Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that, occasionally, may spread to the central nervous system (CNS), being the most common cause of sporadic encephalitis. One of the main neurovirulence factors of HSV-1 is the protein ICP34.5 that, although initially seemed to be relevant only in neuronal infections, it can also promote viral replication in non-neuronal cells. New ICP34.5 functions have been discovered during the recent years, and some of them have been questioned. This review describes the mechanisms of ICP34.5 to control cellular antiviral responses and debates its most controversial functions. One of the most discussed roles of ICP34.5 is autophagy inhibition. Although autophagy is considered a defense mechanism against viral infections, current evidence suggests that this antiviral function is only one side of the coin. Different types of autophagic pathways interact with HSV-1 impairing or enhancing the infection, and both the virus and the host cell modulate these pathways to tip the scales in its favor. In this review, we will summarize the recent progress on the interplay between autophagy and HSV-1, focusing on the intricate role of ICP34.5 in the modulation of this pathway to gain the battle against cellular defenses.

Whole-genome sequencing has advanced our understanding of the population structure of the pathogenic species complex Cryptococcus gattii, which has allowed for the phylogenomic specification of previously described major molecular type groupings and novel lineages. Recently, isolates collected in Mexico in the 1960s were determined to be genetically distant from other known molecular types and were classified as VGVI. We sequenced four clinical isolates and one veterinary isolate collected in the southwestern U.S. and Argentina during 2012-2021. Phylogenomic analysis groups these genomes with those of the Mexican VGVI isolates, expanding VGVI into a clade and establishing this molecular type as a clinically important population. These findings also potentially expand the known Cryptococcus ecological range with a previously unrecognized endemic area.

To demonstrate if botulinum toxin type A (BoNT-A) improves mandibular range of motion and muscle sensibility to palpation in refractory myofascial pain (MFP) patients. METHODS: Eighty consecutive female subjects with refractory MFP, were randomly divided into four equal groups (n=20): BoNT-A low (BoNTA-L/10 U in each temporalis and 30 U in each masseter), BoNT-A medium (BoNTA-M/20 U in each temporalis and 50 U in each masseter), BoNT-A high (BoNTA-H/25 U in each temporalis and 75 U in each masseter) and saline solution 0.9% (SS, placebo control group/0.4 mL in each temporalis and 0.6 mL in each masseter). Clinical measurements of the mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements. Palpation tests were performed bilaterally in masseter and temporalis muscle. Results were expressed as median, minimum, maximum, and means ± standard deviation (SD). Chi-Square Test was used to compare differences among groups. A 5% probability level was considered significant in all tests RESULTS: Regardless of dose, all parameters of mandibular range of motion significantly improve after 180 days in BoNT- A groups, when compared to the control group. Pain to palpation on muscles, significantly reduced in all BoNT- A groups regardless of dose, when compared to the control group, after 28 and 180 days of treatment. CONCLUSIONS: Independent of doses, BoNT-A improved mandibular range of motion and muscle sensibility to palpation in refractory MFP patients when compared to SS injections.

Aim of this study was to evaluate the accuracy and usability of a novel continuous glucose moni-toring (CGM) system designed for needle-free insertion and reduced environmental impact. We assessed sensor performance of two GlucoMen® Day CGM systems worn simultaneously in eight participants with type 1 diabetes. Self-monitoring of blood glucose (SMBG) was performed reg-ularly over 14 days at home. Participants underwent two standardized 5-hour meal challenges with frequent plasma glucose (PG) measurements using a laboratory reference instrument at the research center. When comparing CGM to PG the overall mean absolute relative difference (MARD) was 9.7 [2.6-14.6]%. The overall MARD of CGM vs SMBG was 13.1 [3.5-18.6]%. In the consensus error grid (CEG) analysis, 98% of both CGM/PG and CGM/SMBG pairs were in the clinically acceptable zones A and B. The analysis confirms that GlucoMen® Day CGM meets the clinical requirements for state-of-the-art CGM. The needle-free insertion technology is well toler-ated by users and reduces medical waste compared to conventional CGM systems.

Abstract: The effect of collagen type 1 (Col I) oxidation on Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) remodeling is described as a model for acute oxidative stress. Morphologically, remodeling was presented by a mechanical rearrangement of adsorbed FITC-Col I and a trend for its organization in a fibril-like pattern - a process strongly abrogated in oxidized samples, but without visible changes in cell morphology. The cellular proteolytic activity was quantified in multiple samples utilizing fluorescence de-quenching (FRET effect). In the presence of ADMSCs a significant increase of native FITC-Col I fluorescence was observed, almost absent in the oxidized samples. Parallel studies in cell-free systems confirmed the enzymatic de-quenching of native FITC-Col I by Clostridial collagenase, again showing significant inhibition in oxidized samples. The structural changes in the oxidized Col I was further studied by Differential Scanning Calorimetry: an additional endotherm at 33.6°C along with the typical for native Col I at 40.5°C with sustained enthalpy (∆H) was observed in oxidized samples. Collectively, it has been evidenced that remodeling of Col I by ADMSCs is altered upon oxidation due to the intrinsic changes in the protein structure, thus presenting a novel mechanism for the control of stem cells' behavior toward collagen.

Copper, which can potentially be a highly toxic agent, is an essential nutrient due to its role as a co-factor for cuproenzymes and participation in signaling pathways. In mammals, the liver is a central organ that controls copper turnover throughout the body: copper absorption, distribution, and excretion. In ontogenesis, there are two types of copper metabolism: embryonic and adult, which maintain the balance of copper in each of these periods, respectively. In the liver cells, these types are characterized by specific expression patterns and activity levels of the genes encoding ceruloplasmin, which is the main extracellular ferroxidase and copper transporter and proteins mediating ceruloplasmin metalation. In newborns, the molecular-genetic mechanisms responsible for copper homeostasis and the ontogenetic switch from embryonic to adult copper metabolism are highly adapted to milk ceruloplasmin as a dietary source of copper. In the mammary gland cells, the level of ceruloplasmin gene expression and the alternative splicing of its pre-mRNA govern the amount of ceruloplasmin in milk, and thus, the amount of copper absorbed by the newborn is controlled. In the newborns, absorption, distribution, and accumulation copper are adapted to milk ceruloplasmin. In the newborns, which are not breast-fed at the early stages of postnatal development, the control for alimentary copper balance is absent. We tried to focus on the neonatal consequences of a violation of the balance of copper in the mother / newborn system. Although there is still much to be learned, the time to pay attention to this problem came because the neonatal misbalance of copper may provoke the development of copper related disorders for future life.

The world is currently going through a serious pandemic of viral infection with SARS-CoV-2, a new isolate of coronavirus, resembling and surpassing the crisis that occurred in 2002 and 2013 with SARS and MERS, respectively. SARS-CoV-2 has currently infected more than 142,000 people, causing 5,000 deaths and reaching more than 130 countries worldwide. The very large spreading capacity of the virus clearly demonstrates the potential threat of respiratory viruses to human health, alarming governments around the world that preventive health policies and scientific research are pivotal to overcoming the crisis. Coronavirus disease 2019 (COVID-19) causes flu-like symptoms in most cases. However, approximately 15% of patients will need hospitalization, and 5% require assisted ventilation, depending on the cohorts studied. What is intriguing, however, is the higher susceptibility of elderly individuals, especially those who are more than 60 years old and have comorbidities, including hypertension, diabetes and heart disease. In fact, the death rate in this group may be up to 10-12%. Interestingly, children are somehow protected and not included as a risk group.Thus, here, we discuss some possibilities of molecular and cellular mechanisms by which elderly subjects may be more susceptible to severe COVID-19. In this sense, we raise two main points: i) increased ACE-2 expression in pulmonary and heart tissue of chronic angiotensin 1 receptor (AT1R) blocker users and hypertensive individuals and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. We believe these are pivotal points for a better understanding of the pathogenesis of severe COVID-19 and must be addressed with attention by physicians and scientists in the field.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

Newly characterising 245 Italian and Albanian HCV-2 NS5B sequences collected between 2001 and 2016 was used to reconstruct the origin and dispersion pathways of HCV-2c. The tree of a subset of these sequences aligned with 247 publicly available sequences was reconstructed in spatio-temporal scale using the Bayesian approach, and the effective replication number (Re) was estimated using the birth-death model. Our findings show that HCV-2c was the most prevalent subtype in Italy and Albania, and that GT2 originated in Guinea Bissau in the XVI century and spread to Europe in the XX century. The HCV-2c subtype had two internal nodes respectively dating back to the 1930s and 1950s having as most probable locations Ghana and Italy, respectively. Phylodynamic analysis revealed an exponential increase in the effective number of infections and Re in both Italy between the 1950s and 1980s, and Albania between the 1990s and the early 2000s. It seems very likely that HCV-2c reached Italy from Africa at the time of the second Italian colonisation (1936-1941), but did not reach Albania until the period of dramatic migration to Italy in the 1990s.

Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator, triggering various inflammatory conditions, including eosinophil activation and recruitment. Despite the unclear mechanism underlying the formation and maintenance of nasal polyp in chronic rhinosinusitis with nasal polyps (CRSwNP), there is strongly indication of its association with type 2 inflammation. This study aimed to quantify PAF-associated gene expression, examining enzymes involved in PAF synthesis (lysophosphatidylcholine acyltransferase 1 (LPCAT1), LPCAT2, LPCAT3, and LPCAT4), and PAF degradation (PAF acetylhydrolases 1 B2 (PAFAH1B2), PAFAH1B3, and PAF acetylhydrolases 2 (PAFAH2)), and PAF receptor (PTAFR). Transcriptomic analysis encompassed CRSwNP, including eosinophilic CRS (ECRS) (n=9), nonECRS (n=8), and a subgroup of ECRS with aspirin exacerbated respiratory disease (Asp) (n=3) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria. Gene expression profiles from nasal polyps in CRSwNP patients and the uncinate process in normal subjects (controls) (n=6) were analyzed using bulk RNA barcoding and sequencing (BRB-seq). Hierarchal analysis, utilizing the average linkage method with iDEP1.1, clarified the relationship between Differentially Expressed Genes (DEG) expressions and cluster formation. Two clusters (cluster 1 (n=11) and cluster 2 (n=9)) of CRSwNP divided by hierarchal analysis showed distinct gene expression profiles in the specific pathway of “cytokine-cytokine receptor interaction” in KEGG pathway and upregulated type 2 inflammatory gene expression in cluster 2. In CRSwNP subclassification of ECRS, nonECRS, and Ctrl, PTAFR was only upregulated in ECRS and nonECRS. In cluster analysis, cluster 1 showed significant downregulation of LPCAT2 and upregulation of PTAFR expression, while cluster 2 showed significant upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. These findings suggest that cluster 2, characterized by severe type 2 inflammatory gene expression, manifest a prominent PAF-associated pathophysiology. Understanding this high PAF-associated pathophysiology in cluster 2 could provide valuable insights into the treatment and management of CRSwNP.

Dysferlinopathies comprise a spectrum of muscular dystrophies characterized by progressive muscle weakness and degeneration due to mutations in the DYSF gene, which encodes the dysferlin protein critical for muscle membrane repair. This review delves into the clinical spectra of dysferlinopathies, their molecular mechanisms, and the spectrum of emerging therapeutic strategies. We explore the phenotypic heterogeneity of dysferlinopathies, highlight the incomplete understanding of genotype-phenotype correlations, and discuss the implications of various DYSF mutations. Furthermore, we examine the utility of animal models in elucidating disease mechanisms and the potential of symptomatic, pharmacological, molecular, and genetic therapies in mitigating the disease's progression. We also consider the roles of diet and metabolism in managing dysferlinopathies, as well as the impact of clinical trials on treatment paradigms. By culminating the complexities inherent in dysferlinopathies, this article emphasizes the need for multidisciplinary approaches, precision medicine, and extensive collaboration in research and clinical trial design to advance our understanding and treatment of these challenging disorders.

