Fertility management techniques being promoted in sub-Saharan Africa (SSA) seek to grow indigenous vegetables economically and sustainably. This study was conducted in a phytotron chamber and compared yield, soil carbon (C) speciation and greenhouse gas (nitrous oxide (N₂O) and carbon dioxide (CO₂)) emissions from SSA soils of two ecoregions; the dry savanna (lna, Republic of Benin) and rainforest (Ife, Nigeria) cultivated with local amaranth (Amaranthus cruentus) under manure (5 t/ha) and/or urea (80 kg N/ha) fertilization. Vegetable yield ranged from 1753 kg/ac to 3198kg/ac in the rainforest, RF, soils and 1281 kg/ac to 1951 kg/ac in the dry savanna, DS, soils. Yield in the urea treatment was slightly higher compared to the manure+urea treatment, but the difference was not statistically significant. Cumulative CO₂ emissions over 21 days ranged from 497.06 to 579.47 g CO₂ in the RF, and 322.96 to 624.97 g CO₂ in the DS, while cumulative N₂O emissions ranged from 60.53 to 220.86 mg N₂O in the RF, and 24.78 to 99.08 mg N₂O in the DS. In the RF samples, the combined use of manure and urea reduced CO₂ and N₂O emissions but led to an increase in the DS samples. ATR-FTIR analysis showed that the combined use of manure and urea increased the rate of microbial degradation in the soils of the DS, but no such effect was observed in soils of the RF. We conclude that combining manure and urea fertilization has different effects on soils of the two ecoregions, and that RF farmers can reduce agricultural emissions without compromising soil productivity and yield potential.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

Background and objectives: The initiation of apoptotic death in cancer cells is the aim of many chemotherapeutic strategies. As many anticancer agents have been discovered in natural plant sources, the search for novel phytochemicals displaying anticancer activities continues at a tremendous rate. This study was conducted to evaluate the effect of extractable polyphenols (EPP); non-extractable polyphenols (NEPP); nobiletin (NOB); tectorigenin (TEC) and persicogenin (PERS) from Barhi date palm kernels (BDPK) extracts on the induction of apoptosis in human lung cancer A549 and colon cancer HT29 cell lines. Materials and Methods: The anticancer activities were determined using MTT and trypan blue exclusion assays. Flow cytometry analysis was performed to study the cell viability, cell cycle arrest and apoptosis. The underlying mechanism of apoptosis induced by crude extracts and the purified compounds was investigated using caspase-3, -8 and -9 assays and the mitochondrial membrane potential assay. Results: The findings indicate that both BDPK extracts and the purified compounds do exert induced cell death on A549 and HT29 cells. The results observed from MTT- assay and trypan blue exclusion indicate that the cytotoxic effects of both plant extracts and the three isolated flavonoids are dose-dependent with higher cell death after 72 hours treatment. Treatment of human lung and colon cancer cells with EPP, NEPP, NOB, TEC and PERSI induced late stages of apoptosis as there was evidence of the DNA degradation and high percentage of the cells population was situated at sub-G1 phase, indicating a high population of apoptotic cells. Conclusions: Study of the apoptotic mechanism demonstrated that EPP and NEPP exhibited dependent mitochondrial signalling pathway as seen with caspase-9 and induced receptor-mediated (extrinsic) apoptotic pathway as seen with caspase-8. Therefore, our results suggest that BDPK extracts and the three isolated flavonoids could be a good candidate for developing anticancer agents.

This study presents the validation process of the Questionnaire on Academic Stress in Secondary Education –QASSE-, designed to assess the wide variety of school sources and situations related to academic stress in adolescence, and their relationship with students’ physical and psychological well-being. Participants were 860 Spanish high school students (52.9% girls) with an average age of 14.62 years (SD = 1.8). Through a cross-validation process, EFA and CFA supported QASSE multifactorial structure with four first-order factors -academic overload, interaction with classmates, family pressure, and future-oriented perspective- and a second-order factor of academic stress, showing a significant and intense relationship with adolescents’ psychological and physical well-being. Results also highlight the effects of the gender*educational level interaction on the students’ stress, with girls showing higher levels of stress in the transition courses between educational phases (sophomore and junior years). The QASSE demonstrates good validity and reliability, showing potential for both research and educational application. The results show the high impact of the QASSE dimensions on psychological and physical well-being in adolescence, highlighting its special usefulness for designing and adjusting educational prevention and intervention actions in this area to the students’ specific characteristics and needs

In addition to its use as a food additive, sesame is also very popular in conventional drugs because of its antifungal, anticancer, analgesic, antioxidant, and antiproliferative, vitamin B and E supplier, serum cholesterol and blood pressure-lowering, wound healing potential. In this study, the cytotoxicity, wound healing, and anticancer (antiproliferation) properties of the ex-tract obtained from in vitro cultures of Sesamum orientale L. cv. "Gökova" were investigated using in L929 fibroblast, MCF-7 breast, and A549 lung epithelial cell lines. In our study, the cisplatin was also used as a control group to compare the anticancer efficacy of our plant extract. The IC50 values obtained from cell treatments were 922.73 µg.ml-1 (plant extract) and 33.09 µg.ml-1 (cispla-tin) for A549 µg.ml-1, 1837.07 µg.ml-1 (plant extract) and 19.27 µg.ml-1 (cisplatin) for MCF-7, and 154.70 µg.ml-1 (plant extract) for L929, respectively. The subcytotoxic doses of the treated plant extract provided the healing of artificially created wounds on L929 fibroblast cell cultures within 48 hours. For the evaluation of the anticancer activity, it was also determined that transcriptomic analyzes of BCL-XL gene, which is negatively correlated with apoptotic pathway, and Cas3 and Cas9 genes, which are positively correlated with apoptotic pathway, showed a statistically sig-nificant increase in A549 and MCF-7 cell lines treated with plant extract or cisplatin. In the light of the results obtained from the present study, it was seen that sesame plant extract may have wound healing potential at decreasing doses and anticancer activity potential at increasing dos-es. The present study can be a useful resource for the development of a drug with wound healing and/or antiproliferative potential, with applications to be made in different cell lines in the future.

How the subculture and marginalized community have become the leading sectors in the egalitarian and inclusive creative economy is a growing issue and still needs elaboration. One of the subculture phenomena that happened recently in one of Southeast Asia's countries is known as Citayam Pop-up and Makeshift Fashion Week (CFW). Then this paper aims to elaborate on how the CFW can contribute and play a significant role in the development of an egalitarian and inclusive creative economy. The current CFW was not developed instantly, yet it is through the complexities of push and pull factors that are very typical among SE Asian marginalized people that led to the onset of SE Asian subculture, particularly among the youth. Driven by finding their self-identity, wanting to belong, and combined with economic, family, and peer pressures, this group of suburban youth, at the beginning, find a corner of a city in the middle of the business district as a medium to express their identity in the form of CFW. As a result and in lieu of growing discourses, the CFW has boosted local economic growth, and the adolescents who participated in the CFW have also received endorsement from a startup business for marketing certain teen products. In the long term, the mutual relationships created can lead to job opportunities

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<0.001) and fewer were female (46.1% vs. 49.7%, p<0.001). The patients with PFO had greater mean modified RoPE score (4.0 vs. 3.3, p<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 (<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.

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.

Over the coming decades, global freshwater withdrawals are expected to grow, especially in low and middle-income countries. Unless there are significant improvements in the efficiency of water use by economies, freshwater stress, crises and scarcity will worsen. This paper explores further the economic relationship between water use efficiency and scarcity. Because growing scarcity of freshwater in many regions and countries is not adequately reflected in markets, there is often insufficient incentives for investment and innovation to improve the efficiency of water use. To explore further changes in water use efficiency across countries, we conduct a panel analysis of water productivity changes for 130 countries over 1995 to 2020. Countries with lower initial levels of water use efficiency tended to have higher water productivity growth, whereas more agriculturally dependent economies displayed lower improvements in water use efficiency. Better institutional quality and capacity for innovation may also increase water use efficiency. We discuss the implications of these results for improving water use productivity in economies, and in particular, the opportunities and challenges for improving water markets and trades to alleviate water scarcity. We conclude by identifying further areas of research.

