidal individuals and elderly people with cognitive disorders, we have noticed a connection that requires further exploration. It seems that existential distress may trigger various outcomes. At one end of the spectrum, we observe individuals who strongly resist adverse situations, making them more prone to developing suicidal behaviors. At the other end, we see individuals who exert great biological effort to adapt to the ongoing stresses of life, with Alzheimer's disease being a neurological consequence of this adaptation. To develop our understanding, we conducted an existentialist analysis to conceptualize the underpinnings of the human experience in a stress-filled world.

The dynamic equilibrium of iron homeostasis has an important role in sustaining metabolic and neurological functions during human life. Iron excretion is modest and unregulated hence this overall equilibrium is tightly regulated in normal conditions by increasing deficient or limiting excessive iron assimilation. Here we focus on neural tissue overload, dyshomeostasis that is preceded by excessive assimilation, disturbances in internal homeostasis or both. Normal steps in iron homeostasis include its uptake across the apical membrane of the enterocytes in a mildly acidic duodenal milieu by the major importer of ferrous iron, Divalent Metal Transporter 1 (DMT1) (Nramp2/DCT1/SLC11A2, solute carrier family 11 member 2) [1, 2], responsible for the uptake of Non-Transferrin Bound Iron (NTBI) and divalent metals [3], passage through enterocytes bound to a chaperone and crossing the basal membrane via the only known cellular ferrous iron exporter, ferroportin [4] with the iron bound to transferrin (Tf) as it exits. Cells in peripheral tissues largely utilize circulating iron after uptake by receptor-mediated endocytosis of Tf-bound Iron [5]. Derangement of duodenal NTBI absorption of iron and heavy metals is influenced by systemic iron metabolism associated with inflammation that leads to iron accumulation into peripheral tissues and potential development of neurodegenerative diseases, involving distribution and fine regulation of DMT1 also in the central nervous system, where inflammatory-related acidosis influences DMT1 uptake, via its action as a proton cotransporter. Pharmacological strategies to inhibit NTBI transport selectively will be illustrated in relationship to protection, particularly neuroprotection, against iron overload associated with acidosis, inflammation, neuroinflammation and subsequent neurodegeneration.

Elevated levels of homocysteine (Hcy) and related metabolites are associated with Alzheimer’s disease (AD). Severe hyperhomocysteinemia causes neurological deficits and worsens behavioral and biochemical traits associated with AD. Although Hcy is precluded from entering the Genetic Code by proofreading mechanisms of aminoacyl-tRNA synthetases, and thus is a non-protein amino acid, it can be attached to proteins via an N-homocysteinylation reaction mediated by Hcy-thiolactone. Because N-homocysteinylation is detrimental to protein’s function and biological integrity, Hcy-thiolactone detoxifying enzymes – PON1, BLMH, BPHL – have evolved. This review provides an account of the biological function of these enzymes and of consequences of their impairments leading to phenotypes characteristic of AD.

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence is increasing worldwide in parallel with the obesity pandemic. A lack of insulin or insulin resistance, and consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) is a long-term complication of the central nervous system (CNS), characterized by cognitive impairment and motor dysfunctions. The role of oxidative stress and neuroinflammation in the pathomechanism of DE has been proven. Fractalkine (CX3CL1) has unique properties as an adhesion molecule and chemoattractant, and by acting on its only receptor, CX3CR1, it regulates the activity of microglia in physiological states and neuroinflammation. Depending on the clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects by inhibiting the inflammatory process in microglia or, conversely, maintaining/intensifying inflammation and neurotoxicity. This review discusses the evidence supporting that the CX3CL1-CX3CR1 pair is neuroprotective and other evidence that it is neurotoxic. Interrupting the vicious cycle within neuron-microglia interactions may be a therapeutic goal in DE by limiting the inflammatory response.

