The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally for the first time in order to integrate neurodegeneration within the energetics of the cancer acid-base conceptual frame. At all levels of study, molecular, biochemical, metabolic and clinical, the intimate nature of both processes appears to be opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranged original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) becomes an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Also within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth.

RNA silencing serves key roles in a multitude of cellular processes, including development, stress responses, metabolism, and maintenance of genome integrity. Dicer, Argonaute (AGO), double-stranded RNA binding (DRB), RNA-dependent RNA polymerase (RDR) and DNA-dependent RNA polymerases known as Pol IV and Pol V form core components to trigger RNA silencing. Common bean (Phaseolus vulgaris) is an important staple crop worldwide. In this study, we aimed to unravel the components of the RNA-guided silencing pathway in this non-model plant taking advantage of the availability of two genome assemblies of Andean and Meso-American origin. We identified six PvDCLs, thirteen PvAGOs, 10 PvDRB, 5 PvRDR, in both genotypes, suggesting no recent gene amplification or deletion after the gene pool separation. In addition, we identified one PvNRPD1 and one PvNRPE1 encoding the largest subunits of Pol IV and Pol V, respectively. These genes were categorized into subgroups based on phylogenetic analyses. Comprehensive analyses of gene structure, genomic localization and similarity among these genes were performed. Their expression patterns were investigated by means of expression models in different organs using online data and quantitative RT-PCR after pathogen infection. Several of the candidate genes were up-regulated after infection with the fungus Colletotrichum lindemuthianum.

Conclusions: Molecular classification could provide reliable supplementary information for evaluating prognostic and contribute to treatment option decision-making in EEC patients. Fertility-sparing treatment is not recommended for EEC patients with CNH and MSI-H. Furthermore, fertility-sparing treatment can be attempted in EEC patients with CHL, but regular follow-up should be carried out to early detection of EC relapse and prevention of disease progression.

A polymer inclusion membrane (PIM) composed of 50 wt% poly(vinylidenefluoride-co-hexafluoropropylene) (PVDF-HFP) as its base polymer, 40 wt% Aliquat® 336 as its extractant and 10 wt% dibutyl phthalate (DBP) as plasticizer provided efficient extraction of vanadium(V) from its sulfate solutions adjusted to pH 2.5. It was suggested that V(V) was extracted as VO2SO4− via an anion exchange mechanism. Quantitative back-extraction was achieved in a sulfuric acid solution (6 mol L-1) containing 1 v/v% of hydrogen peroxide. It was assumed that the back-extraction process involved the oxidation of VO2+ to VO(O2)+ by hydrogen peroxide. The newly developed PIM with the optimized composition mentioned above exhibited excellent selectivity for V(V) in the presence of metallic species present in digests of spent alumina hydrodesulfurization catalysts (i.e., Al(III), Co(II), Cu(II), Fe(III), Mn(II), and Ni(II)). The co-extraction of Mo(VI) with V(V) was eliminated by its selective extraction at pH 1.1. The optimized PIM was characterized by contact angle measurements, atomic-force microscopy (AFM), energy dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA)/derivatives thermogravimetric analysis (DTGA), and the stress-strain measurements.

Physical processes play important roles in controlling eutrophication and oligotrophication. In stratified lakes, internal waves can cause vertical transport of heat and nutrients without breaking the stratification, through boundary mixing events. Such is the case in tropical Valle de Bravo (VB) lake, where strong diurnal winds drive internal waves, boundary mixing and hypolimnetic warming during stratification periods. We monitored VB during 18 years (2001-2018) when important water-level fluctuations (WLF) occurred, affecting mixing and nutrient flux. Mean hypolimnetic temperature increase (0.06–1.04°C month-1) occurred in all the stratifications monitored. We analyzed temperature distributions and modeled the hypolimnion heat budget to assess vertical mixing between layers (26,618–140,526 m-3h-1), vertical diffusivity coefficient KZ (6.2x10-7–3.3x10-6 m2s-1) and vertical nutrient entrainment to epilimnion on monthly scale. Stability also varied as a function of WLF. Nutrient flux to the epilimnion ranged 0.36–5.99 mg m-2d-1 for soluble reactive phosphorus (SRP) and 5.8–97.1 mg m-2d-1 for dissolved inorganic nitrogen (DIN). During low water-level years, vertical nutrient fluxes increase and can account for up to >40% of the total external nutrients load to the lake. Vertical mixing changes related to WLF affect nutrient recycling, their flux to sediments, ecosystemic metabolic balance and planktonic composition of VB.

Background: The incidence of intravesical recurrence (IVR) following radical nephroureterectomy (RNU) is reported in up to 50% of patients with upper tract urothelial carcinoma (UTUC). It was suggested that preoperative diagnostic ureteroscopy (URS) could increase the IVR rate after RNU, however, the available data are often conflicting. Thus, in this systematic review and meta-analysis we sought to synthesize that available data for the impact of pre-RNU URS for UTUC on IVR and other oncological outcomes; Materials and methods: A systematic literature search of the PubMed, Embase and Cochrane Library databases was performed in June 2020. Cumulative analyses of hazard ratios (HRs) and their corresponding 95% confidence intervals (CI) were conducted. The primary endpoint was intravesical recurrence-free survival (IVRFS), with the secondary endpoints being cancer-specific survival (CSS), overall survival (OS), and metastasis-free survival (MFS); Results: Among a total of 5489 patients included in the sixteen selected papers, 2387 (43.4%) underwent diagnostic URS before RNU and 3102 (56.6%) did not. Pre-RNU diagnostic URS was significantly associated with worse IVRFS after RNU (HR=1.44, 95% CI: 1.29-1.61, p<0.001) than RNU alone. However, subgroup analysis including patients without biopsy during URS revealed no significant impact of diagnostic URS on IVRFS (HR=1.28, 95% CI: 0.90-1.80, p=0.16). The results of other analyses showed no significant differences in CSS (HR=0.94, p=0.63), OS (HR: 0.94, p=0.56), and MFS (HR: 0.91, p=0.37) between patients who underwent URS before RNU and those who did not. Conclusions: The results of this meta-analysis confirm that diagnostic URS prior to RNU is significantly associated with worse IVRFS, albeit with no concurrent impact on the other long-term survival outcomes. Our results indicate that URS has a negative impact on IVRFS only when combined with endoscopic biopsy. Future studies are warranted to assess the role of immediate postoperative intravesical chemotherapy in patients undergoing biopsy during URS for suspected UTUC.

The use of multi-gene panels for germline testing in breast cancer enables the estimation of cancer risk and guides risk-reducing management options for tested individuals and their family members. We performed an analysis in our clinical database to identify breast cancer patients undergoing genetic testing with positive reports. We reviewed positive results with respect to the different levels of information provided in the reports; risk estimation and management, cascade family testing, information from secondary findings and actionable information for treatment decision-making. A total of 415 positive test reports were identified with 57.1%, 18.1%, 10.8% and 13.5% of individuals having pathogenic/likely pathogenic variants in high (BRCA1, BRCA2, PALB2, PTEN, TP53), moderate (ATM, CHEK2, NBN), low (BARD1, BRIP1, CHEK2, MLH1, MSH2, MSH6, NF1, RAD51C) and with insufficient evidence for breast cancer risk genes (FANCA, FANCM, NBN, MRE11, PMS2, RAD50, RAD51B, XRCC2, MUTYH), respectively. 6.7% of individuals were double heterozygotes with two pathogenic variants. Germline findings in 92% of individuals are linked to evidence-based treatment information and receive risk estimates for predisposition to breast and/or other cancer types. The use of germline findings for treatment decision making expands the indication of genetic testing to include individuals that could benefit from targeted treatments.

Background: Spine shape parameters, such as leg length, kyphotic or lordotic angle, are influenced by low back pain. There is also evidence that the thoracolumbar fascia plays a role in such pa-thologies. This study examined the immediate effects of a myofascial release technique (MFR) on the thoracolumbar fascia and of an osteopathic treatment (OMT) on postural parameters in pa-tients with acute low back pain (aLBP). Methods: This study was a single-blind randomized pla-cebo-controlled trial. Seventy-one subjects (43.8 ± 10.5 years) suffering from aLBP were randomly and blinded assigned to three groups to be treated with MFR, OMT or a placebo intervention. Spinal shape parameters (functional leg length discrepancy (fLLD), kyphotic angle, lordotic an-gle) were measured before and after the intervention using video raster stereography. Results: Within the MFR group, fLLD reduced by 5.2 mm, p < 0.001 and kyphotic angle by 8.2 degrees, p < 0.001. Within the OMT group, fLLD reduced by 4.5 mm, p < 0.001 and kyphotic angle by 8.4 °, p = 0.007. Conclusion: MFR and OMT have an influence on fLLD and the kyphotic angle in aLBP patients. The interventions could have a regulating effect on the impaired neuromotor control of the lumbar muscles.

Given any sequence a = (an)n1 of positive real numbers and any set E of complex sequences, we write Ea for the set of all sequences y = (yn)n1 such that y=a = (yn=an)n1 2 E. In this paper, we use the spaces w1, w0 and w of strongly bounded, summable to zero and summable sequences, that are the sets of all sequences y such that ? n?1Pn k=1 jykj
n is bounded, tends to zero and such that y ? le 2 w0, for some scalar l, respectively, (cf. [24, 22]). These sets where used in the statistical convergence, (cf. [17, Chapter 4]). Then we deal with the solvability of each of the (SSIE) F
 E + F0x where E is a linear space of sequences, F = c0, c, `1, w0, w, or w1 and F0 = c0, c, or `1. For instance, the solvability of the (SSIE) w
 w0+s(c) x consists in determining the set of all sequences x = (xn)n1 2 U+ that satisfy the following statement. For every sequence y that satisfy the condition limn!1 n?1Pn k=1 jyk ? yk?1 ? lj = 0, there are two sequences u and v, with y = u+v such that limn!1 n?1Pn k=1 jukj = 0 and limn!1 (vn=xn) = L for some scalars l and L. These results extend those stated in [11, 12, 10].

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.

In this work epitaxial Au islands have been grown on epitaxial α-Fe2O3 thin film by pulsed laser deposition on SrTiO3(111) substrate. Both Au and α-Fe2O3 layer show an island-type growth with an average particle size of 40 and 62 nm, respectively. The crystallographic coupling of lattices is confirmed with a rotation of 30º between the in-plane crystallographic axes of α-Fe2O3(0001) structure and those of SrTiO3(111) substrate and between the in-plane crystallographic axes of Au(111) and those of α-Fe2O3(0001) structure. α-Fe2O3 is the only phase of iron oxide identified before and after its functionalization with Au nanoparticles. In addition, its structural character-istics are also preserved after Au deposition, with minor changes at short-range order. The func-tional character of the complex systems as gas sensor has been proven at room temperature. Con-ductance measurements of Au(111)/α-Fe2O3(0001)/ SrTiO3(111) system show that the incorpora-tion of Au islands on top of the α-Fe2O3(0001) layer induces an enhancement of the gas-sensing ac-tivity for CO and CH4 gas in comparison to a bare α-Fe2O3(0001) layer grown on SrTiO3(111).

(1) Background: Nursing homes’ preparedness in managing a public health crisis has been fragile, with effects on safety culture. The objective of this study was to assess nursing homes’ COVID-19 preparedness in Southern Portugal, including personnel’s work experiences during the pandemic. (2) Methods: We used a COVID-19 preparedness checklist to be completed by management teams, followed by follow-up calls to nursing homes. Thereafter, a survey to personnel was applied. Data analysis included descriptive statistics, exploratory factor analysis, and thematic analysis of open-end questions. (3) Results: In total, 71% (138/195) of eligible nursing homes returned the preparedness checklist. We conducted 83 follow-up calls and received 720 replies to the personnel survey. On average, 25% of nursing homes did not have an adequate decision-making structure to respond to the pandemic. Outbreak capacity and training were fragile areas among nursing homes’ contingency plans. We identified compliance with procedures and nonpunitive response to mistakes as fragile areas of safety culture, and teamwork as a strong safety area. (4) Conclusions: To strengthen how nursing homes cope with upcoming phases of the COVID-19 pandemic or future public health emergencies, nursing homes’ preparedness and safety culture should be fostered and closely monitored.

Glucose is the primary energy fuel used by the brain and is transported across the blood-brain barrier (BBB) by the glucose transporter type 1 and 2.[1] A GLUT1 genetic defect is responsible for glucose transporter type 1 deficiency syndrome (GLUT1DS). Patients with GLUT1DS may present with pharmaco-resistant epilepsy, developmental delay, microcephaly, and/or abnormal movements, with tremendous phenotypic variability. Diagnosis is made by the presence of specific clinical features, hypoglycorrhachia and an SLC2A1 gene mutation. Treatment with a ketogenic diet therapy (KDT) is the standard of care as it results in production of ketone bodies which can readily cross the BBB and provide an alternate energy source to the brain in the absence of glucose. KDTs have been shown to reduce seizures and abnormal movements in children diagnosed with GLUT1DS. However, little is known about the impact of KDT on cognitive function, seizures and movement disorders in adults newly diagnosed with GLUT1DS and started on a KDT in adulthood, or the appropriate ketogenic diet therapy to administer. This case report demonstrates the potential benefits of using a modified Atkins diet (MAD), a less restrictive ketogenic diet therapy on cognition, seizure control and motor function in an adult with newly-diagnosed GLUT1SD.

Higher-risk myelodysplastic syndrome (HR-MDS) has a poor prognosis in the absence of efficient therapy. The evaluation of new therapies in animal models of HR-MDS is hampered by the absence of accurate in vivo biomarkers of the disease. In this study we compared [18F]Fluoro-desoxyglucose Positron Emission Tomography (FDG-PET) and [18F]Fluoro-thymidine (FLT)-PET imaging for disease follow-up in a triple transgenic MMTVtTA/TetoBCL-2/MRP8NRASD12 mouse model of HR-MDS. Normal control FVB/N mice (G1,n=9) and HR-MDS mice (G2,n=12) underwent both FDG- and FLT-PET procedures at 2-day intervals, on a dedicated small animal device. Blood cell counting, BCL-2 and Mac-1hi/Gr-1lo expression measurements in blood were performed before each PET procedure. Visually, PET images of G2 mice demonstrated homogeneous FDG uptake in the whole skeleton similar to that observed in G1 mice, and abnormal FLT hot spots in bone marrow not observed in G1 mice. The intensity of FLT hot spots in bone marrow was higher in 3-months old G2 mice than in 2-months old G2 mice, concordant with a higher percentage of cells expressing Mac-1hi/Gr-1lo and lower platelets counts. We conclude that FLT-PET/CT imaging is a more valuable surrogate non-invasive quantitative marker of HR-MDS bone marrow involvement than FDG-PET/CT in our mouse model of HR-MDS.

