In the search of potent α-amylase inhibitors, we have synthesized seventeen derivatives of 2-mercaptobenzimidazole bearing sulfonamide (1-17) and evaluated for their α-amylase inhibitory potential. All compounds display a variable degree of α-amylase activity having IC50 values ranging between 0.90 ± 0.05 to 11.20 ± 0.30 µM when compared with the standard drug acarbose having IC50 value 1.70 ± 0.10 µM. Compound 1, 2, 11, 12 and 14 having IC50 values 1.40 ± 0.10, 1.30 ± 0.05, 0.90 ± 0.05, 1.60 ± 0.05 and 1.60 ± 0.10 µM respectively were found many folds better than the standard drug acarbose. The remaining analogs showed good inhibitory potentials. All the synthesized compounds were characterized by HREI-MS, 1H and 13C-NMR. Structure activity relationship (SAR) has been recognized for all newly synthesized analogs. Through molecular docking study, binding mode of active analogs with α-amylase enzyme was confirmed.

Background: Green synthesis of silver (Ag) nanoparticle was performed with the fruit extract of Scindapsus officinalis and test against HepG-2, MCF-7 cancer cell lines. These biosynthesized metal nanoparticles have a potential of therapeutic use as an alternative medicine for the treatment of hepatic & breast cancer cases. Results : AgNPs were identified by change of color & their absobtion at 340 nm measured by UV-visible spectroscopy, FTIR spectral analysis confirmed phenolic compounds presence, morphology & size visualized in SEM, TEM used for determination of size, shape & light scattering analysis. Synthesized silver nanoparticles were spherical in shape and size less than 50 nm. XRD analysis was affirmed the crystalline nature of metal particles. In-vitro cytotoxic result showed an excellent IC50 value of 155.81μg/ml and 114.74 μg/ml against HepG-2 & MCF-7 cell lines. Conclusion: The current study reveals green synthesized AgNPs possess high cytotoxic action against HepG-2 & MCF-7 cell lines which suggested the use of silver nanoparticles as a medicine to treat hepatic & breast cancer.

Indigenous forests cover 24% of New Zealand and provide valuable ecosystem services. However, a national map of forest types, that is, physiognomic types, which would benefit conservation management, does not currently exist at an appropriate level of detail. While traditional forest classification approaches from remote sensing data are based on spectral information alone, the joint use of space-based optical imagery and structural information from synthetic aperture radar (SAR) and canopy metrics from air-borne Light Detection and Ranging (LiDAR) facilitates more detailed and accurate classifications of forest structure. We present a support vector machine (SVM) classification using data from ESA’s Sentinel-1 and 2 missions, ALOS PALSAR, and airborne LiDAR to produce a regional map of physiognomic types of indigenous forest in New Zealand. A five-fold cross-validation of ground data showed that the highest classification accuracy of 80.9% is achieved for bands 2, 3, 4, 5, 8, 11, and 12 from Sentinel-2, the ratio of bands VH and VV from Sentinel-1, HH from PALSAR, and mean canopy height and 97th percentile canopy height from LiDAR. The classification based on the optical bands alone was 73.1% accurate and the addition of structural metrics from SAR and LiDAR increased accuracy by 7.8%. The classification accuracy is sufficient for many management applications for indigenous forest in New Zealand, including biodiversity management, carbon inventory, pest control, ungulate management, and disease management. National application of the method will be possible in several years, once national LiDAR coverage is achieved, and a national canopy height model is available.

Aim: To perform a descriptive analysis of eating patterns and biophysical conditions of previously diagnosed and currently under treatment individuals from a semi-urban Mayan community of Yucatan, and to contrast them with T2DM therapeutic guidelines. Methods: The present study is derived from a randomized clinical trial conducted at Komchen, Yucatan. Participants’ diagnosed with T2DM were included. A 24-hour dietary recall, anthropometric parameters (weight, visceral fat, height, and waist circumference), biochemical (HbA1c) and clinical (blood pressure) variables were evaluated and compared via hypothesis test with T2DM treatment cut-off points (based on World Health Organization criteria). Results: Anthropometric characteristics differ significantly from the ideal criteria. Obesity prevalence within women with T2DM was 92.9%. Only 21% of the participants were under T2DM control (≤7%). Energy and carbohydrates consumption, significantly exceed therapeutic guidelines, whereas protein, fat, and fiber intake were lower than the recommendations. Conclusions: Komchen’s diet, concomitantly with food characteristics, could be related to glycemic decontrol. There is a disproportion in macronutrients consumption in favor of carbohydrates, probably associated with socioeconomic limitations, food availability, and price. Developing nutritional assistance programs which contemplate cultural and economic factors in this Mayan population must be taken into consideration.

Two 2,2':6',2''-terpyridine-based Schiff bases (TPySSB and TPySB) have been synthesized. The TPySSB shows remarkable selective ‘off-on’ fluorescence for Al³⁺ by photoinduced electron transfer (PET) mechanism of sensing. Chemosensor TPySSB binds Al³⁺ in a 1:2 ratio with an association constant 6.8×10⁵ (R²=0.98) and this 1:2 stoichiometric model is established on Job’s plot and ¹H NMR. Compared TPySSB and TPySB, it is of great importance of the existence of salicylidene unit due to its strong binding abilities of both phenol and C=N structure to the Al³⁺.

Digital Elevation Models (DEMs) are essential in watershed delineation, but the sensitivity of simulated runoff to DEM resolution is poorly understood. This study investigates the impact of DEM resolution on topological attributes and simulated runoff in the Mahabad Dam watershed, Iran. To delineate the watershed, DEMs with 12.5 m, 30 m, and 90 m resolutions were acquired from the ALOS PALSAR, Space Shuttle Radar Topography Mission (SRTM), and ASTER global DEM data source, respectively. Watershed and streamlines were delineated in ArcGIS, with hydrologic analyses performed using the Soil and Water Assessment Tool (SWAT). Sensitivity analysis on parameters contributing to runoff was done using Sequential Uncertainties Fitting Ver-2 (SUFI-2) Algorithm, in SWAT Calibration and Uncertainty Procedures (SWAT-CUP) software. Results showed the watershed area, reach lengths, and elevations in the watershed varied due to DEM resolutions. Higher amounts of runoff were generated when DEMs with finer resolutions were implemented. The 12.5 m DEM generated 3.48% and 0.42% more runoff compared with 90 m and 30 m DEMs, respectively. SWAT-CUP results showed the sensitivity of parameters contributing to runoff changes under different DEM resolutions. Regardless of DEM resolution, surface properties, available water capacity, and moisture levels in the soil are the most sensitive parameters. As the distribution of slope changes in different DEM resolutions, surface parameters are most affected. The findings indicate to reduce computation time and speed up computation procedures, researchers may use DEMs with coarser resolutions at the expense of minor decreases in accuracy.

Home Security Systems are very important features of modern residential and office setups. This system is used to keep home safe from harmful gases, fire and intruders. It must be affordable, reliable and effective. In this paper, a GSM based home security system has been designed and implemented. The system consists of a GSM Module, MQ-2 smoke detector, Ultrasonic sonar sensor, LM35 temperature sensor, Arduino Uno and relay module. The MQ-2 smoke detector is used to detect harmful gases i.e. LPG, CH4, CO, Alcohol, Smoke or Propane. Any of the harmful gases stated above is detected it will warn the owner by activating the buzzer and displaying a warning message on the LCD display. It will also send a SMS to the owner. Our system can also measure temperate and if the temperature is increased above a certain range it will compensate it by activating Air Conditioner through the relay module. The system will also send a SMS to the owner. It can also detect intruders using Ultrasonic sensor and warn us through buzzer, SMS and displaying message on the LCD. Our system is reliable as it has very fast response and cost effective and it has been developed using our own technologies.

Home Security Systems are very important features of modern residential and office setups. This system is used to keep home safe from harmful gases, fire and intruders. It must be affordable, reliable and effective. In this paper, a GSM based home security system has been designed and implemented. The system consists of a GSM Module, MQ-2 smoke detector, Ultrasonic sonar sensor, LM35 temperature sensor, Arduino Uno and relay module. The MQ-2 smoke detector is used to detect harmful gases i.e. LPG, CH₄, CO, Alcohol, Smoke or Propane. Any of the harmful gases stated above is detected it will warn the owner by activating the buzzer and displaying a warning message on the LCD display. It will also send a SMS to the owner. Our system can also measure temperate and if the temperature is increased above a certain range it will compensate it by activating Air Conditioner through the relay module. The system will also send a SMS to the owner. It can also detect intruders using Ultrasonic sensor and warn us through buzzer, SMS and displaying message on the LCD. Our system is reliable as it has very fast response and cost effective and it has been developed using our own technologies.

Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor (P-elF2α) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.

Various optically active 2-hydroxyamide derivatives are produced based on the kinetic resolution of racemic 2-hydroxyamides with a diphenylacetyl component and (R)-benzotetramisole [(R)-BTM], a chiral acyl-transfer catalyst, via asymmetric esterification and acylation. It was revealed that a tertiary amide can be used with this novel protocol to achieve high selectivity [22 examples; s-value reaching over 250]. The resulting chiral compounds could be transformed into other useful structures while maintaining their chirality.

Facilitative glucose transporters (GLUT) are transmembrane transporter of proteins involved in glucose transport across the plasma membrane. To date, there is no information about glucose transporter 2 (GLUT2) in blunt snout bream (Megalobram aamblycephala). In this study, GLUT2 were cloned and characterized from blunt snout bream, and its-expression in response to diets with different carbohydrate levels (17.1%; 21.8%; 26.4%; 32.0%; 36.3% and 41.9% of dry matter). In this study, the full-length cDNA of GLUT2 was 2577 bp, including a 5’-untranslated region (UTR) of 73 bp, a 3’-UTR of 992 bp, and an open reading frame of 1512 bp, encoding a polypeptide of 503 amino acids with predicted molecular weight of 55.046 kDa and theoretical isoelectric point of 7.52. GLUT2 has twelve across the membrane area locating at 7-29; 71-93; 106-123; 133-155; 168-190; 195-217; 282-301; 316-338; 345-367; 377-399; 412-434; 438-460 aimo acids respectively. Conservative structure domains located at 12-477 aimo acids belonging to sugar porter family major facilitator superfamily (MFS) transporter. The blunt snout bream GLUT2 showed high identity to their orthologs in other fish species and mammals. Quantitative real-time (qRT)-PCR assays revealed that GLUT2 expression was high in the liver, intestine and kidney; highest in the liver. Compared with the control group (17.1%), high dietary carbohydrate levels (32.0%; 36.3% and 41.9%) resulted in high plasma glucose at 3h after feeding, but high plasma glucose were back to basal at 24h after feeding. Furthermore, high dietary carbohydrate levels significantly improved the glycolysis and inhibitied gluconeogenesis by augmentation of GK and PK expression, inhibition of PEPCK and G6P mRNA levels (P<0.05). However, GLUT2; GK; PK; PEPCK and G6P mRNA levels were back to basal.

The oxidative stress is one of the main cause for cardiovascular diseases (like Hypertension) also one of the results of these diseases. This study involved 56 subjects matched ages and sex divided into two groups; 28 hypertensive subject and 28 healthy subject as control group. The following analysis was done: 4-Hydroxy-2-nonenal(4HNE) and albumin. The results show that there is a significant increase in (4HNE) between patients group and control group. The increase in 4HNE which is a product of lipid peroxidation is attributed to destruction in body cell caused by due to the increase in stress events. It has been concluded that is important nappy on ideal weight, because obesity considered main factors for heart disease and hardening of the arteries. The aim of this study was to investigate the relationship between of some oxidative stress markers and cardiovascular diseases.

Segment Anything Model 2 (SAM 2) is a state-of-the-art development by Meta AI Research, designed to address the limitations of its predecessor, SAM, particularly in the realm of video segmentation. SAM 2 employs a transformer-based architecture enhanced with streaming memory, enabling real-time processing for both images and videos. This advancement is important given the exponential growth of multimedia content and the subsequent demand for efficient video analysis. Utilizing the SA-V dataset, SAM 2 excels in handling the intricate spatio-temporal dynamics inherent in video data, ensuring accurate and efficient segmentation. Key features of SAM 2 include its ability to provide real-time segmentation with minimal user interaction, maintaining robust performance even in dynamic and cluttered visual environments. This study provides a comprehensive overview of SAM 2, detailing its architecture, functionality, and diverse applications. It further explores the model's potential in improving practical implementations across various domains, emphasizing its significance in advancing real-time video analysis.

Hydrogen sulfide is present in active or extinct volcanic areas (mofettas). The habitable premises in these areas are affected by the presence of hydrogen sulfide, which, even in low concentrations, gives off a bad to unbearable smell. If the living spaces considered are closed enclosures, then a system can be designed to reduce the concentration of hydrogen sulfide. This paper presents a membrane way to reduce the hydrogen sulfide concentration to acceptable limits using a cellulosic derivative-propylene hollow fiber based composite membrane module. The cellulosic derivatives considered were carboxymethyl–cellulose (NaCMC), cellulose acetate (CA), methyl 2–hydroxyethyl–cellulose (MHEC), and 2–hydroxyethyl–cellulose (HEC). In the permeation module, hydrogen sulfide is captured with a solution of cadmium that forms cadmium sulfide, usable as a luminescent substance. The composite membranes were characterized by SEM, EDAX, FTIR, FTIR 2D maps, thermal analysis (TG and DSC) and from the perspective of hydrogen sulfide air removal performance. To determine the process performances, the variables were: the nature of the cellulosic derivative–polypropylene hollow fiber composite membrane, the concentration of hydrogen sulfide in the polluted air, the flow rate of polluted air, and the pH of the cadmium nitrate solution. Pertraction efficiency was maximum for the sodium carboxymethyl–cellulose (NaCMC)-polypropylene hollow fiber membrane, a hydrogen sulfide concentration in the polluted air of 20 ppm, polluted air flow rate of 50 L/min, and a pH of 2 and 4.

