COVID-19 pandemic outbreak challenged the global public health in last couple of years. Throughout the pandemic period, numbers of mutant strains of SARS- CoV-2 created challenges for the infected patients with diverse pathophysiology and immune response. Variant of Concern (VOC) alpha (B.1.1.7), delta (B.1.617.2) and omicron (B.1.1.529) grew most notable for causing the epidemiological manifestations, which eventually caused elevated infectivity resulting in significant mortality. This review indicates the comparative analysis of the immune-pathophysiological mechanisms in respect to the aforementioned strains of SARS-CoV-2.

Metabolic surgery can promote comprehensive physiological improvements to alleviate metabolic disorders, particularly for patients with type 2 diabetes. Nevertheless, the therapeutic scope has been limited owing to unexpectedly inconsistent surgical outcomes. Therefore, this study to overcome these obstacles by determining the fundamental mechanism underlying the conflicting outcomes. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified duodenal-jejunal bypass (DJB) procedures, were compared to understand the specific surgical patterns from different perspectives comprehensively. Patients in the nonobese group were exclusively included to prevent confounding effects from overweight patients with type 2 diabetes. Following intestinal anastomosis, the epithelial identity of the succeeding intestine was replaced by that of the proximal epithelium owing to altered crosstalk between the epithelium and opposing mesenchymal cells. Subsequent intestinal compensatory proliferation and rapid turnover rate accelerate the spread of the replaced epithelium. The main factors contributing to inconsistent outcomes of metabolic surgery are inadequate duodenal exclusion and inappropriate biliopancreatic limb length. Replacement of enteroendocrine cells during regeneration can lead to inconsistent outcomes in metabolic surgery. The type and density of enteroendocrine cells distributed at the terminal end of the proximal intestine play a significant role in diverse outcomes of metabolic surgery.

Background We aimed to compare the retinal, optic disc vascular density (ODVD) values, and acircularity index (AI) of patients with idiopathic macular telangiectasia type 2 (IMT) and healthy individuals using the optical coherence tomography angiography(OCTA) device. Methods The study included 39 patients with IMT and 37 healthy controls. The OCTA findings of the patients and controls were examined. Results The total, parafoveal and perifoveal vascular density of the superficial capillary plexus, choriocapillaris blood flow, inside-disc ODVD, retinal nerve fiber layer (RNFL), and retinal thicknesses were found to be statistically significantly lower and the foveal avascular zone value was statistically significantly higher in the IMT group compared to the control group (p=0.001, p=0.01, p=0.02, p=0.01, p=0.009, p=0.002, p=0.02, respectively).There was a statistically significant negative correlation between best-corrected visual acuity (BCVA) and AI (p=0.02), a statistically significant positive correlation between peripapillary vascular density and BCVA(p=0.04). Conclusion We consider that the lower retinal, choriocapillaris, and ODVD values, retinal and RNFL thicknesses in the patients with IMT compared to the controls were due to vascular damage, remodeling, fibrosis, proliferation, and Müller cell damage. Ellipsoid zone defect, AI, and peripapillary vascular density are important indicators in the evaluation of visual acuity in these patients.

Vaccination has proven highly effective against severe acute res-piratory syndrome coronavirus 2 (SARS-CoV-2), but the long-term immunogenicity and the functional preserved im-mune responses of vaccines are needed to inform evolving evi-dence-based guidelines for boosting schedules. We enrolled 205 healthcare workers into a cohort study; all had received three doses of BBIBP-CorV (China Sinopharm Bio-Beijing Company) inactivated vaccine. We assessed SARS-CoV-2 specific binding antibodies, neutralizing antibody, and peripheral T and B cell responses. We demonstrated that more robust antibody re-sponses to SARS-CoV-2 were elicited by booster immunization compared to primary vaccination. Neutralizing antibody titers to SARS-CoV-2 Omicron variant were also efficiently elevated post homologous vaccine booster despite in a lower titer compared to the prototype stain. In addition to S specific humoral and cellular immunity, BBIBP-CorV also induced N-specific antibody and ef-fector T cell responses. The third-dose vaccination led to further expansion of critical polyfunctional T cell responses, likely an essential element for vaccine protection. In particular, a func-tional role for Tfh cell subsets in immunity was suggested by the correlation between both CD4+Tfh and CD8+Tfh with total anti-body, IgG, B cell responses and neutralizing antibodies. Our study details the humoral and cellular responses generated by the BBIBP-CorV booster vaccination in a seven-month follow up study. There is a clear immunologic boosting value of homolo-gous inactivated SARS-CoV-2 vaccine boosters, a consideration for future vaccine strategies.

To control the COVID-19 pandemic, many countries implemented vaccination and imposed societal restrictions both at the national level and for international travel. As a check of the corona status, a COVID pass has been issued. A COVID pass could be obtained when fully vaccinated against COVID-19, having recovered from a documented COVID-19 episode, or a recent (24-48 hours) negative SARS-CoV-2 antigen test. A global analysis of SARS-CoV-2 immune status (determined by past infection and/or vaccination), vaccination rates, as well as societal restrictions in controlling the COVID-19 pandemic is presented.

A mild, efficient, and photocatalytic synthesis of 6-phosphorylated phenanthridines via tandem radical addition/cyclization/aromatization of 2-isocyanobiphenyls with diarylphosphine oxides is reported. The method features operational simplicity, metal-free conditions, using low-cost rose Bengal as catalyst and sustainable air as terminal oxidant at room temperature, and providing the desired products in moderate to good yields.

Early-season crop-type data are required for a variety of agricultural monitoring and decision-making applications. The early season in this study referred to the prophase and middle of a growth season. Early-season detection of crop types remains challenging because of limited discriminative features, especially for landscapes that are characterized by complex cropping patterns. In fact, different remote-sensing satellites can increase the frequency of data acquisition, which can provide more information in the early season. Moreover, optical and radar sensors have different degrees of sensitivity to crop parameters. Therefore, the integration and application of two types of multitemporal data are of great significance to improve the accuracy and timeliness of crop type detection.In deep learning (DL), convolutional neural network (CNN) and recurrent neural network (RNN) models have great potential for temporal feature extraction. Compared with RNNs, CNNs usually have fewer parameters and are more conducive to determining early-season detection dates of different crop types, which requires a lot of training because of the need to model on different dates. Nevertheless, revisit dates and temporal intervals of different satellites are usually different, resulting in different data acquisition time series; these data cannot be directly used as input for the same convolutional layer. To address this challenge, a Dual-1DCNN was bulit based on the CNN model in this study. Moreover, an incremental training method was used to attain the network on each data acquisition date and obtained the best detection date for each crop type in the early season. A case study for Hengshui City in China was conducted using time series of Sentinel-1A (S1A) and Sentinel-2 (S2). To verify this method, classical methods support vector machine (SVM) and random forest (RF) were implemented. The results demonstrated the following: (1) the Dual-1DCNN extracted discriminative features from S1A and S2 time series at the early season by producing the highest overall accuracy (OA: 87.23%); (2) for summer maize, cotton, and common yam rhizome, the Dual-1DCNN achieved F1 values of 92.39%, 87.71%, and 84.38%, respectively, at the early season (moreover, the early seasons were almost 40, 70, and 80 days before the end of the growth seasons, respectively). These findings suggested that the Dual-1DCNN is promising for the accurate and timely detection of crop types.

Background: Dynapenia and non-alcoholic fatty liver disease (NAFLD) are common, especially in the middle and advanced-age diabetic male population. We aimed to examine the clinical features, NAFLD severity, and parameters associated with the presence of dynapenia in type 2 diabetes mellitus (T2DM) cases. Material and Methods: One hundred thirty-five male patients diagnosed with T2DM between 45 and 65 years of age were included. Patients were staged by ultrasonography according to NAFLD status. Results: There were significant differences in muscle strength, upper arm circumference, calf circumference, and up-and-go test scores between the NAFLD groups (p<0.001 for all). The frequency of dynapenia was lower, and arm and calf circumferences were higher in patients without NAFLD. The muscle strength, upper arm circumference, calf circumference, and up-and-go test scores were significantly lower in the dynapenic group compared to the non-dynapenic group (p<0.005 for all). The prevalence of dynapenia increased along with the increase in NAFLD stages (p<0.001). Conclusions: We detected a significant association between NAFLD and dynapenia in middle-aged men with T2DM. As muscle strength decreases, the amount of fat in the liver increases, and as the fat in the liver increases, muscle strength decreases.

We determined the levels of neutralizing antibodies against the SARS-CoV-2 ancestral strain, Delta and Omicron variants of concern (VOCs) in 125 healthcare workers, who received Coro-naVac as their primary vaccination and later received either a single ChAdOx1 or a combination of two consecutive boosters using either two ChAdOx1 doses or a ChAdOx1 or BNT162b2 as the primary and second boosters, respectively, or 2 doses of BNT162b2. The titers 12 weeks after primary vaccination were inadequate to neutralize the all strains. After a single ChAdOx1 boost-er, the levels of neutralization at Day 30 varied significantly, only a small proportion of partici-pants developing neutralizing titers against Omicron at Day 7 and 30. The two doses of ChA-dOx1 as the booster induced lowest activity. A combination ChAdOx1 and BNT162b2 induced greater neutralization than by two doses of ChAdOx1. Two doses of BNT162b2 as the booster had the maximal activity against Omicron VOC.

Large population passages of the SARS-CoV-2 in the past two and a half years have allowed the circulating virus to accumulate an increasing number of mutations in its genome. The most recently emerging Omicron subvariants have the highest number of mutations in the Spike (S) protein gene and these mutations mainly occur in the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the S gene. The eCDC and the WHO recommend partial Sanger sequencing of the SARS-CoV-2 S gene RBD and NTD on the PCR-positive samples in diagnostic laboratories as a practical means of determining the variants of concern to monitor a possible increased transmissibility, increased virulence, or reduced effectiveness of vaccines against them. The author’s diagnostic laboratory has implemented the eCDC/WHO recommendation by sequencing a 398-base segment of the N gene for the definitive detection of SARS-CoV-2 in clinical samples, and sequencing a 445-base segment of the RBD and a 490-509-base segment of the NTD for variant determination. This paper presents 5 selective cases to illustrate the challenges of using Sanger sequencing to diagnose Omicron subvariant when the samples harbor a high level of co-existing minor subvariant sequences with multi-allelic single nucleotide polymorphisms (SNPs) or possible recombinant Omicron subvariants containing a BA.1 NTD and a BA.2 RBD, which can only be detected by using specially designed PCR primers. The current large-scale surveillance programs using next-generation sequencing (NGS) do not face similar problems because NGS focuses on deriving consensus sequence.

Some of the lineages of SARS-CoV-2, the new coronavirus responsible for COVID-19, exhibit higher transmissibility or partial resistance to antibody mediated neutralization and were des-ignated by WHO as Variants of Interests (VOIs) or Concern (VOCs). The aim of this study was to monitor the dissemination of VOIs and VOCs in Venezuela during a year. A 614 nt genomic fragment was sequenced for the detection of some relevant mutations of these variants. Their presence was confirmed by complete genome sequencing, with a correlation higher than 99% between both methodologies. After the previously reported introduction of the Gamma VOC since the beginning of the year 2021, the variants Alpha VOC and Lambda VOI were detected as early as March 2021, at a very low frequency. In contrast, the Mu VOI, detected in May 2021, was able to circulate throughout the country. After the detection of Delta VOC in June 2021, it be-came the predominant circulating variant. With the arrival of the Omicron VOC in December, this variant was able to displace the Delta one in less than one month. This succession of variants was accompanied by a reduction in the Cycle threshold (Ct) values, in agreement with the in-crease in transmissibility described for these variants.

Osteoporosis is a common metabolic bone disease in patients with diabetes, which can develop simultane-ously with Type 2 diabetes (T2D) in postmenopausal women. Bisphosphonate (BP) is administered to pa-tients with both the conditions and may cause medication-related osteonecrosis of the jaws (MRONJ). It affects the differentiation and function of osteoclasts as well as thickness of cortical bone through bone mineralization. Therefore, this study aimed to investigate the effects of T2D on osteoclast differentiation and activity as well as cortical bone formation in postmenopausal patients with MRONJ. Tissue samples were collected from 10 patients diagnosed with T2D and Stage III MRONJ in the experimental group and from 10 patients without T2D in the control group. Histological examination was conducted, and expres-sion of dendritic cell-specific transmembrane protein (DC-STAMP) and tartrate resistant acid phosphatase (TRAP) was assessed. Cortical bone formation was analyzed using CBCT images. The number of TRAP-positive osteoclasts and DC-STAMP-positive mononuclear cells were significantly less in the experi-mental group (p < 0.05). Furthermore, the thickness and ratio of cortical bone were significantly greater in the experimental group (p < 0.05). In conclusion, T2D decreased the differentiation and function of osteo-clasts, and increased cortical bone formation in postmenopausal patients with MRONJ.