Most smallscale farmers still use the traditional way of agricultural crop farming, and relay mostly use of chemical fertilizers (CF). Recently CF have become expensive and could in some way have a negative impact on soil quality after long term application. However, co-application of biogas slurry (BGS) with CF could help reduce farming costs while improving dry matter yields, grain yields, primary macronutrient uptake of (Nitrogen) N, (Phosphorus) P, (Potasium) K, (Calcium) Ca and (Magnesium) Mg and soil concentration of pH, (organic carbon) OC, N, P, K, Ca and Mg after crop harvest. The study was a field experiment conducted in 2016-2017 and 2017-2018 growing seasons. The field experiment was arranged in a randomized complete block design with four replicates. The treatments were based on percentages of recommended N rates of 120 kg N ha-1 for maize production. The BGS/CF treatments were (i) 0/0, (ii) 0/120, (iii) 24/96, (iv) 48/72, (v) 72/48, (vi) 96/24, (vii) 120/0 kg N ha-1. The spreading of the combination of BGS/CF treatments was performed by hand and incorporated into the top soil (0-10 cm) in each experimental plots. BGS/CF (48/72) treatment resulted into higher dry matter yield in 2016-2017, which was higher than all other treatment combinations, while in the 2017-2018 season, treatment of (0/120) resulted into higher dry matter than all other treatment combinations. The 48/72 and 0/120 treatments resulted into similar grain yield in 2016-2017 season which were higher than all other treatments. Treatments of 48/72, 72/48 and 120/0 had higher N, P, K, Ca and Mg uptake than 0/0, 0/120, 24/96 and 96/24 treatments in both seasons. Soil pH, total N, K, and Mg were high from the treatment of (120/0) than all other treatments in 2016-2017 while in the 2017-2018 season, treatment of (48/72) had higher OC, P and K after maize harvest. The findings of his study show that co-application of BGS/CF at 48/72 and 72/48 have maize yield benefits compared to the two resources, BGS/CF (120/0) and BGS/CF (0/120), applied separately in soil especially in the arid and semi-arid regions.

The aim of the study was to assess the chemical and biochemical composition of heat-treated dates palm fruits (Phoenix dactylifera L.) cultivated in Algeria and stored under Modified Atmosphere Packaging (MAP). In this research, fresh dates palm fruits at harvest (Phoenix dactylifera L.) have been subjected at heat treatment at 55 ± 2°C for 20 min in a ventilated oven. The samples were packed in specific Polyethylene Terephthalate packaging (PET) bags with a thickness of 2.5 μm under MAP condition. The effect of this heat treatment on date fruits quality was investigated during 5 months of storage at room temperature storage (22 ± 1°C of temperature with 75 to 80% of relative humidity (RH), and 10 ± 1°C with 85 to 90% of RH). Chemical and biochemical composition of the samples were studied. Results indicated that during storage the Brix degree, protein, and vitamin C content changed significantly (p&lt;0.05). The major change was observed for lipid values varied from about 0.02 to 0.06% at 10°C, and 0.04 to 0.07% at 22°C for samples not heat-treated unpacked after 5 months of storage, these results represent a highly significant difference (p&lt;0.01). Harvesting at Tamr stage followed by treating the fruits with heat disinfestation packed in MAP, and storing at 10 ± 1°C showed to be a promising method for maintaining dates fruits storage quality.

This study aims to develop a clinical trial to test the efficacy of a Mindfulness Based Stress Re-duction (MBSR) and Self Compassion (SC) Program on self-reported values of anxiety, depres-sion, and stress in parents of children with Autism Spectrum Disorder (ASD) in primary school, in order to assess their integration into the framework of community intervention programs in Spain. Methods: A brief 8-week training program using Mindfulness based intervention (MBSR) and self-compassion (SC) has been applied to ten parents from the Valencian ASD parents’. Partici-pants were assigned to two groups, both groups received the same treatment but at two different measurement moments. Depression, Anxiety, Stress, Satisfaction with Life and Mindful Atten-tion Awareness measurements were assessed, in all participants, in three testing moments. Results: Analysis of Variance results suggested that MBSR and SC training reduces stress and anxiety and increases Mindful Attention Awareness. No significant changes were found in Life Satisfaction measurements. Conclusions: The small number of participants prevents us from generalising the results found. More MBSR and SC clinical trials are needed in parents of ASD with results on anxiety, depression and stress in order to demonstrate the relevance of the inclusion of these programmes in community-based early intervention services.

Red mud is a hazardous waste of alumina industry that contains high amounts of iron, aluminum, titanium and REEs. One of the promising methods for the extraction of iron from red mud is car-bothermic reduction with the addition of sodium salts. This research focuses on the process of hy-drochloric high-pressure acid leaching using 10–20% HCl of two samples of non-magnetic tailings obtained by 60-minute carbothermic roasting of red mud at 1300 °C and the mixture of 84.6 wt. % of red mud and 15.4 wt. % Na2SO4 at 1150 °C, respectively, with subsequent magnetic separation of metallic iron. An influence of temperature, leaching duration, solid-to-liquid-ratio and acid con-centration on dissolution behavior of Al, Ti, Mg, Ca, Si, Fe, Na, La, Ce, Pr, Nd, Sc, Zr were studied. Based on the investigation of the obtained residues, mechanism of passing of valuable elements into the solution was proposed. It has shown that 90% Al, 91% Sc and above 80% of other REEs can be dissolved under optimal conditions; Ti can be extracted into the solution or the residue depending on the leaching temperature and acid concentration. Based on the research results, novel flowsheets for red mud treatment were developed.

Objective: To highlight opportunities for future nutrition intervention research within early childhood and education care (ECEC) settings, with a focus on generating evidence that has applicability to real-world policy and practice. Methods: An overview of opportunities to progress the field was developed by authors using a collaborative writing approach and informed by recent research in the field. The group developed a list of recommendations aligned with the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework. Pairs of authors drafted individual sections of the manuscript, which was then reviewed by a separate pair. The first and senior author consolidated all sections of the manuscript and sought critical input on draft iterations of the manuscript. Results: Interventions that employ digital platforms (Reach) in ECEC settings, as well as research in the family day care setting (Effectiveness) were identified as areas of opportunities. Research understanding the determinants of and effective strategies for dissemination (Adoption), implementation of nutrition programs, in addition to de-implementation (Implementation) of inappropriate nutrition practices, is warranted. For maintenance, there is a need to better understand sustainability and sustainment of interventions, in addition to undertaking policy-relevant research. Conclusions: The ECEC setting is prime for innovative and practical nutrition intervention research.

We aimed to explore university students’ perceptions and experiences of SARS-CoV-2 mass asymptomatic testing, social distancing and self-isolation during the COVID-19 pandemic. This qualitative study comprised of four rapid online focus groups conducted at a higher education institution in England during high alert (tier 2) national COVID-19 restrictions. Data were analysed thematically. Participants were purposively sampled university students (n = 25) representing a range of gender, age, living circumstances (on/off campus) and SARS-CoV-2 testing/self-isolation experiences. Six themes with 16 sub-themes emerged from the analysis of the qualitative data: ‘Term-time Experiences’, ‘Risk Perception and Worry’, ‘Engagement in Protective Behaviours’, ‘Openness to Testing’, ‘Barriers to Testing’ and ‘General Wellbeing’. Students described feeling safe on campus, believed most of their peers are adherent to protective behaviours and were positive towards asymptomatic testing in university settings. University communications about COVID-19 testing and social behaviours need to be timely and presented in a more inclusive way to reach groups of students who currently feel marginalised. Barriers to engagement with SARS-CoV-2 testing, social distancing and self-isolation were primarily associated with fear of the mental health impacts of self-isolation, including worry about how they will cope, high anxiety, low mood, guilt relating to impact on others and loneliness. Loneliness in students could be mitigated through increased intra-university communications and a focus on establishment of low COVID-risk social activities to help students build and enhance their social support networks. These findings are particularly pertinent in the context of mass asymptomatic testing programmes being implemented in educational settings and high numbers of students being required to self-isolate. Universities need to determine the support needs of students during self-isolation and prepare for the long-term impacts of the pandemic on student mental health and welfare support services.

Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate and severe asthmatics, we characterized the changes in expression of human coronavirus and influenza viral entry genes relative to sex, airway location and disease endotype. We found sexual dimorphism in expression of COVID-19 genes ACE2, TMPRSS2, TMPRSS4, and SLC6A19. ACE2 receptor downregulation occurred specifically in females in Th2 high asthma, while proteases broadly assisting coronavirus and influenza viral entry, TMPRSS2 and TMPRSS4, were highly upregulated in both sexes. Overall, changes in COVID-19 gene expression were specific to Th2 high molecular endotype of asthma, and different by asthma severity and airway location. The downregulation of ACE2 (COVID-19, SARS) and ANPEP (HCoV-229E) viral receptors correlated with loss of club and ciliated cells in Th2 high asthma, while the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) associated with an increase in goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype and changes in epithelial heterogeneity as factors underlying asthmatic susceptibility, or lack thereof, to COVID-19.

The aim of the study was to evaluate the effect of crude protein (CP) levels in concentrate and Sesbania grandiflora pod meal (SG) supplementations on feed intake, rumen fermentation, and methane (CH4) mitigation in Thai purebred beef cattle. Four cattle with 100 ± 5.0 kg body weight were used in this study. A 2 × 2 factorial experiment in a 4 × 4 Latin square design were conducted, in which factor A was the CP contents in concentrate of 14, and 16% of dry matter (DM) and factor B was the supplement contents of SG at 0.4% and 0.6% DM intake, respectively. The results showed that the CP contents in concentrate and SG had no interaction effect on intake, digestibility, ruminal ecologies, ruminal fermentation products, and nitrogen utilization. Increasing CP contents in concentrate did not influence DM intake and nutrients’ digestibility, and SG supplementation at 0.6% significantly (P<0.05) decreased CP digestibility. Increasing CP content to 16% increased significantly (P<0.05) the ruminal ammonia nitrogen (NH3-N) concentration while decreased significantly (P<0.05) the NH3-N concentration, protozoal number, and blood urea nitrogen (BUN) at 4 h post-feeding. The 0.6% supplementation of the SG increased significantly average total volatile fatty acids (VFAs) and propionate (C3) concentration while decreased significantly average acetate (C2), C2:C3 ratio, and CH4 production, which was 2.71% for C2, 13.17% for C2:C3 ratio, and 4.37% for CH4 production lower than 0.4% supplementation. Fecal nitrogen excretion was significantly decreased when supplemented with 0.6% of the SG. In conclusion, 0.6% of the SG supplementation showed a greater effect on intake, rumen manipulation, and CH4 mitigation and would recommend supplementation to a concentrate-based diet containing either 14% or 16% CP content.

In silico analysis is a promising approach for understanding biological events in complex diseases. Herein, we report an in silico analysis of the entire genome of virus ZikaSPH2015 strain, which was performed in order to identify the occurrence of specific motifs on genomic sequence of Zika Virus that is able to bind and therefore, sequester host’s Transcription Factors (TFs) as well as subsequently predict a possible interactions within host genome. Accordingly to obtained results of this original computational work-flow it is possible to hypothesize that these TFs Binding Motifs might be able to explain the complex and heterogeneous phenotype presentation in Zika Virus affected fe-tus/newborns, as well as the less severe condition in adults. Moreover, the proposed in silico protocol identified thirty three different TFs same as the distribution of TFBSs (Transcription Factor Binding Sites) on ZikaSPH2015 strain, potentially able to influence genes and pathways with biological functions confirming that this approach could find potential answers on disease pathogenesis.

Studies shows that, normal to high serum 25(OH)D status appears to have some beneficial influence on the incidence and severity of some, though not all, types of infections. However, studies with vitamin D supplementation on young children produced conflicting results with respect to the level of vitamin D deficiency among common medical illnesses among children. Method: A systematic review of literatures from PubMed, CINAHL, Web of science, global health and Google scholar electronic databases was conducted to assess the pooled prevalence of vitamin D deficiency among healthy and sick children in sub-Saharan Africa. The data was extracted by two authors independently using standard data extraction format and STATA Version 14 was used for analysis. The heterogeneity of the studies was assessed by using I2 test. A random-effects model was used to estimate the pooled prevalence among both healthy and sick children. Presence of publication bias was checked using Funnel plot and Egger's test. Result: A total of 1212 articles were identified by the total search of utilized data bases of which 13 papers fulfilled the inclusion criteria and accessible with full document. The meta-analysis revealed that the pooled prevalence of vitamin D deficiency among healthy children in this study was 50.06% (95%CI 33.46%, 66.67%) with mean serum vitamin D level of 41.06 nm/L (CI range from 23.82nm/L to 58.31nm/L). The pooled prevalence among the sick children was 39.36% (CI 20.57%, 57.96%) with 66.96nm/L (95% CI 54.81nm/L, 79.11nm/L) mean concentration of vitamin D. Comparing the two level of the pooled prevalence, the prevalence among the healthy children was significantly higher compared to those who have common medical illnesses and the pooled mean concentration among the sick was much higher than the mean concentration among healthy children. Conclusion: The level of pooled prevalence among both group of population was significantly of public health concern and the prevalence among the healthy children was much higher among the sick children implying the need for reconsideration of available recommendations for the prevention of vitamin D deficiency

Background and Objectives The socioeconomics working group of the European ME/CFS Research Network (EUROMENE) has conducted a review of the literature pertaining to GPs’ knowledge and understanding of ME/CFS. Materials and Methods A MEDLINE search was carried out. The papers identified were reviewed following the Synthesis Without Meta-analysis (SWiM) methodology, and were classified according to the focus of the enquiry (patients, GPs, database and medical record studies, evaluation of a training programme, and overview papers), and whether they were quantitative or qualitative in nature. Results 33 papers were identified in the MEDLINE search. The quantitative surveys of GPs demonstrated that a third to a half of all GPs did not accept ME/CFS as a genuine clinical entity and, even when they did, they lacked confidence in diagnosing or managing it. Patient surveys indicated that a similar proportion of patients was dissatisfied with the primary medical care they had received. These findings were consistent with the findings of the qualitative studies that were examined, and have changed little over several decades. Conclusions Lack of knowledge and understanding of ME/CFS among GPs is widespread, and the resultant diagnostic delays constitute a risk factor for severe and prolonged disease. Failure to diagnose ME/CFS renders problematic attempts to determine its prevalence, and hence its economic impact.

