In directional forming processes such as rolling and extrusion, the microstructure is strongly elongated in the forming direction. This results in a preferred alignment of the crystal orientations of the initially randomly oriented grains. These preferred orientations – the texture – and elongations of the grains are the cause of the material anisotropy. This anisotropy leads to phenomena such as earing, which occur during further forming processes, e.g., during deep drawing of sheet metal. Considering anisotropic properties in numerical simulations allows to investigate the effects of texture-dependent defects in forming processes and the development of possible solutions. Purely phenomenological models for modelling anisotropy work by fitting material parameters or applying measured R-values in experiments which are applied to all elements of the part and remain constant over the duration of the simulation. In contrast, methods such as the Visco-Plastic Self-Consistent (VPSC) model, which has been used in this work, provide a deeper insight into the development of the material microstructure. By experimentally measuring the initial texture and using it as an initial condition for the simulations, it is possible to predict the evolution of the microstructure and the resulting effect on the mechanical properties during forming operations. The results of the simulations with VPSC show good qualitative agreement with tests typically used for rolled stock.

We previously reported nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz). Blood, spleen, draining lymph nodes and tumors were harvested at 4-hour, 8-hour, 1-, 3-, 7-day. Additional studies were conducted over 3-month posttreatment intervals for the analysis of frequencies, death and functional markers of various immune cells in addition to suppressor function of regulatory T cells (Tregs). NPT was verified to elicit strong in situ vaccination (ISV) against breast cancer and promoted both acute and long-term T cell memory. NPT abolished immunosuppressive dominance systemically and in the TME by substantially reducing Tregs, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). NPT induced apoptosis in Tregs and TAMs. It also functionally diminished the Treg suppression capacity, likely explained by the downregulation of activation markers, particularly 4-1BB and TGFβ, and a phenotypic shift from predominantly activated (CD44+CD62L-) to naïve (CD44-CD62L+) Tregs. Importantly, NPT selectively induced apoptosis in activated Tregs and spared effector CD4+ and CD8+ T cells. These changes were followed by a concomitant rise in CD8+CD103+ tissue-resident memory T cells and TAM M1 polarization. These findings indicate that NPT effectively switches the TME and secondary lymphatic systems from an immunosuppressive to an immunostimulatory state allowing cytotoxic T-cell function and immune memory formation to eliminate cancer cells and account for the NPT in situ vaccination.

Recently, a concept known as μTRISTAN, which involves the acceleration of μ+, has been proposed. This initiative has led to considerations of a new design for a neutrino factory. Additionally, leveraging the polarization of μ+, measurements of T violation in neutrino oscillations are also being explored. In this paper, we present analytical expressions for T violation in neutrino oscillations within the framework of standard three flavor neutrino oscillations, a scenario involving nonstandard interactions, and a case of unitarity violation. We point out that examining the energy spectrum of T violation may be useful for probing new physics effects.

Lymphocyte collection by apheresis for CAR-T production usually does not include mobilized blood using Granulocyte Colony Stimulating Factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinic, makes necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent work that experimentally verifies the role and functionality of T and NK lymphocytes, and the generation of CAR-T, from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant and the different sub-populations remain stable. In addition, its expansion and proliferation rate are invariant regardless mobilization with G-CSF, as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.

Precise classification of sarcomas is crucial to drive optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC) we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was per-formed to all samples, using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed on the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary on molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for the optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases.

Heart failure is associated with a significant mortality rate, and an elevated prevalence of this condition has been noted among hypertensive patients. The identification of predictive factors for heart failure progression in hypertensive individuals is crucial for early intervention and improved patient outcomes. In this study, we aimed to identify these predictive factors utilizing medical history data for hypertension patients. Specifically, we focused solely on utilizing medical data preceding the diagnosis of hypertension to enable patients to anticipate the onset of potential heart failure at the time of hypertension diagnosis. Age-specific and ICD system-specific predictive factors were identified utilizing the MIMIC-IV database through the application of two analytical approaches: chi-square tests and XGBoost modeling. Our findings reveal 21 overall predictive factors, encompassing conditions such as atrial fibrillation, the use of anticoagulants, kidney failure, obstructive pulmonary disease, and anemia. These factors were assessed through a comprehensive review of the existing literature. We anticipate that the results will offer valuable insights for the risk assessment of heart failure in hypertensive patients.

Introduction: Biliary Atresia (BA) is a common cause of neonatal cholestatic jaundice which, if recognized and treated early, can be life-saving for the infant. If the liver biopsy suggests the presence of BA, exploratory laparotomy is then carried out to confirm the diagnosis, along with the Kasai procedure to provide drainage to the bile secreted by the liver. The purpose of this study is to get a deep dive into all the various imaging modalities that can diagnose BA more effectively and with absolute certitude, thus helping prevent several children from a grave prognosis.Methodology: For the collection of the data, a search was done by two individuals using PubMed, Google Scholar, and Cochrane Library databases for all relevant literature. Each qualifying paper was evaluated independently by two reviewers. Each article was analyzed for the number of patients, their age, procedure modality, complexity of ethology, and incidence of the pre-decided complications. The statistical software packages RevMan (Review Manager, version 5.3), SPSS (Statistical Package for the Social Sciences, version 20), Google Sheets, and Excel in Stata 14 were used to perform the statistical analyses. The data was obtained and entered into analytic software.Results: A total of 39 studies with 3,679 subjects were selected for the study, out of which 7 studies showed sensitivity above or equal to 95%, and an astounding 14 studies showed specificity above 95%. The value of True Positive (TP) was 1280, that of True Negative (TN) was 1817, that of False Positive (FP) was 239, and that of False Negative (FN) was 343. With a confidence interval of 95%, sensitivity, specificity, and positive predictive values were calculated. The sensitivity of Ultrasonography for Biliary Atresia is 0.79, with a CI of 95% in a range of 0.77 to 0.81. The specificity of Ultrasonography for Biliary Atresia is 0.88, with a CI of 95% in a range of 0.87 to 0.90. Conclusion: Even though several radiological techniques at present help to detect BA, USG of the abdomen proves to be an effective diagnostic and a modest screening test for the detection of BA.

The intelligent morphing wing structure has the characteristics of flexibility, large deformation and adaptive change, which are different from those of the conventional wing. The motion law of the variable-camber leading edge is analysed by the numerical simulation method based on kinematics theory to solve the problem of verifying the motion function and structural strength of the variable camber wing. The driving deformation and aerodynamic load simulation of the variable camber leading edge are realised by designing a follow-up load test apparatus. Based on the numerical simulation of the mechanical boundary, the motion trajectory of the upper and lower wing loading points was predicted, and a multi-point cooperative control system was developed. Multi-sensor iteration was used to ensure the loading accuracy of the test control. The test results show that the average error of the deflection angle is 4.59% in the variable camber leading edge motion test. In the variable camber leading edge strength test, the average error of applied load magnitude and direction is 0.54% and 0.24%, respectively.

KLEPTOSE® CRYSMEB is a methylated cyclodextrin derivative displaying less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases. linked in part to cholesterol complexation and immune response, but the impact on inflammatory cascade pathways was not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells in physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® Panel. Finally, the anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects driven by pro-inflammatory cytokine secretion inhibition and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Finally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by well-known anti-inflammatory molecules.

Public transportation scheduling aims to optimize the allocation of transportation resources, enhance transportation efficiency, and increase passenger satisfaction, which is crucial for building a sustainable urban transportation system. As a complement to public transportation, shared bikes provide users with a solution for the last mile of travel, compensating for the lack of flexibility in public transportation and helping to improve its utilization rate. Due to the characteristics of shared bikes, such as peak usage periods in the morning and evening and significant fluctuations in demand across different areas, the optimization of shared bike dispatch can better meet user needs, thereby reducing vehicle vacancy rates and increasing operating revenue. Addressing this issue, this paper designs a comprehensive decision-making approach for spatio-temporal demand prediction and bike dispatch optimization. For demand prediction, we designed a T-GCN based bike demand prediction model. In terms of dispatch optimization, we considered factors such as dispatch capacity, distance restrictions, and dispatch costs, and designed an optimization solution based on genetic algorithms. Finally, this paper validates the approach using shared bike operating data, shows that T-GCN can effectively predict short-term demand for shared bikes. Meanwhile, the optimization model based on genetic algorithms provides a complete dispatch solution verifying the model’s effectiveness. The shared bike dispatch approach proposed in this paper, which combines demand prediction with resource scheduling. This scheme can also be extended to other transportation scheduling problems with uncertain demand, such as store replenishment delivery and intercity inventory dispatch.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

As a new plant slope protection technology, living stumps can effectively improve slope stability. The current study attemptes to investigate the mechanical characteristics of the root system of living stumps and their reinforcement mechanism on slopes by carrying out a three-dimensional living stump slope modeling test. Using ABS materials, a 3D model of a living elm stump was created by 3D printing and a slope model test was carried out. The reinforcement mechanism of the living stump was studied through a combination of model testing and numerical simulation. The results indicate that, due to the presence of living stumps in the lower and middle parts of the slope, the maximum shear stress area of the soil moved to a deeper direction. The stress state of the soil around the living stump was effectively improved due to the existence of the lateral root system.Living stumps in the lower part of the slope cross the potential sliding surface and transferred the soil shear stress gradually to the root system through root-soil interaction. Moreover, the tap roots and lateral roots of living stumps form a robust spatial structure that bears the shear stress of soil together, thus increasing the stability of the slope.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

The liver diseases are posing serious threat to human health associated with abusive use of allopathy medicines, especially in developing economies like Pakistan. The strengthening of detoxification system using natural products might be a suitable option to minimize the liver problems. In this current research, Zingiber officinale and Azadirachta indica were evaluated for their hepatoprotective role. For the purpose, 20 Sprague Dawley rats were equally divided into four groups i.e., negative control, paracetamol positive control, 2.5% ginger and 2% neem powder, respectively. During 42 days study, the levels of bilirubin and liver enzymes significantly elevated due to liver damage. Although, the values dropped (20-25%) in treatment group. Serum glucose and serum lipid profile increased in positive control group, but reduced (5-10%) in both ginger and neem groups. The serum protein profile declined in liver damage group, however, improved (~5%) in treatment groups. The hematological parameters slightly declined in liver damage group, but increased in ginger and neem groups. Moreover, the white blood cells differential count and renal parameters showed abnormal values in liver damage group, but improved after treatment. This study is promising and highlighted the hepato-protective role of neem and ginger that may open several avenues of research.

