Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent data highlight similarities between neurodegenerative diseases including PD and type 2 diabetes mellitus (T2DM) suggesting a crucial interplay between the gut–brain axis. GLP-1R agonists, known for their use in T2DM treatment, are currently extensively studied as novel PD modifying agents. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles and clinical trials regarding GLP-1R agonists and PD, published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Our research was conducted between February 2023 and February 2024. We used the terms “GLP-1”, “GLP-1 receptor”, “GLP-1R agonists”, “PD”, “T2DM”, “insulin”, “neurodegenerative disease”, “glucose”, “animal models”, “clinical trials” in different combinations. Many data on animal models and preclinical studies show that GLP1-R agonists can restore dopamine levels, inhibit dopaminergic loss, attenuate neuronal degeneration and alleviate motor and non-motor features of PD. Evidence from clinical studies are also very promising enhancing the possibility of adding GLP1-R agonists in the current armamentarium of drugs available for PD treatment.

Should our planet be visited by an extraterrestrial civilization, the prevailing assumption would undoubtedly be that the extraterrestrial civilization is Type I i.e. its capacity for interstellar travel results from its technological development. This assumption is dangerous for it unnecessarily leads to the Extraterrestrial Tandem Hypothesis (ETH): the belief than an extraterrestrial civilization technologically capable of interstellar travel must also be technologically compatible with the inexorably rapid annihilation of life on Earth. Such a state of things would compromise the planet’s capacity to stage a confident defense should the extraterrestrials prove belligerent. The presumption of Type I extraterrestrials (on the premise of the capacity for interstellar travel alone) is unfounded as extraterrestrials may be Type II i.e. capable of interstellar travel by virtue of natural intrinsic or extrinsic factors. This paper advances, most importantly, that the fundamental policy of first contact should be the employment of various strategies toward the evaluation of the technological capacity of visiting extraterrestrials. This evaluation must be particularly devoted to the detection of Type II extraterrestrials masquerading as Type I (using concealment and Wizard of Oz strategies). Integral to this detection are the concepts of the precedence relation and The Extraterrestrial Exclusion Principle (EEP). A precedence relation is a qualitative relation expressing the relative difficulty of producing a technological action. The Extraterrestrial Exclusion Principle states that a Type I extraterrestrial life form is excluded from certain actions. Such actions are lower in precedence than interstellar travel and may be described as in violation of the EEP or EEP forbidden. EEP actions reveal extraterrestrials to be Type II. As an example, the value of the Hawking Warning is subjected to EEP analysis. Furthermore, a hypothetical conundrum in linguistics termed the Kryptonian Linguistic Paradox (KLP) is discussed as a case of an EEP forbidden act. Finally, the paper explores the limitations of the stated fundamental policy of first contact.

Background: The COVID-19 pandemic, caused by SARS-CoV-2, has severely impacted children with Type 1 Diabetes (T1D), placing them at high risk for severe outcomes. Despite extensive observational data suggesting a link between T1D and severe COVID-19, there is a lack of understanding regarding the causal effects. This study aims to determine whether Type 1 diabetes (T1D) influences the risk of severe COVID-19 outcomes, particularly respiratory failure, in pediatric ICU patients. Methods: This two-sample Mendelian Randomization (MR) study utilized genetic data from large-scale genome-wide association studies (GWAS). Genetic variants associated with T1D were used as instrumental variables to assess their impact on severe COVID-19 outcomes. The primary datasets included genetic data for T1D from 457,695 individuals (6,447 T1D cases) and severe COVID-19 outcomes from 3,790 individuals (1,610 severe cases). Various MR methods, including Inverse Variance Weighted (IVW), MR-Egger Regression, and Weighted Median, were employed to ensure robust causal inference and eliminate potential biases such as pleiotropy. Results: The MR analysis revealed no causal relationship between T1D and severe COVID-19 outcomes in pediatric patients. Odds ratios (ORs) obtained using MR-Egger, Weighted Median, and IVW methods varied from 0.7648 to 0.9853, with p-values greater than 0.05, indicating no significant causal effect. Sensitivity analyses confirmed the robustness of these findings, showing no evidence of heterogeneity or directional pleiotropy. Conclusion: Our findings indicate no genetic causal link between T1D and severe respiratory failure from COVID-19 in children. These results contrast with numerous observational studies and suggest that metabolic dysfunction and other non-genetic factors should be the focus in managing this susceptible group. The insights gained are crucial for developing targeted interventions and improving clinical management strategies for pediatric ICU patients with T1D during the COVID-19 pandemic.

Let $m$ and $n$ be the fixed positive integers. Suppose $\mathcal{A}$ is a von Neuman algebra with no central summands of type $I_{1}$ and $L_{m}$ be a Lie type higher derivation i.e., an additive (linear) map $L_{m} :\mathcal{A}\to \mathcal{A}$ such that \begin{equation}\label{def2} \[L_{m}(p_{n}(\mathfrak{S}_{1},\mathfrak{S}_{2},\cdots,\mathfrak{S}_{n}))=\sum_{l_1+l_2+\cdots+l_n=m}p_{n}\big(L_{l_1}(\mathfrak{S}_{1}),L_{l_2}(\mathfrak{S}_{2}),\cdots,L_{l_n}(\mathfrak{S}_{n})\big)\] %L_{m}(p_{n}(\mathfrak{S}_{1},\mathfrak{S}_{2},\cdots,\mathfrak{S}_{n}))=\sum_{l_1+l_2+\cdots+l_n=m}p_{n}\big(L_{l_1}(\mathfrak{S}_{1}),L_{l_2}(\mathfrak{S}_{2}),\cdots,L_{l_n}(\mathfrak{S}_{n})\big)\nonumber \end{equation} for all $\mathfrak{S}_{1},\mathfrak{S}_{2},\cdots,\mathfrak{S}_{n}\in \mathcal{A}$. In the present paper, we study Lie type higher derivations on von Neuman algebras and prove that every additive Lie type higher derivation on $\mathcal{A}$ has a standard form at zero product as well as at projection product. Further, we discuss some more related results.

Neurofibromatosis type 2 (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with NF2-deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by NF2-deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

This study evaluated metabolites and lipid composition in the calf muscles of Type 2 Diabetes Mellitus (T2DM) patients and age-matched healthy controls using multi-dimensional MR Spectroscopic Imaging. We also explored the association between muscle metabolites, lipids, and intra-abdominal fat in T2DM. Participants included 12 T2DM patients (60.3 ± 8.6 years), 9 age-matched healthy controls (AMHC) (60.9 ± 7.8 years), and 10 young healthy controls (YHC) (28.3 ± 1.8 years). We acquired 2D MR spectra of calf muscles using an enhanced accelerated 5D echo-planar correlated spectroscopic imaging (EP-COSI) technique, and abdominal MRI with breath-hold 6-point Dixon sequence. In YHC, choline levels were lower in the gastrocnemius (GAS) and soleus (SOL) muscles but higher in the tibialis anterior (TA) compared to AMHC. YHC also showed higher unsaturation index (U.I.) of extramyocellular lipids (EMCL) in TA, intramyocellular lipids (IMCL) in GAS, carnosine in SOL, and taurine and creatine in TA. T2DM patients exhibited higher choline in TA and myo-inositol in SOL than AMHC, while Triglyceride fats (TGFR2) in TA was lower. Correlation analysis indicated associations between IMCL U.I. and various metabolites in muscles with liver, pancreas, and abdominal fat estimates in T2DM. These findings may elucidate the impact of dysfunctional adipose tissues in T2DM.

Background: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). Methods: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 to 2019. The in-hospital mortality rates, length of stay (LoS) and healthcare costs were determined. Results: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p<0.001). The estimated total care cost for all patients with T1DM with CCD was approximately US $326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68-23.79), pulmonary embolism (OR 4.39, 95%CI 2.70-7.13), endocarditis (OR 3.46, 95%CI 1.22-9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92-2.77) and stroke (OR 1.47, 95%CI 1.04-2.09). Conclusions: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.

A construction for the systems of natural and real numbers is presented in Zermelo-Fraenkel Set Thoery, that allows for simple proofs of the properties of these systems, and practical and mathematical applications. A practical application is discussed, in the form of a Simple and Linear Fast Adder (Patent Pending). Applications to finite group theory and analysis are also presented. A method is illustrated for finding the automorphisms of any finite group $G$, which consists of defining a canonical block form for finite groups. Examples are given, to illustrate the procedure for finding all groups of $n$ elements along with their automorphisms. The canonical block form of the symmetry group $\Delta_4$ is provided along with its automorphisms. The construction of natural numbers is naturally generalized to provide a simple and sound construction of the continuum with order and addition properties, and where a real number is an infinite set of natural numbers. A basic outline of analysis is proposed with a fast derivative algorithm. Under this representation, a countable sequence of real numbers is represented by a single real number. Furthermore, an infinite $\infty\times\infty$ real-valued matrix is represented with a single real number. A real function is represented by a set of real numbers, and a countable sequence of real functions is also represented by a set of real numbers. In general, mathematical objects can be represented using the smallest possible data type and these representations are calculable. In the last section, mathematical objects of all types are well assigned to tree structures in a proposed type hierarchy.

This study tested the association between FecXG point mutation located in exon 2 of BMP15 gene and the prolificacy of Dubasi, Shugor and Watish sheep ecotypes, under dryland farming, Sudan. Blood samples were randomly collected from unrelated 100 ewes (Dubasi; n= 30, Shugor: n= 30, and Watish: n= 40). Bone Morphogenetic protein (BMP15) gene was amplified using PCR-RFLP. Two genotypes were found in all studied breeds (heterozygous and wild type). The calculated total genotype frequencies of BB, Bb and bb genotypes were 0.31, 0.69 and 0.00, respectively, while allele frequencies were 0.66 for B and 0.34 for b. Litter size was influenced by the genotypes of BMP15 gene, parities and subtypes (p<0.05), highest for Watish and 4th parity. Alignment of BMP15 samples along with database reference sequence revealed that most sequence regions were identical except for one variable nucleotide at position 111 bp where a guanine (G) was replaced by adenine (A) in Watish and Shugor samples. All amino acids were the same at residue 275. Watish and Shugor breeds are more related. The study concluded that the presence of one copy of FecXG point mutation of BMP15 gene increased the litter size by 0.17 lambs in the studied ecotypes.