Humans are often exposed to various environmental contaminants, among which phthalates are prevalent due to their extensive use as plasticizers in various consumer goods. Di(2-ethylhexyl) phthalate (DEHP), a widely used phthalate, is recognized as an endocrine disruptor chemical (EDC). DEHP is reported to affect various organs. Few studies have addressed the effects of phthalates on bone. However, the effects of DEHP on the bone forming cells (osteoblasts) are obscure. The present study was peformed to determine the cytotoxic effects of DEHP on human osteoblasts in vitro and to delineate the mechansims. In this study, we exposed the human osteo-blastic cell line MG-63 to various concentrations of DEHP (1, 25, 50 and 100 µM) for 24, 48 and 72 h. Cell viability was assessed by MTT assay. Total RNA and protein were collected after 48 h treatment with 1 and 100 µM DEHP and determined for the mRNA and/or protein expression of alkaline phosphatase (ALP), sex steroid receptors (androgen and estrogen receptors), receptor activator of nuclear factor kappa-Β ligand (RANKL), runt-related transcription factor 2 (RUNX2) and peroxisome proliferator-activated receptor alpha (PPARα). The mRNA expression was stud-ied by real-time RT-PCR analysis and the protein expression was determined by western blot analysis. Statistical analyses were done by one-way analysis of variance (ANOVA) followed by the Students–Newman–Keuls (SNK) test. The exposure of MG-63 cells to DEHP caused a signifi-cant decrease in osteoblast viability in all the treatment groups and at all the time points stud-ied. Interestingly, DEHP exposure decreased the mRNA expression of ALP, a bone formation marker. DEHP had differential effects on estrogen receptor alpha (ERα) mRNA and protein ex-pression. However, DEHP treatment downregulated the mRNA and protein expression of ERβ, and androgen receptor (AR). Surprisingly, DEHP downregulated the RANKL mRNA expression. DEHP decreased the protein expression of RUNX2, the key transcription factor and master regu-lator of bone formation. Furthermore, DEHP increased the PPARα protein expression in the os-teoblasts. Importantly, DEHP increased the reactive oxygen species (ROS) molecules and thus oxidative stress in osteoblasts, as observed by increased hydrogen peroxide, hydroxyl radical levels and lipid peroxidation. On the other hand, it decreased the enzymatic and non-enzymatic antioxidant levels namely catalase, superoxide dismutase, glutathione peroxidase activity and reduced glutathione. Our study demonstrated that in vitro exposure to DEHP reduces the osteo-blast viability possibly through alterations in the oxidant-antioxidant system and modulation of the key genes involved in bone formation, highlighting the cytotoxic effects of DEHP on bone forming cells.

Coronavirus Disease-19 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The virus enters host cells through receptor-mediated endocytosis of angiotensin-converting enzyme-2 (ACE2), leading to systemic inflammation, also known as a “cytokine storm,” and neuroinflammation. COVID-19’s upstream regulator, interferon-gamma (IFNG), is downregulated upon the infection of SARS-CoV-2, which leads to the downregulation of ACE2. The neuroinflammation signaling pathway (NISP) can lead to neurodegenerative diseases, such as Parkinson's disease (PD), which is characterized by the formation of Lewy Bodies made of α-Synuclein protein encoded by synuclein alpha (SNCA). This study presents the pathways involved in the downregulation of ACE2 following SARS-CoV-2 infection and its effect on PD progression. Through QIAGEN’s Ingenuity Pathway Analysis, the study identifies the NISP as a top-five canonical pathway/signaling pathway and SNCA as a top-five upstream regulator. Core Analysis was also conducted on the associated molecules between COVID-19 and SNCA to construct a network connectivity map. The Molecule Activity Predictor tool was used to simulate the infection of SARS-CoV-2 by downregulating IFNG, which leads to the predicted activation of SNCA, and subsequently PD, through a dataset of intermediary molecules. Downstream Effect analysis was further used to quantify the downregulation of ACE2 on SNCA activation.

Background: Shortly after the detection of the COVID virus in January 2020 the US Government introduced and enforced a series of restrictions to protect the elderly from a “deadly virus” and the “pandemic of the century”. Persons who disagreed were silenced and punished. Objective: In the 15^th month of COVID epidemic (April 2021), we have access to sufficient statistical data and methods to better understand the nature, origin of the COVID pandemic. It is now possible to reliably evaluate the effectiveness of the restrictions and the human factors / driving forces behind this drastic limitations of our natural freedom in this country. Methods: Publicly available epidemiological and population parameters were collected and analyzed using the ‘political score’ and ‘restriction ranking’ of 50 states and evaluated by simple and usual statistical methods, mainly correlation analyses. The Political Score of the States (D/R) is the ratio of the number of citizens who self-identified as democrats (D) or republicans (R). The political scores of the 50 states altogether defined a wide, continuous scale, the political scale, that could be used to measure (and statistically evaluate) the effect of politics of a state on the numerical parameters of that state, including population and epidemiologic parameters. The COVID Restriction Score of the States were created to rank the states from 1-50, there 1 is the lowest number of restrictions and 50 is the highest number of restrictions applied by the States. It was based on 13 different key metrics. ResultsThis study revealed, that 1) restrictions reduced the number of viral infections, but 2) they totally failed to reduce the number of supposedly COVID related deaths, expressed as mortality, 3) they increased (SIC!) the lethality of coronavirus. The grade of restrictions were/are strongly associated to the 4) left/right political ratio of the States, there States with more democrat citizens practiced more restrictions. It was found that race, religion and Medicare/healthcare spending have significant influence on politic as well as on the grade of restriction orders. Factors moving States toward the political left and harder COVID restrictions have 5) larger ‘non-white’ population, 6) larger number of ‘non-protestant’ believers, 7) larger Jewish population, and 8) more generous Medicare/healthcare spending. It was not possible to see any influence of the size of the 9) senior (65+) population [i.e. those who are allegedly the most vulnerable and are mostly in need of protective restrictions] neither on the States politic nor on the restrictions. Conclusions: The degree of restrictions enforced by different states ware not primarily determined by biological or epidemiological factors (like number of elderly, say 65+ in the state) but by social, political influences instead. Political (a), religious (b) ethnic (c) and economic (d) forces represented the decisive forces on the state’s restrictive orders and not the convincing evidence of the potentially harmful effects of the COVID infection and the well-founded adequacy of the defense against it.

Background: Short after the detection of the COVID virus in January 2020 the US Government introduced and enforced a series of restrictions to protect the elderly from a “deadly virus” and the “pandemic of the century”. Persons who disagreed were silenced and punished. Objective: In the 15^th month of COVID epidemic (April 2021), we have access to sufficient statistical data and methods to better understand the nature, origin of the COVID pandemic. It is now possible to reliably evaluate the effectiveness of the restrictions and the human factors / driving forces behind this drastic limitations of our natural freedom in this country. Methods: Publicly available epidemiological and population parameters were collected and analyzed using the ‘political score’ and ‘restriction ranking’ of 50 states and evaluated by simple and usual statistical methods, mainly correlation analyses. Results: This study revealed, that 1) restrictions reduced the number of viral infections, but 2) they totally failed to reduce the number of supposedly COVID related deaths, 3) they increased (SIC!) the mortality of coronavirus. The grade of restrictions were/are strongly associated to the 4) left/right political ratio of the States, there States with more democrat citizens practiced more restrictions. It was found that race, religion and Medicare spending have significant influence on politic as well as on the grade of restriction orders. Factors moving States toward the political left and harder COVID restrictions have 5) larger ‘non-white’ population, 6) larger number of ‘non-protestant’ believers, 7) larger Jewish population, and 8) more generous Medicare spending. It was not possible to see any influence of the size of the 9) senior (65+) population [i.e. those who are allegedly the most vulnerable and are mostly in need of protective restrictions] neither on the States politic nor on the restrictions Conclusions: The conclusion is that COVID restrictions are primarily politically motivated, they are ineffective to reduce COVID related mortality and they provide no extra health benefit for the so called “vulnerable” minority (elderly).

Mesoporous MgAl2O4+ LnFe0.7Ni0.3O3 (Ln=La, Pr) nanocomposites were prepared by inexpensive one-pot procedure with Pluronic P123 copolymer, Ni+Ru active component was supported by wet impregnation. The real structure of samples was studied by XRD and TEM with EDX, surface properties by FTIRS of adsorbed CO, reactivity by H2 –TPR, catalytic activity was tested in ethanol steam reforming. Disordering of the real structure of nanocomposite supports due to incorporation of transition metal cations into MgAl2O4 results in developed metal-support interface and domination of single surface metal centers. This provides a high catalytic activity in reaction of ethanol steam reforming in the intermediate temperature range ~550 oC close to that of the best known catalysts, and stability to coking. A higher activity for Pr-containing catalyst is provided by a high reactivity of surface oxygen species bound with Pr cations.

The (benzylthio)acetic acid (HBTA) and some aminopyrimidines, namely 2-aminopyrimidine (2-AP), 5-aminopyrimidine (5-AP), 2-amino-4,6-dimethylpyrimidine (2-A-4,6-DMP) and 2,4,6-triaminopyrimidine (2,4,6-TAP), were successfully embodied as structural units into the construction of a total of four novel supramolecular organic frameworks. The received crystalline solids were inspected by single crystal X-ray diffraction (SC XRD) in order to obtain insight into the structural and supramolecular facets. The SOFs deriving from 2-AP, 5-AP as well as 2-A-4,6-DMP crystallize in the form of true co-crystals (1-3), while the one originating from 2,4,6-TAP crystallizes as salt solvate (4). The SC XRD results indicated the different contents of structural residues present in the asymmetric units of the crystals 1-4 despite the using the same molar ratio of molecular co-formers in each case. The molecular structures of co-crystals 1-3 consist of either one neutral residue of each starting components (1 and 3) or a half nonionized residue of aminopyrimidine ingredient and one neutral residue of acidic specie (2). The asymmetric unit of salt solvate 4 is composed of two ionized residues of each co-former (two 2,4,6-TAP+ cations and two BTA- anions) and one MeOH solvent molecule. The most extensive H-bonding network is observed in the crystal structure of salt solvate 4. The relevant molecular ingredients in co-crystals 1-3 are mainly hold together by the neutral Ocarboxylic–H···Npyrimidine and Namine–H···Ocarboxylic H-bonds. In the case of aggregate 4, the corresponding ionic residues are predominantly sustained by the charged-assisted Npyrimidinium–H···Ocarboxylate and Namine–H···Ocarboxylate hydrogen interactions. The MeOH solvent incorporated into the crystal lattice of adduct 4 is also involved in H-bonding by simultaneously serving as the single donor in OMeOH–H···S and the single acceptor in Namine–H···OMeOH H-bonds afforded the structural diversity within the 2,4,6-TAP+ cations and BTA- anions. Other weaker sets of additional non-covalent contacts existing in the crystal structures of analyzed conglomerates are involved in the self-assembly, stabilization and expansion of total supramolecular organic frameworks. The fact of the formation of non-covalent bonded supramolecular organic frameworks in question is also reflected in corresponding results obtained through elemental analysis (EA), Fourier transform infrared spectroscopy (FT−IR) and thermal analysis (TG/DSC).

The extremely controversial conclusions about the function of human interferon-gamma (hIFNγ) C-terminus as well as the lack of a consistent model explaining its role in the receptor binding prompted us to scrutinize the interaction of hIFNγ with its extracellular receptor hIFNGR1 in different scenarios by means of molecular dynamics simulations. We find that the two molecules alone fail to form a stable complex but the presence of heparan-sulfate-like oligosaccharides largely facilitates the process by both demobilizing the highly flexible C-termini of the cytokine and assisting in the proper positioning of its globule between the receptor subunits. An antiproliferative-activity essay on cells depleted from surface sulfation confirms qualitatively the simulation-based multistage complex-formation model. Our results reveal the key role of HS and its proteoglycans in all processes involving hIFNγ signalling.

The complete regression of clear cell renal cell carcinoma (ccRCC) obtained pre-clinically with anti-carbonic anhydrase IX (CAIX) G36 chimeric antigen receptor (CAR) T cells in doses equivalent to 10e8 CAR T cells/ Kg renewed the potential of this target to treat ccRCC and other tumors in hypoxia. The immune checkpoint blockade (ICB) brought durable clinical responses in advanced ccRCC and other tumors. Here we tested CD8/4-1BB compared to CD28-based anti-CAIX CAR PBMCs cells-releasing anti-programmed cell death ligand-1 (PD-L1) IgG4 for human ccRCC treatment in vitro and in an orthotopic NSG mice model in vivo. Using a 10e7 CAR PBMCs cells/ Kg dose, anti-CAIX CD28 CAR T cells releasing anti-PD-L1 IgG highly decrease both tumor volume and weight in vivo, avoiding the occurrence of metastasis. This antitumoral superiority of CD28-based CAR PBMCs cells compared to 4-1BB occurred under ICB via PD-L1. Furthermore, T cell exhaustion status in peripheral CD4 T cells, additionally to CD8 was critical for CAR T cells efficiency. The lack of hepatotoxicity and nephrotoxicity upon administration of 10e7 CAR PMBCs cells/Kg dose is the basis for carrying out clinical trials using anti-CAIX CD28 CAR PBMCs cells releasing anti-PD-L1 antibodies or anti-CAIX 4-1BB CAR T cells, offering exciting new prospects for the treatment of refractory ccRCC and hypoxic tumors.