Among the different steps in software development software testing is one of the inevitable steps. Manual testing is considered to be more expensive and time-consuming, and this led to the formation of automated testing tools. Automated software testing tools offer a comprehensive system testing solution that minimizes the risk of any errors that could result in financial losses. One such tool is selenium. Selenium testing is an advantageous method employed by developers and testers to assess their code. Selenium is compatible with numerous widelyused programming languages like C#, Java, Python, and more. This paper focuses on understanding the in and outs of software testing using selenium

Analyzing BRCA1/2 tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOC) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays, or sequencers used, and data on the execution of tumor tests remains scarce. Therefore, we evaluated characteristics of BRCA1/2 tumor testing in advanced-stage EOC with real-world national data. Pathology reports of patients diagnosed with EOC in 2019 in the Netherlands were obtained from the Dutch Pathology Registry (PALGA), and data regarding histological subtype and BRCA1/2 tumor tests were extracted. A total of 999 patients with advanced-stage EOC were included. Tumor tests were performed for 502 patients (50.2%) and BRCA1/2 TPVs were detected in 14.7%. Of all tests, 48.6% used hybrid capture techniques and 26.5% used PCR-based techniques. More than half of the tests (55.0%) analyzed other genes in addition to BRCA1/2. Overall, this study highlights the heterogeneity in the execution of BRCA1/2 tumor tests. Despite a lack of evidence of quality differences, we emphasize that adequate reporting and internal and external quality monitors are essential for high-quality implementation and execution of reliable BRCA1/2 tumor testing, which is crucial for identifying all patients with BRCA1/2 TPVs.

This study uses a mass-spring-damping system to simulate the repeated strain of liquefaction cyclic triaxial tests. The two results are compared in this paper to understand the feasibility of the mass-spring-damping system developed in this paper and the feasibility of future research on this related topic and development potential. The main factors affecting this mode's repeated strain are the spring coefficient k and the external force Q0. The spring coefficient has an inverse relationship but does not increase in multiples. The external force has a direct proportional relationship but does not increase the result- a non-multiple increase. When the pore water pressure of the liquefied cyclic triaxial test specimen rises, it will cause the specimen to liquefy, decreasing effective stress, shear modulus G, and damping ratio D, causing an increase in strain. The shear modulus and damping ratio are related to the spring coefficients k and c. Both are variables that change with time. This article takes an original thin-tube specimen at point A in the Yunlin area in Taiwan as a testing example. Through Mathematica software, it can be obtained that the mass m=1kg, the spring coefficient k=244e-0.1t kgf/cm, and the damping coefficient c=0.739e-0.257t kgf-s/cm and external force Q0=10.1sin2πt kg; Finally, this study selected the original thin-tube specimens from four locations in the Yunlin area, and simulated the repeated strain amount of the cyclic triaxial test specimens through a spring-damping system. The results show that the spring-damping system is feasible for simulated cyclic triaxial tests because the model is simple and the parameters are easy to understand and obtain, which also shows the extensibility of this model. Preliminary results of the research show that this model can further simulate the repeated strain obtained by cyclic triaxial tests without considering the increased trend in pore water pressure and the decrease in effective stress during cyclic loading.

The rates of obesity and obesity-related diseases continue to increase worldwide, classifying obesity as a global epidemic. Endogenous opioids have been implicated in influencing feeding behavior; however, the role of each opioid peptide is still only partially characterized. Therefore, we assessed the role of the proopiomelanocortin (POMC)-derived peptide beta-endorphin (β-END) in long-term high-fat diet (HFD) feeding and glucose homeostasis and assessed if sex-related differences exist in these processes. Male and female mice lacking the ability to produce β-END and their respective controls were subjected to a 12-week HFD consumption to determine the role of the opioid peptide in food intake and glucose homeostasis. Body weight and food intake were measured weekly for twelve weeks. At weeks 6 and 12, plasma glucose levels were measured using an oral glucose tolerance test. Here, we report that male β-END deficient mice gained more weight and consumed more calories than their wildtype controls; however, this difference was not observed in the female mice. Regardless of genotype, female mice consumed more calories per body weight when compared to male mice despite their smaller body weights. Moreover, our findings suggest differences in glucose homeostasis between the wildtype and knockout mice and that these were only observed at week six but not at week 12. Overall, our study suggests that endogenous β-END may play a role in controlling body weight, feeding behavior, and glucose homeostasis and that sex-related differences may exist in this regard.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by absent accurate, non-invasive uniformly diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers unique to endometriosis allow noninvasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age >18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically histologically-confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30-minutes post water-load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, NPV, PPV and predictive probability or C-Statistic used univariate, multivariate, linear and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: Non-endometriosis cohort differed significantly from endometriosis cohorts (p<0.001) for median (IQR), and AUC percent frequency distribution of power at baseline, 10-minute, 20-minute, and 30-minute post water-load at all frequency ranges 15-20cpm, 30-40cpm and 40-50cpm. Endometriosis cohorts were statistically similar (p>0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV and C-statistic of >99%/98% respectively for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: Non-invasive electroviscerography with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis specific GIMA biomarkers threshold scoring.

Improper sitting positions are known as the primary reason for back pain and the emergence of musculoskeletal disorders (MSD) among individuals who spend prolonged time working with computer screens, keyboards, and mice. At the same time, it is well understood that automated technological tools can play an important role in the process of unhealthy habit alteration, so plenty of research efforts are focused on research and technology development (RTD) activities that aim to provide support to the prevention of back pain or the development of MSD. Here, we report on creating a new resource in support of RTD activities aiming at the automated detection of improper sitting positions. It consists of multimodal multisensory recordings of 100 persons made with a video recorder, camera, and wrist-attached sensors that capture physiological signals (PPG, EDA, Skin temperature), as well as motion sensors (three-axis accelerometer). Our multimodal multisensory dataset (MMD-MSD) opens new opportunities for modeling the body stance (sitting posture and movements), physiological state (stress level, attention, emotional arousal, valence), and performance (success rate on the Stroop test) of people working with a computer. Finally, we demonstrate two use cases: improper neck posture detection from pictures and cognitive load detection from physiological signals.

The interface of a structural system in the soil is usually unsaturated. A decrease in the shear strength of the soil-structure interface can degrade the structure, especially under humid conditions. Studying the shear characteristics of the silt-concrete interface using a shear apparatus. Suction-controlled ring shear tests were carried out on the silt-concrete interface for three interface roughness values. The influence of the matric suction (s) and interface roughness (R) on the shear strength index of the silt-concrete interface was analyzed. The test results showed that high values of s and R improved the shear strength of the interface, but the result was affected by the net normal stress (NNS). High values of NNS and R improved the strain-hardening characteristics. NNS, s, and R significantly affected the interface shear shrinkage. The internal friction angle of the saturated interface was smaller than that of saturated silt, whereas the opposite occurred in the unsaturated state. The cohesion and internal friction angle of the interface rose with an increase in R, and they were larger than that of silt. A shear strength model of the silt and interface was established.

Multiple sclerosis is an autoinflammatory condition that results in damage of myelinated neurons in affected patients. While disease-modifying treatments have been successful in slowing the progression of relapsing remittent disease, most patients still progress to secondary progressive disease that is largely unresponsive to disease-modifying treatments. Similarly, there is currently no effective treatment for patients with primary progressive MS. Innate and adaptive immune cells in the CNS play a critical role in initiating an autoimmune attack and in maintaining the chronic inflammation that drives disease progression. In this review, we will focus on recent insights into the role of T cells with regulatory function in suppressing the progression of MS, and, more importantly, in promoting the remyelination and repair of MS lesions in the CNS. We will discuss the exciting opportunity to genetically reprogram regulatory T cells to achieve immune suppression and enhance repair locally at sites of tissue damage, while retaining a fully competent immune system outside the CNS. In the future, reprogramed regulatory T cells with defined specificity and function may provide life medicines that can persist in patients and achieve lasting disease suppression after one cycle of treatment.

Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic type of tumor. TNBC is often enriched in tumor-infiltrating neutrophils (TINs), which support cancer growth in part by counteracting tumor-infiltrating lymphocytes (TILs). Prior studies identified the enhancer of zeste homolog 2 (EZH2) as a pro-tumor methyltransferase in primary and metastatic TNBC. We hypothesized that EZH2 inhibition in TNBC cells per se would exert anti-tumor activity by altering the tumor immune microenvironment. To test this hypothesis, we used CRISPR to generate EZH2-knockout (KO) and overexpressing lines from parent (wild-type -WT) 4T1 cells, an established murine TNBC model. In vitro, EZH2 KO and OE cells showed little change in replicative capacity and invasiveness, but marked changes in surface marker profile and cytokine/chemokine secretion compared to WT cells. On in vivo injection, EZH2 KO cells showed significantly reduced primary tumor growth and a 10-fold decrease in lung metastasis compared to WT cells, while EZH2 OE cells were unchanged. Compared to WT tumors, TIN:TIL ratios were greatly reduced in EZH2 KO tumors but unchanged in EZH2 OE tumors. Our findings show a tumor-intrinsic role of EZH2 in the 4T1 TNBC model in regulating TIN/TIL poise, primary tumor progression and lung metastasis in vivo.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

Background: Diet is a risk factor for gestational diabetes mellitus (GDM). There are few studies on women´s diet and glucose tolerance test (GTT) results. Objective: To evaluate the relationship between previous diet and the number of abnormal values on the diagnostic GTT in women with GDM. We hypothesized there would be an inverse relation between antioxidant micronutrient consumption and the number of abnormal GTT values. Methods: This cross-sectional study included 60 women diagnosed with GDM (2-hours, 75g-GTT). Shortly after diagnosis, participants answered a validated food frequency questionnaire to assess food consumption in the last 6 months. Mann-Whitney´s test was used to compare the dietary intake of participants with one (group 1) versus two-three (group 2) abnormal GTT values. Results: Participant characteristics were similar. There were no significant differences between groups in median intake of total calories, carbohydrates, lipids and proteins. Participants in group 1 had significantly higher intakes of fiber (11.9 vs. 11.0 g/day p= 0.049), vitamin D (40.6 vs. 40.4 mcg/day p= 0.049) and vitamin C (180.0 vs. 151.0 mg/day p= 0.008) than those in group 2. Conclusion: Results suggest a possible association between consumption of fiber and some antioxidant micronutrients and GDM severity at the time of diagnosis.