The genome of Vibrio cholerae contains three structural genes for the NhaP-type cation-proton antiporter paralogues, Vc-NhaP1, 2 and 3 mediating exchange of K+ and or Na+ for protons across the membrane. Based on phenotype analysis of chromosomal Vc-NhaP1, 2 and 3 triple deletion mutants we suggested that Vc-NhaP paralogues might play a role in the Acid Tolerance Response (ATR) of V. cholerae as it passes through the gastric acid barrier of the stomach. Comparison of the biochemical properties of Vc-NhaP isoforms revealed that Vc-NhaP2 is the most active among all three paralogues. Therefore, Vc-NhaP2 antiporter is a plausible therapeutic target for developing novel inhibitors targeting these ion exchangers. Our structural and mutational analysis of Vc-NhaP2 identified a putative cation binding pocket formed by antiparallel extended regions of two transmembrane segments (TMSs V/XII) along with TMS VI. Molecular Dynamics (MD) simulations suggested that the flexibility of TMS-V/XII is crucial for the intra-molecular conformational events in Vc-NhaP2. In this study, we developed some putative Vc-NhaP2 inhibitors from Amiloride analogs (AAs). Amiloride is a potent inhibitor of human Na+/H+ exchanger-1 (NHE1). Based on the pharmacokinetic properties and potential binding affinity scores we chose six AAs showing high binding affinity scores to Vc-NhaP2. In silico, the six AAs interacted with the functionally important amino acid residues located in TMSs III, IV, V, VI, VIIII and IX either from the cytoplasmic side (three AAs) or the periplasmic side (three AAs) of Vc-NhaP2. Four AAs were modified to reduce their toxicity profile compared to the original AAs. Molecular docking of the modified AAs revealed promising binding. The four selected drugs interacted with functionally important amino acid residues located on the cytoplasmic side of TMS VI, the extended chain region of TMS V and TMS XII and the loop region between TMSs VIIII and IX. Molecular dynamics simulations revealed that binding of the selected drugs destabilized the Vc-NhaP2 and altered the flexibility of functionally important TMS VI.

Background/Objectives: Boscia senegalensis (BS) Pers.) Lam. Ex Poir (Capparaceae), is an important local famine food plant in Africa and widely exploited by healers for its seeds in Sahelian region to reduce hyperglycaemia. Purpose: We studied the efficacy of commercial dosage form of BS namely Boscisucrophage (BSP) on type 2 diabetes (T2DM) patients with Oral antihyperglycemic drugs resistant. Study Design: Clinical benefits of BSP, were evaluated in multicentre cohort observational study on naïve patients (43) or diabetic patients resistant of oral antidiabetic drugs (289). All patients received capsules of the fixed dose containing 350 mg of BSP twice daily for 12 weeks and overactive control on vein blood sugar, glycosylated haemoglobin (HbA1c), urine glucose excretion (UGE), aspartate aminotransferase, alanine aminotransferase, creatinine, and clinical examination of functional symptoms. Results: In clinical study, BSP induced the reduction of glycaemia, HbA1c, and increase UGE, with removal of side effects functional symptoms of T2DM. Conclusions: In clinical studies, our findings lend support to use of BSP to reduce glycaemia, and HbA1c in T2DM patients with Oral antihyperglycemic drugs resistant without over adverse effects. BSP supressed clinical examination of functional symptoms.

Chronic diseases, such as type 2 diabetes (T2D), are difficult to manage because they demand continuous therapeutic review and monitoring. Beyond achieving the target HbA1c, new guidelines for the therapy of T2D have been introduced with the new groups of antidiabetics (GLP-1ra and SGLT2-in). Despite new guidelines, clinical inertia, that can be caused by physicians, patients or healthcare system, results in T2D not being effectively managed. This opinion paper explores the shift in T2D treatment, challenging assumptions and evidence-based recommendations, particularly for family physicians, considering the patient's overall situation in decision-making. We looked for the possible reasons of clinical inertia and poor application of guidelines in the management of T2D. Guidelines for antidiabetic drugs should be more precise, providing case studies and clinical examples to define clinical contexts and contraindications. Knowledge communication can improve confidence and should include clear statements on areas of decision-making not supported by evidence. Precision medicine initiative in diabetes aims to identify subcategories of T2D patients (including frail patients) using clustering techniques from data science applications, focusing on CV and poor treatment outcomes. Clear, unconditional recommendations for personalized T2D management may encourage drug prescription, especially for family physicians dealing with diverse patient contexts and clinical settings.

A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which the fetus is highly susceptible to specific environmental influences that significantly impact health from short to long term. Maternal stress and T2DM during pregnancy are among these influences, likely leading to fetal overexposure to glucocorticoids and suggesting a shared pathway between maternal dysregulated HPA axis and fetal environmental insults. Studies demonstrate that prenatal glucocorticoid exposure alters fetal HPA axis function, affecting brain function, tissue glucocorticoid availability, and fetal growth in utero. These programmed changes, such as altered HPA axis function and reduced fetal growth, contribute to metabolic disorders persisting into adulthood. T2DM is preceded by a prediabetic state, often asymptomatic, which shares similar pathophysiological complications with T2DM, including HPA axis dysregulation observed in animals. Therefore, investigating prediabetes during pregnancy alongside maternal HPA axis function and its effects on fetal outcomes is crucial, as these areas remain understudied. This review aims to synthesize existing literature on pre-existing T2DM during pregnancy, its links to fetal programming via HPA axis changes, and possible links to pregestational prediabetes.

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

The mechanisms underlying the effects of γ-globulin therapy for bacterial infections are thought to involve bacterial cell lysis via complement activation, phagocytosis via bacterial opsonization, toxin neutralization, and antibody-dependent cell-mediated cytotoxicity. Nevertheless, recent advances in the study of pathogenicity in gram-negative bacteria have raised the possibility of an association between γ-globulin and bacterial toxin secretion. Over time, new toxin secretion systems like the type III secretion system have been discovered in many pathogenic gram-negative bacteria. With this system, the bacterial toxins are directly injected into the cytoplasm of the target cell through a special secretory apparatus without any exposure to the extracellular environment and, therefore, with no opportunity for antibodies to neutralize the toxin. However, because antibodies against the V-antigen, which is located on the needle-shaped tip of the bacterial secretion apparatus, can inhibit toxin translocation, this raises the hope that the toxin might be susceptible to antibody targeting. Because multi-drug resistant bacteria are now prevalent, inhibiting this secretion mechanism is attractive as an alternative or adjunctive therapy against lethal bacterial infections. Thus, it would not be unreasonable to define the blocking effect of anti-V-antigen antibodies as the fifth mechanism for immunoglobulin action against bacterial infections.

Background The aims of this study were to assess the peri-operative morbidity, mortality and long-term survival of octogenarians undergoing ATAAD repair, and to compare open and closed distal anastomosis techniques. Methods This was a single-centre retrospective study (2007-2021). Open versus closed distal anastomosis were compared. Uni and multi-variable logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Kaplan-Meier and Cox proportional hazards methods were used to compare long-term survival. Results Fifty octogenarians patients were included (median age - 82 years, closed distal – 22, open distal - 28). Median CPB time was 187 minutes (open distal vs closed distal group; 219 minutes vs 115.5 minutes, p30 days or return to theatre; HR; 4.1, p=0.02) predicted adverse survival. Open distal anastomosis did no impact survival. Conclusions – ATAAD repair in selected octogenarians has favourable short and long-term survival. There is no significant difference between open versus closed distal anastomosis strategies.

While there are millions of reptile images available online, they are not well organized and not easily findable, accessible, interoperable, or reproducible (FAIR). More importantly, they are not standardized and thus hardly comparable. Here we present a reference database of more than 14,000 standardized images of 1,045 reptile species (969 lizard and 76 snake species), that are based on preserved specimens in 20 different collections, including 533 type species of genera and type specimens of 72 species. All images were taken with standardized views, including dorsal and ventral body shots as well as dorsal, ventral, and lateral views of the heads and other body parts. Although only 11 out of the 20 collections are cross-referenced in Vertnet, some others are indexed in GBIF, and this fraction will certainly grow in the near future. The utility of this and similar image collections will further grow with additional material and further cross-referencing, e.g., to DNA sequence databases or citizen science projects. The images are searchable and freely available on Morphobank.org (Project 5121) and on Figshare.com.

Background: Over the past years, there has been a rise in the incidence of type 1 diabetes, partic-ularly among younger individuals. This concerning trend has prompted investigations into po-tential contributing factors, with intestinal dysbiosis emerging as a likely culprit for the escalating annual rates of the disease; (2) Methods: We conducted a retrospective ecologic correlational study involving 37 children from the southern region of Romania between 2019-2021. All participants were within the first six months following the onset of the disease; (3) Results: In the microbiota of the patients we observed a dysbiosis marked by an overabundance of bacteria (Clostridium coccoides, Faecalibacterium, Bacterioides, Enterobacteriaceae) and fungi, compared to the healthy control group. The Spearman correlation revealed a positive association between the presence of Bacteroides (p=0.0442), Butyricicoccus (p=0.0164), and Clostridium leptum (p=0.0023) with recent diabetes onset. Furthermore, a significant correlation was observed between younger age at onset and the pres-ence of Butyricicoccus (p=0.019). The use of antibiotics in the month preceding admission was linked to the presence of fungi in the microbiota (Candida, p=0.0442); (4) Conclusions: The dysbiosis of Romanian type 1 diabetes children correlates with inflammation, more severe onset of the disease and other au-toimmune diseases.

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. Interaction between various genetic variants and environmental factors triggers T2DM. The main aim of this study was to find the risk associated with genetic variant (rs5210) of KCNJ11gene in the development of T2D in Indian Population. A total number of 300 cases of T2D and 100 control samples were studied to find the polymorphism in KCNJ11 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different from the control population. We found a significant association of KCNJ11 (rs5210) gene polymorphism with T2DM in North Indian patients indicating the role of this variant in developing risk for T2DM.