To our best knowledge this is the first study to assess and compare lower limb biomechanics and gait pattern between patients undergoing total knee arthroplasty with use of fixed-bearing medial-pivot and multi-radius design implants. Results of this study show that there were no statistical differences between both types of implants and even though there was significant improvement in patient-reported outcome and gait pattern, those parameters still differ significantly in comparison to healthy volunteers. The problem with dissatisfaction after operative treatment may not lay in the procedure itself, but many different factors may contribute to it. Next studies comparing other designs of implants, as well as proper rehabilitation protocol should be performed

Electrical remodelling as a result of the homeodomain transcription factor 2 (Pitx2)‐dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to Class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology. Experimentally calibrated populations of human atrial action potential (AP) models in both sinus rhythm (SR) and Pitx2-induced AF conditions were constructed by using two distinct models to represent morphological subtypes of AP. Multi-channel pharmacological effects of disopyramide, quinidine, and propafenone on ionic currents were considered. Simulated results showed that Pitx2-induced remodelling increased maximum upstroke velocity (dVdtmax) and conduction velocity (CV), and decreased AP duration (APD) and wavelength (WL). At the concentrations tested in this study, these AADs decreased dVdtmax and CV and prolonged APD in the setting of Pitx2-induced AF. Our findings of alterations in WL indicated that quinidine and disopyramide may be more effective against Pitx2-induced AF than propafenone by prolonging WL.

Ferric uptake regulation protein is a repressor protein which binds an AT rich region of DNA (the iron box). Fur binds as a dimer in a helix turn helix mode and it is activated by iron(II) and other divalent transition metal ions at elevated concentrations in a process to regulate the ion uptake. Each transition metal ion induces certain conformational changes to aid the Fur binding, both the N-terminal and C-terminal domains take part in binding to DNA in addition to His 88 and His 86 residues. The process is discussed in view of experimental reports. Fe(II), Mn(II) and Co(II) activate Fur to bind DNA experimentally but Zinc plays a structural role and does not activate Fur to bind DNA.

This study aims to develop a hybrid approach based on backpropagation Artificial Neural Network (ANN) and spatial analysis techniques to predict particulate matter of size 2.5 µm (PM2.5) from vehicle exhaust emissions in the State of California using Aerosol Optical Depth (AOD) and several climatic indicators (relative humidity, temperature, precipitation, and wind speed). The PM2.5 data were generated using Motor Vehicle Emission Simulator (MOVES), the measured climatic variables and AOD were obtained from the California Irrigation Management Information System (CIMIS), and NASA’s Moderate Resolution Spectroradiometer (MODIS). The data were resampled to a seasonal format and downscaled over grids of 10 by 10 to 150 by 150, and precipitation was determined to be the most important independent variable. Coefficient of determination ( ), Mean Absolute Percentage Error (MAPE), and Root Mean Square Error (RMSE) were used to assess the quality of the ANN prediction model. The model peaked at winter seasons with = 0.984, RMSE = 0.027, and MAPE = 25.311, whereas it had the lowest performance in summer with = 0.920, RMSE = 0.057, and MAPE = 65.214. These results indicate that the ANN model can accurately predict the PM2.5 concentration and can be used to forecast future trends.

In present work, the effects of bioflavonoids (ginkgetin and sciadopitysin) on stimulus-induced superoxide generation, tyrosyl and serine/threonine phosphorylation of proteins in human neutrophils, and the translocation of cytosolic compounds (p47phox, p67phox and Rac) to cell membrane were studied, which were isolated from the needles of Taxus media var. Hicksii. Meanwhile, three normal flavonoids (apigenin, quercetin and isoquercetin) were involved as contrasts. The results indicated that ginkgetin and sciadopitysin were capable of concentration-dependently inhibitory effects on the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), arachidonic acid (AA) and phorbol-12-myristate 13-acetate (PMA). And they also suppressed fMLP- and AA- induced tyrosyl or PMA-induced serine/threonine phosphorylation and the translocation of cytosolic compounds (p47phox, p67phox and Rac) to cell membrane, which were in parallel with the suppression of the stimulus-induced superoxide generation. The effect of these compounds on the radical-scavenging was also investigated. Ginkgetin and sciadopitysin did not show remarkable effect on DPPH radical-scavenging activity, and they didn’t display the radical-scavenging activity on superoxide anion generated by phenagine methoxysulfate (PMS)-NADH system. Apparently, ginkgetin and sciadopitysin had great performance in pharmacological value and they are worthy of in-depth study.

Introduction: Decreasing overweight and obesity prevalence requires precise data at sub-national levels to monitor progress and initiate interventions. This study aimed to estimate baseline age-standardized overweight prevalence at the lowest administrative units among women, 18 years and older, in seven African countries. The study aims are synonymous with indicator 14 of the global non-communicable disease monitoring framework. Methods: We used the most recent Demographic and Health Survey and administrative boundaries data from the GADM. Three Bayesian hierarchical models were fitted and model selection tests implemented. The age-standardized prevalence of overweight among adult women at national, first and second administrative levels were individually reported in each country in the form of maps and tables. Results: Substantial variation in the age-standardized prevalence of adult female overweight was noted across several second-level administrative units. In numerous locations in Tanzania, Nigeria and Zimbabwe, more than half of the adult female population were overweight and in one location in Tanzania, over 72% of the adult female population were overweight. These estimates were roughly twice the national level overweight prevalence and, in some cases, roughly 10 – 20% greater than the overweight prevalence in first-level administrative units. Conclusion: The observed overweight burden in subnational administrative units suggests the presence of an epidemic tantamount to the situation in more affluent economies. African countries lack the resources to effectively handle the fallout from such epidemic, therefore motivating the need for increased urgency in adopting WHO obesity-related intervention guidelines and implementing more rigorous studies to validate the study findings.

Astragalus bone is one of the most important fossil records as it can reconstruct the prehistoric life. Respectively, this study aims to model the body mass, habitat preference, and population density of prehistoric bovid Duboisia santeng (Dubois 1891) in eastern Java island in the early Pleistocene. The astragali from 9 specimens were used to estimate the body mass and population density. Likewise regression models are used to analyze the relationship between astragalus lateral length, width, and body mass compared to the astragalus of extant Bovid species. The result revealed the body mass average was 60.3 kg (95%CI: 58.9-61.7) and this indicates the D. santeng belongs to large herbivores. While the population density was estimated at about 5.39 individuals per km2 (95% CI: 3.18-7.6).

Acknowledging the diverse perceptions about science-religion relationships among learners who come from various religious environments may increase learners’ willingness to learn about evolution. This study is based on a zoology course designed for in-service teachers, which aimed to provide basic scientific knowledge about evolution using the Religious Cultural Competence in Evolution Education framework. The study explores whether learners who were resistant to evolution modify their attitudes and willingness to learn about it, and whether they develop respect toward learners who hold contradicting views. Using qualitative methods, the findings indicate that using the Religious Cultural Competence in Evolution Education framework increased some formerly "resistant" learners’ willingness to learn about evolution and include it in their own teaching, albeit in varying degrees and with various reservations. The learners appreciated the freedom to express their challenges concerning evolution learning or teaching and became more willing to respect opposing perspectives, even though not all the religious learners accepted evolution as an explanation for the development of organisms. This study has international implications for bridging the gap between science and religion, thus reducing resistance to learning and teaching about evolution.

The ascomycete Trichoderma atroviride is well known for its mycoparasitic lifestyle. Similar to other organisms, light is an important cue for T. atroviride. However, besides triggering of conidiation, little is known on the physiological responses of T. atroviride to light. In this study, we analyzed how cultivation under different light wavelengths and regimes impacted the behavior of two T. atroviride wild-type strains, IMI206040 and P1. While colony extension of both strains was slightly affected by light, massive differences in the photoconidation response between the two strains became evident. T. atroviride P1 colonies conidiated under all conditions tested including growth in complete darkness, while IMI206040 required white, blue or green light to trigger asexual reproduction. Interestingly, deletion of the stress-activated MAP kinase-encoding gene tmk3 abolished the ability of strain P1 to conidiate in red and yellow light as well as in darkness. Furthermore, light-dependent differences in the mycoparasitic activity of T. atroviride and in the biosynthesis of the secondary metabolite 6-pentyl--pyrone (6-PP) became evident. 6-PP production was highest upon dark incubation while light, especially exposure to white light as light/dark cycles, had an inhibitory effect on its biosynthesis. We conclude that the response of T. atroviride to light is strain-dependent and impacts differentiation, mycoparasitism and 6-PP production and hence should be considered in experiments testing the mycoparasitic activity of these fungi.

Substantial studies have focused on early detection of Alzheimer's disease (AD). Cerebral amyloid beta (Aβ), is hallmark of AD, can be observed in vivo via positron emission tomography imaging using amyloid tracer or cerebrospinal fluid assessment, but costly expensive. The current study aims to identify and compared predictability in magnetic resonance imaging (MRI) markers and neuropsychological markers to predict cerebral Aβ status in AD cohort using machine learning (ML) approaches. The predictability in candidate markers for cerebral Aβ status was examined by analyzing 724 participants from the ADNI-2 cohort. Demographic variables, structural MRI markers, and neuropsychological test scores were used as input in several ML algorithms to predict cerebral Aβ positivity. Out of five combination of candidate markers, neuropsychological markers with demographics showed the most cost-efficient result. A feature selection model could distinguish abnormal levels of Aβ with the predictability of 0.85, indicating the same performance with MRI-based models. The result has first to identified the predictability in MRI markers using ML approaches, and secondary to demonstrate the neuropsychological model with demographics could predict Aβ positivity, suggesting a more cost-efficient method for detecting cerebral Aβ status compared to MRI markers.

Heavy metals pollution in the Straits of Malacca warrants the development of rapid, simple and sensitive assays. Enzyme-based assays are excellent preliminary screening tool with near real-time potential. The heavy-metal assay based on the protease ficin was optimized for mercury detection using Response Surface Methodology. The inhibitive assay is based on ficin action on the substrate casein and residual casein is determined using the Coomassie dye-binding assay. Heavy metals strongly inhibit the hydrolysis. A Central Composite Design (CCD) was utilized to optimize detection. The results show a marked improvement for the concentration causing 50% inhibition (IC50) for mercury, silver and copper. Compared to One-factor-at-a-time (OFAT) optimization, RSM gave an improvement of IC50 from 0.060 (95% CI, 0.0300.080) to 0.017 (95% CI, 0.0160.019), from 0.098 (95% CI, 0.0770.127) to 0.028 (95% CI, 0.0220.037) and from 0.040 (95% CI, 0.035.045) to 0.023 (95% CI, 0.0200.027), for mercury, silver and copper, respectively. A near real-time monitoring of mercury concentration in the Straits of Malacca at one location in Port Klang was carried out over a 4-h interval for a total of 24 h and validated by instrumental analysis with the result revealing an absence of mercury pollution in the sampling site.

We identify the source of the Mw = 5.6 earthquake that hit west-central Epirus on March 21, 2020 00:49:52 UTC. We use synthetic aperture radar interferograms tied to one permanent Global Navigation Satellite System (GNSS) station (GARD). We model the source by inverting the INSAR displacement data. The inversion model suggests a shallow source on a low-angle fault (39°) dipping towards east with a centroid depth of 8.5 km. The seismic moment deduced from our model agrees with those of the published seismic moment tensors. This geometry is compatible with the Margariti thrust fault within the collision zone between Apulia and Eurasia. We also processed new GNSS data and estimate a total convergence rate between Apulia and Eurasia of 8.9 mm yr-1 , of which shortening of the crust between the Epirus coastal GNSS stations and station PAXO in the Ionian Sea is equivalent to ~ 50% of it or 4.6 mm yr−1. A 60-km wide deformation zone takes up nearly most of the convergence between Apulia-Eurasia, trending N318°E. Its central axis runs along the southwest coast of Corfu, along the northeast coast of Paxos, heading toward the northern extremity of the Lefkada island.

Shape memory alloys (SMAs) are increasingly used in the fields of aviation, automotive and biomedicine due to their unique properties. Nickel-Titanium (NiTi) alloy materials, which are one of the shape memory alloys, are among the most frequently used alloy materials. The shape memory and super elastic effects of NiTi alloys, high ductility and deformation hardening make it difficult to shape burr. An additional problem is the formation of a white layer during machining. In this study, surface milling operations were performed in dry cutting conditions with uncoated cutting tools with different nose radii. The processing parameters were determined based on the experience gained as a result of the preliminary tests. Tungsten carbide cutting tools with different nose radii (0.4mm and 0.8mm) were used for the milling operations. Milling was carried out at three different cutting speeds (20, 35, 50 m/min), feed rates (0.03, 0.07, 0.14 mm/tooth), and a constant axial cutting depth (0.7 mm). As a result of our experimental studies, the best tool life was found to be in 0.8 mm nose radius cutting tools at 20 m/min cutting speed and 0.03 mm/tooth feed rate (0.264 mm). The minimum average surface roughness was found after milling with 0.8 mm nose radius cutting tool at 20 m/min cutting speed and 0.03 mm/tooth feed rate (0.346 μm). It has been determined that increasing the cutting tool nose radius reduces both the flank wear over the cutting tool and the average surface roughness.

COVID-19 thromboembolic disease has brought all of us back to the drawing board. In COVID-19, pre-existing activated endothelium with increased Von Willebrand factor (VWF), low density lipoprotein (LDL) promoting “self-association” and “sticking” of long VWF strings to the vascular endothelial wall, suppressed ADAMTS13 cleavage of VWF, hypoxia induced upregulation and activation of VWF, fibrous network from neutrophil extracellular traps (NETs) with free DNA and histone, all appear to be initiating the thrombogenesis. Worsening complement activation, cytokine storm and resulting endothelial destruction, unregulated thrombogenesis leads to vascular occlusions and hypoxia. At this stage, the presence of abundant extracellular DNA, histone and -defensins appears worse than the SARS-CoV-2 itself. Previously observed in vitro mechanisms like histone “auto-activating” prothrombin, histone activated platelets generating thrombin without FXII, thrombin and plasmin cleaving complement C5 appears highly likely in COVID-19. Megakaryocytes are actively producing platelets in the lungs and appear to play a major role in thrombogenesis of COVID-19 raising suspicion of emperipolesis. This focused review is a compilation of my observations in relation to the pathophysiology of the intravascular environment, mainly in COVID-19 lungs. Pathophysiology based clinical trials are paramount in reducing morbidity and mortality in COVID-19.

As we know, the economy of science is to achieve optimal gains using scarce resources. Similarly, a problem where economies of the world are trying to resolve it is the issue of how to achieve an optimal economic contribution from limited tourism resources. According to the fact that global studies and statistics indicate that good governance is considered as the most important factor in developing countries and is considered as a strong governance of the development and as Information and Communication Technology (ICT) is effective in the interactions and economic and social exchanges of any society, it is the link between the tourism industry and the technology under the form of a robust tool and utilitarian in the tourism process called E-tourism can play a significant role. Therefore, the aim of this study was to investigate the effect of network Readiness Index and good governance on income from tourism industry. In this study, data and information about 14 selected countries were collected from Southwest Asia in the annual period of 2016-2011 in the form of panel data and the proposed model was used and estimated by the generalized torques system method. The estimated results of the model indicate that both hypotheses have a positive and significant impact on the amount of Network Readiness Index in the income of tourism industry, as well as the positive and significant effect of the index the amount of income from the tourism industry is confirmed, and their impact has been positive and significant, as well as exchange rate variables, revenue and commercial openness, also have a positive and significant effect on revenues of the tourism industry.

