β3-Adrenoceptors mediate several functions in rodents that could be beneficial for the treatment of obesity and type 2 diabetes. This includes promotion of insulin release from the pancreas, of cellular glucose uptake, of lipolysis, and of thermogenesis in brown adipose tissue. In combination, they lead to a reduction of body weight in several rodent models including ob/ob mice and Zucker diabetic fatty rats. These findings stimulated drug development programs in various pharmaceutical companies, and at least nine β3-adrenoceptor agonists have been tested in clinical trials. However, all of these projects were discontinued due to lack of clinically relevant changes of body weight. Following a concise historical account of discoveries leading to such drug development programs we discuss species differences that explain why β3-adrenoceptors are not a meaningful drug target for the treatment of obesity and type 2 diabetes in humans.

The inaugural AIDS Program in Brazil was established in São Paulo in 1983, with the Instituto Adolfo Lutz appointed for laboratory assistance. Subsequently, research on HIV infections and HIV/HTLV (HIV/HTLV-1 and HIV/HTLV-2) co-infections were conducted. This narrative review focuses on studies from the Immunology Department (1983–2017) that significantly influenced AIDS diagnosis or provided epidemiological data such as prevalence rates, sex, age, and risk factors. Ten studies, encompassing over 8,000 individuals, are discussed. During 1983–1985, nearly all AIDS cases were attributed to homosexual/bisexual men aged 31 years old. Subsequently, heterosexual men and women emerged as risk groups owing to intravenous drug use (IDU) and/or unprotected sexual intercourse with AIDS patients or multiple partners per year. From 1985 onwards, vertical transmission led to child infections. HIV/HTLV co-infection rates decreased over time, initially associated with male IDU, and in the 2010s, with females, IDU, and individuals aged >40 years. Trends in HIV and HIV/HTLV co-infections among younger men and women (<30 years of age) were observed from 2015–2017. The changing characteristics and risk groups for HIV and HIV/HTLV co-infections over the years underscore the necessity for ongoing public policies to prevent retrovirus transmission, particularly among adolescents and young adults.

Satellite-based data classification performance remains a challenge for research community in the field of land use/land cover mapping. Here we investigated supervised per-pixel classifications performance under different scenarios, based on single and seasonal multispectral data combi-nations of different sensors (Landsat-8 OLI and Sentinel-2 MSI). In case of Landsat, seasonal spectral indices (EVI and NDMI) were included. A typical Mediterranean watershed with a complex landscape comprised of various forest and wetland ecosystems, crops, artificial surfaces, and lake water was selected to test our approach. All available geospatial data from national databases (Forest Map, LPIS, Natura2000 habitats, cadastral parcels, etc.) are used as ancillary data for clas-sification training and validation. We examined and compared the performance of ML, RF, KNN and SVM classifiers under different scenarios for land use/land cover mapping, according to Copernicus Land Cover (CLC2018) nomenclature. In total, eight land use/land cover classes were identified in Landsat-8 OLI and nine in Sentinel-2a MSI for an acceptable overall accuracy over 85%. A comparison of the overall classification accuracies shows that Sentinel-2a overall accuracy was slightly higher than Landsat-8 (96.68% vs. 93.02%). Respectively, the best-performed algorithm was ML in Sentinel-2 while in Landsat-8 was KNN. However, machine-learning algorithms have similar results regardless the type of sensor. We concluded that best classification performances achieved using seasonal multispectral data. Future research should be oriented towards inte-grating time-series multispectral data of different sensors and geospatial ancillary data for land use/land cover mapping.

Background. The type-2 sodium-glucose cotransporters inhibitors (SGLT2i) are a new relevant therapeutic option for patients affected by chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single center, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. Methods. We evaluated the consecutive patients affected by chronic heart failure (CHF) since January 2022. At baseline clinical visit the therapy taken by the patients as well as that prescribed were accurately collected. During a 6-12 month follow-up the the changes in concomitant therapy were analyzed. Results. At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i, 13 with HFrEF, 2 with CHF with mild reduced (HFmrEF) and 2 with preserved ejection fraction (HFpEF). After baseline evaluation, SGLT2i were prescribed to 220 (63%) of all the patients enrolled, among whom 178 (84%) of HFrEF patients, 25 (42%) of HFmrEF and 17 (22%) of HFpEF. After follow-up, SGLT2i therapy was highly tolerated and it was associated with a significant increased prescription of sacubitril/valsartan and a reduced use of diuretics. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. Conclusions. In this single center “real world” study, SGLT2i were prescribed in HFrEF patients most of all already in therapy with the other classes of drugs currently recommended for their treatment. Moreover, a further optimization in prescribed ther-apy was observed during a short term follow-up. These data further support the use of this thera-peutic approach in routine clinical practice.

The study aimed to estimate the prevalence and association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with Type 2 Diabetes Mellitus (T2DM). According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged: 50–80 years) were divided into three groups: Non-sarcopenia (n = 38), Possible Sarcopenia (n = 31, 28.2%), and Sarcopenia (n = 41, 37.3%). Blood samples were collected and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D3 levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, there was a significant association between sarcopenia with BMI, body fat percentage (BF%), and dietary energy and protein intake. Low serum vitamin D3 is a significant risk factor for possible sarcopenia.

Abstract: (1) Background: The relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) is bidirectional: NAFLD increases the risk of T2DM, and T2DM promotes the progression of the disease to non-alcoholic steatohepatitis (NASH). (2) Material and methods: We performed a retrospective, open study that included 59 patients with NAFLD and T2DM who were distributed into two groups: 44 (74.57%) patients were diagnosed with HS and 15 (25.42%) patients were diagnosed with NASH. (3) Results: Among the non-specific inflammatory biomarkers statistically significant (p=0.003 respectively p=0.03) higher mean values were recorded in patients with NASH and T2DM in the case of ferritin and the neutrophil percentage-to-albumin ratio (NPAR). (4) Conclusions: Consequently, it is essential to identify alternative "surrogate" markers for the inflammatory process, particularly in individuals with diabetes, as it is a key characteristic of NASH. This need arises from the desire to avoid the risks associated with liver biopsy procedures and to prevent the unpredictable and unfavorable progression of NAFLD in patients with T2DM.

3,4-Dihydroquinolin-2(1H)-ones represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild and efficient synthetic methods has been widely concerned by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of dihydroquinoline-2(1H)-ones via catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization and photochemical cyclization reactions. Besides, the substrate scope and mechanistic details are also discussed. This paper will provide a useful reference for the development of diverse synthesis methodologies of 3,4-dihydroquinolin-2(1H)-ones.

Personalized recommendation is an important part of ecommerce platform. In the recommendation system, the neural network is used to enhance collaborative filtering to accurately capture user preferences, so as to obtain better recommendation performance. Traditional recommendation methods focused on the results of a single user behavior, ignoring the modeling of multiple interactive behaviors of users, such as click, add to cart and purchase. Although many studies had also focused on Multi-Behavior modeling, two important challenges remained. 1)Since multiple behavioral context information was ignored, it was still a challenge to identify the multimodal relationships of behaviors. 2) Surveillance signals were still sparse. In order to solve this problem, this paper proposes Two-path Multi-behavior Sequence Modeling(TP_MB). First, a two-path learning strategy is introduced to maximize the multiple interaction information of user items learned by the two paths, which effectively enhances the robustness of the model. Second, a multi-behavior dependent encoder is designed. Contextual information is obtained through behavior dependencies in the interaction of different user. In addition, three contrastive learning methods are designed, which not only obtain additional auxiliary supervision signals, but also alleviate the problem of sparse supervision signals. Extensive experiments on two real datasets demonstrate that our method outperforms state-of-the-art multi-behavior recommendation methods.

Type 2 diabetes mellitus may be complicated with chronic complications including diabetic neuropathy (DN). Timely diagnosis is crucial in treatment and maybe reversal of this complication. C reactive protein to albumin ratio (CAR) is considered as a marker of inflammation in various diseases that characterized with acute or chronic inflammation. Since diabetic neuropathy and type 2 diabetes mellitus are also associated with chronic, low grade inflammation, we aimed to study CAR levels of type 2 diabetic subjects with diabetic neuropathy and to compare to those in patients without diabetic neuropathy. Type 2 diabetic patients presented to our institutional outpatient clinics were divided into two according to the presence of DN. Subjects with DN were listed as DN group and others were as non-DN group. Characteristics and laboratory data, including CAR, in DN and non-DN groups were compared. Median CAR of the DN and non-DN groups were 2,19 (0,2-49)% and 0,56 (0,02-5,8)%, respectively (p<0.001). CAR was significantly and positively correlated with age (r=0.15, p<0.001), weight (r=0.19, p=0.01), BMI (r=0.11, p=0.03), waist circumference (r=0.10, p=0.046), fasting plasma glucose (r=0.14, p=0.004), serum creatinine (r=0.25, p<0.001), triglyceride (r=0.17, p<0.001), and LDL-cholesterol (r=0.13, p=0.001) levels. Moreover, CAR was inversely correlated with eGFR levels (r=-0.16, p<0.001). The sensitivity and specificity of CAR (when higher than 1,02%) in predicting diabetic neuropathy were 78% and 73%, respectively (AUC: 0.84, p<0.001, 95% CI: 0,82-0,87). Moreover, high CAR level was an independent risk factor of diabetic neuropathy (p<0.001, OR: 1.34, 95% CI: 0.48-1.62). In conclusion, elevated CAR levels could be considered as a marker of diabetic neuropathy.

Lodging is a common problem in maize production that seriously impacts yield, quality, and the capacity for mechanical harvesting. Evaluation of site-specific lodging risks requires establishment of a method for multi-year monitoring. In this study, spectral images collected by the Sentinel-2 satellite were processed to obtain three types of data: gray-level co-occurrence matrix texture (GLCM), vegetation indices (VIs), and spectral reflectance (SR). Lodging classification models were then established with Random Forest (RF) using each of the three data types separately (the GLCM, VI, and SR models) and in combination (SR+VI model, SR+GLCM model, VI+GLCM mod-el, and SR+VI+GLCM model). By gradually removing features with low importance scores from the SR+VI+GLCM model and analyzing the changes in the overall accuracy (OA), the optimal set of predictive variables was identified and used to construct the optimal model. A model built us-ing data from a single timepoint in 2021 was tested on data collected at a similar timepoint in 2019 and vice versa to assess interannual model generalizability. The results of this study demon-strate that for monitoring maize lodging, models constructed with a single feature type, the GLCM model had significantly lower accuracy compared to the VI and SR models. During certain growth stages, the model constructed with combined features had significantly higher accuracy in monitoring maize lodging compared to models constructed with a single feature. During the pro-cess of selecting the optimal predictive variables, it was found that the accuracy of the model did not increase as the number of predictive variables increased. The results show that the positive and negative validation models had an accuracy of 96.55% and 95.18%, with kappa values of 0.93 and 0.83, respectively. This indicates that the model has strong generality for the same repro-ductive stage between years. This study provides a detailed method for large-scale maize lodging monitoring, allowing for identification of optimal planting practices to reduce the probability of lodging and ultimately improving regional maize yield and quality.

Cancer is a complex disease, considered a major public health problem worldwide. Among the types of cancer, melanoma, and leukemias present high mortality rates in Brazil and worldwide. Currently, conventional cytotoxic treatments cause severe side effects by the non-selectivity between normal cells and cancer cells. Therefore, molecules of natural origin with more efficient anticancer properties and that present fewer adverse effects are of extreme importance for cancer therapy and improvement in patients’ quality of life. This study isolated, identified, and characterized the chemical structure of a new anthraquinone present in the extract of the roots of Senna velutina. In addition, we sought to evaluate the anticancer potential of this molecule against melanoma and leukemic cell lines and identify the pathways of cell death involved. To this end, a novel anthraquinone was isolated from the barks of the roots of S. velutina, analyzed by HPLC-DAD, and its molecular structure was determined by NMR. Subsequently, their cytotoxic activity was evaluated by the MTT method against non-cancerous, melanoma, and leukemic cells. The migration of melanoma cells was evaluated by the scratch assay. By flow cytometry technique, the apoptosis process, caspase-3 activation, analysis of mitochondrial membrane potential, and measurement of ROS were evaluated. In addition, the pharmacological cell death inhibitors NEC-1, RIP-1, BAPTA, Z-VAD, and Z-DEVD were used to confirm the related cell death mechanisms. With the results, it was possible to elucidate the novel compound characterized as 2'-OH-Torosaol I. In normal cells, the compound showed no cytotoxicity in PBMC but reduced the cell viability of all melanoma and leukemic cell lines evaluated. 2'-OH-Torosaol I inhibited chemotaxis of B16F10-Nex2, SK-Mel-19, SK-Mel28 and SK-Mel-103. The cytotoxicity of the compound was induced by apoptosis via the intrinsic pathway with reduced mitochondrial membrane potential, increased levels of reactive oxygen species, and activation of caspase-3. In addition, the inhibitors demonstrated the involvement of necroptosis and CA+ in the death process and confirmed caspase-dependent apoptosis death as one of the main programmed-cell death pathways induced by 2'-OH-Torosaol I. Taken together, the data characterize the novel anthraquinone 2'-OH-Torosaol I, demonstrating its anticancer activity and potential application in cancer therapy.

