The study assessed the risk perception, attitude, and management tools of 260 randomly selected farmers and processors in the rice value chain using data elicited via a structured questionnaire. Descriptive statistics, Equally Likely Certainty Equivalent (ELCE) technique, Binary logistic regression, and a 5-point Likert scale were employed in the data analyses. Descriptive statistics show that the respondents are young, active, and in their productive age with an intermediate education level. Majority of the farmers and processors were risk averse. Risk aversion was common among farmers and processors. Farmers' risk attitudes and perceptions of risk are significantly influenced by a number of factors, including age, access to extension services, farm size, marital status, household size, education, income, training, and experience. Majority of rice farmers consider price risk as the most important risk while majority of processors perceive production risk as the most important risk. Pests and diseases, price fluctuation, drought, and lack of input were the most important source of risk to farmers, while processors perceived price fluctuation, technology adoption, and poor storage facilities as the most important source of risk. Off-farm investment, spraying for pests and diseases, cash contribution, market information, and cooperative were the important risk mitigating management strategies employed by the farmers/processors. The study suggests improvements in the identified risk sources, which could influence the attitude and perception of the farmers and processors.

In this paper, comprehensive analysis of combined effect of major influencing parameters on heat transfer in the single U-tube BHE (sBHE) and double U-tube BHE (dBHE) with two independent circuits was performed by using validated numerical heat transfer model. Geometrical parameters, such as shank spacing (with maximum, average and minimum values) and borehole diameter (large, medium and small borehole sizes) and borehole depth (shallow, average and deep borehole depths) as well as thermal conductivity of soil and grout which ranges from minimum to high value were considered. The combined impact of these parameters was included under four major cases: 1) combined effect of borehole depth, borehole size and shank spacing; 2) combined effect of borehole depth, and soil and grout thermal conductivity; 3) combined effect of soil and grout thermal conductivity and borehole size; and 4) combined effect of soil thermal conductivity, borehole size and shank spacing. Each of these major cases has nine different design options of both sBHE and dBHE. Series of results of heat transfer per unit borehole depth were generated for all the considered various cases. With the given parameters, the BHE case that provides highest heat transfer among the various cases of sBHE and dBHE were obtained.

Machine learning (ML) systems that use sensors obtain observations from sensors and use them to recognize and interpret the current situation. These systems are susceptible to sensor-based adversarial example attacks (AEs); if some sensors are vulnerable and can be compromised by an attacker, the attacker can change the output of the system by changing the values of the sensors. The detection of compromised sensors is important to defend the system against sensor-based AEs, because we can check the sensors and replace them by detecting the sensors used by the attacker. In this paper, we propose a method to detect the sensors used in sensor-based AEs by utilizing the features of the attack that cannot be avoided. In this method, we introduced a model called the feature-removable model (FRM), which allows us to select the features used as inputs into the model. Our method detects the sensors used in sensor-based AEs by finding the inconsistencies between the outputs of the FRM obtained by changing the selected features. We evaluated our method using a human activity recognition model with sensors attached to the user’s chest, wrist, and ankle. We demonstrate that our method can accurately detect sensors used by the attacker and achieves an average Recall of Detection of 0.92, and the average Precision of Detection is 0.72.

Urothelial cell carcinoma (UCC, bladder cancer) remains a difficult to treat malignancy with rising incidence worldwide. In the U.S., UCC is the sixth most incident neoplasm and ~90% of diagnoses are made in those >55 years of age, ~four times more commonly observed in men than women. The most important risk factor for developing bladder cancer is tobacco smoking, which accounts for ∼50% of cases followed by occupational exposure to aromatic amines and ionizing radiation. The standard of care for advanced UCC includes platinum-based chemotherapy and programmed cell death (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors, administered as frontline, second-line, or maintenance therapy. UCC is highly aggressive and remains generally incurable since these cancers are associated with intrinsic and acquired drug resistance. UCC is highly lethal in the metastatic state and characterized by genomic instability, high PD-L1 expression, DNA damage-response mutations, and high tumor mutational burden. Although immune checkpoint inhibitors (ICIs) achieve long-term durable responses in other cancers, their ability to achieve similar results with metastatic UCC (mUCC) is not as well-defined. Here, we discuss the novel therapies to improve the management of mUCC.

During chronic liver injury, inflammation leads to liver fibrosis— particularly due to the activation of hepatic stellate cells (HSCs). However, the involvement of inflammatory cytokines in HSC activation and the relationship among different liver cells is unclear. To examine their interactions, many in vitro liver models are performed in organoid or spheroid culture with random 3D structure, complicating analysis. Herein, we demonstrated the hierarchical coculture of primary rat hepatocytes with non-parenchymal cells such as the human-derived HSC line (LX-2) and liver sinusoidal endothelial cell line (TMNK-1). The cocultured tissue had high usability with simple operation of separating solid and liquid phases with improved liver functions such as albumin production and hepatic cytochrome P450 3A4 activity. We also studied the effects of stimulation by both oxygen tension and the key pro-fibrogenic cytokine, transforming growth factor beta (TGF-β), on HSC activation. Gene expression analysis revealed that lower oxygen tension and TGF-β1 stimulation enhanced collagen type I and alpha-smooth muscle actin expression from LX-2 cells in the hierarchical coculture. Therefore, this hierarchical in vitro cocultured liver tissue could provide an improved platform as a disease model for elucidating the interactions of various liver cell types and biochemical signals in future liver fibrogenesis studies.

We have defined M cycles as modified form of Gleissberg cycles to study the quasi-periodic secular changes in sunspot activity. Using direct and proxy observations for more than 1200 years we have provided evidence for the influence of the above M cyles on the monsoon rainfall variability and occurrences of major droughts in India. The solar cycle averages of All Indian summer monsoon rainfall (AISMR) and probability of observation of below or above normal AISMR is found to show correlated variations with changes in amplitude of sunspot cycles during the years 1901-2018 AD. Major droughts in India show a preference to occur during minima and declining phases of the M cycles during the years 650-2018 AD . We could generally find low probability of occurrence of droughts in India during the medieval solar maximum epoch ( 1100-1250 AD) and during most of the prolonged sunspot minima periods including the Maunder minima. The evolution of mean Indian summer monsoon rainfall during 650-1900 AD is studied using proxy data from multiple sources with maxima during the 12^th century and minima during 14^th and 19^th centuries. The association of Indian droughts with El-Nino and the possibilities of long term prediction of Indian summer monsoon rainfall variability will be also discussed

An investigation was carried out to study the effects of television and internet on academic performance of senior secondary schools students in Rigachukun Inspectorate of Kaduna state. A well structured and designed questionnaire was adopted in eliciting information from the respondents. The respondents were sampled from schools within Kaduna state. The information obtained showed that the percentage of senior secondary school students who made use of internet for academic purpose was as much as those who could not operate a computer or even browse the internet. Good number of students applied internet mostly through phones and computer with internet access in solving their assignment. A larger percentage of students devoted their time to watching non-educative programs on television, even though it was discovered that some of them also watch educative programs. Positive impacts of television and internet are however obscuring and not glaring. Investigation carried out revealed that students in senior secondary schools need to be sensitized and oriented on how they can derive the best from internet and television. Schools should be encouraged in using television and internet as an instrument of learning and teaching.

In 2011, it was reviewed that there is a strong co-occurrence between major depression and chronic fatigue syndrome (CFS), with fatigue and physio-somatic symptoms being key symptoms of depression, and depressive symptoms appearing during the course of CFS. Moreover, the comorbidity between both conditions may in part be explained by activated immune-inflammatory pathways, including increased translocation of Gram-negative bacteria and increased levels of pro-inflammatory cytokines, such as interleukin (IL)-1. Nevertheless, the possible involvement of activated microglia in this comorbidity has remained unclear. This paper aims to review microglial disturbances in major depression, CFS and their comorbidity. A comprehensive literature search was conducted using the PubMed / MEDLINE database to identify studies that are relevant to this current review. Depressed patients present neuroinflammatory alterations, probably related to microglial activation, while animal models show that a microglial response to immune challenges including lipopolysaccharides is accompanied by depressive-like behaviors. Recent evidence from preclinical studies indicate that activated microglia have a key role in the onset of fatigue. In chronic inflammatory conditions, such as infections and senescence, microglia orchestrate an inflammatory microenvironment thereby causing fatigue. In conclusion, based on our review we may posit that shared immune-inflammatory pathways and activated microglia underpin comorbid depression and CFS and that activated microglia are the main orchestrators of this comorbidity. As such, microglial activation and neuro-inflammation may be promising targets to treat the overlapping manifestations of both depression and CFS.

This study evaluates the feasibility of stabilizing clay bricks with marble cutting waste (MCW). This waste currently discarded in huge quantities as a sludge resulted from sawing the marble blocks to slabs, grinding and polishing of marble processes to the landfills located around the marble processing factories located in the Shaq El-Thoban industrial zone, Cairo governorate, Egypt causing negative impacts on the environment, health and sustainable development. Experimental investigations were carried out to explore the effect of addition of the MCW in different clay-base mixes at different percentages up to 25% at the expense of the hydrated lime. Cement, hydrated lime and MCW are the three types of solidification agents used, clay and sand were also added in the formulations of the unfired clay brick specimens. Laboratory cylindrical stabilized and compressed specimens were made, and then they were cured in a humidity chamber for 2 and 4 weeks, then after were air dried, tested and evaluated according to the Egyptian code for the building by the stabilized and compressed earth soil (ECBS, 2016). To enhance the durability of the cured specimens, transparent silicon – based paint was used for this purpose. The laboratory results demonstrate high potential usage of MCW based additives up to 15% incorporating HL. In addition, the used paint could be an effective treatment way for the use of stabilized bricks in a wet environment. The use of eco-friendly building materials will be a great contribution for the environmental advantages and suggest a remarkable economical alternative to the fired building units.

The tumor microenvironment is known to have increased levels of cytokines and metabolites, such as glutamate, due to their release from the surrounding cells. A normal cell around the tumor that responds to the inflammatory environment is likely to be subsequently altered. We will discuss how these abnormalities will support tumor survival via the actions of gap junctions (GJs) and hemichannels (HCs) which are composed of hexamer of connexin 43 (Cx43) protein. In particular, we will discuss how GJ intercellular communication (GJIC) in glioma cells, the primary brain tumor, is a regulatory factor and its attenuation leads to tumor invasion. In contrast, the astrocytes, which are normal cells around the glioma, are "hijacked" by tumor cells, either by receiving the transmission of malignant substances from the cancer cells via GJIC, or perhaps via astrocytic HC activity through the paracrine signaling which enable the delivery of these substances to the distal astrocytes. This astrocytic signaling would promote tumor expansion in the brain. In addition, brain metastasis from peripheral tissues has also been known to be facilitated by GJs formed between cerebral vascular endothelial cells and cancer cells. Astrocytes and microglia are generally thought to eliminate cancer cells at the blood brain barrier. In contrast, some reports suggest they facilitate tumor progression as tumor cells take advantage of the normal functions of astrocytes that support the survival of the neurons by exchanging nutrients and metabolites. In summary, GJIC is essential for the normal physiological function of growth and allowing the diffusion of physiological substances. Therefore, whether GJIC is cancer promoting or suppressing may be dependent by what permeates through GJs, when it is active, and to which cells. The nature of GJs, which has been ambiguous in brain tumor progression, will need to be re-visited and understood together with new findings on Cx proteins and HC activities.

Objective: The primary objective of this trial was to assess the transfer of drospirenone to breast milk after daily administration of an oral test preparation containing 4 mg of drospirenone at the steady state. The secondary objective of the trial was to assess the safety of the preparation based on safety clinical and laboratory measurements (at the beginning and at the end of the trial) and reporting of adverse events and/or adverse drug reactions. Patients and Methods: This was an open label, non-comparative single center study. Drospirenone 4mg per day was the first postpartum contraceptive for the study participants who were no longer breastfeeding yet were still lactating. It was administered for 7 (seven) days to achieve steady-state concentration. All participants were volunteers who planned to use oral contraceptives as their family planning method in the future. Results: A total number of 12 volunteers completed the trial according to the protocol and the samples of all the 12 study completers were analyzed. The average concentration-time curve of drospirenone in plasma 24 h after the administration of the last dose (AUC(0-24h)) was 635.33 ng*h/mL and 120 h after the single repeat dose administration (AUC(0-120h) was 1180.57 ng*h/mL, respectively. The average Cmax was 48.64 ng/mL. The average concentration-time curve of drospirenone in milk 24 h after the administration of the last dose (AUC(0-24h)) was 134.35 ng*h/mL and 120 h after the single repeat dose administration (AUC(0-120h) was 227.17 ng*h/mL respectively. The average Cmax was 10.34 ng/mL. Conclusion: On average 18.13% of plasma drospirenone made it to breast milk and the highest concentration of drospirenone in breast milk was 17.55% of that in plasma. The total quantity of drospirenone passing to breast milk is on average 4478 ng during a 24 h period representing 0.11% of the maternal daily dose. Thus, at the recommended doses, no effects on breastfed newborns/infants are anticipated with drospirenone 4 mg.