Introduction: Type 2 diabetes (T2D) is a major driver of health care costs, thus treatments enabling T2D reversal may reduce expenditures. We examined the impact of a T2D continuous care intervention (CCI) on health care utilization. Previous research documented that CCI, including individualized nutrition supported by remote care, simultaneously reduced hemoglobin A1c and medication use and improved cardiovascular status after two years; however, the impact on utilization is unknown. Methods: This study used four years of data (two years pre-intervention, two years post-intervention) from the Indiana Network for Patient Care (INPC) health record. Two methods estimated the impact of CCI on utilization. First, an interrupted time series (ITS) including only CCI participants (n=193) compared post-intervention utilization to expected utilization had the pre-intervention trend persisted. Deviation from the trend was estimated non-parametrically for each 6-month interval after the implementation of CCI . Second, a 1:3 matched comparator group (n=579) was constructed and used for a difference-in-differences (DiD) analysis. The primary outcome was annualized outpatient encounters. Secondary outcomes included emergency encounters and hospitalizations. Results: In two years prior to intervention, CCI participants had a mean of 5.77 annualized encounters (5.62 outpatient, 0.04 hospitalizations, 0.11 emergency). The CCI group showed a reduction in outpatient utilization after intervention. In ITS analysis, 1.6 to 1.9 fewer annualized outpatient encounters occurred in each 6-month interval post-intervention relative to expected utilization based on pre-intervention trends (p<0.01 each 6-month period; 28-33% reduction). The DiD analysis suggested a larger reduction; 5 fewer annualized outpatient encounters in the quarter after intervention, diminishing to 2.5 fewer after 2 years (p<0.01 each quarter). The study was underpowered to draw conclusions about hospitalization and emergency encounters due to the limited number of CCI patients and the rarity of encounters. Conclusions: Outpatient encounters were significantly reduced for a T2D patient population up to 2 years after receiving an individualized intervention supporting nutrition and behavior change through remote care.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

The incidence of Type 1 Diabetes (T1D) in the Arab world, particularly, oil and gas rich Gulf Cooperative Council (GCC) countries has more than doubled in the last twenty years. Therefore, there is a dire need for careful systematic familial cohort studies, especially in high-risk populations. Several immunogenetic factors affect the pathogenesis of the disease. Genes in the human leukocyte antigen (HLA) account for the major genetic susceptibility to the disease. The triggering agents initiate disease onset by destruction of pancreatic β-cells. The autoantibodies against glutamic acid decarboxylase (GADA), insulinoma antigen-2 (IA-2A), insulin (IAA), and zinc transporter-8 (ZnT-8A) comprise the most reliable biomarkers for T1D in both children and adults. Although three of the GCC countries, namely Kuwait, Saudi Arabia and Qatar are among the top 10 countries with high incidence rate of T1D, no proper diagnostic and prediction tools were applied in the region. Understanding the disease sequelae in a homogenous gene pool with high consanguinity in the GCC could help solve the challenges in understanding pathogenesis, as well as hasten the prevention of T1D. Arab states must incorporate T1D predictive and intervention policies on a war-footing basis to minimize the burden of this serious disease.

Flares, sometimes accompanied by coronal mass ejections (CMEs), are the result of sudden changes in the magnetic field of stars with high energy release through magnetic reconnection, which can be observed across a wide range of the electromagnetic spectrum from radio waves to the optical range to X-rays. In our review, we attempt to collect some fundamental new results, which can largely be linked to the Big data era that has arrived due to the expansion of space photometric observations of the last two decades. We list the different types of stars showing flare activity, their observation strategies, and discuss how their main stellar properties relate to the characteristics of the flares (or even CMEs) they emit. Our goal is to focus, without claiming to be complete, on those results that may in one way or another challenge the "standard" flare model based on the solar paradigm.

Buildings’ thermal energy needs are inherently linked to climate conditions. Consequently, it is crucial to evaluate how climate changes affect these energy demands. Despite extensive analysis, a comprehensive assessment involving a diverse range of building types has not been consistently conducted. The primary objective of this research is to perform a coherent evaluation of the influence of climate changes, construction element properties, and the Heating, Ventilation, and Air Conditioning (HVAC) system type of control on the energy requirements of six buildings (residential, services, and commercial). The buildings are considered located in a temperate Mediterranean climate. Our focus is on the year 2070, considering three distinct climatic scenarios: (i) maintaining the current climate without further changes, (ii) moderate climate changes, and (iii) extreme climate changes. The buildings are distributed across three different locations, each characterized by unique climatic conditions. Buildings’ envelope features a traditional External Thermal Insulation Composite System (ETICS) and expanded polystyrene (EPS) serves as thermal insulation material. Two critical design factors are explored: EPS thickness ranging from 0 (no insulation) to 12 cm; and horizontal external fixed shading elements varying lengths from 0 (absence) to 150 cm. Six alternative setpoint ranges are assessed for the HVAC system control: three based on the Predicted Mean Vote (PMV) and three based on indoor air temperature (Tair). Results were obtained with a validated in-home software tool. They show that, even under extreme climate conditions, the application of thermal insulation remains energetically favorable, however its relative importance diminishes as climate severity increases. Then, proper insulation design remains important for energy efficiency. The use of external shading elements for glazing (e.g., overhangs, louvers) proves beneficial in specific cases. As climate changes intensify, the significance of shading elements grows. Thus, strategic placement and design are necessary for good results. The HVAC system’s energy consumption depends on the level of thermal comfort requirements, on the climate characteristics and on the building’s type of use. As climate change severity intensifies, energy demands for cooling increase, while energy needs for heating decrease. However, it’s essential to recognize that the impact of climate changes on HVAC system energy consumption significantly depends on the type of building.

Abstract: The study used whole-genome sequencing (WGS) and bioinformatics analysis for the genomic characterization of 60 isolates of Listeria monocytogenes isolated from cattle farms, cattle abattoirs, and retail outlets in Gauteng province, South Africa. The isolates' sequence types (STs), clonal complexes (CCs), and lineages were determined using in silico multilocus sequence typing (MLST). We used BLAST-based analyses to identify virulence and antimicrobial genes, plasmids, proviruses, and the CRISPR-Cas system. The study investigated any association of the detected genes to the origin in the beef production chain of the L. monocytogenes isolates. Overall, in 60 isolates of Listeria monocytogenes, there were 7 STs, 6 CCs, 44 putative virulence factors, 2 resistance genes, 1 plasmid with AMR genes and 3 with conjugative genes, 1 CRISPR gene, and all 60 isolates were positive for proviruses. Among the 7 STs detected, ST204 (46.7%) and ST2 (21.7%) were the most prominent, with ST frequency varying significantly (p&lt;0.001). The predominant CC detected were CC2 (21.7%) and CC204 (46.7%) in lineages I and II, respectively. Of the 44 virulence factors detected, 26 (across Listeria Pathogenicity Islands, LIPIs) were present in all the isolates. The difference in the detection frequency varied significantly (P&lt;0.001). The two AMR genes (fosX and vga(G)) detected were present in all 60 (100%) isolates of L. monocytogenes. The only plasmid, NF033156, was present in 3 (5%) isolates. A CRISPR-Cas system was detected in 6 (10%), and all the isolates carried proviruses. Significant differences were detected in the frequencies of STs and virulence factors regarding the source and sample type of the L. monocytogenes isolates. The presence of both fosX and vga(G) genes in all the isolates from the three industries (cattle farms, abattoirs, and retail outlets) can potentially cause therapeutic implications. Our study, which characterized L. monocytogenes recovered from the three levels in the beef production chain in the country, provides the first evidence of the distribution of the pathogen with potential food safety and therapeutic implications.

Abstract: Several publications have raised the issue that the development of diabetes is preceded by alteration of the microbiome (dysbiosis) and hence, the role of environmental factors, triggering dysbiosis, should be considered. Antibiotics are powerful agents inducing dysbiosis and the authors wanted to explore the possible relationship between the consumption of different major classes of antibiotics and the prevalence of diabetes (type-1, /T1D/, type-2 /T2D/) in thirty European countries. According to our hypothesis, if such association exists, the dominant use of certain major antibiotic classes might be reflected in the prevalence of T1D and T2D in different countries. Comparisons were performed between the prevalence of diabetes (T1D and T2D) estimated for 2019 and featured in the Diabetes Atlas with the average yearly consumption of major antibiotic classes of the previous 10 years (2010-19) extracted from the ECDC yearly reports on antibiotic consumption in Europe. Pearson correlation and variance analysis were used to estimate the possible relationship. Strong, positive (enhancer) associations were found between the prevalence of T1D and the consumption of tetracycline (J01A /p: 0.001/) and the narrow spectrum penicillin (J01CE /p: 0,006/, CF /p: 0.018/). Strong negative (inhibitor) association was observed with broad-spectrum, beta-lactamase resistant penicillin (J01CR /p: 0.003/), macrolide (J01F /p: 0.008/) and quinolone (J01M /p: 0.001/). T2D showed significant positive associations with cephalosporin (J01D /p: 0.048/) and quinolone (J01M /p: 0.025/), and a non-significant negative association was detected with broad-spectrum, beta-lactamase-sensitive penicillin (J01CA /p: 0.67/). Countries with the highest prevalence of diabetes (first 10 positions) showed concordance with the higher consumption of “enhancer” and the lower consumption of “inhibitor” antibiotics (first 10 positions) as indicated by variance analysis. Countries with high prevalence of T1D showed high consumption of tetracycline (p: 0.015), and narrow spectrum, beta-lactamase sensitive penicillin (p: 0.008), and low consumption of “inhibitor” antibiotics (broad-spectrum, beta-lactamase resistant, combination penicillin (p: 0.005), cephalosporin (p: 0.036), and quinolone (p: 0.003). Countries with a high prevalence of T2D consumed more cephalosporin (p: 0.084), quinolone (p: 0.54), and less broad-spectrum, beta-lactamase sensitive penicillin (p: 0.012) than other countries. Conclusion/Interpretation: The development of diabetes-related dysbiosis might be attached to higher consumption of specific classes of antibiotics, showing positive (enhancer) associations with the prevalence of diabetes, and the low consumption of other classes of antibiotics shoving negative (inhibitory) associations. Those groups of antibiotics are different in T1D and T2D

We introduce a new kind of extended Hermite-based Frobenius type Eulerian polynomials and then derive diverse explicit and implicit summation equations including some symmetric formulas by utilizing series manupulation method. Multifarious summation formulas and identities given earlier for some well known polynomials such as Eulerian polynomials and Frobenius type Eulerian polynomials are generalized.

Accurate and prompt determination of fire types is essential for effective firefighting and reducing damages. However, traditional methods such as smoke detection, visual analysis, and wireless signals pose unavailability in identifying fire types. This paper introduces FireSonic, an acoustic sensing system that leverages commercial speakers and microphones to actively probe the fire using acoustic signals, effectively identifying indoor fire types. By incorporating beamforming technology, FireSonic first enhances signal clarity and reliability, thus mitigating signal attenuation and distortion. To establish a reliable correlation between fire types and sound propagation, FireSonic quantifies the Heat Release Rate (HRR) of flames by analyzing the relationship between fire heated areas and sound wave propagation delays. Furthermore, the system extracts spatiotemporal features related to fire from channel measurements. Experimental results demonstrate that FireSonic attains an average fire type classification accuracy of 95.5% and a detection latency of less than 400 ms, satisfying the requirements for real-time monitoring. This system significantly enhances the formulation of targeted firefighting strategies, boosting fire response effectiveness and public safety.

