Background: The global pandemic of coronavirus disease 2019 (COVID-19) resulted to many deaths from fulminant respiratory failure. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There has been great concern regarding the impact of COPD on COVID-19 illness. Methods: Data from the Philippine CORONA Study were analyzed to determine the association of COPD and COVID-19 in terms of mortality, disease severity, respiratory failure, mechanical ventilation, and lengths of stay in the intensive care unit (ICU) and hospital. The influence of smoking on COVID-19 disease severity and mortality were also reviewed. Results: A total of 10,881 patients were included in the study and 156 (1.4%) patients had been diagnosed with COPD. Majority of COVID-19 patients with COPD had other existing comorbidities: hypertension, diabetes mellitus, chronic cardiac disease, and chronic kidney disease. COPD patients more commonly present with severe or critical COVID-19. COPD patients with COVID-19 were at higher risk to experience in-hospital mortality, respiratory failure, and to be admitted in the ICU. Smokers were more likely to present with higher COVID-19 severity and experience in-hospital mortality. Conclusion: Our study supports that the growing evidence that COPD among COVID-19 patients is a risk for higher mortality, more severe form of COVID-19, higher ICU admission, and higher respiratory failure needing ventilatory support. Smoking increases risk for developing severe COVID-19 and mortality.

Introduction: Galectin-13 (Gal-13) is predominantly produced by the syncytiotrophoblast, while laeverin is expressed on the outgrowing extravillous trophoblast, and both are thought to be biomarkers of preeclampsia. The aim of this study was to assess the correlation between concentrations of Gal-13 and laeverin measured in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic assessment of the fetoplacental measurements. Materials and methods: Fetal biometric data, and placental volume and perfusion indices were measured in 62 singleton pregnancies. Serum and amniotic levels of Gal-13 and laeverin levels were measured using a sandwich ELISA. Results: Both amniotic fluid and serum Gal-13 levels expressed a negative correlation to the plasma laeverin level in mid-pregnancy. Serum laeverin level correlated positively with the gestational length at delivery (β=0.39, p

This study presents an in–depth analysis and strategic planning techniques for approaching a situation or achieving progress related to information technology services of Nueva Ecija University of Science and Technology, particularly the San Isidro Campus. As an educational organization and one in the region excellence providers in education, the University has so much vital information to manage and services to offer to provide the student's needs through the Management Information System department, application of IT services as a competing instrument to combat tedious tasks such as online admission, grade release, enrollment information, and online learning, university announcement, and possible students’ internship. The objective of this study is to determine the influence of information technology in day–to–day activities of the organization and strategy applied to streamline processes more conveniently. The researchers develop a conceptual model that would analyze the IT services' impact by identifying its strengths, weaknesses, opportunities, and threats and cleverly act on it using the TOWS Matrix in generating strategic decisions. The overall results were beneficial to the University and MIS as a basis for formulating competitive strategies and integrating it in an extended development plan.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

Androgen receptor signaling is crucial for prostate cancer growth and is positively regulated in part by intratumoral CYP3A5. As African American (AA) men often carry the wild type CYP3A5 and express high level of CYP3A5 protein, we blocked the wild type CYP3A5 in AA origin prostate cancer cells and tested its effect on androgen receptor signaling. q-PCR based profiler assay identified several AR regulated genes known to regulate AR nuclear translocation, cell cycle progression and cell growth. CYP3A5 processes several commonly prescribed drugs and many of these are CYP3A5 inducers or inhibitors. In this study, we test the effect of these commonly prescribed CYP3A5 inducers/inhibitors on AR signaling. The results show that the CYP3A5 inducers promoted AR nuclear translocation, downstream signaling and cell growth whereas CYP3A5 inhibitors abrogated them. The observed changes in AR activity is specific to alterations in CYP3A5 activity. Both the inducers tested demonstrated increased cell growth of prostate cancer cells, whereas the inhibitors showed reduced cell growth. Further, characterization and utilization of the observation that CYP3A5 inducers and inhibitors alter AR signaling may provide guidance to physicians prescribing CYP3A5 modulating drugs to treat comorbidities in elderly patients undergoing ADT, particularly AA.

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

The aim of the study was the comparison of conventional sintering versus additive manufacturing techniques for β-TCP bioceramics, focusing on mechanical properties and biocompatibility. A "critical" bone defect requires surgical intervention beyond simple stabilization. Autologous bone grafting is the gold standard treatment for such defects but it has its limitations. Alloplastic bone grafting using synthetic materials is becoming increasingly popular. The use of bone graft substitutes has increased significantly and current research was focused on optimizing these substitutes, whereas this study compares two existing manufacturing techniques and the thereby produced β-TCP implants. The 3D-printed β-TCP hybrid structure implant was fabricated using two components, a column structure and a freeze-foam, which were sintered together. The conventionally manufactured ceramics were made by pouring. Both scaffolds were characterized according to porosity, mechanical properties and biocompatibility. The hybrid structure had a total porosity of 74.4 ± 0.5%. Microporous β-TCP implants had a porosity of 43.5 ± 2.4%, while macroporous β-TCP implants had a porosity of 61.81%. Mechanical testing revealed that the hybrid structure had a compressive strength of 10.4 ± 6 MPa, significantly lower than the microporous β-TCP implant’s with 32.9 ± 8.7 MPa. Biocompatibility evaluations showed a steady increase in cell proliferation over time for all β-TCP implants, with minimal cytotoxicity. This study provides valuable insight into the potential of additive manufacturing for β-TCP bioceramics in the treatment of bone defects.

The removal of sulfur from fossil fuels is one of the most important processes in modern refineries. It is accomplished via hydrodesulfurization (HDS) of the sulfur organic compounds in presence of heterogeneous catalysts. In the current work, heterogeneous catalysts containing cobalt and mo-lybdenum supported on mesoporous materials type SBA-15 and AlSBA-15 were synthesized for application in the HDS reactions of thiophene in n-heptane stream. The mesoporous materials were synthesized by hydrothermal method starting from TEOS, pseudobohemite, hydrochloric ac-id and water. Pluronic P123 was used as template. The best calcination conditions for removal of the organic template were optimized by thermogravimetry analysis (TG/DTG). The calcined SBA-15 and AlSBA-15 supports were submitted to co-impregnation with solutions of cobalt nitrate and ammonium heptamolybdate, aiming the production of 15% in mass of metal loading with atomic ratio of [Co/(Co+Mo)]=0.45. The obtained materials were dried and calcined for obtaining the mesoporous catalysts in the form of CoMo/SBA-15 and CoMo/AlSBA-15. The catalysts were char-acterized by XRD, TG/DTG, SEM and nitrogen adsorption. From XRD analysis, it was verified that after decomposition of the cobalt and molybdenun salts, were formed MoO3, Co3O4 and Co-MoO4 oxides on the supports, being attributed to these chemical species the activity for the HDS reactions. The activity of the obtained catalysts was evaluated in a continuously flowing tubular fixed-bed microreactor coupled on-line to a gas chromatograph, using n-heptane stream contain-ing 12070 ppm of thiophene (ca. 5100 ppm of sulfur) as a model compound. From the catalytic tests it was verified that the synthesized catalysts presented good activity for the reaction, and the main obtained products were cis- and trans-2-butene, 1-butene, n-butane and low amounts of iso-butane. The presence of 1,3-butadiene and tetrahydrothiophene (THT) were not detected. A mechanism of the primary and secondary reactions and subsequent formation of the olefins and paraffins, in the CoMo/SBA-15 and CoMo/AlSBA-15 mesoporous catalysts were proposed, con-sidering steps of desulfurization, hydrogenation, dehydrogenation, THT decyclization and isomerization.

In hepatocellular carcinoma (HCC), recurrence usually occurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce recurrence rates. In this report, the in vivo mouse effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance was evaluated. A phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in HCC recurrence in patients who have undergone curative surgery for HBV-related HCC. In animal modeling, HBV suppression was significantly greater with rmIFN-α and anti-PD1 sequential combination treatment than with their treatment alone. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks at the dose of 450 µg for six doses, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease or clearance of HBV surface antigen was observed in two patients. Dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was determined. Currently no HCC recurrence has been observed. The treatment modality was well tolerated. The data support further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

Abstract Tetraspanin CD63 is a cluster of cell surface proteins with four transmembrane domains which associates with tetraspanin-enriched microdomains and typically localizes to late endosomes and lysosomes. CD63 plays an important role in cellular trafficking of different proteins, EV cargo sorting and vesicles formation. We have preciously shown that CD63 is important in LMP1 trafficking to EVs and this also affects LMP1 mediated intracellular signaling including MAPK/ERK, NF-κB and mTOR activation. Using the BioID combined with mass spectrometry, we sought to define the broad CD63 interactome and how LMP1 modulates this network of interacting proteins. We identified a total of 1600 total proteins as proximal interacting newtwork of proteins to CD63. Biological process enrichment analysis revealed significant involvement in signal transduction, cell communication, protein metabolism and transportation. The CD63 only interactome was enriched in Rab GTPases, SNARE proteins and sorting nexins while adding LMP1 into the interactome increased presence of signaling and ribosomal proteins. Our results showed that LMP1 alters the CD63 interactome, shifting the network of proteins enrichment from protein localization and vesicle mediated transportation to metabolic processes and translation. We also show that LMP1 interacts with mTor, Nedd4L and PP2A indicating formation of a multiprotein complex with CD63 thereby potentially regulating LMP1 dependent mTor signaling. Collectively, the comprehensive analysis of CD63 proximal interacting proteins provides insights into network of partners required for endocytic trafficking, extracellular vesicle cargo sorting, formation and secretion.