The leather industry is one of the most polluting industries in the world due to the large amounts of waste following the raw hides processing, but also due to the high content of chemicals present in their composition. The main problem of chromium-tanned leather solid waste is related to their storage, because of the ability of chromium to leach in soil or water, and also owing to the high ability of trivalent chromium to oxidize to its toxic form, hexavalent chromium. The purpose of this study is to present the latest methods for extracting trivalent chromium from the composition of solid leather wastes. The extraction methods identified in the present study are based on acid/basic/enzymatic hydrolysis and substitution with the help of organic chelators (organic acids and organic acid salts). In addition, the study includes a comparative analysis between the advantages and disadvantages of each identified extraction method. At the same time, the study also presentes alternative chromium extraction methods based on the combination of conventional extraction methods and ultrasound-assisted extraction.

The accurate detection and assessment of stress play a pivotal role in enhancing individual well-being and healthcare outcomes. Traditional methods of stress detection often grapple with limitations in accuracy and scalability. With the advent of machine learning (ML), the potential to revolutionize stress detection has emerged. This paper presents a comprehensive study on the application of ML algorithms for stress detection, with a focus on physiological and behavioral data analysis. Central to our approach is the integration of SHapley Additive exPlanations (SHAP), an Explainable Artificial Intelligence (XAI) technique, to interpret ML models. SHAP provides a novel lens to understand the impact of individual features in the complex decision-making processes of ML models, thereby enhancing the transparency and reliability of stress predictions. We demonstrate how SHAP not only aids in elucidating model decisions but also contributes to refining the models for greater accuracy. Our results highlight the effectiveness of ML in detecting stress and the pivotal role of XAI in making these models more interpretable and trustworthy. This study underscores the synergy between advanced ML techniques and XAI, paving the way for more nuanced and reliable stress detection methodologies that are essential in diverse settings, from healthcare to workplace environments.

Background: Vaccination against influenza has proven to reduce influenza-caused hospital entries, treatment times in intensive care units and hospitalisation costs for treating people with Diabetes Mellitus. Despite the existing influenza vaccination recommendations for all persons with Diabetes Mellitus, in Spain, vaccination rates lag behind target. We aimed to assess predictors for vaccination uptake and reasons for non-adherence. Methods: Data from the 2020 European Health Interview Survey were analysed using uni-and multivariable logistic regression models, stratified by age group and including possible confounders and vaccination as an outcome. Associations to the sociodemographic profile, healthcare access and substance use were explored. Results: Our analysis included 2,194 individuals with Diabetes Mellitus over the age of 15, showing an influenza vaccination rate of 53%. The findings revealed significant predictors of vaccination uptake, including age over 60 years and robust social support. Conversely, younger age, higher education levels, infrequent healthcare interactions, and economic barriers emerged as significant obstacles to vaccination. Conclusions: To enhance vaccination rates, targeted public health interventions should emphasize the importance of vaccination for younger, more educated individuals with DM, those facing economic barriers, and those with lower levels of social support could bridge the existing gap in vaccination coverage.

Cowpea chlorotic mottle virus (CCMV) is a plant virus explored as a nanotechnological platform. The robust self-assembly mechanism of its capsid protein allows for drug encapsulation and targeted delivery. Additionally, the capsid nanoparticle can be used as a programmable platform to display different molecular moieties. In view of future applications, efficient production and purification of plant viruses is a key step. In established protocols, the need for ultracentrifugation is a significant limitation due to cost, difficult scalability, and safety issues. In addition, the purity of the final virus isolate often remains unclear. Here, an advanced protocol for the purification of CCMV from infected plant tissue was developed, focusing on efficiency, economy, and final purity. The protocol involves precipitation with PEG 8000, followed by an affinity extraction using a novel peptide aptamer. The efficiency of the protocol was validated using size exclusion chromatography, MALDI-TOF mass spectrometry, reversed-phase HPLC, and sandwich immunoassay. It was demonstrated that the final eluate of the affinity column is of exceptional purity (98.4%) determined by HPLC and detection at 220 nm. The scale-up of our proposed method seems to be straightforward, which opens the way to the large-scale production of such nanomaterials. This highly improved protocol may facilitate the use and implementation of plant viruses as nanotechnological platforms for in vitro and in vivo applications.

SLM Additive Manufacturing has demonstrated great potential for aerospace applications when structural elements of individual design and/or complex shape need to be promptly supplied. 3D-printable AlSi10Mg (RS-300) alloy is widely used for the fabrication of different structures in aerospace industry. The importance of the evaluation of residual stresses that arise as a result of complex 3D-printing process thermal history is widely discussed in literature, but systematic assessment remains lacking for their magnitude, spatial distribution, and comparative analysis of different evaluation techniques. In this study we report the results of a systematic study of residual stresses in a 3D-printed double tower shaped samples using several approaches: the contour method, blind hole drilling laser speckle interferometry, X-ray diffraction, and Xe pFIB-DIC micro-ring-core milling analysis. We show that a high level of tensile and compressive residual stresses is inherited from SLM 3D-printing and retained for longer than 6 months. The stresses vary over a significant proportion of the material yield stress. All residual stress evaluation techniques considered returned comparable values of residual stresses even regardless of dramatically different dimensional scales from millimeters for the Contour Method down, laser speckle interferometry and XRD and down to small fractions of a mm (70 μm) for Xe pFIB-DIC ring-core drilling. The use of residual stress evaluation is discussed in the context of optimizing the printing strategy to enhance the mechanical performance and long-term durability.

Breeding for low hydrogen cyanide (HCN) varieties is a major objective of programmes targeting boiled cassava food product. To enhance breeding for low HCN, knowledge on genetic variation and trait heritability is essential. In this study, 64 cassava clones established across four locations and evaluated for HCN using three HCN assessment methods; 1 to 9 scale, 0 ppm to 800 ppm scale and a quantitative assay based on spectrophotometer readings (HCN_Spec). Data were also collected on the weather variables precipitation, relative humidity, and temperature. Significant differences were observed among clones (P < 0.001) and locations (p < 0.001). There were also significant (p < 0. 001) clone by environment interactions. Locations Arua and Serere posted higher HCN scores among clones and were associated with significantly higher (p < 0.001) mean daily temperature (K) and lower relative humidity (%) across 12-hour and 18-hour intervals. Within locations HCN broad sense heritability estimates ranged 0.22 – 0.64 while combined location heritability estimates ranged 0.14 to 0.32. Relationships between the methods were positive and strong (R2 = 0.75 – 0.92). It is expected that the information herein will accelerate efforts towards breeding for low HCN cassava varieties.

Background: Several hereditary-familial syndromes associated with various types of tumors have been identified to date, evidencing that hereditary cancers caused by germline mutations account for 5-10% of all tumors. Advances in genetic technology and the implementation of Next Generation Sequencing (NGS) have accelerated the discovery of several susceptibility cancer genes, allowing the detection of cancer-predisposing mutations in a larger number of cases. The aim of this study is to highlight how the application of an NGS-multi gene panel to a group of oncological patients subsequently leads to the improvement of healthy pathogenic variants/likely pathogenic variants (PVs/LPVs) carriers' identification and prevention of the disease in these cases. Methods: Starting from a total of 110 cancer patients carrying PVs/LPVs in genes involved in cancer susceptibility detected by a customized NGS panel of 27 cancer-associated genes, we enrolled 250 healthy collateral family members from January 2020 to July 2022. The specific PVs/LPVs identified in each proband were tested in healthy collateral family members by Sanger sequencing. Results: 131 out of the 250 cases (52%) weren’t carriers of the mutation detected in the affected relative, while 119 were carriers. Of these, 81/250 patients carried PVs/LPVs on BRCA1/2 (33%), 35/250 harbored PVs/LPVs on other genes beyond BRCA1 and BRCA2 (14%), and 3/250 (1%) were PVs/LPVs carriers both on BRCA1/2 and on another susceptibility gene. Conclusion: Our results show that the analysis of BRCA1/2 genes only would have resulted in a missed diagnosis in a number of cases and in the lack of prevention of the disease in a considerable percentage of healthy carriers with a genetic mutation (14%).

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachythera-py has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision-making regarding radiological parameters by radiation oncologists. Combined use of LDR brachytherapy with other therapeutical modalities, such as external beam radiation and androgen deprivation therapy, for clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology depart-ments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

It is unclear how maternal glycemic status and maternal iodine status influence birth weight in mild-to-moderate iodine deficiency (ID). We studied the association between birth weight and both maternal glucose levels and iodine intake in pregnant women with mild-to-moderate ID. Glucose values were assessed using a glucose challenge test (GCT), non-fasting glucose before delivery; iodine status was assessed using an iodine food frequency questionnaire, serum thyroglobulin (Tg) and urinary iodine concentrations (UIC). Thyroid antibodies and free thyroxine (FT4) were measured. Obstetric and an-thropometric data were also collected. Large for gestational age (LGA) was predicted using a Cox proportional hazards model with multiple confounders. Tg>13g/L was in-dependently associated with LGA (adjusted hazard ratio = 3.4, 95% CI: 1.4–10.2, p=0.001). Estimated iodine intake correlated with FT4 among participants reporting io-dine-containing supplements (ICS) after adjusting for confounders (β = 0.4 95 %CI: 0.0002-0.0008, p=0.001). Newborn weight percentiles were inversely correlated with maternal FT4 values (β=-0.2 95 %CI:-0.08 - -56.49, p=0.049). We conclude that in mild-to-moderate ID regions, maternal insufficient iodine status may increase LGA risk. Iodine status and ICS intake may modify the effect maternal dysglycemia has on offspring weight.

Dengue infection is one of the most important vector-borne diseases worldwide and is a significant public health problem in the tropics. Mosquito control continues to be the primary approach to reducing the disease burden and the dengue virus (DENV) spread. Aside from the traditional larviciding and adulticiding interventions, autodissemination using pyriproxyfen-treated (AD-PPF) ovitraps is one of the promising methods to complement existing vector control strategies. Our paper assessed the efficacy of AD-PPF in reducing DENV infection in two barangays in Parañaque City. Using saliva samples from the participants from both the control and intervention sites, we collected the seroprevalence data for three months in each of the two years. Spatial analysis was conducted to determine hotspot areas and identify DENV infection distributions across the trial periods. Results showed that the intervention site was identified as having clustering of DENV infection in Month 0 of Year 1 and shifted to random dispersion of dengue cases at the end of Month 3 in Year 2. The disappearance of the clustering of the intervention site translates to a decrease in the cases of DENV infection relative to the control site. Furthermore, we also identified that DENV infection transmission occurs at a small-scale level that did not go beyond 86 meters. In conclusion, AD-PPF is suggested to be an effective strategy and may be used as an additional vector control approach, albeit in its short-term implementation.

Klebsiella pneumoniae is a multidrug-resistant opportunistic human pathogen related to various infections. As such, synthetic peptides have emerged as potential alternative molecules. Mo-CBP3-PepI has presented great activity against K. pneumoniae by presenting an MIC50 at a very low concentration (31.25 µg mL-1). Here, fluorescence microscopy and proteomic analysis revealed the alteration in cell membrane permeability, ROS overproduction, and protein profile of K. pneumoniae cells treated with Mo-CBP3-PepI. Mo-CBP3-PepI led to ROS overaccumulation and membrane pore formation in K. pneumoniae cells. Furthermore, the proteomic analysis highlighted changes in essential metabolic pathways. For example, after treatment of K. pneumoniae cells with Mo-CBP3-PepI, it was seen a reduction in the abundance of protein related to DNA and protein metabolism, cytoskeleton and cell wall organization, redox metabolism, regulation factors, ribosomal proteins, and resistance to antibiotics. These reductions lead to the inhibition of DNA repair, inhibition of cell wall turnover, protein turnover, and ROS accumulation leading to cell death. Our findings indicated that Mo-CBP3-PepI might have mechanisms of action against K. pneumoniae cells, mitigating the development of resistance and thus being a potent molecule to be employed in producing new drugs against K. pneumoniae infections.

In a meta-analysis, we examined the behavioral portfolio of invasive brown anoles (Anolis sagrei) and native green anoles (Anolis carolinensis) in urban and non-urban environments. We hypothesized that invasive anoles should display more agonistic and bold signals (head bobbing, dewlap extensions and pushups) than their native range counterparts, and their native competitors. We found that in urban settings, anoles of both species signaled more with dewlap extensions than with head-bobs. The brown anoles displayed significantly higher in non-urban habitats and their native range compared to urban habitats and invasive ranges. The outcome of our analysis suggests that brown anoles have plastic behavioral portfolios, whereas the green anole have relatively balanced preferences for head-bobbing irrespective of the habitat in which the populations were collected. We attribute the success of the brown anole invasion to the flexible strategy in face of higher mate competition, higher predation risks, and less resource competition in the urban environments and invasive ranges. Lastly, we observed publication biases. More studies are conducted with urban and invasive brown anoles and specifically in manipulative mesocosm experimental settings - transplanting populations from native field settings. We show this altered the display rates across all studied signals.