Foxtail millet (Setaria italica (L.) P. Beauv) is an important food and forage crop that is well adapted to nutrient-poor soils. However, little is known about how foxtail millet adapts to low nitrogen (LN) at the physiological and molecular levels. In the present study, two foxtail millet varieties with contrasting low nitrogen (LN) tolerance properties were investigated through integrative analyses of physiological featureparameters and transcriptomics. The physiological results showed that JG20 (high tolerance to LN) had higher biomass accumulation, nitrogen content and nitrogen use efficiency compared with JG22 (low tolerancesensitive to LN) under LN. JG20 had higher soluble sugar and soluble protein concentration in shoots compared with JG22 under LN, while contcentrations of soluble sugar and soluble protein contents were higher in the roots of JG22. Higher levels of CTK contentzeatin concentration were found in the shoots of JG20 com-pared with JG22, and a higher ABA contcentration was found in both the shoots and roots of JG22 compared with JG20 under LN. In the transcriptomics results, JG20 had more differentially ex-pressed genes (DEGs) than JG22 both in shoots and roots in response to LN. These LN-responsive genes were enriched in glycolysis, starch and sucrose metabolism, photosynthesis, biosynthesis of amino acids, hormone metabolism and nitrogen metabolism. Furthermore, the high-affinity nitrate transporter gene, SiNRT2.1, and glutamine synthetase gene, SiGS5, chlorophyll apoprotein of photosystem II gene, SiPsbQ, ATP synthase subunit gene, b, auxin-responsive protein gene, SiIAA25, and aldose 1-epimerase gene, SiAEP, in shoots, and high-affinity nitrate transporter gene, SiNRT2.3, SiNRT2.4, and glutamate synthase gene, SiGOGAT2, auxin-responsive protein gene, SiIAA4, fructose-bisphosphate aldolase gene, SiAEP5, in root, were important genes in-volved in the LN tolerance of foxtail millet. These results provide a detailed description of the physiological and transcriptome response of foxtail millet under LN condition.

The characteristics of the Sentinel-2 mission with a decametric resolution and frequent acquisitions allow to improve the identification of crops. The majority of the studies on crop classification using RS were targeted at herbaceous and gramineous crop classes while fewer results were obtained on woody crops which present a strong variability in management practices that make their identification difficult. Thus, this study aimed to propose a rapid, accurate, and cost-effective analytical approach for the delineation of fruit orchards (OC), vineyards (VY), and olive groves (OL) in the Mediterranean (Southern France) considering two locations. A classification based on phenology metrics (PM) de-rived from temporal Sentinel-2 time series was developed to perform the classification. The PM were computed by fitting a double logistic model on temporal profiles of vegeta-tion indices to delineate OC, VY, and a DC class gathering all remaining surfaces. The generated PM were introduced in a random forest (RF) algorithm to identify woody crops across the two sites. The method was tested on different vegetation indices, the best results being obtained with the leaf area index (LAI). To delineate OL in the DC class, the tem-poral features of the green chlorophyll vegetation index (GCVI) were found to be the most appropriated with a typical drop of the signal during the mid-season (DOY 150-250). As a final result, we obtained an overall accuracy ranging from 89-96% and Kappa of 0.86-0.95 by considering each study site and year (2016-2021), separately. This accuracy is much better than applying the RF algorithm on the LAI times series, which led to a Kappa rang-ing between 0.3 and 0.52 and demonstrates the interest of using phenological traits rather than the raw time series of the RS data. The method can be well reproduced from one year to another. Moreover, it is possible to apply the classification model of a given year to an-other, keeping good accuracy. This is an interesting feature to reduce the burden of col-lecting ground truth information. On the contrary, the use of a classification model cali-brated in one site and applied to another led to a strong degradation of the classification accuracy. Woody crop phenology is dependent on site climatic conditions as well as the cultivar and management practices that can differ from one site to another.

This study aimed to investigate the possibility of using one-shot hyperspectral airborne images to recognize crops for an area with many small plots. The results showed that unsupervised clustering methods could classify crops with an accuracy of 80%, which improved to 90% when restricted to only grain crops, using a single airborne hyperspectral recording. However, additional layers such as NDVI, DTM, slope, and aspect did not improve classification accuracy. For comparison, the accuracy of clustering time series Sentinel-2 images with NDVI layers and DTM-derived data yielded an accuracy of: 74% ,Sentinel-2 time series 68% and single one registration before harvest - 39%. The results of the random forest classification were slightly less accurate due to a lack of sufficient reference data. However, it is challenging to verify the reported accuracy of crop recognition in the literature above 90% due to differences in analysis methodologies, reference data selection, pixel/object approaches, metric choice, and calculation formulas used.

The reaction of mercaptoacetic acid esters with pentachloro-2-nitro-1,3-butadiene provides appropriate precursors for the synthesis of 2,3,4-trisubstituted benzo[h]quinolines. These heterocycles are easily accessible via a single-step reaction with 1-naphthyl- or 1-anthracenylamine, respectively. Due to steric bulk and high electron density ring closure to benzo[h]quinolines takes place, exclusively. Such highly substituted annelated pyridine systems can be modified in subsequent, selective reactions to build up new N-heterocycles with promising microbiological properties. Antibacterial and antiproliferative assays against four cell mammalian cell lines demonstrate that some of the sulfur-substituted benzo[h]quinolines analogs display potent phenotypic bioactivities in the single-digit micromolar range.

The effects of morphine (MOR) and dexmedetomidine (DEX) on the MAC of isoflurane were measured in rats chronically treated with the synthetic cannabinoid WIN 55,212-2 (WIN55). Methods: The MAC of isoflurane was determined in 32 male rats from expiratory samples at the time of tail clamping. The effects of morphine (MAC(ISO+MOR)) and dexmedetomidine (MAC(ISO+DEX)) on the MAC of isoflurane in untreated rats and rats treated for 21 days with WIN 55,212-2 (MAC(ISO+WIN55+MOR)) and (MAC(ISO+WIN55+DEX)) were measured. Prior to the administration of morphine and dexmedetomidine, the MAC of the isoflurane was measured in both untreated rats (MAC(ISO)) and those treated with WIN 55,212-2 (MAC(ISO+WIN55)). Results: The minimum alveolar concentration was measured as 1.32 ± 0.06 in the MAC(ISO) group and 1.69 ± 0.09 in the MAC(ISO+WIN55) group. The MAC of the MAC(ISO+MOR) group was 0.97 ± 0.02 (26% less than the control group, MAC(ISO)). MAC was measured as 1.55 ± 0.08 in the MAC(ISO+WIN55+MOR) group (8% less than the MAC(ISO+WIN55) group), 0.68 ± 0.10 in the MAC(ISO+DEX) group (48% less than the control group, MAC(ISO)), and 0.67 ± 0.08 in the MAC(ISO+WIN55+DEX) group (60% less than the MAC(ISO+WIN55) group). Conclusions: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. The sparing effect on isoflurane of morphine decreases in rats chronically treated with the synthetic cannabinoid, WIN 55,212-2. Dexmedetomidine increases its sparing effect on the minimum alveolar concentration of isoflurane in rats chronically treated with WIN 55,212-2.

Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants for mutual benefits. The interactions with a host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of Aspergillus flavus, an endophytic fungus isolated from the roots of the medicinal grass Cynodon dactylon, for its anticancer potential. Ethyl acetate extract from isolated A. flavus showed significant cytostatic effects (IC50: 16.25 μg mL−1) against breast cancer cells (MCF-7). Morphology of cells and DAPI stained nuclei along with the results of flow cytometry annexin V/PI assay suggested apoptosis to be the main process leading to cells’ death. While investigating the mechanism that triggers apoptosis, we found that the extract of A. flavus increased ROS generation and caused loss of mitochondrial membrane potential of MCF-7 cells. To identify the metabolites that might be responsible for the anticancer effect, the extract was examined using gas chromatography-mass spectrometry (GC-MS). Interestingly, nine phytochemicals were found to have potential inhibitory effects of anti-apoptotic protein (Bcl-2) in the breast cancer cells. In the in silico molecular docking and molecular dynamics simulation studies revealed that two compounds: 2,4,7-Trinitrofluorenone and 3alpha, 5alpha-Cyclo-ergosta-7,9(11),22t-triene-6beta-ol exhibited significant binding affinities (-9.20, and -9.50 Kcal mol-1, respectively) against Bcl-2 along with binding stability and intermolecular interactions of its ligand-Bcl-2 complexes. Overall, the study found that the endophytic A. flavus from C. dactylon contains plant-like bioactive compounds that have a promising effect in breast cancer.

We recently proposed that topological quantum computing might be based on $SL(2,\mathbb{C})$ representations of the fundamental group $\pi_1(S^3\setminus K)$ for the complement of a link $K$ in the $3$-sphere. The restriction to links whose associated $SL(2,\mathbb{C})$ character variety $\mathcal{V}$ contains a Fricke surface $\kappa_d=xyz -x^2-y^2-z^2+d$ is desirable due to the connection of Fricke spaces to elementary topology. Taking $K$ as the Hopf link $L2a1$, one of the three arithmetic two-bridge links [the Whitehead link $5_1^2$, the Berge link $6_2^2$, the double-eight link $6_3^2$] or the link $7_3^2$, the $\mathcal{V}$ for those links contains the reducible component $\kappa_4$, the so-called Cayley cubic. In addition, the $\mathcal{V}$ for the later two links contains the irreducible component $\kappa_3$, or $\kappa_2$, respectively. Taking $\rho$ to be a representation with character $\kappa_d$ ($d<4$), with $|x|,|y|,|z| \le 2$, then $\rho(\pi_1)$ fixes a unique point in the hyperbolic space $\mathcal{H}_3$ and is conjugate to a $SU(2)$ representation (a qubit). Even though details on the physical implementation remain open, more generally, we show that topological quantum computing may be developed from the point of view of three-bridge links, the topology of the $4$-punctured sphere and Painlev\'e VI equation. The $0$-surgery on the $3$ circles of the Borromean rings L6a4 is taken as an example.

Observing cultivated crops and other forms of land use is an important environmental and economic concern for agricultural land management and crop classification. Crop categorization offers significant crop management data, ensuring food security, and developing agricultural policies. Remote sensing data, especially publicly available Sentinel 1 and 2 data, has effectively been used in crop mapping and classification in cloudy places because of their high spatial and temporal resolution. This study aimed to improve crop type classification by combining Sentinel-1 (Synthetic Aperture Rader (SAR)) data and the Sentinel-2 Multispectral Instrument (MSI) data. In the study, Random Forest (RF) and Classification and Regression Trees (CART) classier were used to classify grain crops (Barley and Wheat). The classification results based on the combination of Sentinel-2 and Sentinel-1 data indicated an overall accuracy (OA) of 93 % and a kappa coefficient (K) of 0.896 for RF and (89.15%, 0.84) for the CART classifier. It is suggested to employ a mix of radar and optical data to attain the highest level of classification accuracy since doing so improves the likelihood that the details will be observed in comparison to the single-sensor classification technique and yields more accurate results.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

Azobenzene-containing molecules may associate with each other in systems such as self-assembled monolayers or micelles. The interaction between azobenzene units leads to a formation of exciton states in these molecular assemblies. Apart from local excitations of monomers, the electronic transitions to the exciton states may involve charge transfer excitations. Here, we perform quantum chemical calculations and apply transition density matrix analysis to quantify local and charge transfer contributions to the lowest electronic transitions in azobenzene dimers of various arrangements. We find that the transitions to the lowest exciton states of the considered dimers are dominated by local excitations, but charge transfer contributions become sizable for some of the lowest ππ* electronic transitions in stacked and slip-stacked dimers at short intermolecular distances. In addition, we assess different ways to partition the transition density matrix between fragments. In particular, we find that the inclusion of the atomic orbital overlap has a pronounced effect on quantifying charge transfer contributions if a large basis set is used.

Not only does this paper present a novel type-2 fuzzy system for identification and behavior prognostication of an experimental solar cell set and a wind turbine, but also it brings forward an exquisite technique to acquire an optimal number of membership functions and the corresponding rules. It proposes a seven-layered NCPRT2FS. For fuzzification in the first two layers, Gaussian type-2 fuzzy membership functions with uncertainty in the mean, are exploited. The third layer comprises rule definition and the forth one embeds fulfillment of type reduction. The three last remained layers are the ones in which resultant left–right firing points, two end-points and output all get assessed correspondingly. It should not be neglected off the nutshell that recurrent feedback at the fifth layer exerts delayed outputs ameliorating efficiency of the suggested NCPRT2FS. Later in the paper, a modern structural learning, established on type-2 fuzzy clustering, is held forth. An adaptively rated learning back-propagation algorithm is extended to adjust the parameters ensuring the convergence as well. Eventually, solar cell photo-voltaic and wind turbine are deemed as case studies. The experimental data are exploited and the consequent yields emerge so persuasive.