Subsurface drainage systems remove excess water from the soil profile thereby improving crop yields in poorly drained farmland. Knowledge of the position of the buried drain lines is important: 1) to improve understanding of leaching and offsite release of nutrients and pesticides, and 2) for the installation of a new set of drain lines between the old ones for enhanced soil water removal efficiency. Traditional methods of drainage mapping involve the use of tile probes and trenching equipment. While these can be effective, they are also time-consuming, labor-intensive, and invasive, thereby entailing an inherent risk of damaging the drainpipes. Non-invasive geophysical soil sensors provide a potential alternative solution. Previous research has focused on the use of time-domain ground penetrating radar (GPR), with variable success depending on local soil and hydrological conditions and the central frequency of the specific equipment employed. The objectives of this study were 1) to test the use of a stepped-frequency continuous wave (SFCW) 3D-GPR (GeoScope Mk IV 3D-Radar with DXG1820 antenna array) for subsurface drainage mapping, and 2) to evaluate the performance of a 3D-GPR with the use of a single-frequency multi-receiver electromagnetic induction (EMI) sensor (DUALEM) in-combination. The 3D-GPR system offers more flexibility for application to different (sub)surface conditions due to the coverage of wide frequency bandwidth. The EMI sensor simultaneously provides information about the apparent electrical conductivity (EC_a) for different soil volumes, corresponding to different depths. This sensor combination was evaluated on twelve different study sites with various soil types with textures ranging from sand to clay till. While the 3-D GPR showed a high success rate in finding the drainpipes at five sites (sandy, sandy loam, loamy sand, and organic topsoils), the results at the other seven sites were less successful due to limited penetration depth (PD) of the 3D-GPR signal. The results suggest that the electrical conductivity estimates produced by the inversion of EC_a data measured by the DUALEM sensor could be a useful proxy to explain the success achieved by the 3D-GPR in finding the drain lines. The high attenuation of electromagnetic waves in highly conductive media limiting the PD of the 3D-GPR can explain the findings obtained in this research.

In the wake of the novel coronavirus, SARS-CoV-19, the world has undergone a critical situation in which grave threats to global public health emerged. Among human populations across the planet, travel restraints, border enforcement measures, quarantine, and isolation provisions were implemented in an attempt to control and limit the spread of the contagion. Decisions on how to implement and enforce various control policies should be determined based on available real-world evidence and theoretical prediction. In this study, we propose a novel exportation- importation epidemic model associated with the quarantine and hospitalized-isolation policies by considering the two-body system: a source country of a contagious disease and a neighboring country that is initially disease-free. The model is first applied to the original COVID-19 data in China, Italy, and the Republic of Korea (ROK) and observed through consistent fitting results with equivalent goodness-of-fit. Then, the data are estimated per the fitting parameters. Driven by these parametric settings and considering the normalized population, the numerical analysis, and epidemiological exploration, this work further elucidates the substantial impact of quarantine policies, healthcare facilities, and the public counter-compliance effect.

According to current literature and preliminary data, hydroxychloroquine (HCQ) seems potentially effective in the treatment of patients with Covid-19 pneumonia. The concentrations of HCQ in lungs might be well above that of plasma. Most likely, this property of HCQ provides effective drug concentrations in lungs. HCQ has a gradual onset of action in the treatment of rheumatic diseases. This could be valid for the treatment of Covid-19 pneumonia. It was suggested that regular HCQ administration in animals for a certain time might result in gradual accumulation of HCQ in tissues. Reduced perfusion, somewhat distorted architecture of lung tissue, edema and, suggested gradual accumulation of HCQ in lung tissue might cause reduced HCQ concentrations in pneumonic areas of the lungs in Covid-19 pneumonia. Patients with Covid-19 pneumonia and extensive lung involvement might have less HCQ concentrations in their lungs than patients having limited lung involvement. Furthermore, patients with Covid-19 pneumonia and extensive lung involvement might have more viral load than patients having limited lung involvement. That’s why treatment of patients with advanced Covid-19 pneumonia using HCQ might result in treatment failure, however HCQ might be effective in the treatment of patients with mild and moderate Covid-19 pneumonia. Using HCQ in Covid-19 pneumonia prophylaxis seems logical since providing enough accumulation of HCQ in the healthy lungs, before the arrival of the SARS-CoV-2 virus, might prevent Covid-19 pneumonia. However, the purpose of this paper is not to recommend using or not using HCQ for the treatment or for the prophylaxis of Covid-19 pneumonia. The purpose of this paper is only to try to bring a new perspective on the role of HCQ in the treatment or in the prophylaxis of Covid-19 pneumonia. This paper proposes only hypotheses, which need further researches to be confirmed.

In December 2019 a novel human-infecting coronavirus, named SARS-CoV-2 has been recognized to cause a pneumonia epidemic outbreak with different degree of severity in Wuhan, Hubei Province in China. Since then this epidemic spread worldwide an in the last week Europe and Italy also have been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, SARS-CoV-2 has been isolated only recently, therefore a few studies concerning its immunopathogenesis and tretament are available. Therefore, on the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82% of genome homology) and that its characteristics, like the modality of transmission, the route of infection, the organ localization, the type of the immune response it may stimulate, the morbidity and the mortality rates are still poor-known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: 1) the structure of SARS CoV-2 and SARS CoV; 2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the Cytokine Release Syndrome; 3) the modification of the cell microRNome and of the immune response in patients with SARS infection; 4) the possible role of some liposoluble compounds (such as vitamin A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the most important nut crops both in terms of area and production. Over the last decades, an important part of the beneficial actions for health associated with their consumption was attributed to the phenolic compounds, mainly accumulated in almond skin. Interestingly, after cold-pressed oil extraction, most of these antioxidant phenolic compounds are retained in a skin-enriched by-product, so-called almond cold-pressed oil residue. In Morocco, ranked fifth producer in the world, this production generates an important part of this valuable byproduct. In the present study, using a multivariate Box-Behnken design, an ultrasound-assisted extraction (USAE) method of phenolic compounds from Moroccan almond cold-pressed oil residue was developed and validated. Response surface methodology resulted in the optimal extraction conditions: the use of aqueous EtOH 53.0% (v/v) as green solvent, applying an US frequency of 27.0 kHz for an extraction duration of 29.4 min. The present USAE allowed substantial gains in terms of extraction efficiency compared to conventional heat reflux extraction. Applied to 3 different local Beldi genotypes growing at 3 different experimental sites, the optimal USAE conditions led to a total phenolic content of 13.86 mg/g dry weight (DW). HPLC analysis revealed that the main phenolic compounds from this valuable byproduct were: chlorogenic acid followed by protocatechuic acid, p-hydrobenzoic acid and p-coumaric acid. The accumulation of these phenolic compounds appeared to be more dependent on the genetic background than on the environmental impact here represented by the 3 experimental culture sites. Both in vitro cell free and cellular antioxidant assays were performed, and revealed the great potential of these extracts. In particular, correlation analysis evidenced the prominent roles of chlorogenic acid, protocatechuic acid and p-hydrobenzoic acid. To summarize, the USAE method presented here is a quick, green, simple and efficient validated USAE for the possible valorization of antioxidant phenolic compounds from Moroccan almond cold-Pressed oil residues, making it possible to generate extracts with attractive antioxidant activities for future nutraceutical and/or cosmetic applications.

Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n=42) and European American (EA, n=33) women. Using The Cancer Genome Atlas (TCGA) approaches, we analyzed RNA sequencing data to measure changes in genome-wide expression and used logistic regressions to identify ancestry-associated gene expression signatures. To determine global ancestry, GATK best practices were followed for variant calling, and used the 1000 Genomes Project as reference data. We identified >150 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like 2 tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated.

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global threat to human health and disease risk increases with advancing age. The regulation of the ACE2 gene that codes for COVID-19 host receptor ACE2 has been shown to be under epigenetic regulation. Here, we examined whether intensive DNA methylation profiling of the ACE2 gene differed by human host tissue and cell type, gender, and age. Results: Accessing four public datasets, we observed unique human cell-type-specific ACE2 DNA methylation patterns. In human lung tissues, gender differences in DNA methylation at 2 sites related to the ACE2 gene were identified. Further, in freshly isolated airway epithelial cells, DNA methylation near the transcription start site of the ACE2 gene associated with biological age. Conclusion: Epigenetic profiling of host tissue may permit discovery of age and gender-related potential risk factors for COVID-19. How perturbations in ACE2 methylation relate to clinical severity across the ages and gender needs to be determined to guide screening tools and potential epigenetic modification targeting to alleviate COVID-19 morbidity in the elderly.

The spike protein of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2), which is mediated by the receptor binding domain (RBD) of the spike protein. Recently, an analysis based on decade-long structural studies of SARS was reported to illustrate with atomic-level details receptor recognition by the novel coronavirus from Wuhan, i.e., 2019-nCoV. Here, this article reports a comprehensive set of structural electrostatic analysis of all SARS-CoV spike protein RBD-related structures as of February 13, 2020, aiming at identifying the electrostatic hot spots for SARS-CoV spike protein to be complexed with ACE2 and its neutralizing antibodies. First, this article identified a structural action mechanism of the F26G19 antibody (of SARS-CoV spike protein), where its Asp56 residue binds to the Arg426 of the SARS-CoV spike protein RBD against the formation of the interfacial Arg426-Glu329 salt bridges between ACE2 and the SARS-CoV spike protein RBD. Second, a hypothesis is reported that a pair of electrostatic clips exist at the interface between ACE2 and the SARS-CoV spike protein RBD, including both Arg426-Glu329 and His445-Glu23-Lys447 salt bridges. Last, this article reports a structurally identified interfacial Glu35-Arg479 salt bridge which helps stabilize the complex structure of ACE2 and the SARS-CoV spike protein RBD. Overall, the structurally identified electrostatic hot spots reported here may be useful for the design of SARS-CoV-neutralizing antibodies in future.

This paper examines the influence of the petrographic characteristics of sandstones from Klepa Nafpaktias (Greece) on their suitability in construction (concrete) and energy storage applications. For this scope, ten sandstones were collected in order to study their petrographic characteristics using petrographic microscope and a GIS software as well as their basic physical, mechanical and physicochemical properties. Concrete specimens (C25/30) were produced with constant volume proportions, workability, mixing and curing conditions using different sizes of each aggregate type. Aggregates were mixed both in dry and water saturated states in concrete. Three different types of sandstone aggregates were examined and classified in three district groups according to their physicomechanical properties, petrographic characteristics and surface texture. The classification in groups after the concrete compressive strength test (UCS) verified the initial classification in the same three groups relative to their grain size from coarse to fine grained. As the grain size decreases their physicomechanical and physicochemical properties are getting better resulting in higher concrete strength values (25 to 32 MPa). Furthermore, the proposed ratio C/A (crystals/ mm2) seems to influence the aggregate properties which constitute critical factors for the final concrete strength, presenting the more fine grained sandstones as the most suitable for concrete aggregates. Concerning the use of Klepa Nafpaktias sandstones as potential energy reservoirs, the studied sandstones have the appropriate physicochemical properties for the implementation of a financially feasible CO₂ capture and storage scenario.

Grazing exclusion has been proved to be one of the main measures for rehabilitating degraded arid steppes. However, the effect of this management practice on plant species diversity and composition is ambiguous, specially under prolonged droughts. Concurrently considering the responses of individual plant species, diversity of functional groups, α-diversity, and β-diversity (and its components) may be crucial to the holistic understanding of grazing exclusion effects on plant communities under drought conditions. Here, we investigated the response of these diversity measures to short-term sheep exclusion under severe drought episode in arid steppes of Alfa-grass (Stipa tenacissima) with a long evolutionary history of livestock grazing. Individual species responses were tested based on species occurrence and abundance in either grazed or grazing-excluded steppes, in addition, we used indicator species analysis to assess the strength of the association between plant species and management type. Likewise, α-diversity, abundance- and incidence-based β-diversity, as well as the functional groups’ diversities were quantified using Hill Numbers and compared between the two management types. Sheep grazing exclusion enabled the recovery of various Alfa-steppe indicator species and improved the size of regional species pool, overall α-diversity, and the diversity of therophytes. This management practice decreased the abundance-based β-diversity and the nestedness-resultant fraction of the incidence-based β-diversity at the local scale, while at the landscape scale increased the abundance-based β-diversity and its balanced variation fraction and reduced the incidence-based β-diversity and its turnover component. Furthermore, protection from grazing altered β-diversities scaling patterns by maintaining higher balanced variation in species abundance at large spatial scale and greater abundance-gradient in species composition at the fine-scale. Our results suggest that the implementation of short-term grazing exclusion in degraded arid steppes would be the appropriate management practice for vegetation restoration and plant diversity conservation during prolonged drought periods.

Background: This retrospective study evaluates the survival effects of metronomic maintenance therapy with fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. Methods: We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockdout of EGFR gene, we analyzed the capacities of cell proliferation and migration. Results: Postoperative relapse and mortality were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent predictive factor of postoperative relapse and mortality, as well as a prognostic factor of disease-free survival and overall survival. The significant differences of survival between the two groups were only observed in patients with positive EGFR expression. Conclusions: The present study suggested EGFR expression as the prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. By analyzing EGFR expression, we can identify the potential candidates with optimal survival benefit from metronomic maintenance therapy in patients with stage III CRC.

The i-4-1-Health project is a One Health project on the prevalence and spread of antimicrobial resistance in the human and veterinary domain in the Dutch-Belgian cross-border region. This paper describes the main components of the laboratory protocol that was developed to standardise the microbiological methods used for the detection of intestinal carriage of highly-resistant microorganisms.

The human innate immune response to the pore-forming toxin of Vibrio cholerae VCC, is currently under study. Here, in vitro studies on a human macrophage cell line (THP-1), helped explore the activated pathways involved on the onset the innate immune response towards the cytotoxin. The secreted monomeric 65 KDa form interacts with mature macrophages in pg/ml concentrations, determined by dose response experiments after treatments under 1 h. Non vacuolating concentrations (pg/ml) were applied to the cells; immunoblots revealed activation of MAPKs: early overexpression of p38 and ERK. Cell lysis by release of lactate dehydrogenase (LDH) was not apparent in the first hour, nonetheless it was positive after 24 h. Finally, to discern whether the VCC stimulates transcriptional activators via MAPKs pathway, NF-κB and AP-1 were studied by real time quantitation. Increased expression of p50 (NF-κB), cJun and cFos (AP-1) was observed. Given that NF-κB is the transcription factor initiating inflammation of innate immune response and in turn, AP-1 is responsible for cell surviving response, results from this study lead us to conclude that VCC in vitro treatments, induce a pro-inflammatory and a surviving response, in less than one hour on activated macrophages.