The mechanism of immune activation and de-activation is very important. Host should trigger effective immunity against pathogen infection. And, host cannot trigger immunity against self-antigens that will lead to detrimental autoimmune disorders. Spleen and liver have opposite roles in mediating immune responses. Spleen is the organ involving in immune activation, and liver is the organ involving in immune de-activation. Sympathetic nerve system and parasympathetic nerve system have opposite roles in mediating immune responses. Sympathetic nerve system is involving in pro-inflammatory, and parasympathetic nerve system is involving in anti-inflammatory. ACTH and glucocorticosteroid have opposite roles in mediating immune responses. ACTH is involving in activating adaptive immunity with inhibiting innate immunity, and glucocorticosteroid is involving in activating innate immunity with inhibiting adaptive immunity. The molecular chaperons, heat shock proteins, which are induced by fever, have the vital roles in immune activation. On the contrary, IgD B cells and gamma-delta T cells are causing immune de-activation via the mechanism of clonal anergy. These mechanism can help us the know the work of immunological pathways better for better control of infectious diseases and autoimmune disorders.

The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

Graft injury affects over 50% of liver transplant (LT) recipients, but non-invasive biomarkers to diagnose and guide treatment are currently limited. We aimed to develop a biomarker of graft injury by integrating serum metabolomic profiles with clinical variables. Serum from 55 LT recipients with biopsy confirmed metabolic-dysfunction associated steatohepatitis (MASH), T-cell mediated rejection (TCMR) and biliary complications was collected and processed using a combination of LC-MS/MS assay. The metabolomic profiles were integrated with clinical information using a multi-class Machine Learning (ML) classifier. The efficacy of the model was assessed through the evaluation of the Out-of-Bag (OOB) error estimate. Our ML model yielded an overall accuracy of 79.66% with an OOB estimate of the error rate at 19.75%. The model exhibited a maximum ability to distinguish MASH, with an OOB error estimate of 7.4% compared to 22.2% for biliary and 29.6% for TCMR. The metabolites serine and serotonin emerged as the topmost predictors. When predicting binary outcomes using 3 models: Biliary (biliary vs. rest), MASH (MASH vs. rest) and TCMR (TCMR vs. rest), the AUCs were 0.882, 0.972 and 0.96 respectively. Our ML tool integrating serum metabolites with clinical variables shows promise as a non-invasive, multi-class serum biomarker of graft pathology.

Although various atmospheric corrosion simulation models have been developed that give good results, industrial environments are still challenging. This paper aims to investigate the effect industrial atmospheres in Bor on the mechanical properties of structural steel S235JR and to create a constitutive model and also laboratory experimental conditions that will give the best results as an accelerated corrosion test. Atmospheric corrosion tests lasted six months, using sites close to the Electrolytic Refining Plant and Sulphuric Acid Plant, as well as air quality monitoring stations at a remote location in the city of Bor. The laboratory experiments included a salt chamber test lasting 120 h and 240 h and immersing the specimen in the electrolyte from the Electrolytic Refining Plant for 30 days. The results were compared with the standard specimens stored in the laboratory. The X-ray diffraction (XRD) method was used to identify the composition of corrosion products. The scanning electron microscopy (SEM) analysis was applied to analyze the fracture surfaces of the specimens. The use of the Complete Gurson Model (CGM) described the tensile characteristics of the corroded specimens. The study has shown that an enhanced acceleration model and conditions could be developed using numerical analysis of the test results.

Immune responses to influenza (flu) antigens reflect memory to prior infections or vaccinations, which might influence immunity to new flu antigens. Memory of past antigens has been termed “original antigenic sin” or more recently “immune imprinting” and “seniority”. We have researched a comparison between the immune response to live flu infections and inactivated flu vaccina-tions. A brief history of antibody generation theories is presented culminating in new findings about the immune-network theory suggesting that a network of clones exists between an-ti-idiotypic antibodies and T cell receptors. Findings regarding the 2009 pandemic flu strain and immune responses to it are presented, including memory B cells and conserved regions within the hemagglutinin protein. The importance of CD4+ memory T cells and cytotoxic CD8+ T cells responding to both infections and vaccinations are discussed and compared. Innate immune cells like natural killer (NK) cells and macrophages are discussed regarding their roles in adaptive immune responses. Antigen presentation via macroautophagy processes are described. New vaccines in development are mentioned along with the results of some clinical trials. The manu-script concludes with how repeated vaccinations are impacting the immune system and a sketch of what might be behind the imprinting phenomenon, including future research directions.

Background: Open AI developed ChatGPT, a language model based on the GPT architecture, designed for text-based communication. Trained on diverse internet texts, ChatGPT generates contextually appropriate responses using machine learning. It understands input through analysis and context interpretation, generating coherent and contextually relevant responses. Interaction is possible through messaging platforms. Materials and Methods: In November 2023, we utilized ChatGPT 3.5, the default version at that time, to answer questions from the Italian National Residency Program Admission Tests (SSMs) of 2021, 2022, and 2023. The questions cover clinical, diagnostic, analytical, therapeutic, and epidemiological scenarios, sometimes accompanied by images. The study compared ChatGPT's answers to the official corrections on the Italian Ministry of University and Research (MUR) website. The scoring method used for evaluation was 1 point for correct answers, 0 points for unanswered questions, and -0.25 points for incorrect answers, reflecting the SSM test scoring system. Results: In summary, ChatGPT was tested with a total of 420 questions, 140 for each test. It achieved an overall accuracy of 80.48%, providing correct answers for 338 questions and incorrect answers for 82 questions. When faced with questions containing both text and images, it answered 55% correctly and 45% incorrectly. The model's performance varied over time, with an 82.14% accuracy rate in 2021 and 2022 (115 correct out of 140) and a 77.14% accuracy rate in 2023 (108 correct out of 140). Applying thisscoring method to the SSM test, ChatGPT would have scored 105 points in 2021 and 2022, and 100 points in 2023. Conclusions: ChatGPT has exhibited above-average performance in the last three SSM tests, highlighting its robust capability to interpret clinical scenarios and offer precise diagnostic and therapeutic guidance. Despite this, some limitations persist, notably the software's inability to interpret non-textual information.

In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

Drug hypersensitivity reactions (DHR) to platinum-based compounds (PC) are on the rise, and their personalized and safe management is essential to enable first-line treatment of these cancer patients. This study aimed to evaluate the usefulness of basophil activation test by flow cytometry (BAT-FC) and the newly developed sIgE-microarray and BAT-microarray in diagnosing IgE-mediated hypersensitivity reactions to PC. 24 patients with DHR to PC (20 oxaliplatin and four carboplatin) were evaluated: 13 patients diagnosed as allergic with positive skin tests (STs) or drug provocation tests (DPTs), six patients diagnosed as non-allergic with negative STs and DPTs, and five patients classified as suspected allergic because DPTs could not be performed. In addition, four carboplatin-tolerant patients were included as controls. BAT-FC was positive in 2 of 13 allergic patients, with a sensitivity of 15.4% and specificity of 100%. However, the sIgE- and BAT-microarrays were positive in 11 of 13 DHR patients, giving a sensitivity of over 84.6% and a specificity of 90%. Except for one patient, all samples from the non-allergic and control group were negative for the sIgE- and BAT-microarrays. Our experience indicates that sIgE- and BAT-microarray could be helpful in the endophenotyping of IgE-mediated hypersensitivity reactions to PC and may provide an advance in decision-making for drug provocation testing.

This retrospective study examines 248 test-bolus examinations preceding contrast-enhanced magnetic resonance angiography (CE-MRA) to extract clinically relevant data for critical limb ischemia (CLI) management. Methods involved a retrospective review of test-bolus exams, analysing 60 graphs for time-to-peak (TTP), full-width half-maximum (FWHM) time, and time to continual rise in signal intensity. These values were correlated with heart function parameters (ejection fraction, ASA-Classification, Lee-Index, and MET-Score). Results indicate a mean TTP of 31.2 ± 7.3s, showing a correlation between ejection fraction and ASA classification. Patients with atrial fibrillation exhibited prolonged TTP compared to those without. Despite population heterogeneity, findings facilitate risk stratification for limb-saving interventions in CLI. TTP emerges as a potential clinical cardiovascular parameter and a risk factor for vascular interventions. Given the variation in injection protocols across centres, this study underscores the importance of precise bolus arrival time documentation for future multicentre studies.

In the construction sector, the integration of biobased materials has emerged as a pivotal aspect of EU policies, aimed at promoting sustainable practices throughout the value chain to mitigate resource consumption and carbon emissions. This paper explores the development and validation activities of a bio-based façade system within the Basajaun H2020 project, focusing on enhancing the utilization of biobased components within building envelopes to replace conventional solutions with eco-friendly alternatives. This paper reports the methodologies employed to detect requirements and outline the testing protocols undertaken to validate the façade system design devised within the project focusing on the original façade components as the bio composite profile. Vision and opaque façade modules are prototyped and tested following curtain wall standards standard for performance and acoustic assessments, to showcase the efficacy of the developed solution. The conducted tests demonstrate the feasibility of integrating bio-based components into building envelopes, aligning with project expectations, and prevailing standards for curtain wall façade solutions. Notably, the designed façade system meets technical conditions and project objectives. Nevertheless, the research underscores the need for further refinements to facilitate solution industrialization and explore broader market applicability. Future efforts will focus on addressing these improvements and assessing the scalability of the solution.