Mediterranean Diet (MD), rich in minimally processed plant foods and in monounsaturated fats, but low in saturated fats, meat and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratio, lipids, and inflammation markers, and even prevents the development of fatal and non-fatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns on its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbioma.

The main goal of this article is the characterization of Herz-type Besov-Morrey spaces K˙p,qαN˙μ,rs and Triebel-Lizorkin-Morrey spaces K˙p,qαE˙μ,rs via ball means of differences, atomic, molecular and wavelet decompositions. There are provided necessary facts for implying these results, which can help to explore such spaces on different domains in further researches. Proposed spaces allow to extend the class of studying functions, containing Leray projection, heat semi-group and other operators, which can be helpful in exploring weak, strong and mild solutions of nonlinear partial differential equations.

Rural landscapes are acknowledged for their potential to restore human health due to their natural characteristics. However, few studies have systematically analysed the impact of naturalness, landscape types, and combinations of landscape elements on restorativeness using both subjective and objective measurements. This study investigated the restorative effects of various rural landscapes in Guangzhou, employing electroencephalography and eye-tracking technologies to record physiological responses and using the Restorative Components Scale and the Perceived Restorativeness and Naturalness Scale to evaluate psychological responses. The results indicated the following: (1) There was a significant positive correlation between perceived naturalness and restorativeness, surpassing the impact of actual naturalness. (2) Different landscape types had a varying impact on mental health at the equal perceived naturalness. Natural forest landscapes and artificial forest landscapes exhibited the most substantial restorative effects among the natural and semi-natural landscapes examined, respectively, while settlement landscapes showed the highest restorative potential among the artificial landscapes. (3) Restorative properties varied across landscape elements, with identical elements yielding different benefits in different environments. Trees and water significantly enhanced restorativeness, whereas constructed elements such as roads and infrastructure reduced it. This study provides a scientific basis for restorative rural landscape design to enhance mental health and well-being.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

The Standard Model is not a complete description of reality; it omits the existence of dark matter, dark energy, and an explanation as to why no CP violation has been observed. However, some of these phenomena could be explained through a new force mediated by a new boson. If such a boson were massless it would result in a power law potential and if massive the interaction would be Yukawa-like. A previous experiment employing a micro-mechanical oscillator and a spherical test mass interactions was successful in placing the best limits on a mass-mass Yukawa-like interaction, but the data was never analyzed in the context of a power law. Here that data is analyzed considering a power law for powers n = 1-5 where n is the number of boson exchanges. The results show that the limits obtained through power law analysis of this data are not better than the currently accepted limits. A discussion of an experiment design capable of producing better limits on power law extensions to the Standard Model is presented, and suggests micro mechanical oscillators based experiment remains capable of improving the limits by at least one order of magnitude.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.

Infant hepatitis B vaccine coverage in China is high, with over 95% of infants immunized; however, high vaccine coverage can often mask low timeliness. The vaccination interval between the second and third dose is not clearly defined by immunization guidelines in China. This retrospective cohort study assessed the time interval distribution of hepatitis B vaccination among a cohort of randomly selected live births from Centers for Disease Control and Prevention across four provinces or municipalities in China between January 2017 and December 2021. Among the infants analyzed, 163,224 received the first dose of hepatitis B vaccine with 146,905 (90.0%) and 135,757 (83.2%) infants receiving the second and third doses, respectively. A total of 132,577 (90.2%) infants received the second dose between 28–61 days after the first dose. Of the 119,437 (88.0%) infants that completed the hepatitis B series between 61–214 days after the second dose, 87,067 (64.1%) infants were vaccinated with the third dose between 151–180 days after the second dose. The time interval distribution for the three doses of hepatitis B vaccine varied across the four provinces or municipalities (P<0.001). Of the 58,077 infants who completed the hepatitis B vaccine series, 36,377 (62.6%) infants used the same type of hepatitis B vaccine for all three doses. Overall, the timeliness of hepatitis B vaccination for infants was lower than expected, with regional disparities observed. This highlights the need for improved timeliness through the introduction of a defined timeframe for the last two doses of vaccine, and training for obstetricians and related personnel.

A herbarium is a library of preserved dried samples of vascular plants, bryophytes, fungi, algae and/or lichens and is maintained for educational and scientific purposes, and provides detailed information on taxonomy, systematic, biodiversity, ecological and evolutionary research studies. Globally, there are more than 3,000 active public herbaria that preserve around 400 million exsiccates. In Brazil there are 216 active herbaria, of which 162 are indexed in the Index Herbariorum and in the Central region there are 21 herbaria. In this context, the Herbarium of the University of Brasília (international code UB) was founded in 1963 together with the Department of Botany of UnB and is located at the Institute of Biological Sciences of the Campus Darcy Ribeiro, Brasília and it is fifth largest herbarium in Brazil and presents approximately 277 thousand samples. In this study, we present here the bryophytes collection at the UB Herbarium. The collection of bryophytes of UB herbarium has 30,902 samples of all continents and 79 countries and most come from Brazil, Papua New Guinea, Malaysia, United States of America and Argentina.

Thymus is an herbaceous perennials or subshrubs of the Lamiaceae family and is widely distributed worldwide. Essential oils extracted from thymus have attracted much attention owing to their potential biological functions. Here, we evaluated the chemical compositions of eight thyme essential oils (TEOs) using gas chromatography-mass spectrometry and assessed their antioxidant activity and in potential role in antibacterial and tumor therapy. The results showed that (1) the main components in eight TEOs were monoterpene hydrocarbons and oxygenated monoterpenes, and the chemical compositions of TEOs were affected by the specie factor; (2) eight TEOs could be divided into 3 groups (thymol-, geraniol-and nerol acetate-type), and thymol was main type; (3) eight TEOs had some common compounds, such as thymol and p-cymene, which were the main components in seven TEOs; (4) eight TEOs had antioxidant activit, and thymol-type EOs had strong antioxidant activity, while geraniol-type EOs had relatively weak antioxidant activity. In addition, it was found thymol had strong antibacterial activity against the growth of Escherichia coli and Staphylococcus aureus, and antimigratory activity of A549 cell. Overall, our results can provide theoretical basis for further exploring the function of natural products from thyme essential oils.

The Cav3.2 T-type calcium channel is implicated in various pathological conditions, including cardiac hypertrophy, epilepsy, autism, and chronic pain. Phosphorylation of Cav3.2 by multiple kinases plays a pivotal role in regulating its calcium channel function. The calcium/calmodulin-dependent serine/threonine phosphatase, calcineurin, interacts physically with Cav3.2 and modulates its activity. However, it remains unclear whether calcineurin dephosphorylates Cav3.2, the specific spatial regions on Cav3.2 involved, and the extent of the quantitative impact. In this study, we elucidated the serine/threonine residues on Cav3.2 targeted by calcineurin using quantitative mass spectrometry. We identified six serine residues in the N-terminus, II-III loop, and C-terminus of Cav3.2 that were dephosphorylated by calcineurin. Notably, a higher level of dephosphorylation was observed in the Cav3.2 C-terminus, where calcineurin binds to this channel. Additionally, a previously known CaMKII-phosphorylated site, S1198, was found to be dephosphorylated by calcineurin. Furthermore, we also discovered that a novel CaMKII-phosphorylated site, S2137, underwent dephosphorylation by calcineurin. In CAD cells, a mouse central nervous system cell line, membrane depolarization led to an increase in the phosphorylation of endogenous Cav3.2 at S2137. Mutation of S2137 affected the calcium channel function of Cav3.2. Our findings advance the understanding of Cav3.2 regulation not only through kinase phosphorylation but also via calcineurin phosphatase dephosphorylation.

Objective: To compare the overall survival (OS) and surgical outcomes between open and minimally invasive surgery (MIS) in a large cohort of women with Type II endometrial cancer. Methods: Using the National Cancer Database, we identified a cohort of women who underwent hysterectomy for type II endometrial cancer (serous, clear cell, carcinosarcoma) between January 2010 and December 2014. Primary outcome was the comparison of OS between MIS and the open approach. Secondary outcomes included the length of hospital stay, readmission rate, 30- and 90-day mortality. Multivariable logistic regression and inverse propensity weighting analyses were performed. Results: A total of 12,905 patients with Type II, Stage I-III endometrial cancer who underwent hysterectomy were identified. Among these patients, 7,123 (55.2%) underwent MIS. The utilization of MIS increased from 39% to 64% over the four-year period. In propensity-score-weighted analysis, MIS was associated with superior OS (101.7 vs. 86.7 months, p=0.0003 by the log-rank test), with a hazard ratio of 0.9 (CI 0.857-0.954, p=0.0002). MIS was also associated with improved perioperative outcomes, including a shorter length of stay (1 vs. 4 days, p<0.001), lower 30-day readmission rate (2.5% vs. 5%), and lower 30- and 90-day postoperative mortality (0.5% vs. 1.3% and 1.5% vs. 3.6%, respectively; p<0.001). The time interval between surgery and initiation of chemotherapy was shorter in the MIS group (38 vs. 41 days, p<0.001).The increase in MIS adoption correlated with a decrease in 90-day postoperative mortality (2.8% to 2.2%, r=-0.89; p=0.003) and 12-month overall mortality (51% to 38%, r=-0.95, p=0.006). Conclusions: In an epidemiologic study, MIS is associated with improved overall survival and superior perioperative outcomes compared to open surgery in women with Type II endometrial cancer.

Type 1 diabetes is a chronic condition that results from the destruction of insulin-producing β-cells in the pancreas. Current treatments for type 1 diabetes, such as insulin therapy and pancreatic islet transplantation, have several limitations and, hence not quite effective in the long run. As current therapy methods fail to slow disease development, novel strategies such as the development of a bioartificial pancreas are being seriously considered. Over the last decade, research has focused on tissue engineering, which aids in the design of biological alternatives for the repair and replacement of non-functional or damaged organs. Three dimensional (3D) bioprinting technology which employs 3D printing technology to generate 3D tissue-like structures from biomaterials and cells, offers a promising solution for the treatment of type 1 diabetes by providing the ability to generate functional endocrine pancreatic tissue. Bioprinted structures are therefore an important aspect of tissue engineering because they have been found to replicate the native extracellular matrix, promoting cell survival and proliferation. In this review, we extensively discussed about bioprinting endocrine pancreas for the treatment of type 1 diabetes particularly focussing on the choice of cells, biomaterials, growth factors, and essential considerations. Additionally, the key challenges and perspectives towards recapitulation of the pancreatic function of the pancreatic organ engineering technologies have also been discussed.

The heavy-metal-associated (HMA) proteins are a class of PB1-Type ATPases related to the intracellular transport and detoxification of metals. However, due to a lack of information regarding the HMA gene family in the Cucurbitaceae family, a comprehensive genome-wide analysis of the HMA family was performed in ten Cucurbitaceae species: Citrullus amarus, Citrullus colocynthis, Citrullus lanatus, Citrullus mucosospermus, Cucumis melo, Cucumis sativus, Cucurbita maxima, Cucurbita moschata, Cucurbita pepo, and Legenaria siceraria. We identified 103 Cucurbit HMA proteins with various members, ranging from 8 (Legenaria siceraria) to 14 (Cucurbita pepo) across species. The phylogenetic and structural analysis confirmed that the Cucurbitaceae HMA protein family could be further classified into two major clades: Zn/Co/Cd/Pb and Cu/Ag. GO annotation-based subcellular localization analysis predicted that all HMA gene family members were localized on membranes. Moreover, the analysis of conserved motifs and gene structure (intron/exon) revealed the functional divergence between clades. Interspecies microsynteny analysis demonstrated that maximum orthologous genes were found between species of the Citrullus genera. Finally, nine candidates HMA genes were selected, and their expression analysis was carried out via qRT-PCR in root, leaf, flower, and fruit tissues of C. pepo under arsenic stress. The expression pattern of the CpeHMA genes showed a distinct pattern of expression in root and shoot tissues, with a remarkable expression of CpeHMA6 and CpeHMA3 genes from the Cu/Ag clade. Overall, this study provides insights into the functional analysis of the HMA gene family in Cucurbitaceae species and lays down the basic knowledge to explore the role and mechanism of the HMA gene family to cope with arsenic stress conditions.