With the development of salt cavern gas storage construction technology, the construction of large-scale gas storage salt caverns using sediment voids is expected to solve the problem of low effective volume formation rate and poor construction economy of high-impurity salt mines. There are few studies on the long-term operation mechanical behavior of salt cavern gas storage under the influence of sediment accumulation currently. This paper studies the influence of sediment accumulation height, particle gradation, and operating pressure on the stability of salt caverns by constructing a coupling model of sediment particle discontinuous medium and surrounding rock continuous medium. The continuous-discontinuous coupling algorithm is suitable for analyzing the influence of particle accumulation height and particle gradation on the creep shrinkage of salt caverns. The increase of sediment accumulation height slows down the creep shrinkage of the bottom of the salt cavern, strengthens the restraining effect on the surrounding rock of the cavern, and moves the position of the maximum displacement of the surrounding rock to the upper part of the cavern; the sediment particle gradation has little effect on the cavern volume shrinkage rate, and the greater the coarse particle content, the smaller the cavern volume shrinkage rate; the greater the operating pressure, the more conducive to maintaining the stability of the cavern, slowing down the upward movement of the sediment body and increasing the gas storage space in the upper part of the cavern. This research results can provide a reference for evaluating the long-term operation stability of sediment-type high-impurity salt cavern gas storage.

Naegleria fowler, also known as brain-eating amoeba is a thermophilic microorganism that causes primary amoebic encephalitis (PAM) having &gt;98% mortality rate. To date, there are no specific drugs identified to treat this disease. N. fowleri expresses only one form of hexokinase i.e. glucokinase (nGLK) unlike humans that express four isozymes of hexokinase including glucokinase (hexokinase IV) or hGLK that is critical for the first step of glycolysis. Until now, there have not been many studies on glucokinase as a drug target to treat PAM, hence, this study provides an exhaustive analysis of this relatively novel drug target. Thus, it was hypothesized that amoebic glucokinase can arrest carbohydrate metabolism and assist regulating its virulence. To find suitable antagonists to inhibit the activity of nGLK, we first tested the present recommended drugs by the CDC on their ability to bind nGLK. Interestingly our studies show that many of the present recommended drugs can inhibit both amoebic (nGLK) and human (hGLK) homologs of glucokinase. We identified new inhibitors for nGLK and further explored suitable hGLK antagonists for the potential treatment of diabetes. Despite significant structural differences between nGLK and hGLK, it was interesting to note that all our screened inhibitors bound with both nGLK and hGLK. Levomefolic acid; Ziprasidone; and Risperidone were found to be more suited to treat PAM while, Simeprevir; Indacaterol; Crizotinib and Mocetinostat were found to be suited for treating diabetes. The selections were based on multiple criteria including binding affinity; ADME scores; absorption; and its ability to cross the blood brain barrier. This study identifies multiple drugs that have potential not only to treat PAM but also to treat diabetes and also use for lab based biochemical assays for glycolysis inhibitors.

We provide an axiomatic base for the set of natural numbers, that has been proposed as a canonical construction, and use this definition of $\mathbb N$ to find several results on finite group theory. Every finite group $G$, is well represented with a natural number $N_G$; if $N_G=N_H$ then $H,G$ are in the same isomorphism class. We have a linear order, on the quotient space of isomorphism classes of finite groups, that is well behaved with respect to cardinality. If $H,G$ are two finite groups such that $|H|=m<n=|G|$, then $H<\mathbb Z_n\leq G\leq\mathbb Z_{p_1}^{n_1}\oplus\mathbb Z_{p_2}^{n_2}\oplus\cdots\oplus\mathbb Z_{p_k}^{n_k}$ where $n=p_1^{n_1}p_2^{n_2}\cdots p_{k}^{n_k}$ is the prime factorization of $n$. We find a canonical order for the objects of $G$ and define equivalent objects of $G$, thus finding the automorphisms of $G$. The Cayley table of $G$ takes canonical block form, and we are provided with a minimal set of independent equations that define the group. We show how to find all groups of order $n$, and order them. We give examples using all groups with order smaller than $10$, and we find the canonical block form of the symmetry group $\Delta_4$. In the next section, we extend our results to the infinite case, which defines a real number as an infinite set of natural numbers. A real function is a set of real numbers, and a sequence of real functions $f_1,f_2,\ldots$ is well represented by a set of real numbers, as well. In general, we represent mathematical objects using the smallest possible data-type. In the last section, mathematical objects are well assigned to tree structures. We conclude with brief comments on type theory and future work on computational aspects of these representations.

Aims/Hypothesis): Type 1 diabetes is an immune-mediated disease with destruction of the pancreatic β-cells, a process that is conditioned by multiple genes and other factors. HLA counts as the major susceptibility gene. Significant variations in HLA genetic susceptibility to type 1 diabetes between Caucasians, African and Asian and other ethnic groups may have led to the variation in incidence of type 1 diabetes globally. Type 1 diabetes is characterized upon HLA identification. In this chapter we discuss global variations in genetic susceptibility of HLA with regard to type 1 diabetes globally with a particular attention to Arab population. Methods): Haplotype configuration of HLA class I A, B, C and Class II –DR/DQ/DP were studied in Caucasians, African and Asian and in Arab population to see if that is responsible for the exponential rise in the rate of type 1 diabetes. Results): Although Arabs have one of the highest global incidence and prevalence rates of type 1 diabetes, unfortunately, there is a dearth amount of information regarding HLA genetic susceptibility to type 1 diabetes in the Arab world. HLA haplotype configurations contribute to its risk value. However, out of an insufficient present study there are examples of misjudgment of HLA risk according to HLA alleles rather than haplotypes. Conclusion): To date HLA outlooks for the characterization of type 1 diabetes. There is an ethnicity difference in HLA characteristics which is responsible for variation in type 1 diabetes. Although Arab population have contributed heavily in the rise of burden of type 1 diabetes, however, there is significantly a dearth amount of studies on HLA in Arab population. Obviously, any future prediction, prevention or cure of the disease will be based on the HLA genetics. There is a dire need for a systematic screening of HLA for Arab population with type 1 diabetes, identification of Arab HLA-risk values and identify those who are prone to get the disease.

Gastric-type endocervical adenocarcinoma (GAS) is a rare non-human papillomavirus associated mucinous adenocarcinoma of the cervix. Its clinical manifestations are extremely atypical, with hidden lesions and difficulty in obtaining materials, resulting in a low positive rate of screening and biopsy. The pathological morphological features are similar to benign lesions, but the biological characteristics are highly malignant, posing great challenges to diagnosis. The preoperative diag-nostic rate is low, which is prone to misdiagnosis and missed diagnosis, leading to delayed treatment and seriously affecting the prognosis of patients. Here，we reported a case of ovarian endometriosis cyst combined with GAS confirmed by surgery and postoperative pathology, with "pelvic mass" as the initial symptom. Through case report and literature review, the characteristics and current re-search progress of GAS were summarized, in order to provide references for diagnosis of GAS, and provide theoretical guidance for formulating reasonable treatment strategy and improving patient prognosis.

The comorbidity of osteoarthritis and type 2 diabetes mellitus represents a complex clinical challenge and complicates patient management due to the interplay of overlapping pathophysiological mechanisms. The research aimed to analyze the exacerbation of clinical symptoms and biochemical markers in patients with osteoarthritis and type 2 diabetes mellitus compared to those with osteoarthritis. We utilized various assessment methods to measure the patient cohorts' inflammation, oxidative stress, and glycemic control. The study also involved the administration of alpha-lipoic acid to patients with comorbid osteoarthritis and type 2 diabetes mellitus and monitored its effects on joint function, inflammatory markers, oxidative stress levels, and glycemic control. Our findings revealed that the presence of type 2 diabetes mellitus significantly intensified osteoarthritis symptoms and altered biochemical markers, including increased inflammation, elevated oxidative stress, and disrupted immunological balance. The treatment with alpha-lipoic acid resulted in improved joint function, reduced inflammation and oxidative stress levels, and better glycemic control. Additionally, it was identified several potential predictors for developing osteoarthritis and type 2 diabetes mellitus comorbidity. The results underscore the detrimental impact of type 2 diabetes mellitus on osteoarthritis and highlight the beneficial effects of alpha-lipoic acid in alleviating some of the adverse consequences associated with this comorbidity. Nonetheless, further research is necessary to comprehensively evaluate the therapeutic efficacy of alpha-lipoic acid and its long-term effects on managing comorbidity of osteoarthritis and type 2 diabetes mellitus.

The astro-structures with the shape of comet and semi-circle, are found in the electronegative inductively coupled plasmas (ICPs), e.g., Ar/O2 and Ar/SF6. They are formed by means of the self-coagulation theory. This theory is built and based on two-dimensional fluid model simulation dynamic data of the above ICP sources. Concretely, quasi-Helmholtz equation is constructed through the free diffusion transport component and a novel negative chemical source term. The absolute value of recombination rate is higher than the attachment rate and so the net source of simulated anion is negative. This is quite a new chemical phenomenon in the electronegative and gaseous discharging plasmas when compared to the previously reported normal positive chemical source that will generate ambi-polar diffusion potential. In electronegative plasma, the self-coagulation is ambi-polar to sustain the electrical neutrality. Besides, when the anions are accelerated by ambi-polar potential before self-coagulated, the self-coagulation is again advective which leads to the formation of blue sheath. At the ambi-polar self-coagulation of high electronegativity, the electrons dynamics are relatively decoupled from ions and meanwhile they have their own relatively weak, spontaneous, and monopolar self-coagulation in the periphery of astro-structure. At the ambi-polar self-coagulation, both the anion and cation are individually treated as mass point models that carry charge (point charge models, more precisely). When the charge amounts of two individual astr-structures, e.g., semi-circle SF3+ and Ar+, are equal, the coagulated profile of heavy species SF3+ collapses by the expelling effect of Coulomb force that exists between the two point-charges. This is an anti-collective behavior of astro-structure, instead of the collective interaction of plasma, since the collapse of coagulated heavy species creates spatially dispersed charge density that cannot be shielded. The simulation shows that the lighter the species, the easier it self-coagulates, determined by the inertial effect of density quantity. The discharge picture of electronegative plasma is combined by a dynamic continuum transport (e.g., forming the ellipse background) and the mechanical balance contained in the static self-coagulation process (proven by dimensional analysis of continuity equation). The popular astro-structure of electronegative ICP source awaits urgently for the validation of experiment.

