Although distributed additive manufacturing can provide high returns on investment the current markup on commercial filament over base polymers limits deployment. These cost barriers can be surmounted by eliminating the entire process of fusing filament by 3-D printing products directly from polymer granules. Fused granular fabrication (FGF) (or fused particle fabrication (FPF)) is being held back in part by the accessibility of low-cost pelletizers and choppers. An open-source 3-D printable invention disclosed here provides for precise controlled pelletizing of both single thermopolymers as well as composites for 3-D printing. The system is designed, built and tested for its ability to provide high tolerance thermopolymer pellets from a number of sizes capable of being used in a FGF printer. In addition, the chopping pelletizer is tested for its ability to chop multi-materials simultaneously for color mixing and composite fabrication as well as precise fractional measuring back to filament. The US$185 open-source 3-D printable pelletizer chopper system was successfully fabricated and has a 0.5 kg/hr throughput with one motor, and 1.0 kg/hr throughput with two motors using only 0.24 kWh/kg during the chopping process. Pellets were successfully printed directly via FGF and indirectly after being converted into high-tolerance filament in a recyclebot.

This article shows that the recently proposed latent D-scoring model of Dimitrov is statistically equivalent to the two-parameter logistic item response model. An analytical derivation and a numerical illustration are employed for demonstrating this finding. Hence, estimation techniques for the two-parameter logistic model can be used for estimating the latent D-scoring model. In an empirical example using PISA data, differences of country ranks are investigated when using different metrics for the latent trait. In the example, the choice of the latent trait metric matters for the ranking of countries. Finally, it is argued that an item response model with bounded latent trait values like the latent D-scoring model might have advantages for reporting results in terms of interpretation.

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.

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analysed its oral pharmacokinetics and its effects on a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), b) insulin signaling in the liver and c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associate with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation while sustaining glycaemia through liver-based mechanisms of glycolysis control.

It has been more than a century since Erlang published his paper in 1909. The classical queueing system for the M/D/c queue has been investigated by many authors. The key is to find the roots of an equation using explicit or numerical methods. We present an alternate form of explicit solution(s) of this/these root(s) using the Lambert-W function in this paper. In addition, the unsaturated probabilities of the number of customers in the system is derived explicitly in terms of this/these root(s). Finally, the mean number of customers in the system and the mean queueing delay are obtained from these probabilities. The exact queueing delay formula for the M/D/c queue is expressed in closed-form in terms of the root(s). Numerical results show that they are in excellent agreement with the numerical results published by Seelen, Tijms and Van Hoorn.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

A literature review was conducted to summarize the frequency of the D-allele of the angiotensin-converting enzyme-1 in all countries with available data. Using an ecological study design limited to high income countries, we found that the country-level frequency of the D-allele was associated with increased COVID-19 incidence and mortality.

If environmental exposures are shown to cause an adverse health outcome, reducing exposure should reduce the disease risk. Links between exposures and outcomes are typically based on ‘associations’ derived from observational studies, and causality may not be clear. Randomised controlled trials to ‘prove’ causality are often not feasible or ethical. Here the history of evidence that tobacco smoking causes lung cancer – in observational studies – is compared to that of low sun exposure and/or low vitamin D status as causal risk factors for the autoimmune disease, multiple sclerosis. Evidence derives from in vitro and animal studies, as well as ecological, case-control and cohort studies, in order of increasing strength. For smoking and lung cancer, the associations are strong, consistent, and biologically plausible – the evidence is coherent or ‘in harmony’. For low sun exposure/vitamin D as risk factors for MS, the evidence is weaker, with smaller effect sizes, but coherent across a range of sources of evidence, and biologically plausible. The association is less direct – smoking is directly toxic and carcinogenic to the lung, but sun exposure/vitamin D modulate the immune system, which in turn may reduce the risk of immune attack on self-proteins in the central nervous system. Opinion about whether there is sufficient evidence to conclude that low sun exposure/vitamin D increase the risk of multiple sclerosis, is divided. General public health advice to receive sufficient sun exposure to avoid vitamin D deficiency (<50nmol/L) should also ensure any benefits for multiple sclerosis.

Commonly employed methods for reversibly disrupting gene expression, such as those based on RNAi or CRISPRi, are rarely capable of achieving >80-90% downregulation, making them unsuitable for targeting genes that require more complete disruption to elicit a phenotype. Genetic deletion, on the other hand, while enabling complete disruption of target genes, often produces undesirable irreversible consequences such as cytotoxicity or cell death. Here we describe the design, development and detailed characterization of a dual-function "TRE-Lox" system for effecting either (a) doxycycline (Dox)-mediated downregulation or (b) genetic deletion of cathepsin D (CatD), based on targeted insertion of a tetracycline-response element (TRE) and two LoxP sites into the 5' end of the endogenous gene (CTSD). Using an optimized reverse-tetracycline transrepressor (rtTR) variant fused with the Krüppel-associated box (KRAB) domain, we show that CatD expression can be disrupted by as much as 98% in mouse embryonic fibroblasts (MEFs). This system is highly sensitive to Dox (IC50 = 1.46 ng/mL) and results in rapid (t1/2 = 0.57 d) and titratable downregulation of CatD. Notably, even near-total disruption of CatD expression was completely reversed by withdrawal of Dox. As expected, transient expression of Cre recombinase results in complete deletion of the CTSD gene. The dual functionality of this novel system will facilitate future studies of the involvement of CatD in various diseases, particularly those attributable to partial loss of CatD function. In addition, the TRE-Lox approach should be applicable to the regulation of other target genes requiring more complete disruption than can be achieved by traditional methods.

Water reuse for irrigation is increasingly recognized as an essential and economical strategy in areas with water scarcity. A simple, low-cost, low-maintenance, and highly efficient Pond-In-Pond (PIP) treatment system can be used for wastewater reuse. PIP is a treatment technology in which two types of ponds -- anaerobic and aerobic -- are combined into a single pond and consist of a deeper inner section entirely submerged within the outer pond. Previous studies on PIPs and PIP-like systems have reinforced the potential for reuse through promising performance results with BOD removal over 80% and a reduction in land area requirements by approximately 40%. Yet, no prior efforts have been made to understand the performance mechanism of such systems. This study makes use of two, 2-D modeling tools in developing a fundamental understanding of PIP flow dynamics and the expected performance. The modeling results showed that the PIP configuration offers improved flow diversion along with reduced flow velocity. Additionally, the PIP retained approximately 17% more (p<0.05) particles than the traditional pond with most of the particles concentrated within the inner pond. Lower velocity and the higher solids retention in the PIP thus allowed for better treatment performance compared to traditional ponds. The findings from this study can be used as preliminary data for future in-depth investigations of the PIP system leading toward effective and optimal designs. This will help address the major societal concern of water scarcity with low-cost and effective wastewater treatment.

Pyracantha angustifolia has been used in traditional medicine to treat a range of diseases of the stomach and improve digestion, blood circulation, diarrhea, dysentery, and hemostasis. This study evaluated bioactivity-guided fractionation as a means to identify therapeutic phytochemicals from P. angustifolia that can attenuate melanogenesis and oxidation. Seven compounds with inhibitory effects on melanin production and tyrosinase (TYR) activity, as well as ABTS and DPPH radical scavenging activities, and have not been reported as whitening materials, were isolated from the n-butanol fraction from P. angustifolia leaves (PAL). Among the seven compounds, p-hydroxybenzoic acid beta-d-glucosylester (HG), and cimidahurinine (CD) had strong inhibitory effects of melanin production, TYR activity, and ABTS and DPPH radical scavenging activities. Western blot analysis showed that HG and CD suppressed tyrosinase-related protein (TYRP)-1 and TYRP-2 expression. These results suggest that P. angustifolia containing active compounds, such as HG and CH, is a potent therapeutic candidate for the development of hypopigmenting agents.

Background and Aim: Cancer is a disease characterized by uncontrolled cell growth and invasion of tissues. It seems that personality differences and psychological factors are important factors that lead to different reactions to cancer. Therefore, the main purpose of the present study was to investigate the relationship between type D, stress level of life events, personality traits, and anxiety sensitivity in people with breast cancer attending to Tehran Bu-ali Hospital. Methods: The study was a correlational study in which 100 cancer patients referred to Bu-ali Hospital in Tehran, selected by the available sampling method from April to June 2018. The tools used included the Denollet DS-14 Type D Questionnaire, the Paykel Life events Questionnaire, the Eysenck Personality Questionnaire, the ASI Anxiety Scale, Floyd et al., Data analysis in this study is taken place by using SPSS software, two descriptive levels (percentage, frequency, etc.) and regression. Results: The study results showed that there is a relationship between type D personality with stress of life events, neurosis, extraversion, and psychopath dimensions of personality and anxiety sensitivity in breast cancer patients. Conclusion: Psychological factors play a role in the incidence and exacerbation of breast cancer, and ultimately patients with personality type D and personality traits such as psychosis and high anxiety sensitivity and more stress of life events show more symptoms.

Barriers to inventing electronic devices involve challenges of iterating electronic designs due to long lead times for professional circuit board milling or high-costs of commercial milling machines. To overcome these barriers this study provides open source (OS) designs for a low-cost circuit milling machine. First, design modifications for mechanical and electrical sub-systems of the OS D3D Robotics prototyping system are provided. Next, Copper Carve, an OS custom graphical user interface, is developed to enable circuit board milling by implementing backlash and substrate distortion compensation. The performance of the OS D3D circuit mill is then quantified and validated for: positional accuracy, cut quality, feature accuracy and distortion compensation. Finally, the return on investment is calculated for inventors using it. The results show by properly compensating for motion inaccuracies with Copper Carve, the machine achieves a motion resolution of 10 microns, which is more than adequate for most circuit designs. The mill is at least five times less expensive than all commercial alternatives and the material costs of the D3D mill are repaid from fabricating 20-43 boards. The results show that the OS circuit mill is of high-enough quality to enable rapid invention and distributed manufacturing of complex products containing custom electronics.

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.

Though Moracin D derived from Morus alba was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D was never unveiled so far. Thus, in the recent study, the apoptotic mechanism of Moracin D was elucidated in breast cancer cells. Herein, Moracin D exerted significant cytotoxicity in MDA-MB231 and MCF7 cells. Also, Moracin D increased sub G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and attenuated the expression of pro-cysteine aspartyl-specific protease (procaspase 3), c-Myc, cyclin D1, B-cell lymphoma 2 (Bcl-2),and X-linked inhibitor of apoptosis protein (XIAP) in MDA-MB231 cells. Of note, Moracin D reduced expression of Forkhead box M1 (FOXM1), β-catenin, Wnt3a, and upregulated glycogen synthase kinase 3 beta (GSK 3β) on Tyr216 along with disturbed binding of FOXM1 with β-catenin in MDA-MB-231 cells. Conversely, GSK3β inhibitor SB216763 reversed the apoptotic ability of Moracin D to reduce expression of FOXM1, β-catenin, pro-caspase3 and pro-PARP in MDA-MB-231 cells. Overall, these findings provide novel insight that Moracin D inhibits proliferation and induces apoptosis via suppression of Wnt3a/FOXM1/β-catenin signaling and activation of caspase and GSK3β

Thyroid hormones have a catabolic effect on bone homeostasis. Hence, this study aimed to evaluate serum vitamin D, calcium, and phosphate and bone marker levels and bone mineral density (BMD) among patients with different thyroid diseases. This cross-sectional study included patients with underlying thyroid diseases (n=64, hyperthyroid; n=53 euthyroid; and n=18, hypothyroid) and healthy controls (n=64). BMD was assessed using z-score and left hip and lumbar bone density (g/cm2). Results showed that the mean serum vitamin D Levels of all groups was low (<50 nmol/L). Thyroid patients had higher serum vitamin D levels than healthy controls. All groups had normal serum calcium and phosphate levels. The bone marker levels were significantly high in the hyperthyroid group and low in the hypothyroid group. The z-score for hip and spine did not significantly differ between thyroid patients and control groups. The hip bone density was remarkably low in the hyperthyroid group. In all groups, the serum vitamin D levels were below the cutoff value. However, thyroid patients had a higher serum vitamin D level than healthy controls. The carboxy terminal collagen crosslink and procollagen type I N-terminal propeptide levels were high in hyperthyroid patients and low in hypothyroid patients. Further, hyperthyroid patients had a low hip BMD.

