Humans may be exposed to microbial pathogens at recreational beaches via environmental sources, such as water, sand, and aerosols. Although infectious disease risk from exposure to waterborne pathogens has been an active area of research for decades, sand is a relatively unexplored reservoir of pathogens and fecal indicator bacteria (FIB). Beach sand and water habitats provide unique advantages and challenges to pathogen introduction, growth, and persistence, as well as continuous exchange between habitats. Models of FIB and pathogen fate and transport in sandy beach habitats can help predict the risk of infectious disease from recreational water use, but filling knowledge gaps such as decay rates and potential for microbial growth in beach habitats is necessary for accurate modeling. Climatic variability, whether natural or anthropogenically-induced, adds complexity to predictive modeling, but may increase human exposure to waterborne pathogens via extreme weather events, warming of water bodies and sea level rise in many regions. The popularity of human recreational beach activities, combined with predicted climate change scenarios, could amplify the risk of human exposure to pathogens and related illnesses. Other global change trends such as increased population growth and urbanization are expected to exacerbate contamination events and the predicted impacts of increasing levels of waterborne pathogens on human health. Such changes will alter microbial population dynamics in beach habitats, and will consequently affect the assumptions and relationships used in population models and quantitative microbial risk assessment (QMRA). Here, we discuss the literature on microbial population and transport dynamics in sand-water continuum habitats at beaches, how these dynamics can be modeled, and how climate change and other anthropogenic influences (e.g., land use, urbanization) should be considered when using and developing more holistic, beachshed-based models.

The Rosetta software suite for macromolecular modeling, docking, and design is widely used in pharmaceutical, industrial, academic, non-profit, and government laboratories. Considering its broad modeling capabilities, Rosetta consistently ranks highly when compared to other leading methods created for highly specialized protein modeling and design tasks. Developed for over two decades by a global community of scientists at more than 60 institutions, Rosetta has undergone multiple refactorings, and now comprises over three million lines of code. Here we discuss the methods developed in the last five years, involving the latest protocols for structure prediction, protein–protein and protein–small molecule docking, protein structure and interface design, loop modeling, the incorporation of various types of experimental data, and modeling of peptides, antibodies and other proteins in the immune system, nucleic acids, non-standard amino acids, carbohydrates, and membrane proteins. We briefly discuss improvements to the energy function, user interfaces, and usability of the ­­software. Rosetta is available at www.rosettacommons.org.

Water hyacinth (Eichhornia crassipes) is an invasive species that has modified ecosystem functioning in the Sacramento-San Joaquin Delta (Delta), California, USA. Studies in lakes and rivers have shown that water hyacinth alters water quality. In tidal systems, such as the Delta, water moves back and forth through the water hyacinth patch so water quality directly outside the patch in either direction is likely to be impacted. In this study, we asked whether the presence or treatment of water hyacinth with herbicides resulted in changes in water quality in this tidal system. We combined existing datasets that were originally collected for permit compliance and long-term regional monitoring into a dataset that we analyzed with a before-after control-impact (BACI) framework. This approach allowed us to describe effects of presence and treatment of water hyacinth, while accounting for seasonal patterns in water quality. We found that although effects of treatment were not detectable when compared with water immediately upstream, dissolved oxygen and turbidity became more similar to regional water quality averages after treatment. Temperature became less similar to the regional average after treatment, but the magnitude of the change was small. Taken together, these results suggest that tidal hydrology exports the effects of water hyacinth upstream, just as river flow is known to transport the effects downstream, creating a buffer of altered water chemistry around patches. It also suggests that although water hyacinth has an effect on dissolved oxygen and turbidity, these parameters recover to regional averages after treatment.

Studies investigating the acute effect of postprandial exercise (PPE) on glucose responses exhibit significant heterogeneity in terms of participant demographic, exercise protocol, and exercise timing post-meal. As such, this study aimed to further analyze the existing literature on the impact of PPE on glycemic control in individuals with overweight, obesity, and type 2 diabetes (T2D). Literature search was conducted through databases including PubMed, CINAHL, and Google Scholar. Thirty-one original research studies that met the inclusion criteria were selected. The random-effect meta-analysis was performed to compare postprandial glucose area under the curve (AUC) and 24-h mean glucose levels between PPE and the time-matched no-exercise control (CON). Subgroup analysis was conducted to explore whether the glucose-lowering effect of PPE could be influenced by exercise duration, exercise timing post-meal, and disease status of participants. This study revealed significantly reduced glucose AUC (Hedges’ g = -0.317; SE = 0.057; p < 0.05) and 24-hour mean glucose levels (Hedges’ g = -0.328; SE = 0.062; p < 0.05) following PPE than CON. The reduction in glucose AUC was greater (p < 0.05) following PPE lasting >30 min than ≤30 min. The reduction in 24-hour mean glucose levels was also greater (p < 0.05) following PPE initiated ≥60 min than <60 min post-meal and in those with T2D than those without T2D. PPE offers a viable approach for glucose management and can be performed in various forms so long as exercise duration is sufficient. The glucose-lowering effect of PPE may be further enhanced by initiating it after the first hour post-meal. PPE represents a promising strategy, particularly for patients with T2D.

By using hydrogen quench continuous annealing technology, Stelco Inc. has developed a suite of Advanced High Strength Steel (AHSS) grades with tensile strength greater than 1000MPa to meet standard automotive specifications and for unique customer requirements. These grades were optimized by correlating chemical composition and processing parameters with microstructures and mechanical properties. Dual-Phase 980 (Stelco trademarked STELMAXTM 980DP), Multi-Phase 1180 (STELMAXTM 1180MP), Martensitic Steel 1300 (STELMAXTM 1300M) and 1500 (STELMAXTM 1500M) products met strength and formability requirements with excellent flatness and surface quality. Hydrogen quench continuous annealing technology not only ensures all developed AHSS grades have consistent mechanical properties across the entire strip length (from strip head to tail) and width (from edge to edge), but also produces high product yield compared with other continuous annealing processes.

To stabilize the Earth’s climate a large-scale transition is needed to non-carbon emitting renewable energy technologies like wind and solar energy. Although these renewable energy sources are now lower-cost than fossil fuels, their inherent intermittency make them unable to supply a constant load without storage. To address these challenges rechargeable electric batteries are currently the most promising option; however, their high capital costs limit current deployment velocities. To both reduce the cost as well as improve performance 3D printing technology has emerged as a promising solution. This literature review provides the state-of-the-art enhancements of battery properties with 3D printing including efficiency, mechanical stability, energy and power density, customizability and sizing, production process efficiency, material conservation and environmental sustainability as well as the progress in solid-state batteries. The principles, advantages, limitations, and recent advancements associated with the most common types of 3D printing are reviewed focusing on their contributions to the battery field. 3D printing batteries offer design flexibility, material flexibility, reduces pack weight, minimizes material waste, increases the range of applications and has the potential to reduce costs. As 3D printing technologies become more accessible, the prospect of cost-effective production for customized batteries is extremely promising.

Rationale:First discovered in 1990, the endocannabinoid system (ECS) was initially shown to have an intimate relationship with central areas of the nervous system associated with pain, reward, and motivation. Recently, however, the ECS has been extensively implicated in the cardiovascular system with contractility, heart rate, blood pressure, and vasodilation. Emerging data demonstrates modulation of the ECS plays an essential role in cardio metabolic risk, atherosclerosis, and can even limit damage to cardiomyocytes during ischemic events.Patient Concerns:This case describes a 63-year-old male who presented to a primary care physician for a medical cannabis (MC) consult due to unstable angina (UA) not relieved by morphine or cardiac medications; having failed all first- and second-line poly-pharmaceutical therapies. The patient reported frequent, unprovoked, angina and exertional dyspnea.Diagnosis:Having a complex cardiac history, the patient first presented 22 years ago after a suspected myocardial infarction (MI). He re-presented in 2010 and underwent stent placement at that time for inoperable triple-vessel coronary artery disease (CAD) which was identified via percutaneous transluminal coronary angioplasty. UA developed on follow up and, despite medical management over the past 6 years, his UA became progressively debilitating.Interventions and Outcomes:In conjunction with his standard cardiac care, patient had a gradual lessening of UA related pain, including frequency and character, after using an edible form of medical cannabis (MC) (1:1 CBD:THC). Following continued treatment, he ceased long term morphine treatment and describes the pain as no longer crippling. As demonstrated by his exercise tolerance tests, the patient experienced an improved functional capacity and reported an increase in his daily functioning, and overall activity.Lessons:This case uniquely highlights MC in possibly reducing the character, quality, and frequency of UA; while concordantly improving functional cardiac capacity in a patient with CAD. Additional case reports are necessary to verify this.

Lactic acid bacteria are traditionally applied in a variety of fermented food products and have the capability to produce a wide range of bioactive ingredients during fermentation including vitamins, bacteriocins, bioactive peptides and bioactive compounds. The bioactivity and health benefits associated with these ingredients have gained interest in applications in the functional dairy market and have relevance both as components produced in situ and as functional additives. This review provides a brief description of the regulations regarding the functional food market in the European Union as well as an overview of some of the functional dairy products currently available in the Irish and European markets. A better understanding of the production of these ingredients excreted by lactic acid bacteria can further drive the development and innovation of the continuously growing functional food market.

1) Background: Climate change may subject forests to climate conditions to which they are not adapted. Elevated temperatures reduce net photosynthesis by increasing respiration rates and increasingly long droughts dramatically increase morbidity. CO₂ enrichment enhances productivity, but it is not clear to what extent CO₂ enrichment can offset the negative effects of elevated temperatures and longer droughts. 2) Methods: We used a mechanistic landscape model to conduct controlled simulation experiments manipulating CO₂ concentration, temperature, drought length and soil water capacity. 3) Results: We found that elevated CO₂ stimulates productivity such that it dwarfs the negative effect caused by elevated temperature. Energy reserves were not as strongly mitigated by elevated CO₂, and mortality of less competitive cohorts increased. Drought length had a surprisingly small effect on productivity measures, but had a marked negative effect on mortality risk. 4) Conclusions: Elevated CO₂ compensated for the negative effect of longer droughts in terms of productivity measures, but not survival measures.

