A transition-metal-free one-pot direct synthesis of tetrathiophosphates (R1S)2P(S)SR2 from white phosphorus (P4), through inter-mediate S-sodium S,S-dialkylphosphorotetrathioates (R1S)2P(S)SNa, is presented. In the presence of NaSH, various disulfides such as diaryl disulfides and dialkyl disulfides are easily coupled with P4 to give S-sodium S,S-dialkylphosphorotetrathioates (R1S)2P(S)SNa in almost quantitative yield, which react with alkyl halides in one pot to generate (R1S)2P(S)SR2. Furthermore, S-(2-cyanoethyl)-substituted tetrathiophosphates (R1S)2P(S)SCH2CH2CN are successfully designed as a kind of tetrathiophosphorylation reagents to react with diaryl iodonium salts involving deprotection-dealkylation process.

To promote the energy accommodation of both electrical and heating power while considering the source-load uncertainties, this paper proposes a peer-to-peer (P2P) energy trading model among prosumers in the integrated electric-thermal system, considering the energy trading agent (ETA) with self-build energy system. The Solar Heat-Pump Hybrid Thermal Water System (SPTS) and the transferring loss of heating power is considered and modelled based on the principle of steady-state thermal transfer. Since the variations of load and PV cannot be described by any single common distribution, the chance-constraints programming based on the Gaussian mixture model (GMM) is proposed to handle the uncertainty of the net load. As the proposed power trading problem is a non-convex problem with binary variables, an improved distributed alternating direction method of multiplier (ADMM) based on the predictor-corrector and two-stage cycle iterations is proposed to enhance the convergence performance of standard ADMM. Finally, an example simulation verifies the effectiveness, results show that the proposed model can decrease the total cost by 26.7% and enhance local energy balance by 61.8% compared to other cases.

Carbon-Hydrogen-Oxygen Symbiosis Networks (CHOSYNs) enable the centralized use of major atoms among substances.Previous decision-making in CHOSYNs researches always neglect the perspectives of multi-stakeholder, who have a claim on the cash flow of projects and may affect the sustainable operations of CHOSYNs. Hence, this paper proposes a system framework with the Multi-stakeholder decision method to balance the conflicts between stakeholders in the development of a CHOSYN. Multi-stakeholder decision method, which considers the benefits of each stakeholder, can gain a high satisfaction solution by using the dissatisfaction percentage (%D) and weight (ω). First, baseline the sources to get candidates by the multi-scale atomic targeting method. Then the simple objective and the multi-objective optimization method are used to obtain the Utopian point and the Nadir point respectively. Finally, the Multi-stakeholder decision method is used to select the optimal solution. A case study is solved to exhibit the advantages of the framewor

Background: While bacteria identification on respiratory cultures is associated with poor short-term outcomes in children with bronchopulmonary dysplasia (BPD) and tracheostomies, the influence on longer-term respiratory support needs remains unknown. Objective: To determine if respiratory culture growth of pathogenic organisms is associated with ongoing need for respiratory support, decannulation, and death at 3 years post-tracheostomy placement in children with BPD and tracheostomies. Methods: This single center, retrospective cohort study included infants and children with BPD and tracheostomies placed 2010-2018 and >1 respiratory culture obtained in 36 months post-tracheostomy. Primary predictor was any pathogen identified on respiratory culture. Additional predictors were any Pseudomonas aeruginosa and chronic P. aeruginosa identification. Outcomes included continued use of respiratory support (e.g., oxygen, positive pressure), decannulation, and death at 3 years post-tracheostomy. We used Poisson regression models to examine the relationship between respiratory organisms and outcomes, controlling for patient-level covariates and within-patient clustering. Results: Among 170 children, 59.4% had a pathogen identified, 28.8% ever had P. aeruginosa, and 3.5% had chronic P. aeruginosa. At 3 years, 33.1% of alive children required ongoing respiratory support and 24.8% achieved decannulation; 18.9% were deceased. In adjusted analysis, any pathogen and P. aeruginosa were not associated with ongoing respiratory support or mortality. However, P. aeruginosa was associated with decreased risk of decannulation (aRR 0.48, 95% CI 0.23-0.98). Chronic P. aeruginosa was associated with lower survival probability. Conclusion: Our findings suggest that respiratory pathogens including P. aeruginosa may not promote long-term respiratory dysfunction, but identification of P. aeruginosa may delay decannulation.