Part 1 of this 2-paper series identified a wide and deep network of context, generative mechanisms and outcomes responsible for psychosocial development in a performance basketball club. In this – part 2 – study, the stakeholder’s programme theories were tested during a full-season ethnography of the same club. The findings confirm the highly individualised nature of each young person’s journey. Methodologically, immersion in the day-to-day environment generated a fine-grain analysis of the processes involved, including: i) sustained attentional focus; ii) structured and unstructured skill building activities; iii) deliberate and incidental support; and iv) feelings indicating personal growth. Personal development in and through sport is thus shown to be conditional, multi-faceted, time-sensitive and idiosyncratic. The findings of this two-part study are considered to propose a model of psychosocial development in and through sport. This heuristic tool is presented to support sport psychologists, coaches, club administrators and parents to deliberately create and optimise developmental environments.

SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.

We report on the design, characterization and validation of a spherical irradiation system for inactivating SARS-CoV-2, based on UV-C 275 nm LEDs. The system is designed to maximize ir-radiation intensity and uniformity, and can be used for irradiating a volume of 18 liters. To this aim: (i) several commercially available LEDs have been acquired and analyzed; (ii) a complete optical study has been carried out in order to optimize the efficacy of the system. (iii) The re-sulting prototype has been characterized optically, and tested for the inactivation of SARS-CoV-2 for different exposure times, doses and surface types. Results indicate that a 99.9% inactivation can be reached after 1 minute of treatment with a dose of 83.1 J/m2.

With confirmed COVID-19 cases surpassing the 8.5 million mark around the globe, there is an imperative need to deepen the efforts from the international scientific community to gain comprehensive understanding of SARS-CoV-2. Although the main clinical manifestations are associated with respiratory or intestinal symptoms, reports of specific and non-specific neurological signs and symptoms, both at presentation or during the course of the acute phase, are increasing. Approximately 25-40% of the patients present neurological symptoms. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the Central Nervous System (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood-brain barrier (BBB). Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for MERS-CoV. Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to dysbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this work we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV, explore the potential role for astrocytes and microglia in the infection and neuroinflammation, and compare them with the previously described human and animal CoV that showed neurotropism. We also propose possible underlying mechanisms by focusing on our knowledge of glia, neurons, and their dynamic intricate communication with the immune system.

Spike protein is the surface glycoprotein of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) necessary for the entry of the virus via the transmembrane receptors of the human endothelial cells of the respiratoty system for the virus to be engulfed causing COVID-19 disease after priming by type II transmembrane protease TMPRSS2 and then binding with the angiotensin-converting enzyme 2 (ACE2). Therefore, mutations and amino acid variants analysis are essential in understanding the mechanism of binding of spike protein with its receptor to have an insights on possibilities to design a peptide or nucleotide-based vaccine for COVID-19. Here, we employed Iterative Threading Assembly Refinement (I-TASSER) and Multiple Alignment using Fast Fourier Transform (MAFFT) to predict the three-dimensional monomer structure of spike protein of SARS-CoV-2 and to analyze the amino acid variants for protein sequences from GISAID database for samples collected from Jordan in a try to find an explanation for the low confirmed number of COVID-19 in Jordan. Our Protein Homology/analogY Recognition Engine V 2.0 (Phyre2) findings showed four single amino acid variants (SAV) found in 20 samples of SARS-CoV-2. What is equal to 5% of samples showed tyrosine deletion at Y144 located in the SARS-CoV-like_Spike_S1_NTD (N terminal domain), 62% showed aspartate substitution to glycine at D614G located in the SARS-CoV-2_Spike_S1_RBD (spike recognition binding site), 5% showed aspartate substitution to tyrosine at D1139Y and 5% showed glycine substitution to serine at G1167S both located in the Corona_S2 domain. The findings have shown lower mutational sensitivity in all variants that might not affect the function of spike glycoprotein except for D614G, which has the highest mutational sensitivity score (5 out of 9) indicating a higher likelihood to affect the function of the spike protein. This might suggest, in general, a reduced transmitability of SARS-CoV-2 in Jordan.

Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

When working with the novel coronavirus SARS-CoV-2 during a pandemic response, having a rapid, reproducible and reliable assay for infectious virus quantitation and utilization for evaluation of potential therapeutics is critical. Compared to traditional agarose overlay plaques visualized with neutral red, assays performed with Avicel R RC-591 semi-solid overlay provide a simplified format for rapid and easy detection and neutralization testing. The method is easily modified for higher throughput using dispensers or automated processing. Fixation using formalin provides flexibility when dealing with pathogenic agents such as SARS-CoV-2 where tissue culture plates might be removed from biocontainment for staining. Although plaque assays are considered straightforward in principle, having an easily reproducible, consistent plaque assay is an invaluable tool.

We describe a 90-year-old male presenting with disequilibrium, loss of balance and difficulty walking for three days prior to initial presentation. Interestingly, he denied cough, fever or dyspnea prior to arrival. Over the course of 48 hours, the patient developed acute respiratory distress syndrome (ARDS) requiring intubation, diagnosed with COVID-19 infection and was treated in the intensive care unit where he died. Since the initial cases in Wuhan China in Dec 2019, the medical and epidemiological communities have learned much about the presenting features, symptomatology, epidemiology, transmission and common physical, laboratory and radiological findings of this disease. Although common symptoms are already established, it is very important to learn and record atypical symptoms or presentations of this highly contagious disease. By doing so, we will be able to recognize earlier atypical symptoms and prevent the environmental exposure to Health care workers and future patients as well. We report that Central disequilibrium may be such as initial presenting sign and symptom of impending respiratory failure from SARS-CoV-2 virus. These atypical findings such as presyncope may precede common respiratory complications of SARS-CoV-2.

SARS-CoV-2, the novel coronavirus behind COVID-19 pandemic is acquiring new mutations in its genome. Although some mutations provide benefits to the virus against human immune response, a number of them may result in their reduced pathogenicity and virulence. By analyzing more than 3000 high-coverage, complete genome sequences deposited in the GISAID database, here I report a unique 28881-28883:GGG>AAC trinucleotide-bloc mutation in the SARS-CoV-2 genome that results in two sub-strains, described here as SARS-CoV-2g (28881-28883:GGG genotype) and SARS-CoV-2a (28881-28883:AAC genotype). Computational analysis and literature review suggest that this bloc mutation would bring 203-204:RG(arginine-glycine)>KR(lysine-arginine) amino acid changes in the nucleocapsid (N) protein affecting the SR (serine-arginine)-rich motif of the protein, a critical region for the transcription of viral RNA and replication of the virus. Thus, 28881-28883:GGG>AAC bloc-mutation is expected to modulate the pathogenicity of the SARS-CoV-2. Remarkably, SARS-CoV-2g and SARS-CoV-2a strains can be linked with the heterogeneity of COVID-19 cases across different regions within and between countries by analyzing existing data. Sequence analysis suggests that severely affected cities, such as Milan, Lombardy, New York, Paris have the predominant presence of SARS-CoV-2g strains, whereas less affected places like Abruzzo, Lyon, Valencia have a relatively higher presence of SARS-CoV-2a, an indication that the latter strain may contribute to the reduced cases of COVID-19. A similar relationship is observed when Netherlands, Portugal are compared with Spain, France and Germany. These analyses suggest that the SARS-CoV-2 has already evolved into a less infective SARS-CoV-2a affecting COVID-19 cases in different regions. The time a country or region needs to acquire SARS-CoV-2a strains may be indicative to the time it would need to overcome the peak of the COVID-19 cases. To confirm these assumptions, prompt retrospective and prospective epidemiological studies should be conducted in different countries to understand the course of pathogenicity of the SARS-CoV-2a and SARS-CoV-2g. Potential drugs can be designed targeting 28881-28883 region of the N protein to modulate virus pathogenicity.

Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.

Crystalline β-cobalt hydroxide (β-Co(OH)₂) of different morphologies have been successfully synthesized with the addition of sodium hydroxide to cobalt nitrate solution and aging in the mother liquor. The rate of NaOH addition, ranging from 0.1 mL/min to 10 mL/min, influences the surface morphology with the obtained storage capability of the respective electrode. Characterization of the β-Co(OH)₂ was fully developed, including X-ray diffraction, scanning and transmission electron microscopy, and BET analyses. At a lower rate of NaOH addition, particles are like platelets, while for a higher rate (≥2 mL/min) grains are fused together forming a larger crystallite size. This result is supported by the X-ray diffraction structural analysis, where the phase evolution of (002) plane becomes distinct for the higher rate of NaOH addition. Lithium cobalt oxide (LiCoO₂) was synthesized through oxidation from the as-prepared β-Co(OH)₂ and LiOH. The electrochemical performance of as obtained LiCoO₂ is investigated using charge-discharge and cyclic voltammetric studies. The precursor β-Co(OH)₂ prepared at a lower rate of 0.1 mL/min in LiCoO₂ demonstrated the best electrochemical performance of 155 mAh/g. After 50 cycles, the capacity retention rate was 67% compared with the first cycle. Finally, we have attempted to correlate the amount of the available OH^- ions with the formation of platelets and the discharge capacity. This work has developed a methodology for the synthesis of LiCoO₂ using β-Co(OH)₂ in a facile chemical solution process.

DNA methylation is one of the epigenetic mechanisms which have been implicated in cellular differentiation, ageing and disease development. The effect of hypomethylating drug 5-aza-2´deoxycytidine (5-aza dC) on the biosynthetic profile of caudal region chondrocytes from chick sternum was studied in detail. The chondrocytes in culture were treated with varying doses of 5-aza dC for 48h and maintained subsequently without the treatment and harvested at selected time points for analysis of growth and differentiation status. 15µg/ml of 5-aza dC showed optimum Concentration at which there was a significant increase in DNA synthesis and RNA synthesis as per cell basis. There was also a significant increase in total protein synthesis and collagen synthesis as per cell basis at this concentration. This optimal concentration also showed to up regulate the gene expression of Type X collagen and alkaline phosphatase, which are the marker of hypertrophic chondrocyte expression. These results further support the notion that methylation is the major epigenetic factor controlling the differentiation and maturation of chondrocytes.

Super-Resolution Microscopy enables non-invasive, molecule-specific imaging of the internal structure and dynamics of cells with sub-diffraction limit spatial resolution. One of its major limitations is the requirement for high-intensity illumination, generating considerable cellular phototoxicity. This factor considerably limits the capacity for live-cell observations, particularly for extended periods of time. Here, we overview new developments in hardware, software and probe chemistry aiming to reduce phototoxicity. Additionally, we discuss how the choice of biological model and sample environment impacts the capacity for live-cell observations.

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

Fatigue risk to commercial pilots operating under global pandemic conditions had not been in-vestigated prior to COVID-19. Examining how pilots slept during COVID-19 pandemic-specific flights can provide a precedent for estimating fatigue risk for future public health emergencies. Twenty (n=20) pilots flying across five COVID-19 humanitarian missions between Brazil and China wore a sleep-tracking device (the Zulu watch), which has been validated for the estimation of sleep timing (sleep onset and offset), duration, efficiency, and sleep depth (Wake, Interrupted, Light, or Deep Sleep) throughout the mission period. Pilots also reported sleep timing, duration and subjective quality of their in-flight rest periods using a sleep diary. To our knowledge, this is the first report of commercial pilot sleep behavior during ultra-long-range operations under COVID-19 pandemic conditions. Moreover, these analyses provide an estimate of sleep depth during in-flight sleep, which has not been reported previously in the literature.

The intricate functionality of the vertebrate retina relies on the interplay between neurotransmitter activity and calcium dynamics, offering important insights into de-velopmental processes, physiological functioning, and disease progression. Neuro-transmitters orchestrate cellular processes to shape the behavior of the retina under diverse circumstances. Despite research to elucidate the roles of individual neuro-transmitters in the visual system, there remains a gap in our understanding of the holistic integration of their interplay with calcium dynamics in the broader context of neuronal development, health, and disease. To address this gap, the present review explores the mechanisms used by the neurotransmitters glutamate, GABA, glycine, dopamine, and acetylcholine and their interplay with calcium dynamics. This con-ceptual outline is intended to inform and guide future research, underpinning novel therapeutic avenues for retinal-associated disorders.

HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We interrogated mitochondrial function in a human microglia (hμglia) cell line harboring inducible HIV provirus, and in SH-SY5Y cells, after exposure to individual antiretroviral drugs or cART, using the MitoStress assay. cART-induced changes in protein expression, reactive oxygen species (ROS) production, mitochondrial DNA copy number, and cellular iron were also explored. Finally, we evaluated the ability of ROS scavengers or plasmid-mediated overexpression of the antioxidant iron-binding protein, Fth1, to reverse mitochondrial defects. Contemporary antiretroviral drugs, particularly bictegravir, depressed multiple facets of mitochondrial function by 20-30%, with most pronounced effects in latently infected-HIV+ hμglia and SH-SY5Y cells. Latently HIV-infected hμglia exhibited upregulated glycolysis. Increases in total and/or mitochondrial ROS, mitochondrial DNA copy number, and cellular iron accompanied mitochondrial defects in hμglia and SH-SY5Y cells. In SH-SY5Y cells, cART reduced mitochondrial iron-sulfur-cluster-containing supercomplex and subunit expression and increased Nox2 expression. Fth1 overexpression or pre-treatment with N-acetylcysteine prevented cART-induced mitochondrial dysfunction. Contemporary cART impairs mitochondrial bioenergetics in hμglia and SH-SY5Y cells, partly through cellular iron accumulation; some effects differ by HIV latency.

We simulate the effects of diagenesis, cementation and compaction on the elastic properties of shales and sandstones with four different petro-elastical theories and a basin-evolution model, based on constant heating and sedimentation rates. We consider shales composed of clay minerals, mainly smectite and illite, depending on the burial depth, and the pore space is assumed to be saturated with water at hydrostatic conditions. Diagenesis in shale (smectite/illite transformation here) as a function of depth is described by a 5th-order kinetic equation, based on an Arrhenius reaction rate. On the other hand, quartz cementation in sandstones is based on a model that estimates the volume of precipitated quartz cement and the resulting porosity loss from the temperature history, using an equation relating the precipitation rate to temperature. Effective pressure effects (additional compaction) are accounted for by using Athy equation and the Hertz-Mindlin model. The petro-elastic models yield similar seismic velocities, despite the different level of complexity and physics approaches, with increasing density and seismic velocities as a function of depth. The methodology provides a simple procedure to obtain the velocity of shales and sandstones versus temperature and pressure due to the diagenesis-cementation-compaction process.

The financial performance of local governments is closely related to the economic growth of a region. Strong financial performance provides a solid foundation for sustainable economic development. This study analyses the relationship between local government financial performance, capital expenditure, and sustainable economic growth in Banten Province. A quantitative approach was employed, using secondary data from Regional Revenue and Expenditure Budgets and economic growth statistics. Purposive sampling was utilised, and data analysis was conducted using Path Analysis. The findings reveal that several financial ratio variables significantly impact economic growth directly and indirectly through capital expenditure as a mediating variable. Directly, the independence ratio, effectiveness ratio, efficiency ratio, fiscal decentralisation ratio, dependency ratio, and capital expenditure significantly influence economic growth. The independence and effectiveness ratios have a positive impact, indicating that improvements in these variables directly foster economic growth. However, the efficiency and fiscal decentralisation ratios have a negative impact, suggesting that increases in these variables may reduce economic growth. Indirectly, through capital expenditure, the independence, effectiveness, dependency, and compatibility ratios significantly affect economic growth, with the independence ratio being the most dominant. Conversely, the fiscal decentralisation and efficiency ratios do not show significant indirect effects, indicating that capital expenditure is not an effective mediator for these variables.

Innovation is rapidly growing and affecting various industries, including hydrocarbon processing. This study aims to conduct a comprehensive and organized review of the literature on innovation ecosystems and their performance. It will examine existing definitions of innovation ecosystems and related concepts and identify metrics and indicators for measuring innovation and entrepreneurial ecosystems. The term "innovation ecosystem" has gained considerable attention from scholars and practitioners over the past fifteen years. Despite the proliferation of research in this area, there are concerns about its fragmented knowledge base. While previous reviews have highlighted the theoretical connections between innovation ecosystems and related concepts, there is still a need for a more comprehensive understanding of the current state of innovation ecosystem research. The study used a systematic literature review approach that combines bibliographic coupling and content analysis methods, drawing on over 100 studies to identify five streams of current innovation ecosystem research: technology innovation, platform innovation ecosystems, regional development, innovation ecosystem conceptualization and theorization, and entrepreneurship and innovation. The study's contribution lies in decoding the intellectual structure of current innovation ecosystem research and providing targeted recommendations for future research.

Based upon Maxwell's equations, it has long been established that oscillating electromagnetic (EM) fields incident upon a metal surface decay exponentially inside the conductor, leading to a virtual EM vacuum at sufficient depths. Magnetic resonance imaging (MRI) utilizes radiofrequency (r.f.) EM fields to produce images. Here we present the first visualization of a virtual EM vacuum inside a bulk metal strip by MRI, amongst several novel findings. We uncover unexpected MRI intensity patterns arising from two orthogonal pairs of faces of a metal strip, and derive formulae for their intensity ratios, revealing differing effective elemental volumes (voxels) underneath these faces. Further, we furnish chemical shift imaging (CSI) results that discriminate different faces (surfaces) of a metal block according to their distinct nuclear magnetic resonance (NMR) chemical shifts, which holds much promise for monitoring surface chemical reactions noninvasively. Bulk metals are ubiquitous, and MRI is a premier noninvasive diagnostic tool. Combining the two, the emerging field of bulk metal MRI can be expected to grow in importance. The fundamental nature of results presented here may impact bulk metal MRI and CSI across many fields.

Over the past decade, significant developments have occurred in treatment strategies for ovarian cancer, yet targeted therapy with few side effects is still a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs, with a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial for understanding the pathophysiology of ovarian cancer since many isoforms are essential for the metabolism of xenobiotics and steroid hormones, which drive the disease's development. The purpose of this review is to provide a clear understanding of differential CYP expression in ovarian cancer and its implications for the prognosis of ovarian cancer patients, together with their polymorphisms' effect on chemotherapy metabolism. Finally, we provide our thoughts on opportunities to exploit metabolic CYP expression for novel therapeutic development to treat ovarian cancer.

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with variable aggressive clinical behavior. In this retrospective study we aimed to investigate prognostic factors based on clinicopathologic findings in a molecular/immunohistochemical confirmed nationwide multicenter cohort of 57 EHE. Patients had unifocal disease (n=29), multifocal disease (n=5), lymph node metastasis (n=8) and/or distant metastasis (n=15) at the time of diagnosis. The overall survival rate was 69.6% at 1 year and 50.5% at 5 years. Survival did not correlate with sex, age or histo-pathological parameters. No survival differences were observed between multifocal and metastatic disease suggesting that multifocality represents early metastases and treatment options are limited in comparison to unifocal disease. In unifocal tumors, survival could be predicted using the risk stratification model of Shibayama et al. dividing the cases into low (n=4), intermediate (n=15) and high (n=3) risk-groups. Larger tumor size (>3cm) and higher mitotic count (>1/10HPF) was asso-ciated with progressive unifocal disease course. Lymph node metastases at time of diagnosis oc-curred in 14.0% of the cases and was mainly associated with tumor localization in the head and neck area proposing lymph node dissection. In conclusion, our results demonstrate the aggressive behavior of EHE, emphasize the prognostic value of a previous described risk stratification model and may provide new insights regarding tumor focality, therapeutic strategies and prognosis.

Background: Coffee is the second most popular drink in the worldwide, and it has different components with antioxidant and antitumor properties. The objective of this study was to explore the relationship between coffee consumption and the incidence and mortality of stomach cancer in the main consuming countries. Methods: An observational study was performed. Dataset of coffee consumption was obtained from WorldAtlas, and incidence and mortality rates from GLOBOCAN database. Spearman's rank correlation coefficient was calculated. All statistical analysis were performed using STATA software. Results: A total of 25 countries were included in the study. There was a significant linear correlation between coffee consumption kg per person per year and an estimated age-adjusted incidence (r=0.5984, p=0.0016) and mortality (r=0.5877, p=0.0020). Conclusion: Coffee consumption could potentially have beneficial effects on incidence and mortality by stomach cancer.

Curcumin, as the main active component of Turmeric (Curcuma Longa), has been demonstrated with various bioactivities. However, its potential therapeutic applications are hindered by challenges such as poor solubility and bioavailability, rapid metabolism, and pan-assay interference properties. Recent advancements have aimed to overcome these limitations by developing novel curcumin analogues and modifications. This brief review critically assesses recent studies on synthesising different curcumin analogues, including metal complexes, nano particulates, and other curcumin derivatives, focused on the antioxidant, anti-inflammatory, and anticancer effects of curcumin and its modified analogues. Exploring innovative curcumin derivatives offers promising strategies to address the challenges associated with its bioavailability and efficacy and valuable insights for future research directions.

Traceability is the ability to determine the path of a product from purchase to consumption to determine when and where it originated. This paper aimed to determine the factors that influence fishers’ decision-making to participate in tuna traceability program, it also explores the determinants of fish catch for small-scale fishers and the feasibility of implementing tuna traceability in the Davao Gulf, Philippines. The result of the interview showed that the significant factors that highly affected the decision-making of fishers in implementating tuna traceability program: boat capacity, fishing hours and communication of fishers (P≤0.05). Household size, years in community, fishing hours, volume of fish sold, and the fishers' communication in the fishing ground (P≤0.05) were other factors that determined the daily catch of the fishers. The results of this study showed that fishers from the Davao Gulf were willing to be part of traceability program that would sustain and increase the value of their fish catch. Moreover, communication was shown to be critically needed in such programs adjusting it for the fish catch to remain fresh or of good quality. Our study will help in deterring and mitigating illegal, unregulated and unreported fishing (IUU) through fish catch traceability.

The study evaluated the functional and sensory properties of infant complementary foods formulated from millets, orange-flesh sweet potatoes, carrots, periwinkle and oyster. Experimental/cross-sectional design was used. Millet, orange-flesh sweet potato (OFSP), carrots, periwinkle and oyster were purchased, processed into flour using standard methods. The complementary food was formulated on protein basis for infants 6–12 months. The formulated foods were millet/OFSP flours (70:30), millet/OFSP/carrot/periwinkle (49:29:7:15), and millet/OFSP/carrot/oyster (65:20:5:10). Functional properties were carried out using standard methods. Sixty nursing mothers attending Orogbum Health Centre were systematically sampled for the sensory evaluation. ANOVA was used for the study. The result showed packed density (0.77 g/mL) was significantly higher (p < 0.05) in food formulated from millets/OFSP than in millet/OFSP/carrot/oyster (0.68 g/mL). Loosed density was lowest (0.40 g/mL) in millet/OFSP/carrot/oyster. Carr index from ranged from 42.23 in millet/OFSP/carrot/oyster to 44.41 in millet/OFSP. Wettability was highest (45.03) in millet/OFSP/carrot/periwinkle compared to wettability value (26.53) for millet/OFSP. Solubility ranged from 18.36 to 46.62, with the highest (46.62) in millet/OFSP/carrot/periwinkle. The peak viscosity of the infant complementary food samples ranged from 64.53 rapid visco analyzer units (RVU) to 89.33 RVU. The infant complementary food formulated from millet/OFSP had significantly higher (p < 0.05) acceptability score (6.35).

Accurate and reliable measurement of real-world walking activity is clinically relevant, particularly for people with mobility difficulties. Insights on walking can help understand mobility function, disease progression, and fall risks. People living in long-term residential care environments have heterogeneous and often pathological walking patterns, making it difficult for conventional algorithms paired with wearable sensors to detect their walking activity. We designed two walking bout detection algorithms for people living in long-term residential care. Both algorithms used thresholds on the magnitude of acceleration from a 3-axis accelerometer on the lower back to classify data as “walking” or “non-walking”. One algorithm had generic thresholds, while the other used personalized thresholds. To validate and evaluate the algorithms, we compared the classifications of walking/non-walking from our algorithms to the real-time research assistant annotated labels and the classification from an algorithm validated on a healthy population. Both the generic and personalized algorithms had acceptable accuracy (0.83 and 0.82 respectively). The personalized algorithm showed the highest specificity (0.84) of all tested algorithms, meaning it was the best suited to determine input data for gait characteristic extraction. The developed algorithms were almost 60% quicker than the previously developed algorithms, suggesting they are adaptable for real-time processing.