Climacteric fruits are characterized by a dramatic increase in autocatalytic ethylene production, which is accompanied by a spike in respiration, at the onset of ripening. The change in the mode of ethylene production from autoinhibitory to auto-stimulatory is known as the system 1 (S1) to system 2 (S2) transition. Existing physiological models explain the basic and overarching genetic, hormonal, and transcriptional regulatory mechanisms governing the S1 to S2 transition of climacteric fruit. However, the links between ethylene and respiration, the two main factors that characterize the respiratory climacteric, have been largely understudied at the molecular level. Results of recent studies indicate that the AOX respiratory pathway may play an important role in mediating cross talk between ethylene response, carbon metabolism, ATP production, and ROS signaling during climacteric ripening. New genomic, metabolic, and epigenetic information sheds light on the interconnectedness of ripening-associated metabolic pathways, necessitating expanding the current, ethylene-centric physiological models. Understanding points at which ripening responses can be manipulated may reveal key, speciesand cultivar-specific targets for regulation of ripening enabling superior strategies for reducing postharvest wastage.

Background: The dietary factors and nutrients contributing to the prevention of microalbuminuria in type 2 diabetic nephropathy is unclear, so we investigated dietary factors affecting urinary albumin excretion in patients with type 2 diabetes. Methods: 42 patients with type 2 diabetes were participated, the subjects were divided to a normal albuminuria group (urinary albumin / creatinine ratio of less than 30 mg / g Cr) and a microalbuminuria group of 30 mg / g to 299 mg / g Cr. We performed casual blood sampling and conducted a food frequency questionnaire survey. Results: There were no significant differences in age, BMI and other physiological and biochemical data, the average daily intake of energy and many of nutrients, while β-cryptoxanthin was significantly lower in the microalbuminuria group than in the normal group (506.4 ± 793.9 μg/day vs. 715.3 ± 500.3 μg/day, p <0.05). The intake of 17 food groups per day showed that the intakes of fruits were significantly lower in the microalbuminuria group than in the normal group (76.9 ± 134.1 g vs. 111.9 ± 84.5 g, p <0.05). Conclusion: These results suggest that fruits and foods rich in β-cryptoxanthin would make it possible to prevent diabetic nephropathy progression.

Toll-like receptors (TLRs) play a key role in the innate immune response to numerous pathogens, including Acanthamoeba sp. The aim of this study was to determine the expression of TLR2 and TLR4 in the eyes of mice following intranasal infection with Acanthamoeba sp. Amoebae used in this study were isolated from the bronchial aspirate of a patient with acute myeloid leukemia (AML) and atypical symptoms of pneumonia. We found statistically significant differences in the expression of TLR2 and TLR4 in the eyes of immunocompetent mice at 8, 16, and 24 days post Acanthamoeba sp. infection (dpi) compared to control. Immunosuppressed mice showed significant differences in the expression of TLR2 at 16 and 24 dpi compared to uninfected animals. Our results indicate that TLR2 and TLR4 are upregulated in the eyes of mice in response to Acanthamoeba sp. We suggest that it is possible for trophozoites to migrate through the optic nerve from the brain to the eyes.

An oceanic radar altimeter such as TOPEX/Poseidon (T/P) is typically for observing elevation changes over the open oceans or large inland lakes/rivers, with limited applications over solid earth due to its large footprint and susceptibility to waveform contamination and slope effect. Here we demonstrate that it is possible to construct a long-term time series of glacier elevation change from T/P-series radar altimeters over two flat surfaces near a glacier terminus and an icefield (Sites A and B, with slopes of 2° and 0.8°) in Mt. Tanggula, Tibet, at elevations over 5400 m. We retracked radar waveforms using the subwaveform threshold algorithm, selected quality altimeter data (1/4 of the original) with nearly the same slope and adjusted the original elevations by fitting with a time-varying, 2nd order surface. The glacier elevation changes at the two sites from T/P (1993–2002) show seasonal elevation oscillations with linear rates at about −3 m/year and abnormal seasonal changes around the 1997–98 El Niño. Site A is over a deep valley in southern Tanggula. Its elevation dropped about 30 m over 1993–2002 (from T/P) and the glacier almost disappeared by 2016 (from altimeters and satellite images). Despite the sporadic Jason-2 and Jason-3 altimeter data, we also derived long-term rates of glacier elevation change over 1993–2017. Landsat-derived glacier area and elevation changes near the two sites confirm the rapid glacier thinning from the altimeters. The glacier meltwater near Site A supplied increasing source water to Chibuzhang Co west of Mt. Tanggula, contributing partially to its accelerated rising lake level. The glacier thinning at Site B (icefield) was correlated with the increased discharge of the Tuotuo River in eastern Mt. Tanggula, a source region of the Yangtze River. The successful detection of glacier thinning at the two sites shows that T/P-series altimeters can serve as a virtual station at a flat glacier spot to monitor long-term glacier elevation changes in connection to climate change. This virtual station concept is particularly useful for inaccessible glaciers, but its implementation faces two challenging issues: increasing the volume of quality altimeter data and improving the ranging accuracy over a targeted mountain glacier spot.

A visible-light photoredox functionalization of 3,4-dihydro-1,4-benzoxazin-2-ones through a Friedel-Crafts reaction with indoles using an inexpensive organophotoredox catalyst is described. The reaction uses a dual catalytic system formed by a photocatalyst simple and cheap, 9,10-phenanthrenedione, and a Lewis acid, Zn(OTf)₂. 5W white LEDs are used as visible-light source and oxygen from air as a terminal oxidant, obtaining the corresponding products with good yields. The reaction can be extended to other electron-rich arenes.

Here we present an overview of speleothem δ18O records from South America, which mostly are available in the Speleothem Isotopes Synthesis and Analysis (SISAL_v1) database. South American tropical and subtropical δ18O time series are primarily interpreted as being driven by the amount effect and, consequently show the past history of the convection intensity of convergence zones such as the Intertropical Convergence Zone and the South America Monsoon System. We investigate past hydroclimate scenarios in South America related to the South American Monsoon System in three different time scales: Late Pleistocene, Holocene and the last two millennia. The precession driven insolation is the main driver of convective variability over the continent during the last 250 kyrs, including the Holocene period. However a dipole is observed between the west and east portions of the continent. Records located in the central region of Brazil appear to be weakly affected by insolation driven variability and more susceptible to the South Atlantic Convergence Zone. Cold episodic events in Northern Hemisphere increase the activity of the South American Monsoon System on all time scales, in turn increasing rainfall amounts in South America, as was documented during Heinrich events in the late Pleistocene and Bond events in the Holocene, as well as during the Little Ice Age.

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

Wetlands benefits can be summarized but are not limited to their ability to store floodwaters and improve water quality, providing habitats for wildlife and supporting biodiversity, as well as aesthetic values. Over the past few decades, remote sensing and geographical information technologies has proven to be a useful and frequent applications in monitoring and mapping wetlands. Combining both optical and microwave satellite data can give significant information about the biophysical characteristics of wetlands and wetlands` vegetation. Also, fusing data from different sensors, such as radar and optical remote sensing data, can increase the wetland classification accuracy. In this paper we investigate the ability of fusion two fine spatial resolution satellite data, Sentinel-2 and the Synthetic Aperture Radar Satellite, Sentinel-1, for mapping wetlands. As a study area in this paper, Balikdami wetland located in the Anatolian part of Turkey has been selected. Both Sentinel-1 and Sentinel-2 images require pre-processing before their use. After the pre-processing, several vegetation indices calculated from the Sentinel-2 bands were included in the data set. Furthermore, an object-based classification was performed. For the accuracy assessment of the obtained results, number of random points were added over the study area. In addition, the results were compared with data from Unmanned Aerial Vehicle collected on the same data of the overpass of the Sentinel-2, and three days before the overpass of Sentinel-1 satellite. The accuracy assessment showed that the results significant and satisfying in the wetland classification using both multispectral and microwave data. The statistical results of the fusion of the optical and radar data showed high wetland mapping accuracy, with an overall classification accuracy of approximately 90% in the object-based classification. Compared with the high resolution UAV data, the classification results give promising results for mapping and monitoring not just wetlands, but also the sub-classes of the study area. For future research, multi-temporal image use and terrain data collection are recommended.

Obesity is treatment-resistant, and is linked with a number of serious, chronic diseases. Adult obesity rates in the United States have tripled since the early 1960s. Recent reviews show that an increased ratio of omega-6 to omega-3 fatty acids contributes to obesity rates by increasing levels of the endocannabinoid signals AEA and 2-AG, overstimulating CB₁R and leading to increased caloric intake, reduced metabolic rates, and weight gain. Cannabis, or THC, also stimulates CB₁R and increases caloric intake during acute exposures. The present meta-analysis reveals significantly reduced body mass index and rates of obesity in Cannabis users, in conjunction with increased caloric intake. We provide for the first time a causative explanation for this paradox, in which rapid and long-lasting downregulation of CB₁R following acute Cannabis consumption reduces energy intake and storage and increases metabolic rates, thus reversing the impact on body mass index of elevated dietary omega-6/omega-3 ratios.

The mechanisms by which bacteriophage T4 converts the metabolism of its E. coli host to one dedicated to progeny phage production was the subject of decades of intense research in many labs from the 1950’s through the 1980’s. At this point, a wide range of phages are starting to be used therapeutically and in many other applications and also the range of available phage sequence data is skyrocketing. It is thus important to re-explore the extensive available data about the intricacies of the T4 infection process as summarized here, expand it to looking much more broadly at other genera of phages, and explore phage infections using newly-available modern techniques and a range of appropriate environmental conditions.

Structurally related 7-acetyl-2-aryl-5-bromoindoles 2a–d and the 7-acetamido-2-aryl-5-bromoindoles 4a–d as well as their corresponding 3-trifluoroacetyl–substituted derivatives 5a–d and 5e–h were evaluated for potential antigrowth effect in vitro against the human lung cancer (A549) and cervical cancer (HeLa) cells. All of the 3-trifluoroacetyl–substituted 7-acetamido-2-aryl-5-bromoindoles 5e–h were found to be more active against both cell lines when compared to the chemotherapeutic drug, Melphalan. The most active compound 5g induced apoptosis in a caspase dependent manner for both cell lines. Compounds 5e–h were found to significantly inhibit tubulin polymerization. Molecular docking of 5g into the colchicine-binding site suggests that the compounds bind to tubulin by different type of interactions including pi-alkyl, amide-pi stacked and alkyl interactions as well as hydrogen bonding with the protein residues to elicit anticancer activity.

We have previously reported that 60% sucrose diet-fed ChREBP knockout mice (KO) showed body weight loss resulting in lethality. We aimed to elucidate whether sucrose and fructose metabolism are impaired in KO. Wild type mice (WT) and KO were fed a diet containing 30% sucrose with/without 0.08% miglitol, an α-glucosidase inhibitor, and these effects on phenotypes were tested. Furthermore, we compared metabolic changes of oral and peritoneal fructose injection. Thirty percent sucrose diet feeding did not affect phenotypes in KO. However, miglitol induced lethality in 30% sucrose-fed KO. Thirty percent sucrose plus miglitol diet-fed KO showed increased cecal contents, increased fecal lactate contents, increased growth of lactobacillales and Bifidobacterium and decreased growth of clostridium cluster XIVa. ChREBP gene deletion suppressed the mRNA levels of sucrose and fructose related genes. Next, oral fructose injection did not affect plasma glucose levels and liver fructose contents; however, intestinal sucrose and fructose related mRNA levels were increased only in WT. In contrast, peritoneal fructose injection increased plasma glucose levels in both mice; however, the hepatic fructose content in KO was much higher owing to decreased hepatic Khk mRNA expression. Taken together, KO showed sucrose intolerance and fructose malabsorption owing to decreased gene expression.

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

Hybrid organic-inorganic (dendritic polymer-silica) xerogels containing silver nanoparticles (Ag-Nps) were developed as antibacterial leather coatings. The preparation method is environmentally friendly, based on two biomimetic reactions. Silica gelation and spontaneous (Ag-Np) formation were both mediated by hyperbranched poly (ethylene imine) (PEI) scaffolds of variable Mw (2000-750000). The formation of precursor hydrogels was monitored by dynamic light scattering (DLS). The chemical composition of the xerogels was assessed by Infra-Red Spectroscopy (IR) and Energy-dispersive X-ray spectroscopy (EDS) while the uniformity of the coatings was established by scanning electron microscopy (SEM). Release properties of coated leather samples and overall behaviour in water in comparison to untreated analogs were investigated by UV-Vis spectroscopy. Antibacterial activity was tested towards Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and antibiofilm properties against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Acinetobacter baumannii, Enterococcus faecalis while SARS-Cov-2 clinical isolate was employed for the first estimation of their antiviral potential. Toxicity was evaluated using the Jurkat E6.1-cell line. Finally, water contact angle measurements were implemented to determine the enhancement of the leather surface hydrophilicity caused by these composite layers. The final advanced products are intended for use in medical applications.

