We discuss further details on the concepts of “drug-likeness”, “lead-likeness”, and “natural product-likeness”. The discussion will first focus on natural products as drugs, then a discussion of previous studies in which the complexities of the scaffolds and chemical space of naturally occurring compounds have been compared with synthetic, semi-synthetic compounds and FDA-approved drugs. This is followed by guiding principles for designing “drug-like” natural product libraries for lead compound discovery purposes. We end up by presenting a tool for measuring “natural product-likeness” of compounds and a brief presentation of machine learning approaches and a binary quantitative structure-activity relationship (QSAR) for classifying drugs from non-drugs and natural compounds from non-natural ones, respectively.

Despite the continued growth of the sport, particularly among recreational athletes, very little is known about how triathletes prepare for an event. The aim of this study was to identify the training characteristics of recreational-level triathletes and assess how their preparation for a triathlon influences their health and fatigue. During the 6 weeks prior to an Olympic distance triathlon, and the 2 weeks after the event, ten (5 males, 5 females) recreational athletes completed a daily training log to provide information on every training session. In addition, participants answered the Daily Analysis of Life Demands Questionnaire (DALDA), the Training Distress Scale (TDS), and the Alberta Swim Health Questionnaire weekly. Training loads were calculated using session-based rating of perceived exertion (sRPE) and training impulse (TRIMP). Every week of training was compared to week 1 to determine how athletes’ training and health changed throughout the study. In the 6 weeks leading up to the event, training loads, total minutes trained, and time spent in each training zone did not differ significantly. Significant reductions in training duration (Z=2.39, p=0.017, ES = 0.90), training strain (Z=2.59, p=0.009, 0.98), and number of sessions (Z=2.49, p=0.012, ES = 0.94) were seen on week 6. Training intensity distribution favored a threshold approach with athletes spending 56% of their training time at zone 1, 40% at zone 2, and 4% at zone 3. No significant changes were seen in the DALDA or TDS questionnaires. The results show that while the training intensity distribution of recreational-level triathletes does not follow a polarized model, these athletes were able to maintain their health while preparing for an Olympic distance triathlon.

Little is known about how recreational triathletes prepare for an Olympic distance event. The aim of this study was to identify the training characteristics of recreational-level triathletes within the competition period and assess how their preparation for a triathlon influences their health and their levels of fatigue. During the 6 weeks prior to an Olympic distance triathlon, and the 2 weeks after, 9 recreational athletes (5 males, 4 females) completed a daily training log. Participants answered the Daily Analysis of Life Demands Questionnaire (DALDA), the Training Distress Scale (TDS), and the Alberta Swim Fatigue and Health Questionnaire weekly. The Recovery-Stress Questionnaire (REST-Q) was completed at the beginning of the study, on the day before the competition, and at the end of week 8. Training loads were calculated using session-based rating of perceived exertion (sRPE). The data from every week of training was compared to week 1 to determine how athletes’ training and health changed throughout the study. No changes in training loads, duration, or training intensity distribution were seen in the weeks leading up to the competition. Training duration was significantly reduced in week 6 (p=0.041, d = 1.58, 95% CI = 6.9, 421.9), while the number of sessions was reduced in week 6 (Z=2.32, p=0.02, ES = 0.88) and week 7 (Z = 2.31, p=0.02, ES = 0.87). Training was characterized by large weekly variations in training loads and a high training intensity. No significant changes were seen in the DALDA, TDS, or REST-Q questionnaire scores throughout the 8 weeks. Despite large spikes in training load and a high overall training intensity, these recreational-level triathletes were able to maintain their health in the 6 weeks of training prior an Olympic distance triathlon.

Iron is an essential nutrient and necessary for biological functions from DNA replication and repair to transcriptional regulation, mitochondrial respiration, electron transfer, oxygen transport, photosynthesis, enzymatic catalysis, and nitrogen fixation. However, due to iron’s propensity to generate toxic radicals which can cause damage to DNA, proteins, and lipids, multiple processes regulate uptake and distribution of iron in living systems. Understanding how intracellular iron metabolism is optimized and how iron is utilized to regulate other intracellular processes is important to our overall understanding of a multitude of biological processes. One of the tools that the cell utilizes to regulate a multitude of functions is ligation of the iron-sulfur (Fe-S) cluster cofactor. Fe-S clusters comprised of iron and inorganic sulfur are ancient components of living matter on earth that are integral for physiological function in all domains of life. Here we will explore the ways in which the cell utilizes Fe-S clusters to sense the intracellular environment and respond to maintain equilibrium.

The COVID-19 pandemic has led to numerous delays in cancer-related care and cancer-specific screening, but the extent is not fully understood. For those that experience a delay or disruption in care, health related self-management is required to re-engage in care pathways and the role of health literacy in this pathway has not been explored. The purpose of this analysis is to (1) report the frequency of self-reported delays in cancer treatment and preventative screening services at an academic, NCI-designated center during the COVID-19 pandemic and (2) investigate cancer-related care and screening delays among those with adequate and limited health literacy. A cross-sectional survey was administered from an NCI-designated Cancer Center with a rural catchment area during November 2020 through March 2021. Nearly 19 percent of participants were categorized as having limited health literacy. Twenty percent of those with a cancer diagnosis reported a delay in cancer-related care; and 23-30% of the sample reported a delay in cancer screening. In general, the proportions of delays among those with adequate and limited health literacy were similar with the exception of colorectal cacner screening. There was also a notable difference in the ability to re-engage in cervical cancer screening among those with adequate and limited health literacy. Thus, there is a role for those engaged in cancer-related education and outreach to offer additional navigation resources for those at risk to cancer-related care and screening disruptions. Future study is warranted to investigate the role of health literacy on cancer care engagement.

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.

Despite the remarkable success of Carnot’s heat engine cycle in founding the discipline of thermodynamics two centuries ago, false viewpoints of his use of the caloric theory in the cycle still linger, limiting his legacy. An action revision of the Carnot cycle can correct this, showing that the heat flow powering external mechanical work is compensated internally with configurational changes in the thermodynamic or Gibbs potential of the working fluid, differing in each stage of the cycle quantified by Carnot as caloric. Action (@) is a property of state having the same physical dimensions as angular momentum (mrv=mr2ω). However, this property is scalar rather than vectorial, including a dimensionless phase angle (@=mr2ωδφ). We have recently confirmed with atmospheric gases that their entropy is a logarithmic function of the relative vibrational, rotational and translational action ratios with Planck’s quantum of action ħ. The Carnot principle shows that the maximum rate of work (puissance motrice) possible from the reversible cycle is controlled by the difference in temperature of the hot source and the cold sink, the colder the better. This temperature difference between the source and the sink also controls the isothermal variations of the Gibbs potential of the working fluid, that Carnot identified as reversible temperature-dependent but unequal exchanges in caloric. Importantly, the engine’s inertia ensures that heat from work performed adiabatically in the expansion phase is all restored to the working fluid during the adiabatic recompression, less the net work performed. This allows both the energy and the thermodynamic potential to return to the same values at the beginning of each cycle, a point strongly emphasized by Carnot. Our action revision equates Carnot’s calorique, or the non-sensible heat later described by Clausius as ‘work-heat’ exclusively to negative Gibbs energy (-G) or quantum field energy. This action field complements the sensible energy or vis-viva heat as molecular kinetic motion and its recognition should have significance for designing more efficient heat engines or better understanding of the heat engine powering the Earth’s climates.

Clausius’ virial theorem set a basis for relating kinetic energy in a body of independent material particles to its potential energy, pointing to their complementary role with respect to the second law of maximum entropy. In action mechanics, expressing the entropy of ideal gases as a capacity factor for sensible heat or enthalpy plus the configurational work to sustain the relative translational, rotational and vibrational action yields algorithms for estimating chemical reaction rates and positions of equilibrium. All properties of state including entropy, work potential as Helmholtz and Gibbs energies and activated transition state reaction rates can be estimated, using easily accessible molecular properties, such as atomic weights, bond lengths, moments of inertia and vibrational frequencies. Understanding how Clausius’ virial theorem balances the internal kinetic energy with field potential energy justifies partitioning between thermal and statistical properties of entropy, yielding a more complete view of the evolutionary nature of the second law of thermodynamics. The ease of performing these operations is illustrated by three important chemical gas phase reactions, the reversible dissociation of the hydrogen molecules, lysis of water to hydrogen and oxygen and the reversible formation of ammonia from nitrogen and hydrogen. Employing the ergal also introduced by Clausius to define the reversible internal work to overcome molecular interactions plus the configurational internal work of negative Gibbs energy as a function of volume or pressure may provide a practical guide for managing risk in industrial processes and climate change at the global scale.

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.

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.