Malawi has developed an excellent, nation-wide system for monitoring people infected with HIV and keeping track of key epidemic markers. Their success lies in two things: the focus on simplicity and the use of data collection not only to track the epidemic and identify problems but also to give regular feedback and support to every clinic in the country. This achievement is the more remarkable given that Malawi is one of the poorest countries in the world, ranking 190 out of 194 countries by GDP, but has one of the most severe epidemics of HIV in the world, ranking 9th out of 168 countries by HIV prevalence. We first discuss the current state and likely future epidemic trends in Malawi: unless we know where we are and where we are going we cannot decide what to do or how to do it to in order to achieve a better outcome. We then discuss the history and development of Malawi’s patient monitoring system, as reported in their Integrated HIV Program Reports,ix which have been published quarterly since the beginning of 2004. We consider the current state of patient monitoring and support as reflected in the most recent report for the third quarter (Q3) of 2016 and comment on some of the questions that this raises. Finally, we consider ways in which the current system could be improved by strengthening Malawi’s analytical capacity and making better use of this unique data set. The focus here is on HIV in adultsv because if ART is initiated early in all adults living with HIV this should include testing all pregnant women for HIV and starting them on treatment immediately. However, PMTCT is especially important and care must be given to reducing MTCT and identifying the long-term child survivors of mother-to-child transmission and this demands a complementary assessment. There is an ongoing debate about the relative merits of treatment and prevention in reducing transmission and it should be made clear that the primary reason for starting people on treatment early is that it is in the best interest of the individual patient to start treatment as soon as possible after becoming infected. Allowing a person’s immune system to deteriorate to any degree is not consistent with the clinician’s commitment to ‘first do no harm’ and even those with the highest CD4⁺ cell count are at a substantially increased risk of death. What matters, therefore, is to get as many people as possible onto ART, ensure that they remain virally suppressed, and consider prevention in this context.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

The application of smartphone-based color evaluation of passive sampling devices for gases has only been sparsely reported. The present review aims to compile available publications with respect to the configuration of the passive samplers, conditions of smartphone photographing, analytical procedure for color detection and quantification (including calibration processes), and their application to different target gases. The performance of the methods - whenever available - is presented regarding the analytical specifications selectivity, sensitivity, and limit of detection in comparison with other color evaluation methods of passive samplers. Practical aspects like requirements of instrumentation and ease of use will be outlined in view of the potential employment in education and citizen science projects. In one section of the review the inconsistent terminology of passive and diffusive sampling is discussed in order to clarify the distinction of information obtained from the uptake of the passive samplers between gas-phase concentration and the accumulated deposition flux of gaseous analytes. Colorimetric gas sensors are included in the review when applied in passive sampling configurations and evaluation is performed with smartphone-based color evaluation. Differences in the analytical procedures employed after the passive sampling step and prior to the detection of the colored compounds are also presented.

Monitoring drought impacts in forest ecosystems is a complex process, because forest ecosystems are composed of different species with heterogeneous structural compositions. Even though forest drought status is a key control on the carbon cycle, very few indices exist to monitor and predict forest drought stress. The Forest Drought Indicator (ForDRI) is a new monitoring tool developed by the National Drought Mitigation Center (NDMC) to identify forest drought stress. ForDRI integrates 12 types of data, including satellite, climate, evaporative demand, ground water, and soil moisture, into a single hybrid index to estimate tree stress. The model uses Principal Component Analysis (PCA) to determine the contribution of each input variable based on its covariance in the historical records (2003–2017). A 15-year time series of 780 ForDRI maps at a weekly interval were produced. The ForDRI values at a 12.5km spatial resolution were compared with normalized weekly Bowen ratio data, a biophysically based indicator of stress, from nine AmeriFlux sites. There were strong and significant correlations between Bowen ratio data and ForDRI at sites that had experienced intense drought. In addition, tree ring annual increment data at eight sites in four eastern U.S. national parks were compared with ForDRI values at the corresponding sites. The correlation between ForDRI and tree ring increments at the selected eight sites during the summer season ranged between 0.46 and 0.75. Generally, the correlation between the ForDRI and normalized Bowen ratio or tree ring increment are reasonably good and indicate the usefulness of the ForDRI model for estimating drought stress and providing decision support on forest drought management.

South Africa is afflicted with the worst epidemic of HIV in the world a legacy of the system of oscillating migrant labour in the region and the consequent social disruption that was the legacy of Apartheid. The initial response from the national government was slow and ineffective but once the magnitude of the epidemic became apparent the government began to respond. The investment in HIV- and TB-related activities in 2013 was R22 Bn or (US$2.5; 2013 exchange rate) of which the South Africa government contributed 80% and the Presidents Emergency Plan for AIDS Relief (PEPFAR) 17%. South Africa now has the more people on anti-retroviral therapy than any other country and treatment is being started much sooner after infection. Much of the best biomedical, virological, immunological, mathematical and social science around the treatment and prevention of HIV and AIDS and the associated epidemic of TB has been done by South African’s and their international collaborators. If the efforts to control the epidemic are maintained South Africa is on track to meet the UNAIDS 90-90-90target by 2020 and to End AIDS by 2030 in spite of the magnitude of the problem. While individual, patient level data are increasingly available, especially in the Western Cape, much greater efforts need to be made to ensure that the information collected in this way is used to give feedback and support to clinic staff, to ensure that health clinics are providing the best possible service, and to individual patients and people living with HIV to ensure that they are receiving the best possible care and support. South Africa needs to make better use of the rich and detailed data that are being collected from individual clinics and their patients to identify problems or difficulties at the clinic level and to ensure that individual patients are retained on treatment, are virally suppressed and receive the best possible care and support.

(1) Background: The purpose of this study is to evaluate the full arch scan accuracy (precision and trueness) of nine digital intra-oral scanners and four lab scanners. Previous studies have compared the accuracy of some intra-oral scanners, but as this is a field of quickly developing technologies, a more up-to-date study was needed to assess the capabilities of currently available models.; (2) Methods: The present in vitro study compared nine different intraoral scanners (Omnicam 4.6; Omnicam 5.1; Primescan; CS 3600; Trios 3; Trios 4; Runyes; i500 and DL206) as well as four lab light scanners (Einscan SE; 300e; E2 and Ineos X5) to investigate the accuracy of each scanner by examining the overall trueness and precision. Ten aligned and cut scans from each of the intra-oral and lab scanners in the in vitro study were brought into CloudCompare. A comparison was made with the master STL using the CloudCompare 3D analysis best-fit algorithm. The results were recorded along with individual standard deviation and a colorimetric map of the deviation across the surface of the STL mesh; a comparison was made to the master STL, quantified at specific points. ; (3) Results: In the present study, the Primescan had the best overall trueness (17.3 ± 4.9). Followed by (in order of increasing deviation) the Trios 4 (20.8 ± 6.2), i500 (25.2 ± 7.3), CS3600 (26.9 ± 15.9), Trios 3 (27.7 ± 6.8), Runyes (47.2 ± 5.4), Omnicam 5.1 (55.1 ± 9.5), Omnicam 4.6 (57.5 ± 3.2) and Launca DL206 (58.5 ± 22.0). Regarding the lab light scanners, the Ineos X5 had the best overall trueness with (0.0 ± 1.9). Followed by (in order of increasing deviation) the 3Shape E2 (3.6 ± 2.2), Up3D 300E (12.8 ± 2.7), and Einscan SE (14.9 ± 9.5); (4) Conclusions: This study confirms that all current generations of intra-oral digital scanners can capture a reliable, reproducible full arch scan in dentate patients. Out of the intra-oral scanners tested, no scanner produced results significantly similar in trueness to the Ineos X5. However, the Primescan was the only one to be statistically of a similar level of trueness to the 3Shape E2 lab scanner. All scanners in the study had mean trueness of under 60-micron deviation. While this study can compare the scanning accuracy of this sample in a dentate arch, the scanning of a fully edentulous arch is more challenging. The accuracy of these scanners in edentulous cases should be examined in further studies.

Ship detection from synthetic aperture radar (SAR) imagery is crucial for various fields in real-world applications. Numerous deep learning-based detectors have been investigated for SAR ship detection, which require a substantial amount of labeled data for training. However, SAR data annotation is time-consuming and demands specialized expertise, resulting in that deep learning-based SAR ship detectors struggle due to a lack of annotations. With limited labeled data, semi-supervised learning is a popular approach for boosting detection performance by excavating valuable information from unlabeled data. In this paper, a semi-supervised SAR ship detection network is proposed, termed as Multi-Teacher Dempster-Shafer Evidence Fusion Net-work (MTDSEFN). The MTDSEFN is an enhanced framework based on the basic teacher-student skeleton frame, comprising two branches: the Teacher Group (TG) and the Agency Teacher (AT). The TG utilizes multiple teachers to generate pseudo-labels for different augmentation versions of unlabeled samples, which are then refined to obtain high-quality pseudo-labels by using Dempster-Shafer (D-S) fusion. The AT not only serves to deliver weights of its own teacher to the TG at the end of each epoch, but also updates its own weights after each iteration, enabling the model to effectively learn rich information from unlabeled data. The combination of TG and AT guarantees both reliable pseudo-label generation and learning comprehensive diversity information from numerous unlabeled samples. Extensive experiments were performed on two public SAR ship datasets, and the results demonstrated the effectiveness and superiority of the proposed approach.

Dust inhalation is a huge concern in the mining environment and within all its operations. In fact, dust to be one of the most serious occupational hazards in the mining industry. Coal and crystalline silica dust are the causes of serious, sometimes fatal lung diseases such as pneumoconiosis, which affects coal miners, as well as silicosis, tuberculosis, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, and chronic renal disease, which affect coal and other types of miners. The resulting effects both affect workers and nearby communities. The mining industry has in the past, employed several approaches to reduce effects of dust. But these strategies have often been ineffective because the grass withers during the dry season and sprayed water is rapidly absorbed or evaporates. This paper endeavors to review information on dust in the mining environment and how it is a nuisance to workers and communities and establish what strategies exist for this.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

Introduction: The term 3D printing is commonly used to depict an assembling method whereby the final form of an object is the result of the addition of different layers to build the frame of an object. This procedure is more accurately portrayed as additive manufacturing and is likewise alluded to as fast prototyping. The term 3D printing, in any case, is generally new and has been an active part of current developments in Dentistry. Much publicity encompasses the evolution of 3D printing, which is hailed as an innovation that will perpetually change CAM manufacturing, including in the dental sector. This review is the first part in a 3D Printing series that looks at the history of 3D Printing, the technologies available and reviews the literature relating to the accuracy of these technologies. Conclusions: The recent advancement in digital dentistry to incorporate these tools has modernised dental practices by paving the way for computer-aided design (CAD) technology and rapid prototyping. The use of 3D printing has led to 3D digital models produced with intraoral scanners (IOS), which can be manipulated easily for diagnosis, treatment planning, mockups, and a multitude of other uses. Combining 3D Printing with a 3D intraoral scan eliminates the need for physical storage but makes it to retrieve a 3D models for use within all dental modalities.

This is a single tertiary center in southwest Romania, population-based, study. We retrospectively compared data obtained in two periods: January 2008 - December 2013 and January 2018 - De-cember 2023, respectively. The global incidence of transposition of great arteries (TGA) - the ter-minated cases added to the ones resulting in live-born pregnancies, remained almost constant. The live-born incidence of TGA decreased (0.34% to 0.013%). The prenatal detection rate increased slightly (71.42% to 87.5%). The median gestational age at the diagnosis decreased, from 29.3 ges-tational weeks (mean 25.4) to 13.4 weeks (mean 17.2). The proportion of terminated pregnancies significantly increased (14.28% to 75%, p = 0.019).

This research aims to apply Artificial Intelligence (AI) methods, specifically Artificial Immune Systems (AIS), to design an optimal control strategy for a multivariable control plant. Two specific industrial control approaches are investigated: I-PD (Integral-Proportional Derivative) and PI-D (Proportional-Integral Derivative) control. The motivation for using these variations of PID controllers is that they are functionally implemented in modern industrial controllers, where they provide precise process control. The research results in a novel solution to the control synthesis problem for the industrial system. In particular, the research deals with the synthesis of I-P control for a two-loop system in the technological process of a distillation column. This synthesis is carried out using the AIS algorithm, which is the first application of this technique in this specific context. Methodological approaches are proposed to improve the performance of industrial multivariable control systems by effectively using optimization algorithms and establishing modified quality criteria. The numerical performance index ISE justifies the effectiveness of the AIS-based controllers in comparison with conventional PID controllers (ISE₁ = 1.865, ISE₂ = 1.56). The problem of synthesis of the multi-input multi-output (MIMO) control system is solved, considering the interconnections due to the decoupling procedure.

Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal-end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices remains a critical challenge, particularly in a way suitable for large scale adoption. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3 ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Legionella bacteria can proliferate in poorly maintained water systems, posing risks to users. All Legionella species are potentially pathogenic but Legionella pneumophila (L. pneumophila) is usually the primary focus of testing. However, Legionella anisa (L. anisa) also colonises water distribution systems, is frequently found with L. pneumophila and could be a good indicator for increased risk of nosocomial infection. Anonymized data from three commercial Legionella testing laboratories afforded analysis of 565,750 water samples. Data covered July 2019 to August 2021, including the COVID-19 pandemic. Results confirmed L. anisa commonly colonises water distribution systems, being the most frequently identified non-L. pneumophila species. Proportions of L. anisa and L. pneumophila generally remained similar but increases in L. pneumophila during COVID-19 lockdown suggests static water supplies might favour its growth. Disinfection of hospital water systems was effective but re-colonization did occur, appearing to favour L. pneumophila, although L. anisa colony numbers also increased as a proportion of the total. While L. pneumophila remains the main species of concern as a risk to human health, L. anisa’s role should not be under-estimated, either as a potential infection risk or as an indicator of the need to intervene to control Legionella colonization of water supplies.

Although vitamin D deficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH) D) and atherogenic indices predictive of CVD. This study aimed to investigate the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred healthy women, aged 18 to 50 years, from Meknes were included. Fasting 25(OH) D and lipid concentrations were determined using a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (Atherogenic index of plasma (AIP), non-HDL cholesterol (Non-HDL-C), Atherogenic coefficient (AC), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH) D levels associated with high atherogenic indices. 25(OH) D below 20 ng/ml was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, Non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856-12.959); 3.637(2.149-6.158); 3.589(1.673-7.700); 2.074(1.215-3.540), and 2.481(1.481-4.123), respectively. According to ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, Non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/ml, ≤ 17.5 ng/ml, ≤ 19.8 ng/ml, ≤ 20.1 ng/ml and ≤ 19.5 ng/ml, respectively, all p &lt; 0.01. Based on atherogenic indices, this study indicates that vitamin D below 20 ng/ml may increase the risk of cardiovascular disease in adult women. Additional health efforts are needed to raise awareness among women and healthcare providers in preventing and controlling cardiovascular risk factors.

The ability to replicate scientific experiments is a cornerstone of the scientific method. Sharing ideas, workflows, data, and protocols facilitates testing the generalizability of results, increases the speed that science progresses, and enhances quality control of published work. Fields of science such as medicine, the social sciences, and the physical sciences have embraced practices designed to increase replicability. Granting agencies, for example, may require data management plans and journals may require data and code availability statements along with the deposition of data and code in publicly available repositories. While many tools commonly used in replicable workflows such as distributed version control systems (e.g. “git”) or scripted programming languages for data cleaning and analysis may have a steep learning curve, their adoption can increase individual efficiency and facilitate collaborations both within entomology and across disciplines. The open science movement is developing within the discipline of entomology, but practitioners of these concepts or those desiring to work more collaboratively across disciplines may be unsure where or how to embrace these initiatives. This article is meant to introduce some of the tools entomologists can incorporate into their workflows to increase the replicability and openness of their work. We describe these tools and others, recommend additional resources for learning more about these tools, and discuss the benefits to both individuals and the scientific community and potential drawbacks associated with implementing a replicable workflow.

This paper aims to demonstrate that, beyond the small world of Riemann-Liouville and Caputo derivatives, there is a vast and rich world with many derivatives suitable for specific problems and various theoretical frameworks to develop, corresponding to the different paths taken. Notions of time and scale sequences are introduced and general associated basic derivatives, namely right/stretching and left/shrinking, are defined. A general framework for fractional derivative definitions is reviewed and applied to get both known and new fractional order derivatives. Several fractional derivatives are considered, mainly: Liouville, Hadamard, Euler, bilinear, tempered, q-derivative, and Hahn.

The horizontal storm structure surrounding lightning ignited wildfires is examined using Vaisala’s National Lightning Detection Network (NLDN), NCEP’s Stage IV gauge corrected radar precipitation mosaic, and the US Forest Service’s Fire Occurrence Database. Though lightning flash density peaks strongly around fire ignitions on the instantaneous 1 km scale, on the hourly 10 km scale both the lightning and precipitation peaks are typically offset from fire ignitions. Lightning density is higher and precipitation lower around ignition points compared to non-ignition points. Both regression and horizontal distributions are consistent with the claim that positive flashes have a stronger association with ignition than negative flashes, but the statistical significance remains ambiguous

The relationship of Amyotrophic Lateral Sclerosis, Parkinson Disease and other age-related neurodegenerative diseases associated with mitochondrial dysfunction has led to study of the mitochondrial fission gene Drp1 in Drosophila. Drp1 can interact with mitochondrial proteins including parkin and the Drosophila Bcl-2 proteins. Mutations in Drp1 can lead to mitochondrial dysfunction and neuronal loss. Ddc-Gal4 was exploited to direct the expression of Drp1 and the inhibition of Drp1 in neurons. Here, the inhibition of Drp1 seems to compromise locomotor function throughout life but does not alter longevity. The consequences of Drp1 overexpression can be suppressed through overexpression of pro-survival Bcl-2 gene Buffy or by inhibition of the pro-cell death Bcl-2 homologue Debcl. The expression of Buffy suppresses the poor climbing induced by loss of Drp1 function. Interestingly, the loss of parkin function is rescued by the directed inhibition of Drp1. Alteration of the expression of Drp1 acts to phenocopy neurodegenerative disease phenotypes in Drosophila, while overexpression of Buffy can counteract these phenotypes to improve overall health. The pro-survival effect of Buffy can rescue the phenotypic effect due to the Drp1-induced apoptosis. The diminished health due to either overexpression or inhibition of Drp1 has produced a novel model to investigate mechanisms underlying neurodegenerative disease.

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz need to provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT) and fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide POUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm POUT. The calibrated HD2 level is -82.2 dBc at 9.93 dBm POUT, resulting in a transmitter figure of merit (TX_FoM) of -97.52 dB. Higher order harmonic levels remain below -41.2 dBm even at 12.1 dBm POUT, meeting regulatory requirements.

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expression of multiple genes, resulting in liver inflammation and the development of a leaky gut. Molecular mechanism involved for ALD progression is still unclear, and due to that there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of Graphene oxide nanoparticles (GO) was investigated against ethanol-induced damage in the gut-liver axis in in vitro. GO was synthesized using a modified Hummer's method and characterization was done. Given the general concerns regarding nanoparticle toxicity, assessment of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, gene expression of pro- and anti-inflammatory cytokines was done using RT-qPCR. The findings revealed that GOs promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. Gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut permeability and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD.

Hashimoto's thyroiditis (HT) is essentially featured by self-tissue destruction by means of the adaptive immune responses that evade immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review about the relationship between vitamin D status and HT and the role of vitamin D supplementation to reduce HT risk by modulating the immune system. There is an extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titer decreased significantly, However, there are no conclusive results on the effect of vitamin D supplementation on the thyroid function. The confirmation of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases require additional randomized, double-blind, placebo-controlled trials with longer follow-up.

The market for shark fin soup, a fashionable, high-end Chinese dish, has resulted in intensive shark fishing across all oceans. At the same time, 90% of teleost fish stocks are over-exploited, making sharks the most lucrative target: fisheries that have not previously hunted them are now. As top and middle predators, sharks have high ecological value and poor capacity to withstand fishing mortality, but though their numbers are plummeting, the secretive nature of the fin trade, along with the difficulties of obtaining relevant data, obscure their true status. In consumer countries, shark fin is a luxury item and rich consumers are willing to pay high prices. There is little interest in sustainability or legal trade. Thus market demand will continue to fuel the search for sharks and those accessible to fishing fleets are increasingly endangered. Current legal protections are not working, as is clearly seen in the case of the shortfin mako. Claims that sharks can withstand such targeted, industrial hunting and be sustainably fished under these circumstances are shown to be misguided. In the interests of averting a catastrophic collapse across the planet’s aquatic ecosystems, sharks must be given effective protection. We recommend that all sharks, chimaeras, manta rays, devil rays, and rhino rays be protected from international trade through an immediate CITES Appendix I listing. However, a binding international agreement for protection, not only of sharks, but of the loss of biodiversity in general, is what is most needed to allow marine and fresh water ecosystems to recover.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

1) Background: The influence of estrogen on cognitive and perceptual functions is debated. Some research suggests that estrogen increases arousal, improving cognitive function, while others propose that increased arousal might reduce performance on certain tasks. This study investigates the effects of menstrual cycle phase and estrogen levels on lightness perception in cycling women and hormonal contraceptive (HC) users. (2) Methods: Estrogen levels were determined from saliva samples collected at three sessions aligned with different menstrual phases in 16 women (9 with natural cycles, 7 HC users). The effects of wavelength and menstrual cycle phase on lightness perception were analyzed, followed by post-hoc comparisons and correlations between lightness perception and estrogen levels for both cycling women and HC users. (3) Results: Lightness varied by menstrual phase (MCP) in cycling women and was slightly higher during the low estrogen menstrual phase compared to peri-ovulation or luteal phases. In HC users, lightness measures were equivalent across phases. For cycling women, lightness was negatively correlated with estrogen for the green and green-yellow stimuli. There were no such associations among HC users. (4) Conclusions: This report challenges the concept that high estrogen phases of the menstrual cycle always positively influence perception. Conversely, the present results revealed that—at least in cycling, non-hormonal contraceptive users—lightness perception was both at a maximum during the low estrogen menstrual phase and negatively associated with estrogen levels across all tested wavelengths.

There is high confidence that climate change has increased the probability of concurrent temperature-precipitation extremes, changed their spatial-temporal variations, and affected the relationships between drivers of such natural hazards. However, the extent of such changes has been less investigated in Australia. Daily weather data (131 years, 1889-2019) at 700 grid cells (1◦ × 1◦) across Australia was obtained to calculate annual and seasonal mean daily maximum temperature (MMT) and total precipitation (TPR). A nonparametric multivariate copula framework was adopted to estimate the return period of compound hot-dry (CHD) events based on an ‘And’ hazard scenario (hotter than a threshold ‘And’ drier than a threshold). CHD extremes were defined as years with joint return periods of larger than 25 years. Mann-Kendall nonparametric tests was used to analyse trends in MMT and TPR as well as in the frequency of univariate and CHD extremes. A general cooling-wetting trend was observed over 1889-1989. Significant increasing trends were detected over 1990-2019 in the frequency and severity of hot extremes across the country while trends in dry extremes were mostly insignificant (and decreasing). Results showed a significant increase in the association between temperature and precipitation at various temporal scales. The frequency of CHD extremes was mostly stable over 1889-1989, but significantly increased between 1990 and 2019 at 44% of studied grid cells, mostly located in the north, south-east and south-west. Spatial homogeneity (i.e. connectedness) and propagation of extreme events from one grid cell to its neighbouring cells was investigated across Australia. It can be concluded that this connectedness has not significantly changed since 1889.

To account for the very low mass density associated with Dark Energy and the Cosmological Constant, a new approach to the ground state of empty space is presented. The resulting model for the vacuum state associated with empty space proposes a crystalline-like texture for the chromatic structure of empty space. This vacuum state has the appropriate mass density and predicts acceleration for the Universe expansion. Furthermore, the model predicts that this texture is anisotropic and may lead to measurable changes in the production of electron and positron pairs by gamma rays incident on a solid crystal of low mass density such as graphite.