Background: The role of inhaled Nitric Oxide (iNO) in managing Acute Respiratory Distress Syndrome Covid-19 related (C-ARDS) is debatable. The study aimed to analyze the effect of iNO administration in patients with persistent severe hypoxia and Intensive Care Unit (ICU) mortality. Methods: This retrospective study included 98 consecutive critically ill patients with C-ARDS admitted to ICU from 1 October 2020 to 31 October 2021. Results: Of these patients, 28% had received iNO. Twelve (44.4%) were responders. Kaplan-Mayer plot shows mortality was higher in non-responders (86.6 vs 25.0%). Non-response to iNo was the most important predictive value (p. 0.01). The Receiver Operating Characteristic (ROC) curve for a percentage increase in PaO2 from baseline confirmed that it had a higher predictive value for in-hospital survival. A value of 19% can predict the death event with a sensitivity of 81.8% and a specificity of 81.2%. Conclusions: Therefore, we propose to use iNO as a vasoreactivity test for prognostic stratification in patients with persistent severe hypoxia.

In this paper, low circumferential reciprocating load foot-scale tests were performed on two truncated PHC B 600 130 tubular piles with bearing nodes to characterize the damage process and morphology of the specimens and to investigate the load-carrying performance of the members. The test results reveal that under the action of tensile-bending-shear loading, the bearing concrete in the node area buckles and is damaged, the anchored reinforcement in the node area yields, the constraint is weakened, an articulation point is formed, and the node rotational capacity increases. When the embedment depth increases from 200 mm to 300 mm, the ultimate bearing capacities of the positive and negative nodes increase by 57.60% and 54.60%, respectively. A numerical simulation is used to verify the test results. Considering the three types of piles with truncated nodes, the numerical simulation is used to analyze the node-bearing capacity at different embedment depths. Finally, two preferred node types are proposed as follows: pipe pile core-filled longitudinal reinforcement anchored into the bearing node and pipe pile body longitudinal reinforcement anchored into the bearing node + pipe pile core-filled longitudinal reinforcement anchored into the bearing node, with preferred embedment depths of 350 mm and 200 mm, respectively.

A co-curing resin system consisting of 9368 epoxy resin for prepreg and 6808 epoxy resin for resin transfer molding (RTM) was developed. A corresponding preparation method of novel polymer composite bolted T-joint with internal skeleton and external skin was proposed based on prepreg-RTM co-curing process, and novel T-joints were fabricated. A series of conventional configuration T-joints based on RTM process and T-joints made of 2A12 aluminum alloy were prepared simultaneously. Bending performances were studied on these T-joints experimentally. The results indicate that 9368 epoxy resin and 6808 epoxy resin exhibit good compatibility in rheological and thermophysical properties. The novel T-joints prepared with prepreg-RTM co-curing process show no obvious fiber local winding or resin-rich regions inside, and the interface quality between internal skeleton and external skin is excellent. The main failure modes of the novel T-joint under bending load include separation of skin and skeleton and fracture along the thickness on the base panel; the skeleton carries the main bending load, but there is still load transfer between external skin and internal skeleton through their interface. The internal damages of the novel T-joint are highly consistent with surface damages observed visually, facilitating the detection and timely discovery of damages. The initial stiffness, damage initiation load, and ultimate load of the novel T-joint are 1.65 times, 5.89 times, and 3.45 times that of conventional T-joint, respectively. When considering the influence of density, the relative initial stiffness and relative ultimate load of the novel T-joint are 1.44 times and 2.07 times that of aluminum alloy T-joint, respectively.

In order to study the way how to improve the spatial action of precast monolithic composite floor slabs, and would replace the cast-in-place surface layer for reduce the weight of structure, using pseudo-dynamic tests on 1/4 scale models of two-span and three-story frame structure. The lateral load tests compared the stresses and displacements with cast-in-place floor frame-shear wall structure (SJ1) and precast monolithic floor frame-shear wall structure with X horizontal braces at the bottom of the floor (SJ2). The results show the X horizontal braces can improve the spatial action. Structural integrity (SJ2) as well as the effective transmission of the horizontal force can be ensured by additional X bracing at the bottom of the rigidity of the floor without cast-in-place concrete topping. The results show that X horizontal braces more effectively transfer horizontal, which provides a beneficial reference for similar research.

To elucidate the cellular immune response to coronavirus disease (COVID-19) among children, we assessed cellular immunity in 8 children post-vaccination for COVID-19 and 11 children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, using the T-SPOT®.COVID assay for both the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT®.COVID assay for the S protein yielded positive results in all eight children. In contrast, in the post-infection group, the assay for the N protein was positive in 5 of 11 children, with 3 of these 5 children requiring hospital admission, including 2 who needed mechanical ventilation. Therefore, the T-SPOT®.COVID assay is valuable for assessing cellular immunity against COVID-19, and most children infected with COVID-19 may not develop such immunity unless the disease severity is significant.

This article introduces a novel payload structure, which has been experimentally proven to have smaller impact force while the carried internal electronics remains intact. The study describes in details how materials and geometric structures were chosen based on information analysis. It is clarified how possible geometric structures and materials can be chosen to yield optimal efficiency. Finite element method simulations were carried out to investigate the mechanical properties of several geometric structures, which has led to the dodecahedron form. For the frame, Polylactic Acid were chosen as an optimal material. A low air pressure test for parts of the structure, and also the whole structure were carried out with successful results. Drop tests, with force measuring sensors and high speed videos, were carried out for measuring and comparing the maximal impact force of classical payloads and the novel one. Laboratory and real life tests demonstrated that the developed new structure is safer and it is applicable.

Asymptotic theories for fractional cointegrations have been extensively studied in the context of time series data, with numerous empirical studies and tests developed. However, most of the previously developed testing procedures for fractional cointegration were primarily designed for time series data. This paper proposes a generalized residual-based test for fractionally cointegrated panels with fixed effects. The test development is based on bivariate panel series with the regressor assumed to be fixed across cross-sectional units. The proposed test procedure accommodates any integration order between [0,1], and it is asymptotically normal under the null hypothesis. Monte Carlo experiments demonstrate that the test exhibits better size and power compared to a similar residual-based test across varying sample sizes.

A self-propelled electric tea seed-planter is designed to address the lack of tea seed seeding equipment, low seeding efficiency, and poor seeding uniformity. Based on the physical characteristics of the tea seeds and the agronomic requirements of tea planting, the key structure of the planter is designed, and the structural parameters are determined. The motor and battery configurations are determined by calculating the power consumption of the entire machine. In a field experiment, the driving gear (A), ditching depth (B), and planting gear position (C) are used as test factors, and the acceptance index (AI), replay index (RI) and leakage index (LI) are used as test indexes. The test results showed that the driving speed and planting gear position significantly affect the acceptance index, replay, and leakage index, whereas the ditching depth has little effect on the performance indexes. When the driving speed was medium, ditching depth was 30 mm, and planting gear position was in the third gear, the corresponding acceptance index was 87.22%, the replay index was 8.89%, and the leakage index was 3.89%. The test prototype has a good working quality and can provide theoretical guidance for production practices.

Pin-on-plate and pin-on-disk wear tests are typically used for assessing the wear behavior of a given material coupling. Such a behavior is frequently described by a wear coefficient k, which is estimated, according to the Archard’s law, as the ratio between the measured wear volume V and the product of the applied normal force F and the sliding distance s, i.e. k=V/(F s). This study demonstrates that such a relationship is correct for pin-on-plate but not for pin-on-disk, particularly for flat-ended pins. Both analytical and finite element models of the two tests were developed, considering three different distances pin-disk axis. As results, wear volumes, pressure and wear depth maps were examined and compared for the same sliding distance. Though this study is focused only on the initial transient part of the wear tests, some interesting aspects arose: i) rotational effect in pin-on-disk tests affects k estimation, especially when the pin is near to the disk axis; ii) a simple analytical function is defined to correct the wear volume estimation for pin-on-disk tests; iii) due to the different sliding distances of contact points in pin-on-disk tests, pressure redistribution occurs with higher values on the inner side (closer to disk axis); the opposite trend is observed in wear depth maps. From a computational point of view, the pin-on-disk problem, only apparently simple, required very small time increments to correctly describe the circular trajectories of points, with high computational costs. Numerical strategies are currently under investigation to extend the study to the steady state phase of both tests.

The progress in markerless technologies is bringing clinicians tools to rapidly evaluate tests such as Timed Up and Go (TUG) without compromising the time of the assessment, yet it raises questions about the potential trade-off in accuracy compared to traditional marker-based systems, suggesting that the precision of these evaluations is not yet conclusively established. The OpenCap system is an easy tool to process 3D kinematics with two iPhone cameras placed in front of the subject. Previous research has primarily focused on walking and movement towards the cameras with the subject facing the cameras (WF) and thus has been unable to disentangle the differences in the movement directions. We have compared the OpenCap system with a standard marker-based system for both walking directions. In OpenCap, we found significantly worse results capturing walking facing away from the cameras (RW). Compared to the marker-based system, our findings indicate troubles measuring kinematic parameters but provide good accuracy in measuring spatial-temporal parameters. These insights pave the way for refining markerless assessment technologies, potentially enhancing their utility in clinical settings.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

Count data analysis presents unique challenges due to its discrete nature, often exhibiting excessive zeros and overdispersion. To address these complexities, count models, such as Poisson regression and Negative Binomial regression, have been developed, enabling modeling and prediction of count-based phenomena. Additionally, it’s important to notice that zero inflation, a phenomenon commonly observed in count data, requires specialized techniques for robust analysis. This article provides an overview of count data and count models, explores zero inflation, introduces Likelihood Ratio Tests, and explains how the Vuong Test can be used as a model selection criteria. Furthermore, we created a Vuong Test implementation from scratch using the Python programming language. This implementation enhances the accessibility and applicability of the Vuong Test in real-world scenarios, providing a valuable contribution to the academic community, since Python didn’t have an implementation of this statistical test.

