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.

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.

To achieve rapid post-earthquake repair of self-centering ribbed floor flat beam frame structures, a ductile hybrid joint consisting of dog bone weakened energy dissipating steel bars connected to the upper and lower column sections through high-strength threads based on the damage control design concept is proposed. By moving the ductile energy dissipating zone out to the locally weakened section of the energy dissipating steel bars and the locally unbonded prestressed steel bars in the core area, the residual deformation was limited and the seismic performance was improved. Based on the working principle of hybrid joints, low cycle loading tests were conducted on two joint specimens to analyze the influence of lateral prestress on the seismic performance of the hybrid joints. Numerical modeling methods were used to compare the position of the energy-consuming steel bars in the composite layer and the friction performance of joints. The research results indicated that the hybrid joint had stable load-bearing, deformation, and energy dissipation capabilities, with damage primarily concentrated on the energy-consuming steel bars. Even at an inter-story displacement angle of 5.5%, the upper and lower column segments remained elastic. After unloading, the connection seam at the joint was closed, and the self-centering performance was good. When the inter-story displacement angle reached 5.5%, the lateral prestress increased from 150 kN to 250 kN, the ultimate bearing capacity of the joint increased by 16.3%, and the cumulative energy consumption increased by 30.0%. The influence of the friction coefficient of the joint surface on the structural performance was set at a threshold of 0.7. When it was less than the threshold, the ultimate bearing capacity and initial stiffness of the joint increased with an increase in the friction coefficient. After reaching the threshold, the increase in the ultimate bearing capacity of the joint slowed down, and the rate of stiffness degradation gradually accelerated. This joint had excellent seismic performance and can also achieve post-earthquake repair of structures.

Intraoperative load sensors have been developed with the aim of balancing the soft tissue in the knee during Total Knee Replacements (TKRs). Literature has shown success in soft tissue bal-ancing however, concerns regarding the accuracy of these sensors remain. For this reason, pre-vious research has attempted to create robust sensors for intraoperative use. The design of the sensor in this research has aimed to address the concerns outlined in the literature to create a new and novel smart-sensor for soft-tissue balancing. This new intraoperative load sensor included design features to increase accuracy while artificial intelligence allowed for comprehensive sensing across the entirety of the sensor, providing unparalleled insight during the operation. Notably, the sensor was designed to withstand loads of at least 450 N, ensuring robust perfor-mance of the sensor. To optimize the design process while minimizing cost, Finite Element Analysis was employed. This approach ensured the design features fulfilled their function while maintaining structural integrity to withstand loads. Moreover, the novelty of using training data from simulated data will reduce the iterative process of the labor-intensive collection of training data for the artificial intelligence while reducing human error associated with it. Results from the evaluation demonstrated the ability of this design to successfully bridge the current gap in the market by fulfilling all essential design criteria established within the literature. This innovative smart-sensing tool will in turn enhance patient outcomes and alleviate financial burdens to pa-tients and the healthcare systems by reducing the need for early revision surgeries associated with improper joint tension.

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.

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.

Floods are a common natural disaster whose severity in terms of duration, water resource volume, peak and accumulated rainfall-based damage are likely to differ significantly for different geographical regions. In this paper, we first propose a novel hourly flood index (SWRI24−hr−S), derived from normalising the existing 24-hourly water resources index (WRI24−hr−S) in literature, to monitor flash flood risks on an hourly scale. The proposed SWRI24−hr−S is adopted to identify a flood situation and derive its characteristics, such as the duration (D), volume (V) and peak (Q). The comprehensive result analysis establishes the practical utility of SWRI24−hr−S in identifying flood situations at seven study sites in Fiji between 2014 and 2018 and deriving their characteristics (i.e., D, V, and Q). Secondly, this study develops a vine copula-probabilistic risk analysis system that models the joint distribution of flood characteristics (i.e., D, V, and Q) to extract their joint exceedance probability for the seven study sites in Fiji, enabling probabilistic flood risk assessment. The vine copula approach, particularly suited to Fiji’s study sites, introduces a novel probabilistic framework for flood risk assessment. The results show moderate differences in the spatial patterns of joint exceedance probability of flood characteristics in different combination scenarios generated by the proposed vine copula approach. In the worst-case scenario, the probability of any flood event occurring where the flood volume, peak and duration are likely to exceed the 95th-quantile value (representing an extreme flood event) is found to be less than 5% for all study sites. The proposed hourly flood index and the vine copula approach can be feasible and cost-effective tools for flood risk monitoring and assessment. The methodologies proposed in this study can be applied to other data-scarce regions where only rainfall data is available, offering crucial information for flood risk monitoring, assessment, and the development of effective mitigation strategies.

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.”

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.

Background: The main objective of this study is to develop a customized metatarsophalangeal implant for the treatment of various conditions affecting this specific joint. This approach involves replacing the joint with a custom implant designed specifically to fit each patient's unique anatomical structure. The need for custom implants stems from the obvious lack of size variety available, which presents a major challenge when, the search for the ideal size implant can be a hard task, also when considering the possibility of extensive modification of the bone to adapt it to the available implant. This adaptation, often synonymous with bone reduction, can cause significant post-operative pain for the patient and impact healing time. Methods: A comparative study of modeling software was carried out to select the perfect software, by defining and comparing the relevant criteria. Similarly, the different biomaterial options were examined and compared to select the one best suited to this project, mentioning the imaging modality used to determine the types of images used for our approach. Finally, the 3D printers used in this work were represented, highlighting their technical characteristics. Findings: A resin metatarsophalangeal implant prototype was created using 3D modeling and reconstruction software and tools. Interpretation: Reconstruction and 3D modeling techniques are revolutionizing implant creation, offering customized solutions for patients suffering from metatarsophalangeal joint disorders caused by a wide range of diseases. These results have significant implications for disability management and rehabilitation, encouraging further exploration and progress.