Objectives: The tau protein is essential for stabilizing microtubules. Changes in its phosphorylation are identified in many neurodegenerative diseases, such as frontotemporal dementia and Alzheimer's disease. The hyperphosphorylation of the tau protein is linked to various factors, including stress, which has a substantial impact on depressive illness. The present study aimed to systematically review studies that describe the association between tau protein and depression.Design: The present study used the PRISMA statement 2020 as the inclusion criterion for articles describing tau protein in individuals with depression. The exclusion criterion was the lack of comparison of tau protein levels with individuals without depression.Results: A total of 138 papers were identified, of which 21 were ultimately included. One out of every three articles included demonstrated the statistical significance of the tau protein values between the depression group and controls. Only one had an adequate sample but demonstrated results without any major significance.Conclusions: The association between tau protein and depression remains unclear. Studies with adequate sampling are necessary to answer this question.

This article reviews all the major stages in the origins of life. From the emergence of matter in the initial Big Bang to the modern, civilized human being. On an immaterial level, it is proposed and explained how consciousness necessarily takes precedence over matter. Next, we explain how consciousness, with its ability to process information, selected the water molecule to breathe life into the periodic table of elements. We also explain why the notion of entropy allows us to evolve: "Die Entropie der Welt strebt einem Maximum zu" (second principle) and, therefore, takes precedence over the notion of energy, which, on the contrary, encourages us to preserve what we have: "Die Energie der Welt bleibt konstant" (first principle). This is followed by a discussion of the importance of quantum coherence and the need to rely on a second quantization formalism for a proper understanding of the physical-biochemical properties of water. Moreover, throughout the argument developed on the best and most fundamental things science has to offer, care is taken to link this knowledge to the great philosophies of the West (Greece), the East (China, India) or even to practices of a shamanic nature (Africa, America). Hence, finally, the proposal to reconsider all musical practice within the framework of the diapason of water at a frequency of 429.62 Hz, as well as all therapeutic practice on the basis of seven clearly identified and established frameworks of thought.

Information theoretic quantities such as entropy, entropy rate, information gain, and relative entropy are often used to understand the performance of intelligent agents in learning applications. Mean squared error has not played a role in these analyses, primarily because it is not felt to be a viable performance indicator in these scenarios. We build on a new quantity, the log ratio of entropy powers, to establish that minimum mean squared error (MMSE) estimation, prediction, and smoothing are directly connected to Mutual Information Gain or Loss in an agent learning system modeled by a Markov chain for many probability distributions of interest. Expressions for mutual information gain or loss are developed for MMSE estimation, prediction, and smoothing and an example for fixed lag smoothing is presented.

This study examines a new approach to hybdrid neuromorphic devices by studying the impact of omeprazole-proteinoid complexes on Izhikevich neurone models. We investigate the influence of these metabolic structures on five specific patterns of neuronal firing: accommodation, chattering, triggered spiking, phasic spiking, and tonic spiking. By combining omeprazole, a proton pump inhibitor, with proteinoids, we create a unique substrate that interfaces with neuromorphic models. The Izhikevich neurone model is used because it is computationally efficient and can accurately simulate various behaviours of cortical neurones. The results of our simulations show that omeprazole-proteinoid complexes have the ability to affect neuronal dynamics in different ways. This suggests that they could be used as adjustable components in bio-inspired computer systems. We have noticed a notable alteration in the frequency of spikes, patterns of bursts, and rates of adaptation, especially in chattering and triggered spiking behaviours. The findings indicate that omeprazole-proteinoid complexes have the potential to serve as adaptable elements in neuromorphic systems, presenting novel opportunities for information processing and computation that have origins in neurobiological principles. This study makes a valuable contribution to the expanding field of biochemical neuromorphic devices and establishes a basis for the development of hybrid bio-synthetic computational systems.

Oxidative stress constitutes a main molecular mechanism underlying cardiovascular diseases (CVDs). This pathological mechanism can be triggered by NADPH oxidases (NOXs), which produce reactive oxygen species (ROS). In fact, the different NOXs have been associated with myocardial infarction, atherothrombosis, and stroke. More specifically, we will focus on the implications of NOXs in atherothrombotic stroke. Each NOX member participates in a different way in the several stages of this disease: endothelial dysfunction, immune cell infiltration, foam cell genesis, vascular smooth muscle cells (VSMC) proliferation, and atherosclerotic plaque formation. Additionally, some NOXs are involved in plaque instability, thrombosis, ischemic stroke, and ischemia-reperfusion injury (IRI). Interestingly, the effects of NOXs in this pathology depend on the specific homologue, the cell type in which they are activated, and the stage of the disease. In this review we summarize the most up-to-date information about the implications of vascular NOXs in each of these processes. Finally, we highlight some limitations and future perspectives of the study of NOXs in CVDs.

The global need for rapid diagnostic methods for pathogen identification and antimicrobial susceptibility testing (AST) is underscored by the increasing bacterial resistance and limited therapeutic options, especially critical in sepsis management. The evolution from traditional phenotype-based methods to rapid molecular and mass spectrometry techniques has significantly decreased result turnaround times, improving patient outcomes. Despite advancements, the complex decision-making in antimicrobial therapy often exceeds the capacity of many clinicians, highlighting the importance of antimicrobial stewardship programs (ASP). These programs, integrating mHealth and eHealth, leverage technology to enhance healthcare services and patient outcomes, particularly in remote or resource-limited settings. However, the application of such technologies in antimicrobial management remains underexplored in hospitals. The development of platforms combining antimicrobial prescription data with pharmacotherapeutic algorithms and laboratory integration can significantly reduce costs and improve hospitalization times and mortality rates. Yet, the effectiveness of empirical antibiotic therapy, influenced by rapid diagnostic tests, becomes cost-effective when error rates exceed 20%, emphasizing the need for technological integration in ASPs to combat the rising challenge of antimicrobial resistance (AMR) and healthcare sustainability.

The purpose of this narrative review is to provide an overview of the latest literature on bariatric and metabolic surgery for diabetes mellitus type II and obesity (diabesity) and to discuss its implications for future research and clinical practice.

The scientific fields of complexity, artificial life (ALife), and artificial intelligence (A.I.) share commonalities: historic, conceptual, methodological, and philosophical. Although their origins trace back to the 1940s birth of cybernetics, they were only able to properly develop as modern information technology became available. In this perspective, I offer a personal (and thus biased) account of the expectations and limitations of these fields, some of which have their roots in the limits of formal systems. I will use interactions, self-organization, emergence, and balance to compare different aspects of complexity, ALife, and A.I. Even when the trajectory of the paper is influenced by my personal experience, the general questions posed (which outweigh the answers) hopefully will be useful to align efforts in these fields toward overcoming --- or accepting --- their limits.

There is a lot of pressures from organizations to continually redesign the business processes and the technology infrastructure to support the organization, but to also help organizations manage competing stakeholder needs, changing objectives and behaviour, and so on. A key part of this is making sure that all their activities in the different components of the business are interconnected and that they are moving in the same direction. Enterprise Architecture (EA) is an effective way of dealing with the challenge of designing business activities and supporting IT. This paper will summarize the organization of EA and look more closely at some major components of EA: governance architecture, business architecture, information architecture and technical architecture and consider the overlap and constructive interaction involved. Enterprise Architecture can be best understood through business process redesign. So, it is useful to briefly review the leading frameworks for business process redesign, including COBIT from ISACA, LEAN from the Toyota Group, TOGAF from the Object-Management Group, and the Capgemini Integrated Architecture Framework (IAF). All these frameworks allow us to more successful transformation, to return to the central idea of this paper.

Linear Hashing is an important algorithm for many key-value stores. Spiral Storage was invented to overcome the poor fringe behavior of Linear Hashing, but after an influential study by Larson, seems to have been discarded. Since almost 50 years have passed, we repeat Larson’s comparison with in-memory implementation of both to see whether his verdict still stands. Our study shows that Spiral Storage has slightly better look-up performance, but slightly poorer insert performance.