To mitigate the spread of the COVID-19 coronavirus, some countries have enforced more stringent non-pharmaceutical interventions in contrast to those widely adopted (for e.g. the state of Kuwait). In addition to standard practices such as enforcing curfews, social distancing, and closure of non-essential service industries, other non-conventional policies such as the total confinement of highly populated areas has also been implemented. In this paper, we model the movement of a host population using a mechanistic approach based on random walks, which are either diffusive or super-diffusive. Infections are realised through a contact process, whereby a susceptible host may be infected if in close spatial proximity of the infectious host. Our focus is only on the short-time scale prior to the infectious period, so that no further transmission is assumed. We find that the level of infection depends heavily on the population dynamics, and increases in the case of slow population diffusion, but remains stable for a high or super-diffusive population. Also, we find that the confinement of homogeneous or overcrowded sub-populations has minimal impact in the short term. Finally, we discuss the possible implications of our findings for total confinement in the context of the current situation in Kuwait.

Infectious diseases are a global health problem affecting billions of people. Developing rapid and sensitive diagnostic tools is key for successful patient management and curbing disease spread. Currently available diagnostics are very specific and sensitive but time-consuming and require expensive laboratory settings and well-trained personnel; thus, they are not available in resource-limited areas, for the purposes of large-scale screenings and in case of outbreaks and epidemics. Developing new, rapid, and affordable point-of-care diagnostic assays is urgently needed. This review focuses on CRISPR-based technologies and their perspectives to become platforms for point-of-care nucleic acid detection methods and as deployable diagnostic platforms that could help to identify and curb outbreaks and emerging epidemics. We describe the mechanisms and function of different classes and types of CRISPR-Cas systems, including pros and cons for developing molecular diagnostic tests and applications of each type to detect a wide range of infectious agents. Many Cas proteins (Cas9, Cas12, Cas13, Cas14) have been leveraged to create highly accurate and sensitive diagnostic tools combined with technologies of signal amplification and fluorescent, potentiometric, colorimetric, or lateral flow assay detection. In particular, the most advanced platforms -- SHERLOCK/v2, DETECTR, or CRISPR-Chip -- enable detection of attomolar amounts of pathogenic nucleic acids with specificity comparable to that of PCR but with minimal technical settings. Further developing CRISPR-based diagnostic tools promises to dramatically transform molecular diagnostics, making them easily affordable and accessible virtually anywhere in the world. The burden of socially significant diseases, frequent outbreaks, recent epidemics (MERS, SARS and the ongoing coronoviral nCov-2019 infection) urgently need the developing of express-diagnostic tools. Recently devised CRISPR-technologies represent the unprecedented opportunity to reshape epidemiological surveillance and molecular diagnostics.

Background: Reliable HPV testing and genotyping are essential for quality assurance in HPV-based primary screening, disease management and for monitoring the impact of HPV vaccination. The clinical validation of HPV molecular diagnostic assays has significantly contributed to these objectives, however little emphasis has been placed in assuring sample quality. This study aims to assess the accuracy of sample cellularity assessment using C-C Motif Chemokine Receptor 5 (CCR5) gene target as a marker of sample adequacy in molecular diagnostics. Methods: Jurkat cell line samples were counted both using Thoma cell-counting chamber and Fluorescent-Activated Cell Sorting (FACS). Jurkat cell line samples at three different concentrations were subsequently evaluated using the OncoPredict HPV Quality Control (QC) real-time PCR assay, employing CCR5 for molecular cellularity quantification. Results: Cellularity values obtained were comparable across the 3 different methods for all dilutions of the cell line tested. Conclusions: The results obtained from this study show that CCR5 represents a promising molecular marker for the accurate quantification of sample cellularity, confirming its use as a reliable sample adequacy control, thus reducing the risk of “false negative” results.

Human Pose Estimation (HPE) is a critical technology in computer vision with diverse applications ranging from healthcare to sports analysis. This project presents a method for detecting the 2D stance of multiple persons in an image using a nonparametric representation known as Part Affinity Fields (PAFs). By leveraging the first 10 layers of the VGG-19 convolutional neural network and training on the COCO dataset, our model effectively identifies and associates key points of the human body.The architecture employs a two-branch system that jointly learns part locations and their associations through sequential prediction. This enables the model to maintain real-time performance while achieving high accuracy, regardless of the number of persons in the image. To enhance accessibility, we developed a mobile application using Flutter and TensorFlow Lite, allowing real-time pose estimation via a mobile device’s front camera. The app provides immediate feedback on physical exercises and yoga poses, making it an invaluable tool for fitness enthusiasts and healthcare professionals. Visual outputs such as heatmaps and PAFs confirm the model’s capability to accurately localize and connect key points. Despite potential challenges such as data quality and hyperparameter tuning, the results indicate that our approach is both reliable and practical for real-world deployment. This project not only advances the state-of-the-art in HPE but also opens up possibilities for future enhancements, including integrating 3D pose estimation and applying the technology in augmented and virtual reality applications.

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

The human mandible's cancellous bone, which is characterized by its unique porosity and directional sensitivity to external forces, is crucial for sustaining biting stress. Traditional CAD models fail to fully represent bone's anisotropic structure and thus depend on simple isotropic assumptions. For our research, we use the latest versions of nTopology and Creo Parametric software to make biomimetic Voronoi lattice models that accurately reflect the complex geometry and mechanical properties of trabecular bone. The porosity of human cancellous bone is accurately modeled in this work using biomimetic Voronoi lattice models. The porosities range from 70% to 95%, which can be achieved by changing the pore sizes to 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm. Finite element analysis (FEA) was used to examine the displacements, stresses, and strains acting on dental implants with a buttress thread, abutment, retaining screw, and biting load surface. The results show that the Voronoi model accurately depicts the complex anatomy of the trabecular bone in the human jaw, compared to standard solid block models. The ideal pore size for biomimetic Voronoi lattice trabecular bone models is 2 mm, taking into account both the von Mises stress distribution over the dental implant, screw retention, cortical bone, cancellous bone, and micromotions. This pore size displayed balanced performance by successfully matching natural bone's mechanical characteristics. Advanced finite element analysis (FEA) improves biomechanical understanding of how bones and implants interact by creating more accurate models of biological problems and dynamic loading situations. This makes biomechanical engineering better.

: Healthcare workers are affected by mental health issues, burnout and turnover, and this burden is even greater during epidemics and pandemics, such as COVID-19. The purpose of this research is to provide an overview of the measures introduced or supported in the institutions of Quebec’s health and social services network during the COVID-19 pandemic with the aim of protecting healthcare workers’ mental health. An online questionnaire survey was administered in 2021 among human resources department personnel in health and social services network institutions involved in workplace mental health in Quebec. A total of 223 key informants representing 31 of the 34 public health and social services institutions in the province of Quebec in Canada responded to the questionnaire. Measures that focus on the needs of staff, involve all levels of authority and the ones that provide flexibility, support and recognition at work were more successful, according to the advisors surveyed. Future research into whether the same measures are considered effective or ineffective outside of a pandemic context is needed.

Sirtuins, especially SIRT1, play a significant role in the regulation of inflammatory response, autophagy, and cell response to oxidative stress. Since their discovery, sirtuins have been regarded as anti-aging and longevity-promoting enzymes. Sirtuin-regulated processes seem to take part in most prevalent placental pathologies, such as preeclampsia. Furthermore, more and more research studies indicate that SIRT1 may prevent pre-eclampsia development, or at least alleviate its manifestations. Having taken this into consideration, we have made a review of recent studies on the role of sirtuins, especially SIRT1, in the regulation of processes determining normal or abnormal development and functioning of the placenta.

Here, we propose a prescriptive simulation model of a process operator’s decision-making assisted by artificial intelligence (AI) algorithm in a technical system control loop. We analyze situations fraught with a catastrophic threat that may cause unacceptable damage. Operators’ decision-making is interpreted in terms of a subjectively admissible probability of disaster and subjectively necessary reliability of its assessment. We distinguish four extreme decision-making strategies corresponding to different ratios between the above variables. An experiment simulating a process facility, an AI algorithm and operator's decision-making strategy was held. It showed that depending on the properties of a controlled process (the speed of hazard onset) and the AI algorithm characteristics (Type I and II error rate), each of such strategies or some intermediate strategy may prove to be more beneficial than others. The same approach is applicable to the identification and analysis of sustainability of strategies applied in real-life operating conditions, as well as to the development of a computer simulator to train operators to control hazardous technological processes using AI-generated advice.

Balanced fear supports human rational decision making and useful behavioral responses. In contrast, overwhelming, persistent, and unbalanced fear can paralyze the individual and result in heightened anxiety, lack of cognitive flexibility, fear-based public compliance and serious mental health issues. Psychobiotics research has established that a healthy microbiome is required for balanced fear and mental health protection via control of fear extinction. The recent Covid-19 pandemic featured daily, persistent, fear-of-a single contagion conditioning on a global scale paired with various behavioral mandates (e.g., lockdowns of the healthy, masks, isolation from environmental microbes and each other) that degraded the human microbiome and isolated us from each other and useful environmental microbes. It also ignored the historic role of secondary bacterial pathobionts, in pandemic deaths. This narrative review examines how institutional promotion of fear-of-a single contagion, lack of balanced risk communication, and appalling disregard of our fundamental nature (as majority-microbial human superorganisms) resulted in problems rather than solutions. This review concludes that government-public health-media promotion of pervasive fear and microbiome-degrading behaviors: 1) increased public compliance, 2) reduced cognitive flexibility, and 3) increased risk of mental health conditions. It further argues that microbiome-first public health should be embraced to ensure that human freedom, rather than paralyzing fear, dominates our future.

Ethylene Oxide (EtO) is a colorless, flammable gas at room temperature, produced by the catalytic oxidation of ethylene. EtO is widely used by medical sterilization facilities to clean medical supplies and equipment. Recent epidemiological studies showed that EtO is a more potent carcinogen than previously documented, leading the Environmental Protection Agency (EPA) to update, in December 2016, the inhalation unit risk estimate for EtO. This resulted in the identification of EtO as a potential health concern in several areas across the US, including the state of Utah. The geography surrounding Salt Lake Valley creates a bowl; ideal for collecting air pollution emissions. The region often experiences inversion episodes which inhibit vertical mixing and cause an accumulation of air pollutants, leading to unhealthy pollution levels. Using the EPA's dispersion modeling software, AERMOD, this study estimated EtO concentrations through facility stack and fugitive emissions modeling results. These values were compared with those of canister-based concentrations from ambient air samples taken near a medical device sterilization facility in the Salt Lake Valley. Stainless steel, whole-air passivated canisters were used to collect 24-hour ambient concentration samples of EtO. Eight locations surrounding a Salt Lake Valley medical device sterilization facility and four background sites were chosen to measure the ambient concentrations. Accounting for potential atmospheric impacts on EtO, measurements were sampled in winter 2022 (January-March) and summer 2022 (July-September). The modeled EtO concentrations were adjusted to account for background values associated with the winter or summer data. Then the two methodologies were compared using a Wilcoxon Sign-ranked, paired test. The statistical analysis resulted in six of the eight sample locations surrounding the sterilization facility being significantly different when comparing canister-based measurements of ambient EtO to modeled estimates. Canister-based measurements taken at sites one, three, and four were statistically greater than the modeled estimates, while sites two, five, and seven were statistically less than the modeled estimates. Also, the summer background value calculated was almost 2.5 times greater than the winter. The results do not suggest whether one method is more or less conservative than the other. In conclusion, the five of the closest sites and site seven were statistically different when comparing measured and modeled ambient concentrations of EtO. The comparison results do not clearly indicate if a correction factor could be derived for future human exposure to cancer risk assessment modeling. However, it is reasonable that the closer to the sterilization facility, the more total EtO exposure will be realized.

The extracellular matrix (ECM) is earning an increasingly relevant role in many disease states and the process of aging. Analyzing these disease states is possible with GWAS and PheWAS methodology, and through our analysis, we aimed to explore the relationships between polymorphisms in the compendium of ECM genes (i.e., matrisome genes) in various disease states. A significant contribution on the part of the ECM polymorphisms is evident in many varying types of diseases, particularly those in the core matrisome genes. Our results confirm previous links to connective tissue disorders, but also unearth new and underexplored relationships with neurological, psychiatric, and age-related disease states. Upon analysis of drug indications for gene-disease relationships, we identified numerous targets that may be repurposed for age-related pathology. The identification of ECM polymorphisms and their contribution to disease plays an integral role in future therapeutic developments, drug repurposing, precision medicine, and personalized care.

This paper looks at key elements of global culture that are driving a new paradigm shift in museums causing them to question their raison d'être, their design and physical space, recognizing the need to accommodate visitor interaction and participation, and to reprioritize institutional outcomes and goals reexamining their priorities. As heritage sharing in online spaces reaches across national, political, and social boundaries on platforms and networks, this has been driven by museum engagement with Internet life during the pandemic. Museum relationships and interactions with communities both local and global, continue to challenge core values and precepts, leading to radical changes in how museums define their roles and responsibilities. In this new cultural landscape, museums are responding to human digital identity in a tidal wave of human interactions on the Internet, from social media to online sharing of images and videos. This is revealing shared perspectives on cultural conflict as being tied to freedom of expression of one’s heritage embedded in digital identity.