Candidate vaccines against African swine fever virus (ASFV) based on naturally attenuated or genetically modified viruses have the potential to generate protective immune responses, although there is no consensus on what defines a protective immune response against ASFV. Studies, espe-cially in sensible host species, focused on unravelling protective mechanisms will contribute to the development of safer and more effective vaccines. The present study provides a detailed analysis of phenotypic and functional data on cellular responses induced by intradermal immunization and subsequent boosting of domestic pigs with the naturally attenuated field strain Lv17/WB/Rie1, as well as the mechanisms underlying protection against intramuscular challenge with the virulent genotype II Armenia/07 strain. The transient mild to moderate increase of IL-8 and IL-10 in serum observed after immunization might be directly correlated with survival. Protection was also associated with a robust ASFV-specific polyfunctional memory T cell response, where CD4CD8 and CD8 T cells were identified as the main cellular sources of virus-specific IFNγ and TNFα. In parallel to cytokine response, these T-cell subsets also showed specific cytotoxic activity as evidenced by the increased expression of the CD107a degranulation marker. Along with virus-specific multifunctional CD4CD8 and CD8 T responses, the increased levels of antigen experienced cytotoxic CD4 T cells observed after challenge in immunized pigs might also contribute to control virulent infection by killing mechanisms targeting infected antigen-presenting cells. Future studies should elucidate whether the memory T-cell responses evidenced in the present study persist and provide long-term protection against further ASFV infections.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

This study compared the efficacy of alfaxalone and propofol to induce anesthesia in bitches undergoing an ovariohysterectomy or cesarean sections. 34 healthy and pyometra-affected females were induced with IV propofol administration, 35 healthy and pyometra-affected bitches were induced with the IV administration of alfaxalone. For the cesarean sections, females were induced with propofol (n=14) or alfaxalone (n=14). Maternal physiological parameters (heart rate, blood pressure, temperature) were recorded throughout surgeries; the viability and a modified Apgar score was recorded in the neonates at 5, 60 and 120 minutes after delivery. The use of propofol and alfaxalone did not show relevant differences over parameters assessed, when ovariohysterectomy was performed in healthy bitches or females with pyometra, as well as when cesarean sections were compared; only, a transient tachycardia appeared after alfaxalone administration. However, a higher percentage of bitches needed extra-doses of propofol. Neonatal mortality was similar between both groups, but when alfaxalone was used a higher neonatal viability was observed. Propofol and alfaxalone showed similar efficacy to perform the ovariohysterectomy in all bitches. Both protocols were optimal for cesarean sections, but alfaxalone was associated with a higher neonatal viability and a higher neonatal survival rate.

Microalgae are highly attractive to various industrial sectors and can serve as indicators of aquatic environmental health. An essential step for cultivating microalgae is assessing the cell density, which is traditionally performed through viable cell counting by optical microscopy (OM). However, this method has some limitations, such as the time involved in the process of counting, and the need for specialized training of laboratory personnel. Spectrophotometry is an affordable alternative, especially when applied to culture growth and toxicological tests. We chose the wavelength of 680 nm to detect the optical density (OD) of the green freshwater microalga Desmodesmus subspicatus and green the marine microalga Tetraselmis sp. The correlation between the number of cells and OD was suitable for both microalgae and accuracy was comparable to traditional OM counting. In toxicological tests, the OD technique allowed the monitoring of microalgal growth in the presence of the chemicals potassium dichromate, potassium chloride and sodium dodecyl sulfate (SDS), with results very close to those reported in the scientific literature. This study sheds light on this well-known technique, which is an important contribution since few articles have explored its potentialities and fragilities, showing the successful application to monitoring green microalgal cultures and toxicological assays.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

In this paper, the Shannon entropy measure was used to assess changes in precipitation and temperature conditions. Due to the short, low-volume sequences of precipitation and temperature data analysed, a bootstrap method was used in the procedure for calculating Shannon entropy. The analysis used minimum and maximum values of monthly precipitation totals and monthly mean temperatures for 377 catchments distributed across the globe. A 110-year data series from 1901 to 2010 was analysed. Entropy values for the estimated parameters of the generalised extreme value distribution (GEV) were calculated for the adopted data. Entropy value calculations were performed for the left-hand constraint, based on minimum values, and for the right-hand constraint, based on maximum values. The applicability of Shannon's entropy measure in the analysis of climate change was demonstrated by allowing the degree of disorder and complexity of the distributions describing climate variables in the form of precipitation and temperature to be measured. This made it possible to obtain information on the directions of changes occurring with regard to minimum and maximum values in the field of monthly precipitation and mean temperatures in the analysed catchments. The study demonstrated the existence of Shannon entropy trends. The evaluation of entropy trends for precipitation and temperature sequences was performed using non-parametric tests. Mann -Kendall tests at the 5% significance level were used for trend analyses. The Pettitt test was performed to determine the point of change in trend for the rainfall and temperature data. The performed analysis was supported by graphical presentations.

(1) Background: Cardiorespiratory fitness (CRF) is a prognostic factor regarding long time morbidity and mortality. To assess CRF the well-known gold standard is cardiopulmonary exercise testing (CPET), which is a time consuming and expensive test. Therefore, alternative methods for routine evaluation of CRF are needed for the general population as well as for specific patient groups such as children and young adults with congenital heart disease. The Stair Climbing Test (SCT) is a simple and resource saving test reported in the current literature. This test is used in various settings to assess different health associated risk factors including cardiorespiratory fitness, muscular resilience, therapy effectiveness or pre- and postoperative morbidity and mortality.

A set of polymer composite bolted T-joints with novel configuration consisting of internal skeleton and external skin was fabricated using a prepreg-RTM co-curing molding process. Experiments were conducted to study their mechanical properties under bending load. A finite element model with a polymer resin area between the skin and skeleton was established and verified by the experimental results. Then, the damage propagation process and failure mechanism of the joint and the influence of three factors related to the layer characteristics of the skin and skeleton were investigated by the validated models. The results show that the bending stiffness and the yield limit load of the novel composite T-joint are 0.81 times and 1.65 times that of the 2A12 aluminum T-joint respectively, while at only 55.4% of its weight. The damage of the joint initiates within the resin area and leads to a degradation of the joint bending performances. The preferred stacking sequence of the skeleton is [0/+45/90/-45]ns when primarily subjected to bending loads. The decrease in bending performances is within 5% with the inclining angle of the skeleton less than 12 degrees. The more layers of 90° in the skin, the better bending performances of the joints, while the more layer of 0°, the poorer bending performances.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

Polymer-based composites are widely used in the automotive, security, aeronautical and space industries, to mention a few. This is because of their good mechanical properties, which are similar to those of metals but with the attraction of being lightweight. Kevlar® as a reinforcement is extensively used in the security industry owing to its good ballistic properties. This investigation presents the mechanical characterization based on in-plane quasi-static tensile testing of Kevlar® composite using a universal testing system. The methodology developed for the preparation of coupons is based on pressure, temperature and time. As a result of this work, elastic moduli (EL and ET), Poisson’s ratio (νLT), shear modulus (GLT) and strengths (XT, YT, S) were obtained. It is worth mentioning that there is scarce or no characterization of this material in the literature, and those studies that do characterize it do not present the coupon thermoforming conditions or the reasons of the specimen dimensions (width, length and thickness).

A Friedmann-Lemaitre-Robertson-Walker space-time model with all curvatures k=0,±1 is explored in f(R,T) gravity. The solutions are obtained via the parametrization of the scale factor that leads to a model transiting from a decelerated universe to an accelerating one. The physical features of the model are discussed and analysed.

Introduction: PP, also called plantar ligament, is a fibrocartilaginous structure found in the metatarsophalangeal (MP) and interphalangeal (IP) joints. The aim of our study is to evaluate the role of MRI, both in standard position and with joint hyperextension, “stress test” (ST), in the study of the plantar plate (PP) disease that involves metatarsophalangeal joints. Material and methods: 25 patients were recruited into our study over a two-year period, 15 positive for metatarsal pain and 10 controls. All symptomatic patients were evaluated before treatment (surgery). Hence, the imaging features were reflective of the natural and true state of the lesions. Results:25 patients were recruited into our study over a two-year period, 15 positive for metatarsal pain and 10 controls. In symptomatic patients: 11/15 demonstrated plantar plate tear/dysfunction on both standard position and stress test, 2/15 had plantar plate tear on stress test (tear not showed on standard position), and 2/12 had no plantar plate tear on both standard position and stress test. The latter two patients showed dorsal subluxation on stress test due to micro-instability for plantar plate failure. In asymptomatic patients, 9/10 were negative for plantar plate dysfunction, and 1/10 was positive for plantar plate dysfunction (dorsal subluxation demonstrated only on stress test), without plantar plate tear. Conclusion:Standard MRI reported, in asymptomatic patients, a specificity of 100% and high NPV (90%), incremented by the ST (NPV and specificity 100%). In symptomatic patients, PP evaluation on standard MRI reported sensitivity of 80%, while stress test increased sensitivity to 100%; in the evaluation of dorsal subluxation of the metatarsophalangeal joint, the sensitivity was 60% (standard MRI) but reached 100% with ST. "Stress test" is an easy task to perform and even affordable in terms of time-consuming (requiring only one additional T2-weighted MRI sequence) for both patients and operators.

Coccomyxa subellipsoidea KJ (C-KJ) is a green alga with unique immunoregulatory characteristics. Here, we investigated the mechanism underlying the modification of T cell function by C-KJ components. The water-soluble extract of C-KJ was fractionated into protein (P) and sugar (S) fractions [acidic (AS), basic (BS), and neutral (NS)]. These fractions were used for the treatment of peripheral blood mononuclear cells stimulated with toxic shock syndrome toxin-1. Transcriptome analysis revealed that both P and AS enhanced the expression of the genes encoding metallothionein (MT) family proteins, inflammatory factors, and T helper (Th) 17 cytokine and suppressed that of those encoding Th2 cytokines in stimulated T cells. The kinetics of MT1 and MT2A gene expression showed a transient increase in MT1 and maintenance of MT2A mRNA after T cell stimulation in the presence of AS. The kinetics of Th17-related cytokine secretion in the early period were comparable to those of MT2A mRNA. Furthermore, our findings revealed that static, a STAT-3 inhibitor, significantly suppressed MT2A gene expression. These findings suggest that the expression of MTs is involved in the immune regulatory function of C-KJ components, which is partially regulated by Th17 responses, and may help develop innovative immunoregulatory drugs or functional foods.