We propose that, at equilibrium, statistically equal temperatures as mechanical torques are exerted on each kind of gas phase molecules as rates of translational action [@t=ʃmvds/dt=ʃmr2ωdϕ/dt=mv2, J]. These torques result from the impulsive density of resonant quantum fields with molecules, configuring the trajectories of gas molecules while balancing molecular pressure (p=NkT) against the density of field energy (J/m3). Gibbs energy fields contain no resonant quanta at zero Kelvin, with this measure of chemical potential diminishing in magnitude as translational action of the vapor molecules and quantum field energy increases with temperature. In illustration, we show how impulsive torques from quantum fields drive the reversible thermodynamics of Carnot’s heat-work engine cycle, sustain the decreasing atmospheric temperature gradient of increasing molecular entropy with altitude, support the translational action and field energy of vortical wind flow in anticyclones, frictionally warming the Earth’s surface while recycling greenhouse infrared absorption of surface radiation, generating electrical power from air flow in wind farms and destructive power in tropical cyclones. These cases all distinguish symmetrically between a causal field of impulsive quanta (Σhν) that energizes the action of matter and the resultant vis viva of molecular mechanics (mv2). The quanta of these different fields display mean wavelengths from 10-4 m to 1012 m, with mechanical advantages many orders of magnitude greater than the corresponding translational actions, though with mean quantum frequencies (v) similar to those of radial Brownian movement for independent particles (ω). These energy fields are also thermodynamically reversible reservoirs for heat, optimizing work processes on Earth and delaying the achievement of maximum entropy production from short wave solar radiation in conversion to outgoing long wave radiation to space.

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease. While its etiology remains elusive, current understanding suggests a multifactorial process with contributions by genetic, immunologic, hormonal, and environmental factors. A hypothesis that combines several of these factors proposes that genomic elements, the L1 retrotransposons, are instrumental in SLE pathogenesis. L1 retroelements are transcriptionally activated in SLE and produce two proteins, ORF1p and ORF2p, which are immunogenic and can drive type I interferon (IFN) production by producing DNA species that activate cytosolic DNA sensors. In addition, these two proteins reside in RNA-rich macromolecular assemblies that also contain well-known SLE autoantigens like Ro60. We surmise that cells expressing L1 will exhibit all the hallmarks of cells infected by a virus, resulting in a cellular and humoral immune response similar to those in chronic viral infections. However, unlike exogenous viruses, L1 retroelements cannot be eliminated from the host genome. Hence, dysregulated L1 will cause a chronic, but perhaps episodic, challenge for the immune system. The clinical and immunological features of SLE can be largely explained by this model. Here we review the support for, and the gaps in, this hypothesis of SLE and its potential for new diagnostic, prognostic, and therapeutic options in SLE.

Urban green spaces provide a range of environmental and health benefits, which may become even more critical during times of crisis such as the current COVID-19 pandemic. However, with a radical shift in mobility, additional concerns over safety, and access temporarily restricted during the implementation of social distancing policies, the experience and use of urban green spaces may be reduced. This is particularly concerning for densely populated cities like New York, considered the first U.S. epicenter or vanguard of the outbreak. To better understand the impact of COVID-19 on the perception and use of urban green spaces, we conducted a social survey during the early months of the Covid-19 pandemic in New York City (May 13 - June 15, 2020). The results of the survey show respondents continued to use urban green spaces during the pandemic and consider them to be more important for mental and physical health than before the pandemic began. However, the study revealed a pattern of concerns residents have about green space accessibility and safety, and found key differences between the concerns and needs of different populations, suggesting a crucial role for inclusive decision-making, support for additional management strategies, and urban ecosystem governance that reflect the differential values, needs and concerns of communities across the City. As urban centers face looming budget cuts and reduced capacity, this study provides some empirical evidence to illustrate the value of urban green spaces as critical urban infrastructure, and may have implications for funding, policy, and management, of urban green spaces in NYC, with potential applications to other cities, particularly during times of crisis.

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.

Scientists can use the Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 system, which is a powerful and flexible tool for changing the genome, to change only certain parts of the genome. This has helped researchers figure out how target genes work in biology and disease. CRISPR/Cas9 is made up of a sequence-specific CRISPR RNA (crRNA) set and a generic Cas9 nuclease. The crRNA set tells Cas9 where to cut DNA and cause double-strand breaks. In the next step of cellular DNA repair, insertions, deletions, and swaps are made at specific spots. For CRISPR/Cas9-mediated DNA cleavage to be specific, the target sequences must match the crRNA, and a protospacer nearby motif must be placed after the target sequences. In this article, we talk about how CRISPR/Cas9 works at the molecular level, what it can be used for, what it can't do, and what its future clinical treatment promise might be.

The global use of alcohol based hand sanitizers (ABHS) as a means of controlling the transmission of infectious disease increased dramatically in 2020 as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. The hand sanitizer tetrahedron, is a novel concept that considers both ABHS formulation factors and product performance factors from a multi-dimensional perspective. The four faces of the tetrahedron represent input/formulation factors: 1) the type and amount of alcohol, 2) inactive ingredients, 3) the type of formulation/delivery system and 4) manufacturing practices. The four corners of the tetrahedron represent output/product performance factors: 1) efficacy, 2) sensory characteristics, 3) usage, usability and compliance and 4) product safety/adverse effects. All factors are of importance to ensuring the effectiveness and utility of these products.

The purpose of this study was to assess if self-regulation of intensity based on rating of perceived exertion (RPE) is a reliable method to control the intensity of metabolic conditioning of functional-fitness session. In addition, the relationship between RPE and changes in heart rate and lactate responses was also analyzed. Eight male participants (age 28.1 ± 5.4 years; body mass 77.2 ± 4.4kg; VO₂max: 52.6 ± 4.6 mL·(kg·min)⁻¹) completed three randomly sessions (5 to 7 days apart) under different conditions: (1) all-out (ALL); (2) self-regulation of intensity based on a RPE of 6 (hard) on the Borg CR-10 scale (RPE6); and (3) a control session. Rate of perceived exertion, LAC and HR response were measured pre, during and immediately after the sessions. The RPE and LAC during the ALL-OUT sessions were higher (p ≤ 0.05) than the RPE6 and control sessions for all the analyzed time points during the sessions. Regarding HR, the 22 min area under the curve of HR during ALL-OUT and RPE6 sessions were significantly higher (p ≤ 0.05) than the control session. The average number of repetitions was lower (p ≤ 0.05) for the RPE6 session (190.5 ± 12.5 repetitions) when compared to the ALL session (214.4 ± 18.6 repetitions). There was a significant correlation between RPE and LAC (p = 0.001; r = 0.76; very large) and number of repetitions during the session (p = 0.026; r = 0.55; large). No correlation was observed between RPE and HR (p = 0.147; r = 0.380). These results indicate that self-regulation of intensity of effort based on RPE may be a useful tool to control exercise intensity during a metabolic conditioning session of functional-fitness.

The past two decades has seen a growing demand for high-power, high-voltage utility scale inverters mostly fueled by the integration of large solar PV and wind farms. Multilevel inverters have emerged as the industry choice for these megawatt range inverters because their reduced voltage stress, capable of generating an almost sinusoidal voltage, in-built redundancy, among others. This paper present a new Switched-Source Multilevel Inverter (SS MLI) architecture. The new inverter show superior over existing topologies. It has reduced voltage stress on the semiconductor, uses less number of switches –reduced size/weight/cost and increased efficiency. The new SSMLI is comprised of two voltage sources (V₁, V₂) and 6 switches. It is capable of generating 5-level output voltage in symmetric modes (i.e., V₁ = V₂), and 7-level output voltage in asymmetric modes (i.e., V₁ ≠ V₂). To demonstrate the validity of the proposed inverter, simulations results using MATLAB^® /Simulink^® for 5- and 7-level output voltages are presented . The simulations are also verified experimentally using a laboratory prototype.

A convenient practical model for accurately estimating the total entropy (ΣSi) of atmospheric gases based on physical action is proposed. This realistic approach is fully consistent with statistical mechanics, but reinterprets its partition functions as measures of translational, rotational and vibrational action or quantum states, to estimate the entropy. With all kinds of molecular action expressed as logarithmic functions, the total heat required for warming a chemical system from 0o K (ΣSiT) to a given temperature and pressure can be computed, yielding results identical with published experimental third law values of entropy. All thermodynamic properties of gases including entropy, enthalpy, Gibbs energy and Helmholtz energy are directly estimated using simple algorithms based on simple molecular and physical properties, without resource to tables of standard values; both free energies are measures of quantum field states and of minimal statistical degeneracy, decreasing with temperature and declining density. We propose that this more realistic approach has heuristic value for thermodynamic computation of atmospheric profiles, based on steady state heat flows equilibrating with gravity. Potentially, this application of an action principle can provide better understanding of emergent properties of many natural or evolving complex systems, including modelling of predictions for global warming.