Middle East region experiences a high prevalence of hypovitaminosis D, yet most genetic studies on Vitamin D have focused on European populations. Furthermore, there is a lack of research on the genomic risk factors affecting the elderly population, who are more susceptible to health burden. We investigated the genetic determinants of 25-hydroxyvitamin D levels in elderly Lebanese individuals (n=199) through a whole exome-based genome-wide association study. We identified new loci with suggestive evidence of an association with Vitamin D levels, including rs141064014 in the MGAM gene (P-value of 4.40 × 10−06) and rs7036592 in PHF2 (P-value of 8.43 × 10−06). A meta-analysis of the Lebanese data and the largest European genome-wide association study confirmed consistence replication of numerous variants, including rs2725405 in SLC38A10 (P-value of 3.73 x 10-08). Despite the lower performance of European-derived polygenic risk scores compared to the European estimations, it still effectively predicted Vitamin D deficiency among elderly Lebanese individuals. Our findings provide novel insights into the genetic mechanisms of Vitamin D deficiency in Middle Eastern elderly populations, facilitating the development of personalized approaches for more effective management of hypovitaminosis D. Additionally, we demonstrated that whole exome-based genome-wide association study is an effective method for identifying genetic components associated with phenotypes.

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

Background: the nature of alpha-D-mannose - natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections - in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. Methods: PRISMA systematic review approach was applied; Delphi Panel method used to target consensus on statements retrieved from evidence. Results: Based of regulatory definitions and research evidences, the mechanism of D-mannose does not involve a metabolic or immunological action while there is an uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue. Therefore, its mechanism of action is not directed to host structures but to structures (bacteria) external to the host's tissues. Conclusions: From a regulatory perspective, D-mannose maintains the current medical device classification: new regulations and legal judgments can add further considerations. From a pharmacological perspective, research is driven versus synthetic mannosides: no further considerations are expected on alpha-D-mannose.

This research emphasizes a meta-heuristic Modified Ant Lion Optimizer (MALO) optimization approach for simultaneous utilization of DSTATCOM devices and distributed Photovoltaic (PV) sources with network reconfiguration in a radial power distribution scheme. In a radial power distribution network with network reconfiguration majority of the research is based on Constant Power model analysis. However, it is noticed that load models have a substantial impact on the distributed PV sources and the D-STATCOM device's optimal size and position. The effect of the Constant Power (CP) and Polynomial (ZIP) with load growth load models for the simultaneous insertion of distributed PV sources and DSTATCOM devices with network reconfiguration examined in this research work for power system planning. The penetration levels of distributed PV sources considered for the investigation are 25%, 50%, 75%, and 100%. The principal objective of this research is to reduce network total power losses, enhance the voltage magnitude profile at all buses, and reduce the overall operating cost while adhering to equality and inequality constraints. The proposed algorithm verified on 118-node test systems. The investigation is carried out for planning network upgradation to a High Voltage Distribution System(HVDS) on 317 nodes in the rural Bangalore Electricity Supply Company Limited(BESCOM) radial distribution scheme. Simulated results obtained by this method are validated with the BAT algorithm and available techniques in the literature.

Several observational studies have indicated the potential associations between calcium, vitamin D(Vit-D) and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subjected to residual confounding factors and reverse causation. Therefore, we aim to explore the bidirectional causal effects between serum calcium, Vit-D, PTH and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratio (OR) with their 95% confidence intervals (CIs). The results of the inverse-variance-weighted method did not re-veal any causal relationship shared between genetically predisposed calcium (OR = 0.92, 95% CI: 0.80-1.06, P = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83-1.19, P = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a de-creased level of PTH (beta: -0.19, 95%CI: -0.34 to -0.04, P = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms by which IBS affects serum PTH need to be further investigated.

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.

Low 25 OH vitamin D (25(OH)D) in preterm infants is a risk factor of bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and lung histological alterations evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120nmol/L is also a risk factor for BPD or death. This retrospective single-center cohort study included all infants born <31 weeks gestational age without major malformation with at least a determination of 25(OH)D <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120nmol/L (50.5% vs 43.9%, p=0.53). The logistic regression identified weight (OR 0.997, 95%CI [0.995-0.998]) and term (OR 0.737, 95%CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95%CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.

(1) Background: The issue of human adaptation to the Arctic environmental factors is relevant. The adaptation can be assessed through dynamic monitoring of the functional state of a person during his/her stay there. The vitamin D level in blood is one of the markers of the functional reserves of the human body and can contribute to more successful adaptation in the Arctic. (2) Methods: The study involved 38 participants in the scientific and educational expeditionary project "Arctic Floating University-2021". Blood collection for determination of vitamin D content was carried out at the beginning of the expedition. A dynamic study was carried out for 20 days in the morning and in the evening during a marine scientific expedition to the Arctic. The main parameters of the functional state of the participants were assessed using instrumental psychophysiological, projective and questionnaire methods. Statistical methods: Mann-Whitney U-test, correlation analysis using the Spearman coefficient. (3) Results: It was found that at the beginning of the expedition, the functional state of participants with severe vitamin D deficiency is characterized by a shorter average duration of RR intervals and reduced SDNN values, which may indicate a higher level of regulatory mechanisms tension. The pronounced differences in the nature of the dynamic series of objective and projective working capacity parameters were manifested most clearly. According to the subjective questionnaire characteristics of well-being, activity and mood, no significant features of the participants with vitamin D deficiency were revealed. (4) Conclusion: The participants with vitamin D deficiency in blood are characterized by a reduced adaptive capacity during the expedition to the Arctic.

Open-source 3-D printing has played a pivotal role in revolutionizing the additive manufacturing (AM) landscape, by making distributed manufacturing economic, democratizing access, and fostering far more rapid innovation than antiquated proprietary systems. Unfortunately, some 3-D printing manufacturing companies began deviating from open-source principles and violating licenses for the detriment of the community. To determine if a pattern has emerged of companies patenting clearly open-source innovations, this study presents three case studies from the three primary regions of open-source 3-D printing development (EU, U.S. and China) as well as three aspects of 3-D printing technology (AM materials, an open-source 3-D printer, and core open-source 3-D printing concepts used in most 3-D printers). The results of this review have shown that non-inventing entities called patent parasites are patenting open-source inventions already well-established in the open source community and in the most egregious cases commercialized by one (or several) firms at the time of the patent filing. Patent parasites are able to patent open-source innovations by using a different language, vague patent titles and broad claims that encompass enormous swaths of widely diffused open-source innovation space. This practice poses a severe threat to innovation and several approaches to irradicate the threat are discussed.

In this paper, an intelligent blind guide system based on 2D LiDAR and RGB-D camera sensing is proposed, and the system is mounted on the smart cane. The intelligent guide system relies on 2D LiDAR, RGB-D camera, IMU, GPS, Jetson nano B01, STM32 and other hardware. The main advantage of the intelligent guide system proposed by us is that the distance between the smart cane and obstacles can be measured by 2D LiDAR based on Cartographer algorithm, thus achieving Simultaneous localization and mapping (SLAM). At the same time, through the improved yolov5 algorithm, pedestrians, vehicles, pedestrian crosswalks, traffic lights, warning posts, stone piers, tactile paving and other objects in front of the visually impaired can be quickly and effectively identified. Laser SLAM and improved yolov5 obstacle identification tests were carried out inside a teaching building on the campus of Hainan Normal University and on a pedestrian crossing on Longkun South Road in Haikou City, Hainan Province. The results show that the intelligent guide system developed by us can drive the wheels and omnidirectional wheels at the bottom of the smart cane, and give the smart cane a self-leading blind guide function like a "guide dog", which can effectively guide the visually impaired to avoid obstacles and reach the predetermined destination, and can quickly and effectively identify the obstacles on the way out. The laser SLAM speed of this system is 25~31FPS, which can realize the short-distance obstacle avoidance and navigation function both in indoor and outdoor envionments. The improved yolov5 helps to identify 86 types of objects, the recognition rate for pedestrian crosswalks and for vehicles are 84.6% and 71.8%, respectively; the overall recognition rate for 86 types of objects is 61.2%, and the obstacle recognition rate of the intelligent guide system is 25-26FPS.

This study aims to test empirical research on the effect of financial resource ability, research and development (R &amp; D) on innovation orientation and competitive position. This study also examines the critical mediating role of innovation orientation and competitive position to achieving new products performance (NPP). This study used a quantitative research approach by comparing data from service industry and manufacture industry in Indonesia included in Indonesian-State-Ownership companies. The analysis unit in this study used middle managers and top managers who responsible for managing divisions within the Indonesian-State-Ownership companies. The number of respondents studied in this study was 287 sample. The purposive sampling technique was used in taking the research sample. This study indicated that financial resources abilities, research and development (R &amp; D) abilities positive effect on innovation orientation and competitive position. This study also testing the importance role of innovation orientation and a competitive position to enhancing new products performance (NPP).

Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A-D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A-D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The investigation involves the utilization of molecular modeling and computational chemistry tools, with a specific focus on Conceptual DFT. These techniques are applied to examine the chemical reactivity of Talarolide A and Talaropeptides A-D, shedding light on their potential for interacting with various biological targets. The research reveals insights into the chemical reactivity of Talarolide A and Talaropeptides A-D, uncovering active reaction sites and potential biological targets. Talarolide A demonstrates robust anti-inflammatory properties and antitumor activity against diverse cancer cell lines, while Talaropeptide A displays antimicrobial efficacy against both bacteria and fungi. The study underscores the significance of comprehending the chemical reactivity of natural marine products for advancing pharmaceutical development. By employing computational tools such as Conceptual DFT, this research uncovers crucial information about the active sites and potential targets of Talarolide A and Talaropeptides A-D. The findings contribute to the broader understanding of marine-derived peptides and their prospects as pharmaceutical agents, though further investigations are necessary to fully elucidate their pharmacological attributes.

Background: Studies have demonstrated the link between vitamin D-related genetic variations and non-skeletal outcomes. We aimed to identify all available data on the association of vitamin D-related genetic variations with non-alcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible study must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3,495 articles were identified. After systematic review, twelve studies were in-cluded. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indi-cating the role of vitamin D in the pathogenesis of NAFLD.

A nanostructured electrochemical bi-sensor system for analysis of milks has been developed using the Layer by Layer technique. The non-enzymatic sensor [CHI+IL/CuPcS]2, is a layered material containing a negative film of the anionic sulfonated copper phthalocyanine (CuPcS) acting as electrocatalytic material, and a cationic layer containing a mixture of an ionic liquid (IL) (1-butyl-3-methylimidazolium tetrafluoroborate) that enhances the conductivity and chitosan (CHI) that facilitates the enzyme immobilization. The biosensor ([CHI+IL/CuPcS]2-GAO) results from the immobilization of galactose oxidase on the top of the LbL layers. FTIR, UV-vis and AFM have confirmed the proposed structure and cyclic voltammetry has demonstrated the amplification caused by the combination of materials in the film. Sensors have been combined to form an electronic tongue for milk analysis. Principal Component Analysis has revealed the ability of the sensor system to discriminate between milk samples with different lactose content. Using PLS-1 calibration models, correlations have been found between the voltammetric signals and chemical parameters measured by classical methods. PLS-1 models provide excellent correlations with lactose content. Additional information about other components such as fats, proteins and acidity can also be obtained. The method developed is simple and the short response time permits its use in assaying milk samples on-line.