The advanced industrial systems are characterized by complex event-driven processes. The specification and computer analysis are illustrated by the common problem of a servo drive with the PWM controller. A mathematical model from the class of Cauchy problems with non-liner control logic is presented to resolve the task discussed. The designed model is performed in two stages: the mathematical model specification (modeling) and implementation (simulation). Two approaches to make a model specification are considered, the first one is the traditional structural technique, and the advanced method is based on the finite state machine paradigm. Structural and finite state software models are built in progressive simulation tools. Computer implementation of the software models of hybrid systems is performed using platform built-in libraries with numerical methods and algorithms for correct event detection. The results of computational experiments for transient processes of phase variables are qualitatively identical, that proves the adequacy of the developed models. The algorithm for asymptotic event detection is considered in detail. This technique demonstrated the best results by the one-sidedness criterion, which is explained by using the author’s algorithm for the integration step determining and the event function dynamics monitoring in the vicinity of the event limits.

We examine the relation between environmental, social, and governance commitment levels (ESG) and firm dividend payer status. Given that larger and more profitable firms are positively associated with both payer status and ESG, it could be that ESG and dividends are complements. However, given that both dividends and ESG relate to firm spending decisions, it may be that the choice is “either/or” and that ESG and dividends are substitutes. We document a positive relation between ESG and dividend payer status in U.S. firms over the period 1991-2016. In particular we find that the proportion of dividend payers is roughly 13% higher for firms with positive ESG compared to those with negative ESG. Including ESG in the models used to predict payer status provides, on average, a nearly 26% improvement in relative forecast accuracy. Our results are robust to estimation techniques and the inclusion of variables known to be determinants of payer status.

The power of movement in plants” by Charles Darwin details many examples of oscillatory growth exemplified more recently at the single cell level by pollen tube tip oscillations and associated ion fluxes, particularly Ca²⁺and H⁺. That implies an underlying growth oscillator based on the recent discovery that classical AGPs bind Ca²⁺ at the cell surface. The juxtaposition of AGPs with three other components embedded in the plasma membrane is evidence of a Ca²⁺ cycle that generates cytosolic Ca²⁺. It involves Ca²⁺ channels, auxin efflux “PIN” proteins and an auxin-activated proton pump that dissociates AGP-Ca²⁺ on demand. While the apparent simplicity of this system satisfies Occam’s Razor its hypothetical role as a global growth oscillator demands rigorous experimental appraisal. The wide ramifications extend from pollen tubes to stomatal guard cells. Stomata act as crucial components of a water hypercycle that contributes to homeostasis of a warming planet by regulating evaporative cooling, reflective cloud cover generated by vast forests and the high albedo of snow-capped mountains including polar ice-caps . The Gaia hypothesis of James Lovelock and Lynn Margulis is a brilliant metaphor.

Origin, mechanics and properties of the Solar System are analysed in the framework of the Complete Relativity theory (by the same author). According to Complete Relativity, everything is relative. Any apparent absolutism (notably invariance to scale of dimensional constants, absolute elementariness, invariance to time) is an illusion stemming from limits imposed by [or on] polarized observers that will inevitably lead to misinterpretation of phenomena (another illusion) occurring on non-directly observable scales or even on observable but distant scales in space or time. If everything is relative, reference frames will exist where particles are planets and where planets are living beings. Earth is, therefore, analysed here in more detail, both as a particle and, as a living evolving being (of, hypothesized, extremely introverted intelligence). The analysis confirms the postulates and hypotheses of the theory (ie. existence of discrete vertical energy levels) with a significant degree of confidence. During the analysis, some new hypotheses have emerged. These are discussed and confirmed with various degrees of confidence. To increase confidence or refute some hypotheses, experimental verification is necessary. Main conclusions that stem from my research and are further confirmed in this paper are: universes are, indeed, completely relative; Solar System is a scaled (inflated, in some interpretations) Carbon isotope with a nucleus in a condensed (bosonic) state and components in various vertically excited states; life is common everywhere, albeit extroverted complex forms are present on planetary surfaces only during planetary neurogenesis; anthropogenic climate change is only a part (trigger from one perspective) of bigger global changes; major extinction events on a surface of a planet are relative extinctions, a regular part of transformation and transfer of life in the process of planetary neurogenesis.

Structural and functional asymmetries are traceable in every form of life and, at all cases, are a phenomenon of homology. Functionally speaking, the division of labour between the two halves of the brain is a basic characteristic of the nervous system that arose even before the appearance of vertebrates. The most prominent consequence of this specialization in humans and animals is handedness. Even if handedness is far more commonly associated with the presence of a nervous system, it is also observed in aneural organism such as plants. To date, little is known regarding the possible functional significance of handedness in plants, and many questions remain open (among these, whether it reflects a generalized behavioural asymmetry). Here, we propose a comparative perspective to the study of handedness, including plants, by taking advantage of the experimental models and paradigms already used to study laterality in humans and various animal species. By taking this approach, we aim to enrich our knowledge on the concept of handedness across natural kingdoms.

Primary ciliary dyskinesia (PCD) is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. Low nasal NO (nNO) is a biomarker for diagnosis in patients with features of PCD; but the reason why it is low is unclear. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33- mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Variants in genes underlying the function of cilia, can be associated with poor lung function, even in the absence of PCD. Single nucleotide polymorphisms in PCD – related genes can be associated with increased asthma severity. The role of cilia and antigen stasis is the pathophysiology of asthma is an important area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma and asthma-like symptoms.

Preeclampsia, a hypertensive disease of pregnancy of unknown etiology, is intensely studied as a model of cardiovascular (CVD) disease not only due to multiple shared pathologic elements, but also because changes that develop over decades in CVD disease appear and resolve within days in preeclampsia. Those affected by preeclampsia and their offspring experience increased lifetime risks of CVD. At the systemic level, preeclampsia is characterized by increased cellular, membrane, and blood levels of cholesterol, however, cholesterol dependent signaling such as canonical Wnt/βcatenin, Hedgehog, and endothelial nitric oxide synthase is downregulated indicating a cholesterol deficit with upregulation of cholesterol synthesis and efflux. Hypoxia related signaling in preeclampsia also appears paradoxical with increased Hypoxia Inducible Factors (HIF) in the placenta but measurably increased oxygen in maternal blood in placental villous spaces. This review addresses the molecular mechanisms by which excessive systemic cholesterol and deficient cholesterol dependent signaling may arise from the effects of dietary lipid variance causing the cellular hypoxia which characterizes preeclampsia.

This article conducts a bibliometric analysis focusing on the influence of globalization and technology in the academic context. Previous studies have focused on analyzing the relationship between the number of research citations and international collaboration, but no study has explored it in the scope of consumer behavior and retail. Leveraging the Scopus database, the research analyzes a significant corpus of 2,111 documents from 1971 to 2022. The findings reveal a distinct surge in academic output related to the topic of technology, reflecting a growing interest in understanding the interaction between technological factors and consumer behavior. The study also explores trends in international collaboration in publications as well as its impact on citation counts.

The Schwarzschild metric emerges independent of Einstein's field equations, offering a straightforward derivation solely reliant on Newtonian mechanics and Minkowskian proper acceleration. This approach provides a clear path to understanding the gravitational field around a spherically symmetric mass without the need for the complexities of Einstein's full theory of General Relativity. Transitioning to our exploration of the cosmic Friedmann equations, we adopt a novel perspective rooted in a Lagrangian formulation grounded in Newtonian mechanics and the first law of thermodynamics. Our investigation operates under the assumption that the universe is populated by either a perfect fluid or a scalar field. By elucidating the intricate interplay between the Lagrangian formulation and the cosmic Friedmann equations, we uncover the fundamental principles governing the universe's dynamics within the framework of these elemental constituents. In our concluding endeavor, we embark on the task of harmonizing the classical equations—namely, the conservation, Euler, and Poisson equations—with the principles of General Relativity. This undertaking seeks to extend these foundational equations to encompass the gravitational effects delineated by General Relativity, thus providing a comprehensive framework for understanding the behavior of matter and spacetime in the cosmic context.

Let a,b,c be positive integers such that a²+b²=c², 2|b,gcd(a,b)=1. In 1956, Jesmanowicz conjectured that for any positive integer w, the only solution of (aw)^x+(bw)^y=(cw)^z in positive integers is (x, y, z) = (2, 2, 2). In this paper, based on Gaussian integer ring, we show that Je$\acute{s}$manowicz' conjecture is true for any positive integer

A proof is given showing the Collatz Conjecture is true for all positive integers. The proof was possible once the perspective of the proof was changed from looking at the pattern of the positive integers to looking at the conjecture rules. The conjecture rule for even numbers organizes all positive integers into unique sets and the rule for odd numbers interconnects the unique sets into dendritic pathways to “1.” Infinite loops, other than the minor 4-2-1 loop after reaching “1,” and pathways to infinity are shown to be mathematically impossible. The proof predicted a general equation that shows all positive integers ultimately reach a final value of “1," and calculates the values and locations of the odd positive integers during the iterations for each tested positive integer.