This article presents data of incidence, cause, and other knowledge we have about non cutaneous melanomas. What we found is that when analyzing cases with this type of cancer in Asturias, the incidence is much higher than what it is described in the literature for other parts of the world. It is interesting because the study has been carried out in the Central hospital of Asturias, it is the reference hospital in this province of northern Spain. My opinion is that the life expectancy of the region, combined with the lifestyle we have in Asturias, influences these data in a very noticeable way.

Background: To understand the changing trends in reporting of race and sex as a demographic variable in phase III lung cancer clinical trials published over the last 35 years. Methods: A total of 426 articles reporting results of phase 3 lung cancer clinical trials published from 1984 to 2019 were identified in PubMed. Statistical analysis on trends over time on percentage of minority and female participation were performed. Results: Only 137 (32.2%) of the 426 studies analyzed reported race of participants. Among those studies, we found that the mean participation rate of white participants was significantly higher (82.65%) (p < 0.001). We found a decrease in African American participants and an increase in Asian participants over time. When looking at sex, we found that although the rate of male participation (69.02%) was significantly higher than that of female participation (30.98%), the female participation has improved with time at a rate of 0.65% per year. Conclusions: We found that the reporting and participation of minority races continues to lag that of other demographic factors like sex in phase III clinical trials in lung cancer. Especially in African Americans, where the participation in lung cancer phase III clinical trials has declined despite the rising incidence in lung cancer.

The developable surface is a surface that can be unfolded on a plane without tearing or stretching, which is widely used in many fields of engineering and manufacturing. This work presents a new version of developable ruled surfaces in Euclidean 3-space. First, we establish an adapted frame along a spatial curve, denoted by the quasi-frame. We then introduce a parametric representation of a developable ruled surface and call it a directional developable ruled surface. At the core of this paper, we investigate the existence and uniqueness of such developable surfaces, then study their classification by singularity theory and unfolding method. Some examples are given in the final.

Scrutiny of experimental observations of bending of EM radiation, one of the determinant proofs of General Relativity, suggests a clue of profound significance; gravity appears to deflect EM radiation proportionally to its frequency. Differences in the deflection of light beams and microwave radiation are minimal, but statistically appreciable. The GEM Experiment described in this paper, patent released on December 2022 by the Italian “Ministero delle Imprese e del Made in Italy’‘, aims to employ a tunable source of gamma-rays, about the Higgs resonance, as the one tendered by the LHC facilities at CERN. The gamma-ray source is tunable for being tunable the energy employed to let Hadrons collide. The proposal is based on a critical discussion of the clues (fully detailed in the text “A critical discussion about Gravitation” ISBN 978-1-7948-5105-4) that the general theory of relativity suggests. Those lead to the resurrection of an Ether concept, not in the sense of a rigid structure where to drift through, but as a medium where to move. This eventually suggests a quantum approach based on a graviton conjecture. This model adds a NNLO correction to the NLO one provided by GR. The correctness of the model would finally explain the statistical bias observed above the value of deflection of the EM radiation, as expected from GR, and its remarkable dependence on frequency. The theory and the Experiment discussed in this paper aim to complete the general theory of relativity, and so propose a new way of construing Physics.

This paper deals with the study of existence of multiple positive solutions to a type of nonlinear fractional differential equation D α ( y ) + p ( t ) f ( y ( t ) ) = 0 , t ∈ ( 0 , 1 ) , 1 < α ≤ 2 together with the boundary condition y ( 0 ) = 0 , y ′ ( 1 ) = 0 , where D α represents the α-th order Riemann-Liouville type differential operator. p( t) is a positive continuous function on [0,1], and f:[0 ,∞)→[0 ,∞) is a continuous function. We use Schauder’s fixed point theorem to obtain at least one positive solution as well as we use Avery-Peterson fixed point theorem to obtain at least three positive solutions. . AMS Subject Categories: 34B18, 26A33 and 34B15.