The emergence of the COVID-19 pandemic has propelled the use of alcohol-based hand sanitizers to the fore as a SARS-CoV-2 control measure. To be effective these products must comply with relevant quality parameters such as alcohol concentration, methanol limits and purity. The current study was designed to determine the quality of alcohol-based hand sanitizer products in the Nairobi metropolitan area. For this purpose, 74 commercially marketed samples were collected and subjected to analysis by gas chromatography. Only three samples (4.1%) complied with the regulatory specifications for alcohol content, methanol limits and pH. Five samples (6.8%) complied with the specification for alcohol content but did not meet methanol or pH limits. A total of 44 (59.5%) samples had methanol levels that exceeded threshold limits. Eleven samples (14.9%) were found with methanol substitution (i.e., methanol, instead of ethanol or isopropanol, was the main alcohol component). The results show that users of alcohol-based hand sanitizers are being exposed to substandard and falsified products which in addition to being non-efficacious pose harm due to unacceptable levels of toxic impurities. Regular, routine post-market surveillance is needed to prevent such products from reaching the market.

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.

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.

Road collisions are among the world’s critical issues causing many casualties, deaths, and economic losses. To deal with this scenario, precise analysis is required. In this paper, we use Machine Learning (ML) techniques to assess and predict road traffic collisions. An ensemble machine learning model with two layers was developed to analyze simulation data from the driving simulator. The first (base) layer integrates supervised learning techniques namely, k- Nearest Neighbors (k-NN) AdaBoost, Naive Bayes (NB), and Decision Trees (DT). The second layer predicts road collisions by combining the base layer outputs by employing the stacking ensemble method using logistic regression as a meta-classifier. The data for this study were imbalanced; therefore, we performed a SMOTE resampling strategy to handle the dataset imbalance. To simplify the model, the PSO algorithm was used to select the most important features in our dataset. The two-layer ensemble model proposed had the best outcomes with an accuracy of 88%, F1 score of 83%, and an AUC of 86% as compared with k-NN, DT, NB, and AdaBoost.

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.

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.

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

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.

This paper aims to provoke fundamental thinking and action around the value and importance of socially-equitable development to the economic advancement, resilience, and prosperity of communities, as we contend with the 21^st Century grand challenge of the changing climate and disasters. As local communities and the global community have experienced an increased frequency, intensity and duration of natural and man-made disasters over the past several decades, opportunities have also grown to identify and reap the benefits of socially-equitable economic development. Reflecting on the COVID-19 pandemic, we discuss the critical importance of socially-equitable economic development to the resilience and sustainability of communities and the infrastructure that supports them. To this end, we: (1) examine what constitutes socially-equitable economic development at different spatial scales of community; (2) explore whether socially-equitable development can occur at different scales of community; (3) explicate the importance of formally considering the inputs, processes, outputs and outcomes for socially-equitable development; (4) explain why the pursuit of equal distribution of the benefits and burdens of development is a necessary but not sufficient endeavor for socially-equitable economic development; (5) analyze the relationships between socially-equitable development, and resilient and sustainable infrastructure and communities; (6) explain why socially-equitable development should be a key component of infrastructure and community resilience strategies in the 21^st Century; and, (7) explain why socially-equitable development can ultimately be viewed as a long-term strategy for prosperity.

Stretching along the border of North Dakota and Minnesota, The Red River Valley (RRV) of the North has the highest frequency of reported blizzards within the contiguous United States. Despite the numerous impacts these events have, few systematic studies exist discussing the meteorological properties of blizzards. As a result, forecasting these events and lesser blowing snow events is an ongoing forecast challenge. This study presents a climatology of atmospheric patterns associated with RRV blizzards for the winter seasons of 1979-1980 to 2017-2018. Patterns were identified using subjective and objective techniques using meteorological fields from the North American Regional Reanalysis (NARR). The RRV experiences on average, 2.6 events per year. Blizzard frequency is bimodal with peaks occurring in December and March. The events can largely be typed into four meteorological categories dependent on the forcing that drives the blizzard: Alberta Clippers, Arctic Fronts, Colorado Lows, and Hybrids. Objective classification of these blizzards using a competitive neural network known as the Self-Organizing Map (SOM) demonstrates that gross segregation of the events can be achieved with a small (8-class) map. This implies that objective analysis techniques can be used to identify these events in weather and climate model output that may aid future forecasting and risk assessment projects.

Humanity’s social and economic development has been challenged by a range of adversities over the millennia that have caused widespread and unimaginable suffering. At the same time, these challenges have forced humans to evolve more wisely, overcoming adversity through creativity and leading to advancements in science and technology, medicine, ethics and legal systems, and socio-political systems. The dynamics of risks and opportunities caused by COVID-19, in the built, cyber, social and economic environments, present opportunities for deepening our understanding of resilient and sustainable development and infrastructure. This article reflects on five lessons that COVID-19 is teaching us about what it means to develop sustainably through the lens of transportation: (1) sustainable development planning and analytical frameworks must be comprehensive, for long-term sustainability; (2) multi-modal transportation is a superior vision for sustainable development than any one particular mode; (3) tele-activities are part of an effective infrastructure sustainability strategy; (4) economic capital is critically important to sustainable development even when it is not a critical existential threat, and, (5) effective social capital is essential in global disaster resistance and recovery, and can and must be leveraged between fast-moving and slow-moving disasters. Resilient and sustainable infrastructure will continue to be critical to addressing evolving natural and man-made hazards in the 21^st Century.

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.

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.

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.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

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.

Seasonal oscillations in the partial pressure of carbon dioxide (pCO2) in the Earth’s atmosphere stronger in northern latitudes are assumed to show that terrestrial photosynthesis exceeds respiration in summer reducing the pCO2, but increasing in winter when respiration exceeds photosynthesis. We disagree, proposing that variations in the temperature of the surface mixing zone of seawater also regulate the atmospheric pCO2, thermodynamically. We show that carbonate (CO32-) concentrations will therefore increase in summer with CaCO3 (calcite or aragonite) becoming less soluble, so calcium and carbonate ions are predicted to aggregate more while CO2 concentration falls in warmer seawater, thermodynamically favoring lower atmospheric pCO2. In winter, these physical processes are reversed, redissolving suspended calcite thus increasing carbonate alkalinity; carbonate concentration lessens as bicarbonate and soluble CO2 increase, raising the pCO2 in air. Our numerical computation shows that thermal fluctuations in equilibria favor absorption from air of more than one mole of CO2 per square meter in summer, coinciding with calcite formation maximizing in warmer water, potentially augmenting limestone reefs if there is a trend for increasing temperature . Another assumption we challenge is that upwelling from deeper water is the sole cause of increases in dissolved inorganic carbon (DIC) and alkalinity in surface waters, particularly in the southern hemisphere. Instead, calcite dissolution is favored as water temperature falls near the surface. It is well established that the seasonal summer decline in atmospheric CO2 coincides in fertile seawater with higher rates of biotic calcification and acidity, allowing increased CO2 capture by photosynthesis. However, its reversal in winter is proposed to be also a result of the cyclic dissolution of calcite as temperature falls, facilitated by biogenic respiration now exceeding photosynthesis; this can mutually provide the CO2 needed to convert carbonate ion alkalinity from calcite dissolution with bicarbonate increasing. Physical reasons why this oscillation is more obvious in the northern hemisphere include greater seasonal variations in water temperature (ca. 7.1 oC) being almost twice that in the cooler southern hemisphere (ca. 4.7 oC) and the greater depth of the surface mixing zone of seawater in the southern oceans. Evidence from 13CO2 fluxes between surface seawater and air is also assessed to test this hypothesis but questions remain regarding the regional rates of inorganic precipitation and dissolution of CaCO3 in the mixing zone. In summary, rapid biogenic calcification is favored by summer photosynthesis, but slower abiogenic calcification is more likely in warmer water.

Performing optimisation and scale-up studies of crystallisation systems requires accurate and computationally efficient mathematical models. The assumption of the ideal mixing conditions in batch reactors typically produce inaccurate results while the computational expense of CFD models is still prohibitively high. Therefore, in this work, a new intermediary approach is proposed that takes into account the non-ideal mixing conditions in the reactor and requires less computational resources than full CFD simulations. Starting with the Danckwerts concept of the intensity of segregation, an analogy between its application to chemical reactions and the kinetics of the crystallisation phenomena (such as nucleation and growth) has been made. As a result, the modified kinetics expressions have been derived which incorporate the effect of non-idealities present in stirred reactors. This way, based on the experimental measurements of the mixing time using the Laser Induced Fluorescence (LIF) technique, computationally more efficient mathematical models can be developed in two ways: (1) the accurate semi-empirical correlations are available for standard mixing configurations with the most often used types of impellers, (2) CFD simulations can be utilised for estimation of the mixing time; in this case it is necessary to simulate only the mixing process. The benefits offered by the LIF experimental technique have been demonstrated and some frequent problems in its application analysed. The mixing time results for configurations with and without baffles for three types of impellers and four different rotational speeds have been presented. The false shorter mixing times in the non-baffled configurations have been observed and this phenomena explained by the existence of two segregated zones in the reactor and confirmed by additional experiments. The precise measurements in these cases have been shown as difficult using the LIF technique, particularly for higher rpms. The experimental data has been compared to the preliminary simulation results obtained from the Smoothed Particle Hydrodynamics method and the standard k-ε turbulence model with the modest success. The shortcomings of the SPH model have been recognized and the directions for the future work discussed.