After globalization, South Korea’s retail landscape has been saturated with large-scale, corporate type retails. However, recently new commercial districts composed of small retail units are returning and bringing about a change. This study sought to take note of this phenomenon and identify its features and meanings from the perspective of urban ecology. A density-distribution analysis was conducted to investigate how they were forms, and an analysis of traces on the Internet and an analysis on the types of businesses were done to identify sociocultural characteristics. Results showed that they had similar type of locations and growth patterns, that they harmoniously congregated in a form of smaller-individual stores, and that their use of similar names for their stores had an impact of branding their entire districts. It was also noted that a shared culture through social networking services served as a growth boost for their unfavorable location. The spontaneous formation of such commercial districts can be an outcome of an urban ecological process geared toward blank niches burgeoning in the current retail structure of Korea. The causes and conditions found in the cases reveal meaningful policy implications for cities facing the same urban crisis diversity.

Warm cloud-precipitation plays a vital role in the hydrological cycle, weather, and climate. Comprehensive observation and study of warm cloud-precipitation can advance our understanding of the internal physical processes and provide valuable information for developing the numerical models. This paper mainly focused on a study of characteristics of warm cloud-precipitation in South China during the pre-flood season using datasets observed from a Ka-band cloud radar, laser ceilometer and disdrometer. Eighteen kinds of quantities from these three instruments were used to precisely elucidate the distribution, diurnal variation, vertical structure, and physical property of warm cloud-precipitation. The results showed that the occurrence of aloft cloud-precipitation decreased with the increase of height, and most of the hydrometeors were distributed below 2 km. During the observation period, the ground rainfall mainly came from light precipitation; however, short-time and sharp showers contributed to the majority of rain amounts. Most of the cloud layers were single-layer, with base heights below 2.2 km, thickness thinner than 2.1 km, and top heights within 0.6-4.2 km. Warm cloud-precipitation owned certain diurnal variations, with a rising trend of cloud base heights in the afternoon and midnight. During 0230-1100, 1200-1800, and 2100-2300, the convections were relatively active with higher cloud tops, thicker cloud thickness, and higher rainfall occurrences. Separation and statistical results of cloud and precipitation indicated that they owned different vertical structures and physical properties, exhibiting different value ranges and changes of radar reflectivity, vertical air motion, particle size, number concentration, liquid water, and rain rate at different height levels. The particle size distributions of cloud and precipitation both were exponential. Radar-derived raindrop size distribution was very coherent with the ground measurement when the reflectivity of precipitation was within 10-20 dBZ. However, for other reflectivity regimes, instrument sensitivity, sampling height, attenuation, and non-precipitating weak targets can affect the comparison.

Background: Active case finding for TB was implemented in selected sixty high TB burden wards of Kolkata, India. Community volunteers called TOUCH agents (TAs) identified and referred presumptive TB patients (PTBPs) to health facilities for TB diagnosis and treatment. We aimed to describe the ‘care cascade’ of PTBPs identified during July to December, 2018 and to explore the reasons for attrition as perceived by TAs and PTBPs. Methods: An explanatory mixed methods study with quantitative phase of cohort study using routinely collected data followed by descriptive qualitative study with in-depth interviews was conducted. Results: Of the 3, 86,242 individuals enumerated, 1132 (0.3%) PTBPs were identified. Only 713 (63.0%) PTBPs visited referred facility for TB diagnosis. TB was diagnosed in 177 (24.8%) and the number needed to screen for one TB was 2,183 individuals. The potential reasons for low yield were stigma and apprehension about TB, distrust about TA, wage loss for attending health facilities and substance abuse among PTBPs. Conclusion: The yield of ACF was suboptimal with low PTBP identification rate and high attrition rate. Interviewing each individual for symptoms of TB and supporting PTBPs for diagnosis through sputum collection and transport can be adopted to improve the yield.

Background: Recently we demonstrated that Astragalus polysaccharide (PG2), the active ingredient in dried roots of astragalus membranaceus, ameliorates cancer symptom clusters and improve quality of life (QoL) in patients with metastatic disease by modulating inflammatory cascade, against the background that inflammatory cells including macrophages, dendritic cells (DCs), and cytotoxic T lymphocytes (CTLs) in tumor initiation, metastasis, and progression. Nevertheless, the role of PG2 in the modulation of anticancer immunogenicity and therapeutic response remains relatively underexplored and unclear. Purpose: The present study investigates how and to what extent PG2 modulates cellular and biochemical components of the inflammatory cascade, enhance anticancer immunity, and the therapeutic implication of same in patients with lung cancer. Methods and Results: Herein, we demonstrated that PG2 significantly increased the M1/M2 macrophage polarization ratio in non-small cell carcinoma (NSCLC) H441 and H1299 cells. This PG2-induced preferential pharmacologic up-regulation of tumoral M1 population in vitro, positively correlated with the downregulation of tumor-promoting IL-6 and IL-10 expression in NSCLC cell-conditioned medium, with concomitant marked inhibition of cell proliferation, clonogenicity and tumorsphere formation. Our ex vivo results, using clinical sample from our NSCLC cohort, demonstrated that PG2 also promoted the functional maturation of DCs with consequent enhancement of T cell-mediated anticancer immune responses. Consistent with the in vitro and ex vivo results, our in vivo studies showed that mice treated with PG2 exhibited significant time-dependent depletion of the tumor-associated M2 population, synergistically enhanced the anti-M2-based anticancer effect of cisplatin, and inhibition of xenograft tumor growth in the NSCLC mice models. Moreover, in the presence of PG2, cisplatin-associated dyscresia and weight-loss was markedly suppressed. Conclusion: These results do indicate a therapeutically-relevant role for PG2 in modulating the M1/M2 macrophage pool, facilitating DC maturation, and synergistically enhancing the anticancer effect of conventional chemotherapeutic agent, cisplatin; thus laying the foundation for further exploration of the curative relevance of PG2 as surrogate immunotherapy and/or clinical feasibility of its use for maintenance therapy in patients with lung cancer.

Molecular hydrogen (H2) has been shown to have antioxidant and anti-inflammatory activities that may reduce the development and progression of many diseases. In this study, Hydrogen-rich water (HRW) was obtained by reacting hybrid magnesium-carbon hydrogen storage materials with water. Then the effects of intake of HRW on the activities of xenobiotic-metabolizing enzymes, membrane transporters, and oxidative stress in rats were investigated. Rats were given HRW ad libitum for 4 weeks. Results showed that intake of HRW had no significant effect on the activities of various cytochrome P450 (CYP) enzymes (CYP1A1, 1A2, 2B, 2C, 2D, 2E1, 3A, 4A), glutathione-S-transferase and UDP-glucuronosyltransferase. Except for a slight lower plasma glucose concentration, intake of HRW had no effect on other plasma biochemical parameters in rats. P-Glycoprotein and multidrug resistance-associated protein (Mrp)2 protein expressions in liver were elevated after intake of HRW. However, HRW had no significant effects on glutathione, glutathione peroxidase, or lipid peroxidation in liver. Results from this study suggest that consumption of HRW may not affect xenobiotic metabolism or oxidative stress in liver. However, intake of HRW may increase the efflux of xenobiotics or toxic substances from the liver into bile by enhancing the expression of p-glycoprotein and Mrp2 protein.

The study presents a comparative approach between response surface methodology (RSM) and hybridized, genetic algorithm artificial neural network (GA-ANN) in predicting the water absorption, compressive strength, flexural strength split tensile strength and slump for steel fiber reinforced concrete. The effect of process variables such as aspect ratio, water cement ratio and cement content were investigated using the central composite design of response surface methodology. This same experimental design was used in training the hybrid-training approach of artificial neural network. The predicting ability of both methodologies were compared using the root mean sqaured error (RMSE), mean absolute error (MAE), model predictive error (MPE) and absolute average deviation (AAD). The RSM model was found more accurate in prediction compared to hybrid GA-ANN.

Stabilized un-doped Zinc Telluride (ZnTe) thin films were grown on glass substrates under vacuum using closed space sublimation (CSS) technique. A dilute copper nitrate solution (0.1/100 ml) was prepared for copper doping known as ion exchange process in the matrix of ZnTe thin film. The reproducible polycrystalline cubic structure of undoped and Cu doped ZnTe thin films with preferred orientation (111) was confirmed by X-rays diffraction (XRD) technique. Lattice parameter analyses verified the expansion of unit cell volume after incorporation of Cu species into ZnTe thin films samples. The micrographs of scanning electron microscopy (SEM) were used to measure the variation in crystal sizes of samples. The energy dispersive X-rays was used to validate the elemental composition of undoped and Cu-doped ZnTe thin films. The bandgap energy 2.24 eV of ZnTe thin film decreased after doping Cu to 2.20 eV may be due to the introduction of acceptors states near to valance band. Optical studies showed that refractive index was measured from 2.18 to 3.24 whereas thicknesses varied between 220 nm to 320 nm for un-doped and Cu doped ZnTe thin film respectively using Swanepoel model. The oxidation states of Zn⁺², Te⁺² and Cu⁺¹ through high resolution X-ray photoelectron spectroscopy (XPS) analyses was observed. The resistivity of thin films changed from ~10⁷ Ω-cm for undoped ZnTe to ~1 Ω-cm for Cu-doped ZnTe thin film, whereas p-type carrier concentration increased from to respectively. These results predicted that Cu-doped ZnTe thin film can be used as an ideal, efficient and stable intermediate layer between metallic and absorber back contact for the heterojunction thin film solar cell technology.

This study evaluated the microbial safety of vended boiled, pasteurized and UHT milk sold in Nakawa, Kampala-Uganda. 15 milk samples were analyzed; 2 samples had Salmonella, 5 had S. aureus with a count of 1.66 0.02 log₁₀CFU/ml. E. coli was detected in 8 samples with 1.0 0.02 to 3.0 0.01log₁₀CFU/ml count. A high load of 3.0 CFU/ml was obtained in 3 samples with E. coli. Four E. coli positive samples had a contamination load of 2.0 0.015log₁₀ CFU/ml of which one was pasteurized milk. Only a pasteurized milk showed a low E. coli load at 1.0 0.02log₁₀ CFU/ml. All UHT milk had no microbial contamination. Both boiled and pasteurized milk had Salmonella, S. aureus and E. coli in levels above the set threshold limits. Milk consumers in Nakawa stand a potential public health risk of food poisoning reflected by presence of Salmonella, S. aureus and E. coli in some milk sold in the area.

Oleuropein (Ole), a secoiridoid glucoside present in Olea europaea leaves, gained the interest of many scientists thanks to its several biological properties, including the anticancer one. We verified whether Ole might potentiate cytotoxicity of conventional drugs used to treat melanoma, disclosing new potential therapeutic strategy. We tested the cytotoxic action of Ole alone or in combination with chemotherapeutics on A375 human melanoma cells. We found that Ole was able, at a dose of 500 μM, to stimulate apoptosis in melanoma cells, while at a non-toxic dose of 250 μM, it affected cell proliferation and induced the downregulation of pAKT/pS6 pathway. 250 μM Ole did not potentiate the effect of Vemurafenib (PLX4032), but it succeeded in increase the cytotoxic effect of Dacarbazine (DTIC). The mayor effect was found in the association between Ole and Everolimus (RAD001), also on PLX4032-resistant BRAF melanoma cells, possibly cooperating in the inhibition of pAKT/pS6 pathway. Of interest, an olive leaf extract enriched in equimolar Ole was more effective and able to further improve DTIC and, particularly, RAD001 efficacy on BRAF melanoma cells than Ole alone. Therefore, Ole represents a natural product able to potentiate a wide array of chemotherapeutics against BRAF melanoma cells affecting pAKT/pS6 pathway.

Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe neurological disorders are reported. Hence, it is important to characterize the interactions between HEV and its host. Here, we investigated the ability of the non-structural polyprotein encoded by the first open reading frame (ORF1) of HEV to modulate the host early antiviral response and in particular the type I interferon (IFN-I) system. We found that the amino-terminal region of HEV-3 ORF1 (MetPCP), containing a putative methyltransferase (Met) and a papain-like cysteine protease (PCP) functional domain, inhibited IFN-stimulated response element (ISRE) promoter activation and the expression of several IFN-stimulated genes (ISGs) in response to IFN-I. We showed that the MetPCP domain interfered with the Janus kinase (JAK)/signal transducer and activator of transcription protein (STAT) signalling pathway by inhibiting STAT1 nuclear translocation and phosphorylation after IFN-I treatment. By contrast, MetPCP had no effect on STAT2 phosphorylation and a limited impact on the activation of the JAK/STAT pathway after IFN-II stimulation. This inhibitory function seemed to be genotype-dependent as MetPCP from HEV-1 had no significant effect on the JAK/STAT pathway. Overall, this study provides evidence that the predicted MetPCP domain of HEV ORF1 antagonises STAT1 activation to modulate the IFN response.

Natural product especially secondary metabolites that produced by plants under the stressed condition shown to have a different pharmacological impact. Aeluropus lagopoides is one of the typical halophyte plants survivals under stressed conditions. It has been used for wound healing and as a painkiller. The bioactivity and the chemical composition of this plant have poorly investigated. Consequently, chemical components of A. lagopoides leaves were extracted using hexane (nonpolar), ethyl acetate (semi-polar), n-butanol (polar) to extract the most extensive variety of metabolites. The cytotoxicity and anticancer impact of extracted secondary metabolites evaluated against breast (MCF-7), colon (HCT-116), and liver (HepG2) cancer cell lines using SRB test. The mechanism of action verified by observing the appearance of apoptotic bodies using the fluorescent microscope while their antiproliferative impact had been evaluated using flow cytometer. Results revealed that secondary metabolites extracted using hexane and ethyl acetate were having the highest cytotoxicity and thus anticancer activity effect on HepG2 with IC₅₀ (24.29 ± 0.85, 11.22 ± 0.679 µg/mL) respectively. Where apoptotic bodies observed, flow cytometer results exhibited that secondary metabolites can inhibit cell cycle in G0/G1 phase. Accordingly, A. lagopoides hexane and ethyl acetate extracts may consider as a candidate anti-cancer drug.

Addition of the bulky redox-active diphosphine 1,8-bis(diphenylphosphino)naphthalene (dppn) to [Fe2(CO)6(-edt)] (1) (edt = 1,2-ethanedithiolate) affords [Fe2(CO)4(2-dppn)(-edt)] (3) as the major product, together with small amounts of a P-C bond cleavage product [Fe2(CO)5{1-PPh2(1-C10H7)}(-edt)] (2). The redox properties of 3 have been examined by cyclic voltammetry and it has been tested as a proton-reduction catalyst. It undergoes a reversible reduction at E1/2 = –2.18 V and exhibits two overlapping reversible oxidations at E1/2 = –0.08 V and E1/2 = 0.04 V. DFT calculations show that while the HOMO is metal-centred (Fe-Fe -bonding), the LUMO is primarily ligand-based but also contains an antibonding Fe-Fe contribution, highlighting the redox-active nature of the diphosphine. It is readily protonated upon addition of strong acids to afford two isomeric hydride complexes and catalyzes the electrochemical reduction of protons at Ep = –2.00 V in the presence of CF3CO2H. The catalytic current indicates that it is one of the most efficient diiron electrocatalysts for the reduction of protons, albeit operating at quite negative potential.