Type 1 diabetes (T1D) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100 000 persons below 15 years of age. We report the rare case of a 20-year-old female patient with T1D, hemoglobin D (HbD) heterozygote variant and high myopia of -10,00 spheric diopters and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented severe stature deficit (less than 3 standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control, indicated a possible hypopituitarism. The HbA1c level evaluated with high performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to the HbD hemoglobinopathy. On ophthalmic evaluation the angio-OCT scan showed the following retinal microvascular alterations for the RE: the FAZ area vas 0.39 mm2, the FAZ perimeter was 2.88 mm and the circularity index was 0.58; for the LE: the FAZ area vas 0.34 mm2, the FAZ perimeter was 3.21 mm and the circularity index was 0.41. Clinicians should consider high performance retinal screening methods such angio-OCT evaluation for young T1D patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of the HbA1c values are mandatory as hemoglobinopathies can interfere with HbA1c assay methods accuracy.

In this paper, we investigate some elementary properties of two kinds modified Szasz type basis functions, depending on non-negative parameters. We study some shape preserving properties of these operators concerning monotonicity, convexity, starlikeness, semi-additivity and smoothness.

The development of good conductivity p-type β-Ga2O3 is critical to realize its devices and applications. The nitrogen-doped p-type β-Ga2O3 films with enhanced conductivity characteristics were prepared through the thermal oxidation of GaN in the N2O atmosphere. Further measurements were performed on the oxidized films at 1000, 1050, and 1100 °C to have insight into the underlying mechanism of the thermally activated transformation process. The room temperature photoluminescence (PL) spectra demonstrated a moderate ultraviolet emission peak at 246 nm, confirming the generation of gallium oxide with a band gap of ~5.0 eV. The normalized X-ray diffraction (XRD), the high-resolution transmission electron microscopy (HRTEM), and the selected area electron diffraction (SAED) patterns were used to confirm the characteristic of polycrystalline and anisotropic growth. Then, the effects of the oxidation temperature on the amount of incorporated nitrogen were analyzed using secondary ion mass spectrometry (SIMS). Moreover, the ionization energy of the acceptor of films oxidized at 1000, 1050, and 1100 °C was calculated and analyzed using the temperature-dependent Hall test results. The results showed that nitrogen doping was the main contributor to p-type electrical properties. The activation energy of the polycrystalline β-Ga2O3 prepared through thermal oxidation of GaN in the N2O atmosphere was estimated to be 147.175 kJ·mol-1 using the Arrhenius plot, which was considerably lower than that of both dry and wet oxidations of GaN in O2 ambient, thus confirming the efficiency of thermal oxidation of GaN in N2O.

The creation of crop-type maps from satellite data has proven challenging, often impeded by a lack of accurate in-situ data. This paper aims to demonstrate a method for crop-type (ie. Maize, Wheat and Other) recognition based on Convolutional Neural Networks using a bottom-up approach. We trained the model with a highly accurate dataset of crowdsourced labelled street-level imagery. Classification results achieved an AUC of 0.87 for wheat, 0.85 for maize and 0.73 for other. Given that wheat and maize are the two most common food crops globally, combined with an ever-increasing amount of available street-level imagery, this approach could help address the need for improved crop-type monitoring globally. Challenges remain in addressing the noisy aspect of street-level imagery (ie. buildings, hedgerows, automobiles, etc.), where a variety of different objects tend to restrict the view and confound the algorithms

The odontogenic cysts can lead to a bone destruction that can hamper the dental implant place-ment in the ideal 3D position. Different biomaterials and techniques that allow bone regeneration are described in the literature, each with its advantages and disadvantages. This clinical case with 18 months of follow-up shows the enucleation of an odontogenic cyst fol-lowing the guide bone regeneration with fence technique. After 6 months 2, dental implants were placed at the region of tooth 11 and 21, being rehabilitated nine weeks after. The fence technique allowed the recovery of the bone morphology and the placement of the dental implants in the 3D ideal position.

In the last two decades, our knowledge of synaptic proteomes and their relationship to normal brain function and neuropsychiatric disorders has been expanding rapidly through the use of more powerful neuroproteomic approaches. However, mass spectrometry (MS) based neuroproteomic studies of synapses still need cell-type, spatial, and temporal proteome information. With the advancement of sample preparation and MS techniques, we have just begun to identify and understand proteomes within a given cell type, subcellular compartment, and cell-type-specific synapse. Here, we review the progress and limitations of MS-based neuroproteomics of synapses in the mammalian CNS and highlight the recent applications of these approaches in studying neuropsychiatric disorders such as major depressive disorder and substance use disorders. Combining neuroproteomic findings with other omics studies can generate an in-depth, comprehensive map of synaptic proteomes and possibly identify new therapeutic targets and biomarkers of several central nervous system disorders.

The rising global population amidst the growing concerns of climate change will have a dire consequence on global food security and socio-economic activities. Wheat is one of the most important staple foods consumed by more than four billion people in the world, but climate change impacts account for a decline of 5.5% in wheat yield and predictions indicate that the production could further dwindle by nearly 30% in 2050, due to trends in temperature, precipitation, and carbon dioxide. An effective annual crop estimate is necessary not only to inform government the status of national food security, but also is used to determine the benchmark on which agricultural commodities are priced in the market. Thus, annual crop monitoring and yield estimate is paramount to determine the amount of wheat imports required to make up for the shortfalls in the national wheat production in South Africa, which has been a net importer of wheat since 1998. A joint project between South Africa and Poland investigated satellite based-crop growth monitoring using Sentinel 2 and determined the most distinguishable crop phenology for an accurate winter wheat classification during the growing season from August – December with Random Forest (RF) algorithm. The winter wheat crop was more accurately identified during the crop ‘heading’ stage in October yielding the highest user’s (75.56%) and producer’s (92.52%) accuracies, despite the relatively lower overall accuracy (78.14%) compared to that of December with OA of 83.58% obtained during the maturity stage. This study, therefore, confirms the suitability of sentinel 2 for an effective phenology-based winter wheat crop classification during the heading stage, reducing the ambiguity of spectral confusion created with surrounding grass and maize crops.

This paper presents a novel DQ-based multicarrier Pulse Width Modulation PWM for a single-phase, three-level PV-powered grid-connected F-type inverter. The main control objective in the proposed inverter is to regulate the grid current with low total harmonic distortion and load power components compensation. Despite the F-type inverter’s advanced advantages, there are only a few works addressing the control issue in the literature yet. The proposed control and switching methods aim to achieve both DC side voltage balance and lowest switching losses. The proposed scheme has been designed based on a modified multi-carrier PWM switching algorithm. Consequently, the proposed control method able to satisfy the requirements of DC side voltage balance and achieve lower switching losses. A further advantage of the proposed control and switching methods is that they retain the main advantage of the F-Type inverter, which is that only 25% of the power switches are exposed to full DC voltage. This is an important advantage since it reduces the overall cost of the inverter and improves its reliability. Overall, the proposed modified multi-carrier PWM switching algorithm appears to be a promising approach for controlling the F-Type inverter, offering improved performance and efficiency compared to other control methods. The theoretical model was verified through simulation using MATLAB/Simulink. According to the simulation results, the grid current and dc capacitor voltages are successfully managed in all operational situations.

Legionella is an opportunistic pathogen with a biphasic life cycle and humans are occasional hosts of Legionella. The aim of the study was to assess the distribution of virulence genes and genetic diversity among L. pneumophila isolated from water-supply systems of residential buildings in Latvia. In total, 492 water samples from 200 residential buildings were collected. Identification of Legionella spp. was performed according to ISO 11731 and 58 isolates were subjected to whole genome sequencing. At least one Legionella positive sample was found in 112 out of 200 apartment buildings (56.0%). The study revealed extensive sequence type diversity where 58 L. pneumophila isolates fell into 36 different sequence types. A total of 420 virulence genes were identified of which 260 genes were found in all sequenced L. pneumophila isolates. Virulence genes enhC, htpB, omp28, and mip were detected in all isolates, suggesting that adhesion, at-tachment, and entry into host cells are enabled for all isolates. The relative frequency of viru-lence genes among L. pneumophila isolates was high. High prevalence, extensive genetic diver-sity, and the wide range of virulence genes indicated that the virulence potential of environ-mental Legionella is high and proper risk management is of key importance to public health.

How language mediates emotional perception and experience is poorly understood. The present event-related potential (ERP) study examined the explicit and implicit processing of emotional speech to differentiate the relative influences of communication channel, emotion category and task type in the prosodic salience effect. Thirty participants (15 women) were presented with spoken words denoting happiness, sadness and neutrality in either the prosodic or semantic channel. They were asked to judge the emotional content (explicit task) and speakers’ gender (implicit task) of the stimuli. Results indicated that emotional prosody (relative to semantics) triggered larger N100 and P200 amplitudes with greater delta, theta and alpha inter-trial phase coherence (ITPC) values in the corresponding early time windows, and continued to produce larger LPC amplitudes and faster responses during late stages of higher-order cognitive processing. The relative salience of prosodic and semantics was modulated by emotion and task, though such modulatory effects varied across different processing stages. The prosodic salience effect was reduced for sadness processing and in the implicit task during early auditory processing and decision-making but reduced for happiness processing in the explicit task during conscious emotion processing. Additionally, across-trial synchronization of delta, theta and alpha bands predicted the ERP components with higher ITPC values significantly associated with stronger N100, P200 and LPC enhancement. These findings reveal the neurocognitive dynamics of emotional speech processing with prosodic salience tied to stage-dependent emotion- and task-specific effects, which can reveal insights to research reconciling language and emotion processing from cross-linguistic/cultural and clinical perspectives.

Objective: Type I interferon receptor (IFNAR) signaling contributes to several autoimmune and vascular diseases such as atherosclerosis and stroke. The purpose of this study was to assess the influence of IFNAR1 deficiency on the formation and progression of experimental abdominal aortic aneurysms (AAAs). Methods: AAAs were induced in type I interferon receptor subunit 1 (IFNAR1) deficient and wild type control male mice via intra-infrarenal aortic infusion of porcine pancreatic elastase. Immunostaining for IFNAR1 was evaluated in experimental and clinical aneurysms. The initiation and progression of experimental AAAs was assessed via ultrasound imaging prior to (day 0) and 3-, 7-, and 14-days following elastase infusion. Aneurysmal histopathology was analyzed at sacrifice. Results: Increased aortic medial and adventitial IFNAR1 expression was present in both clinical AAAs harvested at surgery and experimental AAAs. Following AAA initiation, wild type mice experienced progressive, time-dependent infrarenal aortic enlargement. This progression was substantially attenuated in IFNAR1 deficient mice. On histological analyses, medial elastin degradation, smooth muscle cell depletion, leukocyte accumulation and neoangiogenesis were markedly diminished in IFNAR1 deficient as compared to wild type mice. Conclusion: IFNAR1 deficiency limited experimental AAA progression in response to intra-aortic elastase infusion. Combined with clinical observations, these results suggest a regulatory role for IFNAR1 activity in AAA pathogenesis.

Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Here, we review the role of exosomes in allergic sensitization and inflammation and we discuss the mechanisms by which exosomes could be used in immunotherapeutic approaches for the treatment of allergic diseases. We propose the following approaches: a) Mast cell derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. c) Exosomes could promote TH1-like responses towards an allergen. d) Exosomes could modulate IgE-facilitated antigen presentation.