We discuss the consequences of the unique symmetry of the de Sitter spacetime. This symmetry leads to the specific thermodynamic properties of the de Sitter vacuum, which produces the thermal bath for matter. The de Sitter spacetime is invariant under the modified translations, ${\bf r}\rightarrow {\bf r} -e^{Ht}{\bf a}$, where $H$ is the Hubble parameter. For $H\rightarrow 0$, this symmetry corresponds to the conventional invariance of Minkowski spacetime under translations ${\bf r}\rightarrow {\bf r} -{\bf a}$. Due to this symmetry, all the comoving observers at any point of the de Sitter space perceive the de Sitter environment as the thermal bath with temperature $T=H/\pi$, which is twice larger than the Gibbons-Hawking temperature of the cosmological horizon. This temperature does not violate the de Sitter symmetry, and thus does not require the preferred reference frame, as distinct from thermal state of matter, which violates the de Sitter symmetry. This leads to the heat exchange between gravity and matter, and to instability of de Sitter state towards the creation of matter, its further heating, and finally to the decay of the de Sitter state. The temperature $T=H/\pi$ determines different processes in the de Sitter environment, which are not possible in the Minkowski vacuum, such as the process of ionization of an atom in the de Sitter environment. This temperature also determines the local entropy of the de Sitter vacuum state, and this allows us to calculate the total entropy inside the cosmological horizon. The result reproduces the Gibbons-Hawking area law, which is related to the cosmological horizon, $S_{\rm hor}=4\pi KA$, where $K=1/16\pi G$. This supports the holographic properties of the cosmological event horizon. We extend the consideration of the local thermodynamics of the de Sitter state using the $f({\cal R})$ gravity. In this thermodynamics, the Ricci scalar curvature ${\cal R}$ and the effective gravitational coupling, $K$, are thermodynamically conjugate variables. The holographic connection between the bulk entropy of the Hubble volume, and the surface entropy of the cosmological horizon remains the same, but with the gravitational coupling $K=df/d{\cal R}$. Such connection takes place only in the $3+1$ spacetime, where there is the special symmetry due to which the variables $K$ and ${\cal R}$ have the same dimensionality. We also consider the lessons from the de Sitter symmetry for the thermodynamics of black and white holes.

Monogenity is a classical area of algebraic number theory that is very actively researched even today. This paper is a collection of the results obtained during the last few years in this area. Several of these results were presented at the series of online conferences "Monogenity and power integral bases".

Metabolic Associated Steatohepatitis Liver Disease (MASLD) currently impacts a quarter of the global population and its prevalence is expected to increase in the future. As a result, the incidence of hepatocellular carcinoma associated with MASLD is also on the rise. Notably, hepatocellular carcinoma in this group does not always develop alongside liver cirrhosis, often leading to a more advanced stage at diagnosis. The challenge lies in accurately identifying patients who are at a higher risk of hepatocellular carcinoma to tailor screening processes effectively. Additionally, several therapeutic approaches are being explored to prevent hepatocellular carcinoma, although there are yet no universally accepted guidelines

Ever since the virus was discovered in the 80s of the 19th century, plant viruses had a great impression within the field of plant pathology. In this book we trace the growth in the research on plant viruses beginning from traditional era (1882-1900) in which a new pathogen was discovered other than fungi and bacteria, later known as virus; biological era (1900-2000) in which the mode of spread and relationship of the virus with its vector was understood; biochemical/biophysical era (1930-1968) that marked the basis of virus purification and chemical characterization; molecular era of plant virology (1943-1995) in which establishment, progression & transmission of plant viruses was described within the host at molecular details ; era of viral molecular genetics (1980–2000), in which a significant role was played by the plant virologists to understand the position and function of genes, methods of viral gene cloning, gene silencing and other viral genome associated properties ; era of plant viral diagnostics (1980 – 2021) which led to rapid, specific and sensitive detection of plant viruses.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including but not limited to imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neu-rostimulation including acupuncture. Lastly, we also touch upon the disease’s different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

In virology, the term reverse genetics refers to a set of methodologies in which changes are introduced into the viral genome and their effects on the generation of infectious viral progeny and their phenotypic features are assessed. Reverse genetics emerged thanks to advances in recombinant DNA technology, which made the isolation, cloning, and modification of genes through mutagenesis possible. Most virus reverse genetics studies depend on our capacity to rescue an infectious wild-type virus progeny from cell cultures transfected with an “infectious clone”. This infectious clone generally consists of a circular DNA plasmid containing a functional copy of the full-length viral genome, under the control of an appropriate polymerase promoter. For most DNA viruses, reverse genetics systems are very straightforward, since DNA virus genomes are relatively easy to handle and modify and are also (with few notable exceptions) infectious per se. This is not true for RNA viruses, whose genomes need to be reverse transcribed into cDNA before any modification can be done. Establishing reverse genetics systems for members of the Caliciviridae has proven exceptionally challenging, due to the low number of members of this family that propagate in cell culture. Despite the early successful rescue of a calicivirus from a genome-length cDNA more than two decades ago, reverse genetics methods are not routine procedures that can be easily extrapolated to other members of the family. Reports of calicivirus reverse genetics systems have been few and far between. In this review, we discuss the main pitfalls, failures, and delays behind the generation of several successful calicivirus infectious clones.