Article explores participant specific study of muscle inherehit dynamics hidden inside the diognostic electromyography (D-EMG) signals during load pull exercises, aiming to uncover underlying patterns and nonlinear behaviors. Employing a multi-step analytical framework, the study first evaluates signal stationarity through Quantile-Quantile (Q-Q) plot and surrogate data analyses, revealing insights into signal stability. Subsequent use of phase space reconstruction techniques exposes intrinsic dynamics within the EMG signals, visualized through Poincar´e maps, elucidating attractor geometry and system dynamics. Histogram analysis further dissects the Poincar´e maps, offering insights into signal behavior relative to physiological processes. Additionally, the study quantifies the largest Lyapunov exponent from the Poincar´e maps, providing a measure of dynamical complexity within the muscle EMG signals during load pull exercises. By integrating these methods, this research sheds light on the nuanced interplay between EMG signals and muscle activity during dynamic exercises, offering valuable insights for rehabilitation strategies.

Dietary vitamin A/all-trans retinol/ROL plays a critical role in human vision. ROL circulates bound to the plasma retinol-binding protein (RBP4) as RBP4-ROL. In the eye, the STRA6 membrane receptor binds to circulatory RBP4 and internalizes ROL. STRA6 is however not expressed in systemic tissues, where there is high-affinity RBP4 binding and ROL uptake. We tested the hypothesis, that the second retinol-binding protein 4 receptor 2 (Rbpr2) which is highly expressed in systemic tissues of zebrafish and mouse, contains a functional RBP4 binding domain, critical for ROL transport. As for STRA6, modeling and docking studies confirmed three conserved RBP4 binding residues in zebrafish Rbpr2. In cell culture studies, disruption of the RBP4 binding residues on Rbpr2 almost completely abolished uptake of exogenous vitamin A. CRISPR generated rbpr2-RBP4 domain zebrafish mutants showed microphthalmia, shorter photoreceptor outer segments, and decreased opsins, that were attributed to impaired ocular retinoid content. Injection of WT-Rbpr2 mRNA into rbpr2 mutant or all-trans retinoic acid treatments rescued the mutant eye phenotypes. In conclusion, zebrafish Rbpr2 contains a putative extracellular RBP4-ROL ligand-binding domain, critical for yolk vitamin A transport to the eye for ocular retinoid production and homeostasis, for photoreceptor cell survival.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Western Iran barb species are scientifically, environmentally, and economically important. Some of them are the largest riverine freshwater species, which will grow in size and weight to 170 cm, and 120 kg respectively. Although these species are vulnerable, there is little information on taxonomy or environmental status of the species Luciobarbus barbulus is one of the important large species. In order to find the new record on the present status of large barb species sampling program carried out in western Iran, during the resent year since 2013 to now. This species overlaps in distinction with L. mystaceus, L scheich, and other similar species. In this study re-description of L.barbulus is given. This species differs from L. mystaceus in having thick and very wide fleshy lip, inferior mouth and slightly shorter head. In Luciobarbus barbulus head is more inferior. The details of differences between these species are given. This species is one of stable growing fish without dimorphism, retain its shape from a fingerling species to a giant fish.

Saturated lights appear brighter than white lights of the same luminance. This phenomenon is known as the Helmholtz-Kohlrausch (H-K) effect and can be estimated by modeling achromatic luminance and saturation to total brightness. These models have been shown to differ between women and men and are more variable in women. The variation in brightness models among women may be due to hormonal changes across the menstrual cycle. To test this, total brightness and achromatic luminance were measured across blue, green, yellow-green, yellow, and red hues. These data were measured along with salivary hormone levels for nine cycling women at points representing the menstrual, peri-ovulation, and luteal phases. These data were also collected for seven oral contraceptive (OC) users. There were no main effects of OC use nor menstrual cycle phase on B/L ratios, but ratios were higher for the red stimulus in cycling women than OC users. Red B/L ratios were also higher for cycling women than OC users during the luteal phase. Estrogen, progesterone, and their interaction predicted 18% of the variation in brightness for cycling women. These models could not be fit for OC users, and estrogen only accounted for 5% of brightness variance with progesterone terms omitted. These findings and potential mechanisms are discussed in the context of previous results.

Introduction: The current generation of 3D printers are lighter, cheaper, and smaller, making them more accessible to the chairside digital dentist than ever before. 3D printers in general in the industrial and chairside setting can work with various types of materials including, metals, ceramics, and polymers. Evidence presented in many studies show that an ideal material used for dental restorations is characterised by several properties related to durability, cost-effectiveness, and high performance. This review is the second part in a 3D Printing series that looks at the literature on material science and applications for these materials in 3D printing as well as a discussion on the potential further development and future evolution in 3D printing materials. Conclusions: Current materials in 3D printing provide a wide range of possibilities for providing more predictable workflows as well as improving efficiency through less wasteful additive manufacturing in CAD/CAM procedures. Incorporating a 3D printer and a digital workflow into a dental practice is challenging but the wide range of manufacturing options and materials available mean that the dentist should be well prepared to treat patients with a more predictable and cost effective treatment pathway. As 3D printing continues to become a commonplace addition to chair side dental clinics, the evolution of these materials, in particular reinforced PMMA, resin incorporating zirconia and glass reinforced polymers offer increased speed and improved aesthetics that will likely replace subtractive manufacturing milling machines for most procedures.

In the pursuit of better treatments, the concept of a chemically-active material, responding to local conditions by causing reactions, or reacting to produce substances that are deemed beneficial, seems laudable. Ultimately, the goal appears to be to recruit natural biological processes such that a natural ‘repair’ is effected. This goal seems to be the reason for prefixing “bio-“ to many terms with a view to advertising the desire, yet without presenting evidence that it has occurred, or indeed that it is capable of occurring, relying instead on non-biological processes to justify the claims. The dogma is such that all work where local ‘responsive’ chemistry is involved must receive the label “bioactive” to legitimize and promote. Nevertheless, the primary evidence adduced is flawed, and the claim must fail. A rethink to restore scientific sense and confidence in the endeavour is essential if real progress is to be made.

Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of estrogen signaling. This review aims to provide a comprehensive analysis of recent advances in our understanding of the molecular mechanisms underlying sex differences in colon cancer and the protective role of membrane and nuclear estrogen signaling in CRC development, progression, and therapeutic interventions. We discuss the epidemiological and molecular evidence supporting sex differences in colon cancer, followed by an exploration of the impact of estrogen in CRC through various genomic and non-genomic signaling pathways involving membrane and nuclear estrogen receptors. Furthermore, we examine the interplay between estrogen receptors and other signaling pathways, in particular the Wnt/-catenin proliferative pathway and hypoxia in shaping biological sex differences and estrogen protective actions in colon cancer. Lastly, we highlight the potential therapeutic implications of targeting estrogen signaling in the management of colon cancer and propose future research directions to address the current gaps in our understanding of this complex phenomenon.

Western Iran barb species are scientifically, environmentally, and economically important. Some of them are the largest riverine freshwater species, which will grow in size and weight to 170 cm, and 120 kg respectively. There is little information on taxonomy or environmental status of these species Luciobarbus barbulus is one of the important large species. During the resent year since 2013, in order to find the new record of large barb species, sampling program carried out in western Iran,. Luciobarbus barbulus briefly described by Heckel (1849) but during the time, have been synonymized with other related species or vice versa, other similar species miss-identically have been known as this species. Also the synonymy of Luciobarbus barbulus with L. pectoralis remains uncertain. The possible syntypes of L. barbulus in Vienna Museum (NMW 53957 and NMW 6596) are in too poor condition to be of any value, being mostly bones, and are dried, and. The fleshy lip of NMW 6596, (measures 119.3 mm standard length) fold of the original description could not be discerned, teeth are missing and the dorsal fin is broken off short. In 1997 this was the only syntype recognized. The catalog in Vienna lists only 1 fish, while Heckel's description refers to several fishes!. So designing of Lecotype and re-description of L. barbulus is essential. In this paper the details of description and differences between these species are given.

Aseptic implant loosening after total joint replacement is partially influenced by material-specific factors when cobalt-chromium alloys are used, including osteolysis induced by wear- and corrosion products, and stress shielding. Here, we aim to characterize a hybrid material consisting of alumina-toughened zirconia ceramics (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a glass solder. The structure of the joint, static and fatigue shear strength, the influence of accelerated aging, and the cytotoxicity using an elution assay with human osteoblasts is characterized. Furthermore, the biomechanical properties of functional demonstrators of a femoral component for total knee replacements are evaluated. TiNbTa-ATZ specimens showed a homogenous joint with statistical distributed micro-pores and a slight accumulation of Al-rich compounds at the glass solder-TiNbTa interface. The static shear strength was 26.4 ± 4.2 MPa (Ti-ATZ reference: 38.2 ± 14.4 MPa, p = 0.117), all specimens survived 107 cycles of shear loading to 10 MPa, and aging did not reduce the strength. TiNbTa-ATZ did not impair the proliferation and metabolic activity of human osteoblasts. Functional demonstrators of TiNbTa-ATZ provided a maximum bearable extension-flexion moment of 40.7 ± 2.2 Nm. Biomechanical and biological properties of TiNbTa-ATZ demonstrate potential application for endoprosthetic implants.

OPMDs (Oral Potentially Malignant Disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of a range of diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also reveals a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD-VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD, and investigate their potential association and ramifications for clinical management of OPMDs.

In the present work we revise and extend the Characteristic Crystallographic Element (CCE) norm, an algorithm used to simultaneously detect radial and orientational similarity of computer-generated structures with respect to specific reference crystals and local symmetries. Based on the identification of point group symmetry elements, the CCE descriptor is able to gauge local structure with high precision and finely distinguish between competing morphologies. As test cases we use computer-generated monomeric and polymer systems of spherical particles interacting with the hard-sphere and square-well attractive potentials. We demonstrate that the CCE norm is able to detect and differentiate, between others, among: hexagonal close packed (HCP), face centered cubic (FCC), hexagonal (HEX) and body centered cubic (BCC) crystals as well as non-crystallographic fivefold (FIV) local symmetry in bulk 3-D systems; triangular (TRI), square (SQU) and honeycomb (HON) crystals, as well as pentagonal (PEN) local symmetry in thin films of one-layer thickness (2-D systems). The descriptor is general and can be applied to identify the symmetry elements of any point group for arbitrary atomic or particulate system in two or three dimensions, in the bulk or under confinement.

Maxillomandibular advancement (MMA) is a surgical intervention that reduces the symptoms of obstructive sleep apnea via anterior repositioning of the upper and lower jaws. Pre-operative orthodontic alignment is often a critical component in aiding MMA. Orthodontia are important in intraoperative anchorage for intermaxillary fixation, healthy post-operative occlusion, and post-operative skeletal stability. Sequential clear aligners (SCA) refer to removable orthodontic appliances that are replaced at regular intervals to stimulate dental migration without the use of bonded hardware. These aligners have demonstrated efficacy in aiding orthognathic surgery for dentofacial deformities, which share some technical similarities with MMA for OSA. Here, we explore the treatment protocol for MMA followed by post-operative SCA treatment. Our experiences show that post-operative orthodontic treatment with SCAs results in similarly successful post-operative surgical outcomes given that the patient’s pre-operative occlusion is stable.