Phosphodiesterases (PDEs) are the principal superfamily of enzymes responsible for degrading the secondary messengers 3’,5’-cyclic nucleotides cAMP and cGMP. Their refined subcellular localization and substrate specificity contribute to finely regulate cAMP/cGMP gradients in various cellular microdomains. Redistribution of multiple signal compartmentalization components is often perceived under pathological conditions. Thereby PDEs have long been pursued as therapeutic targets in diverse disease conditions including neurological, metabolic, cancer and autoimmune disorders in addition to numerous cardiovascular diseases. PDE2 is a unique member of the broad family of PDEs. In addition to its capability to hydrolyze both cAMP and cGMP, PDE2 is the sole isoform that may be allosterically activated by cGMP increasing its cAMP hydrolyzing activity. Within the cardiovascular system, PDE2 serves as an integral regulator for the crosstalk between cAMP/cGMP pathways and thereby may couple chronically adverse augmented cAMP signalling with cardioprotective cGMP signalling. This review provides a comprehensive overview of PDE2 regulatory functions in multiple cellular components within the cardiovascular system and also within various subcellular microdomains. Implications for PDE2 mediated crosstalk mechanisms in diverse cardiovascular pathologies are discussed highlighting the prospective use of PDE2 as a potential therapeutic target in cardiovascular disorders.

Coronavirus disease 2019 (COVID-19) was recently appeared all over the world. The viral main protease (3-chymotrypsin-like cysteine enzyme) controls COVID-19 duplication and manages its life cycle, making it a drug discovery target. Therefore, herein, we analyzed the theoretical approaches of 10 structurally different hydrolysable tannins as natural anti-COVID-19 through binding with the main protease of 2019-nCoV using molecular docking modelling via Molecular Operating Environment (MOE v2009) software. Our results revealed that there are top three hits may serve as potential anti-COVID-19 lead molecules for further optimization and drug development to control COVID-19. Pedunculagin, tercatain, and punicalin were found to faithfully interact with the receptor binding site and catalytic dyad (Cys145 and His41) of COVID-19 main protease, showing their successfully inhibit the protease enzyme of 2019-nCoV. We anticipated that this study would pave way for tannins based novel small molecules as more efficacious and selective anti-COVID-19 therapeutic compounds.

The use of unmanned aerial vehicle (UAV) during emergency response of a disaster has been widespread in recent years and the terrain images captured by the cameras on board these vehicles are significant sources of information for such disaster monitoring operations. Thus, analyzing such images are important for assessing the terrain of interest during such emergency response operations. Further, these UAVs are mainly used in disaster monitoring systems for the automated deployment of sensor nodes in real time. Therefore, deploying and localizing the wireless sensor nodes optimally, only in the regions of interest that are identified by segmenting the images captured by UAVs, hold paramount significance thereby effecting their performance. In this paper, the highly effective nature-inspired Plant Growth Simulation Algorithm (PGSA) has been applied for the segmentation of such terrestrial images and also for the localization of the deployed sensor nodes. The problem is formulated as a multi-dimensional optimization problem and PGSA has been used to solve it. Furthermore, the proposed method has been compared to other existing evolutionary methods and simulation results show that PGSA gives better performance with respect to both speed and accuracy unlike other techniques in literature.

Obesity is a chronic disease that is rapidly increasing in prevalence and affects more than 600 million adults worldwide, and this figure is estimated to increase by at least double by 2030. In the United States, more than one-third of the adult population is either overweight or obese. The global obesity epidemic is a major risk factor for the development of life-threatening arrhythmias occurring in patients with long QT, particularly in conditions where multiple heart-rate-corrected QT-interval-prolonging mechanisms are simultaneously present. In obesity, excess dietary fat in adipose tissue stimulates the release of immunomodulatory cytokines such as interleukin (IL)-6, leading to a state of chronic inflammation in patients. Over the last decade, increasing evidence has been found to support IL-6 signaling as a powerful predictor of the severity of heart diseases and increased risk for ventricular arrhythmias. IL-6’s pro-inflammatory effects are mediated via transsignaling and may represent a novel arrhythmogenic risk factor in obese hearts. The first selective inhibitor of IL-6 trans-signaling, olamkicept, has shown encouraging results in phase II clinical studies for inflammatory bowel disease. Nevertheless, the connection between IL-6 trans-signaling and obesity-linked ventricular arrhythmias remains unexplored. Therefore, understanding how IL6 trans-signaling elicits a cellular pro-arrhythmic phenotype and its use as an anti-arrhythmic target in a model of obesity remain unmet clinical needs.

Obesity is a major risk factor for the development of life-threatening malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Risks may be highest for patients with high levels of the proinflammatory cytokine interleukin (IL)-6. We used our guinea pig model of high-fat diet (HFD) induced Ventricular arrhythmias, that exhibit heightened proinflammatory-like pathology which is also observed in human obesity VT, as well as immunofluorescence, and confocal microscopy approaches to evaluate the pathological IL-6 trans-signaling function and explore the underlying mechanisms. Using blind-stick and electrocardiogram (ECG) techniques, we tested the hypothesis that heightened IL-6 trans-signaling exhibit enhanced Ventricular arrhythmias /SCD incidence and underlying arrhythmia substrates. Remarkably, compared to low-fat (LFD) diet fed controls, HFD promotes phosphorylation of the IL-6 signal transducer and activator of transcription 4 (STAT4) leading to its activation and enhanced nuclear translocation of pSTAT4/STAT4 more than LFD controls and pSTAT3/STAT3 nuclear expression. Overactivation of IL-6 trans-signaling in guinea pigs prolonged the QT interval that resulted in greater susceptibility to VT/SCD with isoproterenol challenge, as also observed with the downstream Janus kinase (JAK) 2 activator. These findings may have potentially profound implications for more effective VT therapy in the vulnerable obese patient population.

Retention of placenta (RP) in crossbred cattle poses health, reproductive, and economic challenges linked to oxidative stress, hormonal imbalances, and complex causative factors. Emphasizing the key role of mitochondria in oxidative phosphorylation (OXPHOS) and hormone synthesis, our study is the first to explore differences in OXPHOS activity, mitochondrial content, and mtDNA-encoded gene expression between normal and RP. In addition, gross morphological examination of placental tissues from both groups revealed noticeable disparities in cotyledons of RP as compared to normal placenta. Moreover, OXPHOS complex I specific activity was decreased in RP, and RT-qPCR analysis unveiled a significant reduction in transcript levels of 10 mtDNA-encoded protein genes. While COX3 and ATP8 genes showed no significant changes, ND6 increased in RP. Whereas, mtDNA copy number varied between animals but showed no statistically significant differences among groups. Retained placenta manifests alterations in the transcript levels of various mitochondrial genes, complex activity, and mtDNA content, potentially linked to heightened energy demands or mitochondrial insufficiency, posing an elevated risk. Overall, our study suggests a link between mitochondrial abnormalities, gene expression, and RP. This connection could influence the removal of fetal membranes by affecting energy supply, hormonal balance, and oxidative stress. This study also offers novel insights and serves as a valuable animal model for studying placental insufficiency in humans. Moving forward, comprehensive investigations are imperative to unravel underlying mechanisms and intricate roles of mitochondria in the context of RP, paving the way for targeted interventions to mitigate health, reproductive, and economic challenges in crossbred cattle.

Novel far-red-sensitive symmetric squaraine (SQ) dyes with terminal alkyl-chain modifications were designed, synthesized and characterized aiming towards imparting multifunctionalities such as photosensitization, dye aggregation prevention and source of electrolyte components. The dye sensitizers SQ-77 and SQ-80 with the alkyl chain terminal modifications consisting of iodine and 1-methylimidazolium iodide, respectively, were designed and synthesized as new dye sensitizers for DSSCs based on the symmetric SQ-5 without any terminal modification used as reference. Upon adsorption on the mesoporous TiO2 surface, The SQ-77 depicted an enhanced dye loading and dye aggregation. On the other hand, SQ-80 demonstrated reduced dye aggregation and stronger binding on the TiO2 surface leading to enhanced durability of DSSCs. Apart from the most common photosensitization behaviour, the newly designed dye demonstrated multifunctionality such as aggregation prevention and electrolyte functionality utilizing iodine-based redox electrolyte in the presence and absence of I2 and LiI additives. In the absence of LiI and I2, a mixture of SQ-77 and SQ-80 demonstrated a photoconversion efficiency of 1.54 % under simulated solar irradiation, which was about 6 times higher as compared to reference dye SQ-5 (0.24 %) having no alkyl chai terminal modification.

Spinal cord stimulation (SCS) is a therapeutic modality for the treatment of various chronic pain conditions that has rapidly evolved over the past 50 years. Unfortunately, over time, patients implanted with SCS undergo a habituation phenomenon leading to decreased pain relief. Consequently, discovery of new stimulation waveforms and SCS applications have shown to prolong efficacy and reduce explantation rates. This article explores various SCS waveforms, their applications and proposes a graded approach to habituation mitigation. We suspect the neural habituation phenomenon parallels that seen in pharmacology. Consequently we urge further exploration of early introduction of these stimulation strategies to abate spinal cord stimulation habituation.

India ranks among the top ten nations in the world for grape production. Fungal pathogens inflict damage to crop plants in turn making cultivators bear huge economical losses. With an output of 1.21 million tons (about 2% of 57.40 million tons produced globally). 1.2% of the nation’s total fruit cropland is covered by grapes. But due to fungal diseases the effect of the yield produced ranges from 5-80% depending on the severity of diseases which will affect the yield of grape vineyard. In precision agriculture, new sensing technologies and artificial intelligence could be used to automatically identify grapevine and disease pest symptoms. Traditional manual disease-monitoring methods are inefficient, labor-intensive, and ineffective. Timely effective and precise evaluation of grape diseases is admitted as a critical step in the field management. In this paper, we are explaining about different optical sensing methods applied for RGB, Multispectral and Thermal cameras. Section-wise we will be describing environmental set up for image-aquation, data-preprocessing, different modelling methods, evaluation matrix, result, and reviewer’s comment.

A Gem-quality rubies and sapphires are often commercially heat treated at about 800°C or higher temperatures to enhance their colour and clarity, and hence quality. For this study, selected corundum samples containing diaspore- and goethite inclusions were heated step-by-step to a maximum of 1000 °C with the aim to monitor the dehydration and phase transformation of these oxyhydroxides to corundum and hematite during heating. Based on our experiments and in agreement with literature, the dehydration of diaspore in corundum occurs between 525 to 550 °C, whereas goethite transforms to hematite already between 300 and 325 °C. As both, diaspore and goethite are common inclusions in rubies, sapphires, and other corundum varieties, these dehydration reactions and phase transformations can be considered important criteria to separate unheated stones from heated ones, specifically in cases in which other methods (e.g. microscopy, FTIR) are unsuccessful.

Since the first published genome sequence of Trypanosoma cruzi in 2005, there has been tremendous technological advance in genomics, reverse genetics, and assay development for this elusive pathogen. However, there is still an unmet need for new and better drugs to treat Chagas disease. Here we introduce a T. cruzi assay strain that is useful for drug research as well as basic studies in host-pathogen interaction. Trypanosoma cruzi STIB980 is a strain of discrete typing unit TcI that grows well in culture as axenic epimastigotes or intracellular amastigotes. We have evaluated the optimal parameters for genetic transfection and constructed derivatives of T. cruzi STIB980 that express reporter genes for fluorescence- or bioluminescence-based drug efficacy testing, as well as a Cas9-expressing line for CRISPR/Cas9-mediated gene editing. The genome of T. cruzi STIB980 was sequenced by combining short-read Illumina with long-read Oxford Nanopore technologies. The latter served for the primary assembly, the former to correct mistakes and fill the gaps. This resulted in a high-quality nuclear haplotype assembly of 28 Mb in 400 contigs, containing 10,043 open-reading frames with a median length of 1077 bp. We believe that T. cruzi STIB980 is a useful addition to the antichagasic toolbox, and propose that it can serve as a DTU TcI reference strain for drug efficacy testing.

Cross flow heat exchangers are commonly used in the thermal industry to transfer heat from hot tubes to cooling fluid. To protect the heat exchanger tubes from corrosion and dust accumulation, microscale coatings are often applied. In this study, we present machine-learning models for predicting heat transfer from hot tubes with different micro-sized coatings to cooling fluid in a turbulent flow using computational fluid dynamics simulations. A dataset of approximately 1000 cases was generated by varying the coating coverage thickness of each tube, the inlet Reynolds number, fluid flow inlet temperature, and wall temperature of tubes. The machine-learning models were generated to predict the overall heat flow rate in the heat exchanger, and it was found that combining the features based on their importance preserved the accuracy of the models while maintaining all the relevant information. The simulation results demonstrate that the proposed method increases the coefficient of determination (R2) for the models. The R2 values for unseen data for Random Forest, K-Nearest Neighbors, and Support Vector Regression were 0.9810, 0.9037, and 0.9754, respectively, indicating the usefulness of the proposed model for predicting heat transfer in various types of heat exchangers.

: This study investigates the use of various thunderstorm indices in predicting severe thunderstorms events during the monsoon season in four different regions in India. The research evaluates the performance of the prediction model using a model skill score and utilizes the Weather Research and Forecasting (WRF) model with the double moment microphysics scheme to simulate model cases. It also compares fifteen thunderstorm indices derived from the ERA5 dataset to identify the most effective index for predicting severe thunderstorms events. The results of this study show that in-corporating thunderstorm indices with model skill scores improves severe thunderstorms fore-casting in the monsoon season in India. The result revealed that determining the optimal threshold for each index is crucial in achieving accurate predictions. The study also highlights the importance of considering multiple indices rather than relying on a single index to predict severe thunderstorms events. The advance indices such as Energy Helicity Index (EHI), Supercell Composite Parameter (SCP), mainly works well with extreme severe thunderstorms. The simplistic indices can predict the weak or severe thunderstorm easily. The use of multiple thunderstorm indices can also help mete-orologists to make more accurate predictions, which can further enhance public safety. In conclu-sion, this study demonstrates the potential of incorporating thunderstorm indices with model skill scores like HSS and TSS and combinations of different skill scores in severe thunderstorms fore-casting during the monsoon season in India. Future research can build upon the findings of this study to develop more accurate and reliable severe weather forecasting models.