Introduction: It has long been accepted that trauma is one of the most important and frequent predisposing factors for onychomycoses . However, the role of direct trauma in the pathogenesis of fungal nail infections was only recently been elucidated in a series of 32 cases of post-traumatic single-digit onychomycosis. The importance of repeated trauma due to foot and toe abnormalities was rarely investigated.Aim of the study: This is a multicenter single-author observational study over a period of 6 years performed at a specialized nail clinic in three countries. All patient photographs taken by the author during this period were screened for toenail alterations and all toe onychomycosis cases were checked whether they contained enough information to evaluate potential foot and toe abnormalities. Particular attention was paid to the presence of hallux valgus, hallux valgus interphalangeus, hallux erectus, inward rotation of the big toe and outward rotation of the little toe, as well as splay foot. Only cases with unequivocal proof of fungal nail infection by either histopathology, mycologic culture or polymerase chain reaction (PCR) were accepted.Results: Of 1653 cases, 185 were onychomycoses proven by mycologic culture, PCR or histopathology. Of these, 179 involved at least one big toenail, 6 affected one or more lesser toenails. Three patients consulted us for another toenail disease and the onychomycosis was diagnosed as a second disease. Eight patients had a pronounced tinea pedum. Relatively few patients had a normal big toe position (n = 9). Most of the cases had a mild to marked hallux valgus (HV) (105) and a hallux valgus interphalangeus (HVI) (143), hallux erectus was observed in 43 patients, the combination of HV and HVI was observed 83 times. Discussion: The very high percentage of foot and toe deformations was surprising. It may be hypothesized that this is not only a pathogenetically important factor but may also play an important role for the localization of the fungal infection as no marked hallux deviation was noted in onychomycoses that affected the lesser toes only. As the management of onychomycoses is a complex procedure involving the exact diagnosis with determination of the pathogenic fungus, the nail growth rate, the type of onychomycosis, its duration and predisposing factors, anomalies of the toe position may be important. Among the most commonly mentioned predisposing factors are peripheral circulatory insufficiency, venous stasis, peripheral neuropathy, immune deficiency and iatrogenic immunosuppression whereas foot problems are not given enough attention. Unfortunately, many of these predisposing and aggravating factors are difficult to treat or to correct. Generally, when explaining the treatment of onychomycoses to the patients, the importance of these orthopedic alterations is not or only insufficiently discussed. In view of the problems encountered with the treatment of toenail mycoses, this attitude should be changed in order to make the patient understand why there is such a low cure rate despite excellent minimal inhibitory drug concentrations in the laboratory.

The delivery of therapeutical molecules through the skin, particularly to its deeper layers is impaired due to the stratum corneum layer, which acts as barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consists on an array of microscale needles. This particular biomedical device had been drawing attention due to their ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size and composition. The design process of a microneedle device must take in account several factors, like the location delivery, the material and manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application, cosmetics, therapy, diagnosis, tissue engineering, sample extraction, cancer research, wound healing, among others.

This article investigates the fundamental principles that establish universal limits in physical phenomena, such as the uniformity of physical laws and Energy conservation, leading to the concepts of maximum speed, locality, and maximum density. These principles guide me to explore Quantum Black Holes—relativistically rotating, miniature charged black holes with a singular core at the highest possible density. Uniquely, these Quantum Black Holes maintain all quantized charges, including gravitational ones. The study further demonstrates that quarks and leptons are composed of these Quantum Black Holes, redefining them as the actual elementary particles.Exploring these particles reveals that they emit Energy outward, modifying the curvature of nearby space-time. This discovery provides new insights into local space-time dynamics, characterized by a single equation that includes the influence of all charges and hidden Energy. By the conclusion of this article, I show that Quantum Black Holes offer explanations for several Standard Model deficiencies: the nature of luminous, dark, and anti-Matter; the mass, size, and quantized charges of all elementary particles (including gravitational); the nature of neutrino oscillations; and the mechanism by which electric charges remain bound even though the same type of electric charge components must repeal each other.

It is proved that there exist two odd prime numbers, p_i and p_j , such that p_i + p_j = 2r + 2(r ⩾ 2), where p_n denote the n-th odd prime number, 1 ⩽ i, j ⩽ n. By the theory of generating functions, we prove that there exist two positive integers, h_i and h_j , such that h_i + h_j = r(r ⩾ 2), where h_n = (p_n − 1)/2，(p_n ⩾ 3).Then we complete the proof.

Industry 4.0 is an industrial paradigm that is causing changes in form and substance in factories, companies and businesses around the world, and is impacting work and education in general. In fact, the disruptive technologies that frame the fourth industrial revolution have the potential to improve and optimize manufacturing processes and the entire value chain, which can lead to an exponential evolution in the production and distribution of goods and services. All these changes imply that the fields of engineering knowledge must be oriented towards the concept of Industry 4.0, for example Mechanical Engineering. The development of various physical assets that are used by cyber-physical systems and digital twins is based on Mechanics. However, the specialized literature on Industry 4.0 says little about the importance of Mechanics in the new industrial era and more importance is given to the evolution of Information and Communication Technologies and Artificial Intelligence. This article presents a frame of reference about the importance of Mechanical Engineering in Industry 4.0 and proposes an extension to the concept of Mechanics 4.0, recently defined as the relationship between Mechanics and Artificial Intelligence. For the analysis of Mechanical Engineering in Industry 4.0, the criteria of the four driving forces that defined Mechanics in the third industrial revolution was used. An analysis of Mechanical Engineering Education in Industry 4.0 is presented, and the concept of Mechanical Engineering 4.0 Education is improved. Finally, the importance of making changes in the educational models of engineering education is described.

The draconian regulation required by the inherent instability of cognitive phenomena -- gene expression, immune function, cancer suppression, wound healing, animal consciousness, machine intelligence, network stabilization, institutional cognition, and their many and varied composites -- can be viewed through the lens of the asymptotic limit theorems of both information and control theories. Here, we explore the dynamics and sometimes highly punctuated failures of the regulation of cognition under increasing `noise'. The approach parallels, and indeed generalizes, the Data Rate Theorem of control theory, extending the theorem's requirement of a minimum channel capacity necessary for stabilization of an inherently unstable system. Various models are explored across different basic underlying probability distributions characteristic of the system under study, and across different hierarchical scales, finding the addition of adaptive -- learned -- regulation greatly extends the reach of innate -- e.g., AI-driven or otherwise pre-programmed -- regulation. This work points toward the construction of new statistical tools for the analysis of observational and empirical data across a wide spectrum of inherent pathologies and adversarial challenges afflicting a wide variety of cognitive processes.

In this paper we present two ways to solve the Jacobian conjecture. The first way is an equivalent statement to the Jacobian conjecture using idempotent ideals. The second way is to use an equivalent thesis to the thesis of the Jacobian conjecture. In both cases we will show that the Jacobian conjecture is true.

Abstract Global marine fish harvest has reached a plateau over the last decade. Efforts to increase aquaculture tend to face limitations in water resources and contamination problems. Of the current fish harvest at least 50% is discarded as waste. The chemical and microbiological contaminations limit the utilization of harvested fish. There is a need to improve fish preservation to minimize spoilage and process them into more appealing products. Instead of resorting to individual food processing methods, the efficiency of processing could best be increased by a combination of conventional and modern processing methods, or combinations of modern processing methods. Fish waste is a rich source of oils containing essential fatty acids, polypeptides, and amino polysaccharides that could be utilized through upscaling of the current scientifically proven methods, to new processing technologies. Separation of collagens, gelatins, bioactive peptides, edible fish oils, and chitosan form the primary stages in the utilization of fish waste. The products need purification to meet food quality and safety standards, and desirable industrial characteristics. The diversity of information and products generated through new methods requires advanced data handling and prediction systems, such as artificial intelligence, to address food safety and get the best out of fish processing and utilization.