This longitudinal study examined the development of executive function and calibration accuracy in pre-adolescents. Two hundred sixty two students(127 females) from grades 4 (n = 91), 5 (n = 89) and 6 (n = 82) took measures of executive function and performance calibration in a sport task, three times within a period of 20 months. A latent growth curve modeling analysis showed a significant relation between the rates of change of executive function and calibration. Further, the results showed a dynamic interplay in the development of executive function and calibration. There were significant inter-individual differences in the estimated population means both in executive function and calibration and in the rate of change of executive function, but not in the rate of change for calibration. The age of the participants had a positive effect only on the estimated population mean of executive function.

Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

: Tunnel instability and lining integrity are intimately tied to the creep properties of the surrounding rock. The acquisition of rock mass creep parameters is critical in ascertaining the appropriate timing for lining construction. Nevertheless, creep tests on rock specimens conducted in a controlled setting cannot be straightforwardly extrapolated to rock mass creep analysis. This study performs laboratory-based creep tests on mudstone samples and establishes the corresponding creep constitutive model. Integration of a Mohr-Coulomb element with the Burgers model in series serves to characterise the yield creep behaviour of the rock mass. Additionally, the research outlines a series of 100 orthogonal experiments utilising randomised creep parameters, and formulates a GA-BP neural network inversion model. Employing long-term deformation measurements from the crown and sidewalls of the project site, this study deduces the creep parameters of the mudstone in the investigated tunnel section and examines the prolonged deformation traits of the surrounding rock. Drawing on the deformation traits of the surrounding rock and the forces impacting the primary support and lining structures, this paper evaluates the earliest and latest viable lining casting periods and pinpoints an optimal timing interval for lining implementation. The methodologies employed herein can serve as a benchmark for analogous endeavors internationally.

Quantifying an imaging modality’s ability to reproduce results is important for establishing its utility. In Magnetic Resonance Spectroscopic Imaging (MRSI), new acquisition protocols are regularly introduced, which improve upon their precursors with respect to signal-to-noise ratio (SNR), total acquisition duration, and nominal voxel resolution. This study has quantified the within-subject and between-subject reproducibility of one such new protocol (reduced-Field-of-View-Density-Weighted-Concentric-Ring-Trajectory (rFOV-DW-CRT) MRSI) by calculating the Coefficient of Variance of data acquired from a test-retest experiment. The Posterior Cingulate Cortex (PCC) and the Right Superior Corona Radiata (SCR) were selected as the Regions of Interest (ROIs) for Grey Matter (GM) and White Matter (WM), respectively. CVs for between-subject and within-subject are consistently around or below 15% for Glx, tCho, and Myo-Ins and below 5% for tNAA and tCr.

Euler sums are alternating (or level two) extension of multiple zeta values (MZVs). Kaneko and Tsumura initiated the study of multiple T-values (MTVs), another level two generalization, by restricting the summation indices in the definition of MZVs to a fixed parity pattern. In this paper, we shall study finite MTVs and their alternating versions which are level two and level four variations of finite MZVs, respectively. We conjecture that all finite MZVs are in the Q-span of finite MTVs which in turn apparently lie in the span of finite Euler sums, and the inclusions are both proper. We shall first provide some structural results for Euler sums of small weights, guided by the author's previous conjecture that the finite Euler sum space of weight w is isomorphic to a quotient Euler sum space of weight w. Then, by utilizing some well-known properties of the classical alternating MTVs, we shall derive a few important Q-linear relations among the finite alternating MTVs, including the reversal, linear shuffle and sum relations. We then compute the upper bound for the dimension of the Q-span of weight w finite (alternating) MTVs for w<9, both rigorously using the newly discovered relations and numerically aided by computers.

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

Hair cosmetics are in fashion. Numerous products are commonly used in combination. Frequent allergens are present in hair cosmetics, which, added to almost daily use, increase the risk of sensitization. Familiarity with the clinical distribution of the eczematous rash is necessary to seriously consider patch testing. There are haptens on the market, although not all of them. It is necessary to know how to patch your own products. When avoidance of the allergen cannot be possible, new treatments are being evaluated to combat allergic contact dermatitis, mainly of the occupational type. In this manuscript, a complete and practical review of the main allergens and contact sources of hair cosmetic origin has been carried out.

Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

Motivated by empirical observations, we propose a possible extension of Gibrat's law. By applying it into the random growth theory of income distribution (Gabaix, 2009), we find that the income distribution is described by a generalized Pareto-type distribution (GPD) with three parameters. We observe that there is a parameter /elta in the GPD that plays a key role in determining the shape of income distribution. By using the Kolmogorov-Smirnov test, we empirically show that, for typical market-economy countries, /elta is close to 0 significantly, such that the income distribution is characterized by a two-class pattern in which the bottom 90% of the population is approximated by an exponential distribution and the richest 1%~3% is approximated by an asymptotic power law. However, we empirically find that, for China both in planned economy period and in early stages of market reformation (from 1978 to 1990), /elta is significantly deviated from 0, such that the bottom of the population no longer conforms to an exponential distribution.

Background: In 2020, the incidence of cancer was 844,778 cases among the population aged 0 to 19 years. Ninety percent of the population under 18 years of age lives in low- and middle-income countries, where cancer survivors report adverse outcomes. disease, which negatively impacts individuals’ general health, emotional state and external factors such as academic performance. Therefore, the objective of this article was to report the performance of the WCST and the sociodemographic characteristics of oncopediatric patients from Cali, Colombia. We report the reliability of the WCST instrument and indicate the association between the type of cancer and executive functioning in patients. Methods: In a cross-sectional observational study, 24 oncopediatric patients were interviewed and evaluated via the WCST. Results: The mean age was 12.08 years (3.98), 20.8% were women, 70.8% had a diagnosis of leukemia, 8 patients had acquired brain deficits, and more than 75% had adequate functioning in terms of the indicators of executive functions. Robust statistics were used to explore the differences between the types of diagnoses and performance in executive functions, and no statistically significant differences were found (p = 0.156). We accumulated evidence that the WCST has a reliable Cronbach's α of 0.804 and that oncopediatric patients without brain deficits had high scores for executive functions (p = 0.002) with a moderate effect size (0.727). Conclusions: The WCST is reliable for discriminating executive function among pediatric cancer patients. The evidence suggests that there are no differences between the types of cancer evaluated and executive functioning in the participants.

This paper offers a theoretical and experimental examination of the concurrent production of electricity and heat using photovoltaic thermal (PV/T) technology. The efficiency performance of the PV/T system is meticulously analyzed using MATLAB/Simulink software environments. Notably, the proposed PV/T system shows reliable performance, and its validity is confirmed through experimental validation on a test stand with a single PV/T panel positioned at a 45-degree angle to the horizontal and a 0-degree azimuth angle.

Oak woodlands are a keystone ecosystem that may not be sustainable under ongoing fire management regimes and climate change. For example, in 2014, sassafras saplings started to emerge in degraded woodlands at the 1200 ha Drury Conservation Area as part of research at the Bull Shoals Field Station in Taney County, Missouri where burning was initiated in 1999. After Spring (March) 2021 burnt, we examined trend in the potential community and ecosystem effects, we assessed sapling density, height, and specific leave weigh (SLW) of white oak and sassafras (<1.0 m) from fall 2021 through fall 2022. In fall 2021, sassafras density was 560/0.1ha with mean height of 25.42cm and SLW of 0.00436g/cm² while white Oak density was 171/0.1ha with mean height of 10.2cm and SLW of 0.00680g/cm. However, in fall 2022, Sassafras density was 582/0.1ha with mean height of 71.689cm and SLW of 0.00366 g/cm² meanwhile, white Oak density was 213/0.1ha with mean height of 50.544cm and SLW of 0.00563 g/cm². We analyzed mass loss for sassafras and white oak after buried for 198 days. The weight loss for sassafras was 0.857g while oak was 0.790g for 61 days of buried. Subsequent sassafras weight loss was 1.942g, 3.343g, 4.222g and 4.82g while that of white Oak was 1.877g, 2.862g, 3.344g and 4.28g for day 105, 153 and 198 respectively. The nutrients composition and carbon sequestration of sassafras and white oak species need to be determined to better understand the effect of their dominance in fire management regime of degraded oak woodland in Southwest Missouri Ozarks.

I demonstrate that Bell's theorem is based on circular reasoning and thus a fundamentally flawed argument. It unjustifiably assumes the additivity of expectation values for dispersion-free states of contextual hidden variable theories for non-commuting observables involved in Bell-test experiments, which is tautologous to assuming the bounds of ±2 on the Bell-CHSH sum of expectation values. Its premises thus assume in a different guise the bounds of ±2 it sets out to prove. Once this oversight is ameliorated from Bell's argument, the bounds on the Bell-CHSH sum of expectation values work out to be ±2√2 instead of ±2, thereby mitigating the conclusion of Bell's theorem. Consequently, what is ruled out by the Bell-test experiments is not local realism but the additivity of expectation values, which does not hold for non-commuting observables in any hidden variable theories to begin with.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

The current study was formulated with the aim of assessing the impact of the Extent of Drug addiction on the Family environment and interventions for drug-addicted youth in rural areas of Dir Lower Khyber Pakhtunkhwa, Pakistan. The study comprised a dependent variable (Extent of Drug addiction) and an independent variable (Family Environment). A sample size of 266 was randomly selected for primary data collection through structured interviews. The collected information was evaluated through descriptive analysis (frequency and percentage distribution) and inferential analysis, specifically utilizing the Chi-square Statistical Test. The study concluded that drug addiction among youth has an adverse impact on the family environment, leading to instability and violent behavior. Further, families of drug-addicted youth experience a high level of dissatisfaction in relationships, often culminating in divorce. Similarly, the families of drug-addicted are characterized by low cohesion, role conflict, and tolerance. Thus, the government should formulate polices and strategies for the prevention of drug addiction, with speedy implementation across all institutional dynamics, including family. Moreover, It is also crucial to rehabilitate the lifeblood of a nation (youth) in terms of socio-economic, emotional and psychological growth. These recommendations were put forward in the light of the current study.