Distracted driving is the leading cause of accidents, the cause of these distractions may include drowsiness, using cell phone, smoking a cigarette, etc. The proposed paper aims at monitoring the attentiveness of the driver and alerting the driver when his/her alertness goes below a certain threshold. It uses image processing using OpenCV (Computer Vision) and You Look Only Once (YOLO) algorithm to detect the eyes and object respectively and sounds an alarm when the driver is either drowsy or using his cell phone or smoking a cigarette.

Although initially conceived for high-risk patients who are ineligible for surgical aortic valve replacement (SAVR), transcatheter aortic valve replacement (TAVR) is now recommended in a wider spectrum of indications including young patients. However, as for SAVR, TAVR is also associated with a risk of infectious complications, namely prosthetic valve endocarditis (PVE). As the number of performed TAVR procedure increases, and despite the low incidence of PVE post TAVR, clinicians should be familiar with the associated risk factors and the clinical presentation. Whereas the diagnosis of native valve endocarditis can be straightforward applying the modified Duke criteria, the diagnosis of PVE is more challenging given its atypical symptoms, lower sensitivity of the criteria, and low diagnostic yield of conventional echocardiography. Delay in proper management can be associated with increased morbidity and mortality. Therefore, clinicians should have a high index of suspicion and initiate proper work-up according to the severity of illness, the underlying host, and the local epidemiology of the causative organisms. The most common causative pathogens are Gram-positive bacteria such as S. aureus, coagulase negative staphylococci, Enterococcus spp. and Streptococcus spp. (particularly the viridans group) and, less likely Gram-negative and fungal pathogens. The high prevalence of antimicrobial resistance complicates the choice of therapy. There remain controversies regarding the optimal management strategies including indications for surgical interventions. Surgical assessment is recommended early in the course of illness and surgical intervention should be considered in selected patients. As in other PVE, duration of therapy depends on the isolated pathogen, the host, and the clinical response. Since TAVR is a relatively new procedure, the outcome of TAVR-PVE is yet to be fully understood.

We present a finite element model updating technique for soil-structure system identification of the Millikan Library building using the seismic data recorded during the 2002 Yorba Linda earthquake. A detailed finite element (FE) model of the Millikan Library building is developed in OpenSees and updated using a sequential Bayesian estimation approach for joint parameter and input identification. A two-step system identification approach is devised. First, the fixed-base structural model is updated to estimate the structural model parameters (including effective elastic modulus of structural components, distributed floor mass, and Rayleigh damping parameters) and some uncertain components of the foundation-level motion. Then, the identified structural model is used for soil-structure model updating wherein the Rayleigh damping parameters, the stiffness and viscosity of the soil subsystem (modeled using a substructure approach), and the foundation input motions (FIMs) are estimated. The identified model parameters are compared with state-of-practice recommendations. While a specific application is made for the Millikan Library, the present work offers a framework for integrating large-scale FE models with measurement data for model inversion. By utilizing this framework for different civil structures and earthquake records, key structural model parameters can be estimated from the real-world recorded data, which can subsequently be used for assessing and improving, as necessary, state-of-the-art seismic analysis and structural modeling techniques. This paper presents an effort towards using real-world measurements for large-scale FE model updating in the soil and structure, uniform soil time domain for joint parameter and input estimation, and thus paves the way for future applications in system identification, health monitoring and diagnosis of civil structures.

The receptor tyrosine kinase Ret plays a critical role in regulating enteric nervous system (ENS) development. Ret is important for proliferation, migration, and survival of enteric progenitor cells (EPCs). Ret also promotes neuronal fate, but its role during neuronal differentiation and in the adult ENS is less well understood. Inactivating RET mutations are associated with ENS diseases, e.g. Hirschsprung Disease, in which distal bowel lacks ENS cells. Zebrafish is an established model system for studying ENS development and modeling human ENS diseases. One advantage of the zebrafish model system is that their embryos are transparent allowing visualization of developmental phenotypes in live animals. However, we lack tools to monitor Ret expression in live zebrafish. Here, we developed a new BAC transgenic line that expresses GFP under the ret promoter. We find that EPCs and the majority of ENS neurons express ret:GFP during ENS development. In the adult ENS, GFP+ neurons are equally present in female and male. In homozygous mutants of ret and sox10 – another important ENS developmental regulator gene – GFP+ ENS cells are absent. In summary, we characterize a ret:GFP transgenic line as a new tool to visualize and study the Ret signaling pathway from early development through adulthood.

Tanning beds have been classified as carcinogenic to humans. As a result, many countries have enacted laws regulating the use of commercial tanning beds, including bans for minors. However, there is no international overview of the current legal status of access restrictions for minors that provides details on their specific design regarding age limits and possible exceptions to the statutory regulation. Therefore, we performed a comprehensive web search of current tanning bed legislation for minors on the three continents North America, Australia, and Europe. Our findings regarding existence and concrete design of access restrictions are presented graphically using maps. We found a wide variety of different legislations. In Australia, a total ban on tanning beds exists, while in New Zealand tanning bed use is banned for minors. In Europe about half of the countries have implemented a strict ban for minors. In North America we found differences in the age limit for access restrictions between the states, provinces and territories for those regions that implemented a ban for minors. In the United States, some states have rather ‘soft bans’ that allow use by minors with different types of parental consent. The patchwork in legislation calls for harmonization. Therefore, our comparison is an important starting point for institutions such as the World Health Organization or the European Commission to advance their goals towards a harmonization of tanning bed legislation in general and for minors in particular.

Mycobacterium tuberculosis is a leading cause of human mortality worldwide and the emergence of drug-resistantstrains, demands the discovery of new classes of antimycobacterials that can be employed in the therapeutic pipeline. Previously, a secondary metabolite Chrysomycin A, isolated from Streptomyces sp. OA161 was shown to have potent bactericidal activity against drug-resistant clinical isolates of M. tuberculosis and different species of mycobacteria. The antibiotic inhibits the mycobacterial topoisomerase I and DNA gyrase leading to bacterial death, but the mechanisms that could cause resistance are currently unknown. To further understand the resistance mechanism, spontaneous resistance mutants were isolated and subjected to whole-genome sequencing. Mutation in a Tet^R family transcriptional regulator MSMEG_1380 was identified in the resistant isolates and was close to an operon encoding membrane protein MSMEG_1381 and MSMEG_1382. Sequence analysis and modeling studies indicated that they are components of the Mmp family of efflux pumps and over-expression of either the operon or individual genes conferred resistance to chrysomycin A, isoniazid, and ethambutol that are in TB therapy. Our study highlights the role of membrane transporter proteins in conferring multiple drug resistance and the utility of recombinant strains overexpressing membrane transporters in the drug screening pipeline.

Turkey is located in the heart of complex transition geography between Eurasia and the Middle East. In the grand scheme, the so-called Eastern Mediterranean Basin is almost amidst the dusty belt and a hot spot of climate change. The downstream location of dust carrying winds from the closer desert sources reveals Turkey as an open plane to particulate matter exposure throughout the year. In order to clarify this phenomenon, it is aimed to find out the desert dust climatology of Turkey via CALIPSO onboard Lidar. This prominent instrument enables us to understand clouds, aerosols and their types and relatedly climatic systems with its valuable products. In this study, 9-year CALIPSO derived pure dust product is formed to explain horizontal and vertical distributions, transport heights and case incidences. Results indicated mass and conditional abundancy are higher with the location shifts from west to east. In the same direction, dominant spring months change to summer and autumn. Mountain range systems surrounding Anatolia are the main obstacles against lofted and buoyant dust particles travelling to northern latitudes. Even if high ridges accumulate mass load on the southern slopes, it also enables elevated particles to reach the ground level of the inner cities.

The extrusion-based additive manufacturing is a popular fabrication method, which has attracted the attention of various industries due to its simplicity, cheapness, ability to produce complex geometric shapes, and high production speed. One of the effective parameters in this process is the feed of filament that is presented in the production G-code. The feed of filament is calculated according to the layer height, the extrusion width and the length of printing path. All the required motion paths and filling patterns created by commercial software are a set of straight lines or circular arcs that are placed next to each other at a fixed distance. In special curved paths, the distance of adjacent ones is not equal at different points, and due to the weakness of common commercial software, it is not possible to create curved paths for proper printing. Therefore, making a special computer code that can be used to create various functions of curved paths is investigated in this research, and also the feed of filament parameter is studied in detail. Next, by introducing a correction technique, the feed of filament is changed during the curved path to distribute the polymer material uniformly. Finally, composite samples (which have variable stiffness) consisting of curved fibers are produced with the proposed method, and the high quality of printed samples confirm the suggested code and technique.

Tooth bud removal called Ibyinyo is the practice of removing the developing tooth buds, usually done on an infant, typically performed by traditional healers who believe that this practice will reduce fever and diarrhea in children. This practice is most prevalent in East-African countries, including Rwanda. These procedures are mostly performed in non-sterile conditions using basic sharp instruments. We will discuss the case of a 10-year-old female patient who was presented at the dental clinic, with two malformed permanent canine teeth. Clinical examination revealed malformed enamel and elongated permanent right maxillary canine tooth left mandibular canine tooth with crown malformation. She was also presented with retained (primary) left maxillary lateral incisor tooth and missing left maxillary canine tooth. In addition, the ectopic eruption of left maxillary central incisor tooth and missing permanent right mandibular canine tooth were noted. All these complications resulted from tooth bud removal that the patient had experienced in her early childhood. Her malformed right maxillary and left lower mandibular canine teeth were reshaped, using composite filling materials, to improve her appearance aesthetically. Ibyinyo is preventable damage, done out of ignorance and superstitious practices that can be stopped by growing social awareness. Therefore, educating parents through community-based campaigns on the detrimental consequences of early childhood tooth bud removal through Ibyinyo practice might be helpful to eradicate this harmful and unnecessary practice.

Social character is the key for someone to interact with the surrounding community. Interaction and socialization need to be introduced early by parents. If the results turned in reverse, then there must be other ways to be learned and practiced in family life. This study aims to cultivate social characters to children in the Juvenile Rehabilitation Institution through poetry learning. Changes continue to occur in handling and coaching juvenile delinquency in Indonesia. Regulations for the management of coaching continue to be carried out from Law No. 3 of 1997 concerning the Law on Juvenile Justice, then it was changed to Act No. 11 of 2012 concerning the System of Juvenile Criminal Justice. Characteristics of this relatively new law contain the main mechanisms of protecting children, who have problems with the law and following the Convention on the Rights of the Child. Education in the Juvenile Rehabilitation Institution has been carried out with all the limitations and can bring changes in the correctional behavior of children to be better that makes education restore the child's identity. Education held at this institution is expected to be able to achieve the ideals of children to be more beneficial after completing a kind of inclusive education. By applying a pragmatic approach, the study expects that there will be a change in children since they can learn the contents of poems, and at the same time, they are able to express their feeling by writing poems as well. From the process of learning, social characters in children such as honesty, openness, tolerance, cooperation, will be growing step by step.

A single tree topology is a commonly employed topology for wireless sensor networks (WSN) to connect sensors to one or more remote gateways. However, its many-to-one traffic routing pattern imposes heavy burden on downstream nodes, as the same routes are repeatedly used for packet transfer, from one or more upstream branches. The challenge is how to choose the most optimal routing paths that minimizes energy consumption across the entire network. This paper proposes a proactive energy awareness-based many-to-one traffic routing scheme to alleviate the above said problem referred to as Energy Balance-Based Energy Hole Alleviation in tree topology (EBEHA-T). This protocol combines updated status of variations in energy consumption pattern around sink-hole zones and distribution of joint nodes among the trees. With this approach, EBEHA-T proactively prevents sink-hole formation instead of just a reactive response after they have occurred. Performance evaluation of EBEHA-T against benchmark method RaSMaLai shows increased energy saving across the entire network and a marked improvement in energy consumption balance in energy-hole zones. This precludes energy hole formation and the consequent network partitioning, leading to improved network lifetime beyond that of the RasMaLai. OMNET++ network simulation software has been used for the evaluation.

Image registration has an imperative role in medical imaging. In this work, a grey-wolf optimizer (GWO) based non-rigid demons registration is proposed to support the retinal image registration process. A comparative study of the proposed GWO-based demons registration framework with cuckoo search, firefly algorithm, and particle swarm optimization- based demons registration is conducted. In addition, a comparative analysis of different demons registration methods, such as Wang’s demons, Tang’s demons, and Thirion’s demons which are optimized using the proposed GWO is carried out. The results established the superiority of the GWO-based framework which achieved 0.9977 correlation, and fast processing compared to the use of the other optimization algorithms. Moreover, GWO-based Wang’s demons performed better accuracy compared to the Tang’s demons and Thirion’s demons framework. It also achieved the best less registration error of 8.36×10^-5.