The present article seeks to study whether there is any relationship between the equation of the rhythmic figures (Lugos Abarca, 2023) and cardiac auscultation using Field's method, which consists of representing cardiac sounds by means of musical notation (Field, 2010). A new meaning is given to the equation, concluding a mathematical equality between the equation of the rhythmic figures and the formula for calculating the RR Interval.

The purpose of this project is to develop and build an extensible fixture. This fixture is ideal to milling, drilling, and shaping operations. Jigs and fittings are often the most cost-effective methods of mass fabricating a component. As a result, jigs and fittings are used and play a vital part in the mass production system. These are specialist work holding and tool-guiding devices. The quality of jigs and fixtures used in a process has a substantial impact on its performance. A fixture is distinctive because it is meant to fit a given area or shape. The basic purpose of a fixture is to find and, in certain instances, hold a workpiece throughout an operation. A jig differs from a fixture in that it leads the tool to the right position or movement during an operation, in addition to locating and supporting the workpiece. When a key is reproduced, the original key serves as a base for the path reader, which regulates the tool's movement to construct the duplicate key. In this situation, a CWC machine's route reader works as a jig, with the original being referred to as the template. Sometimes the template and jig refer to the same part of a production system.

This review aims to consolidate varied information regarding Port Scanning, and examine the tools, techniques, and detection algorithms used. It explores TCP SYN, Full TCP, UDP, and stealth scans, and shows their functions and abilities. Paired with these techniques, it also shows the tools that they can be used by, such as NMap, Zmap, and MASSCAN. It discusses the various detection techniques such as Signature and Anomaly based detection, and discusses the real world impact of this technology, while commenting on the legal and ethical issues posed.

In today’s fast paced, attention-demanding society, executive functions and attentional resources are often taxed. Individuals need ways to sustain and restore these resources. We first review the concepts of attention and restoration, as instantiated in Attention Restoration Theory (ART). ART emphasizes the role of nature in restoring attention. We then discuss essentials of experiments on the causal influences of nature. Next, we expand the concept of ART to include modern, designed environments. We propose a wider perspective termed attentional ecology, in which attention behavior is viewed within a larger system involving the human and their interactions over time with environmental demands. When the ecology is optimal, mental functioning can be a positive “flow” that is productive, sustainable for the individual, and sometimes creative.

The rapid expanse of the metropolitan belt around Budapest and the tension stemming from increasing traffic and insufficiencies of various infrastructures, plus social and economic issues in the outer areas, have put the sustainability of suburbs at the forefront of professional and public debates with oversimplified and overgeneralized statements. The article, instead, attempts to shed light through a case study of a suburban town on the complexity of sustainability using the framework of Smart Growth, focusing on compactness, commuting, and community, using qualitative and quantitative survey data from 2018 and 2023. The findings prove that the analyzed town is relatively compact regarding ordinary and routine services but relies heavily on the center for more specialized ones. The local community is firmly knit and has no signs of atomization. The commuting patterns reveal a more complex picture where polycentricity contributes to new patterns of spatial connections and increasing car dependency despite the relatively low growth in the number of cars. The results underpin that the sustainability of suburbs may not be generally assessed, and scrutiny must be performed on the town level. Second, the sustainability of suburban areas may be separate from the sustainability of more dense, urbanized areas.

This study investigated the relationship between aluminum adjuvant vaccines and the prevalence of 4 childhood diseases (Autism, Allergies, Asthma, ADD/ADHD) using data from the 2020-2021 National Survey of Children's Health (NSCH) [1] and the Centers for Disease Control National Immunization Survey (CDC NIS) [2]. The study found an association with aluminum adjuvant dosage and the prevalence of each disease studied (Autism, Allergies, Asthma, ADD/ADHD) through a weighted regression analysis of disease prevalence against the summed likelihood of aluminum adjuvant vaccine uptake.

We present detailed models at the hydrodynamics and decoherence phenomena observed in ideal quantum gases. The model is expressed in terms of a quantum field theory, where the action involves both hydrodynamic and decoherence terms. The density-current relation is derived, and the current Green function is introduced. The effective action for two fields is presented, and the physical field is defined in terms of the bare action. Identities such as CTP symmetry, transposition, and the Ward identity are discussed. The Green function and its inverse for different components are also explored. These notes provide a comprehensive understanding of the theoretical framework for studying the hydrodynamics and decoherence of ideal quantum gases.

This review highlights the potential and limitations of mRNA vaccines with a particular focus on mucosal delivery as an alternative to parenteral administration. The strengths of mRNA vaccines are: a) Versatility: they can be adapted to target a wide range of pathogens; b) Faster development: designed and produced more quickly than traditional vaccines; c) High efficacy: effective in preventing severe disease, as demonstrated during the COVID-19 pandemic. Current challenges: a) Delivery: current methods (mainly intramuscular injection) may not be optimal for inducing mucosal immunity; b) Stability: mRNA is fragile and needs to be protected from degradation; c) Safety: potential side effects, including myocarditis, blood clotting, allergic reactions need further investigation. Mucosal delivery could be more effective in preventing the transmission of pathogens and is generally better accepted by the population. Pros: offers the potential to induce local immunity at the site of pathogen entry, potentially providing broader protection; Cons: developing effective delivery systems and adjuvants for mucosal delivery is difficult. Extracellular vesicles as a mucosal delivery system are promising and offer a potentially safe, scalable, and needle-free approach. Future directions: a) Optimizing mRNA constructs: strategies like codon optimization and self-amplifying RNA can improve stability and translation efficiency; b) Rigorous pre-clinical studies are essential before human trials.

There is a rich history of cancer treatments which provides a number of important lessons for present and future cancer therapies. We outline this history by looking in the past, reviewing the current landscape of cancer treatments, and by glancing at the potential future cancer therapies.

Coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome 2 virus (SARS-CoV-2) infection, has caused millions of infections and fatalities worldwide. Extensive SARS-CoV-2 research has been conducted to develop therapeutic drugs and prophylactic vaccines, and even though some drugs have been approved to treat SARS-CoV-2 infection, treatment efficacy remains limited. Therefore, preventive vaccination has been implemented on a global scale and represents the primary approach to combat the COVID-19 pandemic. Approved vaccines vary in composition, although vaccine design has been based on either the key viral structural (spike) protein or viral components carrying this protein. Therefore, mutations of the virus, particularly mutations in the S protein, severely compromise effectiveness of current vaccines and the ability to control COVID-19 infection. This review begins by describing the SARS-CoV-2 viral composition, mechanism of infection, role of angiotensin-converting enzyme 2, host defense responses against infection and the most common vaccine designs. Next, this review summarizes the common mutations of SARS-CoV-2 and how these mutations change viral properties, confer immune escape and influence vaccine efficacy. Finally, this review discusses global strategies that have been employed to mitigate the decreases in vaccine efficacy encountered against new variants.

Neurocutaneous disorders, also known as phakomatoses, are congenital and acquired syndromes resulting in simultaneous neurologic and cutaneous involvement. In several of these conditions, the genetic phenomenon is understood, providing a pivotal role in the development of therapeutic options. This review encompasses the discussion of the genetic and clinical involvement of neurocutaneous disorders and examines clinical management and treatment options. With the current advances in genetics, the role of precision medicine and targeted therapy plays a substantial role in addressing management of these conditions. The interconnectedness between therapeutic options highlights the importance of precision medicine in treating each disorder’s unique molecular pathway. This review provides an extensive synthesis of ongoing and current therapeutics in the management of such clinically unique and challenging conditions.

The definitive negative results of various direct searches for dark matter particles and non-observation of them has increasingly indicated that we should consider alternate models like the Modification of Newtonian Dynamics (MOND) and Modification of Newtonian Gravity (MONG). It is puzzling how the Oort cloud, despite its great distance from the Sun, is gravitationally bound to the Sun’s gravity. In this work, we suggest that this could be explained by the modifications to Newtonian dynamics (MOND) and to gravity (MONG).

Segmental bone defects caused by trauma, infection, tumor resection or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard to restore function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in incorporation with host bone as well as cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells and urine-derived stem cells for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hopeful in the future that these preclinical results will translate into new therapies for bone defect repair.