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.

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.

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.

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.

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.

Lower extremity joint kinetic factors are thought to modulate walk–to–run transition (WRT) and run–to–walk transition (RWT). This study aimed to investigate joint stiffness and energetic patterns during the WRT and RWT processes and identify whether gait transitions occurred within a single step or not. Ten healthy subjects participated in treadmill WRT (1.8 m/s – 2.4 m/s) and RWT (2.4 m/s – 1.8 m/s) tests. We investigated two steps before transition (S–2, S–1), two steps after transition (S1, S2) and the transition step (S0). We found significant differences between S2 and S–2 for ankle joint stiffness during WRT and RWT (p < 0.001); and for hip joint stiffness, we found significant differences between S1 and S–1 during WRT and RWT (p ≤ 0.001). Additionally, stance phase mechanical energy generation was observed to transfer from proximal to distal joints at S0 during WRT, and from distal to proximal at S0 during RWT. Transition step ankle kinematic and kinetic patterns were similar to the target locomotion task gait format in both WRT and RWT. Moreover, RWT required longer adaptation time compared with WRT. These findings indicate that WRT and RWT were modulated before and after the actual transitions, not within a single step. Redistribution of joint mechanical work generation was related to gait transition triggers, which modulate the WRT and RWT process.

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).

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.

This paper proposes a lightweight joint with bamboo culm cross connection, which is constructed by screwing one side of the screw into the other side of the wooden plug, its simple construction makes it easy to manufacture and cost-effective. This form connects adjacent bamboo culms to form corner joints, and bolt connects adjacent bamboo culm frames to form edge joints, to explore the mechanical properties of the combination joints formed by corner joints and edge joints, by combining experiments and numerical simulations, the method discovered and explained the relationship and mechanism between the number and position of bolts and the stiffness of edge joints. A calculation model for frame-unit bamboo culm members considering semi-stiffness of joints is proposed, and the conversion equations between linear stiffness of corner and edge joint and their rotational stiffnesses are derived. By establishing the series and parallel relationship between the corner and edge joints in the assembled members, a generalized relational equation between the total stiffness of the assembled joint and the stiffness of the corner and edge joints is derived. A numerical simulation method for frame-unit bamboo culm members with semi-rigid joints is proposed, which can obtain the stiffness calculation formula of edge joints and the average rotational stiffness value of semi-rigid corner joints. A finite element analysis method based on semi-rigid joints is proposed for frame-unit bamboo culm members, and the internal force sketches and calculation methods for bamboo culms and joints are presented, which can be used for the internal force analysis and design of frame-unit bamboo culm lattice structures.

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

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.

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.

Rotational jumps are crucial techniques in sports competitions. Estimating ground reaction forces (GRFs), one of the components constituting jumps, through a biomechanical model-based approach enables analysis even in environments where force plates or machine learning training data cannot be utilized. In this study, rotational jump movements involving twists on land were measured using inertial measurement units (IMUs) and estimated GRFs and body loads using a 3D forward dynamics model. Our estimation method, based on forward dynamics and optimization calculations, generated and optimized body movements using cost functions defined by motion measurements and internal body loads. To reduce the influence of the dynamic acceleration in the optimization calculation, the 3D orientation using sensor fusion composed of acceleration and angular velocity data obtained from IMUs and an extended Kalman filter was estimated. As a result, by generating movements based on the cost function, it was possible to calculate biomechanically valid GRFs while following the measured movements even if not all joints are covered by IMUs. This estimation method allows for 3D motion analysis independent of measurement conditions or training data.

In volleyball, the jump serve is a fundamental and crucial skill that is one of the most commonly used serving techniques. This study aimed to examine the kinematic differences between straight line (SL) and diagonal line (DL) in volleyball jump serves by focusing on torso and attack arm joint motions. Three-dimensional coordinate data were captured using a motion capture system (200 Hz) in 14 right-handed male professional volleyball players who performed SL and DL jump serves. This result suggests that the pelvis and torso backward rotation angles during the arm-clocking phase were smaller when performing DL serves. During ball contact, the servers exhibited greater forward rotation angles of the pelvis and torso to control the upper body facing the diagonal direction of the target zone. In addition, lowering the forward tilt angle of the trunk helped the servers maintain body balance in the air and increased their wrist flexion angle, preventing the ball from flying out of bounds when performing DL. These findings highlight the importance of controlling pelvic and torso rotations in the transverse plane when adjusting for different serving lines. These insights can guide volleyball athletes and coaches in refining their serving techniques.

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.

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.

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.

Biomechanical changes such as increased knee adduction moment (KAM) during walking are known to be involved in the development and severity of knee osteoarthritis (OA). Although various foot progression angle (FPA) modifications during gait have been applied to reduce peak KAM, few studies have investigated effects of applying toe-in or toe-out walking modifications for knee OA on peak KAM and three-dimensional (3D) moments of the ankle joint. Kinetic moment variables were acquired from 35 individuals with medial knee compartment OA. A 3D motion analysis system and two force platforms were used to acquire KAM and 3D moments of both ankle joints during gait. Visual3D motion analysis program was used to obtain final moment data for statistical processing. Repeated-measures analysis of variance with Bonferroni adjustment was used to compare kinetic and kinematic values for each FPA walking condition. The first peak KAM of an internal rotation foot position of the FPA walking condition showed significant decrease compared to normal foot position walking (p < 0.01). The second peak KAM of an external rotation foot position walking showed significant decrease compared to normal foot position walking (p < 0.01). Compared to a normal foot position, peak ankle inversion moment of the external rotation foot position walking showed a significantly decrease (p < 0.05). There were no interactive effects between FPA condition and limb sides for any KAM values (p > 0.05). These results suggest that clinical application of toe-in or toe-out gait modification walking in individuals with knee OA should be performed based on biomechanical evaluations such as peak KAM.