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

Metal-Organic Frameworks (MOFs) are a subclass of porous materials that have unique properties such as varieties of structures from different metals and organic linkers, tunable porosity from a structure or framework design, etc. Moreover, modification/functionalization of the material structure could optimize the material properties and demonstrate high potential for a selected application. MOF materials exhibit exceptional properties and make these materials widely applicable including in energy storage and heat transformation applications. This review aims to give a broad overview of MOFs and their development as adsorbent materials having the potential for heat transformation applications. We summarize current investigations, developments, and possibilities of metal-organic frameworks (MOFs) especially the tuning of the porosity and hydrophobic/hydrophilic design required for this specific application. These materials applied as adsorbent are promising in the thermal driven adsorption for heat transformation using water as working fluid and related application.

The current work addresses the control of two-input two-output (TITO) Wood and Berry model of a binary distillation column. The controller design problem is formulated in terms of multivariable H_∞ control synthesis. The controller structure takes the form of simplest static output feedback (SOF) control. The controller synthesis is performed using a hybrid approach of blending linear matrix inequalities (LMI) and genetic algorithm (GA). The performance of the static output feedback controller is compared with three other controllers designed for Wood and Berry model available in the literature. The first simulation study is performed for the case of tracking a unit step command in the presence of a step change in output disturbance. A second simulation study is performed for rejecting a change in sinusoidal output disturbance.

In an attempt to improve the quality of the agricultural drain in Egypt for its reuse again in the irrigation, low cost solution such as sand filter along with/ without other filtration media have been used in this research, As a result of that, pilot plant of sand filter mixed with other filtration media was tested for its ability to improve the sand performance in removing the suspended solids and organic matters from agricultural drain water of the Belbeis drain (in Sharkia governorate in Egypt). Only sand compared with sand with sponge and sand with Liyan Nanfang activated carbon (L.N.A.C) have been tested to find the optimum mixing sand/ medium ratio &optimum infiltration rate. The work has been done on four runs. It was found that sand mixed with sponge gave the best removal efficiency compared to that of the sand only and the sand mixed with L.N.A.C. The results presented that the concentration of CODt, CODsol and TSS was reduced from 125, 47 and 162 mg/l to 44, 34 and 28 mg/l respectively at optimum infiltration rate of 2 m³/m²/d for sand mixed with sponge.

Machine Learning is increasingly and ubiquitously being used in the medical domain. Evaluation metrics like accuracy, precision, and recall may indicate the performance of the models but not necessarily the reliability of their outcomes. This paper assesses the effectiveness of a number of machine learning algorithms applied to an important dataset in the medical domain, specifically, mental health, by employing explainability methodologies. Using multiple machine learning algorithms and model explainability techniques, the project provides insights into the model workings to help determine the reliability of the machine learning algorithm predictions. The results are not intuitive. It was found that the models were focusing significantly on less relevant features and at times, unsound ranking of the features to make the predictions. The paper therefore argues that it is important for research in applied machine learning to provide insights into explainability of the models in addition to other performance metrics like accuracy. This is particularly important for applications in critical domains such as healthcare. A future direction is to investigate methods to quantify the effectiveness of the machine learning models in terms of the insights from their explainability.

Glycerol is the main residue in the biodiesel production industry; therefore, their valorisation is crucial. Acetalization of glycerol towards fuel additives as solketal (2,2-dimethyl-1,3-dioxolan-4-methanol) is of high interest, promoting circular economy since it can be added to the biodiesel or even fossil-diesel to improve their quality and efficiency. Straightforward prepared metal-organic framework (MOF) materials of MOF-808 family were applied to the valorisation of glycerol for the first time. In particular, MOF-808(Hf) revealed to be an effective heterogeneous catalyst to produce solketal under moderate conditions: small amount of the MOF material (only 4wt% of glycerol), ratio 1:6 of glycerol/acetone and temperature of 60 ºC. The high efficiency of MOF-808(Hf) was associated with the high amount of acid centres present in its structure. Furthermore, its structural characteristics such as window opening cavities size and pore diameters showed to be ideal to reuse this material during at least ten consecutive reaction cycles without losing activity (conversion > 90% and selectivity > 98%). Remarkably, it was not necessary the washing or other activation treatment of the MOF-808(Hf) catalyst between cycles (no pore blockage occurred) and it maintained structural integrity after the ten cycles, confirming to be a sustainable heterogeneous catalyst to the glycerol valorisation.

Nanoporous films of Eu-doped organosilicate glass (OSG) have been synthesized using sol-gel technology and spin-coating, employing evaporation-induced self-assembly (EISA), on silicon wafers. The Eu doping is achieved by dissolution of Eu(NO3)3·6H2O in the precursor solution. The deposited films are characterized by using Fourier transform infrared (FTIR) spectroscopy, ellipsometric porosimetry (EP), X-ray photoelectron spectroscopy (XPS) and photoluminescence spectroscopy. It is observed that Eu doping makes the films more hydrophilic and reduces the pore size and open porosity. The reduction Eu3+ → Eu2+ occurs in the pores of OSG films, which is confirmed by depth profiling XPS. However, Eu3+ still presents on the film’s top surface. Presence of Eu3+ and Eu2+ gives characteristic luminescence emission in the range of 600‒630 nm (Eu3+) and 290‒400 nm (Eu2+). The Eu2+/Eu3+ concentrations ratio depends on CH3 groups concentration in the films. Moreover, concentration of Eu2+ ions in the pores can be reduced by exposure in inductively coupled (ICP) oxygen plasma. The observed shift of the luminescence spectra towards the UV region, in comparison to previously reported Eu-doped organosilicate films, can be attributed to the energy transfer occurring between the host material and Eu2+ ions.

Microcystins (MCs) are cyanobacterial toxins and potent inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), which are involved in plant cytoskeleton (microtubules and F-actin) organization. Therefore, studies on the toxicity of cyanobacterial products on plant cells have so far being focused on MCs. In this study, we investigated the effects of extracts from 16 (4 MC-producing and 12 non-MC-producing) cyanobacterial strains from several habitats, on various enzymes (PP1, trypsin, elastase), on the plant cytoskeleton and H2O2 levels in Oryza sativa (rice) root cells. Seedling roots were treated for various time periods (1, 12 and 24h) with aqueous cyanobacterial extracts and underwent either immunostaining for α-tubulin or staining of F-actin with fluorescent phalloidin. DCF-DA staining was performed for H2O2 imaging. The enzyme assays confirmed the bioactivity of the extracts of not only MC-rich (MC+), but also MC-devoid (MC-) extracts, which induced major time-dependent alterations on both components of the plant cytoskeleton. These findings suggest that a broad spectrum of bioactive cyanobacterial compounds, apart from MCs or other known cyanotoxins (such as cylindrospermopsin), can affect plants by disrupting the cytoskeleton.

Commercial sleep devices and mobile-phone applications for scoring sleep are gaining ground. In order to provide reliable information about the quantity and/or quality of sleep, their performance needs to be assessed against the current gold-standard, i.e. polysomnography (PSG; measuring brain, eye and muscle activity). We here assessed some commercially available sleep trackers, namely; a commercial activity tracker: Mi band (Xiaomi, BJ, CHN), a scientific actigraph: Motionwatch 8 (CamNTech, CB, UK), and a much used sleep application: Sleep Cycle (Northcube, GOT, SE). We recorded 27 nights in healthy sleepers using PSG and these devices. Surprisingly, all devices had very poor agreement with the gold standard. Sleep parameter comparisons revealed that specifically the Mi band and the sleep cycle application had difficulties in detecting wake periods which negatively affected the total sleep time and sleep efficiency estimations. However, all 3 devices were good in detecting the most basic parameter, the actual time in bed. In summary, our results suggest that, to-date; available sleep trackers do not provide meaningful sleep analysis but may be interesting for simply tracking times in bed. A much closer interaction with the scientific field seems necessary if reliable information shall be derived from such devices in the future.

Hepatitis B Virus (HBV) infection carries a significant health burden worldwide. It is a leading cause of acute and chronic liver disease resulting in cirrhosis and hepatocellular carcinoma (HCC). This virus affects millions globally, and despite several medical advancements, research, and efforts to develop curative treatment, the persistence of HBV in infected individuals by cccDNA and integration pose formidable challenges. This review aims to provide a broad-based overview of HBV persistence, integration and the implications for chronic infection and tumorigenesis. By considering these points, we bring forth insights into the advancement of therapies that aim to disrupt the chronicity of HBV infection and improve clinical outcomes.

This mini-review discusses the development and applications of naturally derived bioconjugates from hydroxycinnamic acids, such as coumaric, sinapic, ferulic, and caffeic acids, combined with various biomaterials. These bioconjugates offer a range of benefits including antioxidant properties, UV protection, customized hydrophilic-lipophilic balance, improved safety, solubility, emolliency, biocompatibility, biodegradability, and targeted delivery for biomedical, cosmetic, and food applications. The increasing demand for sustainable and natural products in the biomedical, cosmetic, and food industries has led to the exploration of these hydroxy cinnamic acids and their derivatives. We discuss the synthesis and modification of hydroxy cinnamic acids with biomaterials such as ω-hydroxy fatty acids, castor and lesquerella oils, glycerol, isosorbides, and synthetic polyethylene glycol to form functional phenolipids for biomedical, sunscreen and skincare applications. Techniques such as encapsulation with β-cyclodextrins and modification of biopolymeric supports like polysaccharides and starch are discussed for enhancing bioavailability and solubility. The fine-tuned development of bioconjugates from hydroxycinnamic acids using glycerol to modify the hydrophilic-lipophilic balance, substitution by water-soluble carboxylic acid groups, vegetable oil-based phenolipids, polysaccharides, PEGylation provide enhanced functionalities and offers a promising avenue for creating sustainable and effective products across various applications.

This research seeks to solve the multi-faceted problem of waste disposal by analyzing the application of waste plastic and tyre material within non-structural concrete to ensure more sustainability and less environmental degradation. Study focusses on material properties including specific gravity, water absorption and bulk density and characteristics of the concrete that is produced by the utilization of the above waste aggregates including workability, compressive strength, flexural strength and tensile strength. This paper employs secondary data collection and MATLAB in the analysis of the findings pointing to the fact that the mechanical properties reduce with the level of waste content yet emphasizing the green aspect of such materials. Thus, a complex and diverse effect is demonstrated by the life cycle assessments (LCA) for global warming, ozone depletion, terrestrial ecotoxicity, and acidification. Furthermore, the utilization of waste materials decreases the compressive, flexural, and tensile strength, but it provides distinct ecological benefits which prove the importance of proper mix proportions for concrete performance. The outcomes of this research will be useful for further investigation in the application of the concept as well as to call for the development of new ideas for the improvement of bonding of wastes to aggregates in concrete.

The term "code smell" refers to an indication of a problem with the quality of source code. Numerous studies have been conducted to identify problematic features in source code. Initially, the focus was on utilizing metric-based and heuristic-based approaches. In recent years, however, there has been a shift towards using machine learning and deep learning (DL) techniques for smell detection. Nevertheless, the current algorithms are still considered to be in the early stages of development. Recognizing the challenges associated with identifying smells using DL methods, both academics and software developers have made efforts to address these obstacles. This work involves constructing and evaluating new DL models for code smell detection. Two models are built upon stacked autoencoders, employing a hybrid architecture that combines bidirectional long short-term memory and convolutional neural network components.

Background and objectives: Effective management for chronic diseases, hereditary and rare diseases and Thalassaemia in particular constitutes an important indicator for the quality of healthcare systems. We aimed at assessing healthcare services in different countries by using publicly available health indicators and by surveying Thalassaemia patients and their caregivers. Materials and Methods: We reviewed official worldwide databases from the WHO, World Bank, and scientific resources and also used a structured patient tailored self-completed questionnaire to survey Thalassaemia patients and their caregivers in 2023. Results: A total of 2,082 participants were surveyed (mean age 27 years, males 42%). About 1 in 4 respondents had less than high school education, while 24% had a bachelor degree. About a third of respondents were married and had either full- or part-time employment. The vast majority (~80%) had initiated transfusion therapy between 1 – 4 years of age. Only 42% reported no delays in receiving blood transfusion, while 47% reported occasional delays and 8% serious delays. About half of patients reported being very satisfied (11%) or satisfied (38%) with the quality of provided services, while 1 in 3 patients reported being unsatisfied or very unsatisfied, and their access to treatment was difficult or very difficult due to traveling expenses and high cost of treatment. Conclusion: Important improvements in the care of Thalassaemia patients have been documented during the past decades. Nevertheless, our recent survey reveals many unmet needs where additional focus is required through national healthcare systems in order to address them effectively and achieve satisfactory patient outcomes.