Causative agent of the viral pneumonia outbreak in the World identified as SARS-CoV2 leads to a severe respiratory illness like SARS and MERS. The pathogen spreading has turned into a pandemic dissemination and increased the mortality rate. Therefore, useful information is urgently necessary for effective control of the disease. Our study shows the existence of unvarying sequence with no mutation, including ORF1ab regions in 134 high-quality filtered genome sequences of SARS-CoV2 downloaded from the GISAID database. We have detected this sequence stability by using MAUVE analysis and pairwise alignment with Global Needleman Wunsch algorithm for each two different sequences, reciprocally. They also confirmed all these results were also with the Clustal W analysis. The first 6500 bp including ORF1ab region is an unvarying sequence. According to the highest TM-score of predicted protein structure analysis, the results showed it is very similar to spike protein of feline infectious peritonitis virus strain UU4 (PDB 6JX7) depending on amino acid sequences encoded by this unvarying region, and N-acetyl-D-glucosamine is the ligand of this protein. These results have confirmed that N-acetyl-D-glucosamine could play an important role in controlling of SARS-CoV-2. Also, our molecular docking analysis data supports a strong protein-ligand interaction of N-acetyl-D-glucosamine with spike receptor-binding domain bound with ACE2 (PDB 6M0J) and RNA-binding domain of nucleocapsid phosphoprotein (PDB 6WKP) from SARS CoV-2. Therefore, binding of N-acetyl-D-glucosamine to these proteins could inhibit SARS CoV-2’s replication. In the present work, we have suggested providing a repurposing compound for further in vitro and in vivo studies and new insights for ongoing clinical treatments as a new strategy to control of SARS-CoV-2 infections.

Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTI; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here we present data from a post-hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), coronavirus disease 2019 (COVID-19)-induced infection is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding, often occurs in subjects with weak multiple risk factors and co-morbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (vWF). Central to activity of these biomarkers are their receptors and signaling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19, and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of vWF, P-selectin and fibrinogen are present with still low levels of D-dimer. Progression to vWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devises and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to the intermediate and elder patients. Therefore, it’s imperative to identify identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify prognostic factors. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients.

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and it has been implicated in the pathogenesis of inflammation, insulin resistance and obesity. Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are the main form of vitamin D: the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity and cardiovascular disease. It's interesting to note that several long-term studies also revealed an inverse correlation between vitamin D level and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects, in fact while some studies demonstrated improvements in insulin sensitivity, glucose and lipid metabolism, others revealed no significant effect on glycemic control and inflammation. The aim of this review is to provide insight into the molecular basis of the relationship between vitamin D, insulin-resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

Polymorphism of vitamin D3 receptor (VDR), has been associated with low bone mineral density and other immune and metabolic disorders; however, its impact on mortality of female dialysis patients is not well studied. This study aimed to identify bone mass-related factors, VDR gene polymorphism, and their interaction with morbid conditions that could influence all-cause mortality. In 246 female dialysis patients, age 43±11 years on continuous ambulatory dialysis peritoneal; 48%, haemodialysis; 23% and automated peritoneal dialysis; 29%. Tscore, Ca, PO4, albumin, hs-CRP, osteoprotegerin, fetuin, osteocalcin, iPTH, PINP and β-CTx were measured. PCR products were digested with Bsml to analyze VDR polymorphisms. Patients n=229; were followed for a median of 17 (15-31) months; 42 patients died. Bsml polymorphism, bb=64% and BB+Bb=36%. Hs-CRP was the risk of death in multivariate Cox Analysis. Patients with bb and inflammation had a higher risk of death (HR 2.48, 95% CI 1.08-5.68) persisted after adjustment for age, diabetes and iPTH (HR 2.33; 95% CI, 1.01-8.33) and after further adjustment for vintage, albumin, osteoprotegerin and vitamin D therapy (HR 3.49; 95% CI, 1.20-10.9). We may conclude that the presences of the bb genotype of VDR and inflammation have additive effects on all cause-mortality in females in CAPD, APD, and HD patients.

Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.

Active vitamin D derivatives (VDDs) – 1α,25-dihydroxyvitamin D3/D2 and their synthetic analogs – are well-known inducers of cell maturation with the potential for differentiation therapy of acute myeloid leukemia (AML). However, their dose-limiting calcemic activity is a significant obstacle to using VDDs as an anticancer treatment. We have shown that different activators of the NF-E2-related factor-2/Antioxidant Response Element (Nrf2/ARE) signaling pathway, such as the phenolic antioxidant carnosic acid (CA) or the multiple sclerosis drug monomethyl fumarate (MMF), synergistically enhance the antileukemic effects of various VDDs applied at low concentrations in vitro and in vivo. This study aimed to investigate whether glutathione, the major cellular antioxidant and the product of the Nrf2/ARE pathway, can mediate the Nrf2-dependent differentiation-enhancing activity of CA and MMF in HL60 human AML cells. We report that glutathione depletion using L-buthionine sulfoximine attenuated the enhancing effects of both Nrf2 activators concomitant with downregulating vitamin D receptor (VDR) target genes and the activator protein-1 (AP-1) family protein c-Jun levels and phosphorylation. On the other hand, adding reduced glutathione ethyl ester to dominant negative Nrf2-expressing cells re-stored both the suppressed differentiation responses and the downregulated expression of VDR protein, VDR target genes, as well as c-Jun and P-c-Jun levels. Finally, using the transcription factor decoy strategy, we demonstrated that AP-1 is necessary for the enhancement by CA and MMF of 1α,25-dihydroxyvitamin D3-induced VDR and RXRα protein expression, transactivation of the vitamin D response element, and cell differentiation. Collectively, our findings suggest that glutathione mediates, at least in part, the potentiating effect of Nrf2 activators on VDDs-induced differentiation of AML cells, likely through the positive regulation of AP-1.

Oil-tea (Camellia oleifera) is a woody oil crop whose nectar includes galactose derivatives that are toxic to honey bees. Interestingly, some mining bees of the genus Andrena can entirely live on nectar (and pollen) of oil tea and are able to metabolize these galactose derivatives. We present the first next-generation genomes for five and one Andrena species that are respectively specialized and non-specialized oil-tea pollinators, and combining with published genomes of six other Andrena species which did not visit oil-tea, we performed molecular evolution analyses on genes involved in metabolism of galactose derivatives. Six genes (NAGA, NAGA-like, galM, galK, galT, and galE) involved in galactose derivatives metabolism were identified in the five oil-tea specialized species, but only five (with the exception of NAGA-like) were discovered in the other Andrena species. Molecular evolution analyses revealed that NAGA-like, galK and galT in oil-tea specialized species appeared under positive selection. RNASeq analyses showed that NAGA-like, galK, and galT were significantly up-regulated in the specialized pollinator A. camellia compared to the non-specialized pollinator A. chekiangensis. Our study demonstrated that the genes NAGA-like, galK, and galT had played an important role in the evolutionary adaptation of the oil-tea specialized Andrena species.

The aim of this study was to develop a novel nanostructured lipid carriers (NLCs) with hepatocytes targeting as carriers for the magnetic resonance imaging (MRI) contrast agent (i.e., magnetic nanostructured lipid carriers, MNLCs), and to evaluate the targeting ability of the MNLCs with T2-weighted MRI both in vitro and in vivo. Here, the galactose-octadecylamine (Gal-ODA) conjugates were synthesized by chemical coupling reaction between lactose acid (LA) and octadecylamine (ODA). Then the superparamagnetic iron oxide (SPIO) loaded nanostructured lipid carrier (conjugated by Gal-ODA, Gal-NLC-SPIO) was prepared by emulsification-ultrasonic method using monoglyceride as lipid materials. The Gal-NLC-SPIO with a diameter of about 50 nm could specifically internalize into LO2 (human hepatic cell line) cells. In vitro MRI results also proved the specific targeting ability of Gal-NLC-SPIO to LO2 cells. The in vivo MR imaging experiments using an orthotopic intrahepatic xenograft tumor model further validated the hepatocytes targeted effect of Gal-NLC-SPIO. The results of this study suggested that Gal-NLC-SPIO can be used as a contrast agent to aid in the diagnosis of hepatic diseases.

In this work we discuss the insights from activity landscape, docking and molecular dynamics towards the understanding of the structure-activity relationships of dual inhibitors of major epigenetic targets: lysine metiltransferase (G9a) and DNA metiltranferase 1 (DNMT1). The study was based on a novel data set of 50 published compounds with reported experimental activity for both targets. The activity landscape analysis revealed the presence of activity cliffs, e.g., pairs of compounds with high structure similarity but large activity difference. Activity cliffs were further rationalized at the molecular level by means of molecular docking and dynamics simulations that led to the identification of interactions with key residues involved in the dual activity or selectivity with the epigenetic targets.

Access to nasopharyngeal swabs for sampling remain a bottleneck in some regions for COVID-19 testing. This study develops a distributed manufacturing solution using only an open source manufacturing tool chain consisting of two types of open source 3-D printing and batch UV curing, and provides a parametric fully free design of a nasopharyngeal swab. The swab was designed using parametric OpenSCAD in two components (a head with engineered break point and various handles), which has several advantages: i) minimizing print time on relatively slow SLA printers, ii) enabling the use of smaller print volume open source SLA printers, iii) reducing the amount of relatively expensive UV resin, and iv) enabling production of handle on more accessible material extrusion 3-D printers. A modular open source UV LED box was designed, fabricated for $45 and tested for batch curing. Swabs can be fabricated for $0.06-$0.12/swab. The results of the mechanical validation tests showed that the swabs could withstand greater forces than would be expected in normal clinical use. The swabs were also able to absorb a significant amounts of synthetic mucus materials and passed abrasion and handling tests. The results show the open source swab are promising candidates for clinical trials.

The influence and importance of research and development (R&D) for business sustainability have gained increasing interests, especially in the high-tech sector. However, the efforts of R&D might cause complex and mixed impacts on the financial results considering the associated expenses. Thus, this study aims to examine how R&D efforts may influence business to improve its financial performance considering the dual objectives: the gross and the net profitability. This research integrated a rough-set-based soft computing technique and multiple criteria decision-making (MCDM) methods to explore this complex and yet valuable issue. A group of public listed companies from Taiwan, all in the semiconductor sector, was analyzed as a case study. Initially, more than 30 variables were considered, and the adopted soft computing technique retrieved 14 core attributes—for the dual profitability objectives—to form the evaluation model. The importance of R&D for pursuing superior financial prospects is confirmed, and the empirical case demonstrates how to guide an individual company to plan for improvements to achieve its long-term sustainability by this hybrid approach.