The potential of using chatGPT in pharmacometrics was explored in this study, with a focus on developing a pharmacokinetic (PK) model for standard half-life factor VIII. Our results demonstrated that chatGPT can be utilized to accurately obtain typical PK parameters from literature, generate a population PK model in R, and develop an interactive Shiny application to visualize the results. ChatGPT’s language generation capabilities enabled the development of R codes with minimal programming knowledge and helped identify and fix errors in the code. While chatGPT presents several advantages, such as its ability to streamline the development process, its use in pharmacometrics also has limitations and challenges, including the accuracy and reliability of AI-generated data, the lack of transparency and interpretability of AI. Overall, our study demonstrates the potential of using chatGPT in pharmacometrics, but researchers must carefully evaluate its use for their specific needs.

A series of immune abnormalities presenting in aplastic anemia (AA) support the immune pathogenesis of AA. However, how abnormal immunity specifically damages hematopoietic stem cells (HSCs) remains ambiguous. The discovery of bone marrow immune privilege (IP) sites which are composed of CD4 +CD25 +FoxP3 + regulatory T cells (Tregs) exclusively to protect HSCs prompted us boldly assumed that it is a loss of IP protection leading to HSCs exhausted in AA. A experiment study to clinically confirm the correlation between HSCs depletion and IP abnormalities in patients with AA was conducted. The distribution of Tregs in bone marrow from children with AA, myelodysplastic syndrome (MDS) and control group was detected by immunohistochemistry. Th1, Th2, Th17 and HSCs as well as cytokines in bone marrow of these children were examined by flow cytometry. Tregs near endostea surface of bone marrow of children with AA was significantly lower than that in control and MDS. Th1 was more predominant in AA than in the control children. TNF-α, IFN-γ and IL-17 levels were also increased in AA. Compared to the control group, HSCs in bone marrow of AA, including Long-term HSCs (LT-HSCs) and Short-term HSCs (ST-HSCs), were at lower level. The results indicate that HSCs depletion is closely related to bone marrow IP abnormalities in AA, and the role of IP abnormalities in the pathogenesis of aplastic anemia deserves further research.

The influence of building direction (0°, 45° and 90°) on high cycle fatigue properties of a selective laser melted Al-Si alloy was investigated through uniaxial loading fatigue tests under stress ratio of 0 in combination with multi-dimensional imaging and electron backscattered diffraction analysis. Surface/subsurface failures were induced by single irregular lack of fusion defect originated from un-melt powder or inhomogeneous microstructure. Fatigue properties decreased as building angle arose, attributing to the size difference of original defect dominating crack nucleation, and the distribution difference of melting pool boundaries deflecting crack growth. According to the stress intensity factor evaluation, the threshold value of long crack growth and the transition size of crack growth exhibited decreasing tendency as building angle increased. Considering the influence of building direction on defect size distribution, a fatigue index parameter controlled crack nucleation life prediction model was established and the prediction result was satisfactory for safety design.