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.

Cheap licit and artisanal illicit spirit drinks have been associated with numerous outbreaks of alcohol poisoning especially with methanol. This study aimed to evaluate the quality of cheap spirit drinks in Kibera slums in Nairobi County, Kenya. The samples consisted of cheap licit spirits (n=11) and the artisanal spirit drink, ‘chang’aa’, (n=28). The parameters of alcoholic strength and volatile composition were used as indicators of quality and were determined using GC-FID and GC-MS respectively. The pH of chang’aa was 3.3-4.2 and 4.4-8.8 for licit spirit drinks while ranges for alcoholic strength were 42.8-85.8 % vol. and 28.3-56.7% vol. for chang’aa and licit spirit drinks respectively. The majority of volatiles were found in artisanal spirits and they included higher alcohols, ethyl esters and carbonyl compounds. The alcoholic strength of all the artisanal spirits (100%) and 91% of the licit spirits was above the 40% vol. of standard spirits such as vodka. The high ethanol content of the alcohol products was the only element of public health significance in this study.

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.

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.

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.

The ability of S. aureus to infect humans and cause a wide range of infections so efficiently is a consequence of the many variant virulence factors that it can produce. Superantigens (SAgs) make up a group of them and include staphylococcal enterotoxins (SE). The main objective of this study was to detect enterotoxin gene cluster (EGC) in S. aureus isolates that caused infections in Paraguayan children in the year 2017, through an observational and cross-sectional study. The detection of the EGC including the seg, sei, sem, sen, seo, and seu genes, was carried out by end-point PCR. 181 S. aureus isolates were collected, most of them caused skin and soft tissue infections (SSTI, n=140, 77%) and came from children under 6 years 50% (n=90). At least one SE gene was detected in 96% (174/181) of isolates and 24% (44/181) carried the entire EGC. An association between methicillin resistance and seg, sei, seo, and seu gene carriage (p ≤0.05) was observed. A high prevalence of EGC was detected in S. aureus isolates collected from infected children attending the main health care centers in Paraguay, its importance is due to the potential of these toxins to aggravate staphylococcal infections.

Stress has emerged as a major concern in modern society, significantly impacting human health and well-being. Statistical evidence underscores the extensive social influence of stress, especially in terms of work-related stress and associated healthcare costs. This work addresses the critical need for accurate stress detection, emphasising its far-reaching effects on health and social dynamics. Focusing on remote stress monitoring, this work proposes an efficient deep learning framework to discern stress from facial videos. In contrast to research on wearable devices, this paper investigates the application of *dl for stress detection based on *rppg. The methodology involves selecting suitable *dl models (*lstm, *gru, *1dcnn), optimising hyperparameters, and investigating augmentation techniques. 1D-CNNv1 model achieved the best performance compared to other approaches, particularly with augmentation techniques such as linear interpolation and white noise, achieving a stress classification accuracy of 95.83% while maintaining excellent computational efficiency. The experimental results demonstrate the use of *dl for stress detection based on *rppg, with the potential to make significant contributions to the international standard in the field.

Pig genetic resources in Africa originate from different regions. Genetic analysis has shown a strong phylogeographic pattern with the pigs on the eastern parts showing a high frequency of alleles from the Far East while the ones on the western parts show a strong European influence. This highlights the influence of trade routes on the genetic legacy of African pigs. They have, however, since adapted to the local environments to produce unique populations with unique attributes. Most of the pigs are now reared in resource-constrained smallholdings under free-range conditions. They are largely owned by women who spread ownership of the resource through kinship networks. Very little work has been done to characterize, conserve and sustainably utilize pig genetic resources in Southern Africa. The risk status of the breeds together with population numbers, distribution and other attributes are largely unknown. This paper proposes several strategies for the sustainable utilization of the pig genetic resources: a market-driven in situ conservation program and two complementary ex situ strategies. In addition, the possibility of community-based breed improvement programs is discussed.

Fowlpox virus (FPV) has been used as a vector for many years. To date, surprisingly, very little data exist on the persistence of fowlpox vaccines in chicken tissues, or what kind of immune cells respond to the vaccination at the site of inoculation. Although both humoral and cellular mediated immunity (CMI) play a part in overall immunity against FPV, little is known regarding the cell-mediated immune responses to FPV infection. The main aim of this paper was to measure persistence of the recombinant fowlpox vaccine in the skin tissues following vaccination. The results showed that the recombinant FPVs do not persist for long, and are cleared by 6 days post-vaccination (dpv). The response of immune cells (macrophages, B cells, CD4+ and CD8+ T cells) that infiltrating the site of vaccination was estimated.

The review scrutinizes the currently performed research on the new methods for enhancing bituminous binder performance through radiation and radical grafting of polymer modifers of bitumen. It investigates innovative methods, including using waste polymers as modifiers, and applying radiation for polymer grafting, to overcome challenges like high costs, low aging resistance and storage stability issues, of which separation of phases polymer/bitumen is the most significant obstacle. These advanced modification techniques promise sustainability through the decrease of the carbon footprint of transportation systems by improving the properties and durability of binders. Additionally, the review discusses the parameters and mechanistic aspects from a scientific perspective, shedding light on the underlying processes that contribute to the improved performance of modified bituminous binders.

In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of betacoronaviruses in the aftermath of the 2002-03 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-20 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind, allowing the follow up of disease spread and transmission dynamics in near real time. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2.

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.

Neurology is a quickly evolving specialty that requires clinicians to make precise and prompt diagnoses and clinical decisions based on the latest evidence-based medicine practices. In all Neurology subspecialties, Stroke and Epilepsy in particular, clinical decisions affecting patient outcomes depend on neurologists accurately assessing patient disability. Artificial intelligence (AI) can predict the expected neurological impairment from an AIS (Acute Ischemic Stroke), the possibility of ICH (IntraCranial Hemorrhage) expansion, and the clinical outcomes of comatose patients. This review article informs readers of artificial intelligence principles and methods. The article introduces the basic terminology of artificial intelligence before reviewing current and developing AI applications in neurology practice. AI holds promise as a tool to ease a neurologist’s daily workflow and supply unique diagnostic insights by analyzing data simultaneously from several sources, including neurological history and examination, blood and CSF laboratory testing, CNS electrophysiologic evaluations, and CNS imaging studies. AI-based methods are poised to complement the other tools neurologists use to make prompt and precise decisions that lead to favorable patient outcomes.

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.

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.

Work in the copper mining industry is often associated with exposure to respirable dust and respirable crystalline silica. This exposure has the potential to cause silicosis, a non-curable occupational respiratory lung disease. This study aimed at establishing the relationship between knowledge, attitudes, work behaviour and practice, compliance with safety standards and exposure to respirable dust. A cross-sectional descriptive survey was conducted on 528 mine workers. Statistical package for social sciences (SPSS) was used for descriptives. Structural Equation Modelling (SEM) with latent variables and partial least-squares (LVPLS) analysis was employed to determine the relationship among these variables. The results indicated that of the four (4) hypotheses, two (2) were supported and two (2) were rejected showing that there is a significant relationship between exposure to respirable dust and work behaviour and practice, as well as compliance with safety standards. Knowledge and attitudes towards respirable dust exposure did not significantly influence exposure. According to the results from the survey, positive work behaviour and practice as well as compliance with safety standards was significantly associated with exposure to respirable dust. It is recommended that the mine should focus on the miners’ work behaviour and practice and compliance with safety standards.

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.

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.

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.

The cryopreservation of gametes and embryos is an important element of biodiversity conservation. One species in need of conservation is the honey bee Apis mellifera L. Changing environmental factors, especially the anthropogenic factor, have led to a reduction in the numbers of this insect species. In this study, we provide an example of the creation of a biobank of honey bee drone sperm. For sperm cryopreservation, drones of the most common subspecies of honey bees common in Russia were selected. These were the dark forest bee, Apis mellifera mellifera from the Republic of Bashkortostan, with three subspecies (A. m. carnica, A. m. carpatica, and A. m. caucasica) from the southern regions of Russia, as well as two breeding stocks, the Far Eastern bee and Prioksky bee. For subspecies identification, morphometric and genetic methods were used. The subspecies of the studied samples were confirmed by the analysis of the tRNAleu-COII locus of mitochondrial DNA and nine microsatellite markers of nuclear DNA. It was shown that bees of the Prioksky breeding stock belong to the subspecies A. m. caucasica based on phylogenetic analysis, and the Far Eastern breeding stock is a stable hybrid, descending on the maternal line from the evolutionary lineage C or O. The results of the morphometric analysis are consistent with the results of the genetic analysis. For the cryopreservation of sperm, we used a honey diluent. As a result, the viability of frozen–thawed sperm decreased by 20.3% compared to fresh sperm, and overall motility decreased by 25-fold. The measurement of the sperm concentration in the spermatheca of artificially inseminated queens showed that it varied from 0.22 to 4.4 million/μL. Therefore, the use of honey in sperm cryopreservation has great potential.