This study delves into the intricate dynamics of classical mechanics, exploring the interplay between force, mass, and energy. Through fundamental principles and mathematical formulations, it elucidates key relationships governing physical systems. Beginning with an overview of classical mechanics, the study establishes the foundational principles laid down by Newton, emphasizing concepts such as inertia, acceleration, and the relationship between force and motion. Central to the investigation is Newton's second law of motion, highlighting the direct proportionality between force and acceleration, and the inverse relationship between acceleration and mass when acted upon by a force. The study extends to the concept of effective mass, elucidating how the application of force influences the inertial mass of an object and contributes to its effective mass through the acquisition of kinetic energy. Furthermore, the study examines the total energy composition of systems, emphasizing the holistic nature of energy as a combination of potential and kinetic forms. Through the work-energy theorem, a direct link between force and kinetic energy is established, revealing how mechanical work done on an object results in changes in its kinetic energy and effective mass. Mathematical formulations and conceptual analyses provide deeper insights into the intricate relationships between force, mass, and energy, shedding light on the underlying mechanisms governing classical mechanical systems. Through validation against empirical observations and experimental data, the study ensures the accuracy and reliability of derived equations, contributing to a richer understanding of classical mechanics and paving the way for further exploration in the field of physics.

Glioblastoma multiforme (GBM) is one of the deadliest human cancers with very lim-ited treatment options available. The malignant behavior of GBM is manifest in a tu-mor which is highly invasive, resistant to standard cytotoxic chemotherapy and is strongly immunosuppressive. Immune checkpoint inhibitors have recently been in-troduced in the clinic and have yielded promising results in certain cancers. GBM however is largely refractory to these treatments. The immune checkpoint CD47 has recently gained attention as potential target for intervention as it conveys a “don’t eat me” signal to tumor associated macrophages via the inhibitory SIRP alpha protein. In preclinical models, administration of anti-CD47 monoclonal antibodies have shown impressive results with GBM and other tumor models. Several well characterized on-cogenic pathways have recently been shown to regulate CD47 expression in GBM cells and Glioma Stem cells (GSCs) include EGFR, beta catenin and LRIG2. Other macro-phage pathways involved in regulating phagocytosis including TREM2 and glycan binding proteins are discussed as well. Finally, Chimeric Antigen Receptor Macro-phages (CAR)-M could be leveraged for greatly enhancing phagocytosis of GBM and repolarization of the microenvironment in general. Here we comprehensively review the mechanisms that regulate about macrophage phagocytosis of GBM cells.

Artificial Intelligence (AI) tools and techniques are comparatively recent advances of present-day globalized world. With their easy availability and friendly user interface AI has affected every sphere of human being. These tools are increasingly becoming popular because of the numerous benefits occurred to the society in many ways. However, there are not only the positive side of these technologies, but also many negative sides. Along with the development and adoption of AI, cyber-attacks are increased and disrupting the information system. Threat actors may misuse artificial intelligence. Hence, these tool designers are working and applying the ability of generative AI can tip the scales in cybersecurity. So, in the age of AI, there is always tension between the cyber attackers and the defenders to make a balanced information system. It is a general rule that defenders must be well in advance in their favor and keep ahead of adversaries. The United National and several governments for example the US, UK, and the big AI giants like Microsoft along with OpenAI, are working on emerging cyberattacks. This research paper explores the concept of information resilience in ML and AI systems, focusing on strategies to enhance their ability to withstand uncertainties, adversarial attacks, and data perturbations.