Background/Objectives: Transient hyperglycemia is an early endocrine effect observed during ALL chemotherapy. The goal of this study was to identify risk factors to hyperglycemia, compare data from two international protocols, and perceive if its occurrence leads to worse outcomes, such as infection, ALL relapse, or death. Methods: Data refers to a cohort of 188 pediatric patients undergoing ALL treatment at GRAACC/UNIFESP between 2004 and 2017. The effect of individual characteristics (protocol treatment, gender, age, ethnicity, family history of diabetes, puberty, nutritional status, ALL cell lineage, and chromosome Philadelphia) on hyperglycemia development was analyzed by univariate and multivariate logistic regression models. The role of hyperglycemia as a risk factor for infection, ALL relapse, and death was analyzed by ordinal logit regression, Fine and Gray competing risks models, and univariate and multivariate Cox regression, respectively. Results: The incidence of hyperglycemia was 43,6%. Puberty led to 7.9 greater risk for hyperglycemia (p=0.017). An increase of one year of age led to a 14% reduction in the chance of hyperglycemia among prepubertal individuals (p=0.039). The intermediate risk for ALL relapse had 67% less chance for hyperglycemia than high-risk patients (p=0.020). Hyperglycemia was not a risk factor for infection during ALL treatment (p=0.840), for ALL relapse (p=0.302), or for death (p=0.134). Conclusions: The identified risk factors for hyperglycemia during ALL chemotherapy were: younger age, puberty, and intermediate risk for ALL relapse. There was no difference in hyperglycemia incidence between patients undergoing GBTLI-2009 or BFM protocols. Hyperglycemia did not lead to worse outcome.

Title: Emerging Therapeutic Options for Sickle Cell Anemia: Enhancing the Current Predominant Treatment

There are no standardized pediatric treatment protocols for monomorphic post-transplant lymphoproliferative disorder (PTLD). We reviewed data from Canadian pediatric centers to determine patient characteristics, treatment approaches and outcomes. There were 55 eligible children diagnosed with monomorphic PTLD between January 2001-December 2021. Forty-nine (89%) underwent reduction of immunosuppression. The majority, 44 (80%), received rituximab, 40/44 (91%) with concurrent chemotherapy. A total of 46 (84%) children received chemotherapy: LMB-96 (48%) and low-dose cyclophosphamide with prednisone (30%) being the favored regimens. Projected 3-year event-free survival and overall survival was 62% and 77%, respectively. Approach to monomorphic PTLD treatment was relatively consistent across Canada.

Identification of previously unknown ion channels is always a challenging work though the transmembrane protein-coding genes in human genome has been comprehensively annotated for years. Despite being the gold standard of functional assay for ion channels, electrophysiological recordings are often accompanied by electrical noise, leak conductance and background currents of the membrane system. These unwanted signals, if not treated properly, lead to mischaracterization of proteins with seemingly unusual ion-conducting properties. In recent ten years, the technical revolution of cryo-electron microscopy (cryo-EM) have greatly advanced our understanding on the structures and gating mechanisms of various ion channels, and also raised concerns about the pore-forming ability of some previously identified channel proteins. In this review, we summarize cryo-EM findings on ion channels with molecular identities recognized or disputed in recent ten years, and discuss current knowledge of proposed channel proteins awaiting cryo-EM analyses. We also present a classification of ion channels according to their architectures and evolutionary relationships, and discuss the possibility and strategy of identifying more ion channels by analyzing structures of transmembrane proteins of unknown function.

Alteration in the physiological state of the endoplasmic reticulum (ER) leads to the specific response known as unfolded protein response (UPR) or ER stress response. The UPR is driven by three sensor proteins, namely: Inositol Requiring Enzyme 1 (IRE1), Protein Kinase RNA like ER kinase (PERK), and Activating Transcription Factor 6 (ATF6) to restore ER homeostasis. Pathogenic infection can initiate UPR activation; some pathogens can subvert the UPR to promote their survival and replication. Many intracellular pathogens, including Leishmania, can interact and hijack ER for their survival and replication, triggering ER stress and subsequently ER stress response. This review aims to provide a comprehensive overview of the ER stress response in infections with the Leishmania species .

Chikungunya virus (CHIKV) is an arbovirus ( Togaviridae family, Alphavirus genus), first identified in 1953 in Tanzania. In 2005, CHIKV emerged in India, and later caused outbreaks in Southeast Asia, Oceania and the Americas. Some Clinical signs are associated with CHIKV infection include fever and/or concomitant arthralgia, neurological manifestations and death. However, in infections caused by other arboviruses, such as the Dengue virus and West Nile virus, its often observed changes in liver enzymes. This study aims to evaluate the profile of the biochemical markers for kidney and liver injury patients infected with CHIKV in acute phase of infection. We found a significant elevation on the levels of creatinine in CHIKV-infected people, possibly associated with myalgia and indicative of muscle damage. The novelty was the elevated levels of creatinine found during a long period.