This is the second of a two-paper series describing a multi-scale modeling approach developed to simulate crack sensing in polymer fibrous composites by exploiting interruption of electrically conductive carbon nanotube (CNT) networks. The approach is based on the finite element (FE) method. FE models at three different scales, namely the micro-scale, the meso-scale and the macro-scale, have been developed using the ANSYS PDL environment. In the present paper, the meso- and macro-scale analyses are described. In the meso-scale, a two-dimensional model of the CNT/polymer matrix reinforced by carbon fibers is used to develop a crack sensing methodology from a parametric study which relates the crack position and length with the reduction of current flow. In the meso-model, the effective electrical conductivity of the CNT/polymer computed from the micro-scale is used as input. In the macro-scale, the final implementation of the crack sensing methodology is performed on a CNT/polymer/carbon fiber composite volume using as input the electrical response of the cracked CNT/polymer derived at the micro-scale and the crack sensing methodology. Analyses have been performed for cracks of two different lengths. In both cases, the numerical model predicts with good accuracy both the length and position of the crack. These results highlight the prospect of conductive CNT networks to be used as a localized structural health monitoring technique.

The active layer thickness (ALT) is affected by local soil material and surface vegetation coverage in Tibetan plateau permafrost region. The human activities and engineering construction along the Qinghai-Tibet Highway (QTH) destroyed the surface vegetation coverage, which have seriously influenced the ALT and heat exchange balance. Meanwhile, the changes of the detailed internal structure in the active layer will affect the stability of engineering infrastructure. Ground-penetrating radar (GPR) was used to detect the ALT in the permafrost region. However, researches on the detailed structure of the active layer and spatial variation information of ALT are rare, the main reason given for this is that the lack of advanced imaging techniques to enhance the GPR images. In this paper, the researchers focus on solving this problem by applying the reverse time migration (RTM) method to GPR field data acquired in the Beiluhe region. Analyses of the results led to conclusions as follows: a) The RTM algorithm is proved to be accurate for imaging the characteristics of the active layer through the dielectric constant model obtained by common midpoint and GPR data velocity analysis. b) The result of RTM profiles show the loose structure and graben-like fine internal structure. Combining with drill data and soil materials information, the researchers deduce the graben-like structure might be coarse gravel layer, which may be related to subgrade settlements in some local area. c) The 2D contour maps not only show the spatial variation feature of ALT at two sides of the highway, but also can compensate the defect of the research for single 2D survey line. The ALT is about 0.6~0.8 m in most areas, and about 0.8~0.9 m near the highway at west side of the QTH on the 2D contour maps. From the RTM interpretation profile, the closer to the plash, the deeper thawed active layer. The detailed internal structure of the active layer and 2D contour maps of ALT have great significance for the study of fine internal structure and the characteristic of ALT spatial variation in the Tibetan plateau under the background of climatic change.

The arrival of new developments in the field of power electronics circuit’s applications in power systems builds new control strategy to improve voltage quality for power grid by overcome interruptions. Wind energy resources are unconventional resources and get advanced problems to power grid when it is connected. Uncertainty of load sharing, peak energy management, climatic conditions, wind velocity and wind energy injected into power grid leads many of power quality problems on power grid based on the existing guidelines specified in IEC-61400 standard. This system plans efficient operation of DFIG to eliminate the voltage collapse and mismatch frequency to power grid. The DFIG connected diode rectifier and rotor side converter wind generator works as an Efficient Static Synchronous Compensator (E-SATCOM) for supplying the demand of reactive power for power grid to mitigate PQ problems. The benefit of using a combined controller was verified by simulink/Matlab and its simulated results used Doubly Fed Induction Generator (DFIG), wind Turbine. This simulation results gives good quality transient and stable state response to manage and support reactive power for both symmetrical and unsymmetrical faults in connection of grid codes to provide continuous quality of power supply, multiple wind generators are required for 140 bus power grid.

Land surface albedo determines the splitting of downwelling solar radiation into components which are either reflected back to the atmosphere or absorbed by the surface. Land surface albedo is an important variable for the climate community and therefore was defined by the Global Climate Observing System (GCOS) as an Essential Climate Variable (ECV). Within the scope of the Satellite Application Facility for Land Surface Analysis (LSA SAF) of EUMETSAT, a near-real time (NRT) daily albedo product was developed in the last decade from observations provided by the SEVIRI instrument on board the geostationary satellites of the Meteosat Second Generation (MSG) series. In this study we present a new collection of albedo satellite products based on the same satellite data. The MSG Ten-day ALbedo (MTAL) product incorporates MSG observations over 31 days with a frequency of NRT production of 10 days. The MTAL collection is more dedicated to climate analysis studies compared to the daily albedo that was initially designed for the weather prediction community. For this reason, a homogeneous reprocessing of MTAL was done in 2018 to generate a Climate Data Record (CDR). The resulting product is called MTAL-R and has been made available to the community in addition to the NRT version of the MTAL product which has been available for several years. The retrieval algorithm behind the MTAL products comprises three distinct modules: one for atmospheric correction, one for daily inversion of a semi-empirical model of the bidirectional reflectance distribution function, and one for monthly composition that also determines surface albedo values. In this study the MTAL-R CDR is compared to ground surface measurements and concomitant albedo products collected by sensors on-board polar-orbiting satellites (SPOT-VGT and MODIS). We show that MTAL-R meets the quality requirements if MODIS or SPOT-VGT are considered as reference. This work leads to 14 years of production of geostationary land surface albedo products with a guaranteed continuity in the LSA SAF for the future years with the forthcoming third generation of European geostationary satellites.

Fogo volcano erupted in 2014-15 producing an extensive lava flow field in the summit caldera that destroyed two villages, Portela and Bangaeira. The eruption started with powerful explosive activity, lava fountains, and a substantial ash column accompanying the opening of an eruptive fissure. Lava flows spreading from the base of the eruptive fissure produced three arterial lava flows. By a week after the start of the eruption, a master lava tube had already developed within the eruptive fissure and along the arterial flow. In this paper, we analyze the emplacement processes on the basis of observations carried out directly on the lava flow field, remote sensing measurements carried out with a thermal camera, SO₂ fluxes, and satellite images, in order to unravel the key factors leading to the development of lava tubes. These were responsible for the rapid expansion of lava for the ~7.9 km length of the flow field, as well as the destruction of the Portela and Bangaeira villages. The key factors leading to the development of tubes were the low topography and the steady magma supply rate along the arterial lava flow. Comparing time-averaged effusion rates (TADR) obtained from satellite and Supply Rate (SR) derived from SO₂ flux data, we estimate the amount and timing of the lava flow field endogenous growth, with the aim of developing a tool that could be used for hazard assessment and risk mitigation at this and other volcanoes.

The traditional Chinese drug Bombyx Batryticatus mori.L (BBm) which is also named the white stiff silkworm has been widely used in Chinese clinics for thousands of years. It is famous for its antispasmodic and blood circulation promoting effects. Cardiomyocyte hypertrophy, interstitial cell hyperplasia and myocardial fibrosis are closely related to the N-glycosylation of key proteins. To examine the alterations of N-glycosylation that occur in diabetic myocardium during the early stage of the disease and clarify the therapeutic effect of 1-DNJ extracted from BBm, we used the db/db mouse model and an approach based on hydrophilic chromatography solid-phase extraction integrated with an LC-MS/MS identification strategy to perform a site-specific N-glycosylation analysis of left ventricular cardiomyocyte proteins. AGEs, hydroxyproline, CTGF and other serum biochemical indicators were measured with ELISA. In addition, the α1,6-fucosylation of N-glycans was profiled with LCA lectin blots and FITC-labelled lectin affinity histochemistry. The results indicated that 1-DNJ administration obviously downregulated myocardium protein N-glycosylation in db/db mice. The expression levels of serum indicators and fibrosis-related cytokines were reduced significantly by 1-DNJ in a dose-dependent manner. The glycan α1,6-fucosylation level of the db/db mouse myocardium was elevated, and the intervention effect of 1-DNJ administration on N-glycan α1,6-fucosylation was significant. To verify this result, the well-known TGF-β/smad2/3 pathway was selected, and core α1,6-fucosylated TGFR-βⅡ was analysed semi-quantitatively with western blotting. The result supported the conclusions obtained from LCA lectin affinity histochemistry and lectin blot analysis. The expression level of FUT8 mRNA was also detected, and the results showed that 1-DNJ administration did not cause obvious inhibitory effects on FUT8 expression. Therefore, the mechanism of 1-DNJ to relieve the DCM-associated fibrosis can be concluded as the inhibition of N-GlcNAc formation and the reduction of substrate concentration.

The energy, momentum and the action associated with the time domain transition radiation fields are investigated. The results show that for a charged particle moving with speed $v$, the longitudinal momentum associated with the transition radiation is approximately equal to $E/c$ for values of $1-v/c$ smaller than about 10^-3 where $E$ is the total radiated energy and c is the speed of light in free space. The action of the transition radiation, defined as the product of the energy dissipated and the duration of the emission, increases as $1-v/c$ decreases and, for an electron, it becomes equal to $h/4\pi$ when $v=c-v_m$ where $v_m$ is the speed associated with the lowest energy state of a particle confined inside the universe and h is the Plank constant. Combining these results with Heisenberg’s uncertainty principle, an expression for the electronic charge based on other fundamental physical constants is derived. The best agreement between the experimentally observed electronic charge and the theoretical prediction is obtained when one assumes that the actual size of the universe is about 250 times larger than the visible universe.

There are currently around 78 Nuclear Power Plants (NPP) in the world based on Boiling Water Reactors (BWR). The current parameter to assess BWR instability issues is the linear Decay Ratio (DR). However, it is well known that BWRs are complex non-linear dynamical systems that may even exhibit chaotic dynamics that normally preclude the use of the DR when the BWR is working at a specific operating point during instability. In this work a novel methodology based on an adaptive Shannon Entropy estimator and on Noise Assisted Empirical Mode Decomposition variants is presented. This methodology was developed for real-time implementation of a stability monitor. This methodology was applied to a set of signals stemming from several NPPs reactors (Ringhals-Sweden, Forsmark-Sweden and Laguna Verde-Mexico) under commercial operating conditions, that experienced instabilities events, each one of a different nature

An increased risk of multiple sclerosis (MS) had been found when individuals had consumed large amounts of processed meat and sausages at young age (Lauer, 2014). Furthermore it was found in many studies that MS patients had acquired a number of common childhood infections at higher ages than controls. Therefore, MS patients from an epidemiological long-term investigation in Germany and different hospital controls, were evaluated for a statistical interaction of these two factors. 324 MS patients and 242 hospital controls were inquired. The study focussed on age 0 - 16. Subjects were tested for additive interaction by multiple linear regression analysis (Knol et al., 2007). There was an additive interaction of the age at any common childhood infection with the consumption of scalded sausages (regression estimate = 0.1370; standard error = 0.0603; p = 0.0239). In contrast, no such interaction could be shown for: animal fats; smoked meat (e.g. ham and bacon); and cold - smoked German salami. Thus there was a synergy of the intake of scalded sausages (e.g. frankfurters, bolognas, etc.) and age at common childhood infections, for the later risk of MS.

Seroconversion surveys of anti-SARS-CoV-2 antibodies provide accurate estimates of the SARS-CoV-2 infection. This nationwide population-based cross-sectional serosurvey aimed to evaluate the prevalence of SARS-CoV-2 antibodies among residents in Gabon and compare the estimated cumulative number of COVID-19 cases with the officially registered number of laboratory-confirmed cases up to December 2021. Households in each province were randomly selected. Twenty-eight localities including 16 urban and 12 rural, were randomly selected to participate in the study. Whole blood samples were collected in dry tubes from all study participants around the country within 15 days. Serum samples were used to measure the total Immunoglobulin antibodies. Overall, data of 1672 households were analyzed. Out of the 3659 participants, 3175 were found positive for SARS-CoV-2 antibodies, resulting in a crude seroprevalence of 86.77%. Stratification of study participants by age group has shown highest seroprevalences in 20–29 and 40-49 age groups with 91.78% (95% CI:89.5–93.6) and 91.42% (95% CI:88.7–93.5), respectively. Nyanga province had the lowest prevalence (72,8%), and Estuaire and Ogoué-Lolo provinces had the highest prevalence (90 and 92%, respectively). Our results suggest a high transmission rate in the Gabonese population, 21 months after the first SARS-CoV-2 case in the country. This high seroprevalence estimate could indicate that the applied infection control measures may not have been adequately implemented or appropriately adhered to by the population.

The integration of artificial intelligence, particularly Large Language Models (LLMs), has the potential to significantly enhance therapeutic decision-making in clinical oncology. Initial studies across various disciplines have demonstrated that LLM based treatment recommendations can rival those of multidisciplinary tumor boards (MTBs); however, such data are currently lacking for urological cancers. This study provides the methodological foundation for the prospective CONCORDIA trial, which will generate this data for the first time. In this preliminary work, we evaluated the proposed measurement tool for the CONCORDIA study -the System-Causability-Scale (SCS) and its modified version (mSCS) - based on recommendations from ChatGPT-4 and an MTB for 40 urological cancer-scenarios. Both scales demonstrated strong validity, reliability (all aggregated Cohen’s K &gt; 0.74), and internal consistency (all Cronbach’s Alpha &gt; 0.9), with the mSCS showing superior reliability, internal consistency, and clinical applicability (p&lt;0.01). Two Delphi processes were used to define the LLMs to be tested in the CONCORDIA study (ChatGPT-4 and Claude 3.5 Sonnet) and to establish the acceptable non-inferiority margin for LLM recommendations compared to MTB recommendations. The forthcoming ethics-approved and registered CONCORDIA non-inferiority trial will require 110 urological cancer scenarios, with an mSCS difference threshold of 0.15, a Bonferroni corrected alpha of 0.025, and a beta of 0.1. Blinded mSCS assessments of MTB recommendations will then be compared to those of the LLMs. In summary, this work establishes the necessary prerequisites prior to initiating the CONCORDIA study and validates a modified score with high applicability and reliability for this and future trials.