Low-lying coastal communities are often threatened by compound flooding (CF), which can be determined through the joint occurrence of storm surges, rainfall and river discharge either successively or in close succession. The trivariate distribution can demonstrate the risk of the compound phenomenon more realistically rather than considering each contributing factor independently or in a pairwise dependency. Recently vine copula has been recognized as the highly flexible approach to constructing a higher dimensional joint density framework. In such construction, parametric class copula with parametric univariate marginal distributions is often involved. Such incorporation can lack flexibility due to parametric functions with prior distribution assumptions about their univariate marginal and/or copula joint density. This study introduces the vine copula approach in a nonparametric setting by introducing Bernstein and Beta kernel copula density in establishing trivariate flood dependence. The proposed model is applied to 46 years of flood characteristics collected on the west coast of Canada. The univariate flood marginal distribution is modelled using nonparametric kernel density estimation (KDE). The 2-D Bernstein estimator and Beta kernel copulas estimator are tested independently in capturing pairwise dependencies to establish D-vine structure in a stage-wise nesting approach in three alternative ways, each by permutating the location of the conditioning variable. The best-fitted vine structure is selected using goodness-of-fit (GOF) test statistics. The performance of the nonparametric vine approach is also compared with the vine constructed in the parametric and semiparametric fitting procedure. Investigation reveals that the D-vine constructed using Bernstein copula with normal KDE marginals nonparametrically performed well in capturing dependence of the compound events. Finally, the derived nonparametric model is used in the estimation of trivariate OR- and AND-joint return periods, further employed in estimating failure probability (FP) statistics. The trivariate return periods for the AND-joint case are higher than for the OR-joint case for the same flood combination. Also, the trivariate flood hazard results in a high-value FP than bivariate and univariate events. Ignoring the trivariate dependence could result in the underestimation of FP

This paper explores the Wilsonian renormalization group of probe-D-branes, focusing on the Dirac-Born-Infeld (DBI) action. The analysis involves deriving the constant of motion and formulating the Wilsonian renormalization group equation. The study extends to the infrared regime, considering both zero and non-zero temperatures. Additionally, thermodynamic aspects related to the functional form of the grand potential are discussed. The investigation provides insights into the renormalization of probe-D-branes and their thermodynamic properties.

The absolute time and relative time are defined in terms of the 4-D Euclidean space. Our universe is the 3-D x₁x₂x₃ quantized photon space which follows the absolute time simultaneity when the universe moves along the absolute time axis of ct. The length expansion of Dx = gDx₀ is derived under the condition of the absolute time (ct) simultaneity. From the similarity between this length expansion of Dx = gDx₀ and the energy increasing of E = gE₀, it is assumed that the energy is proportional to the particle size of Dx. The extension of this assumption to the 4-D Euclidean space gives the new definition that the particle energy (E) is the 4-D volume. Then, the particle mass energy is defined as E= mc² = cDtDV = gE₀. The masses of the elementary particles are originated from the 4-D warped volume of the photon space because the particle is the warped photon space with the velocity of v < c. Therefore, the Higgs boson concept in the standard model (SM) is not needed in the present 3-D quantized space model (TQSM). The scalar boson with the spin of zero, photon with the spin of 1 and graviton with the spin of 2 are the two-boson states. Therefore, the observed Higgs boson is reinterpreted as the two-boson state of the scalar boson with the spin of zero. The cosmic muon observation and twin paradox are explained by using the absolute time and relative time. The relative time is the observed time in the twin paradox and cosmic muon observation. In the twin paradox, a person who travels the long distance is more aged than a person on the earth in terms of the relative time ages because of the space and time conversion effect (STCE effect) of the moving space distance (x). But twins are in the same ages in terms of the absolute time without STCE effect. The fast-moving cosmic muon has the expanded half-life from the time expansion of the relative time. Also, the quantum entanglement and Pauli exclusion principle are explained. The quantum base of the photon space line connects two entangled particles. Two particles and quantum base system is fluctuated along the absolute time axis by the time clicking when one particle is measured. Another particle is instantly selected by the time clicking. This is called as the quantum entanglement. The photons which are the flat photon space with the constant speed of c along the space axis and absolute time axis have the 4-D photon velocity of c_eff = 2^0.5 c. Total 10-D Euclidean space including three 3-D quantized spaces and one absolute time axis is required for the electric charges (EC), lepton charges (CC) and color charges (CC) of the elementary particles. The 3-D photon space is very stiff along the absolute time (ct) axis and very soft along the space axes. The Coulomb force through the photons (2EM waves) of the space fluctuations is much stronger than the Gravitational force through the gravitons (G waves) of the time fluctuations between two electrons.

Structure-based design and synthesis of two biphenyl-N-acyl-β-D-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

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.

The aim of this work is to compare two softwares (MAUD and TOPAS) based on the Rietveld algorithm and to test the concept of tolerance factor using the dissolution at high temperature of yttrium into BaTiO₃. In general, both softwares give up different values of the crystalline parameters however the trends are similar in most cases but the analysis of the strain and crystallite size in the BaTiO₃ crystals suggests that, in this particular case, MAUD offered results more consistent with the expected behavior. Using the crystalline parameters calculated by Rietveld, the tolerance factor values were obtained and these data suggest even better stability in the crystalline structure than that expected using theoretical parameters. Tolerance factor concept also indicates that Ti⁴⁺ should be preferred.

Calorie restriction (CR) has been shown to prolong the lifespan of humans, but enforcing long-term CR is difficult. Therefore, a compound that reproduces the effect of CR without CR is needed. In this review, we summarize the current knowledge on compounds with CR mimetic (CRM) effects. More than 10 compounds have been listed as CRMs, some of which are conventionally categorized as upstream-type CRMs showing glycolytic inhibition while the others are categorized as downstream-type CRMs that regulate or genetically modulate intracellular signaling proteins. Among these, we focus on upstream-type CRMs and propose their classification as compounds with energy metabolism inhibition effects, particularly glucose metabolism modulation effects. The upstream-type CRMs reviewed include chitosan, acarbose, sodium-glucose cotransporter 2 inhibitors, and hexose analogs such as 2-deoxy-D-glucose, D-glucosamine, and D-allulose, which show anti-aging and longevity effects. Finally, we discuss the molecular definition of upstream-type CRMs.

Rapid industrialization, urbanization, and population explosion in sub-Saharan Africa escalate environmental Lead levels with subsequent elevation of blood Lead levels in children. Nutrition status, age, and genetics govern one’s susceptibility to Lead toxicity. This study expounded this susceptibility by relating blood Lead levels, d-aminolevulinic acid dehydratase enzyme activity (ALAD), and genetic variations of proteins that code for ALAD enzyme in urban children of Uganda. Spectrophotometric analysis for blood Lead (BL), hemoglobin levels, and determination d-levels aminolevulinic acid dehydratase enzyme activity of the blood samples from 198 children were performed prior to a polymerase chain reaction and restriction fragment length digestion for ALAD polymorphism was done. Up to 99.5% of samples coded for the ALAD1 allele whereas 0.05% coded for ALAD2. Genotypes ALAD2-2 members had elevated BLL (mean 14.1 µg/dL) and reduced ALAD enzyme activity compared to others. This, therefore, implies that the majority of children hoard BL which may affect them later in life.

Most authors have investigated the role of mannoproteins on wine quality but very few analyze the use of grape derived polysaccharides as they are not commercially available. Purified grape derived polysaccharides from red wine (WPP) and winemaking by-products (DWRP: Distilled Washing Residues Polysaccharides) were used as potential fining agents to modulate white wine flavour. Phenolics and volatile compounds were analyzed in control and wines treated with WPP, DWRP and commercial mannoproteins (CM) after one and twelve months of bottling, and a sensory analysis was conducted. WPP and DWRP, rich in rhamnogalacturonans-II, showed as good modulators of wine aroma and astringency. Improvement of wine aroma was related to an increase of all volatile families expect higher alcohols and volatile acids. The modulation of astringency and bitterness was related to a reduction in the proanthocyanidin content and its mean degree of polymerization. Extracts with polysaccharides with higher protein contents presented higher retention of volatile compounds, and DWRP extract showed more positive effects on the overall aroma. Our novel results open the possibility of obtaining valuable polysaccharides from distilled washing residues of wine-pomaces, which could promote its valorization as by-product. This is the first time to describe the potential use of this by-product.

Cellulose nanocrystals (CNCs) are a kind of nano-inclusions that have experienced tremendous expansion in the material industry due to their outstanding mechanical qualities, sizable surface area, and capacity for functional tuning. Due to their vast potential, however, present practises fall short of fully using them. For example, employing CNCs in various matrices with various surface chemistries can be challenging; this problem tends to get worse if the focus is furthered on bio-based applications. This paper reviews the use of CNCs as fillers in natural and man-made polymers; we have explored in depth the production, characterisation, and of CNCs from various sources and their inclusion into various matrices. Surface alterations and the introduction of CNCs in biodegradable polymer can have a significant impact on several industrial behemoths such as tissue engineering and biomedical applications; therefore, pursue of current manuscript is extremely warranted. Throughout the manuscript various assembly techniques that involves alteration and adjustment of polymer network in building up a hydrogel with higher fracture energy and mechanical properties are also included. From rheological perspective the hydrogel processing is also discussed with some models routinely used in the literature to describe these hydrogels. Finally, bio-based hydrogels mechanically reinforced with CNCs such as Xanthan Gum, Alginate, protein, and polysaccharides were discussed.

Chronic oxidative stress in long-distance runners adversely affects conditioning. Therefore, it is important to objectively assess and monitor oxidative stress but measuring oxidative stress can be invasive or require skill to measure. Therefore, this study aimed to verify whether skin autofluorescence (SAF), a noninvasive, rapid, and easily calculable metric for calculating advanced glycation end products (AGEs), is useful as an oxidative stress biomarker. The subjects were 50 young Japanese male long-distance runners (aged 20.2 ± 1.2 years); 35 average male university students (aged 19.8 ± 1.1 years) served as controls. The interactions and relationships between SAF and plasma pentosidine and oxidative stress markers (reactive oxygen metabolite-derived compounds [d-ROMs], biological antioxidant potential [BAP], and the BAP/d-ROMs ratio) in runners were examined, and SAF in the runners and controls was compared. The results suggest that plasma pentosidine in runners is associated with oxidative stress markers and that plasma pentosidine can assess oxidative stress. However, SAF was not validated as an oxidative stress marker because it was not associated with oxidative stress marker. In future, clarifying the factors affecting SAF may clarify the relationship between SAF, plasma pentosidine, and oxidative stress markers.

With the advent of COVID19, the attitude of health authorities around the world, led mainly by the West, demanded a level of proof as evidence for cheap, non-patented remedies while promoting expensive, patented, and untested remedies by using emergency use authorization and special provisions afforded to the status of a pandemic emergency. Western science has neither a tested nor a valid historical basis of a logical system that informs to authenticate scientific practices. Here we use a logical heuristic derived from ancient Buddhist logic, which is consistent with the conduct of modern science. We applied the heuristic to show that enough evidence was available for using cost-effective early therapies such as vitamin D supplementation as a public health measure during the first half of 2020. Strong supporting evidence has since accumulated. Apart from political and financial decisions incompatible with science and other conflicts of interest, a critical barrier to evaluating and approving early therapies appears to be the fallacy that the randomized controlled trial (RCT) is the superior proof method in medical hypotheses, including those for nutrients. Logically, no reason exists why properly designed retrospective, ecological, and naturalistic studies with adequate sample sizes and applied appropriate statistical methods would not be as valid as RCTs, especially when elucidating a causative factor instead of treatment. That assertion is particularly true for nutrient deficiencies, interventions, and other cost-effective therapies. Leading health authorities’ failure or refusal to consider other study types (because of either poor logic or vested interest) probably contributed to the spread of misinformation, symptomatic disease, complications, and deaths from COVID19. Partial immunity derived from vaccines and the later development of more contagious variants—and thus a sense of acceptance that SARS-CoV-2 had progressed from a pandemic to an endemic—shows the hollowness of the initial promotions and mandates of vaccines as a cure. Adequate knowledge was available in 2020 to advise that SARS-CoV-2 will continue to mutate, with variants emerging a few times per year, making the vaccine less effective. Emerging evidence confirms that natural immunity better protects against new variants than vaccination against the spike protein. Had vitamin D been adopted as part of the public health measure through a broader supplementation program in 2020 or even today (through sun exposure or as a prophylactic or adjunct therapy early on), the viral spread and symptomatic disease may have been suppressed, with minimal lockdowns and quarantine, and economic harm. The pandemic could have been halted with a significantly reduced need for hospitalization, complications, and deaths, potentially saving millions of lives.