Taiwan's bed and breakfast (B&B) development has been more than 25 years ago, from the first generation of retirement to the B&B industry, serving tourists from all over the world accom-modation, providing breakfast and accommodation mode to the present, after the change of employees from the second generation, more and more attention is paid to the cultivation and cultivation of business ability. With the advent of the era of AI technology networking, the ca-pabilities required for B&B operation are more focused on all aspects of service, and the good marketing ability of B&B can promote a green chimney-free tourism economy, which is also a favorite industry of various governments and the public. This study explores the basic vocational competency indicators required for running a B&B, with (1)EQ emotion management skills, (2)Financial management ability, (3)(SK) technical skills, and (4)Marketing and promotion management capabilities. Through the study method, the K-S Z test was determined by the con-sensus conclusion of expert reliability and validity p value

The Rev. Martin Luther King Jr. and Nelson Mandela were two of the world's most iconic civil (political) (human) rights advocates and leaders of all time. Both advocated for, and to varying degrees, applied elements of peaceful protests to the achievement of their goals. Both spent time in jail, often concurrently, but eventually forced their respective countries to extend the same rights that white populations had denied Africans and African Americans. For the US, civil rights, voting rights, right to education, housing and housing loans suggested that equality had been achieved, capped in South Africa by the election of Nelson Mandela as the first majority-rule president, and in the US, by Barack Obama’s election to the presidency. Yet the historical over-policing, police mistreatment and more generally, the judicial system’s inordinate ‘targeting’ of African Americans, with egregious cases running from Emmett Till to Rodney King to Walter Scott to Breonna Taylor to George Floyd to Rayshard Brooks and thousands of others shows the danger of such magical thinking. The now-persistent global wave pursuing human rights, civil rights and the right to be treated equally, primarily driven by the loosely-organized Black Lives Matter (BLM) movement, has become the leading voice in pursuit of equality. Riots such as those in LA, protests in Ferguson and everywhere in summer 2020 has ushered new civil rights campaign. In the US and elsewhere, it has morphed to include historical issues such as monuments to colonialism, the US civil war, slavery and slave owners and traders, institutions, companies and people whose wealth and existence has links to slavery. Instructively, the protests persisted even as COVID-19, the hundred-year plague, continues to ravage the world. Lost in the moment is the absence of central leadership and leaders such as MLK or Mandela. Their charisma and effectiveness has been lacking for 50 years. This paper evaluates whether this has led to inconsistent civil and human rights pursuit for equality, or whether perchance, Mandela and MLK were extraordinary, once-in-a-lifetime transformative leaders uniquely selected by history for their time.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

Demand for green technologies and energy is in continuous growth in the last years. Compact efficient antennas are crucial for energy harvesting portable systems. Small antennas have low efficiency. The efficiency of communication and energy harvesting systems may be improved by using efficient passive and active antennas. The system dynamic range may be improved by connecting amplifiers to the printed antenna feed line. Design, design considerations, computed and measured results of wearable meta-materials antennas with high efficiency for energy harvesting applications are presented in this paper. All antennas were analyzed by using 3D full-wave software. The antennas electrical parameters on human body are presented. The directivity and gain of the antennas with Split-ring resonators, SRR, is higher by 2.5dB than the antennas without SRR. The resonant frequency of the antennas with SRR is lower by 5% to 10% than the antennas without SRR.

This note applies the Logistic model approximation to determine the suitable start and end dates for the observed epidemic curves in the total number of cases for different countries. The Logistic model is presented and explicit relations for the beginning and end dates are obtained together with the total epidemic duration. Using data from Brazil, Germany, Italy, and South Korea, the extreme dates are calculated. Since the epidemic onset time is found, a fair comparison of the epidemic curve for these countries is obtained. The result does not depend on the poor statistics available in the early phase of the epidemic when the initial number of infectives is unknown. In fact, the total duration depends only on the characteristic time parameter of the LM model.

The first two decades of the 21st-century have seen the emergence of the modern citizen science movement, increased demand for niche eco and wildlife tourism experiences, and the willingness of people to voluntarily share information and photographs online. To varying extents, the rapid growth of these three phenomena has been driven by the availability of portable smart devices, access to the Web 2.0 internet from almost anywhere on the planet, and the development of applications and services, including social media/networking sites (SNSs). In addition, the number of peer-reviewed publications that explore how text and images shared on SNSs can be data-mined for academic research has surged in recent years. This systematic quantitative review has two goals. The first goal is to provide an oversight of how the photographs that ecotourists share online are contributing to wildlife tourism research. The second goal is to promote the emerging photovoice technique as a theoretical context for social research based on the photographs and comments that ecotourists share on SNSs. From the perspectives of community benefits, conservation behaviours, and environmental education, there are many similarities between authentic ecotourism experiences and quality ecological citizen science programs. Much of the literature regarding the theory and practice of citizen science reports on the difficulties of attracting, training, motivating and retaining community members. The synthesis of this review is that crowdsourcing wildlife and tourism data from comments and photographs that ecotourists share on SNSs is a credible method of research that provides a self-replenishing pool of citizen scientists.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n=3) and rectal cancer (n=2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the DIDA-Seq error-correction method, we serially interrogated plasma cell-free DNA at 28-41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

This study presents a novel polyurethane-activated carbon composite (PACC) as an effective and sustainable adsorbent for treating lead-ion-contaminated waters. The PACC was characterized using SEM-EDX, FTIR, BET, XRD, and TGA to evaluate its physicochemical and thermal properties. Furthermore, the PACC was employed in an experimental column adsorption setup to investigate its adsorption performance and to develop a dynamic method suitable for industrial implementation. Parameters such as bed height (50, 100, 150 mm), flow rate (4, 6, 8 mL min-1), pH (2, 4, 6), and initial metal ion concentrations (10, 50, 100 mg L-1) were examined. The experimental data exhibited strong agreement with the Thomas and Yoon-Nelson models (R2 ≥ 0.96), indicating efficient adsorption mechanisms. Remarkably, the depleted adsorbent has the potential for facile regeneration without substantial loss in capacity. The PACC demonstrated excellent adsorption performance for lead ions in aqueous solutions in a fixed-bed column system. Thus, the novel PACC material holds potential for scalable application in industrial settings to address water pollution challenges, especially in regions with uncontrolled effluent discharge.

This work presents significant results obtained by the application of global optimization techniques to the design of finite, normal form games with mixed strategies. To that end, the Fuzzy ASA global optimization method is applied to several design examples of strategic games, demonstrating its effectiveness in obtaining payoff functions whose corresponding games present a previously established Nash equilibrium. In other words, the game designer becomes able to choose a convenient Nash equilibrium for a generic finite state strategic game and the proposed method computes payoff functions that will realize the desired equilibrium, making it possible for the players to reach the favorable conditions represented by the chosen equilibrium. Considering that game theory is a very significant approach for modeling interactions between competing agents, and Nash equilibrium represents a powerful solution concept, portraying situations in which joint strategies are optimal in the sense that players cannot benefit from individually modifying their current strategies provided that other players do not change their strategies as well, it is natural to infer that the proposed method may be very useful for strategists in general. In summary, it is a genuine instance of artificial inference of payoff functions after a process of global machine learning, applied to their numerical components.

In this study, we successfully obtained a 2Mg-Fe mixture through mechanical alloying (MA) and processed it via accumulative roll bonding (ARB) (MA+ARB). Our primary focus was to analyze the impact of ambient air exposure while also evaluating the processing route. Some powder samples were exposed to air for 12 months before undergoing ARB processing. The Mg samples obtained after ARB processing exhibited a (002)-type texture. Our results demonstrate that all samples, including those processed via ARB, could rapidly absorb hydrogen within a matter of minutes, despite considerable differences in surface area between powders and rolled samples. ARB-processed samples reached approximately 60% of their maximum acquired capacity within just 24 minutes, compared to powders stored for a year which took 36 minutes. Also, the desorption temperatures were lower than those of MgH2. The absorption and desorption kinetics remained fast even after prolonged exposure to air. Although there were minor variations in capacities, our overall findings are promising since scalable techniques such as ARB have the potential to produce hydrogen storage materials that are both safe and cost-effective in a highly competitive market.

The electronic transport stability in nanodevices composed by metal/trans-polyacetylene /metal with different long length has contributed greatly for performance, homogeneity, stability, organization of the chains, reproducibility and higher conductivity. In this paper, we present an analytical study of the electronic transport characteristics from dimerized trans-polyacetylene (trans-PA) molecules containing an odd-even number of sites coupled to metal leads (left and right) in T-shaped geometry using the extended Su-Schrieffer-Heeger (SSH) model based on tight-binding Hamiltonian with the Non-Equilibrium Green´s Function (NEGF) via Heisenberg´s equation of motion and the Keldysh´s formalism. Due to the complexity of the T-shaped odd-even chain, our proposal was to test the effects on the finite-length network for three, four, five sites and furthermore foresee for 17-sites. We show how to tune dimerization strength () coupling to the parameters and T-shaped geometry of the device to which it affects the overlap integral localized at the three endpoints of the T-shaped system, making both the odd and even chains to undergo a metal-insulator transition in their electronic behavior. The results reached through control parity of the chain plane of the parameters governing () the electronic and experimental tunneling allow a better understanding of the subject.

The growing concerns about floods have highlighted the need for accurate and detailed precipitation data as extreme precipitation occurrences can lead to catastrophic floods, resulting in significant economic losses and casualties. Integrated Multi-satellitE Retrievals for the Global Precipitation Measurement (GPM-IMERG) is a commonly used high-resolution gridded precipitation dataset and is recognized as trustworthy alternative sources of precipitation data. The aim of this study is to comprehensively evaluate the performance of GPM IMERG Early (IMERG-E), Late (IMERG-L), and Run Final (IMERG-F) in precipitation estimation and their capability in detecting extreme rainfall indices over southwestern Iran during 2001-2020. The Asfezari gridded precipitation data which are developed using a dense of ground-based observation were utilized as the reference dataset. The findings indicate that the IMERG-F performs reasonably well in capturing many extreme precipitation events (defined by various indices). All the three products showed a better performance in capturing fixed and non-threshold precipitation indices across the study region. The findings also revealed that both IMERG-E and IMERG-L have problems in rainfall estimation over elevated areas showing values of overestimations. Examining the effect of land cover type on the accuracy of the precipitation products suggest that both IMERG-E and IMERG-L show large and highly unrealistic overestimations over inland water bodies and permanent wetlands. The results of the current study highlight the potential of IMERG-F as a valuable source of data for precipitation monitoring in the region.