Predicting type 2 diabetes mellitus (T2DM) using phenotypic data with machine learning (ML) techniques has received significant attention in recent years. PyCaret, an ML tool that enables the simultaneous application of 16 different algorithms, was used to predict T2DM using phenotypic variables from the “Nurses’ Health Study” and “Health Professionals’ Follow-up Study” datasets. Ridge classifier, Linear Discriminant Analysis, and Logistic Regression (LR) were the best-performing models for the male-only data subset. For the female-only data subset, LR, Gra-dient Boosting Classifier, and CatBoost Classifier were the strongest models. The AUC, accuracy, and precision were 0.77, 0.70, and 0.70 for males and 0.79, 0.70, and 0.71 for females, respective-ly. The feature importance plot showed that familial history of diabetes (famdb), never having smoked, and high blood pressure (hbp) were the most influential features in females, while famdb, hbp, and current smoking were the major variables in males. In conclusion, PyCaret was used successfully for speed analysis for the prediction of T2DM by simplifying complex ML tasks. Gen-der differences are an important consideration for T2DM prediction. Despite this comprehensive ML tool, phenotypic variables alone may not be sufficient for early T2DM prediction; genotypic variables could also be used in combination for future studies.

By generalizing the notion of pointwise 1-type Gauss map, the generalized 1-type Gauss map has been recently introduced. Without any assumption, we classified all possible ruled surfaces with generalized 1-type Gauss map in a 3-dimensional Minkowski space. In particular, null scrolls do not have the proper generalized 1-type Gauss map. In fact, it is harmonic.

In order to understand the effect of Pb-CuI co-doping on the thermoelectric performance of Bi₂Te₃, n-type Bi₂Te₃ co-doped with x at% CuI and 1/2x at% Pb (x = 0, 0.01, 0.03, 0.05, 0.07, and 0.10) were prepared via high temperature solid state reaction and consolidated using spark plasma sintering. Electron and thermal transport properties, i.e., electrical conductivity, carrier concentration, Hall mobility, Seebeck coefficient, and thermal conductivity, of CuI-Pb co-doped Bi₂Te₃ were measured in the temperature range from 300 K to 523 K and compared to corresponding x% of CuI-doped Bi₂Te₃ and undoped Bi₂Te₃. The addition of a small amount of Pb significantly decreased the carrier concentration, which could be attributed to the holes from Pb atoms, thus the CuI-Pb co-doped samples show a lower electrical conductivity and a higher Seebeck coefficient compared to CuI-doped samples with similar x values. The incorporation of Pb into CuI-doped Bi₂Te₃ rarely changed the power factor because of the trade-off relationship between the electrical conductivity and the Seebeck coefficient. The total thermal conductivity(κ_tot) of co-doped samples (κ_tot ~1.4 W/m∙K at 300 K) is slightly lower than that of 1% CuI-doped Bi₂Te₃ (κ_tot~1.5 W/m∙K at 300 K) and undoped Bi₂Te₃ (κ_tot ~1.6 W/m∙K at 300 K) due to the alloy scattering. The 1% CuI-Pb co-doped Bi₂Te₃ sample shows the highest ZT value of 0.96 at 370 K. All data on electrical and thermal transport properties suggest that the thermoelectric properties of Bi₂Te₃ and its operating temperature can be controlled by co-doping.

Obesity, type 2 diabetes, and different forms of cancers are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches. Diabetes and cancer are among the most frequent and complex diseases and based on epidemiological evidence and study it can be concluded that the patients suffering from diabetes are considered to be significantly at higher risk for a number of cancer types. Both these diseases are among the highly complex and heterogeneous in nature. There are a number of evidences which support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of both these diseases type 2 diabetes and different types of cancers. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic. With so many known challenges, it is critical to understand the relationships and the common shared causes between type 2 diabetes and cancer which is difficult to unravel and understand. Furthermore, the real complexity arises during diagnosis from contended corroborations that specific drug(s) (individually or in combination) during diagnosis process of type 2 diabetes may increase or decrease the cancer risk or affect cancer prognosis. In this review article, we have presented the recent and most updated evidences from the studies where the origin, biological background, correlation between them have been presented or proved. Furthermore, we have summarized the methodological challenges and tasks that are frequently encountered. we have also outlined the physiological links between type 2 diabetes and cancers. Finally, we have presented and summarized the outline of the hallmarks for both these diseases diabetes and cancer.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

In this paper, we study nonlocal problems for a fractional diffusion equation and a degenerate hyperbolic equation with singular coefficients in the lower terms. The uniqueness of the solution to the problem is proved by the method of energy integrals. The existence of a solution is equivalently reduced to the question of the solvability of Volterra integral equations of the second kind and a fractional differential equation. For a particular solution of the proposed problem, its visualization is carried out for various values of the order of the fractional derivative. It is shown that the order of the derivative affects the intensity of the diffusion process (subdiffusion), as well as the shape of the wave front.

The 3 31 nucleotide minihelix tRNA theorem describes evolution of type I and type II tRNAs to the last nucleotide. In databases, type I and type II tRNA V loops (V for variable) were improperly aligned, but alignment based on the theorem is accurate. Type II tRNA V arms were a 3’-acceptor stem (initially CCGCCGC) ligated to a 5’-acceptor stem (initially GCGGCGG). The type II V arm evolved to form a stem-loop-stem. In Archaea, tRNALeu and tRNASer are type II. In Bacteria, tRNALeu, tRNASer and tRNATyr are type II. The positioning of the type II V arm is determined by the number of unpaired bases just 5’ of the Levitt base (Vmax). For Archaea, tRNALeu has 2 unpaired bases, and tRNASer has 1 unpaired base. For Bacteria, tRNATyr has 2 unpaired bases, tRNALeu has 1 unpaired base and tRNASer has 0 unpaired bases. Thus, the number of type II tRNAs is limited by the possible set points of the arm. From analysis of aminoacyl-tRNA synthetase structures, contacts to type II V arms appear to adjust allosteric tension communicated primarily via tRNA to aminoacylating and editing active sites. To enhance allostery, it appears that type II V arm end loop contacts may tend to evolve to V arm stem contacts.

Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and in particular the interferon response form the important first line of defense against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by the viral infection is less prevalent in literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, the influence of antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging viruses belonging to the coronaviruses, alphaviruses and flaviviruses.

We discuss two queueing-inventory systems with catastrophes in the warehouse. Catastrophes occur according to Poisson process and upon arrival of a catastrophe all inventory in the system is instantly destroyed. But consumer customers in the system (in the server or in the buffer) continue still waiting for the replenishment of the stock. The arrivals of the consumer customers follow a Markovian Arrival Process (MAP) and they can be queued in an infinite buffer. Service time of a consumer customer follows a phase-type distribution. The system receives negative customers whose have Poisson flows to service facility and upon arrival of a negative customer one consumer customer is pushed out from the system, if any. One of two replenishment policies can be used in the system: either (s,S) or (s,Q). If upon arrival of the consumer customer, the inventory level is zero, then according to the Bernoulli scheme, this customer is either lost (lost sale scheme) or join the queue (backorder sale scheme). The system is formulated by a four-dimensional continuous-time Markov chain. Steady state distribution is obtained using the matrix-geometric method. A comprehensive numerical study is performed on the performance measures under various replenishment policies. Finally, an optimization study is presented.

Detection of PLA2R and THSD7A among primary membranous glomerulonephritis (MGN) patients transformed the diagnosis, treatment monitoring and prognosis. Anti-PLA2R can be detected in 70-90% of primary MGN patients while anti-THSD7A in 2-3% of anti-PLA2R negative primary MGN patients depending on the technique used. Serum and urine samples are less invasive and non-invasive respectively and can detect the presence of anti-PLA2R and anti-THSD7A with higher sensitivity and specificity, significant in patients’ monitoring and prognosis better than exposing patients to frequent biopsy which is an invasive procedure. Different techniques of detection of PLA2R and THSD7A in patients’ urine and sera were reviewed with the aim of providing newer and alternative techniques. We proposed the use of biomarkers (PLA2R and THSD7A) in making the diagnosis, treatment decision and follow up of patients with primary MGN. We also reviewed other prognostic renal biomarkers like retinol binding protein (RBP) and beta-2 microglobulin in order to detect progression of renal damage for early intervention.

Previously we discovered that among 15 DNA-binding plant secondary metabolites (PSMs) possessing anticancer activity, 11 compounds cause depletion of the linker histones H1.2 and/or H1.4 from chromatin fraction. Chromatin remodeling or multiH1 knocking-down is known to promote the upregulation of repetitive elements, ultimately triggering an interferon response. Herein, using HeLa cells and applying fluorescent reporter assay with flow cytometry and quantitave RT-PCR, we found that among PSMs depleting linker histones, 8 compounds significantly activate type I interferon signaling pathway. Out of these compounds resveratrol, berberine, genistein, delphinidin, naringenin and curcumin also caused LINE1 expression detected by quantitate RT-PCR and by immunefluorescent staining analysis of ORF1 LINE1 and γ-H2AX. Fisetin and quercetin, which also induced linker histone depletion, significantly activated only type I interferon signaling, but not LINE1 expression. Curcumin, sanguinarine and kaempferol, causing depletion of the linker histone H1.4 more intensively respectively to H1.2, activate interferon signaling less intensively without any changes of LINE1 expression. For 4 PSMs, which did not cause linker histone depletion, we did not observe effects of interest. Thus, we have shown for the first time that activation of type I interferon signaling accompanies chromatin remodeling caused by PSMs, and LINE1 expression often impacts this activation.

Recent reports suggest that the clinical course of coronavirus disease 2019 (COVID-19) in previously healthy children is usually milder as compared to adults. However, children with comorbid conditions such as diabetes are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as morbidity and mortality due to COVID-19. Experience in adults with diabetes shows that they are prone to faster metabolic decompensation, develop diabetes-related complications, and have a poor prognosis when hospitalized with COVID-19. Data on children are limited. The aim of this mini-review is to discuss the possible risks to children and adolescents with diabetes during the current pandemic and the special considerations in management in those affected with COVID-19. The challenges for children who develop new-onset type 1 diabetes during the COVID-19 lockdown, especially in accessing healthcare, are also discussed.