Background/Aim: Rapid onset of facial ptosis can impact physical appearance and compromise the outcomes of facelift procedures. The level of vitamin D has a potential correlation with collagen formation and its deficiency with inflammatory processes that affect the breakdown of hyaluronic acid. This study aims to investigate the potential relationship between accentuated facial ptosis in women and low levels of vitamin D. Furthermore, it aims to explore preventive measures or strategies to slow down facial ptosis and enhance the longevity of facelift results. Materials and Methods: The study was focused on monitoring the vitamin D levels in women and men with advanced facial ptosis and comparing them with a control group. Results: Notably, a direct association between gender and serum vitamin D levels was observed, indicating less sustainable outcomes in women. Conclusion: Women face additional challenges in the aging process due to hormonal shifts after menopause or premenopausal, which are associated with osteoporosis and lower vitamin D levels.

Brain fog with compromised ability to concentrate has been the most frequent Long Covid (LC) complaint. This is due to an increased transforming growth factor (TGF) β/interferon (IFN)-γ ratio with consequently increased bradykinin (BKN), especially in Caucasian females. Brain and lung blood vessels “leak.” This same ratio is increased in Alzheimer’s disease (AD), but decreased in Parkinson’s disease (PD), because CD4⁺ and CD8⁺ T cells are differentially affected by the invading associated viruses, e.g., SARS CoV2, HIV, Varicella Zoster (VZV) aka Human Herpesvirus 3 (HHV3), HBV, HCV, …. In Covid-19 CD147 receptors on immune cells are critical in generating the increased TGF-β/IFN-γ and those on endothelial cells, platelets, and erythrocytes are critical to the abnormal microvascular blood flow. ACE2 receptors on pneumocytes and enterocytes enable pulmonary and GI entry, initiating gut dysbiosis. Epigenetics, methylation, magnesium, vitamin D, the B vitamins, and antioxidants suggest that these issues can be surmounted. Biochemical, physiologic, and epidemiologic data are analyzed to answer these questions. An LC model is presented and discussed in the context of the most recent research. Suggestions to avoid these and other worrisome concerns are included. Other topics discussed include estrogen, the gut microbiome, type 2 diabetes (T2D), and homocysteine.

This research aims to obtain empirical evidence of the influence of the masculinity of male CEOs on the of research & development, this research seeks to identify the influence of the face of mas-culinity of male CEO’s on the of research & development. The study used a quantitative approach with population and research samples using companies listed on the Indonesia Stock Exchange from 2016 to 2021. The study collected images of faces identified as male CEOs from data from the Indonesia Stock Exchange website and company as utilizing Google searches. The data analysis method in this study used Regression Ordinary Least Square (OLS) with Stata Software. Stata software is one of the regression completion procedures that has a high degree of flexibility in re-search that connects theories, concepts and data that can be done on variables in research. The findings empirically explain that the higher the face value of male CEO masculinity has an impact on reducing research & development costs, and vice versa the lower the face value of male CEO masculinity has an impact on increasing research & development. The practical implications of the research results can help the Indonesian Association of Accountants in developing Financial Accounting Standard No. 19 in Indonesia. The theoretical implications of the research results can explain the Theory of Agency and the Theory of Consistency of Behavior. The policy implications of the results of the study can provide empirical evidence that the higher the facial value of male CEO masculinity has an impact on reducing research & development, while also the lower the face value of male CEO masculinity has an impact on increasing research & development.

Abstract: The genus Acaryochloris is unique among phototrophic organisms due to the dominance of chlorophyll d in its photosynthetic reaction centres and light-harvesting proteins. This allows Acaryochloris to capture light energy for photosynthesis over an extended spectrum of up to ~760 nm in the near infra-red (NIR) spectrum. Acaryochloris sp. has been reported in a variety of ecological niches, ranging from polar to tropical shallow aquatic sites. Here, we report a new Acarychloris strain isolated from an NIR-enriched stratified microbial layer 4-6 mm under the surface of stromatolite mats located in the Hamelin Pool of Shark Bay, Western Australia. Pigment analysis, by traditional spectrometry/fluorometry, flow cytometry and spectral confocal microscopy identify unique patterns in pigment distribution that likely reflect niche adaption. For example, unlike the original A. marina species (type strain MBIC11017), this new strain, Acarychloris LARK001, shows little change in the chlorophyll d/a ratio in response to changes in light wavelength, displays a different Fv/Fm response and lacks detectable levels of phycocyanin. Indeed, 16S rRNA analysis supports the identity of the A. marina LARK001 strain as distinct from the A. marina HICR111A strain first isolated from Heron Island, previously found on the Great Barrier Reef, under coral rubble on the reef flat. Taken together, A. marina LARK001 is a new cyanobacterial strain adapted to the stromatolite matts in Shark Bay.

Adequate serum vitamin D and iron levels are thought to positively influence physical training adaptations and mood. The purpose of this prospective, observational, study was to investigate relationships between serum 25-OH vitamin D and serum ferritin levels with body composition and athlete burnout symptoms. Seventy-three collegiate athletes (49 female) from 7 indoor and outdoor sports were tested pre-season and post-season for: nutrient biomarkers (serum 25-OH vitamin D and serum ferritin) via venipuncture; body composition (total lean mass, bone mineral densi-ty/BMD, and % body fat) via dual energy x-ray absorptiometry (DXA) scans; and athlete burnout symptoms (post-season) via the athlete burnout questionnaire (ABQ). When male and female co-horts were combined, significant relationships were noted between pre-season serum 25-OH vit-amin D versus the change (∆: post-season minus pre-season) in both BMD (r=-0.34;p=0.0003) and % body fat (r=-0.28;p=0.015). Serum ferritin ∆ was significantly associated with lean mass ∆ (r=-0.34;p=0.003). For burnout symptoms, serum 25-OH vitamin D ∆ significantly explained 20.6% of the variance for devaluation of sport in the male cohort only. Across time, serum 25-OH vitamin D levels increased while serum ferritin levels decreased, non-significantly, in both males and fe-males. Relationships between nutrient biomarkers and body composition were opposite of physio-logical expectations.

Since it was proposed, the Robot Operating System (ROS) has fostered solutions for various problems in robotics in the form of ROS packages. One of these problems is Simultaneous Localization and Mapping (SLAM), a problem solved by computing the robot pose and a map of its environment of operation at the same time. The increasingly availability of robot kits ready to be programmed and also of RGB-D sensors often pose the question of which SLAM package should be used given the application requirements. When the SLAM subsystem must deliver estimates for robot navigation, as is the case of applications involving autonomous navigation, this question is even more relevant. This work introduces an experimental analysis of GMapping and RTAB-Map, two ROS compatible SLAM packages, regarding their SLAM accuracy, quality of produced maps and use of produced maps in navigation tasks. Our analysis aims ground robots equipped with RGB-D sensors for indoor environments and is supported by experiments conducted on datasets from simulation, benchmarks and from our own robot.

Organic light-emitting diodes (OLEDs) have garnered considerable attention in academic and industrial circles due to their potential applications in flat panel displays and solid-state lighting technologies, leveraging the advantages offered by organic electroactive derivatives over their inorganic counterparts. The thin and flexible design of OLEDs enables the development of innovative lighting solutions, facilitating the creation of customizable and contoured lighting panels. Among the diverse electroactive components employed in the molecular design of OLED materials, the benzophenone core has attracted much attention as fragment for synthesis of organic semiconductors. On the other hand, the benzophenone also functions as a classical phosphor with high intersystem crossing efficiency. This characteristic makes it as compelling candidate for effective reverse intersystem crossing, potentially leading to the development of thermally activated delayed fluorescent (TADF) emitters. These emitting materials witnessed a pronounced interest in recent years due to their incorporation in metal-free electroactive frameworks and the capability to convert triplet excitons into emissive singlet excitons through reverse intersystem crossing (RISC), consequently achieving exceptionally high external quantum efficiencies (EQEs). This review article comprehensively overviews the synthetic pathways, thermal characteristics, electrochemical behaviour and photo-physical properties of the derivatives based on benzophenone. Furthermore, we explore their applications in OLED devices, both as host materials and emitters, shedding light on the promising opportunities that benzophenone-based compounds present in advancing OLED technology.

Cathode materials based on SrCoO3- perovskite-type oxides hold great potential, given the huge oxygen permeability exhibited by the cubic phase of this oxide, which must be stabilized though suitable cationic substitutions. We present here two novel materials of the series Sr1-xYxCoO3- (x= 0.1, 0.2), prepared by solid state reactions. The crystalline structure was explored by neutron powder diffraction. At RT, we identified a subtle tetragonal superstructure, yet preserving the wanted framework of vertex-sharing CoO6 octahedra. A noteworthy result of the neutron analysis is the presence of conspicuous amounts of oxygen vacancies, ordered in layers and responsible for the formation of the mentioned superstructure. The stability was investigated by thermal analysis, using thermogravimetry (TGA). The electrical conductivity gave a maximum value of 800 °C of 122 S·cm–1. To determine the resistance associated with the oxygen reduction reaction (ORR), electrochemical impedance spectroscopy as a function of temperature was carried out, finding a value for the activation energy of Ea= 0.82 eV. This is a much lower value than that usually obtained for cathodes with a high catalytic activity for the oxygen reduction reaction. In single-cell tests, the materials generated a power density up to 0.25 Wcm−2 at 800ºC, using pure H2 as fuel. All these features make this perovskite a suitable candidate as cathode material in intermediate-temperature SOFCs

Long Covid has become a blight, its economic consequences overwhelming. But Long Covid (LC) may represent persistent Covid-19 in those with preexisting Candida overgrowth (CO). The features shared by both are striking. LC may be a growing subset of CO. The altered tryptophan metabolism encountered in LC is driven by IFN-γ in reaction to CO. Females are robust producers of IFN-γ, yet estrogen promotes CO.The consequent decline in serotonin and melatonin triggers the mood swings and sleeplessness respectively in LC. The low serotonin, the primary messenger in the gut brain axis, creates autonomic dysfunction. The CO induced gut dysbiosis and leaky gut initiate an autoimmune path. TNFα seen in both LC and this opportunistic yeast is at the center of the cytokine triad that leads to neurodegeneration. The Western diet, high in carbohydrates, alcohol, and glutamate, is exploited by this commensal turned parasite. Residual SARS CoV2 and Candida generate abundant ROS, inducing mitochondrial dysfunction. Alcohol tastes different for many with LC, because acetaldehyde requires functioning hepatic mitochondria. This article delves into the complex physiology and biochemistry that drive the symptoms of this conspicuous connection. Recent research has revealed innovative approaches that might address this global scourge, including D-mannose for the immune dysfunction and butyrate for the gut dysbiosis created by and seen in both LC and intestinal Candidiasis.