Global coverage and scale up of interventions to reduce newborn mortality remains low, though progress has been achieved in improving newborn survival in many low-income settings. An important factor in the success of newborn health interventions, and moving to scale, is appropriate design of community-based programs and strategies for local implementation. We report the results of formative research undertaken to inform the design of a newborn health intervention in Cambodia. Information was gathered on newborn care practices over a period of three months using multiple qualitative methods of data collection in the primary health facility and home setting. Analysis of the data indicated important gaps, both at home and facility level, between recommended newborn care practices and those typical in the study area. The results of this formative research have informed strategies for behavior change and improving referral of sick infants in the subsequent implementation study. Collection and dissemination of data on newborn care practices from settings such as these can contribute to efforts to advance survival, growth and development of newborns for intervention research, and for future newborn health programming.

In South Sudan, three case-control studies found a positive association between Nodding Syn-drome (NS) and a Mansonella perstans infection. To investigate whether M. perstans could play the primary and sole causal role in the development of NS, we examined blood films of persons with and without epilepsy in rural villages affected by NS in Mahenge, Tanzania, to identify M. perstans infections. Study participants were also examined for onchocercal nodules and skin lesions and tested for the presence of anti-O. volvulus antibodies (Ov16 ELISA). One hundred and thirteen epilepsy cases and 132 controls were enrolled, with a mean age of 28.3 years (interquartile range 22 – 34 years); 125 (51%) were females. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria. M. perstans infection was absent in all participants, but Ov16 prevalence and oncho-cerciasis-associated skin manifestations were positively associated with epilepsy, including probable NS. Onchocercal nodules in the mothers of cases were also positively associated with epilepsy. In conclusion, in contrast with O. volvulus, M. perstans is likely not endemic in Mahenge and therefore cannot be a co-factor for NS in the area. Hence, this filaria cannot be the primary and sole causal factor in the development of NS.

Functional dependence of the axial zero-field splitting parameter D with respect to a properly chosen geometrical parameter (Dstr) in metal complexes is termed the Magnetostructural D-Correlation. In mononuclear hexacoordinate Ni(II) complexes with the ground electronic term 3B1g (3A2g in the regular octahedron) it proceeds along two intercepting straight lines allowing to predict the sign and magnitude of the D-parameter by knowing the X-ray structure alone; Dstr is constructed from the metal-ligand bond lengths. In hexacoordinate Co(II) complexes it is applicable only in the segment of the compressed bipyramid where the ground electronic term 4B1g is orbitally non-degenerate so that the spin Hamiltonian formalism holds true. The D vs Dstr correlation is strongly non-linear and it is represented by a set of decreasing exponentials. In tetracoordinate Co(II) complexes, on the contrary, the angular distortion from the regular tetrahedron is crucial so that the appropriate structural parameter Dstr is constructed of bond angles. All of these empirical correlations originate in the electronic structure of metal complexes that can be modelled by the generalized crystal-field theory. As the barrier to spin reversal in the single-molecule magnets is proportional to the D-value, for a rational tuning and/or prediction of the single-molecule magnetic behavior knowledge/prediction of the D-parameter is beneficial. In this review, we present the statistical processing of an extensive set of structural and magnetic data of Co(II) and Ni(II) complexes, which were published over the past 15 years. Magnetostructural D-correlations defined for this data set are reviewed in detail.

This paper presents high-resolution digital measurements at low cost, combining oversample and averaging. Experiments of processing data between samples and between multiple temperature sensors in the same environment are conducted. They provide results with effective increase in the analog to digital converter bits, in correspondence with the minimization on the effects of noise. It is shown that averaging a set of small, low-cost sensors at a small microcontroller can give flexible access to improved measurement accuracy.

Vitamin D plays an important role in maintaining healthy mineralized skeleton. It is also consid-ered an immunomodulatory agent that regulate the innate and adaptive immune systems. Multi-ple observational studies have demonstrated the association between low level of serum 25-hydroxyvitamin D [25(OH)D] and presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies and oste-oarthritis (OA). Nevertheless, the specific benefits of vitamin D supplement for treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for improvement of disease ac-tivity of RA, SLE and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently from others since inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain serum 25(OH)D level at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis and fracture, and possibly 40 – 60 ng/mL (100 – 150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

The study addresses the urgent environmental issue of climate change, focusing specifically on the role of local food, which is produced and consumed locally, helps reduce carbon emissions by eliminating the need for long-distance transportation. Through quantitative analysis, this study elucidates the potential benefits in environmental impact achieved through the consumption of local food: the significant reduction in carbon emissions. Specifically, the consumption of local food is found to yield an annual decrease of 2,421,296 tCO2 emissions, representing 2.5% of South Korea’s total greenhouse gas emissions from the transportation sector. This reduction further translates into an estimated economic value of USD 54.23 million (KRW 70.5 billion). This study underscores the potential of local food consumption as a tangible strategy to overcome environmental problems. Moreover, its academic contribution lies in its comprehensive analysis of the economic and empirical impacts of local food consumption on environment. Moving forward, we propose policies such as supporting local food distribution networks, providing public education on local food, fostering the local food industry, and providing incentives to revitalize local food consumption.

Glycerol represents a useful functional component of heat-transfer fluids. Glycerol is known to be triboelectrically active. We report how the flow of glycerol, stopped in a cylindrical coiled pipe, influences horseradish peroxidase (HRP) enzyme. Namely, glycerol flow was pumped through the coil and then stopped. After that, we incubated the 0.1 µM solution of HRP near the side of the coil, and then adsorbed HRP onto mica. This operation markedly increased the HRP aggregation on mica in comparison with the control sample. We explain this phenomenon by the influence of triboelectrically induced electromagnetic fields. Our results can be useful in the development of flow-based systems for biosensors and bioreactors.

A series of D–π–A diketopyrrolopyrrole (DPP)-based small molecules have been designed for organic light-emitting diodes (OLEDs) and organic solar cells (OSCs) applications. Appling the PBE0/6-31G(d,p) method, the ground state geometry and relevant electronic properties were investigated. The first excited singlet state geometry and the absorption and fluorescent spectra were simulated at the TD-PBE0/6-31G(d,p) level. The calculated results reveal that the photophysical properties are affected through the introduction of different end groups. Furthermore, the electronic transitions corresponding to absorption and emission exhibit intramolecular charge transfer feature. It was disclosed that the designed molecules act not only as luminescent for OLEDs, but also donor materials in OSCs. Moreover, they also can be used as potential electron transfer materials using for OLEDs and OSCs.

The global population is at risk of vitamin D deficiency due to low exposure to sunlight and low intake of the vitamin through diet. The aim was to investigate in women the association between vitamin D status and parathyroid hormone (PTH), ultraviolet radiation, lifestyle, ethnicity, social conditions, and residential greenness. A 1-year longitudinal study assessed vitamin D status in 309 women, latitude 51° 14' N. Blood samples were taken four times throughout the year for analysis of 25(OH)D and serum PTH concentration. After each seasonal visit, the individuals completed 4-day diet diaries and used two dosimeter badges for 1 week to estimate weekly UVR exposure. A questionnaire was applied to provide information about lifestyle and their ethnicity. Residential greenness was measured by Normalized Difference Vegetation Index (NDVI), within a 1000 m radius around each participant’s home address. Women living in greener spaces were more likely to have improved vitamin D status (RR: 1.51; 95%CI: 1.13 – 2.02), as well as those who were more exposed to UVR (RR: 2.05; 95%CI: 1.44 – 2.92). Our results provided a first insight into the connection between vitamin D, residential greenness, and lifestyle in a region of temperate climate and with a high degree of urbanization.