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently SARS-CoV-2, al-ready four other coronaviruses have been circulating in the human population. The alpha coronaviruses NL63 and 229E and the beta coronaviruses OC34 and HKU1. These circulating coronaviruses all cause mild respiratory illness during the winter seasons and most people are already infected in early life. Could antibodies and/or T cells, es-pecially against the beta coronaviruses have offered some form of protection against SARS-CoV-2? Related is the question whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory, generated during the SARS-CoV-2 pandemic, ei-ther by infection or vaccination offer protection against future coronaviruses? Or rather than protection, could antibody dependent enhancement have taken place, a mecha-nism by which circulating corona antibodies enhance the severity of COVID-19? An-other related phenomenon, the original antigen sin, would also predict that the effec-tivity of the immune response to future coronaviruses would be impaired because of reactivation of memory against irrelevant epitopes. Current available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.

Purpose: Pancreatic cancer (PAAD) is one of the most lethal malignancies. Immunotherapy is largely ineffective in PAAD. T-cell exhaustion contributes to the resistance for immunotherapies. We investigated the prognostic potential of T cell exhaustion-related genes (TEXGs). Methods: Single-cell RNA (scRNA) sequencing dataset from TISCH, and bulk sequencing datasets from TCGA and GTEx were applied to screen differently expressed TEXGs. Kaplan-Meier survival, LASSO regression, and Univariate/Multivariate Cox regression analysis were performed to construct TEXGs risk model. This model was used to predict the prognosis, tumor immune microenvironment, and immunotherapy response. PAAD cohorts from ICGC and GSE71729 datasets were used to validate this risk model. Pan-cancer expression of SPOCK2 was performed in TISCH database. Results: A six-gene (SPOCK2, MT1X, LIPH, RARRES3, EMP1, and MEG3) risk model was constructed. Low-risk PAAD patients had longer survival time in both training dataset (TCGA-PAAD, n=178) and validation datasets (ICGC-PACA-CA, ICGC-PAAD-US, and GSE71729, n=412). Multivariate Cox regression analysis demonstrated that the risk score was an independent prognostic variable for PAAD. High-risk patients correlated with cancer-related KEGG pathway enrichment, higher mutation frequency of KRAS and TP53 genes, and immunosuppressive status. Immunohistochemistry staining confirmed the changes of TEXGs in clinical samples. Moreover, pan-cancer scRNA sequencing datasets from TISCH analysis indicated that SPOCK2 might be a novel marker of exhausted CD8+ T cells. Conclusion: In conclusion, we established and validated a T cell exhaustion-related prognostic signature for PAAD patients. Moreover, our study suggests that SPOCK2 may be a novel marker of exhausted CD8+ T cells.

The capacitor-mismatch among diverse defects caused by the manufacturing process variations significantly affects the linearity of capacitor-array used to implement the capacitive digital-to-analog converter (CDAC) in the successive-approximation-register (SAR) analog-to-digital converter (ADC). Accordingly, the linearity of the SAR ADC is limited by that of capacitor-array, resulting in serious yield loss. This paper proposes an efficient foreground self-calibration technique to enhance the linearity of the SAR ADCs by mitigating the capacitor-mismatch based on the split ADC architecture along with variable capacitors. In this work, two ADC channels (i.e., ADC1 and ADC2) for the split ADC architecture include their capacitive DACs (CDACs) whose binary-weighted capacitor-arrays consist of variable capacitors. A charge-sharing SAR ADC is used for each ADC channel. In the normal operation mode, their digital outputs are averaged to be the final ADC output, as in a conventional split ADC. In the calibration mode, every single binary-weighted capacitor for the two ADCs is sequentially calibrated by making parallel or/and antiparallel connection among two or thee capacitors from the two channels. For instance, because the capacitors of the CDACs ideally exhibit the binary-weighted relation as Cn=2×Cn−1, variable capacitor Cn of ADC1 can be updated to be closest to the sum of Cn−1 of ADC1 and Cn−1 of ADC2 for the calibration. For the process, the two capacitor-arrays of the two ADCs can be reconfigured to be connected to each other, so that Cn of ADC1 can be connected with two of Cn−1 of ADC1 and ADC2 in antiparallel. The two voltages at the top and the bottom plates of the CDAC are compared by a comparator of ADC1, and the comparison results are used to update Cn. This process is iterated, until Cn is in agreement with the sum of two of Cn−1. Finally, all the capacitors can be calibrated in this way to have the binary-weighted relation. The simulation results based on the proposed work with a split SAR ADC model verified that the proposed technique can be practically used, by showing that the total-harmonic-distortion and the signal-to-noise-and-distortion ratio were enhanced by 21.8-dB and 6.4-dB, respectively.

The Bunyavirales order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses are responsible for an increasing number of outbreaks worldwide and represent a threat to public health. Infection in humans can be asymptomatic, or it may present with a range of conditions from a mild, febrile illness to severe hemorrhagic syndromes and/or neurological complications. There is a need to develop safe and effective vaccines, a process requiring better understanding of the adaptive immune responses involved during infection. This review highlights the most recent findings regarding T cell and antibody responses to the five bunyavirus families with known human pathogens (Peribunyaviridae, Phenuiviridae, Hantaviridae, Nairoviridae, and Arenaviridae). Future studies that define and characterize mechanistic correlates of protection against bunyavirus infections or disease will help inform the development of effective vaccines.

To better understand how immunity develops against SARS-CoV-2 during the pandemic period of 2020 to 2022, we analyzed the immune response of a small group of university staff and students who were either infected or vaccinated. We investigated the levels of receptor-binding domain (RBD)-specific and nucleocapsid (N)-specific IgG and IgA antibodies in serum and saliva samples taken early (around 10 days after infection or vaccination) and later (around 1 month later), as well as N-specific T-cell responses. One patient who had been infected in 2020 developed serum RBD and N-specific IgG antibodies, but declined 8 months later, then mRNA vaccination in 2021 produced a higher level of anti-RBD IgG than natural infection. In the vaccination of naïve individuals, vaccines induced anti-RBD IgG, but it declined after 6 months. A third vaccination boosted the IgG level again, albeit to a lower level than after the second. In 2022, when the Omicron variant became dominant, familial transmission occurred even among vaccinated people. In infected individuals, the levels of serum anti-RBD IgG antibodies increased later, while anti-N IgG peaked earlier. The N-specific activated T cells expressing IFN- or CD107a were detected early. In saliva, SARS-CoV-2-specific IgG but not IgA was detected. Interestingly, two individuals showed a temporary peak in RBD- and N-specific IgA antibodies in their saliva on the second day after infection. Thus, SARS-CoV-2 infection triggers typical immune responses in humans against acute viral infections, but mucosal immune responses, which are temporarily induced early during infection, may be more important for protection than current intramuscular vaccines.

Lumpy skin disease (LSD) is a viral disease of cattle and water buffalo characterized by cutaneous nodules, biphasic fever and lymphadenitis. LSD is endemic in Africa and Middle East but in recent years has spread in different Asian countries. Drop of animal productions, vaccination campaign, surveillance costs and trade restrictions have significant impact on the economy of affected countries. The disease is well characterized in cattle while little is known in buffaloes and no experimental studies have been conducted in this species. Six buffaloes and two cattle were inoculated with an Albanian LSD virus (LSDV) field strain. Over a period of 42 days animals were clinically monitored and sampled for serological and virological analysis. Only two buffaloes showed clinical sign, fever, skin nodules and lymphadenitis. All samples tested in real time PCR (blood, swabs, biopsies and organ) gave negative results. Three buffaloes seroconverted at day 39 and 42 post-inoculation, detected by ELISA, but all sera were negative in serum neutralization test. Cattle showed more severe clinical signs. Moreover, viraemia and virus shedding were proven by positive PCR results and antibodies were detected by both ELISA and serum neutralization test. These findings demonstrated the limited susceptibility of buffaloes compared to cattle once experimental infected with LSDV. Further studies are needed to investigate the epidemiological role of the buffaloes.

With end-to-end encryption for video streaming services becoming more popular, network administrators face new challenges in preserving network performance and user experience. Video ads may cause traffic congestion and poor Quality of Experience. Because of the natural variation in user interests and network situations, traditional algorithms for increasing QoE may face limitations. To solve this problem, we suggest a novel method that uses user facial emotion recognition to deduce QoE and study the effect of ads. We use open-access Face Emotion Recognition (FER) datasets and extract facial emotion information from actual observers to train machine learning models. Participants were requested to watch ad videos and provide feedback, which will be used for comparison, training, testing, and validation of our suggested technique. Our tests show that our approach beats the ITU-T P.1203 standard in terms of accuracy by 37.1%. Our method provides a hopeful answer to the problem of increasing user engagement and experience in video streaming services.