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.

LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, conspicuously during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to human, despite their secondary role for proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules, and CLPX on multi-enzyme condensates, near the inner mitochondrial membrane, as first-aid system. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, in mitochondrial RNA granules and nucleoids, and in D-foci-mediated degradation of toxic double-stranded mtRNA / mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination, and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, like peptidases MPP at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.

Parallel-serial (hybrid) manipulators represent robotic systems composed of kinematic chains with parallel and serial structures. These manipulators combine the benefits of both parallel and serial mechanisms, such as increased stiffness, high positioning accuracy, and a large workspace. This study discusses the existing architectures and applications of parallel-serial robots and the methods of their design and analysis. The paper reviews around 500 articles and presents over 150 architectures of manipulators used in machining, medicine, and pick-and-place tasks, humanoids and legged systems, haptic devices, simulators, and other applications, covering both lower mobility and kinematically redundant robots. After that, the paper considers how researchers have developed and analyzed these manipulators. In particular, it examines methods of type synthesis, mobility, kinematic, and dynamic analysis, workspace and singularity determination, performance evaluation, optimal design, control, and calibration. The review concludes with a discussion of current trends in the field of parallel-serial manipulators and potential directions for future studies.

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

Diabetes is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of type 2 diabetic patients with MCI are linked to sarcopenia and/or its criterion remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, BMI, duration of diabetes, hypertension, dyslipidemia, smoking, drinking, eGFR, HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This is the first study to show that slow walking speed is a sole determinant for the presence of MCI in patients with type 2 diabetes. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.

We address weighted composition operators ψCφ from α-Bloch spaces to Bers-type spaces of bounded holomorphic functions on Y, where Y is a generalized Hua domain of the first kind, and obtain some necessary and sufficient conditions for the boundedness and compactness of those operators.

The Ni-laterite deposit at the San Felipe plateau, located 30 km northwest of Camagüey, in cen-tral Cuba, is the best example of a clay-type deposit in the Caribbean region. San Felipe resulted from weathering of mantle peridotites of the Cretaceous Camagüey ophiolites. In this study, a geochemical and mineralogical characterization of two profiles (83 and 84) from the San Felipe deposit has been performed by XRF, ICP-MS, quantitative XRPD, oriented aggregate mount XRD, SEM, FE-SEM and EMPA. Core 83 with a length of 23 m, and drilled in the central part of the plateau, presents a notable concentration of cryptocrystalline quartz fragments and a rather poor content in NiO, averaging 0.87% wt. Core 84, which is 12 m long, and drilled at the border of the plateau, lacks silica fragments and presents a higher NiO content, averaging 1.79 %wt. The smectite structural formulae reveal that they evolve from trioctahedral to dioctahedral towards the top of the laterite profiles. Quantitative XRD analyses indicate that smectite is a dominant Ni bearing phase, accompanied by serpentine and minor chlorite. Serpentine, as smectite, is en-riched in the less soluble elements Fe3+, Al and Ni towards the top of the profiles. Core 83 seems to have been affected by collapses, replenishments, whereas core 84 may have remained undis-turbed.

Research on climacteric syndrome among middle-aged men remains scant than the research among women. Research is also scant on climacteric syndrome among older adults living alone, particularly men, who are more vulnerable than such females. This cross-sectional study investigated whether the prevalence of climacteric syndrome is associated with the type of household middle-aged men live in and identified the determinants of climacteric syndrome based on the household type. Six hundred middle-aged men living in multi-person households and 600 living alone were surveyed about general characteristics, diet-related factors, and climacteric syndrome. Data were analyzed using Pearson’s chi-squared test, Fisher’s exact test, and logistic regression. The risk of climacteric syndrome in single-person households was found to be 1.6 times higher than that among in multi-person households (p = 0.006). In multi-person households, income and breakfast frequency predicted climacteric syndrome (p < 0.05), while age, breakfast frequency, dinner frequency, and weekly eating out frequency predicted climacteric syndrome in single-person households (p < 0.05). Thus, dietary factors are more closely linked to the prevalence of climacteric syndrome in single-person households than in multi-person households. This highlights the need for climacteric syndrome interventions for middle-aged men whose health concerns may persist into older adulthood.

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.

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

Klippel-Feil disease is a condition characterized by a defect in the spine, consisting in the fusion or non-separation of two or more vertebrae of the cervical tract. It usually affects 1 every 50.000 newborns, and the pathogenesis remains unknown to date, although the role of certain genes deputed in segmentation processes is being studied. A single case of gene Myosin Heavy Chain 3 (MYH3) mutation is described by researchers. Affected patients are often characterized by a relatively short neck and, therefore, poor mobility, a low hairline and obesity and may have other health problems of different nature. The frequent presence of comorbidities worsens the quality of life of these young patients. The following case describes the synergistic effect of Incobotulinum toxin type A and physiotherapy in a small patient with MYH3 mutation-related Klippel-Feil Syndrome (KFS) complicated by bilateral paraplegia, to improve the spasticity condition of the lower limbs. To assess improvements over time, the patient underwent rating scales to determine spasticity (Modified Ashworth Scale: MAS), the neck’s range of motion (ROM), and muscle tone by using MyotonProÒ. Specifically, measurements were taken on the day of the first medical examination (T0), the month after the injection and the startup of therapeutic exercise (T1), at three months (T2), and then once a month for a total of 6 months (T3, T4 and T5). This therapeutic approach led to entirely satisfactory results with the child’s well-being, prolonged until the sixth month and with a total absence of any side effects.

The Upper Hunter Valley is a major coal mining area in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. The early part of this study identified two air quality subregions in the valley. This paper aims to provide a holistic summarisation of the relationships between elevated PM10 pollution in two subregions and the local- and synoptic-scale meteorological conditions for spring and summer, when PM10 pollution is relatively high. A catalogue of twelve synoptic types and a set of six local meteorological patterns have been quantitatively derived and linked to each other using the self-organising map (SOM) technique. The complex meteorology-air pollution relationships have been visualised/interpretated on the SOM planes for two representative locations. It was found that the influence of local meteorological patterns differed significantly for mean PM10 levels vs the occurrence of elevated pollution events and between air quality subregions. In contrast, synoptic types showed generally similar relationships with mean vs elevated PM10 pollution in the valley. Two local meteorological patterns, the hot-dry-northwesterly wind conditions and the hot-dry-calm conditions, were found most PM10 pollution conducive in the valley when combined with a set of synoptic counterparts. These synoptic types are featured with the influence of eastward migrating continental high pressure system and westerly troughs, or a ridge extending northwest towards coastal northern NSW or southern Queensland from the Tasman Sea. The method and results can be used in air quality research for other locations of NSW, or similar regions elsewhere.

We have investigated the interfacial dislocations in InxGa1–xN/GaN (0 ≤ x ≤ 0.20) heterostructures using diffraction contrast analysis in a transmission electron microscopy. The analysis indicate that the structural properties of the interface dislocations depend on the indium composition. For lower indium composition up to x = 0.09, we observed that the screw-type dislocations and dislocation half loops occurred at the interface even though the former do not contributes toward elastic relaxation of the misfit strain in the InGaN layer. With the increase of indium composition (0.13 ≤ x ≤ 0.17), in addition to the network of screw-type dislocations, edge-type misfit dislocations were found generated with their density gradually increasing. For higher indium composition (0.18 ≤ x ≤ 0.20), all the interfacial dislocations are transformed into a network of straight misfit dislocations along the <10-10> directions leading to partially relaxation of the InGaN epilayer. The presence of dislocation half loops may be explained by slip on the basal plane, the formation of misfit dislocations are attributed to punch-out mechanism.

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

The relentless challenges posed by the COVID-19 pandemic have placed immense pressure on densely populated regions, such as Hong Kong, particularly in the context of an aging population. The burgeoning demand for healthcare services has necessitated the optimization of resource al-location within healthcare systems. This research presents an innovative analytical queueing model specifically tailored to address the intricate gridlock dynamics prevalent in healthcare systems, with a focused application in the challenging landscape of COVID-19 management. Hong Kong, like numerous other regions, has experienced a demo-graphic transition leading to heightened healthcare demands. Traditional methodologies for scrutinizing gridlock issues in healthcare settings, including simulation models, often prove suboptimal within the context of sophisticated optimization frameworks. This study, however, delves into analytical queueing models, offering a more efficient and effective approach. These models have been underexplored, primarily due to the intricacies involved in modeling gridlock propagation within restricted capacity, a critical concern magnified by the COVID-19 pandemic. The novel Queueing Model introduced in this research incorporates the maintenance of queue capacities and topological aspects as exogenous parameters, rendering it exceptionally adaptable for diverse gridlock-related applications. This adaptability is especially pertinent to healthcare management during the COVID-19 crisis. The model meticulously integrates the concept of gridlock, furnishing a comprehensive comprehension of its origins and repercussions. Validation of this model involves rigorous comparison with established methodologies, exact results, and simulation data, consistently high-lighting its versatility and precision. By applying the model to healthcare management, we scrutinize the dynamics of patient flow within a Hong Kong hospital, placing specific emphasis on the critical issue of bed blockage, further exacerbated by the COVID-19 pandemic. The model's gridlock decomposition unearths the nuanced impact of bed blockage on distinct hospital units, addressing the imperative requirement for quantifying in-patient bed blockage within healthcare systems during a pandemic.

A mass mortality event of Asian seabass Lates calcarifer juveniles occurred in Zhuhai, the main Asian seabass cultured area in mainland China. The fish samples were pooled for pathogen identification and both high viral loads of ISKNV and NNV were detected by real-time microfluidic quantitative PCR. Immunohistochemistry and immunofluorescence showed that strong ISKNV signals were examined in spleen and liver, while strong NNV signals were detected in brain and eye. The multi-tissue homogenates were inoculated into MFF-1 cell and SSN-1 cell, respectively. After several viral passages, both ISKNV and NNV were purely isolated from each other, and designated as ASB-ISKNV-23 and ASB-NNV-23, respectively. The whole genome sequences of ASB-ISKNV-23 and ASB-NNV-23 were determined and annotated. The result showed that ASB-ISKNV-23 and ASB-NNV-23 are composed of 112,236 bp and 4,538 bp, respectively. Phylogeny analysis showed that ASB-ISKNV-23 belongs to ISKNV-II sub-genotype and ASB-NNV-23 belongs to RGNNV genotype. Collectedly, coinfection of ISKNV-II and RGNNV were firstly documented in mass mortality of Asian seabass in mainland China. Importantly, both ISKNV-II and RGNNV were purely isolated using two different permissive cell lines. Our study provides useful information for better understanding the complex pathogenesis regarding the coinfection with ISKNV and NNV in farmed fish.