The most recent National Research Council Nutrient Requirements for Sheep and Goats was published in 2007, one of the most consequential nutrient requirement recommendations for sheep and goats in the world. It is pertinent to continue the refinement and discussion of nutrient utilization and requirements for the purposes of enhancing the efficiency of production systems, maximizing resource economy, and minimizing the carbon footprint, among others. Progress has been made in the estimation of energy and protein requirements in sheep and goats, mainly utilizing empirical feeding experimentation, comparative slaughter technique and minimum endogenous loss method. In sheep, newer estimates of energy and protein requirements for maintenance and growth and partial efficiencies had been reported since 2007. There were suggestions that energy and protein requirements could have been affected by breed, wool growth, gender and size; with these reported values being similar or lower than the recommended values in international feeding systems such as NRC, ARC, INRA and AFRC. In goats, energy and protein requirements for growing goats were reported to be either higher or lower than the established recommendations, depending upon meat or dairy breeds. Effect of gender on energy requirement appeared to be related to the stage of growth or degree of maturity. Newer data also suggested that the guidelines of the major feeding systems for the entire growth phase may not be adequate for non-pregnant and non-lactating pubertal females. In multiparous pregnant goats, energy and protein requirements for maintenance did not appear to be affected by days of pregnancy, but efficiencies of metabolizable energy and metabolizable protein utilization for pregnancy were. There were suggestions that that metabolizable protein synthesis in the rumen can be predicted from energy intake using combined equations that encompass both sheep and goats, but more data on goats were called for to account for specific differences in nutrition. In addition to sulfur, there has been progress made on the estimation of maintenance and growth requirements of calcium, phosphorus, potassium and magnesium in goats, with suggestions on the consideration of gender and breed differences. Species, level of Intake, genotype, mature size, age, gender, body composition, use of tissue energy, activity, season, and acclimatization continue to be important considerations for the estimation of nutrient requirements in sheep and goats, with emerging factors such as climate change, heat stress, parasitism and secondary plant compounds. Model equations and partial efficiencies used by NRC to predict energy and protein requirements for maintenance, growth, lactation, and fiber have been highlighted and discussed for the purpose of a more focus discussion and refinement for the future. Potential and limitation of both traditional and emerging methodologies in determining the nutrient requirements in sheep and goats were discussed. To justify the research investment, emerging methodologies such as nutrigenomics will have to be linked more directly to the improvement of production efficiency via more precise prediction of nutrient requirement.

Abstract: NFinFET transistors with fin channel length 90nm and a planar MOSFET transistor with channel length 180nm and 90nm are presented with characteristic curves at various gate biases. A finalized algorithm with kink effects is effectively responsible for addressing the field effect transistors. The algorithm includes the modified conventional current-voltage formula and a nonlinear heat-associated kink solution which is simplified as a Gaussian form. Three parameters in modified model includes kN (related with channel width, channel length, and gate oxide capacitor, and proportional to the mobility of carriers)Vth(Threshold Voltage), and (the inverse of Early Voltage). Those parameters are determined to minimize the discrepancies between the measured data and the fitting values, but leave kinks located at around (VGS－Vth), which are deliberately eliminated by the Gaussian form because of the agitation of thermal kink effects. The whole fitting is made to be as close as the as-measured IDS-VDS. In the mean time, those determined parameters are physically meaningful after the analysis has been done.

Microfluidic devices which integrate both rapid mixing and liquid jetting for sample delivery are an emerging solution for studying molecular dynamics via X-ray diffraction. Here we use finite element modelling to investigate the efficiency and time-resolution achievable using microfluidic mixers within the parameter range required for producing stable liquid jets. Three-dimensional simulations, validated by experimental data, are used to determine the velocity and concentration distribution within these devices. The results show that by adopting a serpentine geometry, it is possible to induce chaotic mixing, which effectively reduces the time required to achieve a homogeneous mixture for sample delivery. Further, we investigate the effect of flow rate and the mixer microchannel size on the mixing efficiency and minimum time required for complete mixing of the two solutions whilst maintaining a stable jet. In general, we find that the smaller the cross-sectional area of the mixer microchannel, the shorter the time needed to achieve homogeneous mixing for a given flow rate. The results of these simulations will form the basis for optimised designs enabling the study of molecular dynamics occurring on millisecond timescales using integrated mix-and-inject microfluidic devices.

With the increasing use of genome sequencing as a surveillance tool for molecular epidemiology of antimicrobial resistance (AMR), databases and clear nomenclature for AMR gene families are critical. Due to the convoluted nomenclatural history of the integron-associated trimethoprim-resistant dihydrofolatereductase (dfr) gene family, we decided to conduct a literature review, comparative sequence analysis, and phylogenetic investigation of the dfr family, the results of which are presented here and available at the Comprehensive Antibiotic Resistance Database (CARD). Overall, literature review and phylogenetic analysis resolved gene name synonyms based on sequence. We recommend adoption of phylogenetic methods to help guide AMR gene naming efforts and relegation of misleading names to synonyms.

Relationships of the three bryophyte lineages (liverworts, mosses, and hornworts) to vascular plants is a pivotal question in the study of origin and evolution of land plants. In recent decades, this question has been subject to intense phylogenetic analyses using morphological characters, multigene DNA sequences, and genome structural characters. A tentative consensus reached ten years ago suggested that bryophytes are a paraphyletic group, with liverworts being sister to all other land plants and hornworts being sister to vascular plants. However, several more recent nuclear phylogenomic studies have concluded that bryophytes represent a monophyletic group that is sister to vascular plants. A discussion is presented here on strengths and weaknesses of different types of characters (morphological traits, nucleotide sequences, and genome structural arrangements), and their suitability for resolving deep phylogenetic relationships. Moreover, several criteria for credible phylogenetic reconstruction are proposed. Strong statistical support for reconstructed relationships should be derived from high quality, independent characters selected for suitability to the particular question being addressed. The relationships inferred in a study should be congruent with those from as many other lines of phylogenetic evidence as possible. Any incongruities should be explicable by well-understood biological mechanisms. It is concluded that the relationships of the three bryophyte lineages to vascular plants should currently be viewed as unresolved. This is a difficult phylogenetic problem; the land plants underwent a rapid radiation a long time ago. Yet, further exploration of analytical methods and careful choice of characters should lead to eventual elucidation of diversification patterns among early land plants.

D-type cyclins encode G1/S cell cycle checkpoint proteins, that play a crucial role in defining cell cycle exit and progression. Precise control of cell cycle exit is vital during embryonic development, with defects in the pathways regulating intracellular D-type cyclins resulting in abnormal initiation of stem cell differentiation in a variety of different organ systems. Furthermore, stabilisation of D-type cyclins is observed in a wide range of disorders characterised by cellular over-proliferation, including cancers and overgrowth disorders. In this review, we will summarise and compare the roles played by each D-type cyclin during development and provide examples of how their intracellular dysregulation can be an underlying cause of disease.

Electric energy is one of the driving forces in every country. The supply of electrical energy continues to present various challenges, such as high costs associated with procuring raw materials for generation, sparsely populated areas that are not connected to the main grid, and the need for infrastructure to support generation and network delivery. These challenges have contributed to the growing adoption of renewable energy sources, particularly solar photovoltaics (PV).In this study, we have developed a practical method to assess the spatial PV potential in a selected urban area. The methodology combines data collected from an unmanned aerial vehicle (UAV) photogrammetry, Geographic Information System (GIS), and the energy output from three remote photovoltaic systems installed at different locations. The results obtained from this approach not only provide the energy generated per square meter, per year (kWh m-2 yr-1), but also provides a base to calculate the potential distance that electric cars could travel based on the energy generated. To illustrate the application of this method, two practical cases were selected: Senglea, Malta, and Munxar, Gozo. These examples highlight the versatility and effectiveness of our approach for evaluating and harnessing solar energy through photovoltaic panels in different contexts.

Study Objectives: The aim of this study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). Methods: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS>10) and those without EDS (ESS

Background: Once a widely used analgesic in the United States (US), meperidine offered an alternative to other opioids as a pain reliever. However, within the last two decades, meperidine has gone from a drug to be utilized only when patients exhibit atypical reactions to opioids (e.g., morphine and hydromorphone) to being taken off the World Health Organization List of Essential Medications and receiving strong recommendations for the overall avoidance. The aim of this study was to identify changes in meperidine distribution in the US and regional disparities as reported to the Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (DEA ARCOS) and Medicaid. Methods: Data related to the meperidine distribution was obtained through ARCOS (2001 –2021) and Medicaid public use files (2016 –2021). Heat maps were used to visualize regional disparities in distribution by state. States outside a 95% confidence interval were statistically significant. Results: Meperidine distribution between 2001 and 2021 decreased by 97.4% (R=.-97, P &lt; .0001). There was a 34-fold state-level difference in meperidine distribution between Arkansas (16.8 mg/10 persons) and Connecticut (0.5 mg/ 10 persons) in 2020. Meperidine distribution in 2020 was elevated in Arkansas, Mississippi, and Alabama. In 2021, Meperidine distribution was highest in Arkansas ( 1.67 /10 persons) and lowest in Connecticut (0.08 /10 persons). Total prescriptions of meperidine as reported by Medicaid decreased by 73.8% (R= -0.67, P = 0.045) between 2016 and 2021. Conclusion: We observed a decrease in the overall distribution of meperidine in the past two decades with similar recent declines in prescribing to Medicaid enrollees. The shortage of some parenteral formulations is an important contributor to these declines. This data may reflect plans to phase out the use of this opioid, especially in the many situations where preferred opioids are available.

The COVID-19 pandemic continues to ravage the world, with the United States being highly affected. A vaccine provides the best hope for a permanent solution to controlling the pandemic. However, to be effective, a vaccine must be accepted and used by a large majority of the population. Structural equation modelling was used to analyze the relationships of several factors with attitudes toward potential COVID-19 vaccination. The survey was administered to 316 respondents across the United States by a survey corporation. Prior vaccine usage and attitudes predicted attitudes towards COVID-19 vaccination. Assessment of the severity of COVID-19 for the United States was also predictive. Approximately 68% of all respondents were supportive of being vaccinated for COVID-19, but side effects, efficacy, and length of testing remained concerns. Longer testing, increased efficacy and development in the United States were significantly associated with increased vaccine acceptance. Messages promoting COVID-19 vaccination should seek to alleviate the concerns of those who are already vaccine-hesitant. Messaging directed at the benefits of vaccination for the United States as a country would address the second predictive factor. Enough time should be taken to allay concerns about both short and long-term side effects before a vaccine is released.

We provide quantitative results from GIS-based modelling of urban emission functions for a range of representative low- and mid-rise locations, ranging from individual streets to residential communities within cities as well as entire towns and city regions with the aim of whether lantern photometry or built environment has the dominant effect on light pollution. We demonstrate the scalability of our work by providing results for the largest urban area modelled to date, comprising the central 117 km2 area of Dublin City and containing nearly 42,000 public lights. Our results show a general similarity in the shape of the azimuthally-averaged emission function for all areas examined, with differences in total light output distribution depending primarily on the nature of the lighting and, to a smaller extent, on the obscuring environment including seasonal foliage effects. A comparison with global satellite observations shows that they are consistent with the deduced angular emission function for other low-rise areas worldwide. We further validate our approach by comparing results for a range of urban locations by the close agreement observed in a detailed comparison of with calibrated imagery from the International Space Station. To our knowledge, this is the first such detailed quantitative verification of light loss calculations.