Combustion parameters are the important aspects in the development and research of an internal combustion engines. Hence present work is an attempt to develop an artificial neural network (ANN) model for anticipating the combustion characteristics of computerized CI DI VCR, four strokes, single cylinder, and water cooled engine using mixture of two biodiesel and diesel blends as a fuel. The two biodiesel selected are Jatropha and Simarouba and mixed in the ratio of 75:25. Two biodiesel mixtures is used for the preparation of various blends with diesel. Experiments are carried out at different compression ratio, at different % load and blends B20, B40, B60and neat diesel (B00) fuel to accumulate the assorted combustion data. The input variables are % load, compression ratio, blends and crank angle. The outputs well thought-out are cylinder pressure (CP), net heat release rate (NHRR), cumulative heat release (CHR), rate of pressure rise (RPR), mass fraction burned (MFB) and maximum cylinder pressure. The assessment is focused on developing artificial neural network for the prediction and verifying the combustion characteristics of engine. MATLAB software is used for analysis of different combustion aspects of the engine. Multilayer neural network perceptions are used with Feed-Forward Back Propagation algorithm with performance function for mapping the input and output parameters. The experimental outcomes are compared with ANN estimated results for the analysis. The outcome from the study authenticate that experimental results are in match with ANN results. The accuracy of the ANN model shows the developed model can effectively predict the engine combustion characteristics with excellent regression coefficients ‘R’ and its values are close to unity and the mean square errors are extremely less. ANN model approach is competent towards predicting the combustion aspect of diesel engine with good accuracy

ABSTRACT Objectives: Typical Diagnostic Reference Levels (DRL) in terms of Computed Tomography Dose Index (CTDI) and patient dose in terms of Effective Dose (ED ) and Size Specific Dose Estimate (SSDE) were estimated in Computed Tomography (CT) guided biopsy procedures. Materials and Methods: A total of 226 CT biopsy procedures - Iliac bone, liver, lung, mediastinum and para-aortic tissue - were retrospectively analyzed and Typical DRL extracted based on ICRP 135 instructions. Results: For helical mode acquisitions, DRLs in terms of CTDIvol were 9.7 mGy for Iliac bone, 8.9 mGy for liver, 8.8 mGy for lung, 7.9 mGy for mediastinal mass and 9 mGy for para-aortic lymph nodes biopsy procedures. For biopsy acquisitions, DRL values were 7.3 mGy, 7.7 mGy, 5.6 mGy, 5.6 mGy and 7.4 mGy respectively. Also, SSDE median values ranged from 7.6 mGy to 10 mGy for biopsy acquisitions and 11,3 mGy to 12,6 mGy for helical acquisitions, as well as the median values for effective dose ranged from 1.6 mSv to 5,7 mSv for biopsy scans and 3.9 to 9.3 mSv for helical scans. Conclusions: The use of DLR as an optimization tool for CT-guided biopsy procedures revealed that helical scans across the entire anatomical region greatly affect radiation dose compared to biopsy acquisitions.

Spectacularly, particulate matter pollution influences human health by aggravating numerous diseases and causing premature deaths. In order to eliminate its concentration in the ambient air, plant species can act as natural bio-filters and capture, degrade, and metabolize air pollutants inside their foliage. In a study carried out at three sites with different pollution levels and plant types. The immobilization efficiency of Particulate Matter (PM) was investigated in the leaves of three species (shrub, climber, and herb) in the southwestern of Japan with a time gap of 14 days. Two healthy mature leaf samples of each specimen were carefully collected and analyzed using the gravimetric analytical method. A significant quantity of PM in three-size fractions with aerodynamic diameters ranging between (0.1-100 μm) was captured inside the leaf foliage of the analyzed species. Fine particles (2.5 -10 μm) dominated the highest portion of the PM deposition captured by the analyzed species with 70.6 μg.cm-2(39.5%). Shrub species represented with Elaeagnus pungens proved to be the most efficient species among the analyzed species. Leaf traits such as grooves, trichomes, roughness, and margin are considered key factors associated with positive PM deposition, whereas the total surface area of the leaves had no direct correlation to PM deposition.

Family Integrated Care (FICare) is associated with improved developmental outcomes and decreased parental mental health risks in stable preterm infants. However, less is known about its application in critically ill infants who are at greater risk for adverse outcomes. The objective of this study was to assess the safety and feasibility of implementation of FICare in critically ill infants in the first few weeks of life. In this prospective cohort study, 41 critically ill infants were enrolled: 17 in observational group receiving standard care (SC)and 24 in the FICare Plus group. Resources were developed for staff and parents to support earlier engagement in infant care. Outcomes were assessed using standardized questionnaires. The t-test or Wilcoxon Rank-Sum test were used to compare continuous variables, while Chi-square or Fisher exact test were used for categorical variables, respectively. Baseline maternal and infant characteristics were similar in both groups. The tools and procedures developed for FICare Plus successfully supported greater engagement in the care of their infant with no increase in adverse events and no increase in parent stress. Preliminary measures of infant efficacy were similar in both groups. Total anxiety scores were high among all parents at enrolment {83.1 (67-94) vs 77.3 (66-86); p-value 0.4}. However, the scores prior to discharge were lower in FICare Plus group {78 (71-90) vs 63 (52-74.5); p-value 0.02}. This pilot study showed that it is feasible and safe to implement family integrated care in critically ill infants.

The purpose of this in vitro study is to evaluate the effectiveness of incorporating a new irrigation system into a surgical guide and monitor its effect on heat generation during implant bed preparation. A total of 48 surgically guided osteotomies were performed on 12 bovine ribs divided into 4 groups, using different irrigation techniques: Group A (test) had entry and exit channels incorporated into the guide; Group B had a similar design with an entry channel only; Group C had conventional external irrigation; Group D (control) had no irrigation. Heat generation during the osteotomies was measured using thermocouples placed at a depth of 2 mm and 6 mm. The lowest mean temperature was observed in Group A (22.1°C at 2mm and 21.4°C at 6mm), this was statistically significant when compared with Groups C and D (p<0.001). Group A showed a lower mean temperature compared with Group B as well, however statistically significant only at 6mm depth (p<0.05). In conclusion, the proposed guide has significantly reduced heat generation during implant osteotomy. The integration of an exit cooling channel can resolve limitations found in previously designed surgical guides and can be easily incorporated into computer designing and 3D printing software.

Auto-labeling is one of the main challenges in 3D vehicle detection. Auto-labeled datasets can be used to identify objects in LiDAR data, which is a challenging task due to the large size of the dataset. In this work, we propose a novel methodology to generate new 3D based auto-labeling datasets with a different point of view setup than the one used in the most recognized datasets (KITTI, WAYMO, etc.). The performance of the methodology has been further demonstrated with the development of our own dataset with the auto-generated labels and tested under boundary conditions on a bridge in a fixed position. The proposed methodology is based on the YOLO model trained with the KITTI dataset. From a camera-LiDAR sensory fusion, it is intended to auto-label new datasets while maintaining the consistency of the Ground Truth. The main contribution of this work is a novel methodology to auto-label autonomous driving datasets using YOLO as the main labelling system. The performance of this approach is measured retraining the contrast models of the KITTI benchmark.

Based on orbital angular momentum (OAM) properties of Laguerre Gaussian beams LG(p,ℓ), a robust optical encoding model for efficient data transmission applications is designed. This paper presents an optical encoding model based on intensity profile generated by a coherent superposition of two OAM-carrying Laguerre-Gaussian modes and Machine-learning detection method. In the encoding process, the intensity profile for data encoding is generated based on selection of p and ℓ indices, while the decoding process is performed using support vector machine (SVM) algorithm. Two different decoding models based on SVM algorithm are tested to verify the robustness of optical encoding model, finding a BER =10−9 for 10.2dB of signal-to-noise ratio in one of the SVM models.

The fluid flow field at the upper airways is highly complex due to the complex structure of the airway. The inhaled particle flow, the air streamline and the interaction of the continuum and discrete phase could significantly affect the transport behaviour of the inhaled particles. A range of analytical, mathematical and computational fluid dynamics (CFD) models analyzed the airflow and particle transport in different idealized and asymmetric airway models. A precise understanding of the continuum and discrete phase interaction in realistic human airways is missing, and this study aims to develop a CFD-DEM model for particle transport in realistic airways. This study uses the CFD model for the continuum phase and the discrete element method (DEM) for the discrete phase. A soft sphere approach is used for the interaction of the discrete phase. Proper validation is performed for particle transport efficiency. The CFD-DEM model analyzed the particle transport in an idealized and realistic airway model, and different methods are used to analyze the transport behaviour. During the particle-particle interaction, a stagnation point and a high-pressure zone are observed at the airway model's carinal angle. The numerical results report higher deposition efficiency (DE) for particle-particle interaction than without interaction. The flow field becomes highly complex with the spring constant values, and higher DE is found for high spring constant values. The spring dashpot friction-dshf method shows higher deposition at the upper part of the airways than other interaction methods. The findings of this study and more case-specific analysis would improve the knowledge of aerosol transport in airways and the health risk assessment of the patient.

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.

Consumption of prebiotic fibers to modulate the human gut microbiome is a promising strategy to positively impact health. Nevertheless, given the compositional complexity of the microbiome and its inter-individual variances, generalized recommendations on the source or amount of fiber supplements remain vague. This problem is further compounded by availability of tractable in vitro and in vivo models to validate certain fibers. We employed a gnotobiotic mouse model containing an a priori characterized 14-member synthetic human gut microbiome (SM) for their ability to metabolize a suit of fibers in vitro; the SM contains 14 different strains belonging to five distinct phyla. Since soluble purified fibers have been a common subject of studies, we specifically investigated the effects of concentrated raw fibers (CRFs)—containing fibers from pea, oat, psyllium, wheat and apple—on the compositional and functional alterations in the SM. We demonstrate that, compared to a fiber-free diet, CRF supplementation increased the abundance of fiber-degraders namely Eubacterium rectale, Roseburia intestinalis and Bacteroides ovatus and decreased the abundance of the mucin-degrader Akkermansia muciniphila. These results were corroborated by a general increase of bacterial fiber-degrading α-glucosidase enzyme activity. Overall, our results highlight the ability of CRFs to enhance the microbial fiber-degrading capacity.

The maker movement has reached the optics labs, empowering researchers to actively create and modify microscope designs and imaging accessories. 3D printing has especially had a disruptive impact on the field, as it entails an accessible new approach in fabrication technologies, namely additive manufacturing, making prototyping in the lab available at low cost. Examples of this trend are taking advantage of the easy availability of 3D printing technology. For example, inexpensive microscopes for education have been designed, such as the FlyPi. Also, the highly complex robotic microscope OpenFlexure represents a clear desire for the democratisation of this technology. 3D printing facilitates new and powerful approaches to science and promotes collaboration between researchers, as 3D designs are easily shared. This holds the unique possibility to extend the open-access concept from knowledge to technology, allowing researchers from everywhere to use and extend model structures. Here we present a review of additive manufacturing applications in microscopy, guiding the user through this new and exciting technology and providing a starting point to anyone willing to employ this versatile and powerful new tool.

This work is part of an ongoing research project to develop an unmanned flying social robot to monitor dependants at home in order to detect the person’s state and bring the necessary assistance. In this sense, this paper focuses on the description of a virtual reality (VR) simulation platform for the monitoring process of an avatar in a virtual home by a rotatory-wing autonomous unmanned aerial vehicle (UAV). This platform is based on a distributed architecture composed of three modules communicated through the Message Queue Telemetry Transport (MQTT) protocol: the UAV Simulator implemented in MATLAB/Simulink, the VR Visualiser developed in Unity, and the new emotion recognition (ER) System developed in Python. Using a face detection algorithm and a convolutional neural network (CNN), the ER System is able to detect the person’s face in the image captured by the UAV’s on-board camera and classify the emotion among seven possible ones (surprise, fear, happiness, sadness, disgust, anger or neutral expression). The experimental results demonstrate the correct integration of this new computer vision module within the VR platform, as well as the good performance of the designed CNN, with around 85% in the F1-score, a mean of the precision and recall of the model. The developed emotion detection system can be used in the future implementation of the assistance UAV that monitors dependent people in a real environment, since the methodology used is valid for images of real people.

Background: Physical activity is recommended to mitigate the incidence of obesity, but delivery of community wide initiatives is cumbersome. The challenges met by such programs are magnified when implementation transpires in the remote villages of Alaska. To overcome the difficulty of this challenge in the Arctic, the Skiku/AK Nordic cross-country skiing program was developed. The objective of this study was to evaluate whether access to Skiku/AK Nordic program would promote physical activity levels that met the daily recommendations for physical activity in Alaska Native children. Methods: Eight children (4 females and 4 males; 10±2 years/age) were recruited from Kaktovik, Alaska for participation in this study. Expert coaches and staff provided one week of cross-country ski instruction and access to ski equipment. Physical activity was monitored using ActiGraph GT3X+ accelerometers. Data collected from the devices was then downloaded and analyzed using ActiLife software. Results: The participants expended ~586 calories/day devoted to physical activity. Light and moderate physical activity was 68±38 minutes/day and 447±248 minutes/day, respectively. Conclusions: Delivery of the Skiku/AK Nordic program promoted favorable levels of physical activity in Alaska Native children. Further research is needed to assess the longitudinal and seasonal effectiveness of the Skiku/AK Nordic program.

T cell function is determined by transcriptional networks that are regulated by epigenetic programming via posttranslational modifications (PTMs) of histone proteins and DNA. Bottom-up mass spectrometry (MS) can identify histone PTMs, whereas intact protein analysis with high-field Fourier transform ion cyclotron resonance MS (FTICR-MS) can detect species missed by bottom-up approaches. We used high-resolution reversed-phase liquid chromatography (RPLC) FTICR-MS, alternating electron transfer dissociation (ETD) and collision-induced dissociation (CID) on precursor ions to maximize fragmentation of uniquely modified species. First online RPLC separation sorted histone families then weak cation exchange hydrophilic interaction liquid chromatography (WCX-HILIC) separated species heavily clad in PTMs. Tentative PTM identifications were assigned by matching peptide masses to predicted theoretical masses that were verified with tandem MS. We used this innovative approach for Histone-intact protein PTM mapping (HiPTMap) and to quantify PTMs on core histones purified from CD8+ T cells directly isolated ex vivo post-influenza infection. Activation significantly reduced PTMs in vivo following influenza infection, histone maps changed as T cells migrated to infections, and T cells responding to secondary heterologous infections had significantly more PTMs enhancing transcriptional activation. Thus, HiPTMap identifies and quantifies PTMs on CD8+ T cell histones and determines their combinations in T cell states.