Models of quantum measurements are presented, including observers subject to the laws of quantum mechanics. Observers perform multiple measurements in an attempt to disprove the collapse hypothesis. It is shown that under reasonable assumptions the effort cannot succeed. Under a unitary evolution the end state is a correlation between the result of the first measurement and the result(s) of the others, consistent with the observer's collapse hypothesis. The observer may conclude that the laws of nature include a non-unitary collapse mechanism, even if one does not actually exist. Discard of information is the crucial factor which distinguishes entanglement from measurement.

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, unresponsive to nutritional support, and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.

in the following article I analyze the trend of cultural and creative employment in the Italian regions between 2004 and 2022 through the use of ISTAT-BES data. After presenting a static analysis, I also present the results of the clustering analysis aimed at identifying groupings between Italian regions. Subsequently, an econometric model is proposed for estimating the value of cultural and creative employment in the Italian regions. Finally, I compare various machine learning models for predicting the value of cultural and creative employment. The results are critically discussed through an economic policy analysis.

RNA transcripts play a crucial role as witnesses of gene expression health. Identifying disruptive short sequences in RNA transcription and regulation is essential for potentially treating diseases. Let’s delve into the mathematical intricacies of these sequences. We’ve previously devised a mathematical approach for defining a “healthy” sequence (10.14218/GE.2023.00079). This sequence is characterized by having at most four distinct nucleotides (denoted as nt≤4). It serves as the generator of a group denoted as fp. The desired properties of this sequence are as follows: fp should be close to a free group of rank nt−1, it must be aperiodic, fp should not have isolated singularities within its SL2(C) character variety (specifically within the corresponding Groebner basis). Now, let’s explore the concept of singularities. There are cubic surfaces associated with the character variety of a four-punctured sphere denoted as S24. When we encounter these singularities, we find ourselves dealing with some algebraic solutions of a dynamical second-order differential (and transcendental) equation known as the Painlevé VI equation (10.3390/dynamics4010001). In certain cases, S24 degenerates, in the sense that two punctures collapse, resulting in a “wild” dynamics governed by the Painlevé equations of an index lower than VI. In our paper, we provide examples of these fascinating mathematical structures within the context of miRNAs. Specifically, we find a clear relationship between decorated character varieties of Painlevé equations and the character variety calculated from the seed of oncomirs. These findings should find applications in cancer research.

Tinea incognito is a kind of skin infection that is caused by a fungus which has been changed by the use of topical or systemic steroids or other immunosuppressive medications. This alteration in the typical clinical presentation of the infection makes it difficult to diagnose for general practitioners and dermatologists. Delayed diagnosis, spread of the infection to critical body surfaces, resistance to antifungal drugs, and increased costs due to prolonged hospitalization and multiple treatment regimens often complicate tinea incognito. This condition can affect individuals of all ages and genders, but it is more common in children. Tinea incognito is a type of fungal skin infection that can present with various and non-specific clinical features, such as sudden onset of itching in an area that was previously unaffected, making it challenging to differentiate from other diseases such as eczema, seborrheic dermatitis, lupus erythematosus, psoriasis, or other non-fungal skin conditions. The treatment of tinea incognito usually involves stopping the use of topical steroids or other immunosuppressive medications. Preventive measures and management of the underlying fungal infection are necessary and can be achieved with antifungal drugs. Patients should wear loose cotton clothes, use boiling water for laundry, and iron their clothing before wearing them. Additionally, they should avoid sharing bed linens, towels, clothes, and shoes. This review aims to raise awareness of tinea incognito among health practitioners, provide tips for suspecting the disorder, include it in the differentials, and evaluate the available diagnostic procedures. The therapy utilized in published studies is also reviewed.

In the century and a half since Maxwell first conjured his “finite being” which Lord Kelvin subsequently dubbed a “daemon”, researchers have explored the connections between non-equilibrium thermodynamics, entropy, and information theory. In recent years various Thermodynamic Uncertainty Relations (TURs) have been derived to inform upon the relationship between the entropy production and the precision possible in thermodynamic machines and processes. In this paper the recently derived TURs are applied to the hypothetical thermodynamic economy as described by Parker [1]. The TURs define the lower bound on the total entropy production of the economy. Changes in this entropy production rate has consequences on the stability of the economic system and plays a central role in the business cycle. This new perspective has important implications for policy makers, researchers, and other economic actors.