Background: Opinions on the impact of cancer on patients with haemophilia literature are contradicting. There is a lack of data on the clinical presentation and management of cancer in patients with haemophilia (PWH). Methods: Papers were found following a comprehensive search in PubMed, Google Scholar, and Scopus using the terms “cancer” and “haemophilia” without time limits and using the English language as a filter. The references of all retrieved original articles and reviews were assessed for additional relevant articles. Results: Overall, 116 papers were collected. Managing cancer in patients with congenital bleeding disorders, such as haemophilia A and B, requires careful evaluation of bleeding risk and the effect of antitumor treatments on blood coagulation. Generally, patients with haemophilia do not have an increased risk of developing cancer compared to the general population; increased risk is found in the presence of HIV or hepatitis infection. However, if a patient with haemophilia develops cancer, the treatment must be managed to minimise the risk of bleeding. Bleeding and thrombotic complications are important causes of morbidity and mortality in critically ill patients with cancer; replacement therapy with factor VIII or IX or others should be maintained during antitumor treatment. Conclusion: Overall, managing cancer in patients with haemophilia requires careful evaluation and individualised planning involving a multidisciplinary team of physicians experienced in haematology, oncology, and surgery.

Along with the rapid development and wide application of Artificial Intelligence (AI), discussions regarding AI Sustainability have emerged. Employing a systematic mapping study, this paper reviews research about AI Sustainability from diverse fields and viewpoints, including three dimensions economic, social, and environmental. Our analysis indicates a transformative shift in research focus, evolving from fragmented approaches to a more holistic understanding of AI Sustainability. This maturation is reflected in the interplay between multiple dimensions and the integration of both "AI as a tool for sustainability" and "Sustainability of AI" perspectives. As the field continues to mature, researchers should embrace a comprehensive and unbiased exploration of AI Sustainability across all dimensions and approaches, ensuring a well-rounded foundation for future advancements in this rapidly evolving domain.

Non-coding RNAs, specifically microRNAs (miRNAs), exhibit altered expression and contribute significantly to the pathological processes observed in numerous diseases, encompassing various types of human cancers. Recent discoveries regarding miRNAs underscore their crucial roles in tumor pathogenesis and their responses to diverse therapeutic interventions. miRNAs are a subset of non-coding RNAs that regulate the expression of a multitude of genes post-transcriptionally and thus are potential diagnostic, prognostic, and predictive biomarkers and have also emerged as potential therapeutics. Because miRNAs are involved in the post-transcriptional regulation of their target mRNAs via repressing gene expression, defects in the miRNA biogenesis pathway and miRNA expression perturb the expression of a multitude of oncogenic or tumor-suppressive target genes that are involved in the pathogenesis of various cancers. As such, numerous miRNAs have been identified to be downregulated or upregulated in many types of cancers functioning as either oncomiRs or oncosuppressor miRs. Moreover, dysregulation of miRNA biogenesis pathways can also change miRNA expression and function in cancer. Profiling deregulated miRNAs in many cancer types has been shown to correlate with disease diagnosis, indicate optimal treatment options, and predict response to a specific therapy. Specific miRNA signatures can track all stages of disease including many cancer types and hold potential as biomarkers and therapeutic targets as well as therapeutics as miRNA mimics and inhibitors (antagomirs). As such, identifying specific miRNAs and mRNAs they regulate in many types of cancer along with downstream pathways can be used as potential therapeutic targets. Because a single miRNA can regulate a pool of targets involved in similar cellular processes and pathways, thereby amplifying the cellular response, this potentially makes miRNAs powerful therapeutics to restore cell functions that are altered as part of a disease phenotype. However, because a single miRNA regulates multiple gene expressions their cellular effects are numerous leading to potential off-target effects. Besides their intended targeting issues, there is a need to reduce the immunogenic reactions and determine the minimal dosing to achieve the desired effect while minimizing side effects. As such, a careful risk evaluation of miRNA therapeutics is needed to minimize off-target effects and to avoid overdosing of miRNA drugs. Furthermore, a limited understanding and validation of the specific roles of miRNAs limits their clinical application. In addition, there are many challenges concerning the delivery, sensitivity, specificity, toxicity, and applicability of the potential utility of miRNAs as therapeutic targets or therapeutics. Thus, future work will warrant if miRNAs can be used as cancer biomarkers as well as therapeutics for clinical application.

Coffee is one of the most widely consumed beverages in the world, with important repercussions on the health of the individual. Dysbiosis in the gut microbiota is implicated in the occurrence of numerous diseases, and knowledge of it has also proven to be of fundamental importance for the development of new therapeutic strategies. In this narrative review, we thoroughly investigated the link between coffee consumption and its effects on the gut microbiota and their consequences on human health. We have selected the most significant articles published on this very interesting link, with the aim of going deeper in the light of the latest evidence more and more about the relationship that links coffee consumption and its repercussions on the composition of the gut microbiota and on human health.

Metasurface holography offers significant advantages, including a broad field of view, minimal noise, and high imaging quality, making it valuable across various optical domains such as 3D displays, VR, and color displays. However, the conventional pure-structured metasurface holographic devices face a limitation: once fabricated, their functionality remains fixed, restricting practical applications. In recent developments, the landscape of metasurface holography has witnessed a notable shift from passive to active elements, spurred by the introduction of multiplexed and reconfigurable metasurfaces. This paper provides a comprehensive review of the latest advancements in multiplexing and reconfigurable metasurface holography, delving into fundamental characteristics, design strategies, and diverse applications. In conclusion, we offer a brief summary of this rapidly evolving research area, suggest potential future directions, and explore applications. Finally, we briefly summarize this rapidly growing area of research, propose future directions and potential applications.

This paper presents a model for archival and retrieval of the videos of natural flowers. To design an efficient video retrieval system the stages namely, keyframe selection, feature extraction, feature dimensionality reduction and indexing are essential for fast browsing and accessing of videos. Three different keyframe selection approaches are proposed using clustering algorithms after segmenting flower regions from its background. Deep Convolutional Neural Network is used as a feature extractor. After keyframe selection, a video is represented with a set of keyframes. To reduce the feature dimension of a video, two feature selection methods are utilized. For an efficient archival and fast retrieval of flower videos an indexing method called KD-tree is recommended. For a given query video, similar videos are retrieved both in relative and absolute search modalities. An extensive experimentation conducted on a relatively large flower video dataset. The data set consists of 7788 videos of 30 different species of flowers. The videos are captured with three different devices in different resolutions. The comparative study reveals proposed keyframe selection approaches gives better results. It has also been observed that the videos retrieved in absolute approach with features selected from Binormal separation metric and indexing gives good results.

Re-interpretation of the Fermat principle governing propagation of light in media within the Ramsey Theory is suggested. Complete bi-colored graphs corresponding to the light propagation in media are considered. The vertices of the graphs correspond to the points of the real physical space, in which light sources or sensors are placed. Red links in the graphs correspond to the actual optical paths, emerging from the Fermat principle. A variety of optical events: refraction, reflection, etc. may be involved in the light propagation. Green links, in turn, denote the trial/virtual optical paths, which actually do not occur. The Ramsey Theorem states that within the graph containing six points, inevitably, actual or virtual optical cycle will be necessarily present. Implementation of the Ramsey Theorem to the light propagation in metamaterials is discussed. The Fermat Principle states that in metamaterials a light ray in going from point S to point P must traverse an optical path length L that is stationary with respect to variations of this path. Thus, bi-colored graphs built of links corresponding to maxima or minima of optical paths become possible. Graphs, comprising six vertices, inevitably will demonstrate optical cycles, built of the mono-colored links corresponding to the maxima or minima of the optical path. The notion of the “inverse graph” is introduced and discussed. The total number of triangles in the “direct” (source) and “inverse” Ramsey optical graphs is the same, Optical interpretation of the infinite Ramsey Theorem is suggested.

How does fiscal devolution affect the probability of a sovereign debt crisis? Using annual cross-country panel data from 82 advanced and developing countries, the association between the sovereign debt crisis and fiscal decentralization is investigated. We employ an instrumental variable panel probit model to address potential endogeneity. The results reveal that local tax autonomy reduces the probability of a sovereign debt crisis. In contrast, expenditure devolution is found to increase the probability of a sovereign debt crisis. These favorable and unfavorable effects of fiscal devolution are found to be more evident in the case of decentralization to local governments than in the case of decentralization to subnational governments. In terms of relative magnitudes, our discrete choice analysis demonstrates that the undesirable effects of expenditure decentralization are greater than the favorable effects of tax revenue decentralization. Therefore, countries should be cautious about risks associated with fiscal devolution, particularly the contrasting impact of tax revenue and spending decentralization on the likelihood that sovereign debt crises occur.