Hallux valgus deformity (HVD) involves subluxation of the first metatarsophalangeal joint. While HVD is primarily considered a forefoot condition, midfoot instability may play a significant role in its development and severity. Therefore, this review had a particular focus on understanding midfoot instability based upon weightbearing imaging assessments of the TMT joint. This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched five databases for studies on midfoot instability in HVD patients. Severity of HVD was defined by hallux valgus angle (HVA) and distal metatarsal articular angle (DMAA). Data was extracted, and articles were graded using the Methodological Index for Non-Randomized Studies (MINORS). Of 547 initially retrieved articles, 23 met inclusion criteria. Patients with HVD showed higher HVA and DMAA on weight-bearing radiographs (WBRG) and weight-bearing computed tomography (WBCT) compared to healthy individuals. Midfoot instability was assessed through intermetatarsal angle (IMA) and tarsometatarsal angle (TMT angle). Patients with HVD exhibited greater IMA and TMT angles on both WBRG and WBCT. This review highlights the importance of weight-bearing imaging assessments for midfoot instability in HVD. IMA and TMT angles can differentiate between healthy individuals and HVD patients, emphasizing the significance of midfoot assessment in understanding HVD pathology.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of <1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

High concentrations of sodium (Na+), chloride (Cl-), calcium (Ca2+), and sulphate (SO42-) are fre-quently found in saline soils. Crop plants cannot successfully develop and produce because salt stress impairs the uptake of calcium, potassium, and water into plant cells. Different intracellular and extracellular ionic concentration changes by salinity, including those of calcium, potassium, and protons. These cations serve as stress signaling molecules in addition to being essential for ionic homeostasis and nutrition. Maintaining an appropriate K+: Na+ ratio is one crucial plant mechanism for salt tolerance, which is a complicated trait. Another important mechanism is the ability for fast extrusion of Na+ from the cytosol. Calcium is established as a ubiquitous secondary messenger, which transmits various stress signals into metabolic alterations that cause adaptive responses. When plants are under stress, the cytosolic-free Ca2+ concentration can rise to 10 times or more from its resting level of 50-100 nanomolar. Reactive oxygen species (ROS) are linked to the calcium alterations, and are produced by stress. Depending on the type, frequency and intensity of the stress, the cytosolic calcium signals oscillate, are transient, or persist for a longer period and exhibit specific "signatures". Both the input and efflux of Ca2+ from the cytosol affect the length and amplitude of the signal. According to several reports, under stress calcium alterations can occur not only in the cytoplasm of the cell but also in the cell walls, nucleus and other cell organelles and the calcium waves propagate through the whole plant. Here, we will focus on how wheat and other important crops absorb Na+, K+ and Cl- when plants are under salt stress, as well as how calcium, potassium, and pH cause intracellular signaling and homeostasis. Similar mechanisms in the model plant Arabidopsis will also be considered.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

A large number of novel treatments for myeloma have been developed and approved, however alkylating drugs continue to be part of standard regimens, additionally, novel alkylators are currently being developed. We performed a non-systematized literary search for relevant papers and communications at large conferences, as well as exploiting the authors knowledge of the field to review the history, current use and novel concepts around traditional alkylators cyclophosphamide, bendamustine and melphalan and current data on the newly developed pro-drug melflufen. Even in the era of targeted treatment and personalized medicine, alkylating drugs continue to be part of standard-of-care in myeloma, and new alkylators are coming to the market.

Soccer is the leading cause of all sports-related ocular injuries in Europe and Israel and leads to blindness at a disproportionately high rate, especially among children (Thompson et al., 2019). With soccer being the most popular sport in the world, it is surprising the only solution to ocular injuries are sports glasses which can cause direct damage to the eye and impair peripheral vision by 15%, calling for an alternative (Smith & Jones, 2020). This work, based on an imported facial model, focuses on both the qualitative and quantitative aspects of building a personalized, low-cost (through optimizing material needed), superior apparatus to conventional sports glasses. The quantitative side examines a modified and model-validated (through a SRS of thirty unique extrapolated points) multivariate linear regression equation, based on horizontal and vertical rotation angles (n=60) trained with residual and computer simulation data, that can accurately extrapolate and quantify ocular impact from all horizontal and vertical rotation angles and a modified Hertzian Contact Stress Equation to determine the thickness of the apparatus using the elasticity modulus, impact force, and geometrical facial and soccer-ball features. The qualitative side examines where firstly, ocular impact is most prevalent, and secondly, where most impact is seen from rotating the ball horizontally and vertically through analysis of Pearson’s Correlation Coefficient at the supraorbital, medial canthus, infraorbital, and lateral canthus regions from both regression equations as well as a cost-benefit analysis for comparison with conventional sports glasses. The findings discovered in this work lay the groundwork for future research to build a customized low-cost ocular injury prevention device which can simultaneously ensure complete ocular safety while enhancing athletic performance for over 250,000,000 players (Johnson & Garcia, 2022).

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

The long-term impact of treatment of dogs with steroid-responsive enteropathy (SRE) on the fe-cal microbiome and metabolome has not been investigated. Therefore, this study aimed to evaluate the fecal microbiome and metabolome of dogs with SRE before, during, and following treatment with standard immunosuppressive therapy and an elimination diet. We retrospec-tively selected samples from 9 dogs with SRE enrolled in a previous clinical trial, which received treatment for 8 weeks, and had achieved remission as indicated by the post-treatment clinical scores. Long-term (1 year) samples were obtained from a subset (5/9) of dogs. Samples from 13 healthy dogs were included as controls (HC). We evaluated the microbiome using 16S rRNA sequencing and qPCR. To evaluate the recovery of gut function, we measured fecal metabolites using an untargeted approach. While improvement was observed for some bacterial taxa after 8 weeks of treatment, several bacterial taxa remained significantly different from HC. Seven-ty-five metabolites were altered in dogs with SRE, including increased fecal amino acids and vitamins, suggesting malabsorption as a component of SRE. One year after treatment, however, all bacterial species evaluated by qPCR and 16S rRNA gene sequencing, and all but thirteen me-tabolites were no longer different from healthy controls.

During the 2008 Great Recession, many families with children relied on cash assistance from Temporary Assistance for Needy Families (TANF) program. The present study applied Exploratory Spatial Data Analysis (ESDA) tools to analyze geographically varying spatial clusters of states’ unemployment rates, TANF caseload growth rates, TANF policy choices such as benefit levels and TANF responsiveness rates to the recession. We analyzed 45 contiguous states and Washington D.C. A standardized TANF responsiveness index was developed to compare states’ TANF growth rates relative to their labor market conditions. The western states were found to be very responsive to the recession with ratios greater than one. In contrast, Texas and Arizona, with ratios below 1, were unresponsive to the recession. The presence of strong spatial clusters in unemployment rate and TANF maximum aid were found. In the case of maximum aid, there was a strong presence of Low-Low spatial clusters in Southern States and High-High clusters in Northeastern States. The findings suggest that several neighboring states in the northeast and some in the south had similar levels of financial commitment during the 2008 recessionary as the ones found by earlier research conducted during non-recessionary periods. The findings have implications for future federal actions and for state level collaboration.

In the context of growing global political tension and introduction of world trade barriers, the urgent task is to develop new tools for assessing their consequences. In the paper we present the agent-based model of trade wars, considering organizations, states and residents generated using initial statistical data. Simulation determines changes in output and supplies of organizations under trade restrictions. Results of calculations on the developed model and comparison of various model complexes forecasts with real consequences of trade wars between the USA and China in 2018 and Western countries against Russia in 2022 are presented. Within calculations four scenarios were considered: (1) baseline, (2) new restrictions between China and the USA, (3) more serious sanctions against China and Russia by the USA and the EU, (4) a global trade war. In the second scenario deviation GDP of the USA and China from the baseline scenario does not exceed 0.5%. In the third scenario, the range of countries involved is expanding, and the fall in GDP in them is expected at the level of 0.7-1%. In the fourth scenario, the entire world economy experiences a serious slowdown, and the EU are facing the most severe consequences, going into recession.

Clinical rehabilitation and sports performance analysis both require the objectification of movement. Kinovea^© is a free 2D motion analysis software that enables the establishment of kinematics parameters. This low-cost technology has been used in sports sciences, as well as clinical field and research work. Although it has been validated as a tool with which to assess time-related variables, this is not yet the case regarding angular and distance variables. The main objective of this study was to determine the validity and reliability of the Kinovea software in obtaining angular and distance data at different perspectives of 90°, 75°, 60° and 45°. For this purpose, a figure with 29 points was designed (in AutoCAD) and 24 frames analysed. Each frame was examined by three observers who each made two attempts. For each export data item, 20 angles and 20 distance variables were calculated, with intra- and inter-observer reliability also analysed. To evaluate Kinovea reliability and validity a multiple approach was applied involving the following analysis: -systematic error with a two-way ANOVA 2x4; -relative reliability with ICC and CV (95% confidence interval); -absolute reliability with Standard Error. The results thus obtained indicate that the Kinovea software is a valid and reliable tool that is able to measure accurately at distances up to 5 m from the object and at an angle range of 90°–45°. Nevertheless, for optimum results an angle of 90° is suggested.

In a continuation and extension of an earlier publication, the calculation of the refractivity and polarizability of organic molecules at standard conditions is presented, applying a commonly applicable computer algorithm based on an atom-group additivity method, where the molecules are broken down into their constituting atoms, these again being further characterized by their immediate neighbor atoms. The calculation of their group contributions, carried out by means of a fast Gauss–Seidel fitting calculus, used the experimental data of 5988 molecules from literature. An immediate subsequent ten-fold cross-validation test confirmed the extraordinary accuracy of the prediction of the molar refractivity, indicated by a correlation coefficient R^2 and a cross-validated analog Q^2 of 0.9997, a standard deviation σ of 0.38, a cross-validated analog S of 0.41, and a mean absolute deviation of 0.76%. The high reliability of the predictions has been exemplified with three classes of molecules: ionic liquids, silicon- and boron-containing compounds. The corresponding molecular polarizabilities have been calculated indirectly from the refractivity using the inverse Lorentz-Lorenz relation. In addition, it could be shown that there is a close relationship between the "true" volume and the refractivity of a molecule, revealing an excellent correlation coefficient R^2 of 0.9645 and a mean absolute deviation of 7.53%.

Here we explore the emerging role of NKG2D CAR-T cell therapy in the realm of solid tumor treatment. Unique capabilities of NKG2D CAR-T cells to recognize stress-induced ligands on cancer cells are discussed, highlighting the therapy's potential for targeted and precise antitumor responses. We also examine the challenges and opportunities associated with NKG2D CAR-T cell therapy, emphasizing the ongoing advancements and clinical trial progress shaping its future. Ultimately, the discussion underscores the transformative promise of NKG2D CAR-T cell therapy in revolutionizing the landscape of solid tumor treatment and enhancing the prospects for improved patient outcomes.

Background: The Davidson Airway Function & Nasal Evaluation (DAFNE) Scoring System was developed as an intuitive and research-based scoring system that could be validated through beta testing and easily introduced to healthcare providers of several subspecialties who treat nasal obstruction and breathing disorders (MDs, PAs, PTs, APRNs, DDSs, and DCs). This scoring system was shown to increase the knowledge of airway function, nasal measurement parameters, and identification of proper treatment options for sleep and breathing disorders. The basis for the DAFNE score was developed from a systematic review of nasal measurement data. Methods: Electronic searches of PubMed, MEDLINE, EMBASE Cochrane Library, and Scopus of publications between 1988-2022 were used to identify studies validating nasal function measurement parameters to create the algorithm for the DAFNE Score™. The systematic review was accomplished using the 2020 ‘Preferred Reporting Items for Systematic Reviews’ (PRISMA) guidelines. Results: Twenty studies met the inclusion criteria for systematic review. Primary outcomes measurements demonstrated reliability, repeatability and validity of the DAFNE measurement technologies, data and output. Conclusions: The data analysis and systematic review uncovered a need and framework to develop and validate a web-based software algorithm for global access to improve the understanding of data interpretation of nasal measurements from three nasal measurement technologies. DAFNE Scoring should be used as an adjunct tool in routine clinical practice and research to further understand the technology data output and how to collaborate with other healthcare providers to improve patient outcomes.