It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, mainly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was performed in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% CI: 0.90-0.96, p < 0.001; OR = 0.80, 95% CI: 0.72-0.89, p < 0.001, respectively) and cancer-related mortality (RR = 0.89, 95% CI: 0.86-0.93, p < 0.001; RR = 0.67, 95% CI: 0.58-0.78, p < 0.001, respectively). When meta-analyses whose primary reports included only randomized controlled trials were pooled, there was no significant association between Vit-D intake and cancer risk (OR = 0.99, 95% CI: 0.97-1.01, p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002; OR = 0.88, 95% CI: 0.83-0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality, however, careful evaluation according to cancer types is critically important and recommended.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the extrusion-based 3D printing modalities emphasizing biosensor applications. We highlighted the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis was placed on the approach by which the sensing molecules were introduced during the fabrication process. Finally, the future perspective was provided.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

We evaluated the potential of using fish species and functional traits as indicators of land use impacts to fish assemblages. We used environmental data collected at multiple spatial scales (local, reach, and upstream catchment) for 19 tributary and main stem sites in the Nolichucky River watershed in Tennessee. Canonical correspondence analyses showed that temperature, elevation, specific conductivity, sediment yield, impervious surfaces, and row crop cover at the catchment scale were strongly associated with fish assemblage structure, as well as forest cover from all three spatial scales. Blocked indicator species analysis, with stream size as the block, showed that significantly strong indicators of the least-impacted riparian land use condition (≥60% forest cover) were Saffron Shiner (Notropis rubricroceus), Rainbow Trout (Oncorhyncus mykiss), Longnose Dace (Rhynichthys cataractae), Creek Chub (Semotilus atromaculatus), and Mottled Sculpin (Cottus bairdi). Traits indicative of the least-impacted sites were the herbivorous trophic guild, mean female age-at-maturity, longevity, rock-gravel spawners, montane geology and pelagic swimmers. Specific conductivity was strongly related to multiple catchment-scale land use variables, and was a strong local-scale influence on fish assemblage structure. Our results show promise for using a relatively common but endemic southern Appalachian fish species, the Saffron Shiner, as an indicator for land-use related impacts to these streams.

The Asian clam Corbicula fluminea is a native aquatic species in Eastern Asia and Africa but has become one of the most ecologically and economically harmful invasive species in aquatic ecosystems in Europe, North America, South America. Due to their natural characteristics as a hermaphroditic species with high fecundity and dispersal capacity, Asian clams are extremely difficult to eradicate once they have infiltrated a waterbody. This is an emerging issue for states in the Northeastern United States as Asian clams expand their range farther North due to climate change. There has been extensive research conducted to develop chemical treatments to reactively control invasive mollusc populations and proactively prevent their further spread. However, treatments are mostly targeted toward biofouling bivalves in industrial settings. A comprehensive review of Asian clam chemical treatments used in open water systems was performed to evaluate molluscicides and identify toxicity ranges of emerging treatments that maximize Asian clam mortality and minimize negative impact to water quality and non-target species. The potential chemical applications in Asian clam control and management are summarized in this report to assist resource managers and practitioners on invasive Asian clam management.

This paper explores the tuning and results of two-part models on rich datasets provided through the Casualty Actuarial Society (CAS). These data sets include BI (bodily injury), PD (property damage) and COLL (collision) coverage, each documenting policy characteristics and claims across a four year period. The datasets are explored, including summaries of all variables, then the methods for modeling are set forth. Models are tuned and the tuning results are displayed, after which we train the final models and seek to explain select predictions. All of the code will be made available on GitHub. Data was provided by a private insurance carrier to the CAS after anonymizing the data set. This data is available to actuarial researchers for well-defined research projects that have universal benefit to the insurance industry and the public. Our hope is that the methods demonstrated here can be a good foundation for future ratemaking models to be developed and tested more efficiently.

Buprenorphine, an analogue of thebaine, is a Schedule III opioid in the United States used for opioid-use disorder and as an analgesic. Research has shown drugs like buprenorphine have a complicated pharmacology with characteristics that challenge traditional definitions of terms like agonist, antagonist, and efficacy. Buprenorphine has a high affinity for the mu (MOR), delta (DOR), kappa (KOR), and intermediate for the nociceptin opioid receptors (NOR). Buprenorphine is generally described as a partial MOR agonist with limited activity and decreased response at the mu-receptor relative to full agonists. In opioid naïve patients, the drug’s analgesic efficacy is equivalent to a full MOR agonist, despite decreased receptor occupancy and the “ceiling effect” produced from larger doses. Some argue buprenorphine’s effects depend on the endpoint measured, as it functions as a partial agonist for respiratory depression, but a full-agonist for pain. Buprenorphine’s active metabolite, norbuprenorphine, attenuates buprenorphine's analgesic effects due to NOR binding and respiratory depressant effects. The method of administration impacts efficacy and tolerance when administered for analgesia. There have been eleven-thousand reports involving buprenorphine and minors (age < 19) to US poison control centers, the preponderance (89.2%) with children. The consequences of prenatal buprenorphine exposure in experimental animals and humans should continue to be carefully evaluated. In conclusion, buprenorphine’s characterization as only a partial mu-agonist is an oversimplification. Contemporary research shows the traditional explanation of the pharmacology of buprenorphine does not take into account changes to receptor theory, pharmacological terminology, route of administration, and biologically active major metabolites.

Fatty acids play a major role in determining membrane biophysical properties. Staphylococcus aureus produces branched-chain fatty acids (BCFAs) and straight-chain fatty acids (SCFAs), and can incorporate exogenous SCFAs and straight-chain unsaturated fatty acids (SCUFAs). Many S. aureus strains produce the triterpenoid pigment staphyloxanthin, and the balance of BCFAs, SCFAs and staphyloxanthin determines membrane fluidity. Here, we investigated the relationship of fatty acid and carotenoid production in S. aureus using a pigmented strain (Pig1), its carotenoid-deficient mutant (Pig1ΔcrtM) and the naturally non-pigmented Staphylococcus argenteus that lacks carotenoid biosynthesis genes and is closely related to S. aureus. Fatty acid compositions in all strains were similar under a given condition indicating that staphyloxanthin does not influence fatty acid composition. Strain Pig1 had decreased membrane fluidity as measured by fluorescence anisotropy than the other strains under all conditions indicating that staphyloxanthin helps maintain membrane rigidity. We could find no evidence for correlation of expression of crtM and fatty acid biosynthesis genes. Supplementation of medium with glucose increased SCFA production and decreased BCFA and staphyloxanthin production, whereas acetate-supplementation also decreased BCFAs but increased staphyloxanthin production. We believe that staphyloxanthin levels are influenced more through metabolic regulation than responding to fatty acids incorporated into the membrane.

The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the (in)effectiveness of the antioxidative defense mechanisms. Primary sources of ROS are the respiratory electron transfer and the activity of NADPH oxidases (NOX), while Superoxide dismutases (SOD) are the main key reg-ulators that control the levels of ROS and reactive nitrogen species intra- and extracel-lularly. Because of their central role, SODs are the subject of research on human ovarian dysfunction, but the sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study, we clarify the localization of the ROS producing enzyme dNox within ovaries of Drosophila melanogaster and by a tissue specific knockdown, we show that dNox derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg laying behavior, but not the chorion hardening process.

The lack of reliable rainfall projection records remains a major challenge to Uganda. In the advent of extreme wetness or drought events, reliable rainfall estimates for local planning and adaptation are essential. The present study used two main datasets to conduct a historical analysis from 1981 to 2019, coupled with future projections under representative concentration pathway (RCP 8.5) for the period 2020-2050. Historical analysis revealed bimodal annual rainfall pattern for March-May (MAM) and September-November (SON) gradients representing heavier to lighter rainfall events respectively over the study area. Investigation of recent trends in rainfall patterns revealed an upward trend from 2010 onwards in annual and seasonal rainfall. Moreover, results for future projections show wet conditions are projected to occur over the study area between the months of April/May and October. Contrarily, March is likely to experience a reduction in wet conditions. Mann-Kendall test employed to make future projections of rainfall depicted decreasing patterns during MAM season whilst increasing tendencies with strong shift was highlighted for SON season over the study region. Meanwhile, annual projections indicate huge variations with linear trends showing a marginal increase as compared to historical trends. Findings would serve as baseline print to propel further studies that could delve into impact analysis of drought extreme events which pose significant threats to the agricultural sector which is heavily reliant on rainfall.

This work addresses the problem of automatic head pose estimation and its application in 3D gaze estimation using low quality RGB--D sensors without any subject cooperation or manual intervention. The previous works on 3D head pose estimation using RGB--D sensors require either an offline step for supervised learning or 3D head model construction which may require manual intervention or subject cooperation for complete head model reconstruction. In this paper, we propose a 3D pose estimator based on low quality depth data, which is not limited by any of the aforementioned steps. Instead, the proposed technique relies on modeling the subject's face in 3--D rather than the complete head, which in turn, relaxes all of the constraints with the previous works. The proposed method is robust, highly accurate and fully automatic. Moreover, it does not need any offline step. Unlike some of the previous works, the method only uses depth data for pose estimation. The experimental results on the Biwi head pose database confirm the efficiency of our algorithm in handling large pose variations and partial occlusion. We also evaluate the performance of our algorithm on IDIAP database for 3D head pose and eye gaze estimation.

Over the last decades, in addition to the improvement of pathophysiological knowledge regarding the role and mechanisms of action of Vitamin D, there has been a progressive advancement in analytical technologies for its determination, as well as in methodological standardization. A significant number of scientific works, meta-analyses, and guidelines have been published on the importance of Vitamin D and the need for supplementation in deficient individuals. However, it appears necessary to clarify the fundamental elements related to the determination of Vitamin D (both at the strictly analytical and post-analytical levels) and the scientific evidence related to the efficacy/safety of supplementation. Additionally, given the important interrelations between Vitamin D, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF23), the analytical issues and clinical utility of these biomarkers will be discussed.

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD), are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiologic mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

Background: given the various clinical manifestations that characterize coronavirus disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant protein A (SP-A) and D (SP-D) play a crucial role in ensuring proper alveolar function and an alteration of their serum levels have been reported in several pulmonary diseases characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Consid-ering that such clinical manifestations can also occur during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. Methods: in this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n=51) at admission (T0) and after 7 days (T1) and compared with healthy donors (n=11). Results: SP-D increased in COVID-19 patients com-pared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. Conclusions: In the light of these results SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia and the early detection of SP-D serum levels could be crucial for a preventive clinical management.

This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

Noise in requirements has been known to be a defect in software requirements specifications (SRS). Detecting defects at an early stage is crucial in the process of software development. Noise can be in the form of irrelevant requirements that are included within a SRS. A previous study had attempted to detect noise in SRS, in which noise was considered as an outlier. However, the resulting method only demonstrated a moderate reliability due to the overshadowing of unique actor words by unique action words in the topic-word distribution. In this study, we propose a framework to identify irrelevant requirements based on the MultiPhiLDA method. The proposed framework distinguishes the topic-word distribution of actor words and action words as two separate topic-word distributions with two multinomial probability functions. Weights are used to maintain a proportional contribution of actor and action words. We also explore the use of two outlier detection methods, namely Percentile-based Outlier Detection (PBOD) and Angle-based Outlier Detection (ABOD), to distinguish irrelevant requirements from relevant requirements. The experimental results show that the proposed framework was able to exhibit better performance than previous methods. Furthermore, the use of the combination of ABOD as the outlier detection method and topic coherence as the estimation approach to determine the optimal number of topics and iterations in the proposed framework outperformed the other combinations and obtained sensitivity, specificity, F1-score, and G-mean values of 0.59, 0.65, 0.62, and 0.62, respectively.