Directional protective relaying based on amplitude comparison of traveling wave on continuous co-phase auto-transformer(AT) power transmission system was proposed. Phase-model transformation is used for decoupling transient fault signals and get aerial mode component. The forward and backward traveling wave are obtained by calculating aerial mode component, then the intrinsic mode function(IMF) components can be obtained through Variational Mode Decomposition(VMD), the module maxima are obtained through calculating the IMF components. The fault direction is determined by the ratio of fault components. If two faults relays at the ends of electric traction networks detect a fault to be in the forward direction, the fault occurred in the internal area, the protection would operate properly. The simulation tests indicate that the protection scheme is feasible, and the proposed protection method can discriminate internal faults from external faults under various fault types, and its performances are immune to fault initial angle, ground resistance, etc.

Data from Earth Observation (EO) satellites are increasingly used to monitor the environment, understand variability and change, inform evaluations of climate model forecasts and manage natural resources. Policy makers are progressively relying on the information derived from these datasets to make decisions on mitigating and adapting to climate change. These decisions should be evidence based, which requires confidence in derived products as well as the reference measurements used to calibrate, validate or inform product development. In support of the European Union’s Earth Observation Programmes Copernicus Climate Change Service, the Quality Assurance for Essential Climate Variables (QA4ECV) project fulfilled a gap in the delivery of climate quality satellite derived datasets by prototyping a robust, generic system for the implementation and evaluation of Quality Assurance (QA) measures for satellite-derived ECV climate data record products. The project demonstrated the QA system on six new long-term, climate quality ECV data records for surface Albedo, Leaf Area Index, FAPAR, NO₂, HCHO and CO. Provision of standardized QA information provides data users with evidence-based confidence in the products and enables judgement on the fitness-for-purpose of various ECV data products their specific applications.

Though Cyber Physical Systems (CPS) become very popular in last the decade, dependability of CPS is still a critical issue and related survey is rare. We try to spell out the jigsaw of technologies and figure out the technical trends of dependable self-managing CPS. This survey first recalls the motivation and the similar concepts. By analyzing four generic architectures, we summarize the common characteristics and related assurance technologies, and propose a more generic environment-in-loop processing flow of CPS and a formal interaction flow between physical space and cyber space. Further, the similarity between correctness and dependability is formally analyzed and the new five research questions of dependable self-managing CPS are presented. Then we review the critical technologies and related correctness verification & validation (V&V) methods, the architectures for dependable self-managing CPS. Further, the detail dependability management and V&V technologies are surveyed, which covers the areas of running-time fault management methods and whole life cycle V&V technologies, maintenance and available tool sets. For holistic CPS development, Modeling techniques and MDE (model driven engineering) based V&V methods are analyzed in detail. Then we complete the jigsaw of technologies and figure out the missing part. Further, we propose the technical challenges and the further direction. To our best knowledge, this is the first comprehensive survey on dependable self-managing CPS development and evaluation.

We report a small footprint cost-effective isothermal rapid DNA amplification system, with integrated microfluidics for automated sample analysis and detection of SARS-CoV-2 in human and environmental samples. Our system measures low-level fluorescent signal in real-time during amplification, while maintaining the desired assay temperature, on a low power, portable system footprint. A unique soft microfluidic chip design was implemented to mitigate thermocapillary effects and facilitate optical alignment for automated image capture and signal analysis. The system-on-board prototype coupled with the LAMP primers designed by BioCoS, is sensitive enough to detect viral loads of SARS-CoV-2 in a broad concentration range corresponding to a threshold cycle range of 16 to 39. Clinical specimens were tested at Kingston Health Sciences using a clinically validated PCR assay and variants were determined using whole genome sequencing.

Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declined within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster shots of BNT162b2 or ChAdOx1 among health care workers who previously received CoronaVac as their primary immunization. Fifty-six participants received ChAdOx1 and forty-two participants received BNT162b2 were enrolled into this study which evaluated the immune responses including anti-SARS-CoV-2 spike total antibodies (Elecsys®), surrogated viral neutralization test (sVNT) to ancestral strain (cPass™; GenScript) and five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) (Luminex; multiplex sVNT) and the ELISpot with spike (S1 and S2) peptide pool against the ancestral SARS-CoV-2 strain. The samples were analyzed at baseline, 4, and 12 weeks after primary immunization as well as 4 and 12 weeks after receiving the booster. This study showed a significantly higher B-cell response among the BNT162b2 than the ChAdOx1 booster group, particularly against the Omicron variant, as well as a trend of good T-cell immune response in the BNT162b2 group. Moreover, the immune response rapidly declined at 12 weeks after the booster. A fourth dose or a second booster should be recommended, especially for reducing Omicron severity.

This research paper focuses on the synthesis and characterization of Cu-doped Mg-Co ferrites with varying compositions (Mg_0.6-xCo_0.4Cu_xFe₂O₄, where x = 0.0, 0.1, 0.2, and 0.3) using a solid-state reaction method. This paper also investigates the structural, morphological, magnetic, and electrical characteristics of synthesized Mg_0.6-xCo_0.4Cu_xFe₂O₄, where x = 0.0, 0.1, 0.2, and 0.3. The X-ray diffraction (XRD) technique confirms the ferrites spinel structure in the Fd-3m space group, with average crystallite sizes ranging from 57.29 to 48.57 nm. Fourier Transform Infrared (FTIR) spectroscopy verifies chemical and structural changes, while scanning electron microscopy (SEM) reveals cubic crystal growth with an average grain size of 1 to 1.5 μm. DC electrical resistivity decreases with increasing temperature and Cu²⁺ substitution, ranging from 1.4 x 10⁶ Ω-cm to 6.7 x 10⁵ Ω-cm. The study suggests a correlation between resistivity and Cu²⁺ concentration. Magnetic behaviour, studied using a Vibrating Sample Magnetometer (VSM), shows dependence on dopant concentration, with coercivity ranging from 157 Oe to 256 Oe. The results indicate potential applications in magnetic storage devices, antennas, transformers, and high-frequency electronics.

The mushroom industry generates large amounts of stems, a co-product with valuable sensory and health characteristics. This work aimed to study the influence of particle size (L — &gt;0.510 mm; LI — 0.510-0.315 mm; SI—0.315-0.180 mm; S — &lt;0.180 mm) and species in the characterization and antioxidant activity of flours from stems of Agaricus bisporus (ABSF) and Pleurotus ostreatus (POSF). ABSF was rich in protein (14 g/100 g), calcium (428.23-700.77 mg/100 g), and sorbitol (22.57-26.60 g/100 g), while POSF in β-glucans (36.62-40.34 g/100 g) and linoleic acid (20.57-39.86 g/100 g of lipid). Both species were flush in amino acids with umami flavor. The highest hydration properties and oil holding capacity were exhibited in the S size of both species. ABSF showed elevated values for emulsifying activity than POSF. ABSF-S recorded the heightened antioxidant capacity in vitro, in consonance with the total phenolic compounds (0.91 mg/g). However, this antioxidant assays in POSF presented a positive correlation with β-glucans content. According to these results, there could be several food applications for these co-products, such as emulsifier stabilizer, sweetener or fortifier in the development of functional food.

This study presents a comprehensive systematic review that addresses the critical transition from ROS 1 to ROS 2, spotlighting the significant enhancements and the pressing need for a detailed exploration of ROS 2 within the robotics community. Despite the extensive deployment and adaptations of ROS in varied robotics applications, literature lacks a cohesive synthesis that delineates the advancements, limitations, and broader impacts of ROS 2 compared to its predecessor, ROS 1. Our contribution bridges this gap by assembling the largest database of ROS-related research, encompassing 7,498 articles, with a focused analysis in this survey on 431 ROS2-specific publications. We categorize these into i.) articles that discuss and analyze core ROS 2 concepts, ii.) articles that propose frameworks or tools for ROS 2, and iii.) articles utilizing ROS 2. Furthermore, we summarize literature findings of ROS 2 challenges, advancements, and future direction in the fields of a.) security, b.) real-time, c.) middleware, d.) embedded and distributed systems, e.) communication reliability and QoS, and f.) multi-robot systems. The methodology involved meticulous data collection and categorization from multiple databases, facilitating an in-depth online accessible resource. Results underscore ROS2’s enhancements in modularity, real-time capabilities, and security, extending its applicability across various robotic platforms and industries. However, challenges in scalability and reliability persist, signaling avenues for future enhancements. This review not only deepens the understanding of ROS2’s contributions but also charts a path for ongoing improvements in robotic systems design. The original data presented in the study are openly available in https://www.ros.riotu-lab.org/.

The PediCenter and Niles Children’s Clinic provide pediatric primary and urgent care services in central California. We remained open throughout the COVID-19 pandemic, providing scheduled well child-care and sick visits. Beginning in September 2020, we implemented a COVID-19 screening program. Screening was performed on all patients presenting for care and was made available to patients requiring testing for any purpose. Herein, we provide results from that program, including a description of clinical characteristics of COVID-19 in our patients. Key findings: 11,649 COVID-19 antigen screening tests were performed (age range 0.1 to 17.0, mean 8.7, SD 4.5). In total, 1,560 pts. (13.4%) tested positive. Among these, 665 (43%) were asymptomatic, 560 (36%) had mild disease, 318 (20%) had moderate disease, and 17 (1%) had severe disease. No critical cases or transfers to the emergency room were reported. Younger patient age was associated with an increased severity of illness, as was time from onset of pandemic. 4,446 patients reported no symptoms at the time of screening, 15% of whom tested positive. 7,203 patients reported symptoms at the time of testing. Among these, 87.6% tested negative and 12.4% tested positive. Disease severity was similar between these 2 groups. COVID-19 is generally a mild respiratory tract infection in healthy children. Screening is effective in identifying cases, including asymptomatic cases. Statistical models further revealed associations between patient age, time from the onset of the pandemic and disease severity.

This study presents an optimized design for a Segmented Sinusoidal Parameter Winding with Magnetic Wedge Variable Reluctance Resolver (SSPWMW-VRR), addressing challenges like winding asymmetry and harmonic distortion in conventional designs. By integrating Particle Swarm Optimization (PSO) for winding design, Magnetic Equivalent Circuit (MEC) analysis for leakage flux, and machine learning techniques (XGBoost and Multi-Layer Perceptron), the stator slot shape was fine-tuned for improved accuracy. XGBoost outperformed MLP in prediction accuracy with a Mean Absolute Error (MAE) of 0.1172. Finite Element Analysis (FEA) simulations and experimental validation demonstrated a reduction in position errors from ±30’ in conventional VRRs to ±5’ in the optimized design, along with significant harmonic reduction.

This paper presents the development and testing of the passive Almaty Ankle Exoskeleton V.2. The device features a new design with three electric linear actuators, and the shin and foot platforms are connected by links with spherical and universal joints. Functional testing demonstrates the prototype's ability to operate effectively within the natural range of ankle joint movements. Preliminary results indicate that the exoskeleton can reduce calf muscle activation in the work limb where the device is applied. In this the passive exoskeleton is designed for dorsiflexion and plantarflexion, whose operation with numerical results is highlighted by focusing on parameters such as angular velocity, linear acceleration, and angles. These measurements provide valuable information about the exoskeleton's performance and efficiency.

In the frame of the I-MOVE-COVID-19 project, a cohort of 2050 patients admitted in two Spanish reference hospitals between March 2020 and December 2021 was selected, and a range of clinical factors data were collected at admission to assess their impact on the risk COVID-19 severity outcomes through a multivariate adjusted analysis and nomograms. The need for ventilation and ICU admission were found directly associated with a higher mortality risk (OR 6.9 and 3.2, respectively). The clinical predictors of mortality were need for ventilation and ICU, advanced age, neuromuscular disorders, thrombocytopenia, hypoalbuminaemia, dementia, cancer, elevated CPK and neutrophilia (OR between 1.8 and 3.5), whilst the presence of vomiting, sore throat and cough diminished risk of death (OR 0.5, 0.2 and 0.1 respectively). Admission to ICU was predicted by the need for ventilation, abdominal pain and elevated LDH (OR 371.0, 3.6 and 2.2, respectively) as risk factors; otherwise, it was prevented by advanced age (OR 0.5). In turn, the need for ventilation was predicted by low oxygen saturation, elevated LDH and CPK, diabetes, neutrophilia, obesity and elevated GGT (OR between 1.7 and 5.2), whilst prevented by hypertension (OR 0.5). These findings could enhance patient management and strategic interventions to combat COVID-19.

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed an HBV screening in all Romanian adults hospitalized in 4 COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment or immunosuppressive conditions, whom we followed virologically at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed in 13 patients with positive hepatitis B surface antigen (HbsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) in all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish an appropriate and cost-effective management in these patients.

Chiral oxazolidine moiety is an important core in asymmetric synthesis due to its ability to participate in various stereoselective chemical reactions and because forms a part of more complex important active compounds. Therefore, in this letter we report a convenient diastereoselective and practical strategy for the synthesis of chiral methyl 2-((4R)-3-acryloyl-4-phenyloxazolidin-2-yl)acetates starting from (R)-(–)-2-phenylglycinol and methyl propiolate which were obtained via simple two chemical and stereoselective reactions.