Elevated resting heart rate is frequently observed in cancer patients, and is associated with increased mortality. Although specific chemotherapeutic agents can induce cardiotoxicity, the presence of sinus tachycardia in chemotherapy-naive patients suggests other factors likely contribute to this clinical presentation. Despite its prevalence, cancer-associated resting sinus tachycardia has not been fully recognized and comprehensively described as a separate clinical entity. Secondary effects of cancer, especially structural cardiac changes, secretory factors (inflammatory cytokines), and thromboembolic disease can cause resting tachycardia. Alternatively, rapid heart rate may reflect compensatory mechanisms responding to increased metabolic demands, raised cardiac output states, and even pain. Hence, cancer-associated tachycardia presents a clinical dilemma; acute life-threatening conditions (such as sepsis, pulmonary embolism, etc.) must be ruled out, but cancer itself can explain resting sinus tachycardia and more conservative management can avoid unnecessary testing, cost and patient stress. Furthermore, identification and management of cardiac conditions associated with cancer may improve survival and the quality of life of cancer patients.

The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion as well as the total phase-change entropy of liquid crystals. The present method is based on the complete break-down of the molecules into their constituting atoms and their immediate neighbourhood; the respective calculations of the contribution of the atomic groups by means of the Gauss-Seidel fitting method is based on experimental data collected from literature. The feasibility of the calculations for each of the mentioned descriptors was verified by means of a 10-fold cross-validation procedure proving the good to high quality of the predicted values for the three mentioned enthalpies and for the entropy of fusion, whereas the predictive quality for the total phase-change entropy of liquid crystals was poor. The goodness of fit (Q²) and the standard deviation (σ) of the cross-validation calculations for the five descriptors was as follows: 0.9641 and 4.56 kJ/mol (N=3386 test molecules) for the enthalpy of vaporization, 0.8657 and 11.39 kJ/mol (N=1791) for the enthalpy of sublimation, 0.9546 and 4.34 kJ/mol (N=373) for the enthalpy of solvation, 0.8727 and 17.93 J/mol/K (N=2637) for the entropy of fusion and 0.5804 and 32.79 J/mol/K (N=2643) for the total phase-change entropy of liquid crystals. The large discrepancy between the results of the two closely related entropies is discussed in detail. Molecules, for which both the standard enthalpies of vaporization and sublimation were calculable, enabled the estimation of their standard enthalpy of fusion by simple subtraction of the former from the latter enthalpy. For 990 of them the experimental enthalpy-of-fusion values are also known, allowing their comparison with predictions, yielding a correlation coefficient R² of 0.6066.

The calculation of the vapour pressure of organic molecules at 298.15K is presented using a commonly applicable computer algorithm based on the group-additivity method. The basic principle of this method rests on the complete breakdown of the molecules into their constituting atoms, further characterized by their immediate neighbour atoms. The group contributions are calculated by means of a fast Gauss-Seidel fitting algorithm using the experimental data of 2036 molecules from literature. A ten-fold cross-validation procedure has been carried out to test the applicability of this method, which confirmed excellent quality for the prediction of the vapour pressure, expressed in log(pa), with a cross-validated correlation coefficient Q2 of 0.9938 and a standard deviation  of 0.26. Based on these data, the molecules' standard Gibbs free energy G°vap has been calculated. Furthermore, using their enthalpies of vaporization, predicted by an analogous group-additivity approach published earlier, the standard entropy of vaporization S°vap has been determined and compared with experimental data of 1129 molecules, exhibiting excellent conformance with a correlation coefficient R2 of 0.9598, a standard error  of 8.14 J/mol/K and a medium absolute deviation of 4.68%.

Grape foods fermented with probiotics are sources of beneficial bacteria for the GI tract and also have a high antioxidant capacity. The addition of probiotics to ferment food has always been a traditional process; therefore, probiotic dairy and non-dairy products might contribute to a daily antioxidant diet to improve consumers’ life quality and health. This research was undertaken to determine the viability of 4 wild isolates of Lactobacillus for storage at 5 and 25ºC within 90 days in simulated synthetic grape media and a standard grape marmalade formulation. Changes in active culture numbers, pH level, glucose concentration, and antioxidant properties were evaluated. Most of the isolates demonstrated higher growth in the grape marmalade than the synthetic grape marmalade, which was greater than 7 Log cfu/g within 90 days of storage at 5ºC. In addition, most of the wild isolates grew beyond the critical count of 106 cfu/g in sampling between 60 and 90 days of storage. Moreover, fermented grape marmalade with probiotics showed a strong antioxidant capacity that failed to differ significantly with the synthetic medium. The study confirmed L. paraplantarum, L. plantarum, W. paramesenteroides, and E. feacalis were ideal probiotics for fermentation process of grape marmalade.

Abstract: Background: The diagnosis of nasal airway disorders relies on questionnaires, subjective data, and objective data. Interpretation of objective data obtained from measurement technology is not well understood by providers and researchers who use the equipment to test nasal airway function, justifying the need to cre-ate a new clinical tool. The Davidson Airway Function & Nasal Evaluation (DAFNE) Scoring System is a web-based scoring system that allows healthcare providers (MDs, PAs, PTs, APRNs, DMDs, DDSs, SLPs, and DCs) and researchers who treat nasal obstruction and breathing disorders to make more accurate diagnostic decisions, select the appropriate treatment for individualized patient care, monitor treatment progression and outcomes, and show how to approach a collaborative care model with other healthcare professionals. The current technologies, such as 4-phase rhinomanometry, use a simple approach that relies on a measurement tracing intersecting a color-coded y-axis on a four-quadrant graph with diagnostic numeric data output de-scribing nasal airflow and resistance. This is a good source of biofeedback demonstrating abnormal nasal breathing patterns but lacks interpretation guidelines to describe the severity of disease. The more sophisti-cated proprietary DAFNE approach uses multiple parameters which include airflow restriction, speed, vol-ume, and patient characteristics to identify patients’ disease progression much more accurately. Additionally, it explains how to segregate patients into appropriate treatment options which minimizes risks and compli-cations associated with sleep and breathing disorders while improving patient outcomes. Methods: Electronic searches of PubMed, MEDLINE, EMBASE Cochrane Library, and Scopus of publications between 1988-2022 were necessary to identify studies which determined the ranges of nasal function measurement parameters among three airway measurement technologies used in writing the DAFNE Score algorithm. The performance of DAFNE was evaluated compared to the research data and patient demographics used in previous studies. Results: By using primary outcome measurements from the literature, we were able to create a reliable, re-peatable, and validated tool to facilitate patient identification, treatment stratification, and collaboration for sleep and nasal breathing dysfunction. Subsequently, we found DAFNE could be used to identify the appro-priateness of a sleep study. Conclusions: DAFNE Scoring System has demonstrated the ability to detect high risk patients in the pediatric and adult populations susceptible of sleep apnea and breathing dysfunction needing a sleep study and treatment to improve nasal airway function and sleep. DAFNE Scoring System should be used as an adjunct tool in routine clinical practice and research to further understand the technol-ogy data output, identify patients at risk, stratify treatment options, progress, and stabilization after treatment, and how to collaborate with other healthcare providers to improve patient outcomes.

Biomechanics is a branch of biophysics that deals with mechanics applied to biology. The biomechanics of the cornea plays a significant role in managing patients with glaucoma. While evidence suggests a higher risk of glaucoma in patients with thin and stiffer corneas, it also affects the measurement of intraocular pressure (IOP). We reviewed the pertinent literature to help the understanding of corneal biomechanics and how it can help optimize clinical and surgical treatments and a better approach to diagnosing and managing patients with glaucoma.

The Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first emerged in 2019 in China and has resulted in millions of human morbidities and mortalities across the globe. It has been shown that this novel virus originated in animals, mutated, and made the cross-species jump to humans. At the time of this communication, the Coronavirus disease (COVID-19) may be on way to an endemic form, however the threat of the virus is more for susceptible (older people and immunocompromised) people. The human body has more bacterial cells than its own, thus making us more bacterial than humans. As a consequence, the bacteriomes in the human body heavily influence human health and disease. The bacteriomes in the body and the immune system seem to be in constant association during bacterial and viral infections. In this review, we identify various bacterial spp. in major bacteriomes (oral, nasal, lung, and gut) of the body in healthy humans and compare them with dysbiotic bacteriomes of COVID-19 patients. We try to identify key bacterial spp. that have a positive effect on the functionality of the immune system and human health. These select bacterial spp. could be used as potential probiotics to counter or prevent COVID-19 infections. In addition, we try to identify key metabolites produced by probiotic bacterial spp. that could have potential anti-viral effects against SARS-CoV-2. These metabolites could be subject to future therapeutic trials to determine their anti-viral efficacy.

Abstract: This study presents a methodological framework for AD and MCI diagnosis using radiomic analysis of 18FDG-PET imaging and conducts non-invasive predictions and in-depth analysis of AD and MCI and the associated small number of regions and features. Our methodology follows a structured process commencing with data preprocessing and labeling, facilitating segmentation through FastSurfer, a tool that efficiently segments the brain into 95 ROIs using the DKT-atlas. Subsequently, Feature extraction was carried out using PyRadiomics, calculating 120 features for each of the 95 ROIs (11,400 per image). These extracted features form the foundation of our radiomics analysis, primarily for early diagnostic purposes. In the feature selection phase, we explored a set of eight commonly employed techniques, including ANOVA, PCA, and LASSO, originating from the four main categories, namely filtered, embedded, wrapper, and hybrid methods, to identify a pertinent subset of features. Our evaluation assessed the performance of nine classification methods, such as GradientBoosting, RandomForest, and GaussianNB, in conjunction with eight feature selection techniques. The choice of feature selection method and classifiers was predicated on their ability to achieve the best area under the ROC curve with independent data. For all three predictions AD vs. CN, AD vs. MCI, and CN vs. MCI the Random Forest (RF) classifier with LASSO feature selection demonstrated the highest accuracy with an AUC of 0.976 for AD vs CN, AUC=0.917 for AD vs MCI, and AUC=0.877 for MCI vs CN. In conclusion, our RAB-PET platform enables efficient AD and MCI diagnosis from FDG-PET images using a radiomics pipeline. It also offers a general hardware and software tool for the investigation of other brain disorders.