Abstract: Background: Cytidine/uridine monophosphate kinase 2 (UMP-CMP kinase 2, CMPK2) has been reported as an antiviral interferon-stimulated gene (ISG). We previously observed that the expression of CMPK2 was significantly upregulated after Zika Virus (ZIKV) infection in A549 cells. However, the role of CMPK2 in ZIKV replication remains to be determined. Methods: CMPK2 or retinoic acid inducible gene I (RIG-I) was overexpressed by plasmid transfection or knocked down by siRNA, respectively in A549 cells before the cells were infected with ZIKV. ZIKV RNA and NS1 protein were detected by RT-qPCR and Western Blot, respectively. The activation status of Jak-STAT signaling pathway was determined by the evaluation of the phosphorylation level of STAT1 (p-STAT1, by Western Blot), interferon stimulated response element (ISRE) activity (by dual luciferase assay) and interferon stimulated gene (ISG) expression (by RT-qPCR). Results: We found that ZIKV infection induced CMPK2 expression dependent on RIG-I. Overexpression of CMPK2 inhibited while CMPK2 knockdown promoted ZIKV replication. Mechanically, we found that CMPK2 inhibited ZIKV replication probably through the activation of Jak/STAT signaling pathway as shown by the increased level of p-STAT1, enhanced activity of ISRE, and the up-regulated expression of some downstream ISGs. Conclusion: ZIKV infection induced CMPK2 expression, which activated the Jak/STAT signaling pathway to inhibit ZIKV replication. Keywords: CMPK2; ZIKV; Jak/STAT signaling pathway

Nowadays, Land Degradation Neutrality (LDN) is on the political agenda as one of the main objectives in order to respond to the increasing degradation processes affecting soils and territories. Nevertheless, proper implementation of environmental policies is very difficult due to a lack of the operational, reliable and easily usable tools necessary to support political decisions when identifying problems, defining the causes of degradation and helping to find possible solutions. It is within this framework that this paper attempts to demonstrate that a new type of Spatial Decision Support System (S-DSS) that is developed on a Geospatial Cyberinfrastructure (GCI) might provide a valuable web-based operational tool which could be offered to EU administrative units (e.g. municipalities) so that they may better evaluate the state and the impact of land degradation in their territories. The land degradation data utilized were obtained from a platform named Trends.Earth, designed to monitor land change by using earth observations, and post-processed to correct some of the major artefacts relating to urban areas. The S-DSS ([www.landsupport.eu](http://www.landsupport.eu/)) has also been designed to encourage use by multi-user communities (from citizens to scholars, associations and public bodies). Moreover, it supports the acquisition, management and processing of both static and dynamic data, together with data visualization and computer on-the-fly applications, in order to perform modelling, all of which is potentially accessible via the Web. The Land Degradation tool, is designed to support land planning and management by producing data, statistics, reports and maps for any EU area of interest. It is in line with this LDD special issue which requires to report on “ advanced approaches and methods in land-based geoSpatial Decision Support Systems… implementation of S-DSS to address the various sustainable land uses in different sectors such as …environmental and human health”. The tool will be demonstrated through a short selection of practical case studies where data, table and stats are provided to challenge land degradation at different spatial extents. Currently there are WEBGIS system to visualise land degradation maps but – to our knowledge – this is the first SDSS tool enabling a customized LDN reporting at any NUTS level for the entire EU territory.