Background/Objectives: Multisystem Inflammatory Syndrome in children (MIS-C) is a rare but severe post-infectious complication of COVID-19, that often requires admission to the Pediatric Intensive Care Unit (PICU). The present study aimed to compare the demographic, clinical and laboratory characteristics between children diagnosed with MIS-C who were admitted to the PICU or did not require PICU admission. Methods: Children diagnosed with MIS-C from September 2020 to April 2023 were included in this case-control study. Patient’s demographic, clinical and laboratory data, were collected from medical records. Results: Fifty children with MIS-C were included in the study [median (IQR) age: 7.5 (4.3, 11.4) years, 28/50 (56%) males]. Twenty-two (22/50, 44%) children required admission to the PICU. In the multivariate regression analysis, hepatic (OR:12.89, 95%CI: 1.35-123.41, p-value=0.03) and cardiological involvement (OR:34.55, 95%CI: 2.2-541.91, p-value=0.01) were significantly associated with hospitalization at the PICU. Regarding the laboratory and imaging parameters during the first 48 hours from admission, D-dimer levels higher than 4μg/mL and decreased Left Ventricular Ejection Fraction were associated with an increased risk of PICU admission (OR:7.95, 95%CI:1.48-42.78, p-value=0.02 and OR=1.28, 95%CI:1.07-1.53, p-value=0.01). Children who were admitted to the PICU were more likely to develop complications during their hospitalization (10/22, 45.5% vs. 3/28, 10.7%, p-value=0.005) and were hospitalized for more days, than children in the pediatric wards (median length of stay (IQR): 20 (15,28) days vs. 8.5 (6, 14) days, p-value&lt;0.001). Conclusions: In the present study, cardiovascular, hepatic involvement and increased D-dimer levels in children with MIS-C were associated with admission to the PICU.

Well-annotated gene and genomic sequences serve as a foundation for making inferences in molecular biology and evolution, and can directly impact public health. The first SARS-CoV-2 genome was submitted to GenBank and used to develop the two successful vaccines. Conserved protein domains are often chosen as targets for developing antiviral medicines or vaccines. Mutation and substitution patterns provide crucial information not only on functional motifs and genome/protein interactions but also for characterizing phylogenetic relationships among viral strains. These patterns, together with the collection time of viral samples, serve as the basis for addressing the question of when and where the host-switching event occurred. Unfortunately, viral genomic sequences submitted to GenBank undergo little quality control, and critical information in the annotation is frequently changed without being recorded. Researchers often have no choice but to hold blind faith in the accuracy of the sequences. There have been reports of incorrect genome annotation but no report that casts doubt on the genomic sequences themselves because it seems theoretically impossible to identify genomic sequences that may not be authentic. This paper takes an innovative approach to show that some SARS-CoV-2 genomes submitted to GenBank cannot be possibly authentic. Specifically, some SARS-CoV-2 genomic sequences deposited in GenBank with collection time in 2023 and 2024, isolated from saliva, nasopharyngeal, sewage, and stool are identical to the reference genome of SARS-CoV-2 (NC_045512). The probability for such occurrence is effectively 0. I also compile SARS-CoV-2 genomes with changed sample collection time. One may led astray in bioinformatic analysis without being aware of errors in sequences and sequence annotation.

Comprehending the replication kinetics of SARS-CoV-2 variants helps explain why certain var-iants spread more easily and are more contagious, and pose significant health menaces to the global populations. The replication kinetics of Malaysian isolates of the Alpha, Beta, Delta, and Omicron variants were studied in the Vero E6 cell line. Their replication kinetics were deter-mined using the plaque assay, quantitative real-time PCR (qRT-PCR), and viral growth curve. The Beta variant exhibited the highest replication rate at 24 hours post-infection (h.p.i), as evi-denced by the highest viral titers and lowest viral RNA multiplication threshold. The plaque phenotypes also varied among the variants, in which the Beta and Omicron variants formed the largest and smallest plaques, respectively. All studied variants showed strong cytopathic effects after 48 h.p.i. The whole-genome sequencing highlighted cell-culture adaptation, where the Beta, Delta and Omicron variants acquired mutations at the multibasic cleavage site after three cycles of passaging. The findings suggest a strong link between the replication rates and their respec-tive transmissibility and pathogenicity. This is essential in predicting the impacts of the upcom-ing variants on the local and global populations and is useful in designing preventive measures to curb the virus outbreaks.

Long COVID, characterized by persistent symptoms lasting from weeks to several months following initial infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), significantly impacts individuals' quality of life and poses a potential long-term burden on global healthcare systems. Clinical manifestations of Long COVID are diverse, affecting multiple systems including respiratory, cardiovascular, neurological, and gastrointestinal. While the precise mechanisms underlying Long COVID remain unclear, emerging evidence suggests involvement of various bodily pathways. This study employs bioinformatics tools to investigate the mechanisms of Long COVID and identify potential drug targets associated with key pathways, including inflammation, cytokines, immune response, coagulation, mitochondrial function, oxidative stress, and autonomic dysfunction. Tools such as the National Center for Biotechnology Information (NCBI) database, PubChem, UniProt, and iGEMDOCK were utilized for pathway analysis and molecular docking. The analysis aimed to identify drug molecules that may interact with target proteins to regulate or inhibit pathway activity, yielding several potential drug candidates for further investigation.

The presence of clays in copper minerals has a significant negative impact during their processing, leading to low recoveries during the flotation process. In saline environments such as seawater, the presence of clays contribute to an increase in operational problems caused by salinity, a decrease in the grade of the copper concentrate, alteration of the rheology of the mineral pulp, a decrease in the selectivity of copper during the flotation process, a reduction in the quality of clarified water, and excessive corrosion of metallic components. This study explores the electroflotation of kaolinite and montmorillonite clays in NaCl solutions using a modified Hallimond tube coupled with Ti Gr. 2 electrodes for bubble generation via water electrolysis, and the corrosion analysis of these electrodes applying the superposition model. The electroflotation results show recovery of clays close to 72.68% for kaolinite, 88.44% for montmorillonite, and 67.36% for a mixtures of both clays. The presence of clays helps reduce the corrosive effects of Ti Gr. 2 from 0.069 A/m2 in NaCl to 0.0073 A/m2 in NaCl with montmorillonite clay.

Growth factor receptor-bound protein 2 (GRB2) is a negative regulator of insulin signaling and positive regulator of angiogenesis. Its expression is increased in a mouse model of retinal neovascularization and in patients with type 2 diabetes mellitus (T2DM). This case-control study aimed to investigate the association between the rs9896052 polymorphism (A>C) upstream of GRB2 and proliferative diabetic retinopathy (PDR) in patients with T2DM from Southern Brazil, taking into consideration self-reported skin color (white or non-white) and the known duration of diabetes (< 10 years or ≥ 10 years). Genotypes were determined using real-time PCR in 838 patients with T2DM (284 cases with PDR and 554 controls without DR). In the total study group and in the analysis stratified by skin color, the genotype and allele frequencies were similar between the cases and controls. However, among patients with less than 10 years of diabetes, the C allele was more frequent in cases than in controls (63.3% versus 51.8%, p = 0.032), and the CC genotype was independently associated with an increased risk of PDR (adjusted OR = 2.82, 95% CI 1.17-6.75). In conclusion, our findings support the hypothesis that the rs9896052 polymorphism near GRB2 is associated with PDR in Brazilian patients with T2DM.

Seroprevalence of anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies in the postvaccination period in Kenya remains to be elucidated. This study aimed to determine the seroprevalence of anti-SARS-CoV-2 IgM and IgG and evaluate vaccination uptake in Nairobi, Kenya. This was a cross-sectional study conducted in a university setting. Serum anti-SARS-CoV-2 IgM and IgG levels were assayed using enzyme-linked immunosorbent assays. Mann–Whitney U test was used for binary comparisons and Kruskal–Wallis Test for multigroup comparisons. Statistical significance was set at p &lt; 0.05. A total of 189 participants were enrolled (median age, 21 years; female, 50.8%). The seroprevalence of anti-SARS-CoV-2 was 12.7% for IgM and 87.8% for IgG. Anti-SARS-CoV-2 IgG titers were higher among the vaccinated vs. non-vaccinated individuals (p &lt; 0.001, U = 2817.5), females vs. males (p = 0.024, U = 3616), and those vaccinated &lt; 6 months before the study vs. those vaccinated &gt;1 year earlier (p = 0.002, H = 12.359). The vaccination hesitancy rate was 43.4% and the underlying reasons included mistrust (22.4%), health concerns (19.7%), and lack of information (18.4%). Despite the high seroprevalence of anti-SARS-CoV-2 IgG, the high vaccine hesitancy rate necessitates community engagement and education prior to vaccines roll out.

Knowing the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many places during the first wave of COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain), during “Falles” mass gathering events in March 2020, a cross-sectional study was performed in June 2020 querying public health register. Logistic regression models were used. From a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak by anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), thus an underreporting of 92.3% (95% Confidence Interval [CI] 89.5%-94.6%), 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting were no medical assistance for COVID-19 disease, adjusted odds ratio [aOR] 10.83 (95% CI 2.49-47.11), no chronic illness, aOR=2.81 (95% CI 1.28-6.17), middle and lower social classes, aOR=3.12 (95% CI 1.42-6.85), younger age, aOR=0.97 (95% CI 0.94-0.99), shorter duration of illness, aOR=0.98 (95% CI 0.97-0.99). To improve surveillance, studies of representative population samples are necessary to estimate the magnitude of future epidemics, and novel approaches are recommended.

Introduction: This population-based retrospective cohort study assesses rates of adverse events (AEs) involving cerebral thromboembolism (CTE) after COVID-19 vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) Vaccine Adverse Event Reporting System (VAERS) database from January 1, 1990 to December 31, 2023. CTE AEs after COVID-19 vaccines were compared to those after influenza vaccines and after all other vaccines using proportional reporting ratio (PRR) analysis by time. Results: There are 5137 cerebral thromboembolism AEs reported in the 3 years (36 months) after COVID-19 vaccines compared to 52 AEs for the influenza vaccines over the past 34 years (408 months) and 282 AEs for all other vaccines (excluding COVID-19) over the past 34 years (408 months). The PRR’s are significant when comparing AEs by time from COVID-19 vaccines to that of the influenza vaccines (p < 0.0001) or to that of all other vaccines (p < 0.0001). The CTE AEs PRR by time (95% confidence intervals) for the COVID-19 vaccine AEs vs influenza AEs is 1120 (95% confidence interval (723-1730), p < 0.0001) and for COVID-19 vaccines vs all others is 207 (95% confidence interval (144-296), p < 0.0001). Cerebral venous thromboembolism AEs are female predominant with a female/male odds ratio of 1.63 (95% confidence interval (1.52-1.74), p < 0.0001). Conversely, cerebral arterial thromboembolism has a nonsignificant male preponderance. Cerebral venous thromboembolism is far more common than cerebral arterial thromboembolism over 36 months with an odds ratio (OR) of 14.8 (95% confidence interval 14.0-15.5, p < 0.0001). Atrial fibrillation, the most common identifiable cause of cerebral arterial thromboembolism, occurs far more commonly after the COVID-19 as compared to all other vaccines with a PRR of 123 (95% CI 88.3-172, p < 0.0001) Conclusions: There is an alarming breach in the safety signal threshold concerning cerebral thrombosis AEs after COVID-19 vaccines compared to that of the influenza vaccines and even when compared to that of all other vaccines. An immediate global moratorium on the use of COVID-19 vaccines is necessary with an absolute contraindication in women of reproductive age.

2019-n-CoV is the seventh coronavirus known to infect humans and cause serious illness, and due to its lethality there was a worldwide mobilization for the development of new drugs and new vaccines for Covid-19. Therefore, the present work aims to carry out a virtual screening of terpenes with potential anti SARS-CoV-2 activity. To perform the ligand-based virtual, a model was constructed regarding the compounds which already showed inhibitory activity of the SARS-CoV-2. The test series corresponded to terpenes isolated in the Fabaceae Family. The compounds that were most likely to activity were subjected to Molecular Docking and the best poses obtained were subjected to Molecular Dynamics (MD) simulations carried. The molecules under study were submitted to in vitro evaluation to assess inhibitory activity of compounds against SARS-CoV-2 in a phenotypic screening model of the virus. The compounds selected by in silico screening corresponded to triterpenoids from the lupane series. In the in vitro test, both demonstrated activity against the SARS-CoV-2 virus. The virtual screening performed managed to identify the compounds with the highest probability of activity, as well as the most stable compounds, and the method used was validated by the in vitro study carried out.

SARS-CoV-2 is an obligatory intracellular pathogen that requires of a lipid bilayer membrane for its transport, to build its nucleocapsid envelope and to fuse with the host cell. The biological membranes are constituted by phospholipids (PLs) and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if the treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFA), fatty acid of the phospholipids (FAPL), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6) and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HS). COVID-19 patients showed a decrease in Vit E, TPLs, FAPL and TFA in serum in comparison to HS (p≤0.01) and Vit E treatment restored their levels (p≤0.04). Likewise, there was an increase IL-6 and CRP in COVID-19 patients in comparison with HS (p≤0.001) and the treatment with Vit E decreased their levels (p≤0.001). Treatment with Vit E contributes to restore the modified profile of the PLs in the SARS-CoV-2 infection and this leads to a decrease of OS and of the inflammatory process.

The aim of this study was to investigate the relationship between postprandial glycemic levels based on flash-monitoring and the production of intestinal hydrogen (H2) and methane (CH4) gases based on measurement of the amount of these gases in exhaled air. We studied 14 subjects with type 2 diabetes mellitus (T2DM) and 10 individuals without diabetes (control) with 3 food-load tests with simultaneous determination of gases in exhaled air and assessment of glucose levels. In 15.4% of patients with T2DM, there was a non-significant increase in exhaled H2. How-ever, all subjects in the control group had significant increase in exhaled H2. Moreover, the level of H2 in exhaled breathafter food load in patients with T2DM was lower than in normoglycemic subjects. Also, in normoglycemic subjects there was an inverse correlation between maximum glucose rise and maximum H2 in exhaled air after food load. At the same time in patients with T2DM the level of CH4 in exhaled air directly correlated with the parameters of postprandial glycemia in the test with lactulose. Confirmation of a causal relationship between decreased H2 production, increased intestinal CH4 production, and more severe postprandial glycemia may identify new therapeutic targets in the correction of postprandial glycemia in patients with T2DM.