Toxoplasma gondii (T. gondii) is one of the most common parasites that infect humans. The parasite exists in approximately 40 million people in the United States. Latent infections are frequently associated with tissue cysts of T. gondii in the skeletal muscle and brain tissue that can lead to mental disorders, congenital disorders, and vision dysfunction. Furthermore, self-directed violence, impulsivity, and aggression are associated with T. gondii infection. Dopamine is associated with human behavior including pleasure, aggression, memory, and substance use disorder; however, the result of the studies on the association of T. gondii infection and drugs of abuse are not well understood. The frequency of substance use may be associated with substance-induced modification of dopamine-receptor densities and basal dopaminergic activity. Likewise, T. gondii can directly or indirectly influence dopaminergic activity in infected cells. Based on this hypothesis, the current paper aimed to systematically review all published literature on the association between drugs of abuse and T. gondii infection. Systematic review of controlled studies on T. gondii infection and substance use effects in adults were searched on the electronic databases. Studies have shown that individuals infected with T. gondii display increased risky behavior, such as excessive alcohol consumption. Furthermore, it was observed that T. gondii seropositive subjects had a reduced likelihood of self-reported substance use compared to T. gondii seronegative subjects. This study confirms that SUD is a potential risk factor for behavioral and psychiatric complications associated with T. gondii infection. Ultimately T. gondii infection in the context of drug dependence and the development of SUD remain to be elucidated. Therefore, it is necessary to conduct further research characterizing the mechanisms associated with dopamine metabolism of drug dependence and withdrawal in the context of a T. gondii infection, evaluating the role of inflammation, and identifying potential drug-and-sex specific underpinnings of these associations.

: Drought monitoring and early detection have improved greatly in recent decades through the development and refinement of numerous indices and indicators. However, a lack of guidance, based on user experience, exists as to which drought monitoring tools are most appropriate in a given location. This review paper summarizes the results of targeted user engagement and the published literature to improve the understanding of drought across North America, and to enhance the utility of drought monitoring tools. Workshops and surveys were used to assess and make general conclusions about the perceived performance of drought indicators, indices and impacts information used for monitoring drought in the five main Köppen climate types (Tropical, Temperate, Continental, Polar Tundra, Dry) found across Canada, Mexico, and the United States. In Tropical, humid Temperate, and southerly Continental climates, droughts are perceived to be more short-term (less than 6 months) in duration rather than long-term (more than 6 months). In Polar Tundra climates, Dry climates, Temperate climates with dry warm seasons, and northerly Continental climates, droughts are perceived to be more long-term than short-term. In general, agricultural and hydrological droughts were considered to be the most important drought types. Drought impacts related to agriculture, water supply, ecosystem, and human health were rated to be of greatest importance. Users identified the most effective indices and indicators for monitoring drought across North America to be the U.S. Drought Monitor (USDM) and Standardized Precipitation Index (SPI) (or another measure of precipitation anomaly), followed by the Normalized Difference Vegetation Index (NDVI) (or another satellite-observed vegetation index), temperature anomalies, crop status, soil moisture, streamflow, reservoir storage, water use (demand), and reported drought impacts. Users also noted the importance of indices that measure evapotranspiration, evaporative demand, and snow water content. Drought indices and indicators were generally thought to perform equally well across seasons in Tropical and the colder Continental climates, but their performance was perceived to vary seasonally in Dry, Temperate, Polar Tundra, and the warmer Continental climates, with improved performance during warm and wet times of the year. The drought indices and indicators, in general, were not perceived to perform equally well across geographies. This review paper provides guidance on when (time of year) and where (climate zone) the more popular drought indices and indicators should be used. The paper concludes by noting the importance of understanding how drought, its impacts, and indicators are changing over time as the climate warms, and by recommending ways to strengthen the use of indices and indicators in drought decision-making.

Popular devotions are reflections and expressions of the people’s faith. They are expressions of how people recognize God in their lives, and as a shared experience, they foster expressions of devotion and thus become a manifestation of prayer. Popular devotions as forms of prayer and worship do not contradict the Sacred Liturgy but are acknowledged as legitimate by the Apostolic See. Moreover, popular devotions, in general, lead to the cultivation of some values. One of the most popular devotions among Filipino Catholics is the devotion to the Black Nazarene, a life-sized statue of Jesus Christ kneeling in one knee carrying the cross-dressed in a maroon robe. His face is marked with wounds and blood. His head is crowned with thorns with three gold-plated metal rays on the top of his head, with his eyes looking up to heaven. The Black Nazarene devotion balances Christology from below and above, i.e., Christ does not remain crucified. Instead, he brings the hope of resurrection to those who fervently approach him with faith, hope, and love. It suffices to say that the Black Nazarene serves as a means for the Filipino faithful to encounter Christ in their lives. Given this, this paper aims to appraise the Black Nazarene Devotion as a means that contributes to the New Evangelization among Filipino Catholics. More specifically, this paper seeks to answer how the devotion to the Black Nazarene aids Filipino Catholics in their desire to sustain and grow in their faith amidst the crises and problems they are facing.

Enteric viruses are the major cause of gastroenteritis and enteric hepatitis worldwide, but in some areas like Saudi Arabia little data is known about their presence in water sources. The available information from clinical samples is not enough to figure their actual prevalence. The aim of this study was to gather information for the first time in Saudi Arabia on the presence of Norovirus (NoV) genogroup GI and GII, hepatitis A virus (HAV) and hepatitis E virus (HEV) in water. For this purpose, thirteen monthly samples were collected in lake Wadi Hanifa and surrounding wells from December 2014 to November 2015. Viruses were detected and quantified by Real-time RT-qPCR. Despite HEV findings were anecdotic, our results highlight interesting behaviors of the other viruses. There was a higher prevalence of noroviruses in Wadi Hanifa samples than in well water samples (46.43% vs12.5% of NoV GI; 66.67% vs8.33% of NoV GII). On the contrary, similar levels of HAV positivity were observed (40.48% in surface water vs 43.06% in well water). Also, a strong influence of flooding events on HAV and NoV GI occurrence was observed in both surface and well water samples, being NoV GII apparently not affected.

Bioenergetics, genetic coding, and catalysis are all difficult to imagine emerging without pre-existing historical context. That context is often posed as a “Chicken and Egg” problem; its resolution is concisely described by de Grasse Tyson: “the egg was laid by a bird that was not a chicken”. The concision and generality of that answer furnish no details—only an appropriate framework from which to examine detailed paradigms that might illuminate paradoxes underlying these three life-defining biomolecular processes. We examine experimental aspects here of five examples that all conform to the same paradigm. The paradox in each example is resolved by coupling if, and only if, conditions for two related transitions between levels. One drives, and each restricts fluxes through, or “gates” the other. That reciprocally-coupled gating, in which two gated processes constrain one another, maps onto the formal structure of “strange loops”. That mapping may help unite the axiomatic foundations of genetics, bioenergetics, and catalysis. As a physical analog for Gödel’s logic, biomolecular strange-loops provide a natural metaphor around which to organize these data, linking biology to the physics of information, free energy, and the second law of thermodynamics.

Studies on crop response to light quality [red (R) to far-red (FR) light ratio] often recommend early weed removal to reduce the effects of shade avoidance responses on crop yield. However, it is unclear whether crops are able to distinguish reflected light quality of kin from that of non-kin. We evaluated the response of sugarbeet (Beta vulgaris L.) to reflected FR light from sugarbeet, common lambsquarters (Chenopodium album L.), Kentucky bluegrass (Poa pratensis L.), alfalfa (Medicago sativa L.), and bare soil (control) under outdoor conditions in 2016 and 2017. Treatments were completely randomized with 10 replications per treatment. The study methods ensured there was no direct resource competition. The reflected R:FR of plant species ranged from 0.06 (common lambsquarters) to 0.24 (sugarbeet) compared to 0.7 for the bare soil. In both 2016 and 2017, there were 2 to 4 more leaves in the sugarbeet surrounded by soil compared to sugarbeet surrounded by neighboring species. There was up to 47, 57, 43, and 23% reduction in sugarbeet leaf area, shoot dry weight, root diameter, and root dry weight, respectively, due to reflected R:FR light from neighboring species. Sugarbeet did not respond differently to reflected light quality of kin compared to non-kin.

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

The work proposes a new approach for evolutionary global optimization which, in simple terms, may be described as a fusion of quantum and simulated annealing. This becomes possible by using basic concepts from Homotopy Theory, conjugated to the already existing Fuzzy Adaptive Simulated Annealing paradigm and other components. In this fashion, it occurs a temporal and nonlinear superposition of the two types of annealing, provoking interesting effects in runtime, including the so-called quantum tunneling, when there is a sudden transition between attraction basins of different minima without "climbing" potential barriers. In addition, the proposal includes a generalization of the "deformation" of Hamiltonians used in quantum annealing by suggesting the use of general homotopies between the surface corresponding to the cost function under processing and another specific landscape, being this possible because of the ability of Fuzzy ASA of handling time-varying objective functions. The proposed paradigm shows that it is possible and beneficial to superpose the two types of annealing, displaying amazing numerical results and suggesting a kind of interlacing or synergic behavior - perhaps we could call it an "annealing entanglement". Finally, given the fast advances in commercial quantum annealing processors, it seems sensible to expect that an implementation of the proposed approach using such devices may occur very soon. In order to demonstrate the efficacy of the proposed algorithm, some significant and detailed examples are included in the text, so as to illustrate and clarify the presented ideas.

In this paper the problem of sampling from uniform probability distributions is approached by means of space-filling curves (SFCs), a topological concept that has found a number of important applications in recent years. Departing from the theoretical fact that they are surjective but not necessarilly injective, the investigation focused upon the structure of the distributions obtained when their domain is swept in a uniform and discrete manner, and the corresponding values used to build histograms, that are approximations of their true PDFs. This work concentrates on the real interval [0,1], and the Sierpinski space-filling curve was chosen because of its favorable computational properties. In order to validate the results, the Kullback-Leibler distance is used when comparing the obtained distributions in several levels of granularity with other already established sampling methods. In truth, the generation of uniform random numbers is a deterministic simulation of randomness using numerical operations. In this fashion, sequences resulting from this sort of process are not truly random.

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

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

Reef-dwelling calcifiers face numerous environmental stresses associated with anthropogenic carbon dioxide emissions, including ocean acidification and warming. Photosymbiont-bearing calcifiers, such as large benthic foraminifera, are particularly sensitive. To gain insight into their resistance and adaptive mechanisms to climate change, Amphistegina lobifera from the Gulf of Aqaba were cultured under elevated pCO2 (492, 963, and 3182 ppm) fully-crossed with elevated temperature (28°C and 31°C) for two months. Differential protein abundances in host and photosymbionts amongst treatments were investigated alongside physiological responses and microenvironmental pH variations. Over 1000 proteins were identified, of which one-third varied significantly between treatments. Thermal stress induced protein depletions, along with reduced holobiont growth. Elevated pCO2 caused only minor proteomic alterations and color changes. However, combined stressors reduced pore sizes and increased microenvironmental pH, indicating adaptive modifications to gas exchange. Notably, substantial proteomic variations at moderate-pCO2 and 31°C indicate cellular stress, while stable physiological performance at high-pCO2 and 31°C is scrutinized by putative decreases in test stability. Our experiment shows that the effects of climate change can be missed when stressors are assessed in isolation, and that physiological responses should be assessed across organismal levels to make more realistic predictions for the fate of reef calcifiers.