Manipulating cloth-like deformable objects (CDOs) is a long-standing problem in the robotics community. CDOs are flexible (non-rigid) objects that do not show a detectable level of com- pression strength while two points on the article are pushed towards each otherand include objects such as ropes (1D), fabrics (2D) and bags (3D). In general, CDOs’ many degrees of freedom (DoF) introduce severe self-occlusion and complex state-action dynamics as significant obstacles for perception and manipulation systems. These challenges exacerbate existing issues of modern robotic control methods such as imitation learning (IL) and reinforcement learning (RL). This review focuses on the application details of data-driven control methods on four major task families in this domain: cloth-shaping, rope manipulation, dressing and bag manip- ulation. Furthermore, we identify specific inductive biases in these four domains that present challenges for more general IL and RL algorithms, and summarise the future direction for the development of the field.

The analysis of the human movement patterns based on the mobile network data makes it possible to examine a very large population cost-effectively, and led to several discoveries about human dynamics. However, the application of this data source is still not common practice. The goal of this study was to analyze the commuting tendencies of the Budapest Metropolitan Area using mobile network data and propose an automatized alternative to the current, questionnaire-based method. Commuting is predominantly analyzed by the census, but that is performed only once in a decade in Hungary. To analyze commuting, the home and the work locations of the subscribers are determined based on their appearances during and outside the working hours. The home locations were compared to census data at a settlement level. Then, the settlement and district level commuting tendencies were identified and compared to the findings of census-based sociological studies. It has been found that commuting analysis based on mobile network data strongly correlates with the census-based findings, even though home and work locations have been estimated by statistical methods. All the examined aspects, including commuting from sectors of the agglomeration to the districts of Budapest and demographic distribution of the commuters, show that mobile network data can be an automatized, fast, cost-effective, and relatively accurate way of commuting analysis, that could provide a powerful tool to the sociologists interested in commuting.

Reinvigorated public interest in human space exploration has led to the need to address the science and engineering challenges described by NASA's Space Technology Grand Challenges (STGCs) for expanding the human presence in space. Here we define Space Bioprocess Engineering (SBE) as a multi-disciplinary approach to design, realize, and manage a biologically-driven space mission as it relates to addressing the STGCs for advancing technologies to support the nutritional, medical, and incidental material requirements that will sustain astronauts against the harsh conditions of interplanetary transit and habitation offworld. SBE combines synthetic biology and bioprocess engineering under extreme constraints to enable and sustain a biological presence in space. Here we argue that SBE is a critical strategic area enabling long-term human space exploration; specify the metrics and methods that guide SBE technology life-cycle and development; map an approach by which SBE technologies are matured on offworld testing platforms; and suggest a means to train the next generation spacefaring workforce on the SBE advantages and capabilities. In doing so, we outline aspects of the upcoming technical and policy hurdles to support space biomanufacturing and biotechnology. We outline a perspective marriage between space-based performance metrics and the synthetic biology Design-Build-Test-Learn cycle as they relate to advancing the readiness of SBE technologies. We call for a concerted effort to ensure the timely development of SBE to support long-term crewed missions using mission plans that are currently on the horizon.

Abstract: Spatially explicit, fine-grained datasets describing historical urban extents are rarely available prior to the era of operational remote sensing. However, such data are necessary to better understand long-term urbanization and land development processes and for the assessment of coupled nature-human systems, e.g., the dynamics of the wildland-urban interface. Herein, we propose a framework that jointly uses remote sensing derived human settlement data (i.e., the Global Human Settlement Layer, GHSL) and scanned, georeferenced historical maps to automatically generate historical urban extents for the early 20th century. By applying unsupervised color segmentation to the historical maps, spatially constrained to the urban extents derived from the GHSL, our approach generates historical settlement extents for seamless integration with the multi-temporal GHSL. We apply our method to study areas in countries across four continents, and evaluate our approach for two U.S. study sites against historical settlement extents derived from the Historical Settlement Data Compilation for the US, HISDAC-US, achieving Area-under-the-Curve values >0.9. Our results are largely in agreement with model-based urban areas from the HYDE database, and demonstrate that the integration of remote sensing derived observations and historical cartographic data sources opens up new, promising avenues for assessing urbanization, and long-term land cover change in countries where historical maps are available.

We developed two human induced pluripotent stem cell (hiPSC)/human embryonic stem cell-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we used the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated. The protein yielded a single but very broad band from 480 to 1,236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.

The present paper investigates the effect of poverty on foreign direct investment (FDI) inflows in developing countries. It complements the important extant literature on the effect of FDI inflows on poverty by examining the issue the other way around. The analysis is conducted using a sample of 117 countries over the period 1980-2017, and the two-step system Generalized Methods of Moments (GMM) technique. It has relied on two indicators of poverty, namely poverty headcount ratio and poverty gap. Findings indicate that over the full sample, poverty influences negatively FDI inflows, including through its adverse effect on human capital (that is, both education and health). Unsurprisingly, low-income countries (considered as poorest countries in the full sample) experience a higher negative effect of poverty on FDI inflows than other countries. On another note, participation in international trade matters for the effect of poverty on FDI inflows. In fact, an increase in poverty levels results in lower FDI inflows in countries that experience low workers' productivity, a less developed financial sector, and a low level of infrastructure development. Furthermore, the effect of poverty on FDI inflows does not depend on the prevailing economic growth rate. Finally, the analysis has revealed the existence of a non-linear effect of poverty on FDI inflows for the poverty headcount indicator, but not for the poverty gap indicator. The non-linear effect of poverty headcount on FDI inflows is such that a rise in poverty headcount ratio results in lower FDI inflows, but an additional increase in poverty more than further discourages FDI inflows. The conclusion discusses the implications of these findings.

Biosensors and wearable sensor systems with transmitting capabilities are currently developed and used for the monitoring of health data, exercise activities, and other performance data. Unlike conventional approaches, these devices enable convenient, continuous, and unobtrusive monitoring of a user’s behavioral signals in real time. Examples include signals relative to hand an finger movement/pressure control reflected by individual grip force data. As will be shown here, these directly translate into task, skill and hand-specific (dominant versus non-dominant hand) grip force profiles for different measurement loci in the fingers and palm of the hand. On the basis of thousands of sensor data from multiple sensor locations, individual grip force profiles of an task expert, a trained user and a highly proficient user (expert) performing an image-guided and robot-assisted precision task with the dominant or the non-dominant hand are analyzed in several steps following Tukey’s “detective work” approach. Correlation analyses (Person’s Product Moment) reveal skill-specific differences in individual grip force profiles across multiple sources of variation, functionally mapped to the somatosensory brain networks which ensure grip force control and its evolution with control expertise. Implications for the real-time monitoring of individual grip force profiles and their evolution with training in complex task-user systems are brought forward.

Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they caused requires the sampling of body fluids (blood, lymph, peritoneal fluid, cerebrospinal fluid, etc.) or organ biopsies (bone marrow, spleen, etc.), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, Google. The information of each selected article (n=333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on Human African Trypanosomiasis and a the absence on animal Trypanosomiasis. Among the collected data high heterogeneity in terms of the I² statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigen for leishmaniasis and Chagas disease. Data on conjunctival swab can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristle showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristle for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

Interviews from strength and conditioning coaches across all levels of athletic competition identified their two biggest concerns with the current state of wearable technology: (a) the lack of solutions that accurately capture data "from the ground up" and (b) the lack of trust due to inconsistent measurements. The purpose of this research is to investigate the use of liquid metal sensors, specifically Liquid Wire sensors, as a potential solution for accurately capturing ankle complex movements such as plantar flexion, dorsiflexion, inversion, and eversion. Sensor stretch linearity was validated using a Micro-Ohm Meter and a Wheatstone bridge circuit. Sensors made from different substrates were also tested and discovered to be linear at multiple temperatures. An ankle complex model and computing unit for measuring resistance values were developed to determine sensor output based on simulated plantar flexion movement. The sensors were found to have a significant relationship between the positional change and the resistance values for plantar flexion movement. The results of the study ultimately confirm the researchers' hypothesis that liquid metal sensors, and Liquid Wire sensors specifically, can serve as a mitigating substitute for inertial measurement unit (IMU) based solutions that attempt to capture specific joint angles and movements.

The genetic transformation of Coffea arabica L. is an alternative strategy for obtaining plants with agronomic traits of interest that is less time-consuming than conventional breeding methods. Given the importance of coffee cultivation in Colombia, this study evaluated the main factors interfering with the genetic transformation of C. arabica using Agrobacterium tumefaciens. An effi-cient and reproducible method was accordingly established that involved the propagation of “early” embryogenic tissue in a liquid proliferation medium, supplemented with 3 mg l−1 BAP for eight months, which was subsequently sonicated for 300 sec in a suspension of LBA4405 OD600 of 0.5 harboring pC1301 and incubated in this same suspension for 1 hr. This plasmid contained the uidA gene under control of the 35S promoter. The Agrobacterium suspen-sion was subsequently removed from the embryogenic tissue using a micropipette, after which the tissue was deposited on filter paper to remove the remaining Agrobacterium suspension. The embryogenic tissue was co-cultured for four days in a solid differentiation medium supple-mented with 100 µM acetosyringone on filter paper. Subsequently, the tissue was post-cultured for four days in liquid differentiation medium under orbital shaking at 100 rpm with 300 mg l−1 Claforan (Hoechst), followed by selection with 50 mg l-1 hygromycin at 26 °C in the dark, with subcultures at 20-day intervals until somatic embryos were formed for subsequent culturing in germination medium. Molecular analysis confirmed the presence of the uidA gene in coffee seedlings transformed with strains LBA4405 and EHA105 and vectors pC1301 and pC2301. This method successfully enables the stable integration of genes of interest in the coffee plant ge-nome

Zinc Oxide nanoparticles functionalized with APTES were obtained to evaluate their CH4 and CO2 adsorption and separation behavior. First, ZnO nanoparticles were obtained by a precipitation method and subsequently coated with (3-aminopropyl)-triethoxysilane (APTES). The nanoparticles sample was characterized by UV-Vis, FT-IR spectroscopy, TGA, XRD, TEM/EDX, XPS and N2 adsorption at 77 K. CH4 and CO2 adsorption experiments were carried out at 298 K in a range between 0-10 bar. It was observed that the amount of gas adsorbed on the surface of the nanostructure is very small in comparison with other materials traditionally used for this purpose but slightly higher than those obtained in naked nanoparticles evaluated in previous studies.

This study explores the integration of genome sequencing and polymerase chain reaction (PCR) based methods for tracking the diversity of Covid-19 variants in wastewater. The research focuses on monitoring various Omicron subvariants during a period of significant viral evolution. Genome sequencing, particularly using Oxford Nanopore Technology (ONT), provides a detailed view of emerging variants, surpassing the limitations of PCR-based detection kits that rely on known sequences. This study highlights the effectiveness of combining these methodologies to enhance early detection and inform public health strategies, especially in regions with limited clinical sequencing capabilities.

Wide-bandgap tin oxide (SnO₂) thin-films are frequently used as an electron-transporting layers in perovskite solar cells due to superior thermal and environmental stabilities. However, its crystallization by conventional thermal methods requires typical temperatures between 300 and 900 ◦C [1] with up-to 60 min crystallization times. These post-processing conditions severely limit the choice of substrates and reduce the large-scale manufacturing capabilities. This work describes the intense pulsed light-induced crystallization of SnO₂ thin films using only 500 μs of exposure time. Thin-film properties are investigated using both impedance spectroscopy and photoconductivity characteristic measurements. Nyquist plot analysis establishes that the process parameters have a significant impact on the electronic and ionic behaviors of the SnO2 films. Most importantly, we demonstrate that light-induced crystallization yields improved topography and excellent electrical properties through enhanced charge transfer, improved interfacial morphology and better ohmic contacts compared to thermally-annealed SnO₂ films.

The dissolution of CO₂ in seawater in the form of bicarbonate ions is an attractive alternative to the storage in geological formations, on the conditions that the storage is stable over long times and does not harm the marine environment. In this work, we focus on the long-term chemical stability of CO₂ absorbed in seawater as bicarbonate, by monitoring the physico-chemical properties of the solutions (pH, dissolved inorganic carbon and alkalinity), in six different sets of experiments on both natural and artificial seawater lasting up to three months. The bicarbonate treatment of natural seawater consists in pouring pre-equilibrated solutions obtained from the reaction of CO₂ and Ca(OH)₂. If the pre-equilibrated mixture does not exceed a critical threshold (ca. 1000-1500 mmol/L), the resulting bicarbonate-rich solutions can be stable for over three months.