OS EFEITOS DA IMAGEM MENTAL EM DILEMAS MORAIS EM UMA SEGUNDA LINGUA

Background: Workforce shortages are key challenges facing veterinary practice. Anecdotal evidence suggests that veterinary students are less interested in entering equine practice than previously. Objectives: To investigate veterinary students’ perceptions about their equine veterinary education and about working in equine practice. Study Design: On-line survey. Methods: Survey distributed via social media to veterinary students at UK veterinary schools. Questions to document intended career path of students and evaluate perceptions about careers in equine practice. Results: 744 students completed the survey - from all 10 veterinary schools. 88.8% intended to work in clinical practice (32.9% mixed; 25.3% small animal; 20.2% equine; 10.9% farm; 10.7% other/undecided). Factors considered most important for their first job included: mentoring and support (47.0%), team and practice culture (26.2%), working hours (including out-of-hours) (9.2%), location (6.6%), salary and benefits (5.7%) and familiarity with the practice (3.1%). 55.2% felt there were barriers to entering equine practice. 46.9% had ridden a horse regularly; 14.2% had never ridden. Respondents in clinical years rated their university training in equine practice as ‘Excellent’ (10.0%), ‘Good’ (45.9%), ‘OK’ (35.3%), ‘Poor’ (7.0%) and ‘Rubbish’ (1.8%). 48.9% respondents felt EMS had contributed most to their equine training. Statistical associations were identified between the following variables and intention to work in equine practice: owning a horse, having ever ridden a horse, confidence in handling horses, student membership of BEVA, and desire to undertake an internship. Main Limitations: Potential selection bias. Conclusions: 20% of students reporting an intention in equine work does not explain problems with recruitment of equine vets. Potential mismatch between numbers of students interested in equine practice and availability of equine jobs for new graduates. Students with pre-existing equine interest /experience were more likely to want to enter equine practice. EMS appears important for students’ training in equine medicine.

Background: A reduction in the Egg Reappearance Period (ERP) has been suggested to be an early indication of emerging anthelmintic resistance in strongyles. Objective:To measure the strongyle ERP following moxidectin treatment of horses in the southeast of England. Study Design: Prospective study. Methods: Horses with a faecal egg count (FEC) of > 400 strongyle eggs per gram (EPG) in a routine screening sample were enrolled into the study. Moxidectin (400 mcg/kg) was administered per os and FEC tests repeated every 2 weeks for 16 weeks. Results: Forty-eight horses completed the study. The mean EPG prior to treatment was 1047 (range 375 – 2137 EPG). In all but two horses, FEC was 0 EPG 2 weeks after moxidectin administration. In the remaining two, the FECs were 12.5 EPG (97.8-98.3% reductions compared to pre-treatment FEC). At 4 weeks post-treatment, 6 horses had positive FECs (96.6-99.2% reductions). At 6 weeks, 11 horses had positive FECs (83.8% reduction in one horse; >90% reduction in 10). At 8 weeks, 21 horses exhibited positive FECs (<90% reduction in 2). At 10 weeks, 27 horses had positive FECs (<90% in 6). At 12 weeks, 31 horses had positive FECs (<90% reduction in 11). At 14 weeks, 34 horses had positive FECs (<90% reduction in 13). At 16 weeks, 38 horses had positive FECs (<90% reduction in 17). Limitations: Weights of some horses were estimated using weigh tapes rather than a weighbridge. Dosing of the horses with moxidectin was carried out by owners. Conclusions: The results indicated acceptable efficacy of moxidectin at 14 days after treatment; however, the ERP pattern measured across the group suggest that this anthelmintic has a considerably shorter suppressive effect on strongyle egg shedding than measured when it was first introduced ( >13 weeks and up to 24 weeks).

Due to climate warming, forests are expanding to higher elevations and latitudes at the expense of tundra vegetation. While the subsequent increase in aboveground biomass is well-documented, there is much speculation regarding the effects on soil organic carbon (SOC) stocks. To provide insight into the consequences of tree encroachment into treeless tundra, we sampled SOC stocks across 36 forest-tundra ecotones along a 1100 km latitudinal gradient in Norway. Our results show that SOC stocks vary greatly within, as well as among treeline ecotones, and that tree biomass and tree species are not correlated with this variability. Instead, SOC stocks increase with temperature, and vary with slope steepness, slope aspect, and soil parent material. Applying a ‘space-for-time substitution’ perspective, our findings suggest that tree encroachment into tundra is unlikely to have immediate consequences for SOC stocks.