Ependymoma is responsible for 8–10% of all pediatric brain tumors and constitutes the third most common brain tumor in children. No robust molecular markers are yet in routine clinical use. Surgical resection and adjuvant radiotherapy cure approximately 40-70% of pediatric patients with ependymoma. In our centre, we have been using prophylactic valproic acid treatment for brain tumor patients. Initial observations indicated that valproate could have a beneficial effect in the survival of patients. Recent observations by other authors have shown that patients with glioblastoma benefited from the treatment with valproic acid, a histone deacetylase inhibitor. We have used random survival forest, a novel ensemble survival modelling method to study a single- center, small number cohort of pediatric patients with ependymoma. This analysis has confirmed surgery resection extent and treatment with radiotherapy as independent predictors of overall survival. Treatment with valproic acid was also a predictor of higher survival in this cohort. These results highlight the potential usefullness of the random survival forest model in gathering information from retrospective data. More data is needed about the possible influence of histone deacetylase inhibition by valproic acid in the survival of patients with ependymoma.

Assessment of the environmental impact of organic chemicals has become an important subject in chemical science. Efficient quantitative descriptors of their impact are their partition coefficients logPow, logKoa and logKaw. We present a group-additivity method that has proven its versatility for the reliable prediction of many other molecular descriptors for the calculation of the first two partition coefficients and indirectly of the third with high dependability. Based on the experimental logPow data of 3332 molecules and the experimental logKoa data of 1900 molecules at 298.15K the respective partition coefficients have been calculated with cross-validated standard deviations of only 0.42 and 0.48 log units and a goodness of fit Q^2 of 0.9599 and 0.9717, respectively, in a range of ca. 17 log units for both descriptors. The third partition coefficient logKaw has been derived from the calculated values of the former two descriptors and compared with the experimentally determined logKaw values of 1937 molecules, yielding a standard deviation of 0.67 log units and a correlation coefficient R^2 of 0.9467. This approach enabled the quick calculation of 29462 logPow, 27069 logKoa and 26220 logKaw values for the more than 37100 molecules of ChemBrain's database available to the public.

The concept of ecosystem services (ESs) provides a valuable approach to communicate societies' dependence on natural ecosystems, assisting in the evaluation of measures to protect vegetation in watersheds that promote water-related ESs. Vegetation cover and land use are important factors related to the capacity of ecosystems to provide soil loss regulation and sediment retention services, which are highly relevant for sediment management in watersheds draining into reservoirs with multiple water uses. This study aims to assess the relationship between potential changes in land use and land cover and the sediment retention service provided by riparian vegetation in a watershed draining into a hydroelectric reservoir in the Brazilian Cerrado. Sediment load was selected as a physical variable that affects different water uses in reservoirs, with these uses being dependent on the quality or quantity of stored water. Scenarios were analyzed to represent landscape reconfigurations from a baseline condition in order to account for the recovery of riparian vegetation by the agricultural sector, as foreseen in the Brazilian Forest Code. To map and quantify variations in annual sediment retention, the InVEST model was used, which allows estimating an integrated response of the drainage basin to large-scale land use changes over time and space. The results show that for the drainage basin of the Corumbá IV Hydroelectric Power Plant (HPP), the recovery of riparian areas occupied by annual crops has the potential to generate greater benefits to water use in the reservoir. In the studied catchment area, 14% of the total vegetation deficit in riparian areas is occupied by crops, while 86% is occupied by pastures. This highlights the buffering role of riparian vegetation as an effective practice for managing sediment flows originating from sheet erosion in agricultural landscapes. The methodology employed in this study allows for the quantification and mapping of the effects of soil and water conservation measures in river basins. This enables the prioritization of sectoral efforts for the restoration of native vegetation, considering the highest returns in benefits perceived by water users affected by sediment input in reservoirs. The study's results reinforce the importance of conserving vegetation in riparian areas and their surroundings for sediment retention, highlighting the role of these areas as assets in providing water-related ecosystem services.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

Systemic Lupus Erythematosus (lupus) and B-cell lymphoma (lymphoma) are serious diseases. Lupus and lymphoma co-occur at higher-than-expected rates and primarily depend on B-cells for their pathology, implicating shared inflammation-related B-cell molecular mechanisms as a potential cause of co-occurrence. We consequently implemented a novel Immune Imbalance Transcriptomics (IIT) algorithm and applied IIT to lupus, lymphoma, and healthy B-cell RNA-seq data to find shared- and contrasting mechanisms potentially targetable for treatment. We observed 8,562 genes significantly dysregulated in both lupus and lymphoma. Of those genes, we found 5,335 to have a significant immune imbalance, defined as significant dysregulation by both diseases, as determined by IIT. Gene Ontology (GO) term and pathway enrichment of IIT genes yielded immune-related “Neutrophil Degranulation” and “Adaptive Immune System”, validating that the IIT algorithm isolates biologically relevant genes in immunity and inflammation. We found that 389 IIT gene products are drug-targetable with established or repurposed drugs. Among our results, we found 40 known and 349 novel lupus targets, along with 151 known and 238 novel lymphoma targets. Known disease drug targets in our IIT results further validate that IIT isolates genes with disease-relevant mechanisms. We anticipate the IIT algorithm and shared and contrasting gene mechanisms uncovered here will contribute to the development of immune-related therapeutic options for lupus and lymphoma patients.

Metal nanoparticles are used to modify/enhance the properties of a polymer matrix for a broad range of applications in bio-nanotechnology. Here, we study the properties of polymer/gold nanoparticle (NP) nanocomposites through atomistic molecular dynamics, MD, simulations. We probe the structural, conformational and dynamical properties of polymer chains at the vicinity of a gold (Au) NP and a functionalized (core/shell) Au NP, and compare them against the behavior of bulk PE. The bare Au NPs were constructed via a systematic methodology starting from ab-initio calculations and an atomistic Wulff construction algorithm resulting in the crystal shape with the minimum surface energy. For the functionalized NPs the interactions between gold atoms and chemically adsorbed functional groups change their shape. As a model polymer matrix we consider polyethylene of different molecular lengths, from the oligomer to unentangled Rouse like systems. By computing the different properties the concept of the interface, and the interphase as well, in polymer nanocomposites with metal NPs are critically examined. Results concerning polymer density profiles, bond order parameter, segmental and terminal dynamics show clearly that the size of the interface / interphase, depends on the actual property under study. In addition, the anchored polymeric chains change the behavior/properties, and especially the chain density profile and the dynamics, of the polymer chain at the vicinity of the Au NP.

Satellite communication (Satcom) is an artificial geostationary satellite that facilitates a wide range of telecommunications. Considering its quality of service (QoS) and security is crucial in government/military applications. The most challenging situation for efficient Satcom is radio frequency interference (RFI) environment. Thus, it is necessary to ensure that transmissions are incorruptible or at least sense the quality of its spectrum. This paper presents a new method to recognize received signal characteristics using a hierarchical classification in a multi-layer perceptron neural network. We consider signal modulation and the type of RFI as the characteristics of a real-time video stream transmitted in the direct broadcast satellite. Four different modulation types are investigated in this study. Moreover, the combination of the communication signal with various kinds of interference and their effects on the classification method widely have been analyzed. Besides, two robust feature selection techniques have been developed to reduce the data-set dimensional, which leads to optimizing the classification process. The results show that the Genetic Algorithm (GA) slightly outperforms Principal Component Analysis (PCA) for feature selection. Furthermore, the robustness of the proposed techniques is assessed to detect unknown signals at different signal to noise ratios.

A useful and increasingly common additive manufacturing (AM) process is the selective laser melting (SLM) or direct metal laser sintering (DMLS) process. SLM/DMLS can produce full-density metal parts from difficult materials, but it tends to suffer from severe residual stresses introduced during processing. This limits the usefulness and applicability of the process, particularly in the fabrication of parts with delicate overhanging and protruding features. The purpose of this study was to examine the current insight and progress made toward understanding and eliminating the problem in overhanging and protruding structures. To accomplish this, a survey of literature was undertaken, focusing on process modeling (general, heat transfer, stress and distortion, and material models), direct process control (input and environmental control, hardware-in-the-loop monitoring, parameter optimization, and post-processing), experiment development (methods for evaluation, optical and mechanical process monitoring, imaging, and design-of-experiments), support structure optimization, and overhang feature design; approximately 140 published works were examined. The major findings of this study were that a small minority of the literature on SLM/DMLS deals explicitly with the overhanging stress problem, but some fundamental work has been done on the problem. Implications, needs, and potential future research directions are discussed in-depth in light of the present review.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

The spread of antimicrobial resistance (AMR) is a global challenge. Close and continuous surveillance for quick detection of AMR can be difficult, especially in remote places. This narrative review focuses on the contributions of pharmacovigilance (PV) as an auxiliary tool for identifying and monitoring the ineffectiveness of, resistance to, and inappropriate use of antibiotics (ABs). The terms “drug ineffective,” “therapeutic failure,” “drug resistance,” “pathogen resistance,” and “multidrug resistance” were found in PV databases and dictionnaires, and denote ineffectiveness. These terms cover a range of problems that should be better investigated because they are useful in warning about possible causes of AMR. “Medication errors,” especially those related to dose and indication, are highlighted in the literature, suggesting inappropriate use of ABs. Hence, the included studies show that the terms of interest related to AMR are not only present but frequent in PV surveillance programs. This review illustrates the feasibility of using PV as a complementary tool for antimicrobial stewardship activities, especially in scenarios where other resources are scarce.

This article discusses an international scientific expedition to Greenland that researched geography, geodesy, botany, and glaciology of the area. The results here focus on the geodetic and glaciological results obtained with the eBee drone in the eastern part of Greenland at the front of the Knud Rasmussen glacier. From two overflights nearby the glacier front, it was possible to obtain the speed of the glacier flow and the distribution of velocities in the glacier stream. The results correlate with other measurement methods and this technology has been shown as feasible. Of course, there are more accurate and long-term options or devices for monitoring the flow of glaciers. In this case of short-term visits to the site, the possibility of using a drone is interesting and the results show not only the flow speed of the glacier, but also the shape and structure from a height of up to 200m. The second part of the paper focuses on the analysis of modern satellite images of the Knud Rasmussen glacier from Google Earth (Landsat series 1984-2016) and a comparison with historical aerial images from 1932-1933. Experimentally, historical images were processed photogrammetrically into a 3D model.