This paper presents the deformation of the joined sheet after the clinch-riveting process. The DX51D steel sheet with zinc coating was used. The samples to be joined with clinch riveting technology had a thickness of 1±0.05 mm and 1.5±0.1 mm. The sheet deformation was measured before and after the joining process. The rivet was pressed in the sheets with the same dimension between the rivet axis and three sheet edges: 20, 30 and 40 mm. For fixed segments of the die, from the rivet side close to the rivet, the sheet deformation was greater than that of the area with movable segments. The movement of die sliding element caused more sheet material to flow in the space between the fixed part of the die and movable segments. Hence, the sheet deformation in these places was smaller than for the die fixed element – sheet material was less compressed. For sheets thickness 1.5 mm and width 20 mm, the bulk of the sheet was observed. For a sheets width of 20 mm, it was observed that the deformation of the upper and lower sheets in the area of the rivet is greater than for sheets width of 30 or 40 mm.

An 8-months old male American Staffordshire terrier was referred for a no weightbearing lameness of the right pelvic limb, hyperthermia, lethargy and inappetence caused by hematogenous osteomyelitis. Orthopedic, radiographic and tomographic examinations revealed a bone sequestrum of 4 x 1.4 cm and active periosteal reaction of the caudo-lateral cortical in the metaphysis and the distal third of the right femoral diaphysis, medullary osteolysis and interruption of the cranio-medial cortical profile, with involvement of the femoral trochlea leading to a secondary medial patella luxation. Once skeletally mature, after 4 months from surgical debridement and aggressive antibiotic therapy against Klebsiella oxytoca revealed by bacteriological exam, the patient underwent prosthetic surgery for the application of a custom-made patellar groove replacement (PGR) to fill the bone defect and restore the femoral trochlea surface. Despite the serious injury that afflicted the right pelvic limb, the surgery had satisfactory outcomes until the last 18-months postoperative follow up.

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.

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.

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.

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.

This study aimed to investigate the fatigue performance and interfacial strengthening mechanisms of Al6061-to-Cu dissimilar lap joints via electromagnetic pulse welding (EMPW). The load-bearing capacity of the joints at discharge voltages of 14 kV and 16 kV was superior to that of 12 kV. Furthermore, the fatigue life of the 14 kV joints was one order of magnitude higher compared to the 12 kV joints. SEM observation of the fatigue fracture surface revealed the presence of typical "tire-mark" fatigue striations only in the 14 kV joint, indicating higher ductility and the ability to withstand extended plastic deformation. Notably, ultra-fine nanocrystalline Al2Cu phase, amorphous phase, and numerous dislocations hindered EBSD acquisition in the transition zone. Nevertheless, dense low-angle grain boundaries (LAGBs) and refined grains were examined at the bonding interface. This suggests that the high-velocity collision caused severe plastic deformation and led to the formation of substructures. The interfacial strength was attributed not only to the "wave-like" or "inverted hook-like" diffusion layer but also to the presence of refined grains along the interface and nanocrystalline Al2Cu in the transition zone. Furthermore, the hybrid nanocrystalline-amorphous microstructure strengthened the joint by regulating the balance between strength and ductility.

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.

This study investigated the fatigue properties and interfacial strengthening mechanisms of Al6061-to-Cu dissimilar welded joints via electromagnetic pulse welding (EMPW). The load-bearing capacity of the joints at discharge voltages of 14 kV and 16 kV was superior to that of 12 kV. Meanwhile, the fatigue life of 14 kV joints was one order of magnitude higher than that of 12 kV. The SEM observation on the fatigue fracture surface shows that the typical “tire-mark” fatigue striation just appeared on the 14 kV joint, indicating higher ductility for handling more extended plastic deformation. The high EBSD acquisition was achieved except for the transition zone due to the formation of ultra-fine nanocrystalline Al2Cu phase and amorphous phase, along with many dislocations. Dense low-angle grain boundaries (LAGBs) and refined grains are formed along the bonding interface. This indicates that severe plastic deformation induced dislocations to form the substructure in such an instant (40-60 μs) during the high-velocity collision. The interfacial strength is not only due to the continuous interfacial diffusion layer with a “wave-like” or “inverted hook-like” pattern but also benefits from refined grains along the interface and in the transition zone, as well as the hybrid amorphous-nanocrystalline microstructure, which strengthens the joint through increasing ductility induced by refined grains and regulating amorphous or nanocrystalline phases to affect the balance between strength and ductility of the Al/Cu joint.

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.

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.