Obesity causes insulin resistance (IR) through systemic low-grade inflammation and can lead to type 2 diabetes mellitus (T2DM). However, the mechanisms that cause IR and T2DM in non-obese individuals are unclear. The Goto-Kakizaki (GK) rat develops IR spontaneously and is a model of non-obese T2DM. These rats exhibit hyperglycemia beginning at weaning and exhibit lower body mass than control Wistar rats. Herein, we tested the hypothesis that macrophages of GK rats are permanently in a pro-inflammatory state, which may be associated with a systemic inflammation condition that mimics the pathogenesis of obesity-induced T2DM. Using eighteen-week-old GK and control Wistar rats, we investigated the proportions of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages isolated from the peritoneal cavity. Additionally, the production of inflammatory cytokine and reactive oxygen species (ROS) in cultured macrophages under basal and stimulated conditions was assessed. It was found that phorbol myristate acetate (PMA) stimulation increased GK rat macrophage ROS production by 90-fold compared to basal levels. This response was also three times more pronounced than in control cells (36-fold). The production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), tended to be upregulated in cultured macrophages from GK rats under basal conditions. Macrophages from GK rats produced 1.6 times more granulocyte-macrophage colony-stimulating factor (GM-CSF), 1.5 times more monocyte chemoattractant protein-1 (MCP-1) and 3.3 times more TNF-α than control cells when stimulated with lipopolysaccharide (LPS) (p = 0.0033; p = 0.049; p = 0.002, respectively). Moreover, compared to control cells, GK rats had 60% more M1 (p = 0.0008) and 23% less M2 (p = 0.038) macrophages. This study is the first to report macrophage inflammatory reprogramming towards a pro-inflammatory state in GK rats.

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by re-stricted and repetitive behaviors as well as difficulties with social interaction. Nu-merous studies have revealed aberrant lipid mediators and autoimmunity as a recog-nized etiological cause of ASD that is amenable to therapeutic intervention. Methods: In this study, the relationship between the relative cyclooxygenase-2, / pros-taglandin E2 ratio (COX-2/PGE2) as lipid mediator marker and anti-nucleosome au-toantibodies as autoimmunity marker of ASD was investigated using multiple regres-sion and combined receiver operating characteristic (ROC) curve analyses. The study also sought to identify the linear combination of these variables that optimizes the partial area under the ROC curves. There were forty ASD children and forty age- and sex-matched controls included in the current study. Results: Using combined ROC curve analysis, a notable increase in the area under the curve was seen. Additionally, it was reported that the combined markers had improved specificity and sensitivity. Conclusions: This study shows that using a ROC curve analysis to measure the predictive value of specific biomarkers linked to lipid metabolism and autoimmunity in children with ASD should improve our understanding of the etiological mechanism of ASD and how it is related to metabolism. Early diagnosis and intervention may be facilitated by this knowledge.

Evaluation of drug permeability using cell monolayers is an important in vitro assay in the process of drug development, to identify compounds with favourable pharmacokinetics that may proceed to in vivo studies. When allowed to differentiate on permeable filters for at least 21 days, monolayers of Caco-2 cells develop morphological and functional properties similar to those of the intestinal epithelium. Permeability through Caco-2 monolayers is thus particularly relevant to assess drug absorption after oral administration. The major drawback of this assay is its very low throughput, with the cell monolayers being used in a single permeability assay. We have previously proposed a protocol to allow the re-use of the Caco-2 monolayer on additional permeability assays during the stable period and shown that cell monolayer integrity is maintained. In this work we evaluate the effect of re-use on the permeability of several reference compounds that permeate through passive pathways and show that the cell monolayers can be re-used twice in additional permeability assays. Preliminary results were also obtained regarding active transport pathways, and a new methodology is proposed to quantify the contribution from passive and active transport. This is a major step towards the full validation of the re-use methodology proposed, which at least triplicates the throughput of this important in vitro assay.

There are various approaches to managing polyethylene terephthalate waste, including methods for recycling PET. However, at present, only the cleanest wastes that can already be efficiently recycled using known methods are considered in the scientific literature. The study aims to look at other forms of polyethylene terephthalate waste that pose a challenge: low quality PET flakes, polyester tire cord, PET dust and prepolymer waste. The waste was characterized by FTIR spectroscopy, viscosimetry, differential scanning calorimetry, laser diffraction and sieve analysis. The findings describe the composition and properties of various forms of polyethylene terephthalate waste. Low quality PET flake waste and polyethylene terephthalate dust have been shown to be suitable for all chemical recycling methods. When recycling waste polyester tire cord, it is difficult to completely separate the rubber, so its presence in the final product must be taken into account. The most promising way to process a prepolymer is its depolymerization by hydrolysis, alcoholysis or glycolysis to produce monomers for the synthesis of PET, similar in properties to the primary one.

Primary ciliary dyskinesia (PCD) is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. Low nasal NO (nNO) is a biomarker for diagnosis in patients with features of PCD; but the reason why it is low is unclear. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33- mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Variants in genes underlying the function of cilia, can be associated with poor lung function, even in the absence of PCD. Single nucleotide polymorphisms in PCD – related genes can be associated with increased asthma severity. The role of cilia and antigen stasis is the pathophysiology of asthma is an important area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma and asthma-like symptoms.

Chronic conditions like type 2 diabetes mellitus (T2DM), arterial hypertension (HTN), and obesity are major global health issues, causing significant morbidity and mortality. In Latin America, these conditions contribute to millions of premature deaths annually, posing challenges exacerbated by limited healthcare access and poor primary care quality, particularly in Mexico. Complementary medicine presents a potential solution, offering minimally invasive techniques to improve physical, mental, and spiritual well-being. Effective treatment adherence, crucial for positive outcomes, is influenced by self-efficacy, the ability to manage one's behavior in response to medical conditions. However, treatment adherence rates remain low, indicating a pressing public health concern. This study aimed to explore how perception of complementary medicine and treatment adherence predict self-efficacy among individuals with chronic conditions in Mexico. Analyzing data from 113 participants revealed significant correlations between variables, with treatment adherence positively associated with self-efficacy and perception of holistic medicine negatively correlated with self-efficacy. Regression analysis showed that incorporating perception of complementary medicine and treatment adherence significantly explained self-efficacy levels, suggesting the potential of complementary therapies in holistic healthcare approaches. However, collinearity between variables highlights the need for further research to better understand these relationships and their implications for improving healthcare outcomes in Mexico. Integrating complementary therapies with conventional treatments could enhance overall well-being and treatment adherence, offering promising avenues for addressing chronic conditions in the region. These findings underscore the importance of comprehensive healthcare approaches that integrate both conventional and complementary modalities to optimize health outcomes and quality of life for individuals with chronic conditions in Mexico and beyond.

Aiming at the limitations of single-functionality, limited applicability, and complex designs prevalent in current metasurfaces, we propose a terahertz multifunctional and multiband tunable metasurface utilizing a VO2-metal hybrid structure. This metasurface structure comprises a top VO2-metal resonance layer, a middle polyimide dielectric layer, and a gold film reflective layer at the bottom. This metasurface exhibits multifunctionality, operating independently of polarization and incident angle. The varying conductivity states of the VO2 layers, enable the metasurface to achieve various terahertz functionalities, including single-band absorption, broadband THz absorption, and multiband perfect polarization conversion for linear (LP) and circularly polarized (CP) incident waves. Finally, we believe that the functional adaptability of the proposed metasurface expands the repertoire of options available for future terahertz device designs.

Analyzing BRCA1/2 tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOC) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays, or sequencers used, and data on the execution of tumor tests remains scarce. Therefore, we evaluated characteristics of BRCA1/2 tumor testing in advanced-stage EOC with real-world national data. Pathology reports of patients diagnosed with EOC in 2019 in the Netherlands were obtained from the Dutch Pathology Registry (PALGA), and data regarding histological subtype and BRCA1/2 tumor tests were extracted. A total of 999 patients with advanced-stage EOC were included. Tumor tests were performed for 502 patients (50.2%) and BRCA1/2 TPVs were detected in 14.7%. Of all tests, 48.6% used hybrid capture techniques and 26.5% used PCR-based techniques. More than half of the tests (55.0%) analyzed other genes in addition to BRCA1/2. Overall, this study highlights the heterogeneity in the execution of BRCA1/2 tumor tests. Despite a lack of evidence of quality differences, we emphasize that adequate reporting and internal and external quality monitors are essential for high-quality implementation and execution of reliable BRCA1/2 tumor testing, which is crucial for identifying all patients with BRCA1/2 TPVs.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

A comprehensive investigation was undertaken at Vytautas Magnus University Experimental Station, located at 54°52’50” N latitude and 23°49’41” E longitude on soil (Epieutric Endocalcaric Planosol – PLe-gln-w) since 1999, to understand the impacts of different agrotechnical measures on soil health and crop yield. Two primary factors were assessed. Factor A incorporated practices of straw removal versus straw chopping and spreading, while Factor B evaluated a spectrum of tillage techniques: conventional deep ploughing, shallow ploughing, ploughless tillage, single seedbed discing, and two no-tillage practices, one of which involved cover crops. Findings from this long-term study highlight the significant potential of specific farming systems in enhancing soil organic carbon. It has a positive effect on the release of CO2 emissions from the soil, thus promoting soil resilience and increasing plant productivity. These insights are paramount in devising sustainable agricultural strategies to counter the challenges of climate change on agroecosystems. This research showcases the profound effects of combining residue management and tillage practices, setting a novel standard for sustainable soil management of climatic uncertainties.

Multilineage-differentiating stress-enduring (Muse) cells, a cell subgroup from mesenchymal stem cells (MSCs), are pluripotent cells with unique characteristics such as non-tumorigenic and pluripotent differentiation ability. After homing, Muse cells spontaneously differentiate into tissue component cells and supplement damaged/lost cells to participate in tissue repair. Importantly, Muse cells can survive in injured tissue for an extended period, stabilizing and promoting tissue repair. In addition, it has been confirmed that injection of exogenous Muse cells exerts anti-inflammatory, anti-apoptosis, anti-fibrosis, immunomodulatory, and paracrine protective effects in vivo. The discovery of Muse cells is an important breakthrough in regenerative medicine. The article provides a comprehensive review of the characteristics, sources, and potential mechanisms of Muse cells for tissue repair and regeneration. This review serves as a foundation for the further utilization of Muse cells as a key clinical tool in regenerative medicine.

Previous studies found high but very variable levels of tetranor-PGEM and PGD-M (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF), which correlated with the severity of the CF transmembrane receptor (CFTR) genetic alteration. This study aims to assess the potential role of cyclooxygenase (COX)-1 and COX-2 genetic polymorphisms in the variability of PG production, and determine the potential role of PG metabolites as markers of symptoms severity and imaging findings. Thirty healthy subjects and 103 pwCF were included in the study. Clinical and radiological CF severity was evaluated using clinical scoring methods and the extent of bronchiectasis and air trapping were assessed by chest computed tomography (CT). Urine metabolites were measured using liquid chromatography/tandem mass spectrometry. The presence of variants in the COX-1 gen (PTGS1 639 C>A, PTGS1 762+14delA, and COX-2 gen: PTGS2-899G>C (-765G>C) and PTGS2 (8473T>C) were analysed. PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in healthy controls. There were also statistically significant differences between clinically mild and moderate disease and severe disease. Patients with bronchiectasis and/or air trapping had higher PGE-M levels than patients without these complications. The four polymorphisms did not associate with clinical severity, air trapping, bronchiectasis, or urinary PG levels. Taken together, the present study suggests that urinary PG level testing can be used as a biomarker of CF severity. We found no relationship between COX-1 and COX-2 genetic polymorphisms in the variability of PG production.

Chemo-resistance is a substantial challenge in the realm of cancer treatment that requires exploring new therapeutic approaches for effective mitigation. Achieving this goal requires examination of the molecular mechanisms involved in both tumor growth and therapeutic interventions. The potential of NRF2 (Nuclear factor E2-related factor 2) in addressing resistance to chemotherapy across diverse cancer types highlights its value as a promising therapeutic approach based on cancer characteristics. Manipulating the NRF2 signaling pathway has a dual impact, offering promise for both preventing and treating cancer, as well as inhibiting carcinogenesis. The influence of the NRF2/KEAP1 pathway on the progression of tumor formation and resistance to drugs has been well-documented. The interplay between the NRF2 signaling pathway and processes such as endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy plays a crucial protective role. A deeper understanding of NRF2's role in the modulating these pathways is necessary to develop novel approaches for improving chemotherapeutic efficacy. This article discusses the significance of the NRF2-KEAP1 pathway in preventing/promoting cancer and resistance mechanisms to various chemotherapeutic agents, with a focus on the complementary effects of antioxidants via NRF2-mediated signaling pathways. This study aims to provide a molecular basis for targeting NRF2 via inhibitors/activators as promising therapeutic strategies to overcome chemo-resistance.

In this work, a ZIF-67/MWCNTs/Nafion sensor platform was constructed based on the good adsorption capacity of ZIF-67, the electrical conductivity of multiwalled carbon nanotubes (MWCNTs) and the excellent chemical stability of Nafion for the detection of Cu2+ in water. Meanwhile, the modified materials were characterized by scanning electron microscopy (SEM), Transmission electron microscopy (TEM), BET specific surface area test, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and Fourier transform infrared spectrometry (FT-IR). Cyclic voltammetry (CV), electrochemical impedance (EIS), and square wave solvation voltammetry (SWSV) electrochemical methods were used to perform applied test studies on ZIF-67/MWCNTs/Nafion/GCE. The results show that ZIF-67/MWCNTs/Nafion/GCE has high sensitivity (57.5 μA/μM) and a low limit of detection (15.0 nM) for the electrochemical detection of Cu2+ ions in an electrochemical sensing system. It has high adsorption selectivity for Cu2+, and the recovery of Cu2+ in real water reached 98.6%-103%. The modified electrode has good repeatability, reproducibility, anti-interference, and stability, which makes this sensing platform can be practically applied to the detection of domestic water.