Twelve overnight fasted, healthy, male volunteers received on separate days a test breakfast consisting of (A) 100 g fresh white bread (providing 50 g starch) and 250 mL drinking water, (B) the same bread with a supplement of 10 g alpha-cyclodextrin dissolved in the drinking water (250 mL), and (C) 250 mL drinking water containing 25 g alpha-cyclodextrin. Capillary and venous blood samples were collected before breakfast and at regular intervals for a period of 3 hours thereafter. Plasma glucose was determined in capillary blood and plasma insulin in venous blood samples. Breakfast (A) let to the expected rise in blood glucose and insulin concentrations. Breakfast (C) did not produce a significant glycemic and insulinemic response, demonstrating that alpha-cyclodextrin is not hydrolyzed to glucose in the human digestive tract. Mild intestinal symptoms after the ingestion of alpha-cyclodextrin were reported by 4 subjects. The postprandial rises of plasma glucose and insulin were significantly smaller after breakfast (B) than (A). Under the conditions of this study, alpha-cyclodextrin reduced the glycemic and insulinemic index of white bread by 57 and 55 %, respectively. The postprandial time profile of plasma glucose and insulin suggests that, in an initial phase, the digestion of starch is inhibited by alpha-cyclodextrin almost completely. Yet, despite the delayed and reduced digestion of starch, the intake of breakfast (B) was not associated with flatulence or any other gastrointestinal symptoms.

The paper examines design and operating data of current concentrated solar power (CSP) solar tower (ST) plants. The study includes CSP with or without boost by combustion of natural gas (NG), and with or without thermal energy storage (TES). The latest, actual specific costs per installed capacity are very high, 6085 $/kW for Ivanpah Solar Electric Generating System (ISEGS) with no TES, and 9227 $/kW for Crescent Dunes with TES. The actual production of electricity is very low and much less than the expected. The actual capacity factors are 22% for ISEGS, despite combustion of a significant amount of NG largely exceeding the planned values, and 13% for Crescent Dunes. The design values were 33% and 52%. The study then reviews the proposed technology updates to produce better ratio of solar field power to electric power, better capacity factor, better matching of production and demand, lower plant’s cost, improved reliability and increased life span of plant’s components. The key areas of progress are found in materials and manufacturing processes, design of solar field and receiver, receiver and power block fluids, power cycle parameters, optimal management of daily and seasonal operation of the plant, new TES concepts, integration of solar plant with thermal desalination, integration of solar plant with combined cycle gas turbine (CCGT) installations and finally, specialization and regionalization of the project specification.

Human ether-a-go-go-related gene (hERG) potassium channel is well-known contributor to drug-induced cardiotoxicity and therefore an extremely important target when performing safety assessments of drug candidates. Ligand-based approaches in connection with quantitative structure active relationships (QSAR) analyses have been developed to predict hERG toxicity. Availability of the recent published cryogenic electron microscopy (cryo-EM) structure for the hERG channel opened the prospect for using structure-based simulation and docking approaches for hERG drug liability predictions. In recent time, the idea of combining structure- and ligand-based approaches for modeling hERG drug liability has gained momentum offering improvements in predictability when compared to ligand-based QSAR practices alone. The present article demonstrates uniting the structure-based SILCS (site-identification by ligand competitive saturation) approach in conjunction with physicochemical properties to develop predictive models for hERG blockade. This combination leads to improved model predictability based on Pearson’s R and percent correct (represents rank-ordering of ligands) metric for different validation sets of hERG blockers involving diverse chemical scaffold and wide range of pIC50 values. The inclusion of the SILCS structure-based approach allows determination of the hERG region to which compounds bind and the contribution of different chemical moieties in the compounds to blockade, thereby facilitating the rational ligand design to minimize hERG liability.

A single paragraph of about 200 words maximum. For research articles, abstracts should give a Ultra-high performance concrete (UHPC) has gained worldwide popularity because of its notable mechanical response. This research studied the compressive strength, modulus of elasticity, and flexural tensile strength of UHPC. Batches were made with the addition of steel and PVA fibers using a standard procedure defined in the research. The experimental data from the compressive strength test was analyzed in the Statistica 10 software to investigate the fibers' influence on UHPC's mechanical properties. An analysis of the elastic modulus prediction was carried out according to international standards. It was found that the normalized equations for the elastic modulus are not adequate for its estimation. The statistical analysis indicated that the range of fiber quantities analyzed did not significantly affect the compressive strength and the elastic modulus. Regarding the optimized mix, its flexural tensile strength indicates that the fiber content must be higher for UHPC to be suitable for structural use.

Chronic Hepatitis B (CHB) Virus infection is major etiological factor for liver cirrhosis and/ or liver cancer. The viral protein, major contributor in predisposition of chronicity and Hepatocellular Carcinoma (HCC) is Hepatitis B x (HBx) protein. Its dynamic subcellular distribution to an extent determines its multifactorial role. It is a regulatory protein which modulates viral as well as host machinery in favours to HBV persistence. An insight on HBx stabilising factors is critical for therapeutic purpose. The precise role of HBx in the pathogenesis of Chronicity of HBV is not known. Summary: This review comprehensively summarizing different mechanisms and their regulation by HBx protein with respect to chronicity and HCC emphasising viral persistence. Key Messages 1. HBx is a key protein for viral persistence. 2. Dynamic subcellular distribution of HBx determines its function. 3. HBx modulates cellular machinery to favours HBV survival. 4. HBx affects various intermediary mechanisms contributing to disease progression. 5. HBx may be a potent target to prevent the disease progression towards HCC.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

Individuals with Parkinson’s disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MRL) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in freezers. Thirty-four freezers were assessed in the ON-medication state. During a functional magnetic resonance imaging protocol of simulated APA task, we assessed beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR), in addition to PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APAs amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2=0.32, P=0.0006) and APA amplitude (R2=0.13, P=0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

Abstract Antibacterial activities can be improved using mixed ligands. Mixed ligands involved in this research are sodium sulfadiazine (Na-sfz) and dithiocarbamate (ai-dtc). One-pot synthesis was used to synthesize ligand of aniline dithiocarbamate (ai-dtc) and the corresponding coordination compounds of [VO(sfz)(ai-dtc)] and [Zn(sfz)(ai-dtc)]. Crystals of ai-dtc, which grew from the solution when refrigerated after five days, were diffracted with technique of single crystal x-ray crystallography to reveal the structure. Other characterization techniques involving physicochemical parameters, FT-IR, UV-Vis and NMR (1H NMR and 13C NMR) were carried out on ligands of ai-dtc, sfz and corresponding coordination compounds. Differences in results of FT-IR, UV-Vis and NMR between ligands and their respective metal ions confirmed the coordination. The in vitro antibacterial studies showed that the ligands (not the metal complexes) had modest activity against Gram negative bacteria: Staphylococcus aureus, whereas, the coordination compounds had modest activities against the Gram negative bacteria: Escherichia coli and Pseudomonas aeruginosa.

Abstract: Seismic performance and loss assessments can have widely varying degrees of uncertainty. An essential issue is whether a particular assessed seismic loss or performance result has sufficient reliability to serve as the basis for risk management decisions and actions, including whether or not a code prescribed performance level is met, or if an assessed loss level is acceptable. A method is developed measuring the reliability of performance and loss assessments for individual buildings and for portfolios. Consideration is given to how well the building investigation and corresponding evaluation process have been performed, the qualifications of the person(s) doing the assessment, the thoroughness of the evaluation, and the technical validity of the assessment procedure or model. The approach characterizes the uncertainty of each component of the assessment procedure for each building in qualitative terms. The resulting reliability measure is likely to be most useful for the cases where an entity is determining whether/or not a building has acceptable life safety performance, or if a portfolio has an acceptably low risk of seismic damage loss over a given period of time. In both cases, the reliability must either be sufficient to warrant action, or serve to indicate need for improved assessment.

This pilot study explores the potential of using a citizen science approach for sourcing volunteered geographic information via social media to research wildlife tourism interactions with endangered Borneo Pygmy Elephants on the lower Kinabatangan River in Sabah, Malaysia. Such information is critical if the lower Kinabatangan region is to achieve the United Nations Sustainable Development Goals through a sustainable tourism industry based around viewing the pygmy elephants. Guests and guides from the Sukau Rainforest Lodge were encouraged to become close-range remote sensors by sharing geotagged photographs of pygmy elephant sightings on Flickr. A ten week on-ground trail generated 247 photographs shared by 17 individual contributors with approximately two-thirds (65%) of photographs being georeferenced for the time and location of the elephant sighting. Plotting those sighting to explore the vegetation matrix (i.e. remnant forest or oil palm plantation) showed almost three-quarter (73%) of the sightings occurred within 1 km of an oil palm plantation. Of greater concern is that one in two sightings (50%) along the river occurred within the 500 m of an oil palm planation, which is inside the riparian buffer that the Sabah Government recommended for conservation of the elephants in their Lower Kinabatangan range. This study therefore demonstrates proof of concept for this research method and its further application at the nexus of wildlife conservation and sustainable ecotourism research.

We estimate the effect of household social expenditure on vulnerability to poverty using the four latest cross-sectional waves of Ghana Living Standard Survey (GLSS) from 1999 to 2017. Using a 3-Stage Least Square and Quantile Regression, our results show a widening consumption ex-post welfare gap between the poorest households and the non-poor households in a per-cedi social expenditure. Also, we estimate the probability of an ex-ante poverty using vulnerability to expected poverty. The results, however, indicate that regardless of poverty status, household vulnerability to poverty increased consistently between 1999 and 2017, and the very poor households showing the severest vulnerability. Hence, it is concluded that social expenditure increases the chances of a poor household falling into chronic poverty a non-poor household into transient poverty in the future.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Many reported sea level records are often not a single measurement. They are then a composition of different records from several tide gauges. Sometimes, they are from the same tide gauge, but the tide gauge stability has been affected by earthquakes. This is the case of Guam as discussed in the present manuscript. The claimed sea level acceleration of Guam is only the result of two earthquakes that have compromised the stability of the tide gauge.

This work presents the computation of reliable warming trends for central Australia around Alice Springs within a circle of radius 1,000 km. Between 1880 and 2011, the average warming for the centre of Australia is +0.166 ºC/century, slightly smaller than the warming of Alice Springs, that is +0.176 ºC/century. Over a shorter time between 1910 and 2011, the centre of Australia is warming +0.794 ºC/century, slightly more than the warming of Alice Springs, that is +0.719 ºC/century.

Peroxiredoxins play central roles in the detoxification of reactive oxygen species and have been modelled across multiple organisms using a variety of kinetic methods. However, the peroxiredoxin dimer-to-decamer transition has been underappreciated in these studies despite the 100-fold difference in activity between these forms. This is due to the lack of available kinetics and theoretical framework for modelling this process. Using published isothermal titration calorimetry data, we obtained association and dissociation rate constants of 93.0 µM-4·s-1 and 102 s-1, respectively, for the dimer-decamer transition of human PRDX1. We developed an approach that greatly reduces the number of reactions and species needed to model the peroxiredoxin decamer oxidation cycle. Using these data, we simulated horse radish peroxidase competition and NADPH-oxidation linked assays and found that the dimer-decamer transition had an inhibition-like effect on peroxidase activity. Further, we incorporated this dimer-decamer topology and kinetics into a published and validated in vivo model of PRDX2 in the erythrocyte and found that it almost perfectly reconciled experimental and simulated responses of PRDX2 oxidation to hydrogen peroxide insult. By accounting for the dimer-decamer transition of peroxiredoxins, we were able to resolve several discrepancies between experimental data and available kinetic models.