Abstract Background Context Pelvic ring fractures are becoming more common in the aging population and can prove to be fatal, having mortality rates between 10% and 16%. Stabilization of these fractures is challenging and often require immediate internal fixation. Therefore, it is necessary to have a biomechanical understanding of the different fixation techniques for pelvic ring fractures. Methods A previously validated three-dimensional finite element model of the lumbar spine, pelvis, and femur was used for this study. A unilateral pelvic ring fracture was simulated by resecting the left side of the sacrum and pelvis. Five different fixation techniques were used to stabilize the fracture. A compressive follower load and pure moment was applied to compare different biomechanical parameters including range of motion (contralateral sacroiliac joint, L1-S1 segment, L5-S1 segment), and stresses (L5-S1 nucleus stresses, instrument stresses) between different fixation techniques. Results Transiliac -trans sacral screw fixation at S1 and S2 showed the highest stabilization for horizontal and vertical displacement at the sacral fracture site and reduction of contralateral sacroiliac joint for bending and flexion range of motion by 165% and 121%, respectively. DTSF (Double transiliac rod and screw fixation) model showed highest stabilization in horizontal displacement at the pubic rami fracture site, while the L5_PF_W_CC (L5-Ilium posterior screw fixation with cross connectors) and L5_PF_WO_CC ( L5-Ilium posterior screw fixation without cross connectors) showed higher rod stresses, reduced L1-S1 (approximately 28%), and L5-S1 (approximately 90%) range of motion. Conclusions Longer sacral screw fixations were superior in stabilizing sacral and contralateral sacroiliac joint range of motion. Lumbopelvic fixations displayed a higher degree of stabilization in the horizontal displacement compared to vertical displacement of pubic rami fracture, while also indicating the highest rod stresses. When determining the surgical approach for pelvic ring fractures, patient-specific factors should be accounted for to weigh the advantages and disadvantages for each technique.

In recent years, semantic communication has received significant attention from both academia and industry, driven by the growing demands for ultra-low latency and high-throughput capabilities in emerging intelligent services. Nonetheless, a comprehensive and effective theoretical framework for semantic communication has yet to be established. In particular, finding the fundamental limits of semantic communication, exploring the capabilities of semantic-aware networks, or utilizing theoretical guidance for deep learning in semantic communication are very important yet still unresolved issues. In general, the mathematical theory of semantic communication and the mathematical representation of semantics are referred to as semantic information theory. In this paper, we introduce the pertinent advancements in semantic information theory. Grounded in the foundational work of Claude Shannon, we present the latest developments in semantic entropy, semantic rate-distortion, and semantic channel capacity. Additionally, we analyze some open problems in semantic information measurement and semantic coding, providing a theoretical basis for the design of a semantic communication system. Furthermore, we carefully review several mathematical theories and tools and evaluate their applicability in the context of semantic communication. Finally, we shed light on the challenges encountered in both semantic communication and semantic information theory.

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.

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.

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.

Powered ankle prostheses have been proven to improve the walking economy of people with transtibial amputation. All commercial powered ankle prostheses that are currently available can only perform one-degree-of-freedom motion in a limited range. However, studies have shown that the frontal plane motion during ambulation is associated with balancing. In addition, as more advanced neural interfaces have become available for people with amputation, it is possible to fully recover ankle function by combining neural signals and a robotic ankle. Accordingly, there is a need for a powered ankle prosthesis that can have active control on not only plantarflexion and dorsiflexion but also eversion and inversion. We designed, built, and evaluated a two-degree-of-freedom (2-DoF) powered ankle-foot prosthesis that is untethered and can support level-ground walking. Benchtop tests were conducted to characterize the dynamics of the system. Walking trials were performed with a 77 kg subject that has unilateral transtibial amputation to evaluate system performance under realistic conditions. Benchtop tests demonstrated a step response rise time of less than 50 milliseconds for a torque of 40 N·m on each actuator. The closed-loop torque bandwidth of the actuator is 9.74 Hz. Walking trials demonstrated torque tracking errors (root mean square) of less than 7 N·m. These results suggested that the device can perform adequate torque control and support level-ground walking. This prosthesis can serve as a platform for studying biomechanics related to balance and has the possibility of further recovering the biological function of the ankle-subtalar-foot complex beyond the existing powered ankles.

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.

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.

Cooling fans are one of the critical components of air-forced (AF) dry-type transformers for regulating internal temperatures. Therefore, effective malfunction detection is crucial to maintain the transformer temperature within an acceptable range and prevent overheating. Regular maintenance occurs periodically and issues with cooling fans may arise between maintenance periods, leading to prolonged operation under malfunctioning conditions and potential failures. In addition, utilities typically have online information about whether a fan works or not without providing information about cooling fan malfunctioning circumstances. To address these challenges, this study proposes learning-based online monitoring techniques to detect malfunctions in AF transformer cooling fans. Random forests (RFs) and convolutional neural networks (CNNs) are developed to classify the audio signals from cooling fans into normal and malfunctioning classes. Unlike RFs, which require separate feature extraction, CNNs are trained based on spectrogram images derived from audio signals. Thus, various time-frequency techniques are utilized for feature extraction in RFs. Besides, multiple data augmentation techniques are employed to enhance the dataset size and diversity. Algorithmic performance is optimized through hyperparameter tuning and classifier threshold adjustment. Simulations reveal that CNNs outperform RFs, whereas the latter provides superior interpretability of acoustic features compared to the former.

The solar heat pump system based on photovoltaic photothermal (PV/T) modules is a new technology that integrates photovoltaics and heat reutilization. It can improve the efficiency of photovoltaic conversion and recovery the remaining heat generated during the photoelectric conversion process, thereby improving the comprehensive efficiency of the whole system. Simulink software is a visual simulation tool, which has the advantages of strong applicability, clear simulation structure and calculation process. The design of its graphical programming greatly simplifies the user modeling process and allows for direct viewing of results, therefore improving the simulation efficiency. At present, there is little research on simulation of solar heat pump systems with PV/T modules based on Simulink software. In this paper, the mathematical models of each component contained in the PV/T solar heat pump system were established based on the system working principle, energy conservation equations and some empirical formulas, and then the operation of the system was simulated by the Simulink software. Due to the operation characteristic of PV/T modules is the key influencing factor for the whole system performance, the model and simulation process for PV/T modules were introduced in detail. The results showed that the surface temperature of PV/T modules under different operating conditions was significantly lower than that of ordinary photovoltaic panels, and the temperature change amplitude was lower. As results, the power generation and photovoltaic conversion efficiency were significantly improved.