The objective of this study is to investigate how different therapies modulating insulin resistance, either causally or consequently, affect metabolic parameters in treatment-naive subjects with T2DM. A total of 212 subjects were assigned to receive either a tight Japanese diet (n=65), pioglitazone at doses ranging from 15-30 mg/day (n=70), or canagliflozin at doses ranging from 50-100 mg/day (n=77) for a duration of three months. Correlations and changes (Δ) in metabolic parameters relative to insulin resistance were investigated. Across these distinct therapeutic interventions, ΔHOMA-R exhibited significant correlations with ΔFBG and ΔHOMA-B, while demonstrating a negative correlation with baseline HOMA-R. However, other parameters such as ΔHbA1c, ΔBMI, ΔTC, ΔTG, Δnon-HDL-C, or ΔUA displayed varying patterns depending on the treatment regimens. Participants were stratified into two groups based on the median value of ΔHOMA-R: the lower half (X) and upper half (Y). Group X consistently demonstrated more pronounced reductions in FBG compared to Group Y across all treatments, while other parameters including HbA1c, HOMA-B, TC, TG, HDL-C, non-HDL-C, TG/HDL-C ratio, or UA exhibited distinct regulatory responses depending on the treatment administered These findings suggest that 1) regression to the mean is observed in the changes of insulin resistance across these therapies. 2) modulation of insulin resistance with these therapies, either causally or consequentially, results in differential effects on glycemic parameters, beta-cell function, specific lipids, body weight or UA.

International law faces numerous challenges in the 21st century, ranging from the traditional issues of sovereignty to emerging threats like cyber warfare and climate change. This article explores the evolving landscape of international law, discussing both the challenges it faces and the prospects for its future. By examining the role of international organizations, the impact of technological advancements, and the growing influence of non-state actors, this article provides a comprehensive overview of the current state of international law and offers insights into how it can adapt to meet the demands of an increasingly interconnected world.

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

Businesses now formally enter the phase of "think power differentiation and gap" in response to the new economic climate. While AI, big data, empowerment via the internet, and other aspects of the digital economy help to improve technical capabilities and save operating costs, they also push businesses to innovate their strategies at a faster rate. Enterprises are strategically choosing to de-enterprise, moving from focusing on a single business functioning benefit to building an ecosystem of platform services that will give them a competitive edge. Additionally, the organization's structure is evolving continually from a vertical model to a curved working style, in order to achieve this, businesses must recognize the importance of data analysis in day-to-day management and operations, encourage the development of an organizational atmosphere that is driven by data, fully utilize digital technology, modularize areas or production links that perform related tasks, and encourage the reform of organizational structures. By streamlining the output of the product or service to the external community while also enhancing the company's financial performance model, switching from process-to result-oriented evaluation, and putting in place a customized authority and accountability framework. Replace outcome-focused evaluation with process-focused evaluation, and create a customized incentive scheme that balances power, accountability, and rewards.

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. 29.8% had no SARS-CoV-2 serologic markers and displayed significantly lower CD4 counts and HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (0.0003), anti-S IgA (p &lt; 0.0001) and lack of neutralizing activity against Omicron variant (p &lt; 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immunity, but retained cellular immune.

Network centrality analyses have proven successful in identifying important nodes in diverse host-pathogen interactomes. The current study presents a comprehensive investigation of the human interactome and SARS-CoV-2 host targets. We first constructed a comprehensive human interactome by compiling experimentally validated protein-protein interactions (PPIs) from eight distinct sources. Additionally, we compiled a comprehensive list of 1,449 SARS-CoV-2 host proteins and analyzed their interactions within the human interactome, which identified enriched biological processes and pathways. Seven diverse topological features were employed to reveal the enrichment of SARS-CoV-2 targets in the human interactome, with Load centrality emerging as the most effective metric. Furthermore, a novel approach called CentralityCosDist was employed to predict SARS-CoV-2 targets, which proved effective in expanding the pool of predicted targets. Pathway enrichment analyses further elucidated the functional roles and potential mechanisms associated with predicted targets. Overall, this study provides valuable insights into the complex interplay between SARS-CoV-2 and the host cellular machinery, contributing to a deeper understanding of viral infection and immune response modulation.

We construct a Bayesian estimator for the dilution of a wastewater sample. When wastewater is diluted by rainwater an estimate of the level of dilution is required if we are to normalise sample measurements of disease markers such as SARS-CoV-2 RNA. We consider the situation where flow measurements are available, but will regularly be unreliable because of the action of combined sewer outflows (CSOs) and wastewater storage tanks, which divert wastewater away from treatment plants when the flow is excessive. However, we also have proxies for the flow from various chemical markers (e.g.\ phosphate, ammonium, electrical conductivity), whose level per unit of population is fixed. The new flow estimator has multiple advantages compared to existing procedures: credible intervals for the estimates; optimal weighting of the chemical markers; systematic handling of missing and censored values; and model based smoothing without lags.

Abstract: Abnormal growth of oligodendrocyte precursor cells (OPCs) importantly contributes to the progression of glioblastoma tumors. Hence, molecules that block OPC growth may be of therapeutic importance in treating gliomas. 2-methoxyestradiol (2ME), an endogenous tubulin interacting metabolite of estradiol is effective against multiple proliferative disorders. Based on its anti-carcinogenic and anti-angiogenic actions it is undergoing phase II clinical trials. We hy-pothesize that 2ME may prevent glioma growth by targeting OPC growth. Here we tested this hypothesis by assessing the impact of 2ME on growth of OPC cell line “Oli-neu” and dissected the underlying mechanism(s). Treatment with 2ME inhibited OPC growth in a concentra-tion-dependent manner and accompanied with significant upregulation in expression of p21 and p27, negative cell cycle regulators. Moreover, treatment with 2ME altered OPC morphology from multi-arm processes to rounded cells. At concentrations of 1uM and greater 2ME induced apoptosis with increased expression of caspase 3, PARP and caspase-7 fragments, externalized phosphatidylserine staining / apopercentage and increased mitochondrial activity. Flow-cytometry and microscopic analysis demonstrated that 2ME triggers endoreduplication in a concentration-dependent fashion. Importantly, 2ME induced cyclin E, JNK1/2 and p53 expres-sion as well as OPC cell fusion, key mechanisms driving endoreduplication or whole-genome duplication. Importantly, inhibition of p53 with pfithrin-α rescued 2ME-induced endoreduplica-tion. The pro-apoptotic and endoreduplication actions of 2ME were accompanied with upregula-tion of survivin, cyclin A, Cyclin B, Cyclin D2, ppRB. Taken together our findings provide evi-dence that 2ME not only inhibits OPC growth and triggers apoptosis, but also activates OPCs in a survival - fight or flight mode leading to endoreduplication. This inherent survival character-istic of OPCs may, in part be responsible for drug resistance in gliomas as observed for many tubulin interacting drugs. Importantly, the fate of OPCs after 2ME treatment may depend on cell-cycle status of the individual cells. Combining tubulin-interfering molecules with drugs, such as pfithrin-α, that inhibit endoreduplication may help inhibit OPC/glioma growth and lim-it drug resistance.

Introduction: The emergency of the SARS-CoV-2 virus spread and its subsequent global pan-demic have raised significant concerns regarding its impact on pregnancy outcomes. This review aims to summarize the emerging data on the risk of preterm delivery in pregnant women infected with SARS-CoV-2. Materials and Methods: A systematic search was conducted from March 2020 to December 2023 using PubMed, following PRISMA guidelines. Studies correlating maternal COVID-19 infection with preterm birth were included. Results: Thirteen studies were analyzed, indicating a higher incidence of preterm birth in SARS-CoV-2 positive pregnant women compared to controls. The average incidence rate of pre-term birth in infected patients was 18.5%, with a median of 12.75%, while non infected women showed an average incidence of preterm birth of 10% with a median of 8.2%. Discussion: Studies suggest an association between SARS-CoV-2 infection during pregnancy and increased risk of preterm birth and cesarean section. Severity of symptoms and underlying comorbidities further elevate this risk. Notably, infections during the third trimester pose the highest risk of preterm birth. Conclusion: Preventing SARS-CoV-2 infection during pregnancy is crucial to mitigate adverse obstetric outcomes. Close monitoring and tailored interventions for infected pregnant women, particularly those in later trimesters and with comorbidities, are imperative to reduce the risk of preterm birth and improve maternal-fetal outcomes.

The main purpose of this article is to consider the smoothness control of a weak solution after some moment if there is known solution regularity until this moment. The necessary tools can be varied. It is possible to control kinetic energy dissipation to fix moment or changing of velocity square or summability of acceleration square to fix at point time.

The emergence of SARS-CoV-2 mutations pose significant challenges to diagnostic tests as these mutations can reduce the sensitivity of commonly used RT-PCR assays. Therefore, there is a need to design diagnostic assays with multiple targets to enhance sensitivity. In this study, we identified a novel diagnostic target, nsp10 gene, using nanopore sequencing. Firstly, we determined the analytical sensitivity and specificity of our COVID-19-nsp10 assay. The COVID-19-nsp10 assay had the limit of detection of 74 copies/mL (95% confidence interval: 48-299 copies/mL) and did not show cross-reactivity with other respiratory viruses. Next, we determined the diagnostic performance of the COVID-19-nsp10 assay using 261 respiratory specimens, including 147 SARS-CoV-2-positive specimens belonging to ancestral strain and Alpha, Beta, Gamma, Delta, Mu, Eta, Kappa, Theta and Omicron lineages. Using the LightMix E-gene RT-PCR assay as the reference method, the diagnostic sensitivity and specificity of the COVID-19-nsp10 assay were 100%. The median Cp values for the LightMix E-gene RT-PCR and our COVID-19-nsp10 RT-PCR were 22.48 (range: 12.95-36.60) and 25.94 (range 16.37-36.87), respectively. The Cp values of the COVID-19-nsp10 RT-PCR assay correlated well with those of the LightMix E-gene RT-PCR assay (Spearman’s ρ = 0.968; P&lt;0.0001). In conclusion, nsp10 is a suitable target for SARS-CoV-2 RT-PCR assay.

This is a SARS-CoV-2 seroepidemiological study in pediatric population(0-16 years) during BA.5 Omicron predominance period in Athens metropolitan area. Serum samples were tested for SARS-CoV-2 nucleocapsid antibodies(Abs-N), representing natural infection during three sub-periods of BA.5 predominance: 01/05/2022-31/08/2022(period A), 01/09/2022-31/12/2022(period B) and July 2023(period C) and epidemiological data were collected. Additionally in period C Abs-N seronegative samples were tested for SARS-CoV-2 spike antibodies(Abs-S). A total of 878 children were tested (males:51.3%) with median age(IQR): 108(36-156) months and seropositivity during the 3 subperiods was: A:292/417(70%), B:288/356(80.9%), C:89/105(84.8%), P-value<0.001. SARS-CoV-2 seropositivity increased for from period A to C for 0-1-year (P-value: 0.044), 1-4 years (P-value: 0.028) and 6-12 years children (P-value: 0.003). Children 6-12y had the highest seroposi-tivity rates in all subperiods (A: 77.3%, B: 91.4% and C: 95.8%). A significant correlation of monthly SARS-CoV-2 median antibody titers with monthly seropositivity rates was detected (rs:0.812, P-value:0.008). During period C, an additional 12/105 (11.4%) Abs-S seropositive and Abs-N ser-onegative samples were detected and total seropositivity was estimated at 96.2% (101/105). The increased SARS-CoV-2 seropositivity detected in current seroepidemiology study illustrates a high exposure rate during BA.5 predominance period. These data could guide public health decisions regarding immunization strategies and protection measures.

In Tropical Monsoon climates, precipitation exceeds evapotranspiration, leading to increased surface runoff, especially in floodplain regions. The Bhagirathi-Hooghly River in India is the focus of the study, which analyses hydrology, sediment yield, and water balance in this floodplain area. This investigation employs the Soil and Water Assessment Tool (SWAT) model within the ArcGIS environment, using remote sensing data. The study area is divided into 4 sub-basins and 40 Hydrological Response Units (HRUs), with a focus on Land Use/Land Cover (LULC) parameters, soil attributes, and slope characteristics. Calibration (1998-2010) and validation (2011-2018) of river discharge and sediment yield are performed using the SUFI-2 algorithm within SWAT-CUP. The calibration process shows a strong correlation between observed and simulated data points, indicating the model's accuracy. The study reveals a pattern of early-year evapotranspiration followed by increasing rainfall during the monsoon season, leading to heightened surface runoff and sediment yield. Excessive rainfall, therefore, emerges as a pivotal driver of flood incidences within the floodplain. The insights derived from the SWAT model's floodplain data have the potential to inform flood control and sedimentation mitigation strategies. The assimilation of this data can empower local stakeholders and contribute to sustainable livelihoods and improved living conditions, offering guidance for future governmental policies.