Mass customization, small batch sizes, high variability of product types and a changing product portfolio during the life cycle of an industrial plant are current trends in the industry. Due to an increasing decoupling of the development of software and hardware components in an industrial context, compatibility problems within industrial control systems arise more and more frequently. In this publication, a strategy concept for compatibility testing is derived and discussed by means of literature review and applied research. This 4-phased strategy concept identifies incompatibilities between software and hardware components in the industrial control environment and enables test engineers to detect problems at an early stage. By automating the compatibility test on an external I-PC, the test can be run both when new software is installed on the industrial controller and when the controller is restarted. Thus, changes to the components are constantly detected and incompatibilities are avoided. Furthermore, early incompatibility detection can ensure that a system remains permanently operational. Based on a discussion, additionally strategies are identified to consolidate the robustness and applicability of the presented concept.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

Red mud (RM), a bauxite residue, contains hazardous radioactive wastes and alkaline material and poses severe surface water and groundwater contamination risks, necessitating recycling. Pretreated RM can be used to make adsorbents for water treatment. However, its performance is affected by many factors, resulting in a nonlinear correlation and coupling relationship. This study aimed to identify the best formula for an RM adsorbent using a mathematical model that examines the relationship between 11 formulation types (e.g., pore-assisting agent, component modifier, and external binder) and nine properties (e.g., specific surface area, wetting angle, and Zeta potential, among others). This model was built using a back-propagation neural networks(BP) based on single-factor experimental data and orthogonal test data. The model trained and predicted the established network structure to obtain the optimal adsorbent formula. The RM particle adsorbents had a pH of 10.16, specific surface area(BET) of 48.92 m2·g−1, pore volume of 2.10 cm3·g−1, compressive strength(ST)) of 1.12 KPa, and 24-h immersion pulverization rate(η_m) of 3.72%. In the removal of total phosphorus in flotation tailings backwater, it exhibited a good adsorption capacity (Q)and total phosphorous removal rate(η) of 48.63 mg·g−1 and 95.13%, respectively.

Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.

PitNETs, although typically benign, comprise a small percentage of therapy-resistant aggressive, occasionally metastatic tumors, underpinning a need to identify novel therapeutic targets. PitNETs carry few mutations but associate with conditions that promote alternative splicing as an oncogenic alternative and express the TrkA neurotrophin receptor, which exhibits oncogenic alternative TrkAIII splicing in other tumors. Alternative TrkAIII splicing was assessed by RT-PCR in 53 PitNETs and compared to HIF1a, HIF2a, SF3B1, SRSF2, U2AF1 and JCPyV large T antigen mRNA expression, unconventional Xbp1 splicing, SF3B1 mutation, and TrkA isoform(s) immunoreactivity by confocal immunofluorescence (IF). Alternative TrkAIII mRNA splicing was detected in all invasive PitNET phenotypes, was significantly elevated in invasive compared to non-invasive PIT1 PitNETs, relatively high in invasive and non-invasive SF1 and TPIT PitNETs, and was associated with IF consistent with intracellular TrkAIII activation but not with hotspot SF3B1 mutations, altered SF3B1, SRSF2 and U2AF1 splice factor mRNA expression, JCPyV large T antigen expression or unconventional Xbp1 splicing. A potential role for hypoxia in TrkAIII mRNA splicing was supported by significant elevation of HIF2a mRNA expression in invasive PIT1 PitNETs. These data demonstrate that alternative TrkAIII splicing, potentially promoted by hypoxia, occurs frequently in PitNETs and may associate with IF consistent with intracellular TrkAIII activation, supporting a potential role for TrkAIII in PitNET pathogenesis and progression, identifying TrkAIII as a novel potential target in refractory PitNETs.

Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate. With the recent advances in next generation sequencing technologies, our understanding of the molecular events associated with sAML evolution has significantly increased and opened new perspectives for the development of novel therapies. The genetic aberrations that are associated with sAML affect genes involved in processes such as splicing, chromatin modification and genome integrity. Moreover, non-coding RNAs’ emerged as an important contributing factor to leukemogenesis. For decades, the standard treatment for secondary AML has been the 7 + 3 regimen of cytarabine and daunorubicin which prolongs survival for several months, but modifications in either dosage or delivery has significantly extended that time. Apart from traditional chemotherapy, hematopoietic stem cell transplantation, CAR-T cell therapy and small molecule inhibitors have also emerged to treat sAML.

The objective of this study was to investigate the liquefaction resistance of chemically improved sandy soils in a straightforward and accurate manner. Using only the existing experimental databases and artificial intelligence, the goal was to make predictions without conducting physical experiments. Emphasis was placed on the significance of data from 20 loading cycles of cyclic undrained triaxial tests to determine the liquefaction resistance and the contribution of each explanatory variable. Different combinations of explanatory variables were considered. Regarding the predictive model, it was observed that a case with the liquefaction resistance ratio as the dependent variable and other parameters as explanatory variables yielded favorable results. In terms of exploring combinations of explanatory variables, it was found advantageous to include all variables as doing so consistently resulted in a high coefficient of determination. The inclusion of the liquefaction resistance ratio in the training data was found to improve the predictive accuracy. In addition, the results obtained when using a linear model for the prediction suggested the potential to accurately predict the liquefaction resistance using historical data.

Estimating the infection risks in indoor environments comprises the assessment of the behavior of virus-laden aerosols, i.e. spreading, mixing, removal by air purifiers etc. A promising experimental approach is based on using non-hazardous surrogate aerosols of similar size, e.g. salt particles, to mimic the virus aerosol behavior. This manuscript addresses the issue how a successful transfer of such experiments can be accomplished. Corresponding experiments in two very different environments, a large community hall and a seminar room, with optional use of air purifiers in various constellations were conducted. While high particle concentrations are advantageous in terms of avoiding influence of background aerosol concentrations, it is shown that appropriate consideration of aggregation and settling are vital to theoretically describe the experimentally determined course of particle concentrations. A corresponding model equation for a well-mixed situation is derived and the required parameters are thoroughly determined in separate experiments independently. It is demonstrated that clean air delivery rates (CADR) of air purifiers determined with this approach may differ substantially from common approaches not explicitly taking into account aggregation.

Small peptides are an important component of the vertebrate immune system. They are important molecules for distinguishing proteins that originate in the host from proteins derived of a pathogenic organism, such as a virus or bacterium. Consequently, these peptides are central for the vertebrate host response to intracellular and extracellular pathogens. Computational models for prediction of these peptides have been based on a narrow sample of data with an emphasis on the position and chemical properties of the amino acids. In past literature, this approach has resulted in higher predictability than models that rely on the geometrical arrangement of atoms. However, protein structure data from experiment and theory are a source for building models at scale, and, therefore, knowledge on the role of small peptides and their immunogenicity in the vertebrate immune system. The following sections introduce procedures that contribute to theoretical prediction of peptides and role in immunogenicity. Lastly, deep learning is discussed as it applies to immunogenetics and the acceleration of knowledge by a capability for modeling the complexity of natural phenomena.

The metrological performance of FBG strain sensing systems is a critical premise for the precision of plastics water support pipeline structural deformation measurement, but the strain transfer loss of FBG attached on the plastics pipe subjected by dynamic force is unclear. This paper presents the first study on the effects of strain transfer between FBG, and acrylate polymer blended with poly resin (ABR)pipe sheets loaded by static and dynamic force. Theoretical methods of dynamic strain transfer theory combine with the exponentially decaying sinusoidal shock force time course is deduced and various dynamic parameters sensitivities studies are carried out, as well as that of the geometric parameters. The result of the dynamic theory is compared with the calibration test outcomes, while the ASTR of FBG attached on ABR sheet is compared with distributed optical fiber sensors (DOFS) and other pipe materials such as PVC, concrete, and steel. Results show that the ASTR of FBG is more accurate than that of the DOFS, and the grows of ASTR depending on the paste length of FBG, the Young's modulus of the middle materials, the thickness of the middle materials and attenuation coefficient. Paste length produced the largest increase, yet the magnitude and loading speed of the external force has unexpectedly little effect on ASTR. FBG seem low error, insensitive with dynamic force and independent with the material of matrix, and this demonstrates benefits that are stronger across the board than DOFS. This is not currently recognized by standards or by most reported studies.

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.

We investigated the potential genetic variants using whole exome sequencing (WES) and evalu-ated the disease course using T cell receptor (TCR) repertoire analysis in rheumatoid arthritis (RA). Fourteen patients with RA and five healthy controls (HCs) were enrolled. For patients with RA, only naïve patients were recruited before treatment, and data were collected at baseline and 6 and 12 months after the initiation of disease-modifying antirheumatic drug (DMARD) treatment. Laboratory data and disease parameters were also collected. Genetic variants were detected using WES, and the diversity of the TCR repertoire was assessed using Shannon-Weiner diversity. Some variants were detected by WES, but their clinical significance should be confirmed by further studies. The diversity of the TCR repertoire in patients with RA was lower than that in HCs; however, after DMARD treatment, it increased significantly. The diversity was negatively cor-related with laboratory findings and disease measures with statistical significance. Variants with a potential for RA pathogenesis were identified and the clinical significance of TCR repertoire was evaluated in Korean patients with RA. Further studies are required to confirm the findings of the present study.

Claudins are a family of 27 proteins that have an important role in the formation of tight junc-tions. They also have an important function in ions exchange, cell mobility, and in in the epitheli-al-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis. Therapeutic targeting of claudins has been investigated to improve cancer outcomes. Recent evi-dence shows improved outcomes when combining monoclonal antibodies against Claudin 18.2 with chemotherapy for patients with gastroesophageal junction cancer. Currently Chimeric anti-gen receptor T-cells targeting Claudin 18 are under investigation.

Background: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR). Methods: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. Results: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3+4 groups, with the GOLD 1 group used as the reference [Hazard Ratio 4.222 (95% CI 1.298 - 13.733), p=0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3+4. The St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3+4, but not between STAR 1 and STAR 2. Conclusion: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.

Chronic lymphocytic leukemia (CLL) is characterized by dysfunctional B cells. Immune checkpoint molecules such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and programmed death-1 (PD-1) are upregulated in patients with CLL and may correlate with prognostic markers such as beta-2 microglobulin (B2M). The aim of this study was to evaluate the levels of immune checkpoints on B-cell subsets and to further correlate them with B2M levels in patients with CLL. We recruited 21 patients with CLL and 12 controls. B cell subsets and the levels of immune checkpoint expression were determined using conventional multi-color flowcytometry. Basal levels of B2M in patients with CLL were measured using an Enzyme-linked immunosorbent assay. Patients with CLL had increased levels of activated B cells when compared to the control group, p< 0.001. The expression of PD-1 and CTLA-4 were increased on activated B cells and memory B cells, p< 0.05. There were no associations between B2M levels and the measured immune checkpoints on B cell subsets, after adjusting for sex and age. African patients with CLL express elevated levels of PD-1 and CTLA-4 immune checkpoints on activated and memory B cell subsets. However, there is no correlation between these immune checkpoint expressions and B2M levels.