Cutaneous T cell lymphoma (CTCL) is a devastating, potentially fatal T lymphocyte malignancy affecting the skin. Despite all efforts, the etiology of the disease remains unknown. Infectious agents have long been suspected as factors or co-factors in CTCL pathogenesis. This review deals with the panel of bacterial and viral pathogens that have been investigated so far in an attempt to establish a potential link between infection/carriage and CTCL development. A special focus is given to a recently discovered human protoparvovirus, namely the cutavirus (CutaV), which has emerged as a plausible CTCL etiological agent. Available evidence in support of this hypothesis as well as alternative interpretations and uncertainties raised by some conflicting data are discussed. The complexity and the multifacetedness of the Parvoviridae family of viruses are illustrated by presenting another protoparvovirus, the rat H-1 parvovirus (H-1PV). H-1PV belongs to the same genus as the CutaV but carries a considerable potential for therapeutic applications in cutaneous lymphoma.

Background: biophysical stimulation therapy, and in particular Pulsed Electromagnetic Fields (PEMFs) and capacitively coupled electric fields (CCEFs) has significantly increased in the last twenty years. For this, it is necessary to have clear information regarding the efficacy, the therapeutic indication and the expected objectives. Methods: we conducted a narrative review taking into consideration different types of studies with different areas of application. The objective was to take into consideration and analyze the different fields of use and the relevant information present in the literature. Results: There is unanimous opinion regarding the usefulness of applying biophysical therapy on the bone compartment both in terms of the tissue healing process and the symptoms associated with this situation. Differently, but no less importantly, in the joint compartment positive opinions were observed mainly on the inflammatory and catabolic process, however, at present,we did not report evidence regarding cartilaginous tissue regeneration. Conclusion: the effectiveness of PEMFs and CCEFs on the bone healing process in the Orthopedic and Traumatology fields is consolidated evidence in the literature. We have also found positive results on symptoms and patient compliance with rehabilitation therapies. Therefore, notable application can be envisaged in the fields of Prosthetic Surgery and Sports Medicine.

Background: Emerging data indicate that radiotherapy can modulate antitumour immune responses. Regulatory T cells (Tregs) are a key immunosuppressive subpopulation of interest. We aimed to evaluate the impact of conventional fractionated radiotherapy on circulating Treg levels in melanoma patients and to determine the correlation between these changes and survival. Understanding radiotherapy–immunity interactions may facilitate personalized combination therapies. Methods: Peripheral blood samples from 32 melanoma patients were analysed to quantify Tregs before and 1-3 months after regional lymph node radiotherapy using flow cytometry. Tregs were characterized as CD4+/CD25+/CD127-. Total CD4+ T cells were also evaluated. Changes were compared to those in a control group of 30 tumor-free patients. Overall survival was correlated with T-cell subset dynamics induced by radiotherapy. Results: At baseline, the median percentage of Tregs was not significantly lower in melanoma patients than in controls (7.4% vs 8.32%, p=0.17). Radiotherapy markedly increased the median Treg count to 10.01% (p=0.0008), with a concomitant increase in total CD4+ cells (to 11.71%, p=0.001), indicating systemic expansion. Patients exhibiting coordinated increases in Treg and CD4+ T cells after treatment had a significantly improved prognosis compared with nonresponders (median OS 27.8 vs 13.1 months, p=0.001). Conclusions: Our study demonstrated the significant effects of standard fractionated radiotherapy on systemic Treg levels in melanoma patients. Radiation-induced changes in T-cell subset proportions hold prognostic value. Monitoring of circulating lymphocyte subsets could facilitate personalized combination therapies.

Co-inhibitory receptors (Co-IRs) are essential in controlling the progression of immunopathology in rheumatoid arthritis (RA) by limiting T cell activation. The objective of this investigation was to determine the phenotypic expression of Co-IRs T cells and to assess the levels of serum soluble PD-1, PDL-2, and Tim3 in Taiwanese RA patients. Co-IRs T cells were immunophenotyped employing multicolor flow cytometry, and ELISA was utilized for measuring soluble PD-1, PDL-2, and Tim3. Correlations have been detected across the percentage of T cells expressing Co-IRs (MFI) and different indicators in the blood, including ESR, high sensitivity CRP (hsCRP), 28 joint disease activity scores (DAS28), and soluble PD-1/PDL-2/Tim3. In RA patients, we recognized elevated levels of PD-1 (CD279), CTLA-4, and TIGIT on CD4+ T cells; TIGIT, HLA-DR, TIM3, and LAG3 on CD8+ T cells; and CD8+CD279+TIM3+, CD8+HLA-DR+CD38+ T cells. The following tests proved to be correlated with hsCRP: CD4/CD279 MFI, CD4/CD279%, CD4/TIM3%, CD8/TIM3%, CD8/TIM3 MFI, CD8/LAG3%, and CD8+HLA-DR+CD38+%. CD8/LAG3 and CD8/TIM3 MFIs are linked to ESR. DAS28-ESR and DAS28-CRP exhibited relationships with CD4/CD127 MFI, CD8/CD279%, and CD8/CD127 MFI, respectively. CD4+CD279+TIM3+% was correlated with DAS28-ESR (p=0.0084, N=46), DAS28-CRP (p=0.007, N=47), and hsCRP (p=0.002, N=56), respectively. In the serum of patients with RA, levels of soluble PD-1, PDL-2, and Tim3 were extremely elevated. CD4+ TIM3+% (p=0.0089, N=46) and CD8+ TIM3+% (p=0.0305, N=46) were correlated with sTIM3 levels; sPD1 levels were correlated with CD4+CD279+% (p<0.0001, N=31) and CD3+CD279+% (p=0.0084, N=30). Co-IRs expressions on CD4+ and CD8+ T cells, as well as soluble PD-1, PDL-2, and Tim3 levels, could function as indicators of disease activity and potentially play crucial roles in the pathogenesis of RA, in accordance to our findings.