Gas sensor arrays, also known as electronic noses, leverage a diverse set of materials to identify the components of complex gas mixtures. Metal-organic frameworks (MOFs) have emerged as promising materials for electronic noses due to their high-surface areas and chemical as well as structural tunability. Using our recently reported genetic algorithm design approach, we examined a set of 50 MOFs and searched through the over 1.125x1015 unique array combinations to identify optimal arrays for the detection of CO₂ in air. We found that despite individual MOFs having lower selectivity for O2 or N2 relative to CO₂, intelligently selecting the right combinations of MOFs enabled accurate prediction of the concentrations of all components in the mixture (i.e. CO₂, O₂, N₂). We also analyzed the physical properties of the elements in the arrays to develop an intuition for improving array design. Notably, we find that diversity among the surface areas in the MOFs leads to improved sensing. Consistent with the observation, we found that, as one might expect, the best arrays consistently had more structural diversity than the worst arrays.

The purpose of this review is to elucidate the actual threat of the most prevalent mycotoxins in agricultural commodities and human/animal food/feed for appearance of foodborne ailments and diseases. The underestimated hazard of joint mycotoxin uptake of animals or humans is critically discussed with regards to synergistic or additive interaction between some target mycotoxins. The real toxicity of target mycotoxin combinations as it happens in practice is evaluated and possible lower limit values or control measures are suggested in such cases. Some critical points in adequate risk assessment, hygiene control and regulation of mycotoxns are discussed. The efficiency of current mycotoxin regulations and control measures is evaluated in regards to human/animal health hazard. The risk assessment in the case of multiple mycotoxin exposure of humans/animals via the food/feed or agricultural commodities is evaluated and some suggestions are proposed in such cases. Appropriate control measures and food safety issues throughout the food supply chain are proposed in order to prevent target foodborne diseases. Some preventive measures and possible veterinary hygiene control or risk assessment are proposed in some practical cases of foodborne diseases for preventing mycotoxin contamination of animal products designed for human consumption and to avoid possible public health issues.

Alginate-gelatin hydrogels are extensively used in bioengineering. However, despite different formulations being utilized for growing different cell types in vitro, their pH and its effect, together with the crosslinking ions, of those formulations are still infrequently assessed. In this work we studied how these elements can affect hydrogel stability and printability and influence U2OS and NIH/3T3 cell viability and metabolism on the resulting 3D prints. In this context, 6% alginate + 2% gelatin hydrogels were prepared with 0.1 M MES buffer with pH 5.5, 6.5, 7.0 or 8.0, printed by extrusion-based 3D printing, and crosslinked immediately after printing with either CaCl2 or BaCl2. Our results showed that both the buffer pH and the crosslinking ion (Ca2+ or Ba2+) influence the swelling and degradation rates of the prints. Moreover, the buffer pH influenced the printability of the hydrogel in air, but when printed directly in a fluid-phase CaCl2 or BaCl2 crosslinking bath. In addition, both U2OS and NIH/3T3 cells showed greater cell metabolic activity on one-layer prints crosslinked with Ca2+. Besides, Ba2+ increased cell death of NIH/3T3 cells while had no effect on the U2OS cell viability. The pH of the buffer also caused an important impact on the cell behaviour. U2OS cells showed a 2.25-fold cell metabolism increase on one-layer prints prepared at pH 8.0 in comparison to those prepared at pH 5.5. Whereas, NIH/3T3 cells showed greater metabolism on one-layer prints with pH 7.0. Finally, we observed a difference on cell arrangement of the U2OS cells growing on prints prepared from hydrogels with acidic buffer in comparison to cells growing on those prepared using neutral or basic buffer. These results show that both pH and crosslinking ion influence hydrogel strength and cell behaviour.

In atomic GdFe$_2$ films capped by 4$d$ and 5$d$ transition metals, we show that skyrmions with diameters smaller than 12 nm can emerge. The Dzyaloshinskii--Moriya interaction (DMI), exchange energy, and the magnetocrystalline anisotropy (MCA) energy were investigated based on density functional theory. Since DMI and MCA are caused by spin--orbit coupling (SOC), they are increased with 5$d$ capping layers which exhibit strong SOC strength. We discover a skyrmion phase by using atomistic spin dynamic simulations at small magnetic fields of $\sim$1 T. In addition, a ground state that a spin spiral phase is remained even at zero magnetic field for both films with 4$d$ and 5$d$ capping layers.

Majority of the studied MADS box members are linked with flowering and fruit traits. However, higher volumes of studies on the type II of their two types so far suggest that florigenic effect of the gene members could just be tip of the iceberg. In current study we used a systematic approach to have general overview on the MADS box members their cross-trait and multifactor associations as well as their pleiotropic potentials based on local reference database curated for MADS box members. While doing so, we screened for the co-occurrence of the terms of interest within the title or abstract of each reference with threshold of 3 hits. Analysis results showed that our approach can retrieve multi-faceted information on the subject of study (MADS box gene members in current case) which could otherwise have been skewed depending on the authors’ expertise and/or volume of literature reference base. Overall, our study discusses on the roles of MADS box members in association with plant organs and traits-linked factors among plant species. Our assessment showed that plants with majority of the MADS box member studies include tomato, apple, rice etc., after Arabidopsis. Furthermore, based on the degree of their multi-trait associations, FLC, SVP, SOC1, etc. are suggested to have relatively higher pleiotropic potential among others in plant growth, development and flowering process. The approach devised in this study is expected applicable for having basic understanding on any study subject of interest regardless of depth prior knowledge.

It is unclear whether military shoes (combat boots and sports shoes) attenuate loading rate or affect force transfer during walking. Therefore, this study compared ground reaction forces (GRF) related to impact and force transfer between combat boots, military sports shoes and running shoes. Ten army recruits walked over a walkway with two force plates embedded. GRF were measured when walking barefoot (for data normalization) and with combat boots, military sports shoes and running shoes. Loading rate, first and second peak forces and push-off rate of force were computed along with temporal analysis of waveforms. Reduced loading rate was observed for the running shoe compared to the combat boot (p = 0.02 and d = 0.98) and to the military sports shoe (p = 0.04 and d = 0.92). The running shoe elicited a smaller second peak force than the combat boot (p < 0.01 and d = 0.83). Walking with military shoes and combat boots led to larger force transfer then running shoes potentially due to harder material used in midsole composition (i.e. styrene-butadiene rubber). These results could lead to a potentially larger risk of injuries while long duration walking in military shoes and boots compared to traditional running shoes.

A significant portion of the harvested land base in western Canada is becoming old enough or entering a phase where thinning is a legitimate option. A comprehensive review of the existing knowledge of commercial thinning (CT) treatments applied to pine and spruce-dominated stands in Alberta was conducted, with particular regard to the intensity, the timing of interventions, method and impacts on crop tree growth responses. Although the geographical focus of this review is Alberta, information on this topic is more complete in other areas of North America, and Europe, where there is a long history of density management. In areas of eastern North America, our review revealed that CT from below, with tree removal levels from 27 to 43% of the basal area could increase the merchantable wood volume from 11 to 60 m3 ha-1, depending on stand age and intensity of thinning. For Alberta conditions, and considering the risks, we conclude that commercial thinning basal area removal should be in the range of 25 to 40%, depending on a variety of factors such as species, wind firmness and insect or disease incidence and risk. Thinning too aggressively and/or too late will increase the blowdown risk but the literature is fairly consistent in suggesting that live crown ratios should be >40% to maximize the chance of growth response and minimize the blowdown risk. In cases where stands are also threatened by stressors such as drought, wind, and insect or disease outbreaks, CT treatments likely offer the potential at limiting the overall risk, but localized knowledge and experience are critical. It is intended that the information presented may support ongoing and future research trials and growth and yield (G&Y) model development with regard to potential CT treatments to apply and the likely results of practical application to commercial forestry.

Viscoelastic testing (VET) by both TEG and ROTEM has demonstrated hypercoagulability early in Covid Associated Coagulopathy (CAC). Additional VET studies demonstrated fibrinolytic shutdown late in a majority of severely ill Covid-19 patients with associated elevation of D-dimer. Elevated d-dimer confirms that coagulation, followed by fibrinolysis, has occurred. These findings imply that, during CAC, three enzymes—thrombin, Factor XIIIa and plasmin—must have acted in sequence. However, limitations in standard VET analyses preclude exploration of the earliest phases of clot induction, as well as clot formation and clot dissolution in flowing blood. Herein we describe a novel method illuminating aspects of this unexplored area. In addition, we created an ex vivo blood flow model in which the interactions of thrombin, Factor XIII and plasmin with fibrinogen can be studied, allowing determination of Soluble Fibrin (SF), the highly unstable form of fibrin that precedes the appearance of a visible clot. This model allows determination of the SF level at which fibrin microclots begin to form and the length of time the resulting microclots persist under normal fibrinolytic attack. In addition, the flow model allows exploration of the late fibrinolytic shutdown that VET has previously demonstrated in CAC through standard methodology.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Fungal keratitis (FK) is an invasive infection of the cornea primarily associated with Aspergillus and Fusarium species. FK is treated empirically with a limited selection of topical antifungals with varying levels of success. Though clinical infections are typically characterized by a dense network of mature mycelium, traditional models used to test antifungal susceptibility of FK isolates exclusively evaluate susceptibility in fungal cultures derived from asexual spores known as conidia. The purpose of this study was to characterize differences in fungal response when topical antifungal treatment is initiated at progressive phases of fungal development. We compared efficacy of voriconazole and luliconazole against in vitro cultures of A. flavus and F. keratoplasticum at 0, 24, and 48 h of fungal development. A porcine cadaver corneal model was used to compare antifungal efficacy of voriconazole and luliconazole in ex vivo tissue cultures of A. flavus and F. keratoplasticum at 0, 24, and 48 h of fungal development. Our results demonstrate phase-dependent susceptibility of both A. flavus and F. keratoplasticum to both azoles in vitro as well as ex vivo. We conclude that traditional antifungal susceptibility testing with conidial suspensions does not correlate with fungal susceptibility in cultures of a more advanced developmental phase. A revised method of antifungal susceptibility testing that evaluates hyphal susceptibility may better predict fungal response in the clinical setting where treatment is often delayed until days after the initial insult.

Background: The association of echocardiographic findings and subsequent risk of left-sided native valve endocarditis (LS-NVE) is undefined. The aim of this study was to determine if transthoracic echocardiographic (TTE) measurements are associated with the subsequent development of LS-NVE in patients without cardiac predisposing conditions. Methods: Institutional databases were evaluated for adults diagnosed with LS-NVE from 2008 to 2020. Patients with prosthetic valves, cardiovascular implantable electronic devices, intracardiac devices, injection drug use, and predisposing cardiac conditions were excluded. Only patients who had a TTE performed 6 months to 3 years before the development of LS-NVE were included as cases. Controls were patients within the same Mayo location with a TTE report and were matched in a 1:3 ratio according to age, gender, Charlson Comorbidity Index, and echocardiography date. Results: There were 148 cases and 431 matched controls. As compared to controls, IE cases had a higher prevalence of diabetes mellitus (46.6% vs. 30.4%) and chronic kidney disease (46.6% vs. 28.1%) (p<0.001). Left ventricular outflow tract velocity (p=0.017), left ventricular ejection fraction (p=0.018), and E: e’ ratio (p=0.050) were associated with LS-NVE. Conclusions: Echocardiographic measurements were associated with subsequent LS-NVE development in this pilot study. A larger cohort of LS-NVE patients, however, is needed to validate these findings.