The transition of people from paediatric to adult diabetes services is associated with worsening glycaemia and increased diabetes-related hospitalisation. This study compared the clinical characteristics of those with and without mental health conditions among attenders at a diabetes young adult clinic diabetes before and after changes in service delivery. Retrospective review of 200 people with diabetes attending a Sydney public hospital over eight years corresponding to the period before (2012-2016) and after (2017-2018) restructuring of a clinic for young adults aged 16-25 years. Characteristics of those with and without mental health conditions (depression, anxiety, diabetes related distress, eating disorders), were compared. Among clinic attenders (type 1 diabetes n=184, 83.2%), 40.5% (n=89) had a mental health condition particularly, depression (n=57, 64%), which was higher among Indigenous than non-Indigenous people (5.6% vs 0.8% p=0.031) but similar between diabetes type. Over eight years, those with, compared with those without a mental health condition had higher HbA1c at the last visit (9.4%[79 mmol/mol] vs 8.7% [71 mmol/mol], p=0.027), the proportion with diabetic ketoacidosis (DKA 60.7% vs 42.7%,p=0.009), smoking (38.4 vs 13.6%,p=0.009), retinopathy (9.0 vs 2.3%,p=0.025), multiple DKAs (28.4 vs 16.0%,p=0.031) were significantly higher. Having a mental health condition was associated with 2.02 (95% Confidence intervals 1.1-3.7) fold increased risk of HbA1c ≥ 9.0%[75mmol/mol]. Changes to the clinic were not associated with improvements in mental health condition (39.0% vs 32.4%, p=0.096). In conclusion, we found that mental health conditions, particularly depression, are common in this population and are associated with diabetes complications. Diabetes type and clinic changes did not affect the reported mental health conditions. Additional strategies are required to reduce complication risks among those with mental health conditions. .

The structural, elastic, anisotropic elastic, electronic, vibrational and properties of the Perovskite type Hydrides RbXH3 (X = Be, Ca, Mg) were performed via Vienna Ab – initio Simulation Pac-kage (VASP) based on Density Functional Theory (DFT). Our results have exhibited a well-agreement with previous calculations and experiments for each compound. In order to de-termine physical properties of RbXH3 has been used the Generalized Gradient Approximation (GGA) with Perdew-Burke-Ernzerhof (PBE) functional at this study. Present compounds were found to be mechanically stable as well as their gravimetric hydrogen storage capacities has been investigated. The Perovskite type Hydrides RbBeH3 and RbMgH3 has an indirect bandgap of 0.274 eV and 2.209 eV while RbCaH3 has a direct bandgap of 3.274 eV respectively and therefo-re these compounds has shown a semiconductor behaviour at equilibrium. Besides directional dependence of anisotropic properties was visualized by representing them with maximum - mi-nimum points..

Leptospirosis is a globally distributed zoonotic disease caused by pathogenic bacteria of the genus Leptospira. This zoonotic disease affects humans, domestic, or wild animals. Colombia is considered an endemic country for leptospirosis; and Antioquia is the second department in Colombia with the highest number of reported leptospirosis cases. Currently, many studies report bats as reservoirs of Leptospira spp. but its prevalence in these mammals is unknown. In the present study we aimed to better understand the role of bats as reservoir hosts of Leptospira species and to evaluate the genetic diversity of circulating Leptospira species in Antioquia-Colombia. We captured 206 bats in the municipalities of Chigorodó (43 bats), Carepa (43 bats), Apartadó (39 bats), Turbo (40 bats), and Necoclí (41 bats) in the Urabá region (Antioquia-Colombia). Twenty bats were positive for Leptospira spp. infection (20/206 - 9,70%) and the species of infected bats were Carollia perspicillata, Dermatura rava, Glossophaga soricina, Molossus molossus, Artibeus planirostris, and Uroderma convexum. These species have different feeding strategies such as frugivorous, insectivores, and nectarivores. The infecting Leptospira species identified were Leptospira borgpetersenii (3/20 – 15%), Leptospira alexanderi (2/20 – 10%), Leptospira noguchii (6/20 – 30%), Leptospira interrogans (3/2 – 15%), and Leptospira kirschneri (6/20 – 30%). The results of this research show the importance of bats in the epidemiology, ecology and evolution of Leptospira in this host-pathogen association. This is the first step in deciphering the role played by bats in the epidemiology of human leptospirosis in the endemic region of Uraba (Antioquia-Colombia).

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. MicroRNA-375 (miR-375) ranks among top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 hour before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to identification of 8 microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients, by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

Shear deformation of a solid-fluid, two-phase material induces a fluid segregation process that produces fluid-enriched bands and fluid-depleted regions, and crystallographic preferred orientation (CPO) characterized by girdles of [100] and [001] axes sub-parallel to the shear plane and a cluster of [010] axes sub-normal to the shear plane, namely the AG-type fabric. Based on experiments of two-phase aggregates of olivine + basalt, a two-phase flow theory and a CPO-formation model were established to explain these microstructures. Here, we investigate the microstructure in a two-phase aggregate with supercritical CO2 as the fluid phase and examine the theory and model, as CO2 is different from basaltic melt in rheological properties. We conducted high‐temperature and high-pressure shear deformed experiments at 1 GPa and 1100ºC in a Griggs-type apparatus on samples made of olivine + dolomite, which decomposed into carbonate melt and CO2 at experimental conditions. After deformation, CO2 segregation and an AG-type fabric occurred in these CO2-bearing samples, inconsistency with basaltic melt-bearing samples. The SPO-induce CPO model was used to explain the formation of the fabric. Our results suggest that the influences of CO2 as a fluid phase on the microstructure of a two-phase olivine aggregate is similar to that of basaltic melt and can be explained by the CPO-formation model for the solid-fluid system.

The need for antiserum for immunohistochemical (IHC) detection of enterovirus (EV) in formaldehyde fixed and paraffin-embedded (FFPE) specimens is increasing. The standard monoclonal antibody against EV-envelope protein (VP1), clone 5D8/1, was proven to cross-react with other proteins. Another candidate marker of EV proteins is 2A protease (2Apro), which is coded by the EV gene and translated by host cells during EV replication. We raised polyclonal antiserum by immunizing rabbits with an 18-mer peptide of Coxsackievirus B1 (CVB1)-2A protease (2Apro) and examined the specificity and sensitivity for EV on FFPE tissue samples. ELISA study showed a high titer of antibody for CVB1-2Apro. IHC demonstrated that antiserum against 2Apro reacted with CVB1-infected Vero-cells. Confocal microscopy demonstrated that 2Apro labelled by the antibody located in the same cell with VP1 stained with 5D8/1. IHC demonstrated dense positive reactions pancreatic islets of EV-associated fulminant type 1 diabetes (FT1DM), and located in the same cell stained positive with 5D8/1. Specificity of IHC staining FT1DM pancreas was confirmed by absorption with an excessive concentration of immunized peptide. In conclusion, our study provides a new polyclonal antiserum against CVB1 2Apro which may be useful for detection of EV-infected human tissues stored as archive of FFPE tissue samples.

The type 6 protein secretion system (T6SS) is prevalently utilized by Gram-negative bacteria to compete for resources and space. Upon activation, toxic effectors from this secretion system are translocated into the competitor prokaryote or eukaryote in a contact-dependent manner. While much has been reported on T6SS-mediated prokaryotic competition, very little is understood about the mechanisms of bacterial interactions with eukaryotic hosts. Likewise, many virulent T6SS effectors are known to be antibacterial. In recent years, however, evidence has emerged on numerous T6SS effectors that interact with related immunity proteins in a range of eukaryotic hosts. Insights into how this effector-immunity pairing alters the physiological responses of the recipient organism might provide opportunities relating to the T6SS agricultural and biotherapeutic applications. We, therefore, summarize the impacts of the T6SS effectors with a special focus on bacterial interactions with animals, plants, and fungi. We further briefly discuss pipelines that are currently used to characterize antieukaryotic T6SS effectors.

The bay is a space barrier for the development of island-type cities and a high-quality waterfront landscape resource. This study takes Xiamen a typical island city in China as an example. First, It use the method of satellite telemetry technology combined with GIS software and spatial syntax, respectively, from the material space level and social space level, to summarize the rapid urbanization process of this city since 1990-2018, focusing on the construction process of three large-scale waterfront park systems in the transition period of inter-island development in it, and comparing the similarities and differences of their spatial forms. Further, from the choice of the axis model and the integrated analysis results, we discuss the spatial efficiency changes. The construction of the three major bay waterfront park systems in this city reflects a huge change in development pattern from lagging construction, synchronous planning, to advanced layout, providing a continuous and variable spatial form for the development of the bay region and improving space efficiency, which one of the important ways to develop and transform island-type cities. We hope to provide the reference for the development including sustainable development of other island cities around the world

We enriched and isolated a novel gammproteobacterial methanotroph; strain FWC3, from tropical freshwater wetland, near Nagaon beach, Alibag, India. FWC3 is a coccoid, flesh pink/peach pigmented, non-motile methanotroph and the cells are present in pairs and as tetracocci. The culture can grow on methane (20%) as well as on a wide range of methanol from concentrations (0.02%-5%). Based on the comparison of genome data, FAME analysis, morphological characters and biochemical characters, FWC3 belongs to the tentatively and newly but not validly described genus ‘Methylotetracoccus’ of which only a single species strain was described, Methylotetracoccus oryzae C50C1. The ANI index between FWC3 and C50C1 strains is 94%, and the DDH value is 55.7%, less than the cut-off values 96% and 70%, respectively. The genome size of FWC3 is smaller (3.4 Mbp) compared to that of C50C1 (4.8 Mbp). Additionally, the FAME profile of FWC3 shows differences in cell wall fatty acid profiles compared to Methylotetracoccus oryzae C50C1. Also, there are other differences on the morphological, physiological and genomic levels. We propose FWC3 to be a member of a novel species of the genus Methylotetracoccus, for which the name Methylotetracoccus aquaticus is proposed. Also, an amended description of the genus Methylotetracoccus gen. nov. is given here. FWC3 is available in two international culture collections with the accession numbers: MCC 4198 (Microbial Culture collection, India) and JCM 33786 (Japan Collection of Microorganisms, Japan).

The objective of this study was to identify circulating miRNAs affected by disease duration in newly diagnosed children with type 1 diabetes. Forty children and adolescents from The Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12 and 60 months after diagnosis. Pancreatic autoantibodies were measured at each visit. Cytokines were measured only the first year. miRNA expression profiling was performed by RT-qPCR and quantified for 179 human plasma miRNAs. The effect of disease duration was analyzed by mixed models for repeated measurements, adjusted for sex and age. Eight miRNAs (hsa-miR-10b-5p, hsa-miR-17-5p, hsa-miR-30e-5p, hsa-miR-93-5p, hsa-miR-99a-5p, hsa-miR-125b-5p, hsa-miR-423-3p and hsa-miR-497-5p) were found to significantly change expression (adjusted p-value < 0.05) with disease progression. Three pancreatic autoantibodies ICA, IA-2A, GADA65 and 4 cytokines IL-4, IL-10, IL-21, IL-22 were associated with the miRNAs at different time points. Pathway analysis revealed association with various immune-mediated signaling pathways. Eight miRNAs, involved in immunological pathways changed expression levels during the first five years after diagnosis in children with type 1 diabetes, and were associated with variations in cytokine and pancreatic antibodies, suggesting a possible effect on the immunological processes in the early phase of the disease.