Chimeric antigen receptor (CAR) T-cell therapy has greatly improved outcomes for patients with relapsed or refractory hematological malignancies. However, challenges such as treatment resistance, relapse, and severe toxicity still hinder its widespread clinical application. Traditional transcriptome analysis has provided limited insights into the complex transcriptional landscape of both leukemia cells and engineered CAR-T cells, as well as their interactions within the tumor microenvironment. However, with the advent of single-cell sequencing techniques, a paradigm shift has occurred, providing robust tools to unravel the complexities of these factors. These techniques enable unbiased analysis of cellular heterogeneity and molecular patterns. These insights are invaluable for precise receptor design, guiding gene-based T cell modification, and optimizing manufacturing conditions. Consequently, this review utilizes modern single-cell sequencing techniques to clarify the transcriptional intricacies of leukemia cells and CAR-Ts. The aim of this manuscript is to discuss the potential mechanisms that contribute to the clinical failures of CAR-T immunotherapy. We will examine the biological characteristics of CAR-Ts, the mechanisms that govern clinical responses, and the intricacies of adverse events. By exploring these aspects, we hope to gain a deeper understanding of CAR-T therapy, which will ultimately lead to improved clinical outcomes and broader therapeutic applications.

Background and Objectives: This study aimed to evaluate the effects of subtalar joint axis-based balance exercises on the anterior talofibular ligament (ATFL) thickness, ankle strength, and ankle stability after an arthroscopic modified Broström operation (AMBO) for chronic ankle instability (CAI). Materials and Methods: The study included 47 patients diagnosed with CAI who underwent AMBO and were randomly divided into three groups: control (n=11), general balance exercise (n=17), and subtalar joint axis balance exercise (n=19), regardless of the affected area. Participants in the exercise rehabilitation group performed exercises for 60 min twice a week for 6 weeks, starting 6 weeks after AMBO. ATFL thickness, ankle strength, and ankle dynamic stability were measured using musculoskeletal ultrasonography, Biodex, and Y-balance test, respectively, before and after treatment. Results: Compared with the remaining groups, the subtalar joint axis balance exercise group had reduced ATFL thickness (p = 0.000), improved ankle strength for eversion (p = 0.000) and inversion (p = 0.000), and enhanced ankle stability (p = 0.000). Conclusions: The study results suggests that subtalar joint axis-based balance exercises may contribute to the early recovery of the ankle joint after AMBO.

Background: Periprosthetic joint infection (PJI) following total hip and knee arthroplasty remains an extremely challenging and relatively high complication. This study aims to develop, validate and evaluate the use of machine learning (ML) algorithm to predict PJI in patients undergoing revision arthroplasties. Methods: A comprehensive review of patients undergoing hip or knee revision arthroplasty from 1 January 2015 to 31 March 2021 was conducted. Clinical data coming from preoperative patients history, laboratory analysis and demographic characteristics of patients were screened. Final data have been used to train a Logistic Regression model with the aim of predicting PJI preoperatively. Results: 1360 patients were enrolled, 1141 in the aseptic cohort and 219 in the infected cohort were included. ML demonstrated good discriminatory performance in predicting PJI in the selected patients (area under the curve 0.770 ± 0.006 in the training set and 0.720 ± 0.057 in the test set), and identified 3 significant predictors of PJI. Conclusion: ML algorithm trained using preoperative clinical data accurately predicted PJI. The incorporation of ML models into preoperative assessment of patients undergoing prosthetic revision procedures are useful in providing specific risk assessment to aid individualised counselling, shared decision making and presurgical optimization.

Prostate cancer (PC) is the second most diagnosed cancer among men. It was observed that early diagnosis of disease is highly beneficial for survival of cancer patients. Therefore, extension and increasing quality of life of PC patients can be achieved by broadening the Cancer Screening programs that are aimed at the identification of cancer manifestation in patients at earlier stages before they demonstrate well-understood signs of the disease. Therefore, there is an urgent need in standard, sensitive, robust, and commonly available screening and diagnosis tools for identification of early signs of cancer pathologies. In this respect, “Holy Grail” of cancer researchers and bioengineers for decades have been molecular sensing probes that would allow diagnosis, prognosis, and monitoring of cancer diseases by their interaction with cell-secreted and cellassociated PC biomarkers, e.g. PSA and PSMA correspondinly. At present, most PSA tests are performed at centralized laboratories using high throughput Total PSA immune analyzers which are suitable for dedicated laboratories and are not readily available for the broad health screening. Therefore, the current trend in detection of PC is developments of the portable biosensors for mobile laboratories and individual use. Phage display since its conception by George Smith in 1985 has emerged as a premier tool in molecular biology with widespread applications. This review describes how the paradigm of molecular evolution and phage display revolutionized the methods of early diagnosis and monitoring of PC.