Pemphigus vulgaris is an autoimmune blistering disease of the epidermis, caused by autoantibodies against desmosomal proteins, mainly desmogleins 1 and 3, which induce an impairment of desmosomal adhesion and blister formation. Recent findings have shown that inhibition of immunoglobulin G binding on the neonatal Fc receptor, FcRn, results in reduced autoantibody recycling and shortens their half-life, providing a valid treatment option for PV. We have here analyzed the role of FcRn in human keratinocytes treated with novel, recombinant anti-desmoglein-3 antibodies that induce pathogenic changes in desmosomes, such as loss of monolayer integrity, aberrant desmoglein-3 localization and degradation of desmoglein-3. We show that blocking IgG binding on FcRn by efgartigimod, a recombinant Fc fragment that is undergoing clinical studies for pemphigus, stabilizes the keratinocyte monolayer, whereas the loss of desmoglein-3 is not prevented by efgartigimod. Our data show for the first time that FcRn may play a direct role in the pathogenesis of pemphigus at the level of the autoantibody target cells, the epidermal keratinocytes. Our data also imply that in keratinocytes, FcRn may have functions different from its known function in IgG recycling. Therefore, stabilization of keratinocyte adhesion by FcRn blocking entities may provide a novel treatment paradigm for pemphigus.

Hyperbaric oxygen (HBO) treatment has been proven to attenuate neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague–Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment, (2) sham burn with HBO treatment, (3) burn with 1-week sham HBO treatment, (4) burn with 2-week sham HBO treatment, (5) burn with 1-week HBO treatment, and (6) burn with 2-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting, and a behavior test was also conducted. The behavior test revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin were significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis results showed that the expression of Gal-3, TLR-4, CD68, and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor (FGF) in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia/macrophage activation in a rat model.

A new synthetic approach to polyfunctional hexahydropyrrolo[3,4-b]pyrroles was developed based on cyclization of N-arylbromomaleimides with aminocrotonic acid esters. A highly chemo- and stereoselective reaction is a Hantzsch-type domino process, involving the steps of initial nucleophilic C-addition or substitution and subsequent intramolecular nucleophilic addition without recyclyzation of imide cycle.

Accurate and timely testing has become an essential measure in combatting the COVID-19 global pandemic. Currently, polymerase chain reaction (PCR) based assays are the most relied on methods for SARS-CoV-2 detection. This traditional workflow involves a viral RNA extraction from the viral transport media storing nasopharyngeal swabs collected from patients, followed by PCR based detection. While accurate, this methodology is time consuming and resource heavy, causing for delays in receiving results or limited access to testing. Herein, we demonstrate a validated method for SARS-CoV-2 detection from viral transport media using a two-step, direct-to-PCR workflow revolving around shaker-mill homogenization. This method completely bypasses the extraction steps of the traditional workflow, replacing it with 30 seconds of mechanical disruption sufficient to allow for COVID-19 detection with a 96.43% sensitivity and 100% specificity when compared to traditional extraction to PCR based methods.

The study aims to determine the trust and presence of police officers in schools in Serbia, as well as the perception of the principals and secretaries, teachers and staff, parents and students on how successful the certain police units dedicated to schools were in fulfilling their tasks. The ex–post analysis was conducted through PEST/SWAT analysis, mapping of the key actors and using batteries of online questionnaires. Besides interviews with the MOI representatives, there were conducted: Survey with personal interviewing, Computer–aided surveying and Desk analysis and content analysis. The survey was conducted in the period from September 2021 to June 2022. The research methods were implemented in 1140 schools in Serbia and 8,617 people were included in surveys: police officers (308); principals and secretaries (1085); the team for protection against discrimination (982); teachers and staff (2988); parents (938) and students (2316). The relationships between the covariates and perception were investigated using the t–test, one–way ANOVA, multivariate linear regression, and binary regression. The results showed that a project of school police officers was not fully recognized as one of the strategically important instruments for safe schools, trust is low but presence is high. Besides that, the results suggest that the entire public believe that a police is needed in schools and that it has a very positive effect on school safety. Regarding school safety policy, it is necessary to undertake three types of measures for sustainable development of trust and presence of police in school: regulatory, informa-tive-educational and institutional-organizational.

Interpretive Structural Modelling (ISM) is widely used to understand the complex connections between different components. This study presents a bibliometric overview of ISM research with a focus on its linkages to the Sustainable Development Goals (SDG) and the impact of COVID-19. The study analyzed 1988 publications on ISM published between 2012 and 2021, of which 1202 were directly mapped to the SDG and 59 were related to COVID-19. The study identified key authors, institutions, countries, and journals involved in the research and their linkages to the SDG. The results showed that ISM research is strongly linked to SDG 12 (Responsible Consumption and Production) and SDG 9 (Industry, Innovation and Infrastructure). We also identified influential SDG based on centrality measures like betweenness and eigenvector. The top four countries contributing to ISM publications were India, China, the United Kingdom, and the United States. The most frequently cited journals were Benchmarking: An International Journal, Sustainability, Journal of Modelling in Management, and Journal of Cleaner Production. Four main clusters were identified in the ISM research, including (1) integration with AHP & Fuzzy Logic for promoting sustainability alignment, (2) ISM-based strategy development for various stakeholders, (3) ISM-based decision-making in various fields, and (4) ISM-based risk evaluation. For the first time studies that used ISM approach to understand the epidemiological characteristics of COVID-19 were identified and their key findings were discussed. The study also identified several emerging topics for future ISM research, such as blockchain & IoT, environmental management systems, climate change adaptation, smart cities, and humanitarian logistics and their potential linkages to SDG.

The COVID-19 pandemic has brought about unprecedented changes to human lifestyles across the world. The virus and associated social restriction measures have been linked to an increase in mental health conditions. A considerable body of evidence shows that spending time in and engaging with nature can improve human health and wellbeing. Our study explores nature’s role in supporting health during the COVID-19 pandemic. We created web-based questionnaires with validated health instruments and conducted spatial analyses in a geographic information system (GIS). We collected data on people’s patterns of nature exposure, associated health and wellbeing responses, and potential socioecological drivers such as relative deprivation, access to greenspaces, and land-cover greenness. We applied a range of statistical analyses including bootstrap resampled correlations and binomial regression models, adjusting for several potential confounding factors. We found that respondents significantly changed their patterns of visiting nature as a result of the COVID-19 pandemic. People spent more time in nature and visited nature more often during the pandemic. People generally visited nature for a health and wellbeing benefit and felt that nature helped them cope during the pandemic. Greater land-cover greenness within a 250 m radius around a respondent’s postcode was important in predicting higher levels of mental wellbeing. There were significantly more food-growing allotments within 100 m and 250 m of respondents with high mental wellbeing scores. The need for a mutually-advantageous relationship between humans and the wider biotic community has never been more important. We must conserve, restore and design nature-centric environments to maintain resilient societies and planetary health.

Combining antiviral drugs with different mechanisms of action can help prevent the development of resistance by attacking the infectious agent through multiple pathways. Additionally, by using faster and more economical screening methods, effective synergistic drug candidates can be rapidly identified, facilitating faster paths to clinical testing. In this work, a rapid method was standardized to identify possible synergisms from drug combinations. We analyzed the possible reduction of antiviral effective concentration of drugs already approved by the FDA, such as ivermectin  (IVM), ribavirin (RIBA) and acyclovir (ACV) against Zika virus (ZIKV), Chikungunya virus (CHIKV) and herpes virus type 2 (HHV-2). Essential oils (EOs) were also included in the study since they have been reported for more than a couple of decades to have broad-spectrum antiviral activity. We also continued studying the antiviral properties of one of our patented molecule with broad-spectrum antiviral activity, the ferruginol analogue 18-(phthalimid-2-yl)ferruginol (phthFGL). In general, the combination of IVM, phthFGL and Oregano EO showed the greatest synergism potential against CHIKV, ZIKV and HHV-2, obtaining a reduction in the EC99 value of up to ~8, and ~27, and ~12-fold for CHIKV, in example, respectively. The ternary combination RIBA, phthFGL, Oregano EO was slightly more efficient than the binary combination RIBA/phthFGL but much less efficient than IVM, phthFGL, Oregano EO which indicates that IVM could contribute more to the differentiations of cell targets (for example by inhibition of host heterodimeric importin IMP α/β1 complex) than ribavirin. PhthFGL showed a good pharmacokinetic profile.

In the Mediterranean area, vegetation dynamics and phenology analyzed over a long time can have an important role in highlighting changes in land use and cover as well as the effect of climate change. Over the last 30 years, remote sensing has played an essential role in bringing about these changes thanks to many types of observations and techniques. Satellite images are to be considered an important tool to grasp these dynamics and evaluate them in an inexpensive and multidisciplinary way thanks to Landsat and Sentinel satellite constellations. The integration of these tools holds a dual potential: on one hand, allowing to obtain longer historical series of reflectance data, while on the other hand, making data available with a higher frequency even within a specific timeframe. The study aims to conduct a comprehensive cross-comparison analysis of long-time series pixel values in the Mediterranean regions. For this scope comparisons between Landsat-7 (ETM+), Landsat-8 (OLI), and Sentinel-2 (MSI) satellite sensors were conducted based on surface reflectance products. We evaluated these differences using Ordinary Least Squares (OLS) and Major Axis linear regression (RMA) analysis on points extracted from over 15,000 images across the Mediterranean basin area from 2017 to 2020. Minor but consistent differences were noted, necessitating the formulation of suitable adjustment equations to better align Sentinel-2 reflectance values with those of Landsat-7 or Landsat-8. The results of the analysis are compared with the most used harmonization coefficients proposed in the literature, revealing significant differences. The root mean square deviation, the mean difference and the orthogonal distance regression (ODR) slope show an improvement of the parameters for both models used (OLS and RMA) in this study. The discrepancies in reflectance values lead to corresponding variations in the estimation of biophysical parameters, such as NDVI, showing an increase in the ODR slope of 0.3. Despite differences in spatial, spectral, and temporal characteristics, we demonstrate that integration of these datasets is feasible through the application of band-wise regression corrections for a sensitive and heterogeneous area like those of the Mediterranean basin area.

Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury termed the response to injury wound healing (RTIWH) mechanism. When injured, regional brain endothelial cells initially undergo activation and dysfunction with initiation of hemostasis, inflammation (peripheral leukocytes and innate microglia and perivascular macrophage cells), proliferation (astrogliosis), remodeling, repair, and resolution phases if the injurious stimuli are removed. In conditions wherein the injurious stimuli are chronic as occurs in obesity, metabolic syndrome, and type 2 diabetes mellitus this process does not undergo resolution and there is persistent RTIWH with remodeling. Indeed, the brain is unique, in that it utilizes its neuroglia: the microglia cell along with peripheral inflammatory cells and its astroglia instead of peripheral scar-forming fibrocytes/fibroblasts. The brain undergoes astrogliosis to form a gliosis scar instead of a fibrosis scar to protect the surrounding neuropil from regional parenchymal injury. One of the unique and evolving remodeling changes in the brain is the development of enlarged perivascular spaces (EPVS), which is the focus of this brief review. EPVS are important since they serve as a biomarker for cerebral small vessel disease and also represent an impairment of the effluxing glymphatic system that is important for the clearance of metabolic waste from the interstitial fluid to the cerebrospinal fluid and disposal. Therefore, it is important to better understand how the RTIWH mechanism is involved in the development of EPVS that are closely associated with and important to the development of premature and age-related cerebrovascular and neurodegenerative diseases with impaired cognition.

Background: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. Method: To determine the effect of a nursing educational intervention on improving healthy sleep, a parallel, open-label clinical trial in subjects with Impaired Fasting Glucose (IFG) or Type 2 Diabetes Mellitus (T2DM) and 18 and older was performed. Study variables were sex, age, fasting glucose, glycated hemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, BMI, antidiabetic treatment and diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. It was intended to develop skills to improve sleep through 9 simple tips. An analysis of covariance was performed on all the mean centered outcome variables controlling for the respective baseline scores. Results: After the intervention, in the experimental group, PSQI dropped, the duration and quality of sleep increased. Further, a decrease in fasting glucose and in HbA1c levels was observed. Conclusion: The proposed intervention has proven to be effective to improve sleep quality, time, and efficiency and in only 3 months, to achieve a decrease in fasting glucose and HbA1c levels. These findings support the importance of sleep and circadian rhythms education focused on improving in T2DM or IFG.