Growing interest has accrued in the co-existence of cardiac amyloidosis and valvular heart disease. Amyloid infiltration from either transthyretin (ATTR) or light chain (AL) origin may affect any structure of the heart, including the valves. Recent literature has mainly focused on aortic stenosis and cardiac amyloidosis, improving our understanding of epidemiology, diagnosis, treatment and prognosis of this dual pathology. Even though of high clinical relevance, data on mitral/tricuspid regurgitation and cardiac amyloidosis is rather scarce and mostly limited to case reports and small cases series. It is the aim of this review article to summarize the current evidence of concomitant valvular heart disease and cardiac amyloidosis including epidemiology, diagnostic approaches, screening possibilities, therapeutic management, and prognostic implications.

As the global demand for renewable energy continues to rise, biogas technology has emerged as a promising solution for sustainable energy generation. This review article presents the advantages of biogas technologies and extensively discusses the main principles of biogas production in the methane fermentation process. In this respect, the main parameters of the process, which require monitoring and are at the same time decisive for its course and efficiency are described, the principles of substrate selection are discussed and the necessity and advantages of the use of organic waste according to the model of a circular economy and the concept of sustainable development, are indicated. The part on biogas production is summarised with an explanation of the necessity to treat and purify biogas, taking into account the share of methane extracted. A special place in this paper is devoted to the design, construction, functioning and operation of biogas plants, based on both scientific and practical aspects. In conclusion of this chapter, the economic aspects and profitability of operating biogas plants are discussed, taking into account, in a theoretical balance sheet – in addition to investment and operating costs and the availability and cost of raw materials – the possibilities of producing and using electricity and heat, as well as environmental and social benefits. The article concludes with a discussion of opportunities and barriers to the development of biogas plants, pointing to: financial issues, access to feedstock, political regulations, public awareness and the geopolitical situation as key factors issues related to biogas plants – in different regions of the world.

Authors evaluated the relevant literature related to the purging which is the interaction between selection and inbreeding where the population may get rid of its inbreeding load at least partially. The backroad of the relevant theory was given and the available methods were described both based on the conventional quantitative genetic approach (based on genealogy data) and based on the latest genomic methods. The different parameters necessary for signalling purging (highlighting those inbreeding coefficients which are not yet been widely known in animal and veterinary science) were presented together with the relevant results of the literature. The available statistical methods together with the softwares and R packages to calculate various inbreeding coefficients and to determine inbreeding depression and purging were provided. The main results of the different approaches obtained in laboratory ZOO and domesticated populations (lethal equivalents, ancestral inbreeding, Inbreeding-Purging Model, genomic approaches) were summarized and presented. Application possibilities and future prospective of purging was also discussed.

Modern anesthesia continues to be impacted in new and unforeseen ways by digital technology. Combining portability and versatility, mobile applications or “apps” provide a multitude of ways to enhance anesthetic and peri-operative care. Research suggests that uptake of apps into anesthetic practice is becoming increasingly routine, especially amongst younger anesthetists brought up in the digital age. Despite this enthusiasm, there remains no consensus in how apps are safely and efficiently integrated into anesthetic practice. This review summarizes the most popular forms of app usage in anesthesia currently and explores the challenges and opportunities inherent in implementing app use in anesthesia, with an emphasis on a practical approach for the modern anesthetist.

in our increasingly interconnected world, sensor networks are critical in gathering and sending data for various applications, from environmental monitoring and industrial automation to healthcare and smart cities. However, as sensor networks expand in importance, so does the need to solve the multidimensional concerns of security, privacy, and forensics. This article explores the complex world of sensor network security, the delicate balance between data privacy and utility, and the emerging area of sensor network forensics. This article focuses on risk assessment of a network.

Background and Objectives: Thyroid disease has been associated with autoimmune disorders. As systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations spanning across all organ systems, the relationship of SLE with thyroid disorders needs investigation. In particular, the relationship of SLE with autoimmune thyroid disease has attracted the interest of the research community. The aim was to evaluate the relationship of SLE with autoimmune thyroid disease. Materials and Methods: A cohort of 45 consecutive patients, mean age 47,97 years (range 21-79 years) and 45 age and sex-matched controls were prospectively studied over a period of 12 months for the presence of thyroid disease and the prevalence of antithyroid antibodies. Results: Four patients (8.9%) were found to suffer from primary hypothyroidism, 5 (11.11%) from subclinical hypothyroidism and 1 (2.22%) from hyperthyroidism, whereas 1 (2.22%) of the controls had primary hypothyroidism and 1 (2.22%) had hyperthyroidism. Five patients (11.11%) had a thyroid hormone profile compatible with the presence of euthyroid sick syndrome. Thyroid peroxidase (TPOab) and thyroglobulin (Tgab) antibodies were detected in 20/45 and 15/45 of the SLE population and in 7/45 and 5/45 of the controls, respectively (p<0.05, chi square test). Conclusions: In conclusion, the incidence of clinical thyroid disease is greater amongst SLE patients than in a control population and in a significant number of these patients antithyroid antibodies are detectable. Thus, a subset of lupus patients appears to be predisposed to the development of thyroid disease and this should be considered when evaluating patients with SLE.

This paper's aim is to extend horizons in symbolic AI. The key to doing so is to establish a scientific basis for knowledge foundations, and specifically for the concept of meaning, and its computation. This led to the creation of the Meaning Computation AI (MCAI). Knowledge structures are at the heart of MCAI. The semantic triple chain, one of such structures, is the subject of this paper. This structure is the core of introducing computational semantic reasoning models across a variety of domains. To efficiently apply knowledge structures to create semantic reasoning applications MCAI contains a development framework consisting of four components. The first component stems from our discovery that knowledge is relational in nature. It can be expressed through implicit relations (which reflect meaning) and semantic relations (which describe how implicit relations act between entities). An algebraical apparatus for relational knowledge, specifically for implicit and semantic relations, represents the first component. Axiomatic models of relational domain ontologies and domain-oriented semantic reasoning models comprise the second and third components. The fourth component contains domain-oriented semantic reasoning engines.

JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining disease pre-antiretroviral therapy that has “reemerged” as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we will discuss evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model is providing insights into the pathogenesis of JCPyV CNS disease.

Recent advances in understanding the Planck scale have led to a new, straightforward method for quantizing the general theory of relativity. This results in a theory of gravity that predicts the same outcomes as general relativity with greater fundamental comprehension connected directly to the Planck scale.

this paper we present approaches for generating random numbers along with potential applications. Rather than trying to provide extensive coverage of several techniques or algorithms that have appeared in the scientific literature, we focus on some representative approaches presenting their workings and properties in detail. Our goal is to delineate their strengths and weaknesses as well as their potential application domains so as the reader can judge what would be the best approach for the application in hand, possibly a combination of the available approaches. For instance, a physical source of randomness can be used for the initial seed, then suitable preprocessing can enhance its randomness and then the output of the preprocessing can feed different types of generators, e.g. a linear congruential generator, a cryptographically secure one and one based on the combination of one way hash functions and shared key cryptoalgorithms in various modes of operation. Then, if desired, the outputs of the different generators can be combined giving the final random sequence. Moreover, we present a set of practical randomness tests which can be applied on the outputs of random number generators in order to assess their randomness characteristics. In order to demonstrate the importance of unpredictable random sequences, we present an application of cryptographically secure generators in domains where unpredictability is one of the major requirements, i.e. eLotteries and cryptographic key generation.

The growing concerns on sustainability urge insurance companies to incorporate Environmental, Social, and Governance (ESG) policies in order to remain competitive. As all dimensions of sustainability involve taxation, it is important to establish if this association reflects on financial performance. Our analysis of worldwide property and casualty (P&C) insurers during 2013-2022 reveals that high ESG insurers pay more taxes, while are less profitable compared to low ESG insurers. This pattern is confirmed using instrumental variable regressions and simultaneous equations systems. We argue that sustainable insurers are less tempted to avoid taxes, and don't shift their tax burdens on policyholders and investors. However, the interplay between taxes and sustainability seems to harm insurers' profitability, potentially sorting negative consequences on investment and economic growth. This is an important insight for tax authorities and insurance managers.