Background Although the management of the majority of patients with IBS is dealt with by General Practitioners, randomized clinical trials and treatment guidelines are developed mostly in academic settings. Probiotics are one of the most investigated treatment modality for this condition. Scarce information is available as regards GPs attitude in this regard. Methods A literature search was performed to identify papers specifically dealing with probiotic treatment of IBS in the general practice setting. Moreover, the preliminary results of a survey on this topic conducted by the authors among general practitioners in a province in northern Italy are reported. Results Five papers specifically addressing probiotic treatment of IBS in general practice were found. The response rate varied from 4 to 100%. The prescription rate of probiotics by GPs in IBS varied from <10 to 46%, regardless of the patients’ bowel habits. Physicians’ satisfaction with this treatment varied from 20 to 93%. The variability of these results probably depends on factors such as differences in the interpretation of the available data on probiotics use in IBS and traditional/ cultural differences. Moreover, compliance with patient satisfaction, may play a role. Conclusions The reported data on the treatment of IBS with probiotics in general practice is scarce and inhomogeneous, thus it does not allow firm conclusions. It is suggested that the involvement in research on the use of probiotics in IBS of physicians working in general practice would be useful in order to pursue more reliable and useful results, since the majority of the IBS population is followed in general practice and may differ from the one represented in academic clinical trials.

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.

Renal uric acid (UA) reabsorption is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). Dotinurad selectively inhibits URAT1 and do not inhibit other UA transporters such as GLUT9, ATP-binding cassette transporter G2 (ABCG2) and organic anion transporter1/3 (OAT1/3). We discovered that dotinurad improved metabolic parameters and renal function in hyperuricemic patients. We consider a significance of high selectivity in inhibiting URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dotinurad inhibits selectively URAT1 and increases UA in the proximal tubules, and UA may compete with glucose for GLUT9, reducing glucose reabsorption. The inhibition of UA entry via URAT1 to liver and adipose tissues by dotinurad increased energy expenditure and decrease lipid synthesis and inflammation in rats. The inhibition of URAT1 in kidney, liver and adipose tissues improve metabolic parameters. CKD patients accumulate uremic toxins such as indoxyl sulfate (IS) in the body. ABCG2 regulates renal and intestinal excretion of IS which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into kidney, increasing plasma IS, which produces oxidative stress, inducing vascular endothelial dysfunction in CKD patients. The high-selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD and CVD.

D-Serine, a co-agonist of NMDA receptors has sparked a contentious debate within the scientific community regarding its status as a gliotransmitter or a neurotransmitter. This comprehensive review delves into the heart of this debate, offering a meticulous analysis of the existing evidence from various research methodologies. Immunostaining studies and cell-selective mutations provide compelling support for D-serine's neuronal origin, bolstering the serine shuttle model. In contrast, the gliotransmission hypothesis, proposing astrocytic synthesis and release, faces critical scrutiny as inconsistencies in supporting data emerge. In vivo microdialysis experiments unveil a neuronal contribution to D-serine release and its profound impact on synaptic plasticity, further strengthening the case for neuronal dominance. Counterarguments in favor of astrocytic D-serine release are systematically dissected, revealing inherent limitations and ambiguities. Collectively, the evidence corroborates D-serine's neuronal source and discounts the astrocytic hypothesis. This review underscores the need for scientific rigor when evaluating contentious topics and affirms the simplicity of the neuronal explanation, aligning D-serine with the serine shuttle model, thus advancing our comprehension of its pivotal role in synaptic function and cognitive processes. As the debate continues to evolve, this exploration encourages ongoing research to unravel the intricate mechanisms governing D-serine neurotransmission.

Centrifuges are commonly required devices in medical diagnostics facilities as well as scientific laboratories. Although there are commercial and open source centrifuges, costs of the former and required electricity to operate the latter, limit accessibility in resource-constrained settings. There is a need for low-cost, human-powered, verified and reliable lab-scale centrifuge. This study provides the designs for a low-cost 100% 3-D printed centrifuge, which can be fabricated on any low-cost RepRap-class fused filament fabrication (FFF) or fused particle fabrication (FPF)-based 3-D printer. In addition, validation procedures are provided using a web camera and free and open source software. This paper provides the complete open source plans including instructions for fabrication and operation for a hand-powered centrifuge. This study successfully tested and validated the instrument, which can be operated anywhere in the world with no electricity inputs obtaining a radial velocity of over 1750rpm and over 50N of relative centrifugal force. Using commercial filament the instrument costs about US$25, which is less than half of all commercially available systems; however, the costs can be dropped further using recycled plastics on open source systems for over 99% savings. The results are discussed in the contexts of resource-constrained medical and scientific facilities.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Background: According to newly published studies, patients with Coronavirus Disease 2019 (COVID-19) have significantly lower serum 25-hydroxyvitamin D 25(OH)D levels than those without the SARS-CoV-2 infection. Vitamin D insufficiency may be a predictor of poor prognosis in COVID-19 patients. Vitamin D supplementation is related to improved clinical outcomes in terms of intensive care unit (ICU) admission and death, particularly in individuals with moderate-to-severe forms of COVID-19 requiring hospitalization. Materials and methods: This placebo-controlled five-day study was performed on 100 hospitalized COVID-19 patients with vitamin D insufficiency randomized into two groups. Vitamin D in the form of a sublingual sprayable microemulsion (LYL love your life® sunD3 LYLmicro™) was given three times daily after breakfast, lunch, and dinner (daily dose 12,000 IU) to 52 patients with blood vitamin D levels below 30 ng/ml. 48 patients in the control group received a placebo spray in the same daily regiment. Results: We observed a statistically significant increase by 8.6 ng/ml in median vitamin D level after five days of high-dose vitamin D3 spray therapy. 90.2% of subjects reached normal serum levels of vitamin D. There was a strong correlation between changes in vitamin D and C-reactive protein (CRP) levels in individuals with moderately severe disease (p<0.05), while mild and severe cases showed no statistical significance comparing case and control groups. There were no statistically significant changes in ferritin and interleukin-6 (IL-6) levels. Conclusions: In this study, we demonstrated the possibility to rapidly increase circulating levels of vitamin D just in 5 days of high-dose intervention and found a statistically significant decrease of CRP levels in patients with moderately severe COVID-19. We were not able to detect statistically significant changes in ferritin and IL-6 levels during the 5-day vitamin D intervention.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

The impact of riparian wetlands on the cycling, retention and export of nutrients from land to water varies according to local environmental conditions and is poorly resolved in catchment management approaches. To determine the role a specific wetland might play in a catchment mitigation strategy, an alternative approach is needed to the high frequency and spatially detailed monitoring programme that would otherwise be needed. Here, we present a new approach using a combination of novel and well-established geochemical, geophysical and isotope ratio approaches. This was developed and tested against a 2-year high-resolution sampling programme in a lowland permeable wetland in the Lambourn catchment, UK. The monitoring programme identified multiple pathways and water sources feeding into the wetland, generating large spatial and temporal variations in nutrient cycling, retention and export behaviours within the wetland. This complexity of contributing source areas and biogeochemical functions within the wetland were effectively identified using the new toolkit approach. We propose that this technique could be used to determine the likely net source/sink function of riparian wetlands prior to their incorporation into any catchment management plan, with relatively low resource implications when compared to a full high frequency nutrient speciation and isotope geochemistry-based monitoring approach.

The post-hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid-immunotherapy (AIT). Previously, we have shown that one subpopulation of T regulatory cells results in phenotypically identifiable as functionally potentiated and memory cells in allergic children after 12 months of this immunoactive treatment. Indeed, AIT is the only known treatment able to reshape the detrimental immune response against the allergen into a not noxious one. Besides, VD is widely considered an immunoregulatory molecule endogenously produced and exogenously provided with foods and supplements that might interact with AIT mechanism and affect its outcome. Therefore, a post-hoc analysis of the clinical and immunological data of three different cohorts of allergic patients was performed. One cohort (N=70) was on standard symptoms-controlling pharmacological treatment while the other two (N=60 and N=35, respectively) were treated with AIT for 12 months. Among the first were observed a lower mean endogenous VD level (&lt;22 ng/ml) along with worse symptoms and higher use of medications. Remarkably, the comparison between two sub-cohorts of patients with serum VD above (N=32) or below (N=28) a cut-off value set at mean value (27 ng/ml) revealed that optimal improvement of all clinical and immune parameters was achieved (as expected by effective AIT), irrespective of the VD level. Notably, the third analysis, carried out on one cohort of AIT patients also taking concomitantly VD3 as food supplement (N=19), was distinguished by uppermost overall treatment outcome (amelioration of symptoms, lowest medications requirement, and reduction of total and allergen-specific IgE) as well as the increase of allergen-specific tolerogenic memory T regulatory cells. These findings suggest that endogenous VD level affects allergy severity and allergen immunotherapy effectiveness. Also, VD3 might be investigated as an add-on supplement to get the best out of immunotherapy in VD deficient/insufficient allergic patients. The immunogenic but low-allergenic mite allergoid used as bioactive agent might have contributed to minimize allergic and highlight immunological effects described here.