Background Hokkaido is the northernmost, least populous, and coldest of the Japanese islands. It was the first prefecture to be affected by COVID-19, while Kanagawa is home to one of the most populous areas of Japan, namely the Tokyo metro area. The Japanese government responded early during the pandemic by identifying infected patients, contact tracing, and performing PCR analysis on anyone who was suspected of having been exposed to SARS-CoV-2. The government has also been publishing information about each individual who tested positive for the virus. Both Hokkaido and Kanagawa started recording COVID-19 cases in the winter of 2020 and have detailed records of thousands of patients, thus providing an invaluable resource for the transmission and behavior of the virus. Methods The current study analyzed the COVID-19 registry data from the Hokkaido and Kanagawa prefectures. The Hokkaido registry contained 1,269 cases (674 (53%) females and 595 (47%) males) recorded between February 14 and July 22, 2020. The Kanagawa registry had 3,123 cases (1,346 (43%) females and 1,777 (57%) males. The final data contained a total of 4,392 cases (2,020 (46%) females and 2,372 (54%) males). By leveraging the information on viral transmission paths available in the registry data, we performed exponential random graph model (ERGM) network analysis to examine demographic and symptomological homophilies of the SARS-CoV-2 viral transmission networks. Results We observed age, symptomatic, and asymptomatic homophilies in both prefectures. Furthermore, those patients who contracted the virus through secondary or tertiary contacts were more likely to be asymptomatic than those who contracted it from primary infection cases. The transmission networks showed that transmission occurred significantly in healthcare settings, as well as in families, although the size of the networks was small in the latter. Most of the transmissions stopped at the primary and secondary levels and no transmission beyond quaternary was observed. We also observed a higher level of asymptomatic transmission in Kanagawa than in Hokkaido. Conclusions Symptom homophilies are an important component of COVID-19 and suggest that nuanced genetic differences in the virus may affect its epithelial cell type range and can thus result in the diversity of symptoms seen in individuals infected by SARS-CoV-2. Moreover, environmental variables such as temperature and humidity may also be playing an important role in the overall pathogenesis of the virus.

Introduction: IFITM3, an innate immune protein linked to COVID-19 severity, has recently been identified as a novel γ-secretase modulator. Independent research has shown that IFITM3 may facilitate SARS-CoV-2 neurotropism in an ACE2-independent manner. In a previous study, we had detected perturbations in IFITM3 networks in both the CNS and peripheral immune cells donated by AD patients. The purpose of this study is to explore the transcriptomic evidence of the SARS-CoV-2 / IFITM3 / AD interplay, validating previous findings from our group. Methods: Exploratory analyses involved meta-analysis of bulk and single cell RNA data for IFITM3 and FYN differential expression. For confirmatory analyses, we performed gene set enrichment analysis (GSEA) on an AD gene signature from AD Consensus transcriptomics; using the Enrichr platform, we scrutinized COVID-19 datasets for significant, overlapping enriched biological networks. Results: Bulk RNA data analysis revealed that IFITM3 and FYN were differentially expressed in two CNS regions in AD: the temporal cortex (AD vs. Controls, adj.p-value=1.3e^-6) and the parahippocampal cortex (AD vs. controls, adj.p-value=0.012). Correspondingly, single cell RNA analysis of IFITM3 and FYN revealed that it was differentially expressed in neuronal cells donated from AD patients (astrocytes, microglia and oligodendrocyte precursor cells), when compared to controls. Discussion: IFITM3 and by extent FYN were found as interactors within biological networks overlapping between AD and SARS-CoV-2 infection. SARS-CoV-2-mediated FYN/IFITM3 induction would mechanistically result in increased Tau fibrilization and Aβ oligomerization. FYN recruitment by viral processes results in abrogation of both fusion of IFITM3 vesicles with lysosomes; immunoevasion, by FYN-mediated impairment of autophagy would then serve to promote impaired detoxification from Aβ, while propagating Tau pathology in an IFITM3-independent manner.

Phylogeny construction can help to reveal evolutionary relatedness among molecular sequences. The spike (S) gene of SARS-CoV-2 is the subject of an immune selective pressure which increases the variability in such region. This study aimed to identify mutations in the S gene among SARS-CoV-2 sequences collected in the Middle East and North Africa (MENA), focusing on the D614G mutation, that has a presumed fitness advantage. Another aim was to analyze the S gene sequences phylogenetically. The SARS-CoV-2 S gene sequences collected in the MENA were retrieved from the GISAID public database, together with its metadata. Mutation analysis was conducted in Molecular Evolutionary Genetics Analysis software. Phylogenetic analysis was done using maximum likelihood (ML) and Bayesian methods. A total of 553 MENA sequences were analyzed and the most frequent S gene mutations included: D614G=435, Q677H=8, and V6F=5. A significant increase in the proportion of D614G was noticed from (63.0%) in February 2020, to (98.5%) in June 2020 (p<0.001). Two large phylogenetic clusters were identified via ML analysis, which showed an evidence of inter-country mixing of sequences, which dated back to February 8, 2020 and March 15, 2020 (median estimates). The mean evolutionary rate for SARS-CoV-2 was about 6.5 × 10^-3 substitutions/site/year based on large clusters’ Bayesian analyses. The D614G mutation appeared to be taking over the COVID-19 infections in the MENA. Bayesian analysis suggested that SARS-CoV-2 might have been circulating in MENA earlier than previously reported.

Mitochondria are classically termed as powerhouse of a mammalian cell. Most of the cellular chemical energy in the form of adenosine tri phosphate (ATP) is generated by mitochondria and dysregulation of mitochondrial functions thus can be potentially fatal of cellular homeostasis and health. Acute respiratory distress has been earlier linked to mitochondrial dysfunction. SARS-CoV-2 infection severity leads to acute respiratory distress syndrome (ARDS) and can be fatal. We tried to investigate possible connection between SARS-CoV-2, ARDS and mitochondria. Here, we report identification of SARS-CoV-2 non-structural proteins (particularly Nsp12 and 13) that have recognition sequence with respect to mitochondrial entry. We also report that these proteins can potentially shuttle between cytoplasm and mitochondria based on the localization signals and help in downstream maintenance of the virus. Their properties to use ATP for enzymatic activities may cause ATP scavenging allowing viral RNA functions in lieu of host cell health.

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China has resulted in an outbreak in China which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 175 countries while affecting nearly 500,000 persons and causing more than 22,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. Till date, no clinically proclaimed, proven therapeutic antibodies or specific drugs and therapeutics, and vaccines have turned up. Several molecular diagnostic tests such as Real Time-PCR, isothermal loop-mediated amplification of coronavirus (i-LACO), full genome analysis by next-generation sequencing (NGS), multiplex nucleic acid amplification, and microarray-based assays are in use currently for the laboratory confirmation of this CoV infection. In this review article, we describe the basic molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.

Statistics of languages are calculated by counting characters, words, sentences, word rankings. Some of these random variables are also the main “ingredients” of classical readability formulae. Revisiting the readability formula of Italian, known as GULPEASE, shows that of the two terms that determine the readability index G – the semantic index G_C, proportional to the number of characters per word, and the syntactic index G_F, proportional to the reciprocal of the number of words per sentence −, G_F is dominant because G_C is, in practice, constant for any author throughout seven centuries of Italian Literature. Each author can modulate the length of sentences more freely than he can do with the length of words, and in different ways from author to author. For any author, any couple of text variables can be modelled by a linear relationship y=mx, but with different slope m from author to author, except for the relationship between characters and words, which is unique for all. The most important relationship found in the paper is, in author’s opinion, that between the short−term memory capacity, described by Miller’s “7∓2 law”, and the word interval, a new random variable defined as the average number of words between two successive punctuation marks. The word interval can be converted into a time interval through the average reading speed. The word interval is spread in the same of Miller’s law, and the time interval is spread in the same range of short−term memory response times. The connection between the word interval (and time interval) and short−term memory appears, at least empirically, justified and natural, and should further investigated. Technical and scientific writings (papers, essays etc.) ask more to their readers. A preliminary investigation of these texts shows clear differences: words are on the average longer, the readability index G is lower, word and time intervals are longer. Future work done on ancient languages, such as Greek or Latin, could bring us a flavor of the short term−memory features of these ancient readers.

This study aimed to compare three different extracts of Saco sweet cherry, namely non-coloured fraction, coloured fraction and total extract concerning phenolic composition, antioxidant and antidiabetic potential, erythrocytes’ protection and effects on Caco-2 cells. A total of 22 phenolic compounds were identified by LC-DAD. Hydroxycinnamic acids were the most predominant in both non-coloured fraction and total extract, while cyanidin-3-O-rutinoside was the main anthocyanin found in the coloured fraction. The total extract was the most effective against DPPH, nitric oxide and superoxide radicals, and in the inhibition of α-glucosidase enzyme. Finally, the protective effect of the extracts to prevent oxidative damage in human erythrocytes was assessed. The coloured fraction revealed the best activity against hemoglobin oxidation and hemolysis. Regarding to Caco-2 cells, the coloured extract exhibited the most cytotoxic effects, while the total extract was the most efficient in protecting these cells against oxidative damage induced by t-BHP.

A good optical quality crystal of 2-aminopyridine (2AP) metal complex crystals was grown by slow evaporation technique at room temperature. The transparent and defect less bulk size of 2-aminopyridine potassium dihydrogen orthophosphate metal complex crystals have been grown by solution growth method. The molecular structure and morphology of grown crystals was drawn and planes are indexed using WINXMORPH software. A optical absorption spectrum, the UV cut-off wavelength, Band gap (Eg), Reflectance (R), Refractive Index (n), Extinction coefficient (K) and Electrical susceptibility (χc) are calculated for 2AP metal complex crystals.

Matrix metalloproteases (MMPS) are a family of well-known enzymes which operate prevalently in the extracellular domain, where they fulfil the function of remodeling the extracellular matrix. Within the about 26 family members, encoded by 24 genes in humans, MMP-2 and MMP-9, have been regarded as the primary responsibility for the basement membrane and pericellular ECM rearrangement. In cases of infiltrating carcinomas, which arise from the epithelial tissues of a gland or of an internal organ, a marked alteration of the expression and the activity levels of both MMPs is known to occur. Present investigation represents the continuation and upgrading of our previous studies, now focusing on the occurrence and intensity levels of MMP-2 and -9, and their proteomic correlations, in a cohort of 80 breast cancer surgical tissues

A series of (benzoimidazol-2-ylmethyl)amine palladium(II) complexes have been employed as catalysts in the homogenous hydrogenation of alkenes and alkynes under mild conditions. A correlation between the catalytic activity and the nature of the ligand was established. Kinetic studies of the hydrogenation reactions of styrene established pseudo-first-order dependence on styrene substrate. On the other hand, partial orders with respect to H2 and catalyst concentrations were obtained consistent with the formation of palladium(II) monohydride species as the active species. The nature of the solvent used influenced the hydrogenation reactions, where coordinating solvents resulted in lower catalytic activities. Density functional theory investigations provided valuable insights into the reactivity trends and influence of complex structure on the hydrogenation reactions.

The article describes facile one-pot, hi-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide (3a–m) and carbohydrazide analogues (5a–l) as potential antifungal and antimicrobial agents. The structural integrity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compound 5h, 5i and 5j were found to be the most potent against A. fumigatus, with MIC value of 0.031 mg/mL. The compound 5f bearing a 2,6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking to the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron related deleterious side effects observed with existing antifungal compounds.

The deployment of Artificial Intelligence (AI) systems in decentralized environments is on the rise, yet representation of shared conceptualization in such scenarios remains a challenging issue. The absence of a shared understanding can lead to suboptimal performance of AI systems and hinders the ability to comprehend the knowledge and beliefs of agents in the domain. This paper proposes a formal model for modeling conceptualization in AI systems that integrates ontology, epistemology, and epistemic logic. The model aims to address the gap in representing shared conceptualization in decentralized environments and enhance the performance of AI systems operating in such environments. The proposed model is a hybrid structure that blends extensional and intensional structures and leverages logic-based languages for modeling purposes. A case study in the healthcare sector is presented to illustrate the application of the proposed model. The study contributes to the existing literature by providing a formal model for representing shared conceptualization in decentralized environments, which can be utilized to optimize the performance of AI systems in these environments.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Two new coordination compounds of Mn(II) and Cu(II) viz. [Mn(bz)2(Hdmpz)2(H2O)] (1) and [Cu(crot)2(Hdmpz)2] (2) (where, bz = benzoate, crot = crotonate, Hdmpz = 3, 5-dimethyl pyrazole) have been synthesized and characterized using single crystal X-ray diffraction technique, FT-IR, electronic spectroscopy, TGA and elemental analyses. Compounds 1 and 2 crystallize as mono-nuclear coordination compounds of Hdmpz based penta-coordinated Mn(II) and hexa-coordinated Cu(II) respectively containing distorted trigonal bipyramidal and distorted octahedral geome-tries. Crystal structure analysis of compound 1 reveals the presence C‒H⋯π and π-stacking in-teractions along with O‒H⋯O, N‒H⋯O and C‒H⋯O H-bonding interactions which stabilizes the layered assembly of the compound. Similarly, the presence of hydrogen bonding along with π-stacking interactions stabilizes the crystal structure of compound 2. We have carried out theo-retical investigations to analyze π⋯π H-bonding and antiparallel CH···π non-covalent interac-tions observed in the compounds. DFT calculations were performed to evaluate strength of these interactions energetically. Moreover, QTAIM and non-covalent interaction (NCI) plot index computational tool were used to characterize them and evaluate the contribution of the H-bonds.