Lifestyle interventions halt the progression of prediabetes to frank type 2 diabetes (T2D). However, the feasibility of a diabetes prevention program promoting tailored interventions on a national scale and conducted by primary care physicians is unclear. To explore this issue, general practitioners dislocated in ten different regions throughout Italy enrolled random subjects without known metabolic diseases to identify individuals with prediabetes and prescribe them an intervention based on physical activity. Using a simple stepwise approach, people referring to their primary care physician for any reason were screened for their diabetes risk with a web-based app of the Findrisc questionnaire. Those at risk for T2D, i.e. with a Findrisc score > 9, were invited to come back after overnight fasting to measure fasting glycaemia (FG). Those with 100 ≤ FG < 126 mg/dL were considered as people with prediabetes and compiled the Physical Activity Readiness Questionnaire (PAR-Q) to then receive a personalized prescription of physical activity. Overall, 5928 people were enrolled and compiled the questionnaire. Of these, 2895 (48.8 %) were at risk for T2D. Among these, FG was measured in 2168 subjects (participation rate 75%). The numbers of individuals with undetected prediabetes and T2D according to FG were 755 and 79 (34.8% and 3.6% of those assessing FG), respectively. Of the 755 subjects in the prediabetes range, 739 compiled the PAR-Q and started a personalized program of physical activity (participation rate 97%). Physicians involved in the study reported a mean of 6 minutes to perform the screening. Overall, these data suggest the feasibility of a national diabetes prevention program developed by general practitioners using a simple stepwise approach starting from a web-app to intercept individuals with prediabetes.

Background: So far, vaccination has been considered the most crucial defense against viral infection, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncology patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. Objective: This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19. Material and methods: 1,668 people were observed. Over two years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in three groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection. Results: The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, and colon cancer, although the response varies significantly depending on the type of cancer. Summary: The size of the humoral response and the presence of specific antibodies directed against the SARS-CoV-2, IgM, and IgG, in response to the supply of the vaccine antigen or assessed after COVID-19, is an indicator of adequate immune protection against reinfection. This study highlights for the first time the phenomenon of increased humoral response in response to a viral infection in patients with certain types of cancer that are assumed to be sensitive to oncological therapy, the initiation of which, according to generally accepted principles, was blocked by infection with the SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also seems to explain the asymptomatic course of SARS-CoV-2 infection in some of the above patients. It remains an open question to what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients.

Multispectral and 3D LiDAR remote sensing data sources are valuable tools for characterizing the 3D vegetation structure and thus understanding the relationship between forest structure, biodiversity and microclimate. This study focuses on mapping riparian forest species in the canopy strata using a fusion of Airborne LiDAR data and multispectral multi-sources and multi-resolution satellite imagery; Sentinel-2 and Pleiades at tree level. The idea is to assess the contribution of each data source in the tree species classification at the considered level. The data fusion was processed at feature-level and decision level. At feature level, LiDAR 2D attributes were derived and combined with vegetation indices. At decision level, LiDAR data was used for 3D tree crown delimitation providing unique trees or groups of trees that are used as a support for the species classification. Data augmentation techniques were used to improve the training process. Best results were obtained by the fusion of Sentinel-2 time series and LiDAR data with a Kappa of 0.66 thanks to red-edge based indices that better discriminate vegetation species and the temporal resolution of Sentinel-2 images that allows monitoring the phenological stages helping to discriminate the species.

The host glycosylation mechanism synthesizes the carbohydrates of glycoproteins of viral envelopes. Due to the loss of the Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase gene by some mammalian species, including humans (negative-CMAH), Neu5Gc is no longer synthesized. Uptake of Neu5Gc by negative-CMAH species, through the intake of food products derived from positive-CMAH mammals, leads to incorporating Neu5Gc-glycans in the glycocalyx (xenosialylation). Neu5Gc, being a Mammalian-associated Carbohydrate Antigen (MCA), acts as a non-self-antigen, inducing an inflammatory reaction (Xenosialitis), and triggering the production of circulating antiNeu5Gc antibodies to attack/remove all incorporated Neu5Gc. In the state of Xenosialitis, the virus-neutralizing antibodies produced by a heavily xenosialylated patient following exposure to viral infection (including SarsCoV2) or anti SarsCoV2 vaccination cross-react against all incorporated non-self Neu5Gc-MCA glycans due to their resemblance with viral envelope antigens synthesized by the host glycosylation mechanism. In addition, the circulating anti-XeSias antibodies determine the massive removal of the circulating neutralizing FC-xeno-contaminated antibodies by the serum, living only the hyper-inflammatory agalattosylated antiviral IgG antibodies. Therefore, we hypothesize that the combination of antibody cross-reaction against non-self Neu5Gc-MCA glycans and the massive removal of the xeno-contaminated newly formed neutralizing antibodies in favor of hyper reactive antibodies, could be the cause of the massive inflammatory reaction (cytokine storm, coagulopathies, neuropathies) observed in Covid 19 patients or after anti-SarsCoV2 vaccination. This analysis is an invitation to investigate the post-infectious and/or post-vaccination adverse phenomena in the light of xenosialization as a key to understanding the severe post viral and post vaccine complications, including SARS-CoV2 infection or related vaccination.

Achieving glycemic control and sustaining functional pancreatic β-cell activity remains an unmet medical need in the treatment of type 2 diabetes mellitus (T2DM). Glucokinase activators (GKAs) constitute a class of anti-diabetic drugs designed to regulate blood sugar levels and enhance β-cell function in patients with diabetes. A significant progression in GKA development is underway to address the limitations of earlier generations. Dorzagliatin, a dual-acting GKA, targets both the liver and pancreas and has successfully completed two Phase III trials, demonstrating favorable results in diabetes treatment. The hepato-selective GKA—TTP399— emerges as a strong contender, displaying clinically noteworthy outcomes with minimal adverse effects. This paper seeks to review the current literature, delve into the mechanisms of action of these new-generation GKAs, and assess their efficacy and safety in treating T2DM based on published pre-clinical studies and clinical trials.

During the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral thera-pies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants, which strongly challenged the containment measures and some therapeutic treatments. To assess whether an impaired immunity could lead to an increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimize the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients expe-rienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low frequency mutations. This study suggests that a compro-mised immune system alone does not affect SARS-CoV-2 within-host genomic variability.

We investigated 328 SARS-CoV-2 cases in Barwon South West Victoria, Australia, in the 2020 pre-vaccination period, comparing infections with symptoms to those that remained asymptomatic. De-identified self-reported data from three sequential questionnaires on case characteristics and symptom progression were examined. Multivariable logistic regression were used to model associations between demographic profile and symptoms. Asymptomatic cases were more than three times as likely to be from ethnic minority groups [OR 3.2, 95% CI 1.5 – 6.7, p&lt;0.01], and approximately seven times more likely to be seniors (≥ 65 years) [OR 7.3, 95% CI 1.0 – 50.1] after adjusting for sex and occupation. The overrepresentation of ethnic minority groups among asymptomatic infections is suggestive of genetic haplotype variability by ethnic group, conferring greater cross protection from other coronaviruses in the early stages of the COVID-19 pandemic. This research should be repeated post-vaccination to reassess symptom expression according to ethnicity, and better comprehend case ascertainment impacts of cultural biases in testing and infection reporting, and the reliance on symptoms to trigger testing. These findings may in part reflect differences in testing patterns by ethnicity and true differences in disease expression, both important for appropriate transmission prevention strategies, and tailoring testing messaging towards ethnic minority communities.

The 2-Acetyl-1-pyrroline (2-AP) is the most important volatile in determining the aroma of fragrant rice, however, the transcriptional regulation mechanism of 2-AP biosynthesis in fragrant rice is still unclear. In this study, the Osp5cs1 knockout mutant lines and OsP5CS1 over-expression lines were constructed by genetic transformation of indica rice cultivar i.e., ‘Zhonghua11’, which was knocked out OsBADH2 to produce fragrance in aromatic rice. The OsP5CS1 gene was also identified as a key gene in the 2-AP biosynthesis pathway of aromatic rice. The OsP5CS1 promoter was used as bait, and the transcription factor OsbZIP60-like was screened by yeast one-hybrid assays. The transcription factor OsbZIP60-like specifically bound to the OsP5CS1 gene. The dual luciferase reporting system found that OsbZIP60-like transcription factor promoted the transcriptional activation of OsP5CS1. Compared with the wild type, the OsP5CS1 gene expression was significantly down-regulated in Osbzip60-like mutant, and resulted in substantial reduction in 2-AP biosynthesis. Moreover, the OsP5CS1 gene expression was significantly up-regulated in OsbZIP60-like over-expressed plants, and the 2-AP concentrations were also increased whereas the Osbzip60-like mutants were found to be sensitive to Zn deficiency. Overall, the OsbZIP60-like transcription factor promoted the 2-AP accumulation. This study provides a theoretical basis for the transcriptional regulation mechanism of 2-AP biosynthesis and explores the function of OsbZIP transcription factor in fragrant rice.

Introduction. This retrospective study aimed to compare the risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Methods. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF23, fetuinA, sclerostin, and VC scores (Adragao method). Multivariable linear regression identified VC predictors. Results: The prevalence of VC was similar in both groups, but HD patients had more pronounced VC scores ≥6. Pre-HD patients were older, with higher prevalence of Balkan endemic nephropathy, hypertension, and less frequent use of calcium phosphate binders. Both groups exhibited similar patterns of hyperphosphatemia, low vitamin D, and iPTH levels. In HD group normal phosphate was significantly common in patients with VC, whereas hyperphosphatemia was significantly common in patients without VC. Fetuin-A levels were higher in pre-HD patients, while FGF23 was elevated in HD patients. In pre-HD patients, male gender was associated with reduced VC risk, while in HD patients, malignancies and serum phosphate levels were negative VC predictors. Conclusion: Effective monitoring and tailored treatment of VC in CKD are still focused on phosphate regulation. Besides, mineral disturbances, hormones and biomarkers regulation, and patient-specific variables need to be considered.

This study is to explore the feasibility using neural network (NN) and deep learning to diagnose three common respiratory diseases with only few symptom words. These three diseases are nasopharyngitis, upper respiratory infection, and bronchitis/bronchiolitis. Through natural language processing, the symptom word vectors are encoded by GPT-2 and classified by the last linear layer of the NN. The experimental results are promising, showing that this model achieves a high performance in predicting all these three diseases. They reach 90% in accuracy, which suggests the implications of the developed model, highlighting its potential use in assisting patients understanding their conditions via a remote diagnosis. Unlike previous studies that focus on extracting various categories of information from medical records, this study directly extracts sequential features from unstructured text data, reducing the effort required for data pre-process.

To study the fermentation process of biocatalyzing decanoic acid to synthesize trans-2-decenoic acid, this study was based on the engineering E.coli constructed in the laboratory in the early stage and studied the effect of seed liquid culture time, culture temperature, inoculum amount, induction temperature, dissolution effects of substrate solvent, metal ions, and substrate loading on the yield of trans-2-decenoic acid. Based on single-factor experimental optimization, the Box–Behnken design was used to conduct response surface testing using the substrate feeding concentration, inducer concentration, and MnCl2 concentration as response variables and trans-2-decenoic acid production as the response value. The optimal fermentation process was determined through experiments: seed culture time 20 h, culture temperature 37°C, inoculation amount 1%, induction temperature 30°C, substrate flow amount 0.15 g/L, inducer concentration 5.60 g/L, MnCl2 concentration was 0.10 mM. Under these conditions, the average production of trans-2-decenoic acid was 1.982 ± 0.110 g/L. Compared with the basic LB medium, the production of trans-2-decenoic acid increased by 1.042 g/L; compared with the previous period, the yield of trans-2-decenoic acid studied increased by 1.501 ± 0.110 g/L, which provides a reliable basis for further research on the fermentation process of biocatalytic decanoic acid synthesis of trans-2-decenoic acid.

(1) Background: Some evidence suggests that cannabidiol (CBD) has potential to help alleviate HIV symptoms due to its antioxidant and anti-inflammatory properties. Here we examined acute CBD effects on various behaviors and the endocannabinoid system in HIV Tat transgenic mice. (2) Methods: Tat transgenic mice (female/male) were injected with CBD (3,10,30 mg/kg) and assessed for antinociception, activity, coordination, anxiety, and recognition memory. Brains were taken to quantify endocannabinoids and related lipids. Additionally, CBD and metabolite 7-hydroxy-CBD were quantified in the plasma and cortex. (3) Results: Tat decreased striatal-related nociception and locomotion, with some sex-dependent effects on coordination. CBD had no effect on nociception and coordination, but increased locomotor activity. For anxiety, differential CBD effects were noted for sex, with decreasing anxiety-like behavior in males only. In the striatum and spinal cord, male sex was associated with lower 2-arachidonoylglycerol and with elevated concentrations of its proinflammatory metabolite arachidonic acid. CBD metabolism was altered by sex and Tat. (4) Conclusion: Findings indicate that acute CBD effects are not altered by HIV Tat, and CBD has minimal effects on behavior and the endocannabinoid system. Interestingly, sex-dependent alterations were noted for endocannabinoids and related lipids, which may be of relevance in view of potential CBD-based treatment options for people living with HIV.

In this paper, we give all non splitting bi-unitary superperfect polynomials divisible by one or two irreducible polynomials over the prime field of two elements. We prove the nonexistence of odd bi-unitary superperfect polynomials over F2.

Postural orthostatic tachycardia syndrome (POTS) and its related symptoms have been identified as a possible complication of COVID-19 infection and vaccination and have recently gained attention. The diagnosis and management of POTS require great care and attention, even under normal circumstances, due to its complex nature. However, the COVID-19 pandemic and its complications have further complicated the diagnosis and management of this syndrome in COVID-19-related settings. The objective of this study is to enhance our comprehension of POTS and POTS-like symptoms in the context of COVID-19. To achieve this, we provide a concise overview of the POTS concept, its potential underlying mechanisms, available clinical reports of POTS following COVID-19 infection and vaccination, as well as the clinical manifestations of this syndrome in COVID-19-related scenarios with a brief overview of its management.