Mountain summit in Madagascar have generally a specific habitat and that figure home a local endemicity of herpetofauna. Mantidactylus pauliani, a typically aquatic and critically endangered amphibian from Ankaratra Mountain, is among of them. This species inhabits high elevation with restricted distribution range. Our study highlights here a new data of this species and its viability with environmental change. So that, we carried out annual monitoring from 2018 to 2021. Nine fixed transects of 100 m were done along the streams between 1762 and 2378 m a.s.l. We followed the herpetofaunal standard technique for collecting data (systematic ecological niche searching and direct observation), and data analysis was performed using χ² tests and Fac-tor Correspondence Analysis. Here we present the new ecological data of M. pauliani. This spe-cies home between 1900 - 2378 m a.s.l. within the humid forest and savannah habitat. We noticed also a fluctuation in population size and migration to the upper throughout the years across the season, and the stream quality and volume of water variation. This habitat change makes it vul-nerable and the annual bushfire surrounding plays a negative impact. Knowledge and under-standing of its ecological guilds is needed for running and updating conservation activities

Understanding the structural intricacies of RNA molecules is essential for deciphering numerous biological processes. Traditionally, scientists have relied on experimental methods to gain insights and draw conclusions. However, the recent advent of advanced computational techniques has significantly accelerated and refined the accuracy of research results in several areas. A particularly challenging aspect of RNA analysis is the prediction of its secondary structure, which is crucial for elucidating its functional role in biological systems. This paper deals with the prediction of pseudoknots in RNA, focusing on two types of pseudoknots: K-type and M-type pseudoknots. Pseudoknots are complex RNA formations in which nucleotides in a loop form base pairs with nucleotides outside the loop and thus contribute to essential biological functions. Accurate prediction of these structures is crucial for understanding RNA dynamics and interactions. Building on our previous work in which we developed a framework for the recognition of H- and L-type pseudoknots, an extended grammar-based framework tailored to the prediction of K- and M-type pseudoknots is proposed. This approach uses syntactic pattern recognition techniques and provides a systematic method to identify and characterize these complex RNA structures. Our framework uses context-free grammars (CFGs) to model RNA sequences and predict the occurrence of pseudoknots. By formulating specific grammatical rules for type K and type M pseudoknots, we enable efficient parsing of RNA sequences to recognize potential pseudoknot configurations. This method ensures an exhaustive exploration of possible pseudoknot structures within a reasonable time frame. In addition, the proposed method incorporates essential concepts of biology, such as base pairing optimization and free energy reduction, to improve the accuracy of pseudoknot prediction. These principles are crucial to ensure that the predicted structures are biologically plausible. By embedding these principles into our grammar-based framework, we aim to predict RNA conformations that are both theoretically sound and biologically relevant.

Viral infections leading to inflammation have been implicated in several common diseases such as Alzheimer’s disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus 1 (HSV-1) has been reported to be associated with AD. We sought to identify the transcriptomic changes due to HSV-1 infection and anti-viral drug (acyclovir, ACV) treatment of HSV-1 infection in dissoci-ated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) to gain potential biological insights into the relevance of HSV-1-induced inflammation in AD and T1D. We observed that differentially expressed genes (DEGs) in HSV-1-infected sc-islets were enriched for genes associated with several autoimmune diseases, most significantly T1D but also rheumatoid arthritis, psoriasis, Crohn’s disease, and multiple sclerosis, whereas DEGs in HSV-1-infected dcOrgs were exclusively enriched for genes associated with AD. ACV treatment of sc-islets did not rescue transcript expression of autoimmune disease-associated genes. Finally, we identified gene ontology categories that were enriched for DEGs that were in common across, or unique to, viral treatment of dcOrgs and sc-islets, such as categories involved in the transferase complex, mitochondrial and autophagy function. Collectively, this studies pro-vide insight to the molecular effects of inflammation in AD and T1D.

Among the many Lysosomal Storage Disorders (LSDs) that would benefit from the establish-ment of novel cell models, either patient-derived or genetically engineered, is Mucopolysaccha-ridosis type II (MPS II). In fact, even though a specific therapeutic approach does exist for this disorder (Enzyme Replacement Therapy, ERT, with recombinant human IDS) and haematopoiet-ic stem cell transplantation (HSCT) may also hold promise whenever the disorder is diagnosed soon enough, both approaches have their own drawbacks. Here we present our results on the establishment and characterization of two MPS II pa-tient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population is isolated from LSD patient samples obtained from the oral cavity. Taking into account our results on the molecular and biochemical characterization of those cells and our first insights on their subcellular MPS phenotype, we consider these cells will be a valuable tool for both pathophysiological assessments and drugs screenings. Ultimately, we believe patient-derived dental pulp stem cells (DPSC) may represent a feasible alternative to induced pluripotent stem cells (iPSC) in many labs with standard cell culture con-ditions and limited (human and economic) resources.

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is an exceedingly rare genetic disorder characterized by the inability to perceive pain, inability to sweat, and various neurological and orthopedic complications. This is a case report of a 3-year-old female patient diagnosed with CIPA syndrome who presented repeatedly to Children’s Clinical University Hospital (CCUH) in Riga, Latvia with severe orthopedic manifestations. The patient had repeated fractures, several surgeries, and extensive spread of the disease throughout the left leg, which caused significant functional impairment and decreased quality of life. Despite aggressive orthopedic interventions including surgical interventions and physical therapy, the patient's condition remained challenging to manage due to the inherent limitations posed by the insensitivity to pain. The council of doctors discussed the patient's condition and changes, deciding that reconstructive surgery is not feasible, and amputation is recommended. Through this case report, we aim to highlight the unique orthopedic challenges encountered in the management of CIPA patients, emphasizing the importance of a multidisciplinary approach involving orthopedic surgeons, pediatricians, geneticists, and physiotherapists. Additionally, we discuss the need for further research to elucidate optimal management strategies and improve outcomes in this rare and complex patient population.

Edaravone is a mitochondrially targeted drug with a suggested capability to modify the course of diverse neurological diseases. Nevertheless, edaravone has not been tested yet in the context of spinocerebellar ataxia 1 (SCA1), an incurable neurodegenerative disease characterized mainly by cerebellar disorder with a strong contribution of inflammation and mitochondrial dysfunction. This study aimed to address this gap, exploring the potential of edaravone to slow down SCA1 progression in a mouse knock-in SCA1 model. SCA1154Q/2Q and healthy SCA12Q/2Q mice were getting either edaravone or saline daily for more than 13 weeks. The functional impairments were assessed via a wide spectrum of behavioral assays reflecting motor and cognitive deficits and behavioral abnormalities. Moreover, we used high-resolution respirometry to explore mitochondrial function, and immunohistochemical and biochemical tools to assess the magnitude of neurodegeneration, inflammation and neuroplasticity. Data were analyzed using (hierarchical) Bayesian regression models combined with the methods of multivariate statistics. Our analysis pointed out various previously documented neurological and behavioral deficits of SCA1 mice. However, we did not detect any plausible therapeutic effect of edaravone on either behavioral dysfunctions or other disease hallmarks in SCA1 mice. Thus, our results did not provide support for the therapeutic potential of edaravone in SCA1.

Abstract Sodium glucose cotransporter type 2 inhibitors are a new class of drugs acting on cardiovascular system, renal and metabolism in a multiple way. Indeed, even their principal action is on the transporter of sodium and glucose in the convoluted distal tubule, they have multiple actions as antifibrotic and endothelial protective action. Their principal mechanism consist in the loss of sodium and glucose. Therefore, they have effect on blood pressure and glucose metabolism. In a first period their use has been in the diabetic general population, later on some studies documented their activity in non-diabetic general population, in heart failure in chronic kidney disease. Only in recent years several small studies documented their efficacy in diabetic and non-diabetic kidney transplant patients, larger studies are few and very recent and open new ways for these drugs

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.

(1) Background: Little research is done on the link of diabetic kidney disease (DKD) progression and diabetic gastroenteropathy in type 1 diabetes (T1D). (2) Methods. We performed a cross-sectional study with 100 T1D patients, 27 of them had progressive DKD, defined as estimated glomerular filtration rate (eGFR) decline≥3 ml/min/year or increased albuminuria stage over the mean follow-up time of 5.89±1.73 years. Newly developed score with 17 questions on gastrointestinal (GI) symptoms was used. Faecal calprotectin was measured by ELISA. Lower GI endoscopies were performed in 21 patients. (3) Results: Gastrointestinal symptom score demonstrated high reliability (Cronbach's α=0.78). Patients with progressive DKD had higher GI symptom scores compared to those with stable DKD (p=0.019). The former group demonstrated more frequent bowel movement disorders (p=0.04). The scores correlated negatively with eGFR (r = -0.335; p = 0.001), positively with albuminuria (r=0.245; p=0.015), Hba1c (r=0.305, p=0.002), diabetes duration (r=0.251, p=0.012). Faecal calprotectin levels did not differ between DKD groups significantly. The most commonly reported histopathological findings of enteric mucosa were infiltration with eosinophils, lymphocytes, plasmacytes, presence of lymphoid follicles and lymphoid aggregates. Conclusion: progression of DKD positively correlated with gastrointestinal symptoms, but more research is needed to clarify the causal relationships of the gut-kidney axis in T1D.

The objective of this study is to assess the hepatic/renal and splenic/renal echointensity ratios in ultrasonography in patients with and without diabetic nephropathy. This retrospective study included patients with diabetes mellitus who underwent ultrasound examinations at our hospital between January 2023 and May 2023. Ultrasound examinations done with renal cortical echogenicity and cortico-medullary differentiation by using B-mode ultrasonography. The hepatic/renal and splenic/renal echo intensity ratios were compared among study groups (diabetic patients with diabetic nephropathy and without nephropathy). The diabetic nephropathy group exhibited significantly higher right renal echointensity and left renal echointensity compared to the non-nephropathic group. Additionally, the splenic/renal echointensity ratio and hepatic/renal echointensity ratio were significantly lower in the diabetic nephropathy group. Urinary microalbumin levels was significantly correlated with Right renal echointensity (r=0.65, p&lt;0.001) and Left renal echointensity (r=0.69, p&lt;0.001). There was also a significant inverse correlation between urinary albumin and splenic/renal echointensity ratio (r=-0.58, p&lt;0.001). Ultrasonography, specifically the assessment of hepatic/renal and splenic/renal echointensity ratios, shows promise as a non-invasive and cost-effective method for evaluating morphological changes in the kidneys in patients with diabetic nephropathy. These findings suggest that ultrasonography can be a valuable tool for monitoring the progression of diabetic nephropathy and contributing to its early detection and management.