Revenue-sharing (RS) contracts are a common approach to incentivize innovation of upstream suppliers by addressing the uneven profit distribution between upstream and downstream firms. Considering the possible overconfidence characterizing decision makers in the supply chain, we investigate the effect of the RS contract and the tendency of overconfidence of supply chain members on the investment in R&D of key components of products in the context of an upstream supplier that is the leader in the R&D and production of key components. We find that regardless of the bargaining power of either party, a RS contract can increase the R&D investment in key components. Regarding the effects of overconfidence of either downstream manufacturer or up-stream supplier, it can increase the R&D investment in key components. Supplier (manufacturer) overconfidence can harm their own profits but increase the profits of the manufacturer (supplier), and when the level of overconfidence is below a certain threshold, the damage to their own profits is less than the increase in each other's profits, thus benefiting the whole supply chain. In addition, we also find a joint effect of RS contracts and overconfidence: when the bargaining power of the supplier is low, the RS contract has a certain compensatory effect on the loss of their own profits caused by overconfidence.

These three syndromes - long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - have many symptoms in common. The common denominator remains elusive. The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis. In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT). The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.

Controlling water and food contamination by pathogenic organisms requires quick, simple, and low-cost methods. using affinity between mannose and type I fimbriae in the cell wall of Escherichia coli bacteria as evaluation elements compared to the conventional plate counting technique enables a reliable sensing platform for the detection of bacteria. In this study, a simple new sensor based on electrochemical impedance spectroscopy (EIS) for rapid and sensitive detection of Escherichia coli was developed. Biorecognition layer of the sensor was formed by covalent attachment of p-carboxyphenylamino mannose (PCAM) to gold nanoparticles (AuNPs) electrodeposited on the surface of glassy carbon electrode (GCE). The resultant structure of PCAM was characterized and confirmed using FTIR. The developed biosensor demonstrated a linear response with a logarithm of bacterial concentration (R2 = 0.998) in the range of 1.3 × 10 1~ 1.3 × 106 CFU.mL−1with the limit of detection of 2 CFU.mL−1 within 60 min. The sensor did not generate any significant signals with two non-target strains, demonstrating high selectivity of the developed biorecognition chemistry. Selectivity of the sensor and its applicability to analysis of the real samples was investigated in samples of tap water. Overall, the developed sensor has shown to be promising for the detection of E. coli pathogen in water due to its high sensitivity, short detection time, low cost, high specificity, and user-friendliness.

Ultraviolet (UV) radiation has both harmful and beneficial effects on human health. It can cause skin damage and cancer, but also provides the primary source of vitamin D. Additionally, UV radiation affects energy metabolism in mice with metabolic diseases and has protective effects on hypertension and cardiovascular diseases.Metabolic Syndrome is a collection of metabolic dysfunctions such as dyslipidemia, hypertension, hyperglycemia, abdominal/central obesity, and insulin resistance. Chronic UVR exposure suppressed obesity and type 2 diabetes in high-fat diet-fed mice, while vitamin D supplementation did not replicate these effects. On the other hand, topical application of nitric oxide (NO) donors replicated UV effects on mice, and NO scavengers prevented the positive impact of UV. UVR may prevent the development of obesity and metabolic syndrome through mechanisms that depend on UVR-induced NO, not vitamin D. Exposure to sunshine has a protective impact on blood pressure and cardiovascular disease. Although lower vitamin D concentration is linked to increased hypertension and the incidence of CVD, oral vitamin D supplementation does not decrease blood pressure or the risk of CVD, indicating that vitamin D may not mediate the beneficial effects of sun exposure. Instead, NO plays a crucial role as an endogenous vasodilator, produced by the vascular endothelium. Solar UVA may release nitrogen oxides from skin storage into the bloodstream, lowering blood pressure and cardiovascular mortality.In conclusion, UVR exposure could be a promising non-pharmacological intervention for metabolic syndrome, hypertension, and CVD prevention, and NO may play a crucial role in mediating these effects. Further research is needed to explore the precise mechanisms and identify the optimal doses and exposure times of UVR.

Background Bangladesh has been attracting international students on various subjects in recent times. Every year students from different parts of the world come to study undergraduate and postgraduate courses, mostly at private universities in Bangladesh. This study evaluates the depression status among international students who are studying dentistry in Bangladesh. Methods This cross-sectional survey was conducted among International undergraduate dental students who enrolled in the Bachelor of Dental Surgery program in nine public and private dental colleges in Bangladesh. A total of 206 students completed the survey, and CES-D 10 items Likert scale questionnaire was used for data collection. The Cronbach alpha for CES-D 10 scale items for this population is 0.812. Results The majority of the students (79.5%) are below 24 years of age, and students who cannot communicate well in Bengali (Bangla), about 60% of them have experienced depression. About 77.3% (p< 0.00) of the international students having financial difficulties exhibited depression. The international students who went through financial problems were two times more likely to suffer from depression (OR=2.38; p-value <0.01). Conclusion This study tried to highlight the struggles faced by international students in Bangladesh studying dentistry. It is evident from the findings that several factors influence students' mental well-being during demanding dental education years.

Background & Aims: The covid19 is a world changing challenge. Furthermore, this disease challenges our capacities to change our point of view in the domain of infectiology, immunology and global public health. Many trials try some drug such as antiviral (lopinavir, remdesivir) interferon, and the chloroquine. Unfortunately, all approach is not really convincing at this time. We are proposing another approach on this issue. In infectiology there are two protagonists : the host and its immune system versus pathogens and its virulence. Our approach focuses on an intervention on the host’s immune system and how stimulate and modulate its reactions. Methods: We searched on PubMed and Google Scholar databases for French and English-language studies, without a limit of date of publications, for randomized clinical trials, meta-analyses, reviews, systematic reviews, observational studies, case report. We performed a review on the field of immunology enhancements by nutrients use. Results: We identified groups of vitamins (D and C), oligo-elements (magnesium, zinc, selenium) and nutrition advice which enhance immune system response. Indeed, these supplements have some proved properties in modulating and stimulating the immune system. For example, a recent study demonstrates that vitamin D deficiency is linked with the severity of covid19. Majority of the population has a deficiency in these elements. According to this, we propose a therapeutic protocol using these elements to reach an efficient therapy against covid19 by enhancing host’s immune system. Conclusion: Due to this serious pandemic, any solutions must not be disregarded. The nutrition way is an entire part of the solution.

The impact of nutrition on immunity is an intense area of research. Malnutrition is linked to a higher risk of microbial infections, while severe infections usually lead to a nutritional imbalance in affected patients. The nutritional status has an impact on the severity of the ongoing SARS-CoV-2 infection. Studies conducted on small numbers of patients have shown the benefits of maintaining optimal vitamin (B12 and D) and mineral (zinc and magnesium) balance in reducing the intensity of COVID-19. Although consuming a balanced diet with a healthy lifestyle is always desirable, the importance of such practice is even more meaningful during the COVID-19 pandemic. Keeping an optimal balance of vitamins and minerals through healthy dietary habits helps to maintain a robust immune system that is essential to combat invading microbial pathogens, including SARS-CoV-2.

Origins of the time, mass, electric charges and magnetic monopoles are explained. The energies, electric charges and magnetic charges of the particles are defined as E = cDtDV and |q| = cDt = E/DV, and |q_m| = c²Dt, respectively, for the 3-D quantized spaces warped along the time axis direction of ct in the 4-D Euclidean space. The energy (or mass) and charges (or electric charges and magnetic charges) are the vectors along the time axis of ct in the 4-D Euclidean space. This new concept is closely connected to the wave function of the quantum mechanics. The electric charges, magnetic charges and energies have the property of the space direction independence. Magnetic monopoles (charges) are the force carrying bosons with the inside electric field time loop. Electric monopoles are the elementary fermions. Photon space fluctuations are explained with the quantized magnetic charges.

The cause of sarcoidosis is unknown, and vitamin D is contraindicated to treat the condition. We therefore ask what causes sarcoidosis and why vitamin D can be dangerous for those so afflicted. We propose a contrary hypothesis: sarcoidosis is a physiological process of defense against cancer that requires the substrate vitamin D. We tested this hypothesis, finding many case reports involving sarcoidosis and cancer—further cases of cancer mimicry by sarcoidosis. Several reports describe spontaneous healing of cancer in the presence of sarcoidosis. In the context of the granulomas of sarcoidosis, monocytes are the site of vitamin D release. Furthermore, active vitamin D can control cancer cells by using the vitamin D receptors of the nucleus. That granulomas consistently do not caseate is explained as a confrontation with human molecules and the cancer cells’ complete absorption. The striking fact that granulomas of sarcoidosis mostly lack cancerous cells is interpreted as a result of a well-functioning sarcoidosis process. We view the typical sarcoidosis monocytic synthesis of active vitamin D as a successful defense against cancer: a theory we call the “endogenous program organizing cancer apoptosis” (EPOCA).

Cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) are endemic threats to cassava production. To fill the existing gaps in the understanding of the epidemiology of these diseases in Côte d’Ivoire, nationwide field surveys were conducted in 2016, 2017 and 2020. The leaf samples collected were analysed by PCR. CBSD was not detected in all fields visited. However, an increase of CMD incidence was observed from 45.95% in 2016 to 51.37% in 2020 while CMD severity remained moderate over the years with a mean value of 2.29. Low whiteflies number was observed in field and decreasing over the years. Molecular analysis allowed detection of East African cassava mosaic Cameroon virus (EACMCMV) in single as well as in mixed infection with African cassava mosaic virus (ACMV). Single EACMCMV infection, which was detected only in three agroecological zones of the eastern Côte d’Ivoire in 2016, spread throughout the country in 2017 and became more widespread in 2020 with a preponderance in the central and southern zones, whereas the ACMV+EACMCMV coinfection has spread to the entire zones studied. Knowing the dynamics of the evolution of these viruses across the country, better disease management strategies could be adopted to control the disease.

Ketamine is a dissociative anesthetic and antidepressant with several biological targets. Among the many targets, ketamine, notably, has an antagonistic effect on molecular N-methyl-D-aspartate (NMDA) receptors and has been identified as a non-competitive inhibitor of these receptors. Although ketamine has a wide range of therapeutic uses in the clinical setting, it is often used recreationally due to its psychoactive and analgesic effects. Regardless of the indication, prenatal exposure to ketamine has been widely investigated. The misuse of this drug, particularly in pregnant women, has been a point of concern. The neurotoxic potential of ketamine positions it as a danger to a developing fetus. Furthermore, the ability of ketamine to cross the blood-placental barrier poses a threat to the health and maturation processes of the neonate. This paper reviewed published work that explores the mechanisms through which prenatal ketamine exposure can cause altered neurodevelopment, neurobehavior, and the physiological consequences that follow. By exploring investigations using multiple different subjects such as: rodents, non-human primates, and human subjects, this paper develops a full picture of the existing data to generate a strong foundation for improved and informed public health policies.

Cardiovascular diseases (CVDs) and chronic kidney disease (CKD) are frequently interconnected and their association leads to an exponential increase in the risk of both fatal and non-fatal events. In addition, the burden of arrhythmias in CKD patients is increased. On the other hand, the presence of CKD is an important factor that influences the decision to pursue cardiac device therapy. Data on CKD patients with device therapy is scarce and mostly derives from observational studies and case reports. Cardiac resynchronization therapy (CRT) is associated with decreased mortality, reduced heart failure symptoms and improved renal function in early stages of CKD. Implantable cardioverter defibrillators (ICDs) are associated with a significant reduction in the mortality of CKD patients only for the secondary prevention of sudden cardiac death. Cardiac resynchronization therapy defibrillator (CRT-D) is preferred in patients that meet the established criteria. The need for cardiac pacing is 3-fold higher in dialysis patients. CKD is an independent risk factor for infections associated with cardiac devices.