For several millennia, doctors and healers used therapeutic ingredients extracted from minerals, plants, and animals. Among the active remedies derived from animals, the placenta was among the most popular ones. The use of placenta-based remedies has retained its significance in our time. The placenta-based therapeutics are indicated for stimulating immunity, wound healing, reduction of skin pigmentation, treatment of various patients suffering from gynecological disorders, etc. By the beginning of the 21st century, the majority of specific functions and chemical ingredients of the placenta were identified and described. However, only now active proteins and peptides with molecular weight of about ten kDa were revealed. Presumably, they play an essential role during the therapeutic application of placental extract. Hopefully, this discovery will start a new era in the research and clinical application of organotherapeutic remedies, including placenta.

Thimerosal (TmHg) has been used in thimerosal-containing vaccines (TCV) and various med-icines, although to our knowledge, there are no studies evaluating its effects on microglia. Microglia are a crucial glial component that have important functions in inflammatory diseases, particularly in the Central Nervous System (CNS). They are also considered a key player in neurotoxicity. Furthermore, microglia are responsible for the activation of immune responses and plays an essential role for the maintenance of brain homeostasis. Microglial response is important for the maintenance of CNS immune regulation. Moreover, microglia cells partici-pate in the removal of cellular debris and pathogens, playing an important role as neuroprotectants in several CNS diseases, including neurodegeneration. The objective of this study was to evaluate the effects of TmHg and its metabolite ethylmercury (EtHg) on microglial cells. Our novel findings demonstrated that microglia are more sensitive to TmHg than to EtHg with EC50 1.4 ± 0.4 μM and 2.3± 0.9 μM for 24h, respectively. The mercury compounds also induced the transcription of pro-inflammatory markers s such as IL-1β; iNOS, and to a lesser extent TNF-α expression. Likewise, the increase in Beclin-1 expression - a protein associated to autophagy - and the number of senescent cells indicate that microglia are activated by TmHg and EtHg. The effects of thimerosal may have different consequences depending on the health status and susceptibility of the populations.

Dyes, as indigo carmine have become indispensable to modern life being widely used in food, textile, pharmaceutical, medicine and cosmetic industries. Although indigo carmine is considered toxic and presents many adverse effects, it is heavily used in the food industry because the blue pigment is difficult to obtain from natural sources and is one of the most used dyes in the textile industry, especially for dyeing denim. Also, indigo carmine is one of the dyes used in medicine as diagnostic agent because it has impressive applicability in terms of diagnostic methods and surgical procedures. In the literature it is reported that indigo carmine is toxic for humans and can cause various pathologies, such as hypertension, hypotension, skin irritations, corneal and conjunctival disorders or gastrointestinal disorders. In this review, we discuss the structure and properties of indigo carmine, its use in various industries and medicine, the adverse effects of its ingestion, injection or skin contact, the effects on environmental pollution and its toxicity testing.

Geothermal energy is a weather-independent, permanently available renewable energy source. In addition to producing heat and electricity, geothermal energy can be used to extract critical raw materials dissolved in the heat-carrying fluid. Researchers working on the frontiers of geothermal energy utilisation may be able to transform ultra-deep metallic mineral formations into “orebody-Enhanced Geothermal Systems”. In the planned technology, the metal-containing geological formation would be manipulated in such a way that cogeneration of energy and metals is possible and can be optimised in the future according to market needs. The potential of geothermal energy for sustainable mineral extraction and energy production aligns with Sustainable Development Goal (SDG) 7, which aims to ensure access to affordable, reliable, sustainable, and modern energy for all. This new technology could substantially decrease Europe’s dependency on importing critical metallic minerals (such as lithium and tungsten) and energy; over and above, it has a small environmental footprint, including very low carbon emissions

The pathogen Cryptococcus neoformans is a major cause of fungal meningitis in humans. As with other melanotic microorganisms associated with human diseases, the cell wall-associated melanin of C. neoformans is a major virulence factor that contributes to its ability to evade host immune responses. The levels of melanin substrate and the regulation of melanin formation could be influenced by the microbiota-gut-brain axis. Moreover, recent studies show that C. neoformans infection causes dysbiosis in the human gut microbiome. In this review, we discuss the potential association between cryptococcal meningitis and the gut microbiome. Additionally, we emphasize the promising prospects of targeting the gut microbiome as a means of diagnosing and treating this debilitating disease.

Unlike trees, shrubs (i.e., multiple-stemmed woody plants) do not need evenly spaced large diameter structural roots and thus can spread further per unit belowground biomass. We therefore hypothesized that compared to trees, shrubs respond more to asymmetric distributions of nutrients and reach nutrient-rich patches of soil faster and with less below-ground biomass. To test these hypotheses we planted individual seedlings of shrubs (Cornus racemosa, Rhus glabra, and Viburnum dentatum) and trees (Acer rubrum, Betula populifera, and Fraxinus americana) in the centers of sand-filled rectangular boxes. In one direction we created stepwise gradients of increasing soil nutrients with slow-release fertilizer; in the other direction no fertilizer was added. Seedlings were harvested when their first root reached the plexiglass-covered fertilized end of their box; time taken as well as above- and below-ground biomass by nutrient segment were determined. There were no consistent differences between the shrubs and trees in belowground architectural plasticity (= ratio of biomass in fertilized and unfertilized volumes of soil) or in the rate and efficiency of lateral growth. Interspecific variation appeared more related to edaphic characteristics of the native habitats than to growth form. The fastest and most efficient roots were produced by the shrub (R. glabra) and the tree (B. populifolia) that are characteristic of poor soils. Root foraging by R. glabra was also facilitated by rapid rhizomatous expansion. The tested shrubs and trees did not consistently differ in nutrient foraging efficiencies or rates but further study is warranted with larger plants and more species.

This essay critically discusses the integration of queer theory into human geography while emphasizing its ties to the principles of traditional geography. The need for a separate sub-discipline called queer geography is questioned. At the same time, legitimate concerns about possible departures from the fundamental goals of geography and the risks of anachronistic interpretations in applying modern concepts to historical landscapes are acknowledged. In this discourse, we strongly advocate for values such as freedom of speech, freedom of expression, and international human rights. It is important to emphasize that it is not the intent of this essay to denigrate campaigns for feminism or equality or to disparage the scholarship that emerges from the application of queer theory. On the contrary, we recognize the emergence of gender theories out of a need to advance social justice approaches. We believe that traditional human geography, itself, is capable of comprehensively examining space, time, and the complexity of human experience and offering workable solutions within its established framework. We therefore believe that the inclusion of queer theory can be harmoniously integrated into the contours of human geography, eliminating the need for a separate sub-discipline while preserving the integrity and purpose of the discipline.

Psoriasis is considered an immune-mediated disease involving the innate and adaptative immune system triggered by environmental risk factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, specially genome and epigenome-wide studies, have allowed a more sensitive study of the genetic and epigenetic mechanisms, allowing an enhanced understanding of its physiopathology and facilitating the development of new drugs. In this review, we aim to summarize the current evidence on genetic and epigenetic mechanisms of psoriasis.

Contrary to popular belief, we have known for many years that the endometrium is not a sterile environment and is considered to be a low-biomass milieu compared to the vagina. Numerous trials and studies have attempted to establish a valid sampling method and assess its physiological composition, but no consensus has been reached. Many factors such as ethnicity, age and inflammation, can influence the microbiome. Moreover, it possesses a higher alpha-diversity and therefore contains more diverse bacteria than the vagina. For instance, Lactobacillus has been shown to be a predominant genus in the vaginal microbiome of healthy women. Consequently, even if a majority of scientists postulate that a predominance of Lactobacillus inside the uterus improves reproductive outcomes, vaginal contamination by these bacteria during sampling cannot be ruled out. Certain pathologies, such as chronic endometritis, have been identified as inflammation perpetrators that hinder the embryo implantation process. This pro-inflammatory climate created by dysbiosis of the endometrial microbiota could induce secondary inflammatory mediators via Toll-like receptors, creating an environment conducive to the development of endometriosis and even promoting carcinogenesis. However, studies to this day have focused on small populations. In addition, there is no clearly defined healthy uterine composition yet. At most, only a few taxa have been identified as pathogenic. As sampling and analysis methods become increasingly precise, we can expect the endometrial microbiota to be incorporated into future diagnostic tools and treatments for women’s health.