We investigated and quantified bacterial accumulation in facemasks used by the general population, using 16S rRNA (Sanger Sequencing), culture and biochemical analysis along with Rose Bengal staining. Additionally, a systematic overview of the literature on face mask contamination was undertaken. We found an average bacterial load of 4.24 × 10⁴ CFU recovered/mask, with a maximum load of 2.85 × 10⁵ CFU. This maximum is 310 times higher than the limit value for contamination of ventilation system outlet surfaces specified by the German standard VDI 6022. Biochemical and molecular identification predominantly found Staphylococcus species (80%), including Staphylococcus aureus, along with endospore-forming Bacillus spp. Literature reports also indicate contamination of masks by bacterial and fungal opportunists of the genera Acinetobacter, Aspergillus, Alternaria, Bacillus, Cadosporium, Candida, Escherichia, Enterobacter, Enterococcus, Klebsiella (including K. pneumoniae), Micrococcus, Microsporum, Mucor, Pseudomonas, Staphylococcus and Streptococcus. Bacterial counts increase linearly with wearing duration, and prolonged use may affect the skin and respiratory microbiomes, promoting consequential eye, skin, oral and airway conditions. These aspects underscore the urgent need for further research and a risk-benefit analysis in respect of mask use, particularly given their unproven efficacy in disrupting the transmission of respiratory viruses and their adverse social consequences.

This paper describes some of the challenges that need to be addressed in order to develop collaborative spectrum sharing systems. The importance of these challenges stems from the assumption that rules for spectrum sharing can change after the deployment of radio networks and the whole system must be able to adapt to them. To address such a requirement, we used a policy-based approach in which transmissions are controlled by a policy interpreter system, and the policies can be modified during system operation. Our primary goal was to develop a prototype of such a system. In this paper, we outline the implementation of policy interpretation, automatic generation of transmission opportunities in case a request for transmission is denied by the policy reasoner, and the generation of rendezvous channels for the synchronization of otherwise asynchronously running software defined radios.

Energy demand has been overgrowing in developing countries. Moreover, the fluctuation of fuel prices is a primary concern faced by many countries that highly rely on conventional power generation to meet the load demand. Hence, the need to use alternative resources such as renewable energy is crucial to mitigate fossil fuel dependency alongside the reduction of Carbon Dioxide emission. Algeria’s being the largest county in Africa has rapid growth in energy demand since the past decade due to the significant increase of residential, commercial, and industry sectors. Currently, the hydrocarbon-rich nation highly dependent on fossil fuels for electricity generation, where renewable energy only has a small contribution to the country’s energy mix. However, the country has massive potential for renewable energy generations such as solar, wind, biomass, geothermal, and hydropower. Therefore, the government aims to diversify away from fossil fuel and promoting renewable energy generations through policies and renewable energy-related programs. The country’s Renewable Energy and Energy Efficiency Development Plan focuses on large scale solar, wind generation as well as geothermal and biomass technologies. This paper provides an update on the current energy position and renewable energy status in Algeria. Moreover, this paper discusses RE policies and programs that aim to increase the country’s renewable energy generation and its implementation status.

Among nonsteroidal anti-inflammatory drugs, ibuprofen, diclofenac, and celecoxib have been frequently used in multimodal analgesia. Recent studies challenge the conventional theory that they exhibit activity and toxicity by acting on cyclooxygenase selectively. We compared their membrane interactions that may be associated with analgesic and gastrointestinal toxic effects. Biomimetic membranes suspended in buffers of different pH were prepared with 1-palmitoyl-2-oleoylphosphatidylcholine, sphingomyelin, and cholesterol to mimic neuronal membranes and with 1,2-dipalmitoylphosphatidylcholine to mimic gastrointestinal mucosae. The membrane interactivity was determined by measuring fluorescence polarization. At pH 7.4, the drugs interacted with neuro-mimetic membranes to decrease membrane fluidity at pharmacokinetically-relevant 0.5–100 μM. Celecoxib was most potent, followed by ibuprofen and diclofenac. At pH 4.0 and 2.5, however, the drugs increased the fluidity of 1,2-dipalmitoylphosphatidylcholine membranes at 0.1–1 mM corresponding to gastroduodenal lumen concentrations after administration. Their membrane fluidization was greater at gastric pH 2.5 than at duodenal pH 4.0. Low-micromolar ibuprofen, diclofenac, and celecoxib structure-specifically decrease neuronal membrane fluidity, which hypothetically could affect signal transmission of nociceptive sensory neurons. Under gastroduodenal acidic conditions, high-micromolar ibuprofen, diclofenac, and celecoxib induce fluidity increases of membranous phosphatidylcholines that are hypothetically associated with gastrointestinal toxic effects, which would enhance acid permeability of protective mucosal membranes.

By tonnage, corn (Zea mays L.) is the #1 crop produced globally, and recent research has suggested that no-till (NT) systems can lead to reduced yields of this important crop. Additionally, there is a lack of long-term data about the effects of tillage and N management on cropping systems. Corn is the most nitrogen (N)-fertilized crop in the USA, and N losses to the environment contribute to significant impacts on air and water quality. We conducted long-term studies on conventional tillage (CT), and conservation tillage systems such as strip tillage (ST) and NT, under different N rates. We found that immediately after conversion to NT, yields from NT were significantly lower than yields from CT (P<0.1), but after five years of NT, the NT yields were 1.5% higher than the CT yields (P<0.1). Initially, the NT yields were lower than the ST (P<0.01), but after seven years of NT, the NT yields were comparable to ST grain yields. Although the total aboveground N uptake with NT immediately after conversion to NT was lower than with CT and ST, these differences were not significant in the long run. The nitrogen use efficiency (NUE) with NT increased over time. The present work highlights the importance of long-term research for determining the cumulative impacts of best management practices such as NT. We found that NT becomes a more viable practice after five or seven years of implementation, demonstrating the high importance of long-term research.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

Hyperaccumulator plant species growing on metal-rich soils can accumulate high quantity of metals and metalloids in aerial tissues and several proteomic studies on the molecular mechanisms at the basis of metals resistance and hyperaccumulation have been published. Hyperaccumulator are also at the basis of phytoremediation strategy to remove more efficiently metals from polluted soils or water. Arabidopsis halleri and Noccea caerulescens are both hyperaccumulators of metals and nano-metals. In this study it was assessed the change in some proteins in A. halleri and N. caer-ulescens after the growth in soil with cadmium and zinc, provided as sulphate salts (CdSO4 and ZnSO4) or sulfide quantum dots (CdS QDs and ZnS QDs). The protein extracts obtained from plants after 30 days of growth were analyzed by 2D-gel electrophoresis (2D SDS-PAGE) and identified by MALDI-TOF/TOF mass spectrometry. A bioinformatics analysis was carried out on quantitative protein differences between control and treated plants. In total, 43 proteins resulted significatively modulated in A. halleri, while 61 resulted modulated in N. caerulescens. Though these two plants are hyperaccumulator of both metals and nano-metals, at protein levels the mechanisms involved do not proceed in the same way but at the end bring to a similar physiological result.

In this study, we examined the effect of salinity and alkalinity on the metabolic potential and taxonomic composition of microbiota inhabiting the sodic soils at different plant communities. The soil samples were collected in the Pannonian steppe (Hungary, Central Europe) under extreme dry and wet weather conditions. The metabolic profiles of microorganisms were analysed by MicroResp method, the bacterial diversity was assessed by cultivation and next generation amplicon sequencing based on the 16S rRNA gene. Catabolic profiles of microbial communities varied primarily according to the alkali vegetation types. Most members of the strain collection were identified as plant associated and halophilic/alkaliphilic species of Micrococcus, Nesterenkonia, Nocardiopsis, Streptomyces (Actinobacteria) and Bacillus, Paenibacillus (Firmicutes) genera. Based on the pyrosequencing data, the relative abundance of phyla Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes and Bacteroidetes changed also mainly with the sample types, indicating distinctions within the compositions of bacterial communities according to the sodic soil alkalinity-salinity gradient. The effect of weather extremes was the most pronounced in the relative abundance of phyla Actinobacteria and Acidobacteria. The type of alkali vegetation caused greater shifts in both the diversity and activity of sodic soil microbial communities than the extreme aridity and moisture.

The immune system plays a major role in the surveillance and control of malignant cells, with the presence of tumor infiltrating lymphocytes (TILs) correlating with better patient prognosis in multiple tumor types. The development of ‘checkpoint blockade’ and adoptive cellular therapy has revolutionized the landscape of cancer treatment and highlights the potential of utilizing the patient’s own immune system to eradicate cancer. One mechanism of tumor-mediated immunosuppression that has gained attention as a potential therapeutic target is the purinergic signaling axis, whereby the production of the purine nucleoside adenosine in the tumor microenvironment can potently suppress T and NK cell function. The production of extracellular adenosine is mediated by the cell surface ectoenzymes CD73, CD39 and CD38 and therapeutic agents have been developed to target these as well as the downstream adenosine receptors (A₁R, A_2AR, A_2BR, A₃R) to enhance anti-tumor immune responses. This review will discuss the role of adenosine and adenosine receptor signaling in tumor and immune cells with a focus on their cell-specific function and their potential as targets in cancer immunotherapy.

In general sound waves propagate radially outwards from a point source. These waves will continue in the same direction, decreasing in intensity, unless a boundary condition is met. To arrive at a universal understanding of the relation between frequency and wave propagation within spatial boundaries, an analysis and comparison is made between the results of Chladni plate experiments and Chladni plate simulations. We consider a finite range of frequencies and plate geometries and present a model that has been shown to successfully recreate the nodal line patterns to a first approximation. We discuss the benefits of such a model and the future work necessary to develop the model to its full predictive capacity.

Multidrug resistance (MDR) among gram-negative bacteria is a global public health threat because it has exhausted all standard therapeutic options. This has necessitated clinicians to reconsider colistin, an “old sort” antibiotic which was deemed toxic for clinical use. Unfortunately, swift resistance towards colistin by K. pneumoniae has been reported in different parts of the world. The study aimed at investigating the genetic determinants of colistin resistance in K. pneumoniae isolated from patients admitted in a tertiary care hospital in Kampala, Uganda. 31 archived multidrug resistant K. pneumoniae isolates obtained from rectal swabs of patients admitted to the Mulago Hospital ICU were retrieved. From this collection, we selected 7 colistin resistant K. pneumoniae isolates for whole genome sequencing and molecular profile analysis. In silico sequence data analyses were performed using established web-based bioinformatics tools. The sequence analysis of the genes involved in colistin resistance revealed several non-synonymous mutations in nucleotide sequences of pmrA, pmrB, phoP, phoQ and mgrB genes. Insertion transposase genes for the insertion sequences IS1 and IS5 which are highly implicated in colistin resistance via modification or inactivation of mgrB gene were identified in all isolates and were located in the chromosomal DNA at different genomic positions. No plasmid-borne mcr genes were detected. More so, the strains harbored numerous multidrug resistant genes. This study underscores the need of genomic surveillance of K. pneumoniae strains to limit further spread of colistin resistance genes to avert the potential risk of pandrug resistance. And high throughput sequencing is imperative.

Milk is newborn’s food and an emulsion full of all necessary components for neonatal growth. Its consumption is worldwide and is the base for all dairy products. Because of the latter, many new technologies are growing, among them proteomics; in order to give new insights in milk’s compounds and to maximize the beneficial potential for consumers’ health. In this review, we aimed to gather data of proteomics studies for the majority of dairy animals and elucidate the role of milk bioactive compounds. Furthermore, special reference was made to milk fat globule membrane (MFGM) peptides and the result of thermal treatment in milk proteins. Finally, the proteomic approach regarding adulterations was included in the review.

In terrain analysis and hydrological modeling, surface depressions (or sinks) in a digital elevation model (DEM) are commonly treated as artifacts and thus filled and removed to create a depressionless DEM. Various algorithms have been developed to identify and fill depressions in DEMs during the past decades. However, few studies have attempted to delineate and quantify the nested hierarchy of actual depressions, which can provide crucial information for characterizing surface hydrologic connectivity and simulating the fill-merge-spill hydrological process. In this paper, we present an innovative and efficient algorithm for delineating and quantifying nested depressions in DEMs using the level-set method based on graph theory. The proposed level-set method emulates water level decreasing from the spill point along the depression boundary to the lowest point at the bottom of a depression. By tracing the dynamic topological changes (i.e., depression splitting/merging) within a compound depression, the level-set method can construct topological graphs and derive geometric properties of the nested depressions. The experimental results of two fine-resolution LiDAR-derived DEMs show that the raster-based level-set algorithm is much more efficient (~150 times faster) than the vector-based contour tree method. The proposed level-set algorithm has great potential for being applied to large-scale ecohydrological analysis and watershed modeling.