The wind industry is looking for ways to accurately predict the reliability and availability of newly installed wind turbines. Failure modes, effects and criticality analysis (FMECA) is a technique utilized for determining the critical subsystems of wind turbines. There are several studies which applied FMECA for wind turbines in the literature, but no studies so far have considered different weather conditions or climatic regions. Furthermore, various design types of wind turbines have been analyzed applying FMECA but no study so far has applied FMECA to compare the reliability of geared and direct-drive wind turbines. We propose to fill these gaps by using Koppen-Geiger climatic regions and two different turbine models of direct-drive and geared-drive concepts. A case study is applied on German wind farms utilizing the WMEP database which contains wind turbine failure data from 1989 to 2008. This proposed methodology increases the accuracy of reliability and availability predictions and compares different wind turbine design types and eliminates underestimation of impacts of different weather conditions.

Lectins are carbohydrate-interacting proteins playing a pivotal role in multiple physiological and developmental aspects of all organisms. They can specifically interact with different bacterial and viral pathogens through the carbohydrate-recognition domains (CRD). In addition, lectins are also of biotechnological interest because of their potential use as biosensor for capturing and identification of bacterial species. In this work, we have characterized the bacterial agglutination properties of three C-type lectins from the Lepidoptera Spodoptera exigua. One of these lectins, BLL2, was able to agglutinate cells from a broad range of bacterial species at an extremely low concentration, becoming a very interesting protein to be used as biosensor or other biotechnological applications involving bacterial capturing.

The study aimed to explore the correlation among Angiopoietin-1, (Ang-1) and Angiopoietin-2, (Ang-2) concentrations and the Angiopoietin-2/Angiopoietin-1 ratio, (Ang-2/Ang-1) with clinical outcomes, potentially serving as disease severity and survival biomarkers. A study at AHEPA University Hospital involved 90 COVID-19 adult patients, with 30 hospitalized in intensive care and 30 in ward units and 30 asymptomatic non-hospitalized individuals as controls. Estimated endothelial dysfunction markers related to angiogenesis were measured, and statistical analysis was performed using IBM SPSS Statistics software, version 29. There was a statistically significant difference only between outpatient and hospitalized patients (non-ICU -ICU groups) for the Ang-1 and Ang-2 indexes. The Ang-2/Ang-1 ratio has differed significantly among all individual patient groups. A ROC analysis was conducted to find an optimal threshold for distinguishing (outpatients – non-ICU) and (non-ICU –ICU) groups. It was based on Youden's Index and was 0.1122 and 0.3825, respectively. The Ang-1, Ang-2 levels, and Ang-2/Ang-1 ratio were analysed as indicators for severity in COVID-19 patients. The Ang-2/Ang-1 ratio demonstrated more excellent prognostic and diagnostic utility than individual biomarker levels. Monitoring the Ang-2/Ang-1 ratio can identify COVID-19 patients at risk and assist clinicians in tailoring treatment strategies for improved outcomes.

The thionamide antithyroid drugs were discovered largely following serendipitous observations by numerous researchers in the 1940s who found that sulfhydryl-containing compounds were goitrogenic in animals. Prof. Edwin B. Astwood was the first to use these compounds to treat hyperthyroidism. In this review, we summarize the history of the development of these drugs and the coordination possibility of 2-thiouracil and its derivatives, as well as the biological activities of some of its complexes. Some of them are used as agents for the treatment of tuberculosis, and arthritis, others have bactericidal and fungicidal activity, the third cytotoxic properties, and could be used to treat various types of cancer.

This study investigated the factors affecting consumers’ acceptance to use cashless payment services in Malaysia through the construction of the Cashless Society Acceptance (CSA) model. The Technology Readiness Index 2.0 and Unified Theory of Acceptance and Use of Technology 2 were employed to create the CSA model. A total of 434 questionnaires were collected from Malaysian consumers, aged 18 years and above. The results show that Perceived Usefulness, Perceived Ease of Use, and Discomfort have the most significant influence on the consumers’ acceptance of cashless payment services with R-square of 71.4%.

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high infectivity in humans, attributed to the strong affinity of its spike (S) protein to human angiotensin-converting enzyme 2 (ACE2). Here, we analyzed the structural similarity of the S protein between SARS-CoV-2 and other SARS-related coronaviruses (CoVs). Methods We performed multiple alignment analysis of nine amino acid sequences of CoV S proteins from NCBI with MAFFT web-based software, followed by phylogeny analysis. Three-dimensional structure modeling was performed by SWISS-MODEL. We calculated the template modeling score between the S protein of SARS-CoV-2 and that of other SARS-related CoVs. Results The S1 domain of the unclassified CoV RaTG13 (the host of which is the intermediate horseshoe bat) was structurally very similar to that of SARS-CoV-2, implying that RaTG13 could be the origin of SARS-CoV-2. In addition, the folding property of the entire S protein was nearly the same between SARS-CoV-2 and RaTG13 after the PRRA amino acid insertion was removed from SARS-CoV-2. Conclusions RaTG13 could have a high binding affinity to ACE2, similar to SARS-CoV-2, and it is therefore highly likely to infect other animals. Therefore, massive research and monitoring of CoVs in animals is necessary to prevent future COVID-19-like disasters.

This paper is devoted to the study of reproducing kernels on 2-inner product Hilbert spaces. We focus on a new structure to produce reproducing kernel Hilbert and Banach spaces. According to multi-variable computing, this structures can be useful in electrocardiographs, machine learning and economy

In this paper, a short survey of the existed results concerning the Jacobian Conjecture is first given. Then the 3-fold linear type polynomial map will be analyzed in detail. The expansion of the Jacobian condition is deduced to obtain its equivalent algebraic equations, and the Jacobian condition will be analyzed to derive two coordinate transformations that can maintain the invariance of the Jacobian condition. Finally, it is proved by mathematical induction method that one general chain expression presented in this paper is just the inverse polynomial map of 3-fold linear type polynomial map, i.e. LJC(n,[3]) holds such that the Jacobian Conjecture holds.

In the present paper, the (p,q)-Hermite based Apostol type Frobenius-Euler polynomials and numbers are firstly considered and then diverse basic identities and properties for the mentioned polynomials and numbers, including addition theorems, difference equations, integral representations, derivative properties, recurrence relations. Moreover, we provide summation formulas and relations associated with the Stirling numbers of the second kind.

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-i in T1D HF management, alongside the emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk, through a comprehensive analysis of clinical trials, observational studies, and reviews. The evidence suggests SGLT2-i significantly reduce HF hospitalization and enhance cardiovascular outcomes. However, their application in T1D patients remains limited due to DKA concerns. CKM technology emerges as a crucial tool in this context, offering real-time monitoring of ketone levels, which enables the safe incorporation of SGLT2-i into treatment regimes by allowing for early detection and intervention in the development of ketosis. The synergy between SGLT2-i and CKM has the potential to revolutionize HF treatment in T1D, promising improved patient safety, quality of life, and reduced HF-related morbidity and mortality. Future research should aim at clinical trials directly assessing this integrated approach, potentially guiding new management protocols for HF in T1D.

Pulmonary hypertension (PH) has a high mortality, and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type 2 and type 17 responses in C57BL/6 mice. Here, we focused on type 2 response related cytokines, specifically Resistin-like-molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild type or RELMα-/- mice. Vascular remodeling was assessed by histology, right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM2.5, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were more prominent in the C57BL/6 strain. Compared to wild type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV ST2-IL-33-receptor were significantly increased in BALB/c wild type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild type or C57BL/6-RELMα-/- mice. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- were not different from their respective wild type controls. In BALB/c mice, RELMα was a key contributor to antigen/PM2.5 induced pulmonary vascular remodeling, RV thickening and RV cytokine responses, highlighting the significance of the genetic background. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELM which makes these mice comparable to a situation where human RELMα levels would be significantly modified, as humans only have one RELM molecule.

The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n=125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, ten influenza A, ten Influenza B and twenty respiratory syncytial virus specimens. Results were com-pared to in-country standard of care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive per-centage agreement (PPA)=95.2%, negative percentage agreement (NPA)=95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA=100%, NPA=98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard of care tests.

Objectives: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. Methods: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Results: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogenously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HP and PPI-L were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Conclusion: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

This paper introduces an intelligent model that combines military expertise with the latest ad-vancements in machine learning (ML) and Geographic Information Systems (GIS) to support humanitarian demining decision-making processes. The model is based on direct input and val-idation from field decision-makers for their practical applicability and effectiveness. With a survey polling the inputs of demining experts, 95% of the responses came with an affirmation of the potential of the model to reduce threats and increase operational efficiency. It includes mili-tary-specific factors that factor in the proximity to strategic locations as well as environmental variables like vegetation cover and terrain resolution. With Gradient Boosting algorithms such as XGBoost and LightGBM, the accuracy rate is almost 97%. Such precision levels further enhance threat assessment, better allocation of resources, and around a 30% reduction in the cost and time of conducting demining operations, signifying a strong synergy of human expertise with algo-rithmic precision for maximal safety and effectiveness in demining

The innovativeness of nongovernmental organisations, the basic institutions of civil society, is conditioned, among other things, by the endogenous potential of agency of the entities operating within them. The article attempts to answer two research questions regarding the above-mentioned issues: (1) how individual components of binding and bridging social capital (in the area of trust, norms and connections) determine innovative activity in a state of morphostasis, i.e. structural and cultural continuity, selected Silesian NGOs. (2) What type of reflexivity and the related nature of agency of the members of the NGOs surveyed dominates when undertaking innovative activities? At the theoretical level, the study was based on the concept of three components of social capital by James S. Coleman and the assumptions of Margaret Archer's morphogenetic theory of structure and agency, in particular, the types of reflexivity as a factor conditioning social agency. Based on them and using qualitative analysis of data obtained during focus group interviews (FGI) and SWOT questionnaires of surveyed organisations, a diagnosis of intraorganisational barriers to innovation was made. The Atlas.ti computer programme was used. This method allows for the examination of structural elements, cultural features of a given organisation, and the capabilities of individual entities. The dominance of bonding social capital components over bridging social capital components was noted (mainly in the dimension of trust), as the basic bond connecting members of the NGOs studied. It was accompanied by a communicative type of reflexivity of the respondents, with the aim of maintaining the existing organisational and social status quo. These key socio-cultural factors determine the morphostatic nature of the organisations studied, i.e., their focus on maintaining the organisational status quo. Such contexts petrify the existing power structure, but also the level of social tensions and distances, and limit the innovation potential.

In Ethiopia, farmers have changed cropland to Eucalyptus globulus plantations for construction, fuelwood and economic benefits. However, it has adverse effects on soil properties. The investigation was, therefore, to evaluate the impact of Eucalyptus globulus plantations on soil properties in northwestern Ethiopia. About 30 soil samples were collected from two soil depths (0-20 and 20-40 cm) and three land uses (Eucalyptus globulus plantations, cropland and grazing land) with five replications. Soil properties were analyzed using a two-way analysis of variance (ANOVA). Based on the result, soil properties such as silt particles, moisture content (MC), organic matter (OM), total nitrogen (TN) and cation exchange capacity (CEC) were significantly higher under the soil of Eucalyptus globulus plantations than in cropland and grazing land. Whereas the lower contents of bulk density (BD), soil pH, available phosphorus (AP), electrical conductivity (EC) and exchangeable bases (Ca, Mg, K, and Na) were recorded in Eucalyptus globulus plantations. Besides, clay, BD, MC, pH, EC, CEC, percent base saturation (PBS) and basic cations increased with soil depth while decreasing sand, silt, TP, OM and AP. The basic cations ( Ca, Mg, K), PBS and AP decreased in the soil of the 25-year old Eucalyptus globulus plantation compared to cropland by 38%, 36%, 43 %, 45% and 47% and grazing land by 56%, 60%, 76 %, 60% and 56%, respectively. Therefore, appropriate and effective land use management principles should be implemented in the study area.