O2 is essential for the life of eukaryotic cells. The ability to sense oxygen availability and initiate a response to adapt the cell to changes in O2 levels is a fundamental achievement of evolution. The key switch for adaptation consists of the transcription factors HIF1A, HIF2A and HIF3A. Their levels are tightly controlled by O2 through the involvement of the oxygen-dependent prolyl hydroxylase domain-containing enzymes (PHDs/EGNLs), the von Hippel-Lindau tumour suppressor protein (pVHL) and the ubiquitin-proteasome system. Furthermore, HIF1A and HIF2A are also under the control of additional post-translational modifications (PTMs) that positively or negatively regulate the activities of these transcription factors. This review focuses mainly on two PTMs of HIF1A and HIF2A: phosphorylation and acetylation.

The targeting-Her-2/neu therapy by passive application with trastuzumab is associated with acquired resistance and subsequent metastasis development, attributed to upregulation of tumoral PD-L1 expression and downregulation of Her-2/neu. We aimed to investigate this association, following active immunization with our recently constructed B cell–peptide based Her-2/neu vaccines in both preclinical and clinical settings. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and combined positive score (CPS), were applied to evaluate Her-2/neu and PD-L1 expression using a murine syngeneic tumor model for Her-2/neu lung metastases, and tumor biopsies from a gastric cancer patient with disease progression. A significant and concomitant reduction of Her-2/neu and upregulation of PD-L1 expression was observed in the vaccinated mice, after 7 but not after 4 weeks of metastases development. A significant increase of tumor-infiltrating B lymphocytes was observed at both time points. Downregulation of Her-2/neu and upregulation of PD-L1 were observed in a patient’s primary tumor at the disease progression time point but not prior to vaccination (Her-2/neu IHC: 3 to 0, FISH: 4.98 to 1.63; PD-L1 CPS: 0% to 5%). Our results further underline the need for combination therapy by targeting PD-L1 to prevent metastasis formation and immune evasion of Her-2/neu positive and PD-L1 negative tumor cells.

Our recent work has focused on the application of infinite group theory and related algebraic geometric tools in the context of transcription factors and microRNAs. We were able to differentiate between “healthy" nucleotide sequences and disrupted sequences that may be associated with various diseases. In this paper, we extend our efforts to the study of messenger RNA metabolism, showcasing the power of our approach. We investigate (i) mRNA translation in prokaryotes and eukaryotes, (ii) polyadenylation in eukaryotes, which is crucial for nuclear export, translation, stability, and splicing of mRNA, (iii) miRNAs involved in RNA silencing and post-transcriptional regulation of gene expression, and (iv) the identification of disrupted sequences that could lead to potential illnesses. To achieve this, we employ (a) infinite (finitely generated) groups fp, with generators representing the r+1 distinct nucleotides and a relation between them [e.g., the consensus sequence in the mRNA translation (i), the poly(A) tail in item (ii), and the miRNA seed in item (iii)], (b) aperiodicity theory, which connects “healthy groups" fp to free groups Fr of rank r and their profinite completion F^r, and (c) the representation theory of groups fp over the space-time-spin group SL2(C), highlighting the role of surfaces with isolated singularities in the character variety. Our approach could potentially contribute to the understanding of the molecular mechanisms underlying various diseases and help develop new diagnostic or therapeutic strategies.

Phosphorus deficiency highly interferes with plant growth and development. Plants respond to the persistent P deficiency by coordinating the expression of genes involved in the alleviation of the stress. Promoters of phosphate transporter genes are of great choice for the development of genetically modified plants with enhanced phosphate uptake abilities, which improve crop yields in phosphate-deficient soils. In our previous study, the sugarcane phosphate transporter PHT1;2 gene, showed a significantly high expression under salinity stress. In this study, the Erianthus arundinaceus EaPHT1;2 gene was isolated and characterized using various in-silico tools. The deduced 542 amino acid residues have 10 transmembrane domains, with a molecular weight and isoelectric point of 58.9 kDa and 9.80, respectively. They displayed 71–96% similarity with Arabidopsis thaliana, Zea mays, and Saccharum hybrid. To elucidate the function of the 5’ regulatory region, the 1.1kb promoter was isolated and validated in tobacco transgenics under Pi stress. The EaPHT1;2 promoter activity was detected using the β-glucuronidase (GUS) assay. While the EaPHT1;2 promoter showed 3 to 4.2-fold higher expression than the most widely used CaMV35S promoter. The 5’ deletion analysis with and without 5’UTR regions, revealed that a small size 374 bp fragment with the highest promoter activity among 5′ truncated fragments, which was 2.7 and 4.2 times higher than the well-used CaMV35S promoter under normal and Pi-deprivation conditions, respectively. The strong and short promoter of EaPHT1;2 with 374 bp showed significant expression in low Pi-stress conditions and it could be a valuable source for the development of stress-tolerant transgenic crops

C-reactive protein to lymphocyte ratio (CLR) has been shown to be associated with diseases characterized by chronic, low-grade inflammation. Since type 2 diabetes (T2DM) is also associated with inflammation, we aimed to study the association between CLR and T2DM. Patients with T2DM who presented to internal medicine outpatient clinics of our institution were divided into 2 groups according to their glycosylated hemoglobin (HbA1c) levels as well-controlled (HbA1c&lt;7%) and poorly controlled (HbA1c≥7%) T2DM groups. Subjects assigned as healthy in routine check-up were included as control group. CLR values of the well and poorly controlled diabetics and control cases were compared. CLR of T2DM group (3.51 (0.03-21.78)) was significantly higher than that of the controls (0.65 (0.02-2.92)) (p&lt;0.001). CLR was found to have a sensitivity of 63.2% and a specificity of 97.3% in predicting T2DM. The CLR value of patients with poor diabetic control was 4.76 (0.06-21.78), while the CLR value of patients with well controlled disease was 2.53 (0.03-12.07) (p&lt;0.001). The sensitivity and specificity of the CLR in demonstrating poor diabetic control was 41.2% and the 86.1%, respectively. In conclusion, elevated CLR in T2DM patients and even more increased levels in poorly controlled diabetics suggest that CLR could be a useful additional diagnostic tool in treatment follow-up of the T2DM population.

A land cover map of two arctic catchments, nearby the Abisko Scientific Research Station, was obtained from a classification of a Sentinel-2 satellite image and a ground survey performed in July 2022. The two contiguous catchments, Miellajokka and Stordalen, are covered by various ecotypes, from boreal forest to alpine tundra and peatland. Two classification algorithms, support vector machine and random forest, were tested and gave very similar results. The percentage of correctly classified pixels was over 88% in both cases. The developed workflow relies solely on open source software and acquired ground observations. Space organization was directed by the altitude as demonstrated by the intersection of the land cover with the topography. Comparison between this new land cover map and previous ones based on data acquired between 2008 and 2011 shows some trends of vegetation cover evolution in response to climate change in the considered area. This land cover map is key input data for permafrost modeling, and hence for the quantification of climate change impacts in the studied area.

Mucinous breast carcinoma is a rare subtype of mammary neoplasm encountered in medical practice. It represents approximately 1-6% of all breast cancers and is more common in postmenopausal women. There are two subtypes of mucinous breast carcinoma: pure and mixed. We report the case of a 73-year-old Caucasian woman diagnosed with mucinous pancreatic cystadenoma in 2007. She underwent a surgical procedure involving pancreatectomy of the body and tail, along with multiple known cardiovascular and metabolic comorbidities. In November 2019, during a clinical-biological evaluation for associated diseases, a mucinous carcinoma of the right breast was accidentally detected and later confirmed through further investigations. For treatment, a surgical procedure was performed involving lower right quadrantectomy with right axillary lymph node dissection. The postoperative clinical course was favorable. In conclusion, we present the case of a patient diagnosed with mixed mucinous breast carcinoma, without axillary lymph node invasion. Postmenopausal women with diabetes, overweight, and obesity have an increased susceptibility to breast cancer, with our patient having all these risk factors. To date, no study has demonstrated the genetic or radiation implication in the occurrence of mucinous carcinomas, nor the possible development of mucinous carcinomas in series in the same patient. Current data are insufficient to provide recommendations for the screening of malignant mucinous tumors in subjects with significant cardiometabolic risk factors.

Alzheimer’s disease(AD) progression correlates with the propagation of hyperphosphorylated Tau (pTau) from the entorhinal cortex to the hippocampus and neocortex. Neutral sphingomyelinase2(nSMase2) is critical in the biosynthesis of extracellular vesicles (EVs), which play a role in pTau propagation. We recently conjugated DPTIP, a potent nSMase2 inhibitor, to hydroxyl-PAMAM-dendrimer nanoparticles which can improve brain delivery. We showed that dendrimer-conjugated-DPTIP (D-DPTIP) robustly inhibited pTau spread in an AAV-pTau propagation model. To further evaluate its efficacy, we tested D-DPTIP in the PS19 transgenic mouse model. Unexpectantly, D-DPTIP showed no beneficial effect. To understand this discrepancy, we assessed D-DPTIP’s brain localization. Using immunofluorescence and fluorescence-activated cell-sorting, D-DPTIP was found to be primarily internalized by microglia where it selectively inhibited microglial nSMase2 activity with no effect on other cell types. Furthermore, D-DPTIP inhibited microglia-derived EV release into plasma without affecting other brain-derived EVs. We hypothesize that microglial targeting allowed D-DPTIP to inhibit tau propagation in the AAV-hTau model, where microglial EVs play a central role in propagation. However, in PS19 mice, where tau propagation is independent of microglial EVs, it had a limited effect. Our findings confirm microglial targeting with hydroxyl-PAMAM dendrimers and highlight the importance of understanding cell-specific mechanisms when designing targeted AD therapies.

Top-down models are defined by hardware architects to provide information on the utilization of the different hardware components. The target is to isolate the users from the complexity of the hardware architecture while giving them insight into how efficiently the code is using the resources. In this paper, we explore the applicability of 4 top-down models defined for different hardware architectures powering state-of-the-art HPC clusters (Intel Skylake, Fujitsu A64FX, IBM Power9, and Huawei Kunpeng 920) and propose a model for AMD Zen 2. We study a parallel CFD code used for scientific production to compare these 5 Top-Down models. We evaluate the level of insight achieved, the clarity of the information, the ease of use, and the conclusions that each one allows us to reach.

Lactic acid bacteria (LAB) have an extracellular proteolytic system that includes a multi-domain, cell envelope protease (CEP) with a subtilisin homologous protease domain. These CEPs have different proteolytic activities despite having similar protein sequences. Structural characterization has previously been limited to CEP homologs of dairy and human derived LAB strains, excluding CEPs of plant derived LAB strains. CEP structures are a challenge to determine experimentally due to their large size and attachment to the cell envelope. This study aims to clarify the prevalence and structural diversity of CEPs by using the structure prediction software AlphaFold 2. Domain boundaries are clarified based on a comparative analysis of 21 three-dimensional structures, revealing novel domain architectures of CEP homologs that are not necessarily restricted to specific LAB species or ecological niches. The C-terminal flanking region of the protease domain is divided into fibronectin type-III-like domains with various structural traits. The analysis also emphasizes the existence of two distinct domains for cell envelope attachment that are preceded by an intrinsically disordered cell wall spanning domain. The domain variants and their combinations provide CEPs with different stability, proteolytic activity and potentially adhesive properties, making CEPs targets for steering proteolytic activity with relevance for both food development and human health.

Polycystic ovary syndrome (PCOS) usually comes along with metabolic disturbances attributed to androgen excess and obesity, but the contribution of each has not been defined, and the occurrence of metabolic disturbances is frequently not investigated. We evaluated 99 PCOS and 41 non-PCOS women. Clinical biomarkers of glucose-, liver-, and endothelial-related metabolic alterations were measured; participants were categorized into four groups according with obesity (OB) and hyperandrogenemia (HA) statuses: Healthy (no-HA, lean), HA (HA, lean), OB (no-HA, OB), and HAOB (HA, OB). Metabolic disturbances were highly frequent in PCOS women (70%). BMI correlated with all biomarkers, while free testosterone (FT) only with glucose- and hepatic-related indicators. Despite insulin sensitivity and liver enzymes were associated with FT, women with obesity exhibited lower M [coeff = 8.56 – 0.080(FT) –3.71(Ob); p &lt;0.001)] and higher aspartate aminotransferase (coeff = 26.27 + 0.532(FT) + 8.08(Ob); p = 0.015)] than lean at the same level of FT. Women with obesity exhibited greater risk of metabolic disorders than lean, independently of hyperandrogenemia. Clinicians are compelled to search for metabolic alterations in PCOS women; obesity must be handled in all cases, but hyperandrogenemia needs to be managed also in those with glucose- or liver-related disturbances.