Fruits play an important role in human diet and to maintain better health. Globally, India ranks second in fruits production after China. Grapes, mangoes, bananas and oranges were the selected fruit crops for study purpose. The study period is from 1990 to 2018. The present study analyzed the growth rates, instability and elasticity of export quantity, prices of selected fruit crops from major producing countries in the world and also dealt with the major export destinations of Indian fruits. The results showed that an exporting countries should export grapes to Peru, Spain and Chile; bananas to the Panama, Philippines and Ecuador; mangoes to Italy, Egypt and Australia; and, oranges to Thailand, Philippines and Mexico for generating higher revenue because in global market those countries were associated with highest export price with the stability. Globally, the export price elasticity was inelastic in all countries of grapes, oranges and bananas except Italy in oranges and panama in bananas. The study found that export price elasticity of mangoes was marginally higher in the Spain and the Netherlands. The study showed that the major destinations for Indian fruits are; USA, Germany and Netherlands for grapes; USA, Belgium and Germany for bananas; USA, the Netherlands and Viet Nam for mangoes; and, Germany, France and Netherlands for oranges. Globally, the current study gave useful data to comprehend competition of prices for fruits to importing countries. This study may assist in preparing major price strategies and policies on fruits and also assisted in foreign earnings for all nations.

We analyzed the SARS-CoV-2 spike (S) protein amino acid sequence extracted from 11,542 viral genomic sequences submitted to the Global Initiative on Sharing All Influenza Data (GISAID) database through April 27, 2020. Consistent with prior reports, we found a major S protein mutation, D614 to G614, that was represented in 56% of all the analyzed sequences. All other mutations combined were less than 10%. After parsing the data geographically, we found most of the Chinese patient samples showed D614 (97%). By contrast, most patient samples in many European countries showed G614 (51 to 88%). In the United States, the genotypic distribution in California and Washington was similar to Asian countries, while the distribution in other US states was comparable to Europe. We observed a dramatic increase in the frequency of G614 over time in multiple regions, surpassing D614 when both were present, suggesting G614 S protein virus outcompetes D614 S protein virus. To gain insight into the consequences of the D614G mutation, homology modeling using a multi-template threading mechanism with ab initio structural refinement was performed for a region of the S protein (S591 to N710) spanning the D614G mutation and the S1 furin cleavage site. Molecular models of this region containing D614 or G614 revealed a major difference in secondary structure at the furin domain (RRARS, R682 to S686). The D614 model predicted a random coil structure in the furin domain whereas the G614 model predicted an alpha helix. Critical residues in the cleavage domain of G614 model were found to better align with the PDB structure of a furin inhibitor. Thus, homology modeling studies suggest a potential mechanism whereby the D614G mutation may confer a competitive advantage at the furin binding domain that may contribute to the rise of the D614G SARS-CoV-2 mutant.

Ebola virus (EBOV) is a zoonotic pathogen causing severe hemorrhagic fevers in humans and non-human primates with high case fatality rates. In recent years, the number and extent of outbreaks has increased, highlighting the importance of better understanding the molecular aspects of EBOV infection and host cell interactions to control this virus more efficiently. Many viruses, including EBOV, have been shown to recruit host proteins for different viral processes. Based on a genome-wide siRNA screen, we recently identified the cellular host factor carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) to be involved in EBOV RNA synthesis. However, mechanistic details of how this host factor plays a role in the EBOV life cycle remain elusive. In this study, we analyzed the functional and molecular interactions between EBOV and CAD. To this end, we used siRNA knockdowns in combination with various reverse-genetics based lifecycle-modelling systems and additionally performed co-immunoprecipitation and co immunofluorescence assays to investigate the influence of CAD on individual aspects of the EBOV life cycle and to characterize the interactions of CAD with viral proteins. Following this approach, we could demonstrate that CAD directly interacts with the EBOV nucleoprotein NP, and that NP is sufficient to recruit CAD into inclusion bodies dependent on the GLN-domain of CAD. Further, siRNA knockdown experiments indicated that CAD is important for both viral genome replication and transcription, while substrate rescue experiments showed that the function of CAD in pyrimidine synthesis is indeed required for those processes. Together this suggests that NP recruits CAD into inclusion bodies via its GLN domain in order to provide pyrimidines for EBOV genome replication and transcription. These results define a novel mechanism by which EBOV hijacks host cell pathways in order to facilitate genome replication and transcription, and provide further basis for the development of host directed broad spectrum antivirals.

This pilot study of Streptococcus mutans ATCC 35668 grown in media with and without polyols (erythritol) measured the resultant metabolites, including the short chain fatty acids by using head space analysis. Brain Heart Infusion Broth (BHI2 or BHI10) supplemented with 2% or 10% sucrose containing no polyols or either erythritol or xylitol and Streptococcus mutans (ATCC 35668) was grown aerobically. After 48 hours of growth the supernatant were harvested and centrifuged to pellet bacteria. Supernatants were removed from bacterial pellets then submitted for Short Chain Fatty Acid (SCFA) analysis with an Agilent Technologies (Santa Clara, CA 95051) system configured from three components, a 5973 mass selective detector, a 6890N gas chromatographer, and a 7697A headspace sampler. Streptococcus mutans growing in Brain Heart Infusion Broth (BHI2 or BHI10) supplemented with 2% or 10% sucrose but containing no polyols produced the following short chain fatty acids: methyl isovalerate, acetic acid, propionic acid, butanoic acid, pentanoic acid, ethyl butaric acid, 4-methylvaleric acid, hexanoic acid. When the Brain Heart Infusion Broth (BHI2 or BHI10) supplemented with 2% or 10% sucrose containing erythritol was used as media for this Streptococcus mutans strain, the following were produced: ethanol, acetoin, and acetic acid. Our results would suggest that constituents of the media may affect the bacterial metabolite production.

In this paper, the columnar supramolecular aggregates of photosensitive star-shaped azobenzenes with benzene-1,3,5-tricarboxamide core and azobenzene arms are analysed theoretically applying a combination of computer simulation techniques. Without a light stimulus, the trans-stars build one-dimensional columns of stacked molecules during the first stage of the noncovalent association. These columnar aggregates represent the structural elements of more complex experimentally observed morphologies -- fibers, spheres, gels and others. Upon UV light exposure, the azobenzene arms isomerise from thermodynamically stable planar trans- to a metastable kinked cis-state influencing the aggregate morphology. Here, we determine the most favourable mutual orientations of the \textit{trans}-stars in the stack in terms of (i) the pi-pi distance between the cores lengthwise the aggregate, (ii) the star slipped displacements and (iii) the rotation promoting the helical twist and chirality of the aggregate by calculating the binding energy diagrams using density functional theory. The model predictions are further compared with available experimental data. The intermolecular forces responsible for the stability of the stacks made of trans-azobenzene stars in crystals are quantified using Hirshfeld surface analysis. Finally, to characterize the self-assembly mechanism of such stars in solution, we calculate the hydrogen bond lengths, the normalized dipole moment and the binding energies as the functions of the columnar length using molecular dynamics trajectories, and conclude about the cooperative nature of this process.

Full waveform (FW) LiDAR holds great potential for retrieving vegetation structure parameters at a high level of detail, but this prospect is constrained by practical factors such as lack of available handy processing tools and technical intricacy of waveform processing. This study introduces a new product, named the Hyper Point Cloud (HPC) derived from FW LiDAR data, and explore its potential applications such as tree crown delineation using the HPC-based intensity and percentile height (PH) surfaces, which show a promising solution to the constraints of using FW LiDAR data. Results of the HPC present a new direction to handle FW LiDAR data and offer prospects for studying the mid-story and understory of vegetation with high point density (~ 182 points/m2). The intensity-derived digital surface model (DSM) generated from the HPC shows that the ground region has larger maximum intensity (MAXI) and mean intensity (MI) than the vegetation region while having smaller total intensity (TI) and number of intensities (NI) at the given grid cell. Our analysis of intensity distribution contours at individual tree level exhibit similar patterns, indicating that the MAXI and MI are decreasing from the tree crown center to tree boundary while a rising trend is observed for TI and NI. These intensity variable contours provide a theoretical justification for using HPC-based intensity surfaces to segment tree crowns and exploit their potential for extracting tree attributes. The HPC-based intensity surfaces and the HPC-based PH Canopy Height Models (CHM) demonstrate promising tree segmentation results comparable to the LiDAR derived CHM for estimating tree attributes such as tree locations, crown widths and tree heights. We envision that products such as the HPC and the HPC-based intensity and height surfaces introduced in this study can open new perspectives to use FW LiDAR data and alleviate the technical barrier of exploring FW LiDAR data for detailed vegetation structure characterization.

The micropaleontological study (radiolarians and foraminifera) of the sediment core AMK-340, Reykjanes Ridge, North Atlantic, combined with the radiocarbon dating and Oxygen/Carbon isotopic record, provided data for the reconstruction of the summer paleotemperature on the water depth of 100 m, and paleoenvironments during the Termination I in the age interval of 14.5–8 ka. The response of the main microfossil species on the paleoceanographic changes within the Bølling-Allerød (BA) warming, the Younger Dryas (YD) cold event, and final transition to the warm Holocene was different. The BA warming was well reflected in the radiolarian and benthic but not planktic foraminiferal record. The high abundances of the cold-water radiolarian species Amphimelissa setosa as the Greenland/Iceland Sea indicator marked a cooling at the end of the BA and within the start of the YD at 13.2–12.3 ka. The micropaleontological and isotopic data together with the paleotemperature estimates for the Reykjanes Ridge at 60° N document that, after the warm BA, the middle YD ca. 12.5–12.2 ka was the next significant step toward the Holocene warming. Start of the Holocene interglacial conditions was reflected in abundant occurrence of the microfossils being indicators of the open boreal North Atlantic environments and lower oxygen isotope values indicating increasing warmth.

Akt1 is a proto-oncogene that is over active in most cancers. Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473 further enhances catalytic activity. Akt1 activity is also regulated via interactions between the kinase domain and the N-terminal auto-inhibitory pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1 in site-specifically phosphorylated forms, the contribution of each activating phosphorylation site to auto-inhibition was unknown. Using a combination of genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1 variants containing programmed phosphorylation to probe the interplay between Akt1 phosphorylation status and the auto-inhibitory function of the PH domain. Deletion of the PH domain increased the enzyme activity for all three phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of the PH domain relieved auto-inhibition by 295-fold. We next found that phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2 inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1T308 and showed 4-fold decreased potency with Akt1 variants phosphorylated at Ser473. The data highlight the need to design more potent Akt1 inhibitors that are effective against the doubly phosphorylated and most pathogenic form of Akt1.

An interdigitated electrode sensor was designed and microfabricated for measuring the changes in the capacitance of three phosphate selective molecularly imprinted polymer (MIP) formulations, in order to provide hydroponics users with a portable nutrient sensing tool. The MIPs investigated were synthesised using different combinations of the functional monomers methacrylic acid (MAA) and N-allylthiourea, against the template molecules diphenyl phosphate, triethyl phosphate and trimethyl phosphate. A cross-interference study between phosphate, nitrate and sulfate was carried out for the MIP materials using an inductance, capacitance and resistance (LCR) meter. Capacitance measurements were taken applying an alternating current (AC) with a potential difference of 1 V root mean square (RMS) at a frequency of 1 kHz. The cross-interference study demonstrated a strong binding preference to phosphate over the other nutrient salts tested for each formulation. The size of template molecule and length of the functional monomer side groups also determined that a combination of a short chain functional monomer in combination with a template containing large R-groups produced the optimal binding site conditions when synthesising a phosphate selective MIP.

This study estimates rainfall interception losses from natural wetland ecosystems based on maximum canopy storage measurements. Rainfall interception losses play an important role in water balance, which is crucial in wetlands, and has not yet been thoroughly studied in relation to this type of ecosystem. Maximum canopy storage was measured using the weight method. Based on these measurements, daily values of interception losses were estimated and then used to calculate long term interception losses based on precipitation and potential evapotranspiration data for the 1971–2015 period. Depending mainly on the number of days with precipitation, the results show that total interception losses for the growing season as well as monthly interception losses are around 13% of gross rainfall. This value is similar to the values observed for some forests. Hence, interception losses should not be disregarded in hydrologic models of wetlands, especially because data trends in meteorological conditions (mainly number of days with precipitation) show that interception losses will increase in the future if those trends stay the same.

Papua is one of part in Indonesia which is the geology research of that place isn’t developed and limited. It causes the seismotectonic of Papua hasn’t been known. WinITDB was used to determine the dip angle plate which was on the north part of Papua. The determination of angle was done through seismicity’s cross section analysis in the area. To show that seismicity, earthquake history data that ever occurred in the area is needed. The result on the seismicity’s cross section of plane A–A’, was confluence by two plates with angle 150° against horizontal on the depth up to ±68 km. On the seismicity’s cross section of plane B–B’ had angle 135° against horizontal on the ±82 km depth. On the plane C–C’ seismicity’s cross section, was confluence of two plate which located between -1,77°S until -4,97°S subducted until 171 km depth on 1,38°N - 4,97°S. It proved that subduction characteristic in the northern Papua which was Australia continent plate subducted to north, followed by collision and the Pacific plate subduction on New Guinea. It is also confirmed by focus mechanism analysis which showed the earthquake activities are controlled by the not really deep active fault.