Background: To evaluate the incidence of postsurgical cystoid macular edema (PCME) after small-gauge pars plana vitrectomy (PPV) for different retinal pathologies and to assess the role of optical coherence tomography (OCT) biomarkers to guide treatment decision in patients with PCME, refractory to medical therapy. Materials and Methods: Medical records of consecutive pseudophakic patients, who underwent PPV for different retinal pathologies, were retrospectively evaluated in this single center, uncontrolled study. The incidence of post-PPV CME was assessed in this population. Eyes that presented with post-PPV CME within the first 2 months after surgery were considered for further evaluation. A minimum follow-up of 12 months, history of previous cataract surgery performed not earlier than 1 year before PPV, the availability of full clinical and OCT data at 1, 3, 6, 9 and 12 months after PPV, constituted the minimal requirements to be included in the 12-months assessment. Mean best corrected visual acuity (BCVA; LogMAR) together with mean central macula thickness (CMT; m) change, and response to different treatments (medical therapy and dexamethasone intravitreal implant) were evaluated. The impact of specific clinical and structural OCT biomarkers on the exposure to dexamethasone (DEX) intravitreal treatment was assessed. Eventual ocular and non-ocular adverse events, potentially related to the treatment, were investigated as-well. Results: Of 346 pseudophakic patients (352 eyes) enrolled in the study, 54 (54 eyes) developed CME within the first 2 months after PPV (incidence of 15.3%). After the exclusion of 6 subjects, the remaining 48 pa-tients were dimed eligible for the 12-months analysis. Preoperative mean BCVA (1.44 ± 0.99 LogMAR) sig-nificantly improved to 0.32 ± 0.37 LogMAR at 12 months (P< 0.001). Mean baseline CMT of 347 (± 123.5) m, significantly decreased to 290 m (± 80.4; P=0.003) by the end of the FU. Twenty-five eyes (52%) re-quired one or more DEX intravitreal implants for CME, refractory to topical therapy. The correlation analy-sis disclosed the existence of significant correlations between mean CMT values at different time points of the FU. Additionally, patients who required intravitreal therapy at months 3 and 9, were more likely to present with the following features at 1 month OCT: intraretinal fluid (IRF), disorganization of inner retinal layers (DRIL), disorganization of outer retinal layers (DROL) and hyperreflective foci (HRF). No major safe-ty issues arose. Conclusion: Topical therapy alone can be a valuable option for post-PPV CME in approximatively 50% of pa-tients. Significant visual acuity recovery and CMT reduction at 12 months, demonstrated DEX intravitreal implant can be a safe and effective second-line treatment for pseudophakic patients with post-PPV CME, refractory to medical therapy. The presence of specific OCT biomarkers may indicate a more severe CME that might benefit from the intravitreal therapy.

This article is a continuation of our previous research on the catalytic capability of chiral copper complex based on commercially available (S)-2-aminomethylpyrrolidine and 3,5-di-tert-butylsalicylaldehyde with various counter-anions in the asymmetric Henry reaction. Our findings indicate that depending on the type of base used, chiral nitroalcohols with yields up to 97% and ee values up to 78%, as well as β-nitrostyrenes with yields up to 82% can be produced. Additionally, it has been found that the outcome of the reaction and the catalytic properties of copper(II) complexes (S)-Cu1 and (S)-Cu2 are influenced by the structure of the aldehyde used.

Complexity of care, adequate staffing levels, and workflow are key factors affecting nurses’ workloads. Clinical complexity classification and related staffing adjustment remain notable gaps in the current evidence limiting the capacity for optimal staffing practices. This study aimed to adapt and validate the WANNNT-SC to the Italian context to allow the assessment of newborns admitted to the NICUs. To evaluate the reliability of the tool among different profes-sionals, a correlation test was performed using Pearson’s correlation, which resulted in a strong correlation (r = 0.967, p = 0.01). In the test-retest phase, there was a significant correlation (r = 0.910 and p = 0.01). Using an analysis of variance, we found that the higher the I-WANNNT-SC score, the higher the predicted death rate (F = 13.05 and p < 0.001). The Italian Winnipeg Surgical Complex Assessment of Neonatal Nursing Needs Tool represents the first tool available for the Italian context that aims to measure the nursing workload in neonatal intensive care. It could allow adjustments in nursing staffing based on NICU activities and patient needs. This study was prospectively approved by the local Ethics Committee “Palermo 1” (Protocol CI-NICU-00).

Background: Bacterial/fungal coinfections (BFC) are associated with antibiotic overuse, poor outcomes such as prolonged ICU stay and increased mortality. Our aim was to develop machine learning-based predictive models to identify respiratory bacterial or fungal coinfections on ICU admission. Methods: Secondary analysis of two prospective multicenter cohort studies with confirmed influenza A(H1N1)pdm09 and COVID-19. Multiple logistic regression (MLR) and random forest (RF) were used to identify factors associated with BFC in the overall population and in each subgroup (influenza and COVID-19). Performance was assessed by area under the ROC curve (AUC) and out-of-bag (OOB) for MLR and RF, respectively. Results: Of the 8,902 patients, 41.6% had influenza and 58.4% had SARS-CoV-2 infection. The median age was 60 years, 66% were male and the crude ICU mortality was 25%. BFC was observed in 14.2% of patients. Overall predictive models showed modest performance with AUC of 0.68 (MLR) and OOB 36.9% (RF). Specific models did not show improved performance. However, age, procalcitonin, CRP, APACHE II, SOFA and shock were factors associated with BFC in most models. Conclusion: Machine learning models for predicting respiratory BFC in patients with pandemic viruses are not able to predict adequately. However, the presence of factors such as advanced age, elevated procalcitonin or CPR and high severity of illness should alert clinicians to the need to rule out this complication on admission to the ICU.

Endocrine-disrupting chemicals (EDCs) significantly damage biological systems related to reproductive, neurological, and metabolic functions. Approximately 1,000 chemicals are known to possess endocrine-acting properties, including bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP). This study primarily focuses on the potential effects of EDCs on the transcriptional levels of innate immune prophenoloxidase (proPO) system-related genes to oxidative stress in the gonad and stomach of the mud crab Macrophthalmus japonicus, an indicator species for assessing coastal benthic environments, when exposed to BPA or DEHP. After EDC exposure, the expression of lipopolysaccharide and β-1,3-glucan-binding protein (LGBP), a pattern recognition protein that activates the proPO system, was upregulated in the stomach of M. japonicus, whereas LGBP gene expression was downregulated in the gonad. In the gonad, which is a reproductive organ, EDC exposure mainly induced the transcriptional upregulation of trypsin-like serine protease (Tryp) at relatively low concentrations. In the stomach, which is a digestive organ, LGBP expression was upregulated at relatively low concentrations of EDCs over 7 days, whereas all proPO system-related genes (LGBP, Tryp, serine protease inhibitor (Serpin), and peroxinectin (PE)) responded to all concentrations of EDCs. These results suggest that the antioxidant and immune defense responses of the proPO system to EDC toxicity may vary, causing different degrees of damage depending on the tissue type in the mud crab.

Introduction: In Ethiopia, maternal undernutrition is a major public health concern. However, comprehensive evidence is lacking in the southern part of Ethiopia, specifically the household and community-level related determinants of undernutrition. Besides, the evidence about the prevalence and determinants of undernutrition is not yet documented in the current study setting. Thus, this study aimed to determine the prevalence of undernutrition and identify its determinants among pregnant women in Hawela Lida district of the Sidama region, Ethiopia.Methods: A community-based cross-sectional study was conducted on a sample of 515 pregnant women from June 1–25, 2024. A multi-stage sampling method was utilized to select eligible pregnant women. We collected data using the Open Data Kit smart phone device and exported it to Stata version 17 for further processing and analysis. A multi-level mixed-effects modified Poisson regression analysis with robust variance was used to account for between and with cluster effects.Result: The prevalence of undernutrition among pregnant women was 41.7% (95% CI: 37.3–45.6). The prevalence of undernutrition was associated with planned pregnancy (adjusted prevalence ratio [APR]: 0.80; 95% CI: 0.66-0.98), household food insecurity (APR: 1.64; 95% CI: 1.26-2.13), inadequate dietary diversity (APR: 1.79; 95% CI: 1.43-2.25), and women’s poor knowledge of nutrition (APR: 1.68; 95% CI: 1.32-2.12) at individual levels. The identified determinants of undernutrition at the community level were low community literacy rates (APR: 4.62; 95% CI: 1.13–18.79) and low community wealth status (APR: 1.91; 95% CI: 1.10–3.31).Conclusion: Two in five pregnant women had an undernutrition problem in the study setting. Individual and community-level determinants contributed to the high prevalence of undernutrition. Thus, any prevention and control approaches to undernutrition should consider inter-sectorial collaboration to account for determinants at various levels. Besides, any program must emphasize the delivery of nutrition education about dietary diversity, particularly targeting pregnant mothers who have poor knowledge of nutrition and unplanned pregnancy at the individual level. Moreover, creating a small business reform for the community with low wealth status using agricultural extension workers must be considered.

Lung macrophage cells play a critical role in various lung disease, and their state can change depending on the progression of the disease by inducing either an inflammatory or anti-inflammatory state. In this review, we investigate the potential therapeutic effects of treatment with antioxidant nanoparticles in airway disease focusing on porcine reproductive and respiratory virus (PRRSV), considering Reactive Oxygen Species (ROS) as one of the factors that regulate M1 and M2 macrophages in the inflammatory and anti-inflammatory states, respectively. In addition, we examine the status of protein structure research on CD163 (one of the markers of anti-inflammatory M2 macrophages) in human and veterinary lung diseases and suggest directions for future applicable research areas.

Infections with Flavobacterium oreochromis pose risks to Colossoma macropomum production. Since no treatment exists, prophylaxis through vaccination is the only form for disease control. The enzyme-linked immunosorbent assay (ELISA) is widely used in aquaculture to assess animal immunity and mainly to validate vaccination protocols. The method based on the use of immunoglobulin Y (IgY) is an alternative to consider due to its advantages over antibodies produced by small mammals. This study aimed to standardize an indirect ELISA (iELISA) protocol to validate the immunization of C. macropomum against F. oreochromis. A hen and fish were immunized to obtain anti-C. macropomum and anti-F. oreochromis antibodies, which were used to standardize the test. The iELISA was composed of the inactivated bacteria in the coating step, C. macropomum anti-Flavobacterium oreochromis as the primary antibody, and anti-C. macropomum IgY as the secondary antibody. The results demonstrate that the highest antibody titers were among the immunized groups, which were bacterin + adjuvant and bacterin. The iELISA enabled the detection of antibodies produced by C. macropomum, which were mediated by IgY specificity.

This comprehensive study looks at how operational conditions affect the performance of a novel seven-channel titania ceramic ultrafiltration membrane for the treatment of produced water. A Full factorial design experiment (23) was conducted to study the effect of the cross-flow operating factors on the membrane permeate flux decline and the overall permeate volume. Eleven experimental runs were performed for three important process operating variables: Transmembrane Pressure (TMP), Crossflow Velocity (CFV), and Filtration Time (FT). Steady final membrane fluxes and permeate volumes were recorded for each experimental run. Under the optimized conditions (1.5 bar, 1 m/s, and 2 hours), the membrane performance index demonstrated an oil rejection rate of 99%, a flux of 297 liters/m2·hr (LMH), a 38% overall initial flux decline, and a total permeate volume of 8.14 L. The regression models used for the steady-state membrane permeate flux decline and overall permeate volume led to the highest goodness of fit to the experimental data with a correlation coefficient of 0.999. A Multiple Linear Regression method and an Artificial Neural Network approach were also employed to model the experimental membrane permeate flux decline and analyze the impact of the operating conditions on membrane performance. The predictions of the Gaussian regression and the Levenberg-Marquardt backpropagation method were validated with a determination coefficient of 99 % and a mean square error of 0.07.

In central area of Liaoning province, the thermal performance of rural building envelopes are mostly non-standardized in Northern China, resulting in a significant heat loss. In this study, The objective was to propose some low-cost and energy-efficient solutions. Through a field of inves-tigations, heating energy consumption was saved by 20% and increased construction costs was less than 8000 RMB, which was acceptable for rural residents. In order to achieve this target, NSGA-II algorithm was integrated with Rhino+Grasshopper and EnergyPlus simulation kernel to establish a thermal performance optimization model for heat transfer of the rural building envelopes. Among the above Pareto optimal solutions, the recommended thickness of insulation layer for the room floors, ceilings, and external walls were 70mm, 50mm, and 40mm respectively. Furthermore, try to reduce the window to wall ratio as much as possible. Finally, based on the lower total cost, three technical solutions that rural residents could select according to their specific needs have been put forward.

Chronic administration of atypical antipsychotics (AAPs) is commonly associated with in-creased cardiovascular disease load. Although the increase in weight gain and related dis-ease risk is generally considered the main contributing factor, direct interference with mi-tochondrial bioenergetics, particularly in the liver, where these drugs are catabolized, is emerging as an additional relevant contributor to metabolic disease risk that needs to be considered. In this study, we compared the effects of two AAPs with disparate metabolic profiles, olanzapine (OLA), which is obesogenic, and aripiprazole (ARI), which is not, on the response of Fao cells to oxidative stress. We found that Fao cells treated with ARI sur-vive better a challenge with H2O2 while OLA treatment has the opposite effect. This en-hanced survival is not related to a reduction in the apoptosis rate. In fact, ARI treated cells display higher apoptotic rates than control cells exposed to H2O2. Gene expression analysis of pro and anti-apoptotic factors revealed that the changes induced by H2O2 were generally dampened in ARI treated cells, but not in OLA treated cells, suggesting a reduced respon-siveness to stimuli, a notion that was consistent with a reduced activation of MAPK and STAT3 phosphorylation in response to H2O2, while OLA enhanced their activation in re-sponse to H2O2. Loss of stress response in ARI treated cells is consistent with the elevation of mitochondrial production of O2•-, a known desensitizing factor. The physiological rele-vance of the increased production of O2•- in ARI treated cells is further supported by the observed elevation of the mitophagy flux in ARI treated cells, likely related to mitochon-drial damage. An additional relevant finding was that OLA treatment protected the pro-teasome activity in Fao cells exposed to H2O2, an effect possibly related to the better preservation of stress signaling and mitochondrial function in OLA treated cells. In sum, this study highlights the underlying alterations in cell physiology derived from the inter-ference of ARI with mitochondrial function, that de-sensitize cells to stress signaling, while OLA has the opposite effect.