This review aims to show, by an analysis of the literature on the topic, that hyperinsulinemia associated with insulin resistance is a multiple risk factor for type 2 diabetes, cardiovascular diseases, cellular senescence and cancer, and neurodegenerative diseases. This condition is progressively increasing in developed and developing countries, and its prevalence has now exceeded 50% of the general population. Since it is asymptomatic or poorly symptomatic, it can last for many years before manifesting itself in the form of type 2 diabetes mellitus, cardiovascular disease, neoplasm, cognitive impairment or dementia, therefore determining enormous social and health care costs. For these reasons, we strongly believe that a screening plan for this pathology should be implemented, in order to identify affected subjects and promptly start them on preventive treatment.

Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are comorbidities that result from the sharing of common genes. The molecular background of comorbidities can provide clues for the development of treatment and management strategies. Here, the common genes involved in the development of the two diseases and in memory and cognitive function are reviewed. Network clustering based on protein-protein interaction networks identified tightly connected gene clusters that have an impact on memory and cognition among the comorbidity genes of AD and T2DM. Genes with functional implications were intensively reviewed, and relevant evidence was summarized. Gene information will be useful in the discovery of biomarkers and the identification of therapeutic targets for AD.

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.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cognitive dysfunction, memory decline, and behavioral disturbance, and pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. Although various hypotheses have been proposed to explain the pathogenesis of AD, including the amyloid beta hypothesis, oxidative stress hypothesis, and abnormal phosphorylation of tau proteins, the exact pathogenic mechanisms underlying AD remain largely undefined. Furthermore, effective curative treatments are very limited. Epidemiologic studies provide convincing evidence for a significant association between type 2 diabetes and AD. Here, we showed energy metabolism using glucose, lactate and ketone bodies and lipids as energy substrates in normal brain, and changes in such energy metabolism due to type 2 diabetes. We also showed the influences of such altered energy metabolism due to type 2 diabetes on the pathology of AD. Furthermore, we comprehensively searched the risk factors related with type 2 diabetes for AD, and showed possible therapeutic interventions based on considering risk factors and altered brain energy metabolism due to type 2 diabetes for the development of AD.

In order to further control the equivalent circulating density,a new type of annular pres-sure-reducing downhole tool for high temperature and high pressure wells-liquid-absorbing ECD tool is designed.Through this tool,the bottom hole pressure of the equivalent circulating drilling fluid can be close to its hydrostatic pres-sure,therebyachieving a deeper drilling depth.The tool is mainly composed of screw mo-tor,vortex blade,annular seal,universal joint and drill string.Its working principle is mainly to use the liquid absorption effect of the tool and the hydraulic energy of the circu-lating fluid extracted by the screw motor to convert it into mechanical energy,and to gen-erate suction force to improve the flow energy of the drilling fluid in the bottom hole an-nulusand reduce the equivalent circulation density.Based on ANSYS-FLUENT analysis andsimulation,the change of pressure drop characteristics under different drilling fluid density,displacement and tool size was simulated.The simulation results show that thedepressurization effect is 1.0MPa when the drilling fluid density is 1.2g/cm3. When the drilling fluid density is 1.5g/cm3,the depressurization is about 1.7MPa,and when thedrill-ing fluid density is 1.8g/cm3,the depressurization is about 1.9MPa.When the drilling fluid density is 2.0g/cm3,the pressure drop is about 2.3MPa.When the flow rate is from 1500-2500L/min,the maximum pressure can be reduced by 2.3MPa.When the viscosity is 40mPa•S and 60mPa•S,the pressure drop almost does not change.The increase of viscosi-ty has little effect on the pressure drop,and it is mainly affected by the flow rate under equal displacement.

Type-2 diabetes mellitus is recognized as a serious public health concern with a considerable impact on human life, long-term health expenditures, and substantial health losses. In this context, the use of dietary polyphenols to prevent and manage Type 2 diabetes mellitus is widely documented. These dietary compounds exert their beneficial effects by several actions, including the protection of pancreatic islet β-cell, the antioxidant capacities of these molecules, their effects on insulin secretion and actions, the regulation of intestinal microbiota, and their contribution to ameliorating diabetic complications, particularly those of vascular origin. In the present review, we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type-2 diabetes patients.

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.

In this paper, a new class of q-Hermite based Frobenius type Eulerian polynomials is introduced by means of generating function and series representation. Several fundamental formulas and recurrence relations for these polynomials are derived via different generating methods. Furthermore, diverse correlations including the q-Apostol-Bernoulli polynomials, the q-Apostol-Euler poynoomials, the q-Apostol-Genocchi polynomials and the q-Stirling numbers of the second kind are also established by means of the their generating functions.

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.

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.

Nine components (C1-C9) were isolated from chloroform fraction of fractionated methanol extracts of Vernonia amygdalina leaves (FMEVA) by column chromatography. All the components C1 to C9 were purified and screened for hypoglycaemic activities in type-2 diabetic rats. The most potent hypoglycaemic component was elucidated on the basis of extensive spectroscopic (1D-, 2D-NMR, GC-MS, FTIR) data analysis. The Component C5 was found to be the most potent hypoglycaemic in reducing blood glucose by 12.55 ± 3.55% at 4 h post-oral administration, when compared to the positive (18.07 ± 1.20%) and negative (-1.99 ± 0.43%) controls. The spectroscopic data analysis reveals that the isolated compound has a structure consistent with 11β,13-dihydrovernolide. The isolated compound is part of the hypoglycaemic components present in V. amygdalina leaves that is responsible for the anti-diabetic activities. Further research is needed in the development of this compound or its derivatives for pharmaceutical use.

Escherichia coli is an indicator microorganism in One Health antibiotic resistance surveillance programmes. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harboured a richer diversity of antibiotic resistance genes, as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%; 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169) were detected at low frequencies. Sequence type complex (STc) 10 were the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2 to HC200 were observed. In conclusion, even though the isolates shared a spatio-temporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles, and cgMLST and HC according to the source of isolation.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

Alexithymia as the inability to describe one's own feelings, is being increasingly researched. According to contemporary psychodynamic theories, negative emotions cannot be adequately named and externalized, but remain trapped in the body. Recent research shows the connection of alexithymia with numerous somatic diseases. Diabetes mellitus type 2 and obesity represent a great challenge in treatment, and the psychological profiles in these diseases are being studied more and more often. Therefore, alexithymia enters the focus of some research as one that could play a significant role namely in these diseases as the factor that makes a difference. The aim of this paper is a review of the literature with the purpose of understanding the current knowledge about the interconnection between alexithymia, obesity and type 2 diabetes mellitus.

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.

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.

More than half of the states in the U.S. report that over 30% of adults are obese. Obesity increases the risk of many chronic diseases, including type 2 diabetes, hypertension, cardiovascular disease, and can even reduce one’s lifespan. Similarly, the prevalence of type 2 diabetes follows a comparable trend. As a result, researchers are striving to find solutions to reduce obesity rates, with a particular focus on gut health, which has been previously linked to both obesity and type 2 diabetes. Recent studies suggest that Akkermansia muciniphila(AKK) may have a positive probiotic effect on preventing the onset of type 2 diabetes and obesity. We conducted a quantitative meta-analysis of 15 qualified animal studies investigating the effects of AKK administration as a probiotic. The statistical analyses showed that AKK administration significantly reduced body weight gain by 10.4% and fasting blood glucose by 21.2%, while also significantly improving glucose tolerance by 22.1% and increasing blood insulin levels by 26.9%. However, our analysis revealed substantial heterogeneity between the control and experimental groups across all subgroups. Overall, AKK appears to be effective at reducing the onset of type 2 diabetes and diet-induced obesity. Long-term studies with larger sample sizes are needed to confirm these beneficial effects, as the current animal studies were of short duration (less than 20 weeks).

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.

Background: The number of people with type 2 diabetes is increasing daily, and therefore effective therapy is needed to successfully regulate glycemia and reduce the risk of associated complications. Recently, an oral formulation of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has become available. Therefore, the aim of our study was to compare the effectiveness of the new oral formulation and the existing injectable formulation of semaglutide in terms of glycemic and body weight control in a real-world setting. Patients and methods: This was a single-center retrospective observational study conducted at the Rijeka Clinical Hospital Centre. A total of 106 patients with inadequately controlled type 2 diabetes (HbA1 ≥ 7%) on different oral or basal insulin supported oral therapy were recruited from the diabetes outpatient clinic, and data from electronic medical records were retrospectively collected and analyzed from May 2021 to November 2022. All subjects were GLP-1 RA naive and consequently prescribed 0.5 or 1.0 mg once weekly injectable semaglutide (IS) or 7 mg or 14 mg once daily oral semaglutide (OS) for at least 6 months. Glycated hemoglo-bin (HbA1c), body weight, and body mass index (BMI) were assessed prior to semaglutide administration and after a 6-month follow-up period. The primary endpoint was the change from baseline in HbA1c, and sec-ondary endpoints were the change in body weight and the proportion of participants with a reduction in body weight of ≥ 5% and ≥ 10%, respectively, 6 months after the initiation of semaglutide treatment. Results: At 6-month follow-up, no significant difference was observed between the two formulations in terms of HbA1c reduction (IS -1.1% vs OS -1.4%, p=0.126) and weight loss (IS -6.50 kg vs OS -5.90 kg, p=0.714). Exactly the same proportion of participants in both groups achieved a weight loss of ≥ 5% (56.7%, n=30). A weight loss ≥ 10% was observed in 20.7% (n=11) of participants administered IS and 15.1% (n=8) of participants adminis-tered OS, respectively (p=0.454). Conclusion: In a real-world setting, oral semaglutide as add-on therapy to ongoing antihyperglycemic treatment in patients with inadequately controlled type 2 diabetes who had not previously received GLP-1 RA demonstrated the same effectiveness as injectable semaglutide in terms of gly-cemic control and weight loss after 6 months of treatment.

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.

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.

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.

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.

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.

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.

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.