The size of the population and the need for residential spaces are increasing. One possible solution is to add new floors to existing buildings. The positive aspects of such a solution with respect to its socio-economic impact and impact on the environment is that large amounts of carbon dioxide release will be avoided, waste and its treatment will be reduced, and agricultural land and green spaces will be preserved. However, adding floors to existing structures might be structurally challenging, especially in terms of the behavior under seismic actions. This paper presents a numerical study of a reinforced concrete frame in an old building to which new floors are subsequently added. The analysis shows that the frame does not behave as a whole with the old part of the structure, nor does it behave the same as if it were made with rigid joints compared to additional ones connected using hinge joints. The change from the corner (knee) joint to the external joint has its own effect on the distribution of internal forces in the structure as a whole and in the joint in particular.

Posterior dislocations of the sterno-clavicular joint (SCJ) are rare events, most commonly due to motor vehicle accidents or sports injuries and they often occur in young and active patients. This injury can represent a real emergency because of the vital structures located posterior to the medial clavicle such as anonymous artery, anonymous vein, trachea, subclavian artery and vein, esophagus and thoracic duct. The diagnosis could be insidious given the not peculiar clinical presentation and it is often necessary to perform a computed tomography to identify it. In case of failure of reduction maneuvers, the surgical treatment becomes a mandatory choice, but unfortunately literature reports a restricted cohort of cases and proposes different stabilization techniques without showing a significant comparison of results. Moreover, due to the rarity and high risk of complications, other than the lack of knowledge about the injury and its repair techniques, the management of these injuries are mutually discharged from orthopedic surgeon to the thoracic surgeon and vice-versa. A deep study of the joint anatomical characteristics and its biomechanics allow the surgeon to face surgery more safely, choosing the most appropriate technique. Given the importance of the SCJ for the movement of the shoulder girdle, authors believe that the surgeon’s goal should be to restore the complete range of movement of the joint in case of dislocation. For this reason, stabilization with semitendinosus tendon graft has to be considered one of the best solutions at our disposal to date.

Objective The aim of this study was to examine the impact of a modern lifestyle on college female students' health, specifically focusing on their hip and knee joint mobility. The objective of this study was to assess the influence of hydraulic resistance training with the self-myofascial release technique on improving joint mobility in female college students. The training also aimed to compare the effectiveness of hydraulic resistance exercise with and without the self-myofascial release technique on hip and knee joint mobility.Methods The study used a randomized controlled trial design to recruit 30 female college students aged 18-25 through campus advertisements and announcements. Medical conditions or injuries that might have affected participation was screened. Participants were indiscriminately allocated to Group A (Hydraulic Resistance Training with Self-Myofascial Technique) or Group B (Hydraulic Resistance Training without Self-Myofascial Technique). The baseline assessments included joint range of motion (ROM) measurements using a goniometer. Certified trainers supervised the training sessions, and the data were analyzed using SD and mean using SPSS. ResultsThis study aimed to evaluate the impact of hydraulic resistance training with self-myofascial release on hip and knee joint mobility in female college students. The results showed that both groups showed improved hip and knee flexion with and without the self-myofascial release technique. However, the Group A using the self-myofascial release technique (Group A) showed a more significant enhancement, as indicated by the smaller p value compared to Group B. It has been suggested that the self-myofascial release technique may improve hip and knee joint mobility. ConclusionThis study concluded that Hydraulic Resistance Training with Self-Myofascial Release (HSMR) could improve hip and knee joint mobility among female college students. These findings suggest that integrating the self-myofascial release technique into training regimens can improve joint mobility. However, further research with larger sample sizes and extended intervention periods was needed to understand the long-term effects and sustainability of these improvements.

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin. This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

(1) Background: Ferric carboxymaltose (FCM) is an intravenous (IV) high-dose iron that is effective in the treatment of iron deficiency anemia. This study was to determine if preoperative IV FCM administration could improve recovery from postoperative anemia in patients undergoing revision total joint arthroplasty. (2) Methods: This prospective randomized controlled study analyzed 82 patients undergoing revision total joint arthroplasty during a single hospitalization. Patients in the iron group (n = 41) were administered 1000 mg of IV FCM two weeks preoperatively, while those in the control group (n = 41) were not. Moreover, patients with anemia defined as a preoperative suboptimal Hb concentration &lt;13.0 g/dl were compared according to IV FCM administration. The absolute Hb levels and changes in Hb levels, iron profiles, transfusion rate, and EuroQOL 5-dimension (EQ-5D) scores were compared. (3) Results: There were no significant differences in recovery of Hb levels at each timepoint between the two groups; however, the changes in Hb levels from baseline to four weeks postoperatively showed marginally significant differences favoring the iron group (p = 0.052). However, for preoperatively anemic patients, the change in hemoglobin (Hb) levels between baseline and four weeks postoperatively was significantly better in the iron group than in the control group (iron group [n = 26], −0.3 ± 0.7 g/dL vs. control group [n = 27], −0.9 ± 0.8 g/dL; p = 0.040), although the absolute Hb levels, transfusion rates, and patient quality of life were comparable (all p &gt; 0.05). The iron group showed improved iron metabolite levels including serum ferritin and transferrin saturation four weeks postoperatively, and no adverse events associated with IV FCM administration occurred in either group. (4) Conclusions: Preoperative IV FCM in anemic individuals undergoing revision joint arthroplasty was effective in accelerating recovery from surgery-related anemia by improving Hb levels without any adverse events, despite similar actual Hb levels between the groups. Our findings are clinically relevant and can facilitate determination of the suitability of IV FCM as a safe and reliable protocol for iron supplementation for anemia correction.