Introduction: When analyzing the current situation in Spain, derived from our current lifestyles far from following a Mediterranean lifestyle, there is an alarming prevalence of diabesity, which increases the global risk of suffering from cardiovascular disease (CVD) and decreases the quality of life related to health (QLRH). In order to guarantee, beyond glycemic control of patients with type 2 diabetes (DM2), adequate control of cardiovascular risk factors (CVRF) in DM2, it will be necessary to carry out a community intervention focused on the application of education programs focused on promoting the acquisition of healthy eating habits through the Mediterranean diet (DMED). This dietary pattern, together with physical exercise, has been shown to contribute to improving the QLRH of patients. Objective: To analyze the quality of life related to health, present in patients with poorly controlled type 2 diabetes, to determine the possible relationship between this and the degree of adherence to the Mediterranean diet and to examine whether there are differences between the sexes. Material and methods: Observational descriptive study in 93 patients diagnosed with DM2 with poor glycemic control (1Ac ≥ 7%), carried out in various health centers in Albacete and Cuenca, in which the baseline relationship between adherence to DMed and the HRQoL. They were administered a data collection sheet that included a survey of the degree of adherence to the DMed (MEDAS-14) and QLRH (SF-12v2) in the Primary Care (PC) medical and nursing consultations. The variables were analyzed: age groups, sex, years of evolution of DM2, body mass index (BMI), as well as basal glycemia (GB) and glycosylated hemoglobin (HbA1c). The “MEDAS-14” (adherence to DMED) was the main variable and the “SF-12v2” (QLRH) was the secondary variable. Material and methods: Observational descriptive study in 93 patients diagnosed with DM2 with poor glycemic control (1Ac ≥ 7%), carried out in various health centers in Albacete and Cuenca, in which the baseline relationship between adherence to DMed and the HRQoL. They were administered a data collection sheet that included a survey of the degree of adherence to the DMed (MEDAS-14) and QLRH (SF-12v2) in the Primary Care (PC) medical and nursing consultations. The variables were analyzed: age groups, sex, years of evolution of DM2, body mass index (BMI), as well as basal glycemia (GB) and glycosylated hemoglobin (HbA1c). The “MEDAS-14” (adherence to DMED) was the main variable and the “SF-12v2” (QLRH) was the secondary variable. Results: Patients with poorly controlled DM2 and with low adherence to the MedDM show a non-significantly greater affectation in the physical sphere: fair general state of health, physical function I (limitation to make moderate efforts such as moving a table, vacuuming or walk more than an hour), physical function II (limitation to climb several flights of stairs), physical role (problems at work or daily activities doing less than loved ones), physical role II (they had to stop performing some tasks at work or activities of daily living) and regular body pain. Presenting less affectation in the mental field: emotional role I, emotional role II, mental health I, vitality and mental health II. Without affectation in the social function since they consider that rarely the emotional or physical problems have hindered their social activities. Conclusions: Diabetic patients with poor glycemic control have low adherence to the MedMD (<9 points) and have poor QLRH. Low adherence to the DMed and obesity are related to a greater affectation in the physical dimension and less affectation in the mental dimension without affectation in the "social function".

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease, is the most common respiratory morbidity in preterm infants. "Old" or "Classic" BPD, as per the original description, is less common now. "New BPD," which presents with distinct clinical and pathological features, is more frequently observed in the current era of advanced neonatal care, where extremely premature infants are surviving due to medical advancements. The pathogenesis of BPD is complex and multifactorial and involves both genetic and environmental factors. This review provides an overview of the pathology of BPD and discusses the influence of several prenatal and postnatal factors on its pathogenesis, such as maternal factors, genetic susceptibility, ventilator-associated lung injury, oxygen toxicity, sepsis, patent ductus arteriosus (PDA), and nutritional deficiencies. This in-depth review draws on existing literature to explore these factors and their potential contribution to the development of BPD.

Nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome in the kidney and the heart is increasingly being suggested to play a key role in mediating inflammation. In the kidney, NLRP3 activation has been associated with the progression of diabetic kidney disease. In the heart, activation of the NLRP3 inflammasome has been related to enhanced release of interleukin-1β (IL-1β) and the subsequent induction of atherosclerosis and heart failure. Apart from their glucose-lowering effects, SGLT-2 Inhibitors have been documented to attenuate activation of the NLRP3, thus, resulting in the constellation of an anti-inflammatory milieu. In this review, we will focus on the interplay between SGLT-2 Inhibitors and the inflammasome in the kidney, the heart and the neurons in the context of diabetes mellitus and its complications.

Disordered eating is a serious health concern globally. The etiology is complex and multidimensional and differs somewhat for each specific eating disorder. Several risk factors have been identified which include psychological, genetic, biochemical, environmental, and sociocultural factors. Poor body image, low self-esteem, teasing, family dynamics, and exposure to media images have also been identified as risk factors. While it is enticing to consider a single behavioral risk factor, doing so fails to consider the documented environmental, social, psychological, biological, and cultural factors that contribute to the development of an eating disorder in a multidimensional and complex integration that is undoubtedly unique to everyone. Focusing only on any one factor without taking the complex etiology into account is remiss. For example, it has been suggested that the use of dietary supplements may lead to eating disorders, despite a lack of evidence to support this conjecture. Therefore, the purpose of this review is to examine the evidence-based risk factors for eating disorders and discuss why connecting dietary supplements to eating disorder etiology is not supported by the scientific literature and may interfere with treatment. Established, effective prevention and treatment approaches for eating disorders should be the focus of public health initiatives in this domain.

Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type, and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.

Digital Elevation Model (DEM) is a representation of elevation data that represent terrain with or without overlaying objects of the Earth. It is the ideal and most widely used method for determining topography. DEMs are generated from various techniques such as traditional Surveying, Photogrammetry, InSAR, LiDAR, Clinometry and radargrammetry. It has been observed that mostly LiDAR-generated DEMs provide the best accuracy. The unavailability of LiDAR data in most of the region restricts global researchers from high-resolution and accurate DEMs. The recent launch of ICESat-2 with a 13m beam footprint and 0.7m pulse interval, promises elevations at high orbital precision. Its accuracy is of the order of few centimeters in complex topography, because of this ICESat-2 proves to be a good source to generate high-accuracy DEMs. ICESat-2 provides discrete photon data with elevations of points on the Earth’s surface. Traditional interpolation techniques tend to over-smooth the estimated space and still are unable to justify the complicated continuity in the topographical data. Machine learning algorithms are widely being used to extract patterns and spatial extent in geographic data. To estimate a DEM from ICESat-2 LiDAR point data, machine learning regression algorithms are implemented in this study. The present study has been performed for a plain region of Ghaziabad, Uttar Pradesh, India. Studies have shown that Cartosat-1 DEM V3 R1 product provides an accuracy of the order of 2m in predominantly plain regions, hence taken for this region. Current work focuses on comparing various regression-based machine-learning techniques to interpolate DEM from ICESat-2 data The RMSE of the interpolated DEM resulted from the Gradient Boosting Regressor, Random Forest Regressor, Decision Tree Regressor, and Multi-Layer Perceptron Regressor was 7.13m, 7.01m, 7.15m, and 3.76m, respectively when evaluated against the TANDEM-X DEM of the same region. The MLP Regressor is found to perform the best among the four algorithms tested.

A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at King Khalid hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii has occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019 the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high resistant proportion of ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.

Dengue is a viral mosquito-borne disease that rapidly spreads in tropical and subtropical countries, including the Philippines. One of its most distinguishing characteristics is the ability of the Dengue Virus (DENV) to easily surpass the innate responses of the body, thus activating B cells of the adaptive immunity to produce virus-specific antibodies. Moreover, Dengvaxia® is the only licensed vaccine for DENV, but recent studies showed that seronegative individuals become prone to increased disease severity and hospitalization. Owing to this limitation of the dengue vaccine, this study determined and compared consensus and unique B cell epitopes among each DENV (1-4) Philippine isolate to identify potential areas of interest for future vaccine studies and therapeutic developments. An in silico-based epitope prediction of forty (40) DENV 1-4 strains, each serotype represented by ten (10) sequences from The National Center for Biotechnology Information (NCBI), was conducted using Kolaskar and Tongaonkar antigenicity, Emini surface accessibility, and Parker hydrophilicity prediction in Immune Epitope Database (IEDB). Results showed that five (5) epitopes were consensus for DENV-1 with no detected unique epitope, one (1) consensus epitope for DENV-2 with two (2) unique epitopes, one (1) consensus epitope for DENV-3 plus two (2) unique epitopes, and two (2) consensus epitopes and one (1) unique epitope for DENV-4. The findings of this study would contribute to determining potential vaccine and diagnostic marker candidates for further research studies and immunological applications against DENV (1-4) Philippine isolates.

Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiot-ropism and high remodeling capacity. Although the expansion of fat mass, by defini-tion, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardio-vascular complications. The dysfunctional fat displays distinct biological signatures, which include enlarged fat cells (i.e., adipocyte hypertrophy), low-grade inflammation, impaired redox homeostasis, and cellular senescence. While these events are orches-trated in a cell-type, context-dependent and temporal manner, the failure of the adipose precursor cells to form new mature adipocytes appears the main instigator of the adi-pose dysregulation, which, ultimately, poses a deleterious milieu either by promoting ectopic lipid overspill in non-adipose targets (i.e., lipotoxicity) or by inducing an al-tered secretion of different adipose-derived hormones (i.e., adipokines and lipokines). This novel paradigm (“expandability hypothesis”) challenges and extends previous “adipocentric view”, which implies a reduced plasticity of the adipose organ at the nexus between “unhealthy” fat expansion and the development of obesity-associated comorbidities. In this review, we will briefly summarize the potential mechanisms by which adaptive changes to variations of energy balance may impair adipose plasticity and promote fat organ dysfunction. We will also highlight the conundrum with the perturbation of the adipose microenvironment and the development of cardio-metabolic complications by focusing on adipose lipoxidation and cellular senescence. Finally, we discuss the sci-entific rationale for proposing adipose organ plasticity as a target to curb/prevent adi-posity-linked cardio-metabolic complications.

Background/methods: For mechanistic studies, in vitro human B cell differentiation and generation of plasma cells are invaluable techniques. However, the heterogeneity of both T cell-dependent (TD) and T cell-independent (TI) stimuli and the disparity of culture conditions used in existing protocols makes interpretation of results challenging. The aim of the present study was to achieve the most optimal B cell differentiation conditions using isolated CD19⁺ B cells and PBMC cultures. We addressed multiple seeding densities, different durations of culturing and various combinations of TD stimuli and TI stimuli including B cell receptor (BCR) triggering. B cell expansion, proliferation and differentiation was analyzed after 6 and 9 days by measuring B cell proliferation and expansion, plasmablast and plasma cell formation and immunoglobulin (Ig) secretion. In addition, these conditions were extrapolated using cryopreserved cells and differentiation potential was compared. Results: This study demonstrates improved differentiation efficiency after 9 days of culturing for both B cell and PBMC cultures using CD40L and IL-21 as TD stimuli and 6 days for CpG and IL-2 as TI stimuli. We arrived at optimized protocols requiring 2500 and 25.000 B cells per culture well for TD and TI assays, respectively. The results of the PBMC cultures were highly comparable to the B cell cultures, which allows dismissal of additional B cell isolation steps prior to culturing. In these optimized TD conditions, the addition of anti-BCR showed little effect on phenotypic B cell differentiation, however it interferes with Ig secretion measurements. Addition of IL-4 to the TD stimuli showed significantly lower Ig secretion. The addition of BAFF to optimized TI conditions showed enhanced B cell differentiation and Ig secretion in B cell but not in PBMC cultures. With this approach, efficient B cell differentiation and Ig secretion was accomplished when starting from fresh or cryopreserved samples. Conclusion: Our methodology demonstrates optimized TD and TI stimulation protocols for more indepth analysis of B cell differentiation in primary human B cell and PBMC cultures while requiring low amounts of B cells, making them ideally suited for future clinical and research studies on B cell differentiation of patient samples from different cohorts of B cell-mediated diseases.

The open-bundle structure of cytochrome c’ as an unfolding intermediate was determined by small-angle neutron scattering experiment (SANS). The four-α-helix bundle structure of Cyt c’ at neutral pH was transited to an open-bundle structure (at pD ~13), which is a joint-clubs consisting of four clubs (α-helices) connected by short loops. The compactly folded structure of Cyt c’ (radius of gyration, Rg = 18 Å for the Cyt c’ dimer) at neutral or mildly alkaline pD transitioned to a remarkably larger “open-bundle” structure at pD ~13 (Rg = 25 Å for the Cyt c’ monomer). Cyt c’ adopts an unstructured random coil structure at pD = 1.7 (Rg = 25 Å for the Cyt c’ monomer). Numerical partial scattering function analysis (joint-clubs) and ab initio modelling gave structures similar to the “open-bundle”, which retains the α-helices but loses the bundle structure.