Caffeine is a naturally occurring alkaloid found in various plants. It acts as a stimulant, antioxidant, anti-inflammatory and even an aid in pain management, and is found in several over-the-counter medications. This naturally derived bioactive compound is the best-known ingredient in coffee and other beverages, such as tea, soft drinks, and energy drinks, and is the most widely consumed substance worldwide. Therefore, it is extremely important to research the effects of this substance on the human body. With this in mind, caffeine and its derivatives have been extensively studied to evaluate its ability to prevent diseases and exert anti-aging and neuroprotective effects. This review is intended to provide an overview of the effects of caffeine on cancer, cardiovascular, immunological, inflammatory, and neurological diseases, among others. The heavily researched area of caffeine in sports will also be discussed. Finally, recent advances in the development of novel formulations, in the form of dietary supplements of caffeine and nanocarriers, to enhance the bioavailability of caffeine and its beneficial effects will be discussed. On the other hand, caffeine may contribute to elevated blood pressure, anemia, and migraine.

This study provides an in-depth examination of the binary system of n-Nonadecane and 1-Octadecanol, representative of plant cuticular waxes. It emphasizes the crystallization and phase transitions in this hydrocarbon mixture. Using Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared (FTIR) spectroscopy, the research uncovers detailed thermal properties and phase behaviors. The findings reveal the distinct phase transitions and enthalpy changes of each component in the binary system. This research is significant for its implications in under-standing the structural properties of plant waxes. Such insights are crucial for enhancing the effi-ciency of fertilizer and pesticide absorption in plant leaves, with broad applications in bionics and materials science. This study not only furthers the understanding of identifying specific phase transitions for each compound, facing challenges in detecting subtle changes using DSC. The re-search enhances understanding of plant cuticle waxes through FTIR analysis, revealing intricate molecular interactions and structural complexities. but also opens avenues for improved agri-cultural practices and material engineering, potentially influencing future innovations in these fields.

Background: The immunomodulatory role of 1,25-Dihydroxy vitamin D3 (1,25(OH)2D3) is exerted through its interaction with the Vitamin D receptor (VDR) present on pancreatic and immune cells. While a deficiency in Vitamin D has been linked to Type 1 Diabetes Mellitus (T1DM), the exact molecular mechanism driving this down-regulation in T1DM is yet to be fully understood. This study aimed to decipher differences in the expression of genes associated with Vitamin D metabolism in T1DM patients and to ascertain if there is a correlation between serum 1,25(OH)2D3 levels and the expression of these genes. We also sought to understand the influence of specific microRNAs (miRNAs) on the expression of Vitamin D metabolism genes in peripheral blood mononuclear cells (PBMCs) of T1DM patients. Furthermore, the study delved into the potential implications of altered Vitamin D metabolism genes and miRNAs on autoimmune processes. Methods: Utilizing real-time PCR, we assessed the expression profiles of genes encoding for 1-hydroxylases (CYP27B1) and 24-hydroxylases (CYP24A1), as well as related miRNAs, in PBMCs from 30 T1DM patients and 23 healthy controls. ELISA tests facilitated the measurement of 1,25(OH)2D3, GAD65, and IA-2 levels. Results: Our findings showcased down-regulated CYP27B1 mRNA levels, while CYP24A1 expression remained stable compared to healthy subjects (CYP27B1, p = 0.0005; CYP24A1, p = 0.205, respectively). In T1DM patients, the levels of has-miR-216b-5p were found to be increased, while the levels of has-miR-21-5p were decreased in comparison to the control group. Notably, no correlation was identified between the expression of CYP27B1 in T1DM patients and the levels of has-miR-216b-5p, has-miR-21-5p, and 1,25(OH)2D3. A significant negative correlation was identified between CYP27B1 mRNA levels in PBMCs of T1DM and IA2, but not with GAD65. Conclusions: The study highlights there were reduced levels of both CYP27B1 mRNA and has-miR-21-5p, along with elevated levels of has-miR-216b-5p in the PBMCs of T1DM. However, the absence of a correlation between the expression of CYP27B1, levels of has-miR-216b-5p, and the status of 1,25(OH)2D3 suggests the possible existence of other regulatory mechanisms. Additionally, the inverse relationship between IA2 autoantibodies and CYP27B1 expression in T1DM patients indicates a potential connection between this gene and the autoimmune processes inherent in T1DM.

(1) Background: Newer generation ophthalmologists practicing in the developed world are not very familiar with some tropical ocular diseases due to the absence of reports in the ophthalmic literature over the past thirty years. Because of world globalization or due to influx of immigrants from Sub Saharan Africa, exotic retinal diseases are being encountered more often in ophthalmology clinics; (2) Methods: Case series of chorioretinitis or optic neuritis with obscure etiology; (3) Results: 4 cases qualified with the diagnosis of ocular onchocerciasis based on their residence near fast rivers in endemic areas, multimodal imaging, long term follow-up showing progressive disease and negative workup for other diseases. Characteristic findings include peripapillary choroiditis with optic neuritis or atrophy, subretinal tracts of the microfilaria, progressive RPE atrophy around heavily pigmented multifocal chorioretinal lesions of varying shapes and subretinal white or crystalline dots. Typical skin findings are often absent in eyes with chorioretinitis rendering the diagnosis more challenging; (4) Conclusions: Familiarity with the myriad ocular findings of onchocerciasis, and a high degree of suspicion in subjects residing in endemic areas can help in the correct diagnosis and implementation of appropriate chemotherapy. Onchocercid chorioretinitis is a slow insiduous progressive and prolonged polymorphous disease.

Digital Image Correlation (DIC) is an optical technique used to measure surface displacements and strains in materials and structures. This technique has demonstrated significant utility in structural examination and monitoring. This manuscript offers a comprehensive review of contemporary research and applications that have leveraged the DIC technique in laboratory-based structural tests. The reviewed works encompass a broad spectrum of structural components, such as concrete beams, columns, pillars, masonry walls, infills, composite materials, structural joints, steel beams, slabs, and other structural elements. These investigations have underscored the efficacy of DIC as a metrological instrument for precise quantification of surface deformation and strain in these structural components. Moreover, the constraints of the DIC technique have been highlighted, especially in scenarios involving extensive or complex test configurations. Notwithstanding these constraints, the DIC methodology has validated its effectiveness as a strain measurement instrument, offering numerous benefits such as non-invasive operation, full-field measurement capability, high precision, real-time surveillance, and compatibility with integration into other measurement instruments and methodologies.

As environmental and health concerns increase, the trend of sustainable agriculture moves toward using biological agents. About 60% of all biological fungicides have Trichoderma species as the active ingredient, with T. harzianum as the most common species in these products. However, the name T. harzianum has often been incorrectly used in culture collections, databases, and the scientific literature due to the division of the Harzianum Complex Clade (HCC) into more than 95 cryptic species with only one being named T. harzianum. In this study, 49 strains previously identified as T. harzianum in three surveys of Trichoderma species from soils in South and Central America were re-identified using phylogenetic analyses based on tef1α, rpb2, and ITS loci and were combined with the corresponding species in two other studies, where the species were correctly identified. Based on the results of the five surveys of the total 148 strains in HCC, 11 species were identified and T. afroharzianum, T. lentiforme, T. endophyticum followed by T. azedevio and T. harzianum were detected as the dominant species of the HCC in South and Central America. This is the first report of identifying dominant Trichoderma species within the HCC in South and Central American soil based on multiple studies, which will be useful in selecting strains within the complex clade for formulation of biocontrol and biofertilizer products in the continent.

The Leave-One-Out (LOO) Green Fluorescent Protein (GFP) approach to biosensor design com-bines computational protein design with split protein reconstitution. LOO-GFPs reversibly fold and gain fluorescence upon encountering its target peptide, which can be redefined by computa-tional design of the LOO site. Such an approach can be used to create reusable biosensors for the early detection of emerging biological threats. Enlightening biophysical inferences for nine LOO-GFP biosensor libraries are presented, with target sequences from dengue, influenza, or HIV, replacing beta strands 7, 8 or 11. An initially low hit rate was traced to components of the energy function, manifesting in the over-rewarding of over-tight side chain packing. Also, screening by colony picking required a low library complexity, but designing a biosensor against a peptide of at least 12 residues requires a high complexity library. This double-bind was solved using a "piecemeal" iterative design strategy. Also, designed LOO-GFPs fluoresced in the unbound state due to unwanted dimerization, but this was solved by fusing a fully functional prototype LOO-GFP to a fiber-forming protein, Drosophila ultrabithorax, creating a biosensor fiber. One in-fluenza hemagglutinin biosensor is characterized here in detail, showing a shifted excita-tion/emission spectrum, a micromolar affinity for the target peptide, and an unexpected pho-to-switching ability.

Introduction: During the COVID-19 pandemic, many countries implemented restrictions, social distancing measures, and lockdowns to limit the spread of the disease. The lockdowns have affected children’s screen time (ST), pain, and physical activity (PA) levels. The present study aimed to explore the relationships between several personal factors during the COVID-19 pandemic. Methods: The caregivers of 329 children (median age=8 years) filled out an online self-reported survey about the children’s PA, ST, and pain before, during, and after the COVID-19 curfew. Spearman’s rank correlation coefficient was used to explore the associations between these variables. Results: After the curfew, pain that existed before the pandemic had a weak negative relationship with PA intensity (-0.11, p=0.04) and a weak positive relationship with ST (r=+0.12, p=0.04). There was a strong positive relationship between ST in all time periods (p&gt;0.01). PA and ST had a weak negative relationship (p&gt;0.05) during the curfew and after the curfew but not before the COVID-19 pandemic. Age had a weak positive correlation with ST in all time periods (p&gt;0.01). In addition, ST was affected by the curfew. Conclusion: The study findings indicated that young children had longer ST during the curfew and after the curfew compared with before the curfew. Increasing PA could lessen children’s ST, which could, in turn, increase the probability that their general pain would decrease.

Despite its growing importance as a dry beneficiation method, there is a lack of studies exploring the fundamentals aspects of dry jigging. In this sense, this study focuses on explore some essential aspects of density-based separation in dry jigs, like pulse profile, energy consumption and, especially, stratification over time, also exploring an innovative operational strategy here called “transient pulsation”. The tests were carried out using density tracers distributed across 11 density ranges (0.4-2.4 g/cm³) and employing a base bed (gravel) to analyze their segregation in a pilot-scale dry jig. Pressure drop and active power data were acquired to measure the pulse characteristics and energy consumption. The findings suggest that establishing the dry jigging cycle is more complex than in hydraulic jigs due to the compressibility of air. Stationary pulsation tests revealed an unstable behavior of stratification over time, contrasting with traditional hydraulic jigs, while transient pulsation tests unveiled varied trends in separation quality. Energy consumption analysis underscored the significant role of the blower drive. These insights have the potential to inform operational enhancements in dry jigging.

This article presents a low-cost insurance system developed for small-hold farms in disaster-prone regions, primarily using free Earth Observation (EO) data and Free Open Source Software (FOSS) – collectively termed sustainable geoinformatics - with a proprietary mobile phone app that enables verification. The study examined 30 farms in Risaralda department, Colombia. A Digital Elevation Model (12.5m pixels) from the ALOS PALSAR satellite sensor was used with a Geographical Information System (GIS) to map the terrain, drainage and geohazards of each farming district. Google Earth Engine (GEE) was used to carry out Time Series Analysis of 15 EO and weather datasets for 1998 to 2020. This analysis enabled the levels of risk from hydrometeorological hazards to be determined for each farm of the study, providing key data for the setting of insurance premiums. A parametric insurance product was piloted using GPS-tagged, time-stamped mobile phone photos to verify crop health. Key features of this insurance system are its low operational cost and rapid damage verification, relative to conventional approaches to farm insurance. It is an affordable form of insurance for small-scale farmers, with the rapid verification and payment of claims. This relatively fast, low-cost and affordable approach to insurance for small-scale farming enhances sustainable development by enabling policy-holder farmers to recover more quickly from disasters.