Commercial production of Choromytilus meridionalis (black mussel) and Mytilus galloprovincialis (Mediterranean mussel) contributes to half of the South African marine aquaculture production per year. However, limited ready-to-eat black mussel products are available. The aim of this preliminary study was to investigate the effects of storage (15 days at room temperature) on the total viable counts (TVC), coliforms, proximate composition, and fat oxidation (TBARS) of a small-scale kitchen-based ready-to-eat hot smoked black mussel product preserved with vegetable oil. Three batches of black mussel meat were smoked at 80ºC for 15 minutes. Half of each batch were packaged in sterile glass jars with heated (50ºC) vegetable oil and half without oil. Microbiological analyses were done at days 1, 3, 9 and 15. Proximate composition was determined at day 1 and TBARS at days 1 and 15. Coliforms for all samples throughout the storage period were undetected. TVC plates for mussels stored without oil had no growth at days 1 to 5, however, reached TVC > 5 log10.g-1 at day 15. TVC for mussels with oil increased from 0 at day 1 to > 5 log10.g-1 at day 3 and remained at counts > 5 log10.g-1. There was no significant difference (P > 0.05) in moisture, protein, and ash for mussels stored with oil and those without oil, while significant differences (P < 0.001) in total fat and carbohydrates (10.27 ± 2.10% and 6.80 ± 2.22% with oil, and 5.05 ± 1.49% and 10.59 ± 3.00% without oil) were detected. These differences were due to the presence of additional fats from the vegetable oil. TBARS at day 15 showed no significant difference (P > 0.05) between mussels stored with oil and those without oil. There were no significant differences in TBARS from day 1 to 15 for both oil and without oil. Small-scale kitchen-based smoked black mussels preserved without vegetable oil could be stored for up to 9 days at room temperature.

Barrett’s esophagus (BE) is a known precursor to Esophageal Adenocarcinoma (EAC). Guidelines recommend BE screening in populations with multiple risk factors, for which non-endoscopic esophageal cell collection with biomarker testing is considered an acceptable alternative to esophagogastroduodenoscopy (EGD). This study presents analytical validation of EsoGuard® (EG), a two gene DNA methylation biomarker assay, in esophageal cell samples collected with the 510(k)-cleared, swallowable EsoCheck® (EC) device. EG is a Next Generation Sequencing (NGS) assay that evaluates methylated Vimentin (VIM) and Cyclin A1 (CCNA1) genes, clinically validated biomarkers for detection of BE and EAC. The studies were conducted according to standards of College of American Pathology (CAP), Clinical Laboratory Improvement Amendments (CLIA), and New York (NY) state requirements for analytical validation of molecular assays. Comparison to Sanger sequencing showed EG was 100% accurate at all 31 CpG sites evaluated by the assay. Analytical sensitivity, specificity and accuracy of the assay was 89%, 100% and 96% respectively. Intra- and inter-assay precision was 100%. Limit of detection (LOD) was 1 in 400 methylated cells and reference range was 84%. In summary, EsoGuard is a robust DNA methylation test to detect BE with high accuracy, repeatability, and reproducibility in samples collected using the EsoCheck device.

In the last decades, numerous studies indicated the substantial role semiconductors could play in photocatalytic processes for environmental applications. Materials that contain a semi-conductor as a photo-catalyst have a semi-permanent capacity for removing harmful gases from the ambient air. In the present work, the focus is on TiO2. Heterogeneous photo-catalysis using TiO2 leads to the degradation of NO/NO2, benzene, toluene, and other priority air pollutants once in contact with the semiconductor surface. Preliminary evidence indicates that TiO2 containing construction materials and paints efficiently destroy the ozone precursors NO and NO2 up to 80% and 30%, respectively. Therefore, the development of innovative coatings containing TiO2 as a photo-catalyst was in the foreground of research activities with the aim to be used as building and construction materials mainly outdoors, e.g. on building facades in high traffic roads for the degradation of priority air pollutants (NOx and volatile organic compounds) in the polluted urban atmosphere. Though the advantages connected with the application of TiO2 due to its band gap of 3.2 eV are limited. TiO2 is effective only in the UV-region (ca. 5%) of the solar spectrum with wavelengths λ

Efficiency serves as a crucial metric in assessing the advancement of scientific research for universities. Reasonable inputs of human resources, finances, materials, and other resources, along with high-quality research output, are important guarantees for the research efficiency of Chinese universities. This study delves into the patterns of changes of research efficiency among universities across the 31 provinces and municipalities of China from 2012 to 2022. By scrutinizing input-output perspectives and utilizing data sourced from the China Statistical Yearbook, the analysis unveils prevailing scenarios of input redundancy and output insufficiency in research efficiency across universities. The static and dynamic trends in research efficiency were further investigated by employing a static non-parametric Data Envelopment Analysis (DEA)-BCC model and a dynamic Malmquist index. Key findings from the analysis from 2012 to 2022 include: (1) notable growth in investments in teaching, research equipment assets, and research and development funds among nationwide universities; (2) a steady increase in the mean value of technical efficiency (TE) from 0.97 to 0.99, indicating continuous enhancement in overall efficiency in research input resource allocation across the provinces; (3) the mean Malmquist productivity index of 1.285, with an average annual increase of 28.5%, signifying a consistent improvement in university research efficiency throughout the study period; and (4) the provinces experiencing varying degrees of input redundancy or output insufficiency were selected to suggest the need for tailored strategies in resource allocation. The study underscores the importance of a holistic evaluation system involving stakeholders from government, universities, and society to optimize research efficiency and promote scientific innovation and social development.

Skin inflammation associated with chronic diseases has the direct action of keratinocytes in its immunopathogenesis, leading to a series of immune responses. However, there are still no highly targeted treatments, and the development of more specific therapies is highly desirable. In the present work, nanocapsules containing quinizarin (QZ/NC) were developed, evaluating their act in a model of the keratinocytes inflammatory process in vitro with the action of Photodynamic Therapy, analyzing the permeation in a 3D skin model. Physicochemical, stability, cytotoxicity and permeation analyses of the nanomaterials were carried out. The nanocapsules showed desirable physicochemical characteristics and were stable during the analysis period, without spectroscopic modifications. The cell viability test carried out showed no cytotoxicity at the lowest QZ/NC concentrations. The permeation and cellular uptake studies showed the permeation of QZ/NC in 3D skin models and the intracellular incorporation and internalization of the drug, enhancing its action in the drug delivery technique. Promising results were presented using the model developed to induce the inflammatory process in vitro and applying the synthesized nanomaterial in conjunction with PDT, where a decrease in the levels of cytokines analyzed was observed, representing a possible new therapeutic approach for inflammatory skin diseases.

Dinoflagellates belonging to Hematodinium are important parasites of marine crustaceans, primarily dec-apods. In this study, we document the first report of H. perezi Chatton & Poisson, 1930 on the African Atlantic coast. This is also the first parasite record in the invasive American blue crab Callinectes sapidus Rathbun, 1896 in Morocco. Specimens of C. sapidus were sampled in winter 2023 from two Ramsar sites on the Atlantic coast of Morocco, namely Merja Zerga and Oualidia Lagoons, and were screened to detect the presence of parasites in their hemolymph. Based on staining fresh hemolymph smears, we did not de-tect Hematodinium in any of the 36 investigated individuals (20 and 16 from Merja Zerga and Oualidia lagoons, respectively), probably due to methodological artifacts. The PCR-based method was revealed to be more accurate in diagnosing the Hematodinium parasite. It showed that 13 blue crabs were infected by the parasite at Merja Zerga Lagoon (prevalence 65%) and four individuals at Oualidia Lagoon (25%). Ge-netic analysis, based on the ITS1 rDNA gene from Hematodinium, confirmed the sequences as being those of Hematodinium perezi.

Colorectal cancer is the third most common malignancy and the second most lethal malignancy of the general population. Right sided colon cancer is less common than left sided, occurring more frequently in females, and associated with an older age and poor prognosis. Intraabdominal abscess formation is a rare complication from colorectal cancer. Thus, we present a case of a 66-year-old male who presented to the emergency department with 4 days of sudden onset, intractable right lower quadrant abdominal pain associated with nausea and vomiting. After further evaluation, he was diagnosed with right sided colon adenocarcinoma complicated by peri-colonic abscess formation. He was treated with hemicolectomy without immunotherapy. Considering the scarcity of data concerning colonic abscess formation and colorectal adenocarcinoma, more research is needed on this dual presentation. These authors reinforce that in older patients presenting with acute abdomen, colorectal cancer should be noted as a differential

Using the phenomenon of transpiration, plants are able to raise soil water to a height of about 100 meters. According to the Cohesion - Tension theory, water moves through the capillaries of plant along a gradient of negative water potential in a single unified flow along a single route from roots to leaves, entering on its way into living cells for their nutrition and evaporating into the atmosphere in significant amounts in the leaves. The paper shows that in a case of artificial transpiration devices (ATD), the flow of rising water can be divided into two streams - the transpiration stream and the passive water stream - and as a result, such devices become capable of raising water to any given height. As proof, the working variant of two-stream ATD is proposed. The development of this ATD was carried out in two stages, discussed in details in the paper. At the first, experimental stage, a physical model was designed and manufactured, in which the flow of rising water was divided into two streams moving along two independent routes. The first route is used exclusively for the purpose of transpiration of water - transporting it into an artificial evaporator for complete evaporation into the atmosphere. The second route is used exclusively to transport passive water using the energy obtained in the first route during the process of transpiration. During many hours of testing, the physical model demonstrated a stable ability to bring masses of passive water, maintaining normal atmospheric pressure in them, to a small height, even in the extreme case not exceeding 10 meters. At the second, analytical stage, this two-stream model was developed into a two-stream multi-stage model, capable of raising water to any given height by choosing the number of stages. The number of stages can be very large, and portions of water can be delivered to any given height, remaining under normal atmospheric pressure. The conclusion part of the paper discusses the prospects of creating on the basis of the developed two-stream ATDs large systems that can, using the phenomenon of transpiration, become a sources of clean energy, similar to how it is realized in the mass of plants.

Dissemination of resistant pathogens via food supply chains is a notable public health danger from farm to fork. The proposed work analysed the distribution of E. coli among various sources of animal-based food supply chain. Overall, 500 samples were heaped up from livestock, poultry sectors, environment, fisheries, and dairy. Standard microbiological procedures were used to isolate and identify E. coli. Further, isolates were confirmed by using MALDI-TOF and virulence associated genes (VAGs). The phenotypic resistance pattern of the isolates was determined by molecular identification of antibiotic resistance genes (ARGs) through PCR using specific primers. Shiga toxin producing E. coli (STEC) were subjected to PCR based O typing using specific primers against different O types. Overall results revealed that 154 (30.5%) samples were confirmed as E. coli, in which77 (50%) isolates were MDR E. coli. Among these, total 52 (67.53%) isolates showed array of VAGs in which 21 (40.38%) were confirmed as STEC based on stx1 and stx2. Furthermore, 12/52 (23.07%) isolates were detected as Non-O157 STEC co-harboring mcr-1 and blaNMD-1. Overall, O26 STEC was found to be the most prevalent among different non-O157 types. Herein, results proposed that detection of such STEC MDR E. coli causing serious public health consequences in developing countries.

Many middle-aged and older adults (MAOA) do not engage in sufficient physical activity (PA) despite its well-documented benefits for healthy aging. Existing PA interventions often fail to reach or engage the target population effectively. This study investigates MAOA's preferences for recruitment strategies to optimize the reach and uptake of PA interventions, thereby enhancing their impact on healthy aging and public health. Qualitative interviews were conducted with 39 MAOA participants (69% female, mean age = 69.46, SD = 7.07), guided by McGuire's Theory on Persuasive Communication. Factors related to the source, message content, channel, receiver characteristics, and target behavior of recruitment strategies were analyzed. Findings suggest a preference for trustworthy sources (e.g., healthcare professionals over commercial entities) and positive, non-ageist messaging. MAOA vary in channel preferences but emphasize the importance of personalization. Despite heterogeneity, MAOA commonly perceive themselves as sufficiently active, necessitating improving knowledge on what constitutes sufficient PA, and easy enrollment or trying-out interventions. Tailoring recruitment strategies to diverse MAOA segments, based on age, seems crucial for effective engagement. Future research could explore quantitative research into how communication factors relate to various target population characteristics.

Honey bee colonies rapidly decline when confined to greenhouses, increasing pollination rental costs as they need to be replaced frequently. We tested a hive system with entrances that can be manipulated to direct bees to inside or outside greenhouses containing a zucchini crop. In one greenhouse, the bees could only forage inside for 15 days; in another, bees were directed to the inside from 5 to 9 AM, after which they foraged outside. This procedure was repeated two more times in each greenhouse with new hives. Data was collected on how the number of bee flower visits affected fruit production, the frequency of flower visits, and the amount of bee brood and food in the hives. Flowers visited by bees four times or more set more and larger fruit. The frequency of flower visits by bees from the hives confined to the greenhouse was reduced after eight days; it was not reduced in the greenhouse with bees that could forage outside. Bee brood area was reduced in the colonies that were confined to the greenhouse, while it was maintained in the semiconfined hives. The hive system with controllable entrances proved effective for pollination, while causing less damage to the bees.

This work presents the mathematical framework of the Second-Order Comprehensive Adjoint Sensitivity Analysis Methodology for Response-Coupled Forward/Adjoint Linear Systems (abbreviated as “2nd-CASAM-L”), which enables the most efficient computation of exactly obtained mathematical expressions of first- and second-order sensitivities of a generic system response with respect to functions (“features”) of model parameters. Subsequently, the first- and second-order sensitivities with respect to the model’s uncertain parameters, boundaries, and internal interfaces are obtained analytically and exactly, without needing large-scale computations. Within the 2nd-FASAM-L methodology, the number of large-scale computations is proportional to the number of model features (defined as functions of model parameters), as opposed to being proportional to the number of model parameters, which are considerably more than the number of features, being incomparably more efficient and more accurate than any other methods (statistical, finite differences, etc.) for computing exact expressions of response sensitivities (of any order) with respect to the model’s features and/or primary uncertain parameters, boundaries, and internal interfaces. The application of the 2nd-CASAM-L methodology is illustrated using a simplified energy-dependent neutron transport model of fundamental significance in nuclear reactor physics.

The genetic bases of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have been comprehensively studied, which is not the case for atypical cases not classified into these diagnoses. In the present study, we aim to contribute to the molecular understanding of the development of non-AD and non-FTD dementia by surveying rare pathogenic variants. The analysis was performed on 91 patients, the DNA samples of which were pooled and then subjected to whole exome sequencing. Among detected variants two are rare pathogenic and show significant difference in frequency between the analyzed pool and gnomAD Bulgarian control exomes. The rs373478202, G&gt;T, B9D1 variant, most likely present in heterozygous state; is causative for the autosomal recessive ciliopathy- Joubert syndrome, which involves specific CNS malformation. The rs148918985, C&gt;T, ASS1 variant leads to arginosuccinate enzyme deficiency and in compound heterozygosity with other rare pathogenic variant detected in the same gene causes the late-onset form of citrullinemia type I. This disorder causes high ammonia levels, which can lead to cerebral dysfunction. In conclusion, the detected rare pathogenic variants suggest that, in certain cases, the development of non-AD and non-FTD dementia can be mediated by structural alterations in neuronal cilia or by hyperammoniemia.