Magnetorheological (MR) fluid is recognized as one of intelligent materials that is widely used for various kinds of controllable devices since its rheological characteristics can be controlled by an external magnetic field (or input current). However, the density mismatch of the compositions between iron particles and carrier oil leads to inevitable sedimentation. Therefore, many works on the sedimentation problem of MR fluids have been carried out to improve the sedimentation stability using appropriate additives, surfactants, nanoparticles, particle coating as well as using several carrier oils with different densities. However, a study on the effect of the current magnitudes and profiles on the sedimentation is considerably rare. This study experimentally investigates the sedimentation behaviors due to the different current magnitudes and different profiles such as square and sine wave. It is shown that average sedimentation rate is 98.61% by applying 1 A of the square wave, while it is 97.83% under the sine type of the current. It is also identified that the higher intensity of the applied current results in stronger electromagnetic which can slow down the sedimentation rate. The results presented in this work are very helpful in designing a controller which provides the input current in terms of the magnitude and profile configuration.

A Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by a complex interplay of genetic, molecular, and cellular factors. It is considered a multifactorial disorder influenced by genetic susceptibility, environmental triggers, and dysregulated immune responses. Understanding the molecular and cellular mechanisms driving SLE pathogenesis has been instrumental in developing targeted therapies to manage the disease and improve patient outcomes. In this essay, we will delve into the intricate molecular and cellular processes underlying SLE and examine the key lessons learned from human therapies.

The rising number of unknown-type attacks on the Internet emphasizes the significance of developing efficient intrusion detection systems, even if machine learning-based techniques can detect unknown types of attacks. The necessity for innovative techniques is highlighted by the possibility that traditional machine learning techniques will not be sufficient for identifying these unknown types of attacks. In this research, we address this difficulty by proposing a deep learning-based solution: the log-cosh variational autoencoder (LVAE). When it comes to understanding intricate data distributions and creating freshly reconstructed data, LVAE inherits the strong modeling skills of the variational autoencoder (VAE). To better imitate discrete features of actual attacks and generate unknown types of attacks, this study develops an effective reconstruction loss term employing the logarithmic hyperbolic cosine (log-cosh) function in the log-cosh variational autoencoder (LVAE). When compared to conventional VAEs, LVAE exhibits promising potential for effectively generating data that closely resembles an unknown attack, a crucial capability for increasing the unknown attack detection rate. To categorize the generated unknown-type data, eight feature extraction and classification techniques were used. Using the most recent CICIDS2017 dataset, numerous experiments were carried out, training under varying amounts of real and unknown-type attacks. Our optimal experimental results outperformed several state-of-the-art techniques with accuracy and average F1 scores of 99.89% and 99.83%, respectively. Outstanding results were also shown by the suggested LVAE strategy for producing unknown attack data. In general, our work sets a strong basis for the accurate and efficient identification of unknown types of attacks and contributes to the development of intrusion detection techniques.

The prevalent pathogens associated with bovine uterine infections are bacteria that appear to increase the host's susceptibility to secondary infections with other bacteria or viruses, among which BoHV-4 is the most frequently found. In this work, the study of the pathways of apoptosis induction was carried out on an experimental model of primary culture of endometrial cells, in order to know the implication of BoHV-4 and the presence of bacterial LPS in the pathogenesis of the bovine reproductive tract. For this, different staining techniques and molecular analysis by RT-PCR were used. The results obtained allowed us to conclude that the level of cell death observed in the proposed primary culture is directly related to the time of viral infection and the presence of LPS in BoHV-4 infection. The apoptosis indices in cells infected with BoHV-4, BoHV-4 + LPS presented a maximum that correlates with the appearance of the cytopathic effect, and the maximum viral titers in the model studied. However, morphological, biochemical and molecular changes were evident during both early and late stages of apoptosis. These findings provide information on the factors that may influence the pathogenesis of BoHV-4 and help to better understand the mechanisms involved in virus infection.

This study aimed to identify and differentiate the factors that may affect the incidence of temporomandibular joint (TMJ) dysfunction in children with type 1 diabetes. We analyzed the TMJ symptoms, clinical and laboratory parameters of type 1 diabetes in a cohort of 101 consecutive patients. The participants were evaluated regarding the presence of pain in the masticatory muscles, TMJ sounds, mouth opening, maximum mouth opening, lateral and protrusive excursions, and Fonseca scores. The overall cohort showed a mean Fonseca score of 20 ± 13.89, referred to mild TMJ dysfunction. Of patients, 34.65% presented at least one clinical symptom and were defined as having dysfunction. The most frequently recorded symptom was TMJ sounds, presented in 16.8% of children. In subjects with dysfunction compared to those without dysfunction, a significant difference was found at height standard deviation scores, Fonseca scores and maximum mouth opening (p&lt;0.001). HbA1c levels, diabetes duration, age and gender did not reveal any significant differences between the patients with and without dysfunction. Type 1 diabetes is often associated with limited mouth opening and mild TMJ dysfunction. This dysfunction may reflect a more chronic condition and possibly exceeds the prevalence of cheiroartropathy. This study could be a starting point towards enhancing our understanding of clinically evident TMJ involvement in type 1 diabetes.

DKA represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM) primarily and, occasionally, T2DM in children and adolescents. It is characterized by the biochemical triad of hyperglycaemia, ketonaemia and/or ketonuria, and acidaemia. Clinical symptoms include dehydration, tachypnoea, gastrointestinal symptoms, and reduced level of consciousness, precipitated by a variably long period of polyuria, polydipsia and weight loss. The present review aims to summarize potential pitfalls in the diagnosis and management of DKA. A literature review was conducted using the Pubmed/Medline databases including articles published from 2000 onwards. Diagnostic challenges include differentiating between T1DM and T2DM, DKA and hyperosmolar hyperglycaemic state (HHS), or between DKA and alternative diagnoses presenting with overlapping symptoms, such as pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen and central nervous system infection. The mainstays of DKA management include careful fluid resuscitation, timely intravenous insulin administration and restoration of shifting electrolyte disorders and underlying precipitating factors. However, evidence suggests that optimal treatment remains a therapeutic challenge. Accurate and rapid diagnosis, prompt intervention and meticulous monitoring are of major importance to break the vicious cycle of life-threatening events and prevent severe complications during this potentially fatal medical emergency.

Diabetes becomes a life threatening non-communicable disease in the world, according to International Diabetic Federation (IDF) in 2023, an estimated 537 million adults (20-79 years) are living with diabetes, which is equivalent to 9.3% of the global adult population. This number is predicted to rise to 643 million by 2030 and 783 million by 2045. Over 3 in 4 adults with diabetes live in low- and middle-income countries. Diabetes is a persistent metabolic condition marked by increased levels of glucose in the bloodstream. It is a significant global health concern, affecting millions of individuals worldwide. It having the symptoms of drowsiness for the whole day if not properly examined or treated well. It is targeted to spread over the younger age community and the number is growing in the exponential fashion. Even day to day many advancements have come from the researcher to diagnose, to find solutions to prevent from newer entry. Authors have taken a dataset with 57 non diabetic and 20 diabetic patients with the total 28735 micro array gene to undergone pre-processing process and reduced up to 22960 gene data using Dimensionality Reduction (DR) such as Detrend Fluctuation Analysis (DFA), Chi square probability density function (Chi2PDF), Firefly algorithm Cuckoo search were used in this research. Meta heuristic algorithms like Particle swarm Optimization (PSO) and Harmonic Search (HS) are used for feature selection. Further seven classification techniques such as Non-Linear Regression (NLR), Linear Regression (LR), Logistics Regression (LoR), Gaussian Mixture Model (GMM), Bayesian Linear Discriminant Classifier (BLDC), Softmax Discriminant Classifier (SDC), Support Vector Machine – Radial Basis Function (SVM-RBF) are using to make a decision, predictive analysis and segregate the data according to the level of blood glucose as Diabetic Patient (DP) and Non-Diabetic Patient (NDP).

Soccer is type of sport that carries a high risk of injury. Injury is not only cause in the unlucky soccer carrier and also team performance as well as financial effects can be worse since soccer is a team-based game. The duration of recovery from a soccer injury typically relies on its type and severity. Therefore, we conduct this research in order to predict the probability of players injury type using machine learning technologies in this paper. Furthermore, we compare different machine learning models to find the best fit model. Supervised classification machine learning models are applied in this paper. We gathered information about 54 professional soccer players who are playing in the top five European leagues based on their career history.

Misuse of measurement units and orientations leads to errors in scientific applications, Cyber Physical Systems (CPS), and IoT C/C++ programs. Standard type system are inadequate in preventing such errors. Although dimensional and orientational analysis in physics can manually detect these errors in equations, analyzing complex code with intricate physical computations is impractical. To overcome this challenge, we propose an advanced type system that incorporates units and orientations as integral components within a specialized type library. Our enhanced type system automatically detects potential errors during compile time by representing physical quantities as types and utilizing dimensional analysis, orientational analysis, and metaprogramming techniques. Our improved type system enables formal verification of C++ software, successfully verifying programs with extensive codebases. We also employ it for runtime verification of dynamic linking and pointer operations in C++ programs. The integration of compile-time verification, dimensional analysis, orientational analysis, and advanced type system enhances the robustness and accuracy of scientific applications, CPS, and IoT C/C++ programs. By leveraging these approaches, we ensure precise calculations and prevent errors related to measurement units and orientations, resulting in substantial improvements in reliability and accuracy.

The corrugated board is a versatile and durable material that is widely used in the packaging industry. Its unique structure provides strength and cushioning, while its recyclability and bio-degradability make it an environmentally friendly option. The strength of corrugated board depends on many factors, including the type of individual papers on flat and corrugated layers, the geometry of the flute, temperature, humidity, etc. This paper presents a new approach to analysis geometric features of corrugated boards based on the images. It allows for precise determination of the geometry of the corrugated layer, as well as the thickness of individual papers in all cardboard layers. The experimental set used in the work and the created software are characterized by high reliability and precision of measurement thanks to the use of an identification procedure based on image analysis and evolutionary algorithms. This allows to quickly find the main geometric characteristics of the corrugated board, which in turn leads to the possibility of performing numerical analyzes taking into account the real model of the corrugated board. Calculations made on a real (correctly mapped geometrically) model allow, for example, a more reliable analysis of the composition of the cardboard, and thus also to obtain greater savings in the optimization process.

Leishmaniasis is a disease caused by parasites of Leishmania genus and transmitted by sand fly vectors. Tegumentary leishmaniasis is the most prevalent clinical outcome in Latin America afflicting people from 18 countries. In Panama, leishmaniasis has annual incidence rates as high as 3000 cases, representing therefore one of the major public health problems. In endemic regions, L. panamensis is responsible for almost eighty percent of the human cases that present different clinical outcomes. This differences in disease outcomes could be result of the local interplay between L. panamensis variants and human hosts with different genetic backgrounds. The genetic diversity of L. panamensis in Panama has only been partially explored, and the variability reported for this species is based on few studies restricted to small populations and/or with poor resolutive markers at low taxonomic levels. Accordingly, in this study we explored the genetic diversity of sixty-nine L. panamensis isolates from different endemic regions of Panama using a MLST approach based on four housekeeping genes (Aconitase, ALAT, GPI and HSP70). Two to seven haplotypes per locus were identified, and regional differences in L. panamensis genetic diversity were observed. Genotype analysis evidenced the circulation of thirteen L. panamensis genotypes, a fact that might have important implications for the local control of the disease.

This article develops dual variational formulations for a large class of models in variational optimization. The results are established through basic tools of functional analysis, convex analysis and duality theory. The main duality principle is developed as an application to a Ginzburg-Landau type system in superconductivity in the absence of a magnetic field. In the first sections, we develop new general dual convex variational formulations, more specifically, dual formulations with a large region of convexity around the critical points which are suitable for the non-convex optimization for a large class of models in physics and engineering. Finally, in the last section we present some numerical results concerning the generalized method of lines applied to a Ginzburg-Landau type equation.