Coronavirus Disease 2019 (COVID-19) exhibits a significant variation in presentation of symptoms ranging from mild to severe life-threatening symptoms, including death. COVID-19 infection susceptibility has been linked with various covariates, but studies in Qatar are limited. Data from Qatar Biobank (QBB) (n = 10,000; 18- to 79-year-old adults) were analyzed for associations between sociodemographic and lifestyle factors and susceptibility to COVID-19. Logistic regression was used to assess the associations between COVID-19 and age, gender, body mass index (BMI), smoking status, education level, dietary patterns, supplement use, physical activity, history of bariatric surgery, diabetes, and hypertension. In total, 10.5% (n = 1045) of the participants had COVID-19. Compared to non-smokers, current and ex-smokers had lower odds of having COVID-19 (odds ratio [OR]= 0.55; 95% CI: 0.44-0.68 and OR= 0.70; 95% CI: 0.57-0.86, respectively). Vitamin D supplement use was associated with an 18% reduction of the likelihood of contracting COVID-19 (OR = 0.82; 95% CI: 0.69-0.97). Obesity (BMI ≥30 kg/m2), history of bariatric surgery and higher adherence to the modern dietary pattern– characterized by consumption of foods high in saturated fat and refined carbohydrates– were positively associated with COVID-19. Our findings indicate that adopting a healthy lifestyle may be helpful in the prevention of COVID-19 infection.

Background: BNT162b2 represents the authorized mRNA vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS–CoV–2) causing Covid–19. Methods: We conducted a prospective, single–center observational study with 273 employees of a medical facility to determine the efficacy and safety of the BNT162b2 third dose in relation to sex and BMI, and explore the possible determinants of neutralizing IgG and 25–hydroxy (25–OH) vitamin D levels. Results: At the median follow–up of 4.7 months, 38 of the participants had Covid–19 following vaccination. The incidence of adverse events (AEs) was significantly higher in females vs. males (p < 0.0108) and subjects with a high BMI of ≥ 30 kg/m2 vs. low BMI (p < 0.0117). The values of IgG were significantly enhanced in males vs. females (p < 0.0004), participants with high BMI vs. low BMI (p < 0.0003), a high number of ≥3 AEs vs. low number of AEs (p < 0.0003), and following infection with Covid–19 vs. without Covid–19 (p < 0.0005). Multivariate analysis (MVA) showed sex, BMI, number of AEs, and Covid-19 to be of predictive significance. On the contrary, 25–OH vitamin D concentrations in individuals with high vs. low BMI were significantly reduced (p < 0.0144) but this was not evident in MVA. Conclusions: This study confirmed the high efficacy of BNT162b2 in real–world scenario and revealed that its safety was affected by sex and BMI. Higher IgG levels suggesting better protection against infection were present in males, participants with high BMI, a high frequency of AEs, and those who overcame Covid-19 following vaccination.

Profiling technologies, such as proteomics, allow the simultaneous measurement and comparison of thousands of plant components without prior knowledge of their identity. The combination of these non-targeted methods facilitates a more comprehensive approach than targeted methods and thus provides additional opportunities to identify genotypic changes resulting from genetic modification, including new allergens or toxins. The purpose of this study was to investigate unintended changes in GM Bt maize grown in South Africa. In the present study, we used bi-dimensional gel electrophoresis based on fluorescence staining, coupled with mass spectrometry in order to compare the proteome of the field-grown transgenic hybrid (MON810) and its near-isogenic counterpart. Proteomic data showed that energy metabolism and redox homeostasis were unequally modulated in GM Bt and non-GM maize variety samples. In addition, a potential allergenic protein – pathogenesis related protein -1 has been identified in our sample set. These finding highlight the suitability of unbiased profiling approaches to complement current GMO risk assessment practices worldwide.

GbtXyl43A, a β-xylosidase that is isolated from Geobacillus thermoleovorans IT-08 and grouped in GH43 family. The substitution of 121Asp residue with Asn in GbtXyl43A caused decrease the enzyme activity. The aim of this study, determine the kinetic characteristics of wild-type GbtXyl43A and D121N variant using Vmax, KM, kcat, and kcat/KM. These parameters indicated catalytic mechanism of GbtXyl43A and its derivative. All of them were produced in Escherichia coli BL21 star. The purification of wild-type GbtXyl43A using affinity chromatography, but D121N variant also required anion-exchange chromatography. The specific activity of wild-type GbtXyl43A and D121N variant were 0.471 U mg-1 in purity level 55,44 and 0.012 U mg-1 in purity level 2,407, respectively. Both enzymes had same molecular weight, ~58 kDa. The kinetic parameters of wild-type GbtXyl43A were KM: 2.845 mM, kcat: 0.033 s-1, Vmax: 0.0033 mM min-1and kcat/KM: 0.0115 s-1mM-1. Furthermore, the KM, kcat, Vmax, and kcat/KM values of D121N variant were 4.565 mM, 1.01 × 10-4 mM min-1, 0.140 × 10-4 s-1, and 0.0307 s-1mM-1, respectively. The KM value of the D121N variant was higher than its wild type and showed the affinity of D121N variant was lower than GbtXyl43A

We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this study, we investigate how cell induced reorganization of fibrin correlates with fibronectin track formation in response to two growth factors present during wound healing: PDGF BB, which stimulates cell spreading and migration; and TGFβ1, which stimulates cellular contraction and myofibroblast transformation. Both PDGF BB and TGF stimulated global fibrin matrix contraction (P < 0.005), however cell and matrix patterning were different. We found that during PDGF BB induced cell spreading, fibronectin was organized simultaneously with the generation of tractional forces at the leading edge of pseudopodia. Over time this led to the formation of an interconnected network consisting of cells, fibronectin and compacted fibrin tracks. Following culture in TGFβ1, cells were less motile, produced significant local fibrin reorganization, and formed fewer cellular connections as compared to PDGF BB (P < 0.005). Although bands of compacted fibrin tracks developed in between neighboring cells, fibronectin labeling was not generally present along these tracks, and the correlation between fibrin and fibronectin labeling was significantly less than that observed in PDGF BB (P < 0.001). Taken together, our results show that cell-induced ECM reorganization can occur independently from fibronectin patterning. Nonetheless, both events seem to be coordinated, as corneal fibroblasts in PDGF BB secrete and organize fibronectin as they preferentially spread along compacted fibrin tracks between cells, producing an interconnected network in which cells, fibronectin and compacted fibrin tracks are highly correlated. This mechanism of patterning could contribute to the formation of organized cellular networks that have been observed following corneal injury and refractive surgery.

We obtain two generalizations of a known theorem of A. Alam and M. Imdad (Fixed Point Theory Appl. 17 (2015) 693–702) showing that some standard proofs can be obtained involving only Cauchy sequences of the successive approximations instead of the usual successive approximations sequences. Suitable examples prove the effective generalization of our results in metric spaces not necessarily complete.

Kinect is a device that has been widely used in many areas since it was released in 2010. Kinect SDK was announced in 2011 and used in many other areas than its original purpose, which was a controller for gaming. In particular, it has been used by a number of artists in digital media art since it is inexpensive and has a fast recognition rate. However, there is a problem. Kinect create 3D coordinates with a single 2D RGB image for x, y value - single depth image for z value. And this creates a significant limitation on the installation for interactivity of media art. Because the Cartesian XY coordinate and the spherical Z coordinate system are used in combination, depth error depending on the distance is generated, which makes real-time rotation recognition and coordinate correction difficult above coordinate system. This paper proposes a real-time calibration method of Kinect recognition range expansion for useful application in the digital media art area. The proposed method can recognize the viewer accurately by calibrating a coordinate in any direction in front of the viewer. 3,400 datasets witch acquire from experiment were measured as five stances: the 1m attention stance, 1m hands-up stance, 2m attention stance, 2m hands-up stance, and 2m hands-half-up stance, which were taken and recorded every 0.5 sec. The experimental results showed that the accuracy rate was improved about 11.5% compared with front measurement data according to Kinect reference installation method.

The study evaluated the impact of supplementing ZH in combination with D3 on growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. Thirty-two Dorper x Katahdin cross lambs (37.3±5.72 kg) were utilized in a 29 d experiment in a complete randomized block design with a 2x2 factorial structure consisting of two levels of ZH for 26 d (0 and 0.20 mg /kg PV-1) and two levels of D3 for 7 d (0 and 1.5x106 IU/d-1). ZH improved (P≤0.05) average daily gain (ADG) and feed efficiency by 9.9% and 17.8%, respectively, as well as hot carcass weight (HCW) and dressing carcass by 4.3% and 2.6%, respectively. (p≤0.03). However, ZH increased (p<0.01) muscle pH and Warner-Bratzler shear force (WBSF) (2.5 and 23.0%, respectively). D3 supplementation negatively affected (P≤0.02) dry matter intake (DMI) (last 7 d) and ADG by 15.7% and 18.1%. On the other hand, D3 improved the pH of the longissimus muscle (LM) by 1.7% (p=0.03) without affecting WBSF. When D3 was supplemented in combination with ZH, it was observed that meat quality was improved by reducing muscle pH compared to lambs treated only with ZH. However, D3 did not improve meat tenderness produced by ZH supplementation.

Côte d’Ivoire has substantially neglected crop residues from farms in rural areas. This study aims to provide strategies for the sustainable conversion of crop residues to hydrogen. Using existing data and theoretical approaches, up to 16,801,306 tons of crop residues of 11 crop types were available in Côte d’Ivoire in 2019. A theoretical hydrogen potential of 1,296,424.84 tons was estimated from the crop residues. Technically, 907,497.39 tons of hydrogen is expected annually. Three scenarios of hydrogen project implementation developed indicated that the Ivorian industries can be supplied with 9,026,635 gigajoules of heat. Moreover, 17,910 cars and 4,732 buses can be supported in the transport sector. It is estimated that 817,293.95 tons of green ammonia for farmers can be supplied. Five million, seven hundred twenty-seven thousand, nine hundred ninety-two (5,727,992) households are expected to have access to 1,718.40 gigawatts of electricity. Due to these changes in transport, energy, industry, and agricultural sectors, a reduction of 1,644,722.08 tons of carbon dioxide per year can be achieved theoretically. With the scenarios, some 263,276.87 tons of hydrogen are exportable to other countries. Conversion of crop residues to hydrogen is a promising opportunity with environmental and socio-economic impact. Therefore, this study requires further extensive research.

Colorectal cancer is the third most common disease and the second most common cause of death in the world. The drug for second-line treatment depends on the drugs used in first-line treatment and biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers are established for selecting angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be hopeful biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients.

Missing observation is a common problem in scientific and industrial experiments, particularly in a small-scale experiment. They often present significant challenges when experiment repetition is infeasible. In this research, we propose a multi-objective genetic algorithm as a practical alternative for generating optimal mixture designs that remain robust in the face of missing observation. Our algorithm prioritizes designs that exhibit superior D-efficiency while maintaining a high minimum D-efficiency due to missing observation. The focus on D-efficiency stems from its ability to minimize the impact of missing observations on parameter estimates, ensure reliability across the experimental space, and maximize the utility of available data. We study problems with three mixture components where the experimental region is an irregularly shaped polyhedral within the simplex. Our designs have proven to be D-optimal designs, demonstrating exceptional performance in terms of D-efficiency and robustness against missing observations. We provide a well-distributed set of optimal designs derived from the Pareto front, enabling experimenters to select the most suitable design based on their priorities using the desirability function.

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms such as diarrhea, bloating, or chronic abdominal pain, CD may also present a wide spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. This review aims to describe the role of CD in the development of skeletal alterations, underlying important clinical aspects and therapeutic implications. The etiopathology of bone lesions in CD is multifactorial and their management is challenging. Here, we provide gastroenterologists and orthopedics with an up-to-date overview on the link between CD and osteoporosis to improve the management of the CD condition.