Self-report measurement is frequently used in human sports to assess training adaptations [1, 2]. This is a technique novel to the equestrian sport. The aim of this study was to describe how elite event riders of Germany evaluate their own fitness as well as that of their horses for the entire duration of an eventing season. Additionally, correlations with possible influencing external factors such as type of training or duration of grazing were also investigated. Short online questionnaires were used to allow eight riders to describe the training of their horses. Five criteria (general performance, ability to concentrate, general state of mind, general muscular condition and emotional wellbeing) were used to assess both, their horse's, as well as their own wellbeing. A 1-10 rating scale was used to score each criterion resulting in an average of 38 points out of 50 (maximum wellbeing) for horse (Std. dev. 0.55) and rider (Std. dev. 0.65) respectively. A total of 120 questionnaires were analysed. A correlation could be demonstrated (Spearman's correlation coefficient = 0.5) between rider and horse score, whereby it only became a linear correlation above 30 points. In addition, the horse score correlates positively with its success at competitions. While the horses were rated similarly throughout the season, the riders’ perceived welfare was higher in the middle of the season compared with the beginning and end of the season. Regularly turned-out horses resulted in higher horse scores (Linear mixed model, p=0,04, n=120). It can be concluded that the self-report measurement of fatigue and wellbeing can be a useful tool for trainers and riders to better determine the horse’s fatigue and recovery. It should be noted that external factors influence both, rider and horse assessment.

Traumatic Brain Injury represents a significant public health concern due to its role in traumatic death and disability, often caused by head impacts or rapid accelerations. Despite advancements in Finite Element Head Models, existing models primarily represent adult males, neglecting anatomical and physiological differences between genders and age groups. Additionally, the mechanistic roles of specific intracranial tissues, such as the dura mater, have conventionally been overlooked. To better understand the mechanical behavior of the brain and its injured regions in the context of TBI, including the dura mater, this study proposes the development of a Female Finite Element Head Model. This model, representative of a middle-aged female subject, was developed using medical image-derived geometry and finite element modeling techniques. The validation results demonstrate a similarity between the numerical displacement curves and those obtained experimentally. In the model with dura mater, the numerical results show analogous behavior to the experimental results, despite minimal variations in the amplitude of the curves. These advancements highlight the significance of including the dura mater in biomechanical brain modeling. Incorporating the dura mater in Finite Element Head Models produces more realistic results than models without it. This emphasizes the importance of enhancing biomechanical models to better represent anatomical complexity.

The growth of demand for metallic minerals has faced with the need for new techniques and improving technologies for all mine life cycle operations. Nowadays, the exploitation of old tailings and mine wastes facilities could represent a solution to this demand, with economic and environmental advantages. W-Sn Panasqueira Mine has been operating for more than 100 years. Its first processing plant “Rio” was located near Zêrere river being the mineral processing residues deposited on the top hillside on the margin of this river in Cabeço do Pião tailings dam. The lack of maintenance and monitoring of this enormous structure in the last twenty years represents high risks to the environment and population of the surrounding region. The re-mining of the tailings by hydrometallurgical methods was considered, in order to satisfy these two enounced conditions - metals demand and environmental risk, aiming for the sale of the metal to pay the environmental intervention. Field samples campaign allowed collecting data and results from laboratory tests driving to use regression optimization. The re-mining solution was studied, taking into account the technical, economic, social, and environmental aspects.

The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for the clinical diagnosis and patient-reported outcome (PRO) in women with acute uncomplicated cystitis (AC). The aim of the current study (part II) was the clinical validation of the Greek ACSS questionnaire. After linguistic validation according to internationally accepted guidelines and cognitive assessment (part I), the clinical validation was performed after ethical approval by using the Greek ACSS study version in 92 evaluable female participants including 53 patients with symptoms suspicious of AC and 39 controls. The clinical outcome using the ACSS questionnaire at different time points after the start of treatment was demonstrated as well. The age (mean±SD) of the 53 patients (44.7±17.0) and 39 controls (49.3±15.9) and their additional conditions at baseline visits, such as menstruation, premenstrual syndrome, pregnancy, menopause, diabetes mellitus, were comparable. There was, however, a significant difference (p&lt;0.001) between patients and controls at baseline visit regarding sum score of the ACSS domains, such as typical symptoms and quality of life. The clinical outcome of up to 7 days showed a fast reduction of the symptom scores and improvement of quality of life. The optimal thresholds for the patient-reported outcome of successful therapy could be established. The linguistically and clinically validated Greek ACSS questionnaire can now be used for clinical or epidemiological studies and also for patient’s self-diagnosis of AC and as a PRO measure tool.

The aim of this paper is to develop an intelligent event-driven Electrocardiogram (ECG) processing module in order to achieve an efficient solution for diagnosis of the cardiac diseases. The suggested method acquires the signal with an event-driven A/D converter (EDADC). The output of EDADC is passed through the activity selection and interpolation blocks. It allows focusing only on the important signal parts and resampling it uniformly. Later on, the signal is de-noised. The autoregressive (AR) method is used to extract the classifiable features of the de-noised signal. Afterwards, the output is classified by employing different robust classification techniques such as support vector machines (SVMs), K- Nearest Neighbor (KNN) and Artificial Neural Network (ANN). The event-driven feature enables to adapt the system processing load according to the signal temporal variations. This interesting feature of the devised system aptitudes a drastic reduction in its processing activity and therefore in the power consumption as compared to the traditional ones. A comparison of the performance of different classifiers is also made in terms of accuracy. Results show that the proposed system is a potential candidate for an automatic diagnosis of the cardiac diseases.

Abstract Metabolic syndrome (MetS) is considered a metabolic disorder that has been steadily increasing globally and seems to parallel the increasing prevalence of obesity. It consists of a cluster of risk factors, which traditionally includes obesity and hyperlipidemia, hyperinsulinemia, hypertension, and hyperglycemia. These four core risk factors are associated with insulin resistance (IR) and importantly, the MetS is known to increase the risk for developing cerebrocardiovascular disease and type 2 diabetes mellitus. The MetS had its early origins in IR and syndrome X. It has undergone numerous name changes with additional risk factors and variables being added over the years; however, it still remains the MetS worldwide for the past three decades. This overview continues to add novel insights to the MetS and suggests that leptin resistance with hyperleptinemia, aberrant mitochondrial stress and reactive oxygen species (ROS), impaired folate-mediated one-carbon metabolism with hyperhomocysteinemia, vascular stiffening, microalbuminuria, and visceral adipose tissues extracellular vesicle exosomes be added to the list of associated variables. Notably, the role of a dysfunctional and activated endothelium and deficient nitric oxide bioavailability along with a dysfunctional and attenuated endothelial glycocalyx, vascular inflammation, systemic metainflammation, and the important role ROS and reactive species interactome are discussed. With new insights and knowledge regarding the MetS, comes the possibility of new findings through further research.

Background: Nutrient supplements are widely used for type 2 diabetes (T2D) yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015–December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycemic control, measures of insulin sensitivity and secretion), adverse events, and GRADE assessments. Quality was assessed using AMSTAR-2. Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C and omega-3 polyunsaturated fatty acids (-3 PUFAs) were superior to placebo for the primary outcome of HbA1c (MD -0.54%, -0.54% and ES -0.27 respectively). Probiotics were superior to placebo for HbA1c (WMD -0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD -0.17%). Magnesium, zinc, Vitamin C, probiotics and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.

The Internet of Things (IoT) is still a relatively new field of research, and its potential for use in the healthcare and medical sectors is enormous. In the last five years, IoT has been a go-to option for various applications such as using sensors for different features, machine-to-machine communication, etc., but precisely, in the medical sector, it is still lagging far behind compared to other sectors. Hence, this study emphasizes the IoT applications in medical fields, Medical IoT sensors and devices, IoT platforms for data visualization, and artificial intelligence in medical applica-tions. A systematic review considering PRISMA guidelines on research articles as well as the websites on IoMT sensors and devices have been carried out. A total of 986 articles after the year 2001 have been initially selected, and by applying the inclusion-exclusion criterion, a total of 597 articles have been identified. From these, 23 studies have been finally selected for this systematic review. This review analyzes different sensor monitoring circuits in detail, considering an Inten-sive Care Unit (ICU) scenario, device applications, and the data management system, including IoT platforms for the patients. Lastly, detailed discussion and challenges have been outlined, and possible prospects have been presented.

In the software development process, the decision-maker (DM) has a range of problems inherent to its function. Wrong choices during software planning can bring great risk to the project. Therefore, the planning of software releases to be delivered to the customer should be well done. This is not an easy task because releases are made up of many requirements that contain complex variables that must be considered, such as precedence, cost, requirement stability, among other features that make the requirements-selection process challenging. To make this process less exhaustive, DM can use tools that facilitate this work. In software engineering, we can find fields of research specialists in this context, such as Search-Based Software Engineering (SBSE). The SBSE makes use of advanced metaheuristics to search for optimal solutions or the closest to it. In this work, we try to use another field of research to solve this same problem type, the Verbal Decision Analysis (VDA). To do this, we elaborate a workflow that will use the same source data, execute two solutions using the two search fields (SBSE and VDA) and compare the results. In the end, we evaluated and commented on the results.

Eurytoma erythrinae Gates & Delvare (Hymenoptera: Eurytomidae), is an important biological control agent of the erythrina gall wasp (EGW), Quadrastichus erythrinae Kim (Hymenoptera: Eulophidae), an invasive species native likely originating in eastern Africa, that is a threat to Erythrina trees in Hawaii and worldwide. Thousands of Erythrina trees in Hawaii succumbed to EGW since 2005 and died within few years of infestation. The endemic wiliwili tree, Erythrina sandwicensis, an important component of Hawaii’s dry forests, and one of few deciduous native trees were severely impacted by this wasp. Early during the invasion by EGW it became evident that the endemic species may be driven to extinction, and exploration programs for natural enemies of the EGW started in December 2005. East Africa was selected as the start point for natural enemy exploration owing to high native Erythina species richness. Several gall formers were found in Tanzania and a putative color variant type of Q. erythrinae was detected in association with three ectoparasitoids. During January 2006, the dominant parasitoid of this gall former was introduced to Hawaii and described as the new species, E. erythrinae. It was found in Ghana, and South Africa attacking other gall wasp species on Erythrina. Eurytoma erythrinae was a voracious ectoparasitoid feeding as a predator on 1 – 5 adjacent EGW immatures to complete its development. Host specificity studies that included seven non-target gall-forming species showed no evidence of attraction or parasitism by this parasitoid. Mean ± SEM longevity of host deprived females (40.4 ± 2.2 days) was significantly higher than males (20.5 ± 1.1 days). Host feeding enhanced longevity of ovipositing female (51.3 ± 1.5 days). Female’s peak fecundity (105 – 239 offspring /female), host feeding biology, short life cycle (18.4 ± 0.1 days), and synchronization with the host, were additional desirable attributes of E. erythrinae. The parasitoid was approved for field release in Hawaii in November 2008. A total of 3998 wasps were distributed on six Hawaiian Islands, with establishment in less than a year. Impacts on high density infestations of EGW were sufficient to prevent tree deaths. Limited rates of parasitism on low density galled leaves, flowers, and seedpods necessitated the consideration for releasing a second parasitoid, Aprostocetus nitens (Hymenoptera: Eulophidae). We report on the reproductive characteristics, and host specificity of E. erythinae that could be of importance for classical biocontrol programs in areas with EGW problem.

Fossil-based plastics are significant contributors to global warming through CO₂ emissions. For more sustainable alternatives to be successful, it is important to ensure that consumers become aware of the benefits of innovations such as bio-based plastics, in order to create demand and a willingness to initially pay more. Given that consumer attitudes and (inaccurate) beliefs can influence the uptake such new technologies, we investigated participants’ attitudes towards fossil-based and bio-based plastic, their perceived importance of recycling both types of plastic, their willingness to pay, and their perceptions of bio-based plastic in four studies (total N = 961). The pre-registered fourth study experimentally manipulated information about bio-based plastic and measured willingness to pay for different types of plastic. The results suggest participants hold very favourable attitudes and are willing to pay more for bio-based products. However, they also harbour misconceptions, especially overestimating bio-based plastic’s biodegradability, and they find it less important to recycle bio-based than fossil-based plastic. Study 4 provided evidence that educating consumers about the properties of bio-based plastic can dispel misconceptions, retain a favourable attitude and a high willingness to pay. We found mixed evidence for the effect of attitudes on willingness to pay, suggesting other psychological factors may also play a role. We discuss how attitudes and misconceptions affect the uptake of new sustainable technologies such as bio-based plastics and consumers’ willingness to purchase them.

Nanotechnology has become a popular topic in agricultural and animal research, generating sig-nificant global interest. Nanoparticles (NPs)-enabled agriculture and animal husbandry (AHs) products have three main principles: crop production, protection, and nutrient enrichment. Re-search on this topic has grown exponentially in recent years, with an increasing number of peer-reviewed literature and patents on NPs-enabled agriculture and AH products. This study examines and collects data on the various applications of NPs-enabled agricultural products for crop production, protection, and livestock improvement from the core nanotechnological database. The search returned several types of NPs and products used in agriculture and AH, countries that utilize these products at a commercial level, and analysis of these data by phyton, R-statistical software. Our findings show remarkable growth of nanotechnology in agriculture, AH, and re-search fields for future sustainability goals in the era of climate change