The glucose-insulin regulatory system and its glucose oscillations is a recurring theme in the literature because of its impact on human lives, mostly the ones affected by diabetes mellitus. Several approaches were proposed, from mathematical to data-based models, with the aim of modeling the glucose oscillation curve. Having such a curve, it is possible to predict, when injecting insulin in type 1 diabetes (T1D) individuals. However, the literature presents prediction horizons no longer than 6 hours, which could be a problem considering their sleeping time. This work presents Tesseratus, a model that adopts a multi-agent approach to combine machine learning and mathematical modeling to predict the glucose oscillation up to 8 hours. Tesseratus uses the pharmacokinetics of insulins and data collected from T1D individuals. Its outcome can support endocrinologists while prescripting daily treatment for T1D individuals, and provide personalized recommendations for such individuals, to keep their glucose concentration in the ideal range. Tesseratus brings pioneering results for prediction horizons of 8 hours for nighttime, in an experiment with seven real T1D individuals. It is our claim that Tesseratus will be a reference for classification of glucose prediction model, supporting the mitigation of short- and long-term complications in the T1D individuals.

Acid fracturing simulation is used widely to optimize carbonate reservoirs and improve acid fracturing treatment performance. In this study, a method was used to minimize the risk of the acid fracturing treatment. First, optimal fracture geometry parameters with UFD methods are calculated. After that, design components change as long as fracture geometry parameters reach their optimal values. The results showed a high flow rate needed to achieve optimal fracture geometry parameters with increasing acid volume. Sensitivity analysis was performed on controllable and reservoir parameters. It observed that a high flow rate should be applied for a low fluid viscosity to achieve the optimization goals. Straight acid reaches optimal conditions at a high flow rate and low volume. These conditions for retarded acids appear only at a low flow rate and high volume. The study of the acid concentration for gelled acid showed that as it increased, the flow rate and volume increased. Besides, for low permeability formation, a large fracture half-length and small fracture width are desirable. In this case, a higher flow rate will be required. The sensitivity analysis showed that the optimum flow rate and acid volume increase and decrease for the high Young's modulus. The effect of closure stress was also investigated and observed for a sample with high closure stress, low flow rate, and high acid volume are required.

We utilized laser irradiation as a potential technique in tuning the electrical performance of NiOx/SiO2 thin film transistors (TFTs). By optimizing the laser fluence and the number of laser pulses, the TFT performance is evaluated in terms of mobility, threshold voltage, on/off current ratio and subthreshold swing, all of which were derived from the transfer and output characteristics. The 500 laser pulses irradiated NiOx/SiO2 TFT exhibited an enhanced mobility of 3 cm2/V-s from a value of 1.25 cm2/V-s for as-deposited NiOx/SiO2 TFT. The laser-irradiated NiOx material likely has a significant concentration of defect gap states, which could also be involved in light absorption processes. Second, and more importantly, the excess energy that the photogenerated charge carriers possess (due to the significant difference between the photon energy and the bandgap of NiOx), combined with the very high light intensity, would result in complex thermal and photo thermal changes thus resulting in an enhanced electrical performance of p-type NiOx/SiO2 TFT structure.

As neck and/or shoulder pain (NSP) frequently occur together with tension-type headache (TTH) and migraine, we explored how concomitant NSP affects perceived treatment responses to an analgesic. An anonymous survey was performed among 895 TTH and migraine sufferers who used the analgesic 400 mg ibuprofen/100 mg caffeine. NSP was relatively abundant among patients (42.4% for TTH; 39.2% for migraine), and associated with &gt;1 additional day with headache per month. Reported pain reduction was independent from NSP for TTH and migraine. More patients became pain-free at 2 h in migraine with NSP (42.9%) compared to migraine without NSP (32.2%), which is different from TTH with NSP (60.6%) and TTH without NSP (71.4%). For both, migraine and TTH, a recurrence of headache on the same day was more prevalent in those with concomitant NSP leading to a greater likelihood of taking a second dose of the analgesic. NSP frequently occurs together with TTH and migraine patients. In migraine, NSP seems to be associated with a better treatment response at 2 h. The more frequent recurrence of pain in those with concomitant NSP indicates that NSP makes both headache types worse. Further studies are needed to substantiate these effects.

This study used secondary data from the 2017 Korean Community Health Survey to compare the associations of socio-physical environment, social support networks, and social activities with happiness among older adults with three different family types. As per the results, there was a significant difference in happiness index between the three groups (F = 86.688, p < .001). Older adults living alone (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.57–0.99) and those living with family (OR = 0.80, 95% CI = 0.65–0.99) showed greater happiness as the frequency of contact with family increased. Older adults living with only their spouse showed an increase in happiness when their contact with friends was higher (OR = 0.69, 95% CI = 0.56–0.84). It was confirmed that there were differences in factors influencing happiness according to the family type of the older adults in this study. Therefore, the happiness of older adults needs to be adequately ensured, while considering their various circumstances, including family type.

Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive peripheral fibres, is a useful model to study central sensitization to pain. Windup is expressed by neurons in of both dorsal and ventral horn of the spinal cord. In juvenile rats, it has been demonstrated both in vivo and in vitro that windup depends on calcium-dependent intrinsic properties and their modulation by synaptic components. However, the involvement of these two components in the adult remain controversial. In the present study, by means of electromyographic and extracellular recordings, we show that windup in adult, in vivo, depends on a synaptic balance between excitatory NMDA receptors and inhibitory glycinergic receptors. We also demonstrate the involvement of L-type calcium channels in both the dorsal and ventral horn of the spinal cord. These results indicate that windup in adults is similar to juveniles rats and that windup properties are the same regardless spinal network, i.e. sensory or motor.

Bianchi type III string cosmological models (massive and geometric) in presence of magnetic field with vacuum energy density following the techniques used by Letelier (1979) and Stachel (1980) are obtained. We find that the energy conditions (dominant as well as weak) given by Hawking and Ellis (1974) are satisfied for the models. Also the solutions obtained satisfy conservation equation for massive string with magnetic field and vacuum energy density. The models in general, represent anisotropic phase of space-time due to the presence of string. However, the models isotropize at late time and in special case. It has also been shown that the magnetic field is directly linked with the matter. For string dust model, the state finder parameters {r,s} are in excellent agreement with Planck results (Sahni et al. (2003)). The physical and geometrical aspects of the models with special cases are also discussed.

In this paper, we define Ulisse Dini-type helicoidal hypersurface with spacelike axis in Minkowski 4-space ${\mathbb{E}}_1^4$ . We compute the Gaussian and the mean curvature of the hypersurface. Moreover, we obtain some special symmetry to the curvatures when they are flat and maximal.

Place attachment is an emotion that people experience in connection to a specific place and it is needed to maintain sustainable neighborhood community. The emotion is affected by various factors, such as experience, function, environment, and satisfaction. This study focuses on commercial structures, which are one feature that characterize the physical environments of neighborhoods. The aim of this study is to determine the effects of commercial activities in different commercial environments on social bonding and place attachment in residents. Two sites were selected for analysis due to their different commercial environments, and path analysis was used to examine the relationships among factors. The results indicate that the type of commercial environment had effects on commercial activities, including shopping frequency, and that commercial activities affected social bonding and place attachment in residents. Also, commercial activities had indirect effects on place attachment through social bonding between residents. These results suggest that the commercial environment is an important element affecting the community and place attachment of residents in neighborhoods.

An analysis of workplace accidents in the mining sector has been done using the database from the Spanish administration between the period 2005-2015 and applying data mining techniques. Data has been processed by means of the software Weka. Two scenarios were chosen regarding the accidents database, surface and underground mining. The most important variables involved in occupation accidents and their association rules have been determined. These rules are formed by several predictor variables that cause an accident, defining its characteristics and context. This study exposes the 20 most important association rules of the sector, either surface or underground mining, based on statistical confidence levels of each rule obtained by Weka. The outcomes display the most typical immediate causes with the percentage of accident basis of each association rule. The most typical immediate cause is body movement with physical effort or overexertion and type of accident is physical effort or overexertion. On the other hand, the second most important immediate cause and type of accident change in both scenarios. Data mining techniques have been proved as a very powerful tool to find out the root of the accidents, apply corrective measures and verify their effectiveness, either for public or private companies.

In this paper, we study the well-posedness and asymptotic behaviour of solutions to a laminated beam in thermoelasticity of type III. We first give the well-posedness of the system by using the semigroup method. Then, we show that the system is exponentially stable under the assumption of equal wave speeds. Furthermore, it is proved that the system is lack of exponential stability for case of nonequal wave speeds. In this regard, a polynomial stability result is proved.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) utilizes Angiotensin Converting Enzyme 2 (ACE2) as its main receptor for cell entry. We have bioengineered a soluble ACE2 protein termed ACE2 618-DDC-ABD that has increased binding to SARS-CoV-2 and prolonged duration of action. Here we investigated the protective effect of this protein when administered intranasally to k18-hACE2 mice infected with the aggressive SARS-CoV-2 delta variant. k18-hACE2 mice were infected with the SARS-CoV-2 delta variant by inoculation of a lethal dose (2x104 PFU) and followed for up to 14 days. ACE2-618-DDC-ABD (10mg/kg) or PBS was administered intranasally six hours prior and 24 and 48 hours post viral inoculation. All animals in the PBS-control group had succumbed to the disease on day 7 post infection (0% survival) whereas, by contrast, there was only one casualty in the group that received ACE2-618-DDC-ABD (90% survival). Mice in the ACE2-618-DDC-ABD group had minimal disease as assessed by a clinical score and stable weight and both brain and lung viral titers were markedly reduced. These findings demonstrate the efficacy of a bioengineered soluble ACE2 decoy with extended duration of action in protecting against the aggressive delta SARS-CoV-2 variant. Together with previous work these findings demonstrate the universal protective potential against current and future emerging SARS-CoV-2 variants.

The treatment of viral infections is challenging owing to the intricate structure and metabolism of the viruses. In addition, they can highjack host cellular metabolism, mutate and adapt to harsh environmental conditions. The novel coronavirus (SARS-CoV-2) displays further resilient attributes, making its eradication even more difficult. SARS-CoV-2 is an enveloped virus whose replication can be targeted by limiting the substrates available for structural incorporation. One such molecule that limits substrate availability and has received much attention lately is 2-Deoxy-d-glucose (2-DG). SARS-CoV-2 infection induces glycolysis, impairs mitochondrial function, and damages the infected cells. Administration of 2-DG can inhibit increased glycolytic flux and some other metabolic processes to cause the cessation of viral replication. This article provides a review of the mechanism of action and safety concerns associated with administering 2-DG in the treatment of COVID-19. The drug can have adverse effects on normal cell metabolism since it targets cells non-selectively, possibly in a dose-dependent manner. In addition, the drug has limited use in SARS-CoV-2 infection associated with stroke, hypoxic-ischemic encephalopathy, and critical illness.

Since December 2019, the worldwide spread of COVID-19 has brought the majority of the world to a standstill, affecting daily lives as well as economy. Under these conditions, it is imperative to develop a cure as soon as possible. On account of some of the adverse side effects of the existing conventional drugs, researchers all around the world are screening natural antiviral phytochemicals as potential therapeutic agents against COVID-19. This paper aims to review interactions of some specific phytochemicals with the receptor binding domain (RBD) of the Spike glycoprotein of SARS-CoV-2 and suggest their possible therapeutic applications. Literature search was done based on the wide array of in-silico studies conducted using broad spectrum phytochemicals against SARS-CoV-2 and other viruses. We shortlisted 26 such phytochemicals specifically targeting the S protein and its interactions with host receptors. To validate the previously published results, we also conducted molecular docking using the AutoDockVina application and identified 6 high potential phytochemicals for therapeutic use based on their binding energies. Besides this, availability of these compounds, their mode of action, toxicity data and cost-effectiveness were also taken into consideration. Our review specifically identifies 6 phytochemicals that can be used as potential treatments for COVID-19 based on their availability, toxicology results and low costs of production. However, all these compounds need to be further validated by wet lab experiments and should be approved for clinical use only after appropriate trials.