The liver is not only a digestive gland, but also an immune tissue that receives a double infusion from the hepatic artery and the hepatic portal vein. Receiving 80% of its blood supply from the intestine through the hepatic portal vein system, the liver is enriched with a large number of innate immune cells, which carry out the process of immune response by detecting pathogens entering the organism through the intestine. The intestine and liver communicate extensively through the bile ducts, portal vein and the somatic circulation, a bidirectional communication known as the intestinal-liver axis. The mammalian gut is considered an important microbial ecosystem. The interplay between the natural immune system and microbes coordinates the physiology of the whole organism, and in specific mammalian lineages, there is a dependency between the host and its associated microbes. To this end, we explored the regulatory mechanisms of natural immunity genes at the genome-wide level. Based on comparative genomics, 1473 bovine natural immunity genes were obtained by collecting the latest reports of human natural immunity genes and updated bovine genomic data for comparison, and a bovine natural immunity gene database was initially constructed to screen and match calf liver natural immunity differential genes mainly affected by the phylum Mimosoidea and the phylum Thick-walled Bacteria, and 16 differentially expressed natural immunity genes were obtained. In addition, the results of IPA analysis indicated that the upstream factor IL-2 initiated the PI3K/AKt/mTOR, mitogen-activated protein kinase (MAPK) pathway and JAK/STAT5 pathway, leading to the liver's involvement in gut microbial immune regulation.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

Preterm birth (PB) is a leading cause of perinatal morbidity and mortality. PB prediction is per-formed by measuring cervical length, with a detection rate of around 70%. Although it is known that a cytokine-mediated inflammatory process is involved in the pathophysiology of PB, no screening method implemented in clinical practice includes cytokine levels as a predictor varia-ble. Here, we quantified cytokines in cervical-vaginal mucus of pregnant women (18-23.6 weeks of gestation) with high- or low-risk for PB determined by cervical length, collecting relevant obstetric information. IL-2, IL-6, IFN-γ, IL-4, and IL-10 were significantly higher in the high-risk group, while IL-1ra was lower. Two different models for PB prediction were created using the Random Forest machine-learning algorithm: the full model with 12 clinical variables and cyto-kine values, and the adjusted model, including the most significant variables -maternal age, IL-2, and cervical length- (detection rate 66 vs 87%, false positive rate 12 vs 3.33%, false negative rate 28 vs 6.66%, and area under the curve 0.722 vs 0.875, respectively). The adjusted model integrat-ing cytokines showed a detection rate 8 points higher than the gold standard calculator, which may allow us to identify PB risk more accurately and implement strategies for preventive in-terventions

The synthesis, anticancer and antioxidant activity of a series of indole-derived hybrid chalcones are reported here. First, using well known Claisen-Schmidt condensation method a set of 29 chalcones has been designed, synthesized, and consequently characterized. Subsequently, screening for the antiproliferative activity of the synthesized hybrid chalcones was performed on the on five cancer (HCT116, HeLa, Jurkat, MDA-MB-231 and MCF7) and two non-cancer (MCF-10A and Bj-5ta) cell lines. Chalcone 18c bearing 1-methoxyindole and catechol structural features, exhibited selective activity against cancer cell lines with IC50 values of 8.0 ± 1.4 µM (Jurkat) and 18.2 ± 2.9 µM (HCT116) and showed no toxicity to non-cancer cells. Furthermore, antioxidant activity was evaluated using tree different methods. The in vitro studies of radical scavenging activity utilizing DPPH radicals, as well as FRAP method, demonstrated the strong activity of catechol derivatives 18a-c. According to the ABTS radical scavenging assay, the 3-methoxy-4-hydroxy substituted chalcones 19a–c were slightly more favorable. In general, a series of 3,4-dihydroxychalcone derivatives showed properties as a lead compound for both antioxidant and anticancer activity.

Recently, NOAA has included GNSS (Global Navigation Satellite System) Radio Occultation (RO) data as one of the crucial long-term observables for weather and climate applications. To include more GNSS RO data in the numerical weather prediction system, the NOAA Commercial Weather Data Pilot program (CWDP) started to explore the commercial RO data available on the market. After two rounds of pilot studies, the CDWP decided to award the first Indefinite Delivery Indefinite Quantity (IDIQ) contract to GeoOptics and Spire Incs. in 2020. This study examines the quality of Spire data products for weather and climate applications. Spire RO data are collected from commercial CubeSats through careful comparison with the data from Formosa Satellite Mission 7–Constellation Observing System for Meteorology, Ionosphere, and Climate-2 (COSMIC-2), ERA-5, and high-quality radiosonde data. The results demonstrated that although with lower Signal-Noise-Ratio (SNR) in general, the pattern of the lowest penetration height for Spire is similar to those for COSMIC-2. The Spire and COSMIC-2 penetrate heights are between 0.6 and 0.8 km altitude at the tropical oceans. Although using different GNSS RO receivers, the precision of Spire STRASP receivers is of the same quality as those of COSMIC-2 Global Positioning System - GPS, GALILEO, and GLObal NAvigation Satellite System – GLONASS (TGRS) receivers. The retrieval accuracy from Spire is very compatible with those from COSMIC-2. We validated Spire temperature and water vapor profiles by comparing them with collocated radiosonde data. Generally, over the height region between 8 km and 16.5 km, the Spire temperature profiles match those from RS41 RAOB very well with temperature biases &lt; 0.02 K. Over the height range from 17.8 to 26.4 km, the temperature differences are ~-0.034 K with RS41 RAOB being warmer. We also estimated the error covariance matrix for Spire, COSMIC-2, and KOMPSAT-5. Results showed that the COSMIC-2 estimated error covariance values are slightly more significant over the oceans at the mid-latitudes (45oN-30oN and 30oS-45oS), which may also be owing to COSMIC-2 SNR being lower at those latitudinal zones.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in humans in Wuhan City at the end of December 2019. Since then, it has spread to all the countries. Therefore, global interest has been focused on discovering treatments and developing successful vaccines. This study sequenced the complete genome of the SARS-COV-2 Omicron Omicron (BA.1) and sub-variants (BA.1.1, BA.2), which were isolated from 40 individuals in Duhok, Iraq. Ninety-five different mutations were identified when the complete genome of the SARS-COV-2 virus discovered in Wuhan, China (accession number: NC 045512.2) was matched to the virus sequence using sequencing technology (Illumina, USA). Sequence analysis revealed 38 mutations in spike glycoprotein (S), 30 of which were found in ORF1a. Additionally, 11 mutations were found in ORF1b, and 7,3,2,1 mutations were found in Nucleocapsid (N), membrane protein (M), Open Reading Frames 6 (ORF6), Open Reading Frames 9 (ORF9), and Envelope (E) genes, respectively. Phylogenetic analysis and transmission further confirmed that the isolates found in Iraq had distinct infection origins and were closely related to those from other countries and states. According to the findings of this study, a new vaccine can be developed based on identifying new Omicron variant mutations and sub-variants such as BA.2, which were identified for the first time in Iraq.

Kidney transplant recipients (KTR) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTR. Between February 1, 2020 and July 1, 2022, 578 KTR were infected with SARS-CoV-2, with 25 (4%) recurrent infections. 208 KTR (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU-admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed, being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both, virological changes in the Omicron variant and vaccination, reduce the risk for morbidity and mortality from COVID-19 in KTR. Our data extend the knowledge from the general population to KTR and provide important insights into outcome during the Omicron era.

The COVID-19 pandemic has posed a significant threat to society in recent times, endangering human health, life, and economic well-being. The disease spreads quickly due to the highly infectious SARS-CoV-2 virus, which has undergone numerous mutations. Despite intense research efforts by the scientific community since its emergence in 2019, no effective therapeutics have been discovered yet. While some repurposed drugs have been used to control the global outbreak and save lives, none have proven universally effective, particularly for severely infected patients. Although the spread of the disease is generally under control, anti-SARS-CoV-2 agents are still needed to combat current and future infections. This study reviews some of the most promising repurposed drugs containing indolyl heterocycle, which is an essential scaffold of many alkaloids with diverse bio-properties in various biological fields. The study also discusses natural and synthetic indole-containing compounds with anti-SARS-CoV-2 properties, as well as computer-aided drug design (in-silico studies) for optimizing anti-SARS-CoV-2 hits/leads.

Developing nanomaterials with the capacity to restrict the growth of bacteria and fungus is of current interest. In this study, nanocomposites of poly(2-hydroxyethyl methacrylate) (PHEMA) and carbon nanotubes (CNTs) functionalized with primary amine, hydroxyl, and carboxyl groups were prepared, and characterized. An analysis by Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy showed that PHEMA chains were grafted to the functionalized CNTs. The morphology of the prepared nanocomposites studied by field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM) shows significant changes with respect to the observed for pure PHEMA. The thermal behavior of the nanocomposites studied by differential scanning calorimetry (DSC) revels that the functionalized CNTs affects strongly the mobility of the PHEMA chains. Tests carried out by thermogravimetric analysis (TGA) were used to calculate the degree of grafting of the PHEMA chains. The ability of prepared nanocomposites to inhibit the growth of the fungus Candida albicans, and the bacteria Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli was evaluated. A moderated antifungal and antibacterial capacity of the prepared nanocomposites was determined.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 enters the host by infecting nasal ciliated cells. Then, the virus can spread towards the oropharyngeal cavity and the pulmonary tissues. The antiviral adaptive immunity is promptly induced in response to virus detection, with virus-specific T lymphocytes appearing before antiviral antibodies. Both breadth and potency of the antiviral CD8+ T cell immunity have a key role in containing viral spread and disease severity. Current anti-SARS-CoV-2 vaccines do not impede the virus replication in the upper respiratory tract, and there is consensus on the fact that the best potency of the antiviral immune response in both blood and upper respiratory tract can be reached upon infection in vaccinees (i.e., breakthrough infection). However, whether the antiviral CD8+ T cells developing in response to the breakthrough infection in the upper respiratory tract diffuse to the lungs also is still largely unknown. To fill the gap, we checked the CD8+ T cell immunity elicited after infection of K18-hACE2 transgenic mice both 3 weeks and 3 months after anti-Spike vaccination. The virus-specific CD8+ T cell immunity was monitored in both blood and the lungs before and after infection. By investigating the de novo generation of CD8+ T cells specific for SARS-CoV-2 viral proteins, we found that both membrane (M) and/or nucleocapsid (N)-specific CD8+ T cells were induced at comparable levels in blood of both unvaccinated and vaccinated mice. Conversely, N-specific CD8+ T cells were readily found in the lungs of control mice, but were either rare or absent in those of vaccinated mice. These results support the idea that the hybrid cell immunity developing after asymptomatic/mild breakthrough infection strengthens the antiviral cell immunity at lungs only marginally, implying that the direct exposition of the viral antigens is required for the induction of an efficient antiviral cell immunity in the lungs.

The altimeter-derived ocean currents have been sparsely evaluated against in situ measurements in the Arctic, particularly for extended time periods. This study uses the extensive mooring array situated in the Fram Strait, representing one of the longest ocean current records, to investigate the relationship between in situ and satellite-derived currents in the region. The primary objective of this research is to analyze the vertical structure of the West Spitsbergen Current (WSC), its spatio-temporal coherence, and its association with surface geostrophic currents during the period of 1997-2012. To assess the vertical structure of the WSC, we utilized the Empirical Orthogonal Functions (EOF) and cross-correlation analysis between neighboring moorings. Remarkably, both velocity components exhibited robust vertical coherence, particularly within the waters of the North Atlantic Inflow, at depths exceeding 800 m. These findings underscore the potential for surface measurements to effectively complement data gaps and facilitate the reconstruction of deeper currents with a monthly temporal resolution. Notably, the surface measurements explain approximately 67% of the variance in the top 800 m of the water column.This comprehensive investigation advances our understanding of the West Spitsbergen Current and its vertical characteristics in the Arctic. Moreover, our findings highlight the valuable synergy between in situ and satellite-derived data, providing critical insights for future ocean current studies in this ecologically sensitive region.

Respiratory infections constitute a major reason for infants and children seeking medical advice and visiting health facilities, thus remaining a significant public threat with high morbidity and mortality. The predominant viruses causing viral respiratory infections are influenza A and B viruses (Flu-A, Flu-B), Respiratory Syncytial Virus (RSV), Adenovirus and Coronaviruses. We aimed to record the incidence of RSV, SARS-CoV-2, Influenza A/B and Adenovirus cases with rapid antigen tests and validate the results with RT-PCR assay of upper respiratory specimens with a wide range of viral loads and (co)-infection patterns in children. Clinical samples were collected from early symptomatic children (presenting with fever and/or cough and/or headache within 5–7 days). The surveillance program was conducted in five private pediatrician dispensaries and one Pediatric care unit, from 10 January 2023 to 30 March 2023 in central Greece. The total sample of specimens collected was 784 young children and infants, of which 383 (48.8%) ware female and 401 were male (51.2%). The mean age of participants was 7.3 + 5.5 years. The sensitivity of FLU A &amp; B test was 91.15% (95% CI: 84.33% -95.67%), and the specificity was 98.96% (95% CI: 97.86% - 99.58%). The sensitivity and specificity of the adenovirus and RSV test was {92.45% (95% CI: 81.79% - 97.91%), 99.32% (95% CI: 98.41% -99.78%)} and {92.59% (95% CI: 75.71% -99.09%), 99.47% (95% CI: 98.65% - 99.86%)} respectively. Lastly, the sensitivity of the SARS-CoV-2 test was 100.00% (95% CI: 79.41%-100.00%) and the specificity was 99.74% (95% CI: 99.06% - 99.97%). We recorded proportion of incidence for the Influenza-A and B, (14.3%), - (3.44%) correspondingly, followed by the adenovirus with a proportion (6.9%) and the RSV with (3.7%) incidence proportion and finally, the SARS-CoV-2 (2.3%). The combination of a new multiple rapid test with multiple antigens, will be probably a useful tool with financial impact for health systems targeting the early detection and right treatment of respiratory infections in the emergency departments in primary health care facilities.