The COVID-19 was described as a respiratory illness, however further studies recognize it as a complex heterogeneous multisystemic disorder. Global efforts have been proposed to combat COVID-19, emerging diverse therapeutic options, in which discovering new drug therapies, development of vaccines and drug repurposing have been considered the most promising approaches to fight the virus. This study aimed to repurpose known drugs for use against the COVID-19, finding better therapeutic options. Seventeen biological databases were used in this study. The genetic algorithm (GA) was performed for a set of drug target classes and COVID-19 proteins as input, whose drug candidates are obtained according to the target similarities found in the target-target similarity predictive network, resulting in a drug-target interaction network. Thus, recommended drugs correspond to the union of the drug subsets found during each GA execution. Twenty-eight drugs were indicated to be the best therapeutic targets for the virus, in special, the Cyclosporine drug was administered as adjuvant to steroid treatment for COVID-19 patients which showed positive outcomes, reducing mortality in moderate and severe cases. The drugs found have used to treat other diseases, evidencing that the COVID-19 is a multisystemic disorder and suggests that the viruses’ mechanism of action presents some comorbidity with other human diseases. Evidence shows that the drugs found in this research might act together to fight the virus in a broader fashion, however further studies including in vitro and in vivo experiments are needed to find the best combination of these drugs.

The purpose of this study is to investigate the perceived benefits of community gardening. A garden colony is a collection of adjacent plots of land primarily for the purpose of gardening. The methodology of this research consists of observations, interviews, questionnaires, and focus group. As a result of this research we found that gardening is a natural and safe way to meet the lifelong demands for a healthy life. We found specific mental and physical benefits as a result of this community gardening. We encourage communities to allow people to buy plots of land away from their homes to promote this healthy activity. The garden colony provides a place for individual renewal and restoration; this urban oasis offers a way to maintain and promote lifelong healthy living, and they are an important contribution to one’s life by adding a sense of meaning and purpose.

The novel coronavirus has presented specimen-access challenges to geoscientific researchers, including paleobiologists interested in fossil ammonoids. Ammonoid sutures are geometric patterns formed by the intersection of the septa and the shell wall, and have long been a diagnostic tool for ammonite researchers for such applications as species identification, taxonomic relationships, ontogenetic change, functional and evolutionary morphology, and other aspects of ammonoid paleobiology. Without access to specimens in museum and institutional collections, researchers must rely on previously published illustrations and photographs of ammonoid sutures. However, many of these illustrations were published decades ago without an index of scale. Suture tracings lacking a scale bar are not usable by researchers interested in applying the quantitativeness of fractal geometry to the interpretation of septal complexity. Additonally, distortion of the marginal elements of suture geometry occurs due to shell curvature near the venter and umbilicus. The revised approach described here eliminates the problem of missing scale information in fractal analysis of ammonite sutures, making use of just the lateral lobe and adjacent saddle. Our revised method’s non-requirement of a full hemisuture also facilitates comparisons among sutures within an ontogenetic sequence, or sutures from multiple ammonite taxa.

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by persistent deficits in social interaction and communication, repetitive movements, abnormal focusing on objects, or activity that can significantly affect the quality of life of the afflicted. Brain neuronal and glial cells have been implicated. It has a genetic component but can also be triggered by environmental factors or drugs. For example, prenatal exposure to valproic acid (VPA) or acetaminophen (APAP) or ingestion of propionic acid (PPA) can increase the risk of ASD. Recently, epigenetic influences on ASD have been brought to the forefront of investigations on the etiology, prevention, and treatment of this disorder. Epigenetics refers to DNA modifications that alter gene expression without making any changes to the DNA sequence. Although an increasing number of pharmaceuticals and environmental chemicals are being implicated in the etiology of ASD, here we specifically focus on the molecular influence of the above-mentioned drugs on epigenetic alterations in neuronal and glial cells and their potential connection to ASD. It is concluded that a better understanding of these phenomena can lead to more effective interventions in ASD.

Peri-urban forests often have extensive networks of greenways that allow for outdoor recreation. However, information associated with these greenways often does not include their degree of naturalness, which is usually reduced to descriptions of flora and fauna and often overlook the factors that reduce naturalness. Therefore, in some cases, the naturalness of these greenways is not as high as expected. Having a quantification of their naturalness would be useful, especially for hikers interested in appreciating and enjoying nature. Additionally, this information would help outdoor recreation managers to design trails or decide which ones to promote as "greenways". The objectives of this study are (1) to design a method to calculate and map the naturalness of greenways using two approaches, one based on perceptual fieldwork and the other on Geographic Information Systems (GIS); (2) to apply the designed method to a specific greenway; and (3) to compare both methodological approaches. The results show that, for the greenway studied, the naturalness scores obtained are low in all three types of analyses used. Around 70% of the greenway sections in the GIS visibility analysis and 80% in the GIS proximity analysis have a low naturalness index, while this value is reduced to 40% with the fieldwork analysis. Although the results of the GIS approach (proximity and visibility) generate naturalness indices and spatial patterns that are very similar, they differ significantly from those derived from the fieldwork analysis. The discussion of the results suggests that the three methodologies used are valid for analysing the degree of naturalness of the trails, but if used together, it would be possible to add flexibility to the type of variables incorporated in the analysis.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Silicates are among the most abundant and important inorganic materials, not only in the Earth’s crust but also in the interstellar medium in the form of micro-/nano-particles or embedded in the matrices of comets, meteorites and other asteroidal bodies. Although the crystalline phases of silicates are indeed present in Nature, amorphous forms are also highly abundant. Here we report a theoretical investigation of the structural, dielectric and vibrational properties of the amorphous bulk for forsterite (Mg₂SiO₄) as a silicate test case by a combined approach of classical molecular dynamics (MD) simulations for structure evolution, and periodic quantum mechanical DFT calculations for electronic structure analysis. Using classical MD based on an empirical partial charge rigid ionic model within a melt-quenching scheme at different temperatures performed with the GULP 4.0 code amorphous bulk structures for Mg₂SiO₄ were generated using as initial guess the crystalline phase. This has been done for bulks with three different unit cell sizes adopting a super-cell approach; i.e., 1×1×2, 2×1×2 and 2×2×2. The radial distribution functions indicated a good degree of amorphisation of the structures. Periodic B3LYP-geometry optimizations performed with the CRYSTAL14 code on the generated amorphous systems were used to analyze their structure, to calculate their high frequency dielectric constants (ε_∞), and to simulate the IR, Raman and reflectance spectra, which were compared with the experimental and theoretical crystalline Mg₂SiO₄. The most significant changes of the physico-chemical properties of the amorphous systems compared to the crystalline ones are presented and discussed (e.g., larger deviations in the bond distances and angles, broadening of the IR bands, etc.), which are consistent with their disordered nature. It is also shown that by increasing the unit cell size the bulk structures present larger degree of amorphisation.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

Hemicellulose is one of the most important natural polysaccharides in nature. Hemicellulose from different sources varies in chemical composition and structure, which in turn affects the modification effects and industrial applications. Grain and oil by-products (GOBP) are important raw materials for hemicellulose. This article reviews the modification methods of hemicellulose in GOBP. The effects of chemical and physical modification methods on the properties of hemicellulose biomaterials were evaluated. The potential applications of GOBP hemicellulose in films, hydrogel, Three-dimensional (3D) printing and adsorbent are discussed. Future research directions and recommendations are also proposed to provide theoretical foundations and technical support for the efficient utilization of these by-products.

Purpose: This integrated review aims to identify and analyze the multifactorial contributors to the longevity of direct restorations, focusing on tooth-, patient-, and dentist-related factors. Materials and Methods: A literature search was performed using an electronic database, PubMed/Medline, Web of Science, and Scopus, between 1980 and 2024. Titles and abstracts of papers that evaluated aspects categorized into tooth-related, patient-related, and dentist-related factors influencing restoration failure were selected and screened. Full-text assessments were conducted, and the extracted data were compiled, summarized, and synthesized. The reference lists of the collected papers were also screened, and relevant citations were included in this review. Data were gathered from clinical and laboratorial studies, systematic reviews, and meta-analyses to provide a comprehensive understanding of restoration longevity. Results: Among the tooth-related factors, multiple-surface restorations, deep margins, tooth location, and tooth vitality significantly impact restoration survival. Patient-related factors such as medical conditions, risk predictors of caries, age, sex, parafunctional habits, smoking, periodontal health, number of restorations, and socioeconomic status all play crucial roles. Regarding dentist-related factors, the decision-making process, age, experience, and dentist manual dexterity are vital aspects. Furthermore, the technique used, including isolation methods for moisture control, as well as the type of dental practice (large group vs. small practice), notably influenced the restoration survival. Conclusions: The longevity of dental restorations is influenced by a complex interplay of tooth-related, patient-related, and dentist-related factors. Strategies to improve restoration outcomes should consider all these multifactorial contributors. Continuing professional education, diligent patient guidance on the factors that influence restoration survival, careful material selection and restorative technique, and tailored individual treatment are crucial factors to reduce failure rates and improve the lifespan of restorations.

This study describes the seasonal course of denitrifying and nitrate reducing bacteria in a dimictic mesotrophic lake (Lake Scharmützelsee, Brandenburg, Germany) within a three-year period from 2011 to 2013. The bacterial cell numbers were quantified by fluorescence microscopy, most probable number (MPN) and PCR dependent quantification of the chromosomal 16S rDNA and of the nirS and nirK gene copy number. The highest seasonal differences (up to three orders of magnitudes) has been measured by MPN in the epilimnion. This variation was not reflected by PCR dependent approaches or direct microscopical enumeration. At adverse conditions (low temperature and/or low nitrate concentrations), the differences between MPN and gene copy numbers increased up to five orders of magnitudes and decreased to one magnitude at favorable environmental conditions. These results can be explained best by an increasing ratio of viable but not cultivable (VBNC) cells or dead cells at impairing conditions. In the hypolimnion, the courses of MPN and nir gene copy numbers were similar. This can be explained by higher feeding pressure and therefore smaller amounts of dormant cells. In the pelagial in general, the total cell numbers enumerated by either microscopical or molecular approaches were similar. In the sediment, more than 99 % of the DNA was obviously not related to viable bacteria but was rather “dead DNA” in dead cells or adsorbed to particle surfaces.