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

This case study focuses on exploring the potential of biogas as a direct substitute for conventional fossil fuels in industrial applications. Instead of being limited to its common uses as a vehicle fuel or for power generation, this research aims to investigate how biogas can be integrated into industrial processes as an advanced and sustainable energy solution. By conducting a detailed analysis of the financial implications associated with the utilization of landfill gas and gas derived from biomass, a comprehensive understanding of their practical applications in the industrial sector can be obtained. This research goes beyond a superficial examination and delves into the intricate aspects of incorporating biogas as a viable alternative fuel source. When we say that utilizing biogas is technically feasible, it means that the necessary infrastructure and technologies are available to support its integration into industrial processes. This implies that there are existing methods and systems in place that can efficiently harness and utilize biogas for various industrial applications. These technologies ensure a seamless transition from conventional fossil fuels to renewable energy sources, leading to a more sustainable and environmentally friendly industrial landscape. Moreover, the statement that utilizing biogas is economically feasible emphasizes that the financial viability of employing biogas in industrial processes is advantageous. This research explores the potential cost savings and benefits associated with substituting conventional fuels with biogas. By carefully examining the economic aspects, such as initial investments, operational costs, and potential revenue streams, a comprehensive understanding of the financial impact of adopting biogas solutions in the industrial sector can be gained. By expanding and broadening the understanding of the technical and economic feasibility of biogas integration, this research aims to provide valuable insights into the potential of advanced biogas solutions for industrial applications. Indeed, to make biogas a viable and sustainable option as a raw material, it is necessary to establish farming subsidies and financial support specifically tailored for biogas production, similar to the existing support provided for food production. These subsidies and financial incentives play a crucial role in promoting and encouraging the growth of the biogas industry. By establishing such support systems, farmers and other stakeholders in the agricultural sector can be incentivized to participate in the production of biogas. This can involve the utilization of agricultural waste, organic residues, or dedicated energy crops for biogas generation. The financial assistance can help offset the initial investment costs, provide incentives for production, and ensure the economic viability of biogas projects. Moreover, when considering large-scale landfills or situations where industrial demands for energy are relatively low, landfill gas becomes a viable and practical option. Landfill gas, which is generated by the decomposition of organic waste in landfills, can be harnessed and utilized for various industrial purposes. This not only helps in managing waste but also provides a valuable source of renewable energy. In summary, while farming subsidies and financial support are crucial for promoting biogas production, landfill gas remains a viable option for large landfills or situations with minor industrial demands. The combination of these two approaches offers a comprehensive outlook on utilizing biogas as a renewable energy source for industrial applications.

This paper presents ensemble learning of multi-source satellite sensors dataset to obtain better predictive performance of the forest biomass. Spectral, spectral-indices, and spectral-textural features were generated from two optical satellite sensors, Landsat 8 Operational Land Imager (OLI) and Sentinel-2 Multispectral Instrument (MSI). In addition, two radar satellite sensors, Sentinel-1 C-band Synthetic Aperture Radar (CSAR), and Advanced Land Observing Satellite (ALOS-2) Phased Array type L-band Synthetic Aperture Radar (PALSAR-2) were utilized to generate backscattering and backscattering-textural features. The plot-wise above ground biomass data available from five forests in New England region were utilized. Ensemble learning of multi-source satellite sensors dataset was carried out by employing four machine learning regressors namely, Support Vector Machines (SVM), Random Forests (RF), Gradient Boosting (GB), and Multilayer Perceptron (MLP). A five-fold cross-validation method was used to evaluate predictive performance of the multi-source satellite sensors. The integration of multi-source satellite features, comprising of spectral, spectral-indices, backscattering, spectral-textural, and backscattering-textural information, through ensemble learning and cross-validation approach implemented in the research showed promising results (R² = 0.81, RMSE = 46.2 Mg/ha) for the estimation of plots-level forest biomass in New England region.

Understanding the dynamics of humoral immune responses throughout the COVID-19 pandemic is crucial for optimizing vaccine strategies. This study aimed to investigate the impact of infection and vaccine-induced immunity on the Albanian population from August 2021 to August 2022. Two independent samples from the Albanian general population were analyzed using an ELISA method to assess IgG class anti-Spike (S1) and anti-Nucleocapsid (N) SARS-CoV-2 antibodies. The results revealed a robust immune response among vaccinated individuals with prior COVID-19 infection who received only one vaccine dose. In the 2022 cohort, most individuals who received one vaccine dose achieved comparable seropositivity and antibody levels to those who received two doses. However, individuals aged 61 and over required two or three vaccine doses to reach the same level of immune response as the younger population. Notably, the time elapsed since infection or vaccination did not significantly impact the immune response. These findings highlight the importance of hybrid immunity and suggest that one vaccine dose may be sufficient for most individuals with prior COVID-19 infection. However, additional doses are necessary for optimal protection in older individuals. This study provides unique insights into humoral immune response dynamics that can be used to refine ongoing COVID-19 population vaccination strategies for middle-income countries with low vaccination coverage.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyper inflammation, vasculitis and multi-organ failures. SARS-CoV-2 causes deterioration of numerous systems with increasing evidence implying that COVID-19 affects endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietins/Tie balance affects vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically the Angiopoietin/Tie pathway.

A green, fast and selective approach for the synthesis of mono-substituted closo-decaborate derivatives [2-B10H9COR]n– has been established via a nucleophilic addition reaction between the carbonyl derivative of closo-decaborate [2-B10H9CO]– and the corresponding Grignard reagent RMgX, where R is the ethyl, iso-propyl, pentyl, allyl, vinyl, and propynyl groups. This approach is accomplished under mild conditions with 70–80% yields. The significance of these derivative is their ability to constitute building blocks for polymeric integration via the allyl, vinyl and propynyl substituents. All products were characterized by 11B, 1H, and 13C NMR, elemental analysis and mass spectrometry.

Searching for bioactive compounds within the huge chemical space is like trying to find a needle in a haystack. Isatin is a unique natural compound which is endowed with different biopertinent activities specially in cancer therapy. Herein, we envisaged that adopting a hybrid strategy of isatin and α,β-unsaturated ketone would afford new chemical entities with strong chemotherapeutic potential. Of interest, compounds 5b and 5g demonstrated significant antiproliferative activities against different cancer genotypes according to NCI assay. Concomitantly, their IC50 against HL-60 cells were 0.38 ± 0.08 and 0.57 ± 0.05, respectively, demonstrating remarkable apoptosis and mod-erate cell cycle arrest at G1 phase. Intriguingly, an impressive safety profile for 5b was reflected by a 37.2 times selectivity against HL-60 over PBMC from a healthy donor. This provoked us to further explore their mechanism of action by in vitro and in silico tools. Conclusively, 5b and 5g stand out as strong chemotherapeutic agents that hold a clinical promise against acute myeloid leukemia.

It is very difficult to repair large bone defects, especially when they have a complex shape. We have developed a new technique to make a desired copy of rabbit bones. A rabbit distal femur was scanned by computed tomography (CT), and a rectangular-shaped beta-tricalcium phosphate (β-TCP) block with 75% porosity was automatically machined using milling tools into a half-scale copy of the distal femur based on the CT data. The β-TCP block was seeded with bone morphogenetic protein-2 and bone marrow cells obtained from the femur and implanted on the periosteum of the femur. At 10 weeks after implantation, most of the β-TCP block had been replaced by bone and a complete copy of the distal femur was reconstructed. Our findings indicate that this technique will be useful in the clinical setting. We also report the representative clinical results of treatment with β-TCP graft in patients with bone defects since 1989.

Abstract: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with ACE2 receptor located in endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease leading to irreversible tissue damage and death of patients with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated to the interaction of SARS CoV-2 with ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

Sars-CoV-2 outbreak represents a public health emergency, affecting different regions of the world. Lung is the organ more damaged due to the high presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection vary from absence of symptomatology to be more severe, characterized by acute respiratory distress syndrome (ARDS), multiorgan failure and sepsis requiring treatment in Intensive Care Unit (ICU).It is not still clear why in a small percentage of patients immune system is not able to efficiently suppress viral replication. It has been documented as predictive factors for severity and susceptibility affections of cardiovascular system such as heart failure (HF), coronary heart disease (CHD) and risk factors for atherosclerotic progression, hypertension and diabetes among others.Atherosclerotic progression, as chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory pattern, including (Interleukin 6) IL-6, Tumor Necrosis Factor α (TNF-α) and IL-1β raise. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results report in severe Sars-CoV-2 infection we have supposed a pathogenetic correlation. Atherosclerosis may be a pathogenetic ideal substrate to high viral replication ability leading to adverse outcomes, how reported in patients with cardiovascular factors. Moreover, level of atherosclerotic progression may impact on a different degree of severe infection and in a vicious circle feeding itself Sars-CoV-2 may exacerbate atherosclerotic progression due to excessive and aberrant plasmatic concentration of cytokines.

Background: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic affecting approximately 490,000 people and accounting for more than 22,000 deaths and has no generally acceptable cure. Here, the recently resolved 3D structure of SARS-CoV-2 receptor binding domain (RBD) in complex with its receptor-the angiotensin converting enzyme-2 (ACE-2) have provided the basis for screening chemical database for novel entry inhibitors. Methods: Molecular docking protocols have been used to rapidly screen FDA database for high affinity interaction at the SARS-CoV-2-RBD/ACE-2 interface. One of the top candidates, ubrogepant has been selected and further studied using atomistic molecular dynamics simulation method. Results: Molecular docking result showed that ubrogepant (UBR) and darunavir have binding energies of -10.4 kcal/mol. MMPBSA free energy analyses of UBR bound to RBD, ACE-2 and RBD/ACE-2 revealed RBD/ACE-2 > ACE-2 > RBD preference. Network analysis showed that interaction captured in the crystal structure were disrupted in UBR-bound state, hydration of the interface and increased atomic fluctuation within the RBD oligomerization interface and ACE-2 zinc binding site. Conclusions: The ability of ubrogepant to rupture the interaction at the RBD/ACE-2 interface residues of SARS-CoV-2 RBD/ACE-2 complex may result in loss of protein function with direct implication on oligomerization formation in RBD and loss of function in ACE-2 thus, making binding, cellular receptor recognition impossible. General Significance: Ubrogepant represents a new therapeutic candidate in the fight against COVID-19, as it binds with relatively high affinity with free RBD, ACE-2 receptor and SARS-CoV-2 RBD/ACE-2 complex based on binding affinity calculations.

Praeruptorin A(PA), a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. So far the anti-cancer effect and molecular mechanism behind Praeruptorin A action in human cervical cancer HeLa cells remain unknown. In the present study, we find that PA reduces cell proliferation and colony formation of human cervical cancer HeLa cells through inducing cell cycle arrest at G0/G1 phase. PA-upregulated p21 and p27 proteins are observed, accompanied with inhibition of cyclin D1 and S-phase kinase-associated protein 2(Skp2) proteins expression. PA could significantly inhibit migration and invasion of human HeLa cells. Meanwhile, PA significantly reduces invasive protein expression of matrix metalloproteinase-2 (MMP-2), and increases protein expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). PA is observed to possess the capacity in suppressing ERK1/2 activation. PD98059 (ERK specific inhibitor) significantly enhances PA-induced downregulation of MMP-2 expression, and upregulation of TIMP-2 expression. Moreover, we found that PA treatment notably inhibits 12-O-tetradecanoylphorbol-13-acetate(TPA)-upregulated ERK1/2 activation, MMP-2 expression, cellular migration and invasion in human HeLa cells. Taken together, these findings are the first to demonstrate the anti-cancer activity of PA, which may act as a promising therapeutic agent for the treatment of human cervical cancer.