Background: To determine vitamin D supplementation frequency among infants, factors that influence adherence, and reasons for discontinuation of initiated vitamin D. Methods: This cross-sectional study was conducted using a questionnaire administered to the mothers via a face-to-face interview on 560 infants aged from 1 to 24 months admitted to outpatient clinics from June to December 2017. Results: A total of 351 infants were administered vitamin D, and the rate of supplementation in the first year of life was 83%, while it was only 28% between 13 and 24 months. The rate of vitamin D supplementation was higher among infants who were exclusively formula-fed (p<.05). When the data were analyzed using logistic regression analysis, only visit family physicians seems to be a statistically significant independent variable in increasing supplementation (p<.05). Compared with family refusal, the rate of discontinuation of vitamin D by the healthcare providers was higher after the first year of life (p<.05). The rates of vitamin D discontinuation by healthcare providers, especially by nurses who considered the duration of supplementation adequate, were statistically significantly higher when compared with the fontanel closure and other reasons (p<0.05). Conclusions: The rate of vitamin D supplementation was higher among families who visited family physicians, which suggests the importance of well-baby visits. Since vitamin D supplementation was less common among exclusively breastfed infants, mothers should be educated. Healthcare professionals need further education about the importance of vitamin D supplementation and indications for discontinuation.

Background: A Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/ml). Methods: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified and the library was prepared and sequenced on the Illumina Miseq platform. Results: The mean (±SD) age was 45.5 (±10.2) years with no defined co-morbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups were observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD while Parabacteroides, Butyricimonas, and Gordonibacter were abundant in the KOA_VDD group and Peptococcus, Intestimonas, Delftia, and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labeled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. Conclusion: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter, and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D, and knee osteoarthritis.

One of the biggest challenges in characterizing 2-D image topographies is finding a low-dimensional parameter set that can succinctly describe, not so much image patterns themselves, but the nature of these patterns. The 2-D Cluster Variation Method (CVM), introduced by Kikuchi in 1951, can characterize very local image pattern distributions using configuration variables, identifying nearest-neighbor, next-nearest-neighbor, and triplet configurations. Using the 2-D CVM, we can characterize 2-D topographies using just two parameters; the activation enthalpy and the interaction enthalpy. Initial investigations with two different representative topographies (``scale-free-like'' and ``rich club-like'') produce interesting results when brought to a CVM free energy minimum. Additional phase space investigations, where one of these two parameters has been set to zero, identify useful parameter ranges. Careful comparison of the analytically-predicted configuration variables versus those obtained when performing computational free energy minimization on a 2-D grid show that the computational results differ significantly from the analytic solution. The 2-D CVM can potentially function as a secondary free energy minimization within the hidden layer of a neural network, providing a basis for extending node activations over time and allowing temporal correlation of patterns.

Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)₂-VD. Extrarenal 1α-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public health-care issue with an estimated prevalence of more than a billion people worldwide. Among individuals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital nonskeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In individuals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.

Gasca D herbal formulation is an antidiabetic medicine for the management of diabetes mellitus produced exclusively from natural ingredients. The level of some essential elements (Copper, chromium, Cobalt, Iron, Manganese, Nickel and zinc) and toxic (Cadmium, Arsenic, Mercury, and Lead) heavy metals were determined using microwave plasma-atomic emission spectrometry (MP-AES). The aim of this study is to evaluate the levels of essential and toxic heavy metals and also identify bioactive compounds present in Gasca D herbal formulation. The result shows no traces of Lead, Mercury, Zinc, Arsenic and Zinc, Iron was found to have highest concentration 67.16 + 7.5 µg/g and Cadmium lowest concentration 0.4 + 0.03µg/g. GC-MS analysis of Gasca D herbal formulation revealed the presence of 14 biologically active compounds which include N-Formyl-beta-alanine, Paromomycin, 3,4-Altrosan, Benzamide, 1,3,4-Thiadiazol-2-amine, Carbamodithioic acid, Carbonic acid, alpha-D-Glucopyranoside, Ethyl isocyanide, 2-Propanesulfinic acid, Propanamide, 2-Butenenitrile, Dicyclopropyl carbinol, Isoxazolidine, 1,5-Hexadiene 10-Azido-1-decanethiol. Conclusion: The result indicates that the mean levels of toxic metals in Gasca D herbal formulation were below WHO permissible levels. Gasca D herbal formulation also contains various bioactive compounds that can have various medicinal application which can be used for the treatment of various diseases.

Blood-based biomarkers are much-needed diagnostic and prognostic tools for ALS. Canine degenerative myelopathy (DM) is recognized animal disease model to study the biology of human ALS. Serum derived exosomes are potential carrier that transport intercellular hormone-like messengers, together with their stability as carrier of proteins and RNA, make them ideal as biomarkers for a variety of diseases and biological processes. We study exosomal TDP-43 pattern as a surrogate biomarker that reflects biochemical changes in central nervous system. We isolated exosomes from canine serum using commercial exosome isolation reagents. TDP-43 and SOD1 profile in spinal cord homogenate lysate and that of serum-derived exosomes were found elevated in dogs with DM. We conclude levels of spinal cord TDP-43 and serum-derived exomes were similar in TDP-43 profiling, which warrant further investigation of disease sensitivity and specificity for establishing as a blood-based biomarker in canine DM.

Gauss quadrature integral approximation is extended to include integrals with a measure consisting of a continuous as well as a discrete component. That is, we give an approximation for the integral of a function plus its sum over a discrete weighted set.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

Vitamin D is a nutrient with anti-inflammatory properties whose role is currently being evaluated in COVID-19. Although studies are conflicting, they seem to suggest a role for vitamin D in reducing disease susceptibility but not in improving clinical outcome. In order to understand why vitamin D does not seem to have much effect on decreasing disease severity, it is essential to appreciate pulmonary vitamin D metabolism. To reach the pulmonary compartment, vascular endothelial cells would need to take up vitamin D from the blood stream, but they lack vitamin D receptor (VDR) and the activating enzyme CYP27B1. Endothelialitis – an important disease manifestation of COVID-19 – is therefore not expected to be directly affected by vitamin D. Bronchial epithelial cells are usually among the first to be infected with SARS-CoV-2. They do express both VDR and CYP27B1, but circulating vitamin D may not reach bronchial epithelial cells without transportation from the blood stream through the blood vessel wall. Inhalation therapy with vitamin D has therefore been suggested as an alternative for oral administration to bypass endothelial cells and efficaciously target bronchial epithelium. In conclusion, based on the principles of pulmonary vitamin D metabolism, it is not expected that vitamin D administration has a significant effect on COVID-19 severity. Vitamin D is more likely to reduce SARS-CoV-2 susceptibility, but reaching the airways with oral supplementation will be difficult and vitamin D inhalation therapy should be considered.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Background: The immunomodulatory role of 1,25-Dihydroxy vitamin D3 (1,25(OH)2D3) is exerted through its interaction with the Vitamin D receptor (VDR) present on pancreatic and immune cells. While a deficiency in Vitamin D has been linked to Type 1 Diabetes Mellitus (T1DM), the exact molecular mechanism driving this down-regulation in T1DM is yet to be fully understood. This study aimed to decipher differences in the expression of genes associated with Vitamin D metabolism in T1DM patients and to ascertain if there is a correlation between serum 1,25(OH)2D3 levels and the expression of these genes. We also sought to understand the influence of specific microRNAs (miRNAs) on the expression of Vitamin D metabolism genes in peripheral blood mononuclear cells (PBMCs) of T1DM patients. Furthermore, the study delved into the potential implications of altered Vitamin D metabolism genes and miRNAs on autoimmune processes. Methods: Utilizing real-time PCR, we assessed the expression profiles of genes encoding for 1-hydroxylases (CYP27B1) and 24-hydroxylases (CYP24A1), as well as related miRNAs, in PBMCs from 30 T1DM patients and 23 healthy controls. ELISA tests facilitated the measurement of 1,25(OH)2D3, GAD65, and IA-2 levels. Results: Our findings showcased down-regulated CYP27B1 mRNA levels, while CYP24A1 expression remained stable compared to healthy subjects (CYP27B1, p = 0.0005; CYP24A1, p = 0.205, respectively). In T1DM patients, the levels of has-miR-216b-5p were found to be increased, while the levels of has-miR-21-5p were decreased in comparison to the control group. Notably, no correlation was identified between the expression of CYP27B1 in T1DM patients and the levels of has-miR-216b-5p, has-miR-21-5p, and 1,25(OH)2D3. A significant negative correlation was identified between CYP27B1 mRNA levels in PBMCs of T1DM and IA2, but not with GAD65. Conclusions: The study highlights there were reduced levels of both CYP27B1 mRNA and has-miR-21-5p, along with elevated levels of has-miR-216b-5p in the PBMCs of T1DM. However, the absence of a correlation between the expression of CYP27B1, levels of has-miR-216b-5p, and the status of 1,25(OH)2D3 suggests the possible existence of other regulatory mechanisms. Additionally, the inverse relationship between IA2 autoantibodies and CYP27B1 expression in T1DM patients indicates a potential connection between this gene and the autoimmune processes inherent in T1DM.