The COVID-19 pandemic cost 7-8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the SARS-CoV2 virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in ARDS and lung injury. Anti-inflammatory intervention with anti-IL6 (anti-IL-6 receptor monoclonal antibodies (mAbs) (e.g., sarilumab, tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and /or steroid-based approach lead to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this short review, we summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus–host immune cross talks and presenting the possibilities of therapeutic intervention.

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.

During one of the worst global health crises, millions of people were vaccinated against SARS-CoV-2. In rare cases, new onset systemic inflammatory diseases were reported with temporal coincidence to the vaccination. We describe a case of severe Eosinophilic Granulomatosis with Polyangiitis (EGPA) in a young asthmatic woman, occurring after a 2nd dose of mRNA-1273 vaccine. She presented with multisystem EGPA with cardiac and central nervous system involve-ment, complicated by secondary immune thrombocytopenia (ITP). We review the reported cases of EGPA coinciding with SARS-CoV-2 mRNA vaccination. All potentially vaccine-related EGPA cases reported so far occurred within 14 days from immunization. EGPA is very rare with an incidence of 1:1’000’000 inhabitants and the number of reported post-vaccination EGPA cases lies within the expected incidence rate for the period. While we cannot prove a causal relationship between the vaccine and EGPA onset, the temporal relationship with the vaccine immune stimulation is intriguing, in a disease occurring almost always in adults with asthma and/or chronic rhinosinusitis and driven by an aberrant Th2 lym-phocyte activation with hypereosinophilia. Nevertheless, cases of inflammatory diseases emerging in the context of vaccination remain rare and the benefits of preventing severe Covid presentations with SARS-CoV-2 mRNA vaccines remains unquestionable.

A land cover map of two arctic catchments, nearby the Abisko Scientific Research Station, was obtained from a classification of a Sentinel-2 satellite image and a ground survey performed in July 2022. The two contiguous catchments, Miellajokka and Stordalen, are covered by various ecotypes, from boreal forest to alpine tundra and peatland. The random forests algorithm correctly identified 88% of polygon pixels reserved for testing. The developed workflow relied solely on open source software and acquired ground observations. Space organization was directed by the altitude as demonstrated by the intersection of the land cover with the topography. Comparison between this new land cover map and previous ones based on data acquired between 2008 and 2011 shows some trends of vegetation cover evolution in response to climate change in the considered area.

Polymorphism in cytochrome P450 (CYP) 2C9 enzyme is known to cause significant inter-individual differences in drug response and occurrence of adverse drug reactions. Different alleles of the CYP2C9 gene have been identified but the notable alleles responsible for reduced enzyme activity are CYP2C9*2 and CYP2C9*3. No pharmacogenetic data is available on CYP2C9*2 and CYP2C9*3 alleles in Pakistani population. In Pakistan pharmacogenetics which examines the relationship between genetic factors and drug response, are in the early stages of development. We for the first time investigated the association between the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 and the incidence of hypoglycemia in diabetic patients who were receiving the sulfonylurea medications. A total of n=400 individuals of Pashtun ethnicity were recruited from ten different districts of Khyber Pakhtunkhwa, Pakistan to participate in the study. The study participants were divided into two distinct groups: the case group (n=200) and the control group (n=200). The case group consisted of individuals with Type 2 Diabetes Mellitus (T2DM) who were receiving sulfonylurea medications and experience hypoglycaemia with it whereas the control group included individuals with T2DM who were receiving sulfonylurea medication but did not experience sulfonylurea-induced hypoglycaemia (SIH). Blood samples were obtained from study participants following informed consent. DNA was isolated from whole blood samples using Wiz-Prep DNA extraction kit. Following DNA isolation, CYP2C9 alleles were genotyped using MassARRAY sequencing platform at centre of genomics Rehman Medical Institute (RMI). The frequency of CYP2C9*2 (low activity allele) was more frequent in the diabetic patients with sulphonylurea-induced hypoglycaemia (SIH) compared to the control group (17.5% vs. 6.0%, p=0.021). The frequency of its corresponding genotype CYP2C9*1/*2 was higher in cases compared to control group (10% vs. 6% with P=0.036), same was true for genotype CYP2C9*2/*2 (7% vs. 3.5 % with P=0.028). Logistic regression analysis evident potential association of CYP2C9*2 allele and its genotypes with SIH. When adjusted for confounding factors such age, weight, sex, daily dose of sulphonylurea and triglyceride level the association between the CYP2C9*2 allele and hypoglycemia remains consistent. Confounding factors played no role in SIH because both groups (cases and controls) were closely matched in term of age, weight, sex, mean daily dose of sulphonylurea and trigyleride levels. Our study suggests that genetic information about a patient's CYP2C9 gene/enzyme can potentially assist physicians in prescribing the most suitable and safest drug based on their genetic make-up.

Background: The therapeutic benefits of fermented foods in the treatment and prevention of Type 2 diabetes mellitus have been reported. Aim: Inhibitory effect of fermented rice beverages on α-amylase, α-glucosidase and pancreatic lipase was evaluated. Method: Two fermented rice beverages-fermented rice alone (FKR) and fermented rice plus roasted peanuts (FKRG) were produced using spontaneous fermentation. Capacity of the beverages to inhibit al-pha-glucosidase, alpha-amylase and pancreatic lipase in vitro was evaluated and compared with standards (positive controls). Results: FKR exerted inhibition of α-glucosidase between 9.23-21.11% and FKRG 1.11-17.36% at the various concentrations respectively, with both samples showing the most significant inhibition (about 20%) at 125 μg/mL. FKRG exhibited greater alpha-amylase inhibition activity than FKR, but for both samples, the most significant (P < 0.05) inhibition occurred at 500 μg/mL. With pancreatic lipase, no significant inhibition was observed for both FKR and FKRG at the tested concentrations compared to Orlistat used as control; how-ever, at 31.25 μg /mL FKRG showed an inhibitory effect of approximately 15%, which was not evident at higher concentrations. Conclusion: Low to moderate inhibition of α-amylase, α-glucosidase and pancreatic lipase by both FKR and FKRG, showed that the fermented rice beverages have potential to modulate hyperglycemia in type 2 diabetes in vitro. This is an indi-cation that fermented rice beverage could prevent postprandial hyperglycemia in vivo.

The Shisa family is a type of single-transmembrane adaptor proteins containing an N-terminal cysteine-rich domain and a proline-rich C-terminal region. Nine Shisa subfamily genes have been proposed in most vertebrates; however, some of them might be species-specific. The number of Shisa genes present in zebrafish remains unclear. The purpose of this study was to investigate the evolutionary relationships among Shisa family genes in zebrafish (TU strain) using phylogenetic and syntenic analyses. The function of shisa-2 was preliminarily examined via CRISPR/Cas13d-mediated knockdown. Following identification in zebrafish,10 Shisa family genes, namely shisa-1, 2, 3, 4, 5, 6, 7, 8, 9a, and 9b, were classified into three main clades and six subclades. Their encoding proteins contained a cysteine-rich N-terminal domain and a proline-rich C-terminal region containing different motifs. A specific syntenic block containing atp8a2 and shisa-2 was observed to be conserved across all species. Furthermore, all these genes were found to be expressed during embryogenesis. shisa-2 was expressed in the presomitic mesoderm, somites, and so on. shisa-2 was identified as a regulator of the expression of the somite formation marker mesp-ab. Overall, our study provides new insights into the evolution of Shisa family genes and the control of shisa-2 over the convergent extension cells of somatic precursors in zebrafish.

Periodontitis is a widely spread chronic inflammatory disease caused by a changed oral microbiome. Although multiple species and risk factors have been associated with periodontitis, Porphyromonas gingivalis undoubtedly stands in the center as a keystone pathogen. The immune-modulatory function of P. gingivalis has been well characterized, but the mechanism by which peptidyl arginine deiminase (PPAD), a citrullinating enzyme, contributes to the infinite loop of inflammation is not fully understood. To determine the functional role of hypercitrullination in the context of periodontitis, we performed a comparative analysis on neutrophils stimulated by the wild type and the PPAD mutant strain that lacks an active enzyme. Our flow cytometric analysis revealed that PPAD contributes to the prolonged neutrophil survival upon bacteria stimulation, which was accompanied by aberrant IL-6 and TNF-α secretion in the experimental environment. To further elaborate on the complex mechanism by which citrullination sustains the chronic inflammatory state, we assessed the ROS production and phagocytic activity of neutrophils. Flow cytometry and colony formation assay demonstrated that PPAD obstructs the resolution of inflammation by promoting neutrophil survival and the release of pro-inflammatory cytokines while making the bacteria itself more resilient to phagocytosis.

Objectives: The aim of this study is to evaluate some mechanisms of the immune response of people infected with SARS-CoV-2 in both acute infection and early and late convalescence phases. Methods: This is a cohort study of 70 cases of COVID-19, confirmed by RT-PCR, followed up to 60 days. Plasma Samples and clinical data were. Viral load, blood count, indicators inflammation were the parameters evaluated. Cellular immune response was evaluated by flow cytometry and Luminex immunoassays. Results: In the severe group, hypertension was the only reported comorbidity. Non severe patients have activated memory naive CD4+ T cells. Critically ill patients have central memory CD4+ T cell activation. Severe COVIS-19 patients have both central memory TCD8+ T cells and activated effector TCD8+ cells. Non-severe COVID-19 cases showed an increase in IL1β, IL-6, IL-10 and TNF and severely ill patients had higher levels of the cytokines IL-6, IL-10 and CXCL8.Conclusion: The present work showed that different cellular responses are observed according to the COVID-19 severity in patients from Brazil an epicenter the pandemic in South America. Also, we notice that some cytokines can be used as predictive markers for the disease outcome, possibility implementation of strategies effective by health managers.

Following the well-known pandemic, declared on 30 January 2020 by the World Health Organi-zation, the request for new global strategies for the prevention and mitigation of the spread of the infection has come to the attention of the scientific community. Nanotechnology has often managed to provide solutions, effective responses, and valid strategies to support the fight against SARS-CoV-2. This work reports a collection of information on nanomaterials that have been used to counter the spread of the SARS-CoV-2 virus. In particular, the objective of this work is to illustrate the strategies that have made it possible to use the particular properties of nanomaterials, for the production of personal protective equipment (DIP) for the defense against the SARS-CoV-2 virus.

Introduction: This study aims to investigate the activity of the remdesivir-nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and to report a case of Coronavirus Disease 2019 (COVID-19) cured with this combination. Methods: A Vero E6 cell-based infection assay was used to investigate the in vitro activity of the remdesivir-nirmatrelvir combination. The SARS-CoV-2 strains tested were 20A.EU1, BA.1 and BA.5. After incubation, a viability assay was performed. The supernatants were collected and used for viral titration. The Highest Single Agent (HSA) reference model was calculated. An HSA score >10 is considered synergic. Results: Remdesivir and nirmatrelvir showed synergistic activity at 48 and 72 h with an HSA score of 52.8 and 28.6, respectively (p<0.0001). This data has been confirmed performing supernatant titration and against the omicron variants: the combination reduced the viral titer better than the more active compound alone. An immunocompromised patient with prolonged and critical COVID-19 was successfully treated with remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab, and dexamethasone, with an excellent clinical-radiological response. However, she required further off-label prolonged therapy with nirmatrelvir/ritonavir up to the negativization. Conclusion: Remdesivir-nirmatrelvir combination has synergic activity in vitro. This combination may have a role in immunosuppressed patients with severe COVID-19 and prolonged viral shedding.

Evaluating the performance of water indices and mapping the spatial distribution of water-related ecosystems are important for monitoring surface water resources. This is particularly the case for Ethiopia since there is limited information available on water resources development over time despite its relevance for the people and ecosystems. To address this problem, this paper evaluates the performance of seven water indices for country-scale surface water detection based on high spatial and multi-temporal resolution Sentinel-2 data, processed using the Google Earth Engine cloud computing system. Results show that the water index (WI) and automatic water extraction index with shadow (AWEIsh) are the most accurate ones to extract surface water. Comparisons are based on qualitative visual inspections and quantitative accuracy indicators. For the latter, WI and AWEIsh obtained kappa coefficients of 0.96 and 0.95, respectively, and an overall accuracy of 0.98 each. Both indices accounted for similar spatial coverages of surface waters with 82,650 km2 (WI) and 86,530 km2 (AWEIsh) for the whole of Ethiopia.

The main problem in creating anti-coronavirus vaccines that target mainly proteins of the outer membrane of the virus remains the rapid variability of the RNA genome of the pathogen that encodes these proteins. In addition, the introduction of technologies that can provide affordable and fast production of flexible vaccine formulas that easily adapt to the emergence of new subtypes of SARS-CoV-2 is required. Universal oligonucleotide vaccine can take into account the dynamics of rapid changes in the virus genome, as well as be synthesized on automatic DNA synthesizers in large quantities in a short time. In this brief report, the effectiveness of four phosphorothioate constructs of the La-S-so type oligonucleotide vaccine will be evaluated for the first time on transgenic mice [B6.Cg-Tg (K18-ACE2)2]. In our primary trials, the oligonucleotide vaccine increased the survival rate of animals infected with SARS-CoV-2 and also reduced the destructive effects of the virus on the lung tissue of mice. The obtained results show the perspective of the development of vaccine constructs of the La-S-so type for the prevention of coronavirus infections, including those caused by SARS-СoV-2.