The leading cause of illness in aging is a group known as Noncommunicable Diseases. There should be some meeting points that modify the cells homeostasis and impaired the cell physiology developing different diseases. Quantum physics studied the atomic and subatomic particles and revolutionized the reality perception with paradoxical and weird concepts. Heisenberg's uncertainty principle established that it is not possible to determine the two characteristic properties of particles with accuracy. Subatomic particles have a wave-particle duality. Two subatomic particles are entangled, something happening over here can have an instantaneous effect over there, no matter how far away there are. All these concepts have tried to apply to biology and life sciences, quantum biology is behind photosynthesis, mitochondrial respiration, enzyme activity, the sense of smell, animal migration, heredity's fidelity, and consciousness. We can apply all these concepts to diseases pathogeny. So, we describe quantum phenomena in oxidative stress, calcification, signal transduction, vitamin D production and cancer mutations. Aging diseases also could be explained by applying quantum physics concepts. It is a new, hard to believe, and an incredible path to be built, but we need to open the treatment options to our patients with new perspectives.

Treatment with calcitriol, the hormonal form of vitamin D, has shown beneficial effects in ex-perimental models of acute lung injury. In this study we aimed to analyze the associations be-tween calcitriol supplementation and the risk of SARS-CoV2 infection or COVID-19 mortality. Individuals ≥18 years old living in Catalonia and supplemented with calcitriol from April 2019 to February 2020 were compared with propensity score matched controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality. Associations between calcitriol supplementation and outcome variables were analyzed using multivariable Cox proportional regression. A total of 8076 patients were identified as being on calcitriol treatment. Advanced chronic kidney disease and hypoparathyroidism were the most frequent reasons for calcitriol supplementation in our population. Calcitriol use was associated with reduced risk of SARS-CoV2 infection (HR 0.78 [CI 95% 0.64-0.94], p=0.010), reduced risk of severe COVID-19 and reduced COVID-19 mortality (HR 0.57 (CI 95% 0.41-0.80), p=0.001) in patients with advanced chronic kidney disease. In addition, an inverse association between mean daily calcitriol dose and COVID-19 severity or mortality was observed in treated patients, independently of renal function. Our findings point out that patients with advanced chronic kidney disease could benefit from calcitriol supplementation during the COVID-19 pandemic.

Non-homologous end joining (NHEJ) is the main DNA repair mechanism for the repair of double strand breaks (DSBs) throughout the course of the cell cycle. DSBs are generated in developing B and T lymphocytes during V(D)J recombination to increase the repertoire of B and T cell receptors. DSBs are also generated during the class switch recombination (CSR) process in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. Thus, NHEJ is important for both V(D)J recombination and CSR. NHEJ comprises core Ku70 and Ku80 subunits that form the Ku heterodimer, which binds DSBs and promotes the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, PAXX, Mri) and downstream core factors (XLF, Lig4 and XRCC4). In recent decades, new NHEJ proteins have been reported, increasing complexity of this molecular pathway. Numerous in vivo mouse models have been generated and characterized to identify the interplay of NHEJ factors and their role in development of adaptive immune system. This review summarizes the currently available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development. We also underline genetic interactions and redundancy in the NHEJ pathway in mice.

Lichen secondary metabolites are generally considered as repellent compounds for lichen feeders. Nevertheless, if the only food available consists in lichens rich in secondary metabolites, lichenophages such as Notodiscus hookeri, a gastropod native from the Possession Island, seem able to implement strategies to overcome the toxicity of these metabolites. Thus, the balance between phagostimulant nutrients and deterrent metabolites appears to play a key role in their feeding preferences. To further understand lichen-gastropod interactions, we studied the feeding behavior of Notodiscus hookeri fed exclusively with Usnea taylori, a lichen rich in usnic acid and arabitol. Snail feeding choice experiments with intact lichens vs acetone-rinsed lichens were carried out to study the influence of secondary metabolites. Simultaneously, usnic acid and arabitol were quantified and localized within the lichen thallus using HPLC-DAD-MS and in situ imaging by mass spectrometry to assess whether their spatial distribution induce preferential snail grazing. Then, no-choice feeding experiments were devised using usnic acid and arabitol embedded in artificial diet, separately or together. This case study demonstrated that the nutritional activity of N. hookerii was governed by the chemical quality of the food and primarily by nutrient availability (arabitol), despite the presence of deterrent metabolites (usnic acid).

Big Data classification has recently received a great deal of attention due to the main properties of Big Data, which are volume, variety, and velocity. The furthest-pair-based binary search tree (FPBST) shows a great potential for Big Data classification. This work attempts to improve the performance the FPBST in terms of computation time, space consumed and accuracy. The major enhancement of the FPBST includes converting the resultant BST to a decision tree, in order to remove the need for the slow K-nearest neighbors (KNN), and to obtain a smaller tree, which is useful for memory usage, speeding both training and testing phases and increasing the classification accuracy. The proposed decision trees are based on calculating the probabilities of each class at each node using various methods; these probabilities are then used by the testing phase to classify an unseen example. The experimental results on some (small, intermediate and big) machine learning datasets show the efficiency of the proposed methods, in terms of space, speed and accuracy compared to the FPBST, which shows great potential for further enhancements of the proposed methods to be used in practice.

In this paper, we investigate the effects of certain variants of the commutative laws on properties of several families of algebras which are in general not commutative, such as groups, linear algebras, or actually quite anti-commutative, such as $BCK$-algebras and $d$-algebras among others. From results obtained it becomes clear that by considering these variants in the presence of yet other axioms it is to be expected that a quite rich and varied set of results may be obtained both in the general and the particular setting of which what has been accomplished in this paper is a substantial sample.

Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder frequently associated with ulcerative colitis (UC). Patients with PSC and UC have higher risk of colorectal neoplasia than patients with UC without PSC. Oncogenic properties of micro RNA 346 (miR-346) have been recently reported. In this study we investigated expressions of miR-346 and its two target genes i.e. the receptor of vitamin D (VDR) and the tumor necrosis factor α (TNF-α), which are known to modulate carcinogenesis. Biopsies from ascending and sigmoid colon were obtained from patients with PSC with and without UC, patients with UC and healthy controls. MiR-346 expression was increased in ascending but not sigmoid colon of patients with PSC and UC when compared to other analyzed groups (p<0.001 for all). In patients with UC an exceptionally low colonic expression of miRNA-346 was accompanied by the increase in VDR expression, and the extensive upregulation of TNF-α gene which protein product is known to be cytotoxic to tumor cells at high concentration. In summary, a substantial upregulation of miRNA-346 in ascending colon of patients with PSC and UC may be responsible for the inhibition of VDR and TNF-α signaling -pathway which may result in an inadequate suppression of neoplasia.

We investigate entropy generation in unsteady three-dimensional axisymmetric MHD nanofluid flow over a non-linearly stretching sheet. The flow is subject to thermal radiation and a chemical reaction. The conservation equations were solved using the spectral quasi-linearization method. The novelty of the work is in the study of entropy generation in three-dimensional axisymmetric MHD nanofluid and the choice of the spectral quasilinearization method as the solution method. The effects of Brownian motion and thermophoresis are also taken into account when the nanofluid particle volume fraction on the boundary in passively controlled. The results show that as the Hartman number increases, both the Nusselt number and the Sherwood number decrease whereas the skin friction increases. It is further shown that an increase in the thermal radiation parameter corresponds to a decrease in the Nusselt number. Moreover, entropy generation increases with the physical parameters.

During the last two decades several cases of venous thrombosis (VTE) after a prolonged period at a computer has been described, denominated “eThrombosis”. Video gaming on a computer has become very popular and can be a social activity where several players are gathered to play against each other or in a virtual environment for several days (“LAN (i.e., Local Area Network) parties”) where the participants are sedentary and consuming calorie-rich food items. The aim of this study was to investigate a potential coagulation activation during a 42 hour LAN party. Nine male gamers volunteered for the LAN party. Citrated blood was sampled before and every 6 hours, and plasma was analyzed for thrombin generation, and Thrombin-antithrombin-complexes (TAT), prothrombin Fragment 1+2 (F1+2), and D-dimer. Thrombin generation increased slightly but not significantly during the LAN party, whereas the coagulation activation markers were unchanged. These results do not indicate that the coagulation system is activated significantly during 42 h gaming with minimal physical activity. Although an increased activity cannot be excluded, it does not directly indicate a risk of VTE in general. It may be specific and particularly susceptible in-dividuals who are prone to thrombosis and, therefore, are at risk of developing e-thrombosis.

D-Glucaric acid is an important bio-based building block of polymers and is a high value-added chemical that can be used in a variety of applications. In the present study, the Udh target genes from Pseudomonas putida and Pseudomonas syringae were used together to construct the expression vector pETDuet-2×Udh. The transformants of BL21(DE3) with vector pETDuet-2×Udh was applied to produce glucaric acid from glucuronic acid. After optimization of induction conditions, the highest Udh expression were achieved when 0.4 mmol L-1 isopropyl-β-d–thiogalactoside (IPTG) was added to cell cultures at an OD600 value of 0.6 followed by culture at 26℃ for 6 hours. The production of glucaric acid substantially reached 5.24 ± 0.015 g L-1 in fed-batch cultures in a 30 L tank. In the present study, a new system for glucaric acid production was established, which was more economic and friendly to environment.

Antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis and/or adverse pregnancy outcome in the presence of persistent laboratory evidence of antiphospholipid antibodies (aPL). Preeclampsia (PE) complicates about 10-17% of pregnancies with APS. However, only early onset PE (< 34 weeks of gestation) belongs to the clinical criteria of APS. The similarities in the pathophysiology of early onset PE and APS emphasize an association of these two syndromes. Overall, both are the result of a defective trophoblast invasion and decidual transformation at early gestation. Women with APS are at increased risk for prematurity; the reasons are mostly iatrogenic due to placental dysfunction, such as PE or FGR. Interestingly, women with APS have also an increased risk for preterm delivery, even in the absence of FGR and PE and therefore not indicated but spontaneous. The basic treatment of APS in pregnancy is low-dose-aspirin and low-molecular- weight-heparin. Nevertheless, up to 20-30% of women develop complications at early and late gestation despite basic treatment. Several additional treatment options have been proposed, with Hydroxychloroquine (HCQ) being one of the most efficient. Additionally, nutritional interventions, such as intake of vitamin D have shown promising beneficial effects. Curcumin, due to its antioxidant and anti-inflammatory properties, might be considered as additional intervention as well.

This study investigated whether export performance is correlated with innovation. We explicitly considered five types of innovation: a) process innovation; b) product innovation; c) process and product innovation; d) product innovation new to the firm; and e) product innovation new to the market. We en-larged the findings of R&D-export and R&D-investment relations using a vast sample of cross-European firms. We considered innovation as endogenous and determined by R&D through a process characterized by the role of the regional technological environment. Our analysis enabled us to propose an integrated model incorporating R&D, innovation and export, in a framework of simultaneous equations which consider their mutual correlations. To the best of our knowledge, this work is the first in recent years to empirically compute the relation between R&D and tangible investment at the micro level. Econometric results showed that product and process innovation are positively linked to the export intensity of European manufacturing firms. The results also showed complementarity effects between the two kinds of innovation. The av-erage effect on export intensity from carrying out process innovation is larger than that found for product innovation, except in cases where the product is new to the market. When both types of innovation have been carried out, a larger effect results than that found for product or process innovation alone. Furthermore, the average marginal effect on export intensity from innovations of any kind among those studied here is highly positive and significant.