Postprandial hyperlipidemia showing postprandial increase in serum triglyceride (TG) is atherogenic and associated with the development of coronary artery disease (CAD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed, however, this test is very time-consuming and is difficult to perform. Ele-vated serum TG levels reflect an increase in TG-rich lipoproteins (TRL) such chylomi-crons (CM), very low-density lipoproteins (VLDL) and their remnants (CM remnant [CMR] and VLDL remnant [VLDLR]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurements of apo B48 which is a constituent of CM and CMR, non-fasting TG which includes TG content in all lipoproteins including CM and CMR, non-high-density lipoprotein-cholesterol (non-HDL-C) which includes TRL and low-density lipoprotein, and remnant cholesterol, are useful to suspect the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an in-ducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with post-prandial hyperlipidemia have various atherogenic properties such as induction of in-flammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss and exercise, positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, bezafibrate, ezetimibe and eicosapentaenoic acid have shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glu-cagon like peptide 1 analogues, have shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments.

Suspended and deposited sediments in streams can interfere with filter-feeding caddisfly larvae by reducing feeding sites and feeding efficiency, potentially lowering densities, growth rates, and secondary production of an important trout prey. We conducted field studies at multiple stream sites with differing suspended sediment loads, and a laboratory study conducted under controlled conditions, together designed to examine the role of suspended sediments in the population dynamics and behavior of Brachycentrus occidentalis (Trichoptera: Brachycentridae) larvae in a Minnesota, USA, trout stream. Stream sites that had elevated turbidities and suspended sediments also had significantly more fine bottom substrates and higher substrate embeddedness. In addition, Brachycentrus densities were reduced, growth rates were slower, secondary production was reduced, and overall benthic macroinvertebrate taxa richness was lowest at the site with the highest suspended sediment loading. Colder water temperatures at one site also influenced Brachycentrus production. In 24-hour laboratory studies conducted in recirculating aquaria, the feeding activities of Brachycentrus larvae were reduced and positioning altered under high turbidities (500 nephelometric turbidity units, NTU) relative to low turbidities (50 NTU or lower). High suspended sediment loads have adversely affected filter-feeding caddisfly larvae by embedding and burying preferred coarse feeding substrates, altering their feeding positions and movements during highest flows, and ultimately impacting densities, growth rates, and secondary production.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

Background: It is assumed that the prevalence of hepatitis D in HBsAg-positive individuals reaches 4.5-13% in the world, and on average about 3% in Europe. Data from several European countries, including Slovakia, are missing or are from an older period. Methods: We analyzed all available data on hepatitis D from Slovakia, including reports from the Slovak Public Health Authority and the results of one prospective study, and three smaller surveys. The determination of anti-HDV IgG and IgM antibodies and/or HDV RNA was used to detect hepatitis D. Results: In the years 2005-2022, no confirmed case of acute or chronic HDV infection was reported in Slovakia. The presented survey includes a total of 343 patients, of which 126 were asymptomatic HBsAg carriers, 33 acute hepatitis B, and 184 chronic hepatitis B cases. In a recent prospective study of 206 HBsAg-positive patients who were completely serologically and virologically examined for hepatitis B and D, only 1 anti-HDV IgG positive and no anti-HDV IgM or HDV RNA positive cases were detected. In other smaller surveys, 2 anti-HDV IgG positive patients were found without the possibility of HDV RNA confirmation. In total, only 3 of 329 HBsAg-positive patients (0.91%) tested positive for anti-HDV IgG antibodies and none of 220 tested positive for HDV RNA. Conclusion: The available data show that Slovakia is one of the countries with a very low prevalence of HDV infection reaching less than 1% in HBsAg-positive patients. Routine testing for hepatitis D is lacking in Slovakia, and therefore it is necessary to implement testing of all HBsAg-positive individuals according to international recommendations.

Classification of human actions from uni-modal and multi-modal datasets is an ongoing research problem in computer vision. This review is aimed to scope current literature on data-fusion and action-recognition techniques and to identify gaps and future research direction. Success in producing cost-effective and portable vision-based sensors has dramatically increased the number and size of datasets. The rise in number of action recognition datasets intersects with advances in deep-learning architectures and computational support, both of which offer significant research opportunities. Naturally, each action-data modality - such as RGB, depth, skeleton, and infrared - has distinct characteristics; therefore, it is important to exploit the value of each modality for better action recognition. In this article we will focus solely on areas such as data fusion and recognition techniques in the context of vision with a uni-modal and multi-modal perspective. We conclude by discussing research challenges, emerging trends, and possible future research directions.

Elevated carbon dioxide (eCO₂) stimulates wheat grain yield, but simultaneously reduces protein (N) concentration. Also other essential nutrients are subject to change. This study is a comprehensive synthesis of wheat experiments with eCO₂, estimating effects on N, minerals (B, Ca, Cd, Fe, K, Mg, Mn, Na, P, S, Zn), and starch. Analysis was made by i) deriving response functions for the relative effect on element concentration in relation to CO₂ concentration, ii) meta-analysis to test the magnitude and significance of observed effects, and iii) relating CO₂ effects on minerals to effects on N and grain yield. Responses range from zero to strong negative effects of eCO₂ on mineral concentration, with largest reductions for the nutritionally important elements N, Fe, S, Zn and Mg. Together with the positive but small and non-significant effect on starch concentration, the large variation in effects suggests that CO₂-induced responses cannot be explained by a simple dilution model. To explain the observed pattern, uptake and transport mechanisms may have to be considered, along with the link of different elements to N uptake. Our study shows that eCO₂ has a significant effect on wheat grain stoichiometry, with implications for human nutrition in a world of rising CO₂.

Cyanobacterial harmful algal blooms (CyanoHABs) are increasing in prevalence and severity globally and locally in the Great Lakes region. CyanoHABs have the potential to produce serious adverse human health effects due to the production of cyanotoxins from cyanobacteria. Common routes of exposure include recreational exposure (swimming, skiing, and boating), ingestion, and aerosolization of contaminated water sources. Cyanotoxins have been shown to adversely affect several major organ systems contributing to hepatotoxicity, gastrointestinal distress, and pulmonary inflammation. We present three pediatric case-reports that coincided with CyanoHABs exposure with a focus on presentation of illness, diagnostic work-up, and treatment of CyanoHAB-related illnesses. Potential cyanotoxin exposure occurred while swimming in the Maumee River and Maumee State Park in Northwest OH during the Summer months which coincide with peak CyanoHAB activity. Primary symptoms included generalized macular rash, fever, vomiting, diarrhea, and severe respiratory distress. Significant labs included leukocytosis and elevated C-reactive protein. All patients ultimately recovered with supportive care. Symptoms following potential cyanotoxin exposure coincide with multiple disease states representing an urgent need to develop specific diagnostic tests of exposure.

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.

2,4-dichlorophenoxyacetic acid (2,4-D) is a globally used herbicide and is frequently found in water samples. This fact has prompted studies on its effects in non-target organisms, revealing significant alterations on liver structure and function. In this review, we evaluated the literature on the hepatotoxicity of 2,4-D, focusing on morphological damages, biomarkers of toxicity and affected liver functions. Searches were conducted on PubMed, Web of Science and Scopus and 83 articles were selected after curation. Among the studies, 72% used in vivo models and 30% used in vitro models. Additionally, 48% used the active ingredient, and 35% used commercial formu-lations in exposure experiments. The most affected biomarkers were related to a decrease in an-tioxidant capacity, including alterations in the activities of catalase and superoxide dismutase, and in the levels of malondialdehyde. Changes in energy metabolism, lipids, liver function, and xenobiotic metabolism were also identified. Furthermore, we found studies about the effects of 2,4-D in mixtures with other pesticides, as well as hepatoprotection trials. The reviewed data in-dicate that the reduction in antioxidant capacity and oxidative stress play an important role in 2,4-D-induced hepatotoxicity. However, the mechanism of action of the herbicide is still not ful-ly understood and further research in this area is needed.

Coronavirus disease (COVID-19) is an infectious disease caused by a new virus which causes respiratory illness. Older adults and people who have previous chronic medical conditions are at higher risk for more serious complications from COVID-19.Hypovitaminosis D is attributed to the increased risk of lung injury and acute respiratory distress syndrome (ARDS) as well as diabetes, Cardiovascular event and associated comorbidities, which are the main causes of severe clinical problem in COVID-19 patients. Considering the protective role of vitamin D through modulating the innate and adaptive immune system as well as inhibition of Renin Angiotensin System (RAS), vitamin D supplementation might boost the immune system of COVID-19 patients and reduce severity of the disease in vitamin D deficient individuals.