Chronic inflammation alters lipoprotein metabolism and causes changes in serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, and immunomodulator. However, unlike in people with inflammatory bowel disease, scarce information is available in dogs with protein-losing enteropathy secondary to chronic inflammatory enteropathy (iPLE). The first aim was to describe and compare the lipid profile, CRP concentrations and PON-1 activity in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data, and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides, and lipoprotein classes obtained by electrophoretic separation. There was a significant difference of all serum analytes between iPLE and healthy dogs. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. Some lipoprotein classes correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. Lipoproteins, CRP and PON-1 activity are altered in dogs with iPLE. Results need to be confirmed in further studies.

Exposure to cadmium sulfate (CdSO4) can lead to neurotoxicity. Nevertheless, the precise molec-ular mechanisms underlying this phenomenon remain unclear, and effective treatment strategies are scarce. This study explored the protective effects of ellagic acid (EA), a natural polyphenolic compound, against CdSO4 exposure-induced neurotoxicity in HT22 cells. Additionally, the inves-tigation sought to elucidate the molecular mechanisms underlying this phenomenon. Our findings demonstrated that exposure of HT22 cells to CdSO4 resulted in apoptosis, which was effectively reversed by EA supplementation. EA supplementation also decreased reactive oxygen species (ROS) and mitochondrial ROS productions, reduced malondialdehyde (MDA) levels, and restored the activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, EA supplementation at 5–20 μM significantly counteracted Cd-induced mitochondrial membrane potential and ATP losses and reduced the ratio of Bax/Bcl-2 and cleaved-caspase-3 protein expression. Furthermore, EA supplementation upregulated Nrf2 and HO-1 protein expression while downregulating the phosphorylation of JNK and p38 proteins. Pharmacological inhibition of JNK partially inhibited CdSO4-induced Nrf2/HO-1 activation and exacerbated its cytotoxicity. In conclusion, our results indicate that EA supplementation provides protection against CdSO4-induced cell apoptosis in HT22 cells by inhibiting oxidative stress and activating the Nrf2 pathway. Activation of the JNK pathway plays a protective role in CdSO4-induced cell apoptosis in HT22 cells.

It was previously reported that the peptide derived from LfcinB, R-1-R exhibited anti-Candida activity and this activity was enhanced in combination with an extract from the Bidens pilosa plant. However, the mechanism of action has not been studied. In the current study, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both SC5314 strain and a fluconazole-resistant isolate of Candida albicans, after incubation with R-1-R. The proteomic data showed that after treatment with R-1-R in the two study strains, most of the differentially expressed proteins in comparison to controls were up-regulated. These proteins were mainly involved in membrane and cell wall biosynthesis, membrane transporters, oxidative stress, the mitochondrial respiratory chain, and response to DNA damage. Besides, the proteomic analysis of C. albicans parental strain SC5314 treated with R-1-R in combination with an ethanolic extract of B. pilosa was also undertaken. The proteins differentially expressed after this treatment were involved in similar functional processes as the proteins differentially expressed after treatment with R-1-R peptide alone, but at different levels and were mostly down-regulated. The biological assays allowed validation of the proteomic results, evidencing damage to the cell surface, generation of reactive oxygen species and decrease in mitochondrial membrane potential. The results provide information to begin to unlock the understanding of the complex antifungal mode of action of the R-1-R peptide, its combination with the extract, and possibly other derivatives of natural products.

We perform new measurements of the expansion rate and the sound horizon at the end of the baryon decoupling and derive constraints on cosmic key parameters in the framework of the ΛCDM model, flat wCDM model, the ΛCDM+ΩK model and the phenomenological emergent dark energy (PEDE) model. We keep rd and H0 completely free and use the recent dark energy spectroscopic instrument (DESI) Year 1 and dark energy survey (DES) Year 6 BAO measurements in the effective redshift range 0.3<z<2.33 combined with the compressed form of the Pantheon sample of Type Ia supernovae, the latest 33 observational H(z) measurements based on the differential age method, and the recent H0 measurement from SH0ES 2022 as an additional Gaussian prior. Combining BAO data with the observational H(z) measurements, and the Pantheon SNe Ia data, we get H0=69.65±1.07 km s−1 Mpc−1, rd=147.71±2.18 Mpc in ΛCDM model, H0=70.06±1.07 km s−1 Mpc−1, rd=147.39±2.50 Mpc in PEDE model. The spatial curvature is Ωk=0.025±0.026 and the dark energy equation of state is w=−1.016±0.056, consistent with a cosmological constant. We apply the Akaike information and the Bayesian information criterion test to compare the four models, and see that PEDE model performs better.

Introduction: Type 1 diabetes mellitus is a chronic disease of autoimmune etiology that is highly prevalent in childhood. In the last decade, the possibility of using the Bacillus Calmette-Guérin vaccine for the treatment of this disease has been studied thanks to its immunomodulatory action . Objectives: The objective of this work is to carry out a systematic review of the available scientific evidence on the relationship between the tuberculosis vaccine and the treatment of diabetes in childhood. Secondarily, the aim is to study the incidence of Type 1 Diabetes Mellitus in a cohort of children from the Basque Country according to whether or not they have received the vaccine. Methods: An exhaustive bibliographic search has been carried out on the evidence available to date. For the epidemiological study in Euskadi, a comparison of accumulated incidences between vaccinated and unvaccinated population groups was made. Results: According to the literature analyzed, There is more and more evidence about the possible use of the tuberculosis vaccine in Type 1 Diabetes Mellitus. The results of our study were not conclusive, but we believe that it is necessary to continue with long-term studies to eliminate biases. Conclusions: The Bacillus Calmette-Guérin vaccine could be used for the treatment of autoimmune, allergic, infectious or oncological processes, although more studies are still necessary in this regard.

Neuronal cells are believed to rely on autophagy to maintain cellular homeostasis. Nevertheless, autophagy may be a therapeutic target for neurodegenerative diseases because of the role it plays in neuronal cell death. Despite Beclin 1 association with autophagy and apoptosis, the molecular mechanisms that underlie Tau-induced vesicular pathology and Tau protein aggregates in humans remain poorly understood. Here, we set out to examine the role of three genes-ATG14L, Beclin 1 and VPS34- in autophagy nucleation failure-associated Tau disorders in fruit fly models. We found that either reduced ATG14L levels improve neuronal outcomes, or transgenic expression of ATG6/Beclin 1 greatly reduced age-dependent neurodegeneration and Tau pathology; whereas, the loss of Beclin 1 exacerbated these effects. Prior to p-Tau accumulation, the neuronal Beclin 1 network is critical for reducing p-Tau accumulation, indicating that the loss of Beclin 1 causes Tau pathology and neurodegeneration. As neurodegeneration progressed, glial cells showed an upregulation of vesicular Beclin 1 immunoreactivities. The reduced VPS34 also resulted in p-Tau accumulation, suggesting that neurons require both Beclin 1 and VPS34 to reduce p-Tau accumulation. Our results provide mechanistic insight into the molecular pathways that cause age-dependent Tau pathology and neurodegeneration due to an excess of autophagy nucleation processes and autophagy activity, and we derive novel inferences on the therapeutic possibilities of rebalanced Beclin 1 network by reducing autophagic specific nucleation component of ATG14L.

The dengue virus (DENV) is an arbovirus belonging to the Flaviviridae family; the species comprises four antigenically distinct serotypes (DENV–1, DENV–2, DENV–3, and DENV–4), which are further subdivided into genotypes. The virus is transmitted to humans through mosquito bites, primarily from the Aedes spp. genus. Dengue is endemic in various parts of the world, including tropical and subtropical regions of Asia, Latin America, Africa, and Oceania. In Brazil, the state of Tocantins, located in north-central Brazil, has experienced a significant number of arboviral disease cases, particularly dengue. This study aimed to monitor DENV circulation within the state by conducting full genome sequencing of viral genomes recovered from 61 patients between June 2021 and July 2022. During this period, both DENV-1 and DENV-2 serotypes were identified. Our findings confirm the circulation of DENV serotypes 1 and 2 in Tocantins, affecting males and females equally, with younger age groups (4 to 43 years old) being the most susceptible. Phylogenetic analysis revealed that the circulating viruses belong to DENV–1 genotype V American and DENV–2 genotype III Southeast Asian/American. The Bayesian analysis of DENV-1 Genotype V sequenced here is closely related to genomes previously sequenced in the state of São Paulo. Regarding DENV-2 genotype III genomes, these are clustered in a distinct, well-supported subclade, along with previously reported isolates from the states of Goiás and São Paulo. In both cases, our results suggest that multiple introductions of these genotypes occurred in the Tocantins state. This observation highlights the significant impact of major population centers in Brazil on virus dispersion, including other Latin-American countries and the USA. In the SNP analysis, DENV-1 displayed 122 distinct missense mutations, while DENV-2 had 44, with significant mutations predominantly occurring in the envelope and NS5 proteins. The analyses performed here reveal the concomitant circulation of distinct DENV-1 and -2 genotypes in some Brazilian states, underscoring the dynamic evolution of the DENV and the ongoing significance of surveillance efforts in supporting public health policies.

Abstract: The spectral and dynamic properties of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)

The human T-cell leukemia virus type 1 (HTLV-1) is the only known human oncogenic retrovirus. HTLV-1 can cause a cancer called adult T-cell leukemia/lymphoma (ATL). The virus is transmitted through body fluids of infected individuals, primarily breast milk, blood, and semen. At least 5–10 million people in the world are infected with HTLV-1. In addition to ATL, HTLV-1 infection can also cause HTLV-I-associated myelopathy (HAM /TSP). ATL is characterized by low viral ex-pression and poor prognosis. The oncogenesis triggered by HTLV-1 is extremely complex and the molecular mechanisms are not fully understood. However, viral regulatory proteins Tax and HTLV-1 bZIP factor (HBZ) have been shown to play key roles in the transformation of HTLV-1-infected T cells. Moreover, several studies have shown that the final fate of HTLV-1-infected transformed T cell clones is the result of a complex interplay of HTLV-1 oncogenic protein expression with cellular transcription factors that subvert the cell cycle and disrupt reg-ulated cell death, thereby exerting their transforming effects. This review provides updated in-formation on the mechanisms underlying the transforming action of HTLV-1 and the potential therapeutic targets to combat ATL.

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

: Consumption of plant-based milk replacers has increased in recent years due to health benefits, benefits attributed mainly to the content of phenolic compounds, fatty acids, or bioactive compounds with antioxidant activity. In this context, we proposed to obtain two types of less studied plant-based beverages, namely lupine and chickpea beverages, as well as the possibility of getting these beverages using germinated seeds and even obtaining probiotic drinks through fermentation with Lactobacillus plantarum 299v. To evaluate the quality of the obtained products, we determined their content of proteins, fatty acids, organic acids, volatile compounds, and phenolic compounds. We evaluated the antioxidant activity of the obtained herbal drinks, and a load of probiotic microorganisms present after the fermentation process. Both lupine and chickpea drinks have the desired properties, high content of fatty acids and phenolic compounds, that bring probiotic benefits.

The prognosis of patients with recurrent or metastatic of the head and neck squamous-cell carcinoma (HNSCC) refractory to platinum-based chemotherapy is severe and, consequently, the identification of therapeutic options for this category of patients is a priority. Nivolumab, an anti- programmed cell death protein 1 (anti-PD-1) monoclonal antibody, has been approved for the treatment of recurrent or metastatic HNSCC after platinum-based therapy progressing. We present the early experience of two academic center including diagnostic, clinical, biological, therapeutic and outcomes characteristics of head and neck cancer (HNC) patients treated with Nivolumab. The purpose of the study is to identify certain peculiarities and to report them compared to the data from the literature in order to generate some hypotheses that coud constitute criteria for the selection of cases with maximum benefit to immunotherapy. Analyzing the data obtained from 18 patients treated in Emergency County Hospital Craiova, "Saint Nectarie" Oncological Hospital Craiova and Euroclinic Oncological Center Iasi January 2020 and March 2023 it could be hypothesized that lower nadir values of neutrophil to lymphocyte ratio (<3.5) and the adition of intensive regimens of chemotherapy and radiotherapy could justify a favorable response in terms of progression free survival (PFS) during immunotherapy with Nivolumab. To our knowledge, the study included the first two cases of second primary malignancy (SPM) in the head neck region treated with Nivolumab. The reported data support a possible benefit of the sequential administration of radiotherapy, immunotherapy for SPM cases. Higher positive dynamic of neutrophil to lymphocyt ratio (NLR) could be associated with worst outcome during immunotherapy. All study observations including the role of infections and antibiotic treatment as well as the possible biomarker value of NLR variation during immunotherapy should be investigated in multicenter clinical trials.

Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, like empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1β, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate–induced VC in mouse VSMCs to investigate the mechanisms underlying empagliflozin’s therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE−/− mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate–induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE−/− mice on a high-phosphate diet.