Organic light-emitting diodes (OLEDs) have ushered in a technological revolution with their remarkable impact on diverse sectors of our daily lives. These versatile devices known for their outstanding display and lighting capabilities, have become indispensable components in various industries including smartphones, tablets, televisions, and automotive applications. This paper delves into the development of a group of twisted donor-acceptor-donor (D-A-D) derivatives incorporating bicarbazole and benzophenone structures for potential use as blue emitters in OLEDs. The synthesized compounds, namely DB14, DB23 and DB29, were designed with various alkyl side chains to enhance their film forming properties as for blue emitters. Characterization and evaluation of these derivatives included photophysical, electrochemical, thermal, and electroluminescent analysis. Some of the OLED devices incorporating these emitters demonstrated promising performance with maximum current efficiency (CEmax) of 2.6 cd/A and external quantum efficiency (EQEmax) of 5.3%. Notably, the DB23 emitter exhibited the highest EQE among all devices. The study also emphasizes the influence of host-guest energy transfer, optimal doping concentrations, and molecular structures on device performance. This research not only contributes to the understanding of advanced OLED materials but also provides insights into designing efficient blue emitters for future display and lighting applications, thereby advancing the field of organic electronics.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population, and is increasing worldwide, due to the pandemic of obesity. Insulin resistance is closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids (FA) released from adipose tissue, increase in FA synthesis and reduced FA oxidation in the liver, and hepatic overproduction of triglyceride (TG)-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease (CVD). Considering that the development of CVD determines the prognosis of MASLD patients, the ideal therapeutic interventions for MASLD should reduce body weight, improve coronary risk factors, in addition to an improvement in liver functiom. Lifestyle modification such as diet and exercise and surgical interventions such as bariatric surgery and intragastric balloons have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to improve coronary risk factors and to suppress the occurrence of CVD. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator, pemafibrate, improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs, and consider whether such drugs and the combination therapy of such drugs could be the ideal treatments for MASLD.

Erastin (ER) induces cell death by utilizing the process of ferroptosis via generation of reactive oxygen species (ROS). Ferroptosis is characterized by accumulation of ROS within the cell, leading to an iron-dependent oxidative damage-mediated cell death. Here, we have examined ferroptosis-dependent mechanism(s) of cytotoxicity of ER in K-RAS mutant human ovarian tumor OVCAR-8 and NCI/ADR-RES cell lines. We used these cell lines to decipher the mechanisms of ER as NCI/ADR-RES cells express higher activities of SOD, glutathione peroxidase and transferases than OVCAR-8 cells. We found that ER was equally cytotoxic to both cells; ER formed more ROS in OVCAR-8 cells than in NIH/ADR-RES cells. Ferrostatin-1, an inhibitor of ferroptosis, inhibited ER-induced cell death in both cell lines. In contrast, RSL3 (RAS-selective lethal 3), an inducer of ferroptosis, significantly enhanced cell death in both cell lines. ER induced significant lipid peroxidation only in OVCAR-8 cells. We found that RSL3 was more cytotoxic to NCI/ADR-RES cells and significantly enhanced ER-induced lipid peroxidation in both cells, indicating GPX4 was involved in the process of ER-mediated ferroptosis. ER treatment also differentially modulated several ferroptosis related genes (e.g., HMOX1/OH1, and CHAC1) in these cells, indicating ER-induced cell death may be mediated differently in OVCAR-8 and NCI/ADR-RES ovarian cells. Our studies suggest that combinations of ER and RSL3 may contribute significantly to the treatment of ovarian cancers, including those that are resistant to other therapeutic agents due to the presence of P-gp or tumors with Ras mutation in the clinic. ER induced ferroptosis may also be an important treatment modality for resistant tumors expressing MDR1 in the clinic.

This work presents a novel approach for the study of the movement of droplets on inclined surfaces under the influence of gravity and chemical heterogeneities. The developed numerical methodology uses data-driven modeling to extend the applicability limits of an analytically derived reduced-order model for the contact line velocity. More specifically, while the reduced-order model is able to capture the effects of the chemical heterogeneities to a satisfactory degree, it does not account for gravity. To alleviate this shortcoming, datasets generated from direct numerical simulations are used to train a data-driven model for the contact line velocity, which is based on the Fourier neural operator and corrects the reduced-order model predictions to match the reference solutions. This hybrid surrogate model, which comprises of both analytical and data-driven components, is then integrated in time to simulate the droplet movement, offering a speedup of five orders of magnitude compared to direct numerical simulations. The performance of this hybrid model is quantified and assessed in different wetting scenarios, by considering various inclination angles and values for the Bond number, demonstrating the accuracy of the predictions as long as the adopted parameters lie within the ranges considered in the training dataset.

Debates regarding human capital disclosure (HCD) emphasise the usefulness of people-related information in stimulating investor confidence and building stakeholder trust. Despite this, human capital (HC) information is interwoven in most international sustainability reporting standards such as the global reporting initiative (GRI), thereby concealing the impact of human resource (HR) practices in shareholder value creation. The aim of this study is to develop a taxonomy to assess HCD in the sustainability reports to capture the true value of HC distinctively. A content analysis-based study with a deductive approach was followed by utilising the GRI standards to isolate and classify people-related information into an HCD sustainability taxonomy. 40% HC metrics were extracted from the GRI standards and subsequently classified into 7 dimensions, namely, human capital allocation, human capital wellbeing, human capital investment, human capital network, human capital governance, human capital risk and human capital earnings. Furthermore, 40 GRI content indexes of the companies listed in the Johannesburg Stock Exchange (JSE) revealed that most disclosures are covered in the human capital governance and human capital earnings categories. HCD sustainability provides investors and HR professionals with a useful tool to assess people-related information from the sustainability reports for isolating the true value of HC.

Aim: To determine whether an AI model and single sensor measuring acceleration and ECG could model cognitive and physical fatigue for a self-paced trail run. Methods: A field-based protocol of continuous fatigue repeated hourly induced physical (~45 minutes) and cognitive (~10 minutes) fatigue on one healthy participant. Physical load was a 3.8 km, 200 m vertical gain, trail run with acceleration and electrocardiogram (ECG) data collected using a single sensor. Cognitive load was a Multi Attribute Test Battery (MATB) and separate assessment battery including the Finger Tap Test (FTT), Stroop, Trail Making A and B, Spatial Memory, Paced Visual Serial Addition Test (PVSAT), and a vertical jump. A fatigue prediction model was implemented using a Convolutional Neural Network (CNN). Results: When the fatigue test battery results were compared for sensitivity to the protocol load, FTT right hand (R2 0.71) and Jump Height (R2 0.78) were the most sensitive while the other tests were less sensitive (R2 values Stroop 0.49, Trail Making A 0.29, Trail Making B 0.05, PVSAT 0.03, spatial memory 0.003). Best prediction results were achieved with a rolling average of 200 predictions (102.4 s), during set activity types, mean absolute error for ‘walk up’ (MAE200 12.5%) and range of absolute error for ‘run down‘ (RAE200 16.7%). Conclusion: We were able to measure cognitive and physical fatigue using a single wearable sensor during a practical field protocol including contextual factors in conjunction with a neural network model. This research has practical application to fatigue research in the field.

Passive microwave measurements have been available on satellites dating back to the 1970s on research satellites flown by the National Aeronautics and Space Administration (NASA). Since then, several other sensors have been flown to retrieve hydrological products for both operational weather applications (e.g., the Special Sensor Microwave/Imager–SSM/I; the Advanced Microwave Sounding Unit–AMSU) and climate applications (e.g., the Advanced Microwave Scanning Radiometer–AMSR; the Tropical Rainfall Measurement Mission Microwave Imager–TMI; the Global Precipitation Mission Microwave Imager–GMI). Here the focus is on measurements from the AMSU-A, AMSU-B and Microwave Humidity Sounder (MHS). These sensors have been in operation since 1998 with the launch of NOAA-15, and are also on board NOAA-16, -17, -18, -19 and the MetOp-A and -B satellites. A data set called the “Hydrological Bundle” is a Climate Data Record (CDR) that utilizes brightness temperatures from Fundamental CDRs to generate Thematic CDRs (TCDR). The TCDR’s include: Total Precipitable Water (TPW), Cloud Liquid Water (CLW), Sea-Ice concentration (SIC), Land surface temperature (LST), Land surface emissivity (LSE) for 23, 31, 50 GHz, rain rate (RR), snow cover (SC), ice water path (IWP), and snow water equivalent (SWE). The TCDR’s are shown to be in general good agreement with similar products from other sources such as the Global Precipitation Climatology Project (GPCP) and the Modern-Era Retrospective Analysis for Research and Applications (MERRA-2). Because of the careful intercalibration of the FCDR’s, little bias is found among the different TCDR’s produced from individual NOAA and MetOp satellites, except for normal diurnal cycle differences.

The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practice (KAP) in Iranian adults who may be at increased risk of vitamin D deficiency. This study was conducted on 527 subjects, aged ≥20 years from Public health care centers in Tehran, Iran. Based on results of literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire with four subscale was developed: 1) general knowledge; 2) nutritional knowledge; 3) attitudes; 4) behaviors. Validity of the developed vitamin D-KAP questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2±7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by the panel of experts. The internal consistency, as measured by Cronbach’s alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. The EFA suggested a four-factor construct and the results of the CFA indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0, 1.1, 2.4, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59±14.52) and nutrition knowledge, the lowest score (42.58±20.40) among the four sub-scales. Results confirm the initial validity and reliability of the vitamin D-related knowledge, attitude and practice questionnaire. Further investigations in different urban and rural population are recommended.

Users with Autism Spectrum Disorder may find human-computer interaction (HCI) challenging due to a number of symptoms experienced, one of which is difficulty coping with change. Through capturing, comparing and statistically analysing the reactions of autistic and neurotypical users to seven individual design changes, it has been possible to identify the changes that cause significant difficulty in autistic users. These difficulty points were then used to form heuristics that can followed by HCI practitioners in the industry to reduce the negative impact of software interface design change on autistic users, hence making software updates more accessible.

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D and its principal catabolite 24,25(OH)2D were measured simultaneously with a validated liquid chromatography tandem mass-spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR=100*(24,25(OH)2D/25(OH)D). The psychometric assessment enclosed: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = -.154, p = .040). Based on the small effect size and the predominantly euthymic sample, further exploitation in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers, and an assessment in different phases of the disease may provide available additional insights.

In this work, we explore a the different forms of a new type of modified gravity, namely f(φ) gravity. We construct the Big Rip type for the energy density and the curvature of the universe. We show that dark energy is a result of the transformation of the field φ mass (dark matter) to energy. In addition, we provide that Ω_{m}≈0,050, Ω_{DM}≈0,2, Ω_{DE}≈0,746, is in excellent agreement with observation data. We explore a generalized formalism of braneworld modified gravity. We also construct a new field equations, which generalize the Einstein field equations. We provide a relation between the extra dimension in 3-brane with the vacuum energy density. We show that the energy density of matter depends directly on the number of dimensions. We manage to find the value of the Gauss-Bonnet coupling α=1/4 which is a good agreement with the results in the literature, this correspondence creates a passage between f(R) gravity and Gauss-Bonnet gravity, this comparison leads to a number of bulk dimensions equal to D=10¹²¹+4.