The principal barrier to an HIV-1 cure is the persistence of infected cells harboring replication-competent proviruses despite antiretroviral therapy (ART). HIV-1 transcriptional suppression, referred to as viral latency, is foremost among persistence determinants, as it allows infected cells to evade the cytopathic effects of virion production and killing by cytotoxic T lymphocytes (CTL) and other immune factors. HIV-1 persistence is also governed by cellular proliferation, an innate and essential capacity of CD4+ T cells that both sustains cell populations over time and enables a robust directed response to immunological threats. Yet when HIV-1 infects CD4+ T cells, this capacity for proliferation can counterproductively enable surreptitious HIV-1 propagation without the deleterious effects of viral gene expression in latently infected cells. Over time on ART, the HIV1 reservoir is shaped by both persistence determinants, with selective forces most often favoring clonally expanded infected cell populations harboring transcriptionally quiescent proviruses. Moreover, if HIV latency is incomplete or sporadically reversed in clonal infected cell populations that are replenished faster than they are depleted, such populations could both persist indefinitely and contribute to low-level persistent viremia during ART and viremic rebound if treatment is withdrawn. In this review, select genetic, epigenetic, cellular, and immunological determinants of viral transcriptional suppression and clonal expansion of HIV-1 reservoir T cells, interdependencies among these determinants, and implications for HIV-1 persistence will be presented and discussed.

Sarcomas are a group of malignancies of mesenchymal origin with plethora of subtypes. Given the sheer heterogeneity of various subtypes and rarity of the disease, management of sarcomas has been challenging with poor patient outcomes. Surgery, radiation therapy and chemotherapy have remained the backbone of treatment in patients with sarcoma. The introduction of immunotherapy has rev-olutionized the treatment of various solid and hematological malignancies. In this review, we discuss basics of immunotherapy and immune microenvironment in sarcomas, various modalities of im-munotherapy such as immune checkpoint blockade, oncolytic viruses, cancer targeted antibodies, vaccine therapy and adoptive cell therapies like CAR T-cell therapy, T cell therapy, TCR therapy.

The T cell composition of the tumor microenvironment (TME) of esophageal adenocarcinoma (EAC) in comparison to the T cell composition of the TME of Barrett esophagus (BE) and in the context of clinicopathologic features and patient survival is unknown. To help fill these knowledge gaps, we used a multiplex immunofluorescence platform to study adaptive T cells and T cell subtypes based on costimulatory/inhibitory markers in EAC (n=54) and matched BE (n=21) samples from 54 patients with EAC and correlated the T cell phenotype distribution with clinicopathologic features and disease-free survival. We observed significant enrichment of cytotoxic T cells (CTCs), memory T cells, effector memory T cells, memory T regulatory cells (MTregs), and T cells expressing costimulatory/inhibitory markers LAG3, TIM3, and ICOS in EAC compared to BE, in the stroma. In EAC, increased TIM3 expression on T cells significantly correlated with increased CTCs but not T regulatory cells (Tregs). In EAC, higher densities of Tregs and MTregs correlated with pT1 disease, low pathologic stage, and absence of lymphovascular invasion. In EAC, patients with higher density of TIM3-expressing T cells had shorter disease-free survival by univariate and multivariate analyses. Our results identify T cell subtypes that are relevant to EAC biology and patient outcome. Furthermore, our results identify TIM3 as a potential target for optimization of immunomodulatory therapy in EAC.

The purpose of the present study was to develop an experimental model for studying of the intra-articular knee movements depending on the work of the knee joint and applied muscle groups in isometric stretching conditions with different tens. The experimental procedure includes ultrasound examination of a knee joint after isometric stretching of healthy men (n=32). The changes in millimeters of the distances between the femur and tibia were measured with ultrasound sonographer at three stages. The first stage was performed on ten (n=10) healthy men at five different sitting and upright positions. In the second and third experimental model stages the lower limbs loading was on 22 participants. Our hypothesis which was confirmed, was that as a result of increasing extraloads on the participants back (2, 5, 10, 15, 17, 20 kg), a intra-articular decrease in the femur-tibia cartilage surface distance wiil be observed. The accuracy of the created experimental model was improved over its three stages from 30% to 9%. Quantitative model data can help to create a mathematical model for the mechanical effects during deformation of the knee joint bone cartilage, as well as to outlines the some future tasks: increasing loading weights; enlarge participant groups; comparison men and women; healthy and pathology comparison.

Trypanosomosis is a global animal issue, causing significant economic losses, particularly in Africa. In Spain, only one pathogenic species, Trypanosoma evansi, has been identified so far. It was first detected in a dromedary camel in the Canary Islands in 1997. Since then, numerous cases of the disease, known as surra, have been diagnosed, prompting various studies and efforts in control and surveillance. Given the lack of a comprehensive database that consolidates the most relevant data in this area, the development of a national atlas, with focus on the Canary Islands, to incorporate all available information on T. evansi in Spain became a necessity. For the development of the atlas, a repository was constructed, encompassing a range of datasets and documents spanning from 1997 to 2022. Information from each source, and in particular georeferenced locations and results of blood tests on animals, were extracted and integrated into a comprehensive database. A total of 31 sources were analysed, providing a total of 99 georeferenced locations and 12,433 animal samples. Out of these samples, 601 (mostly from dromedaries) were found to be positive for T. evansi. The Card Agglutination Test for T. evansi (CATT/T. evansi), a serological test, was the most commonly used diagnostic method, and it showed higher prevalence for all tested animal species. Positive cases were mainly concentrated in the Canary Islands, specifically in the eastern islands, with isolated cases found in the province of Alicante (Iberian Peninsula). This atlas provides an overview of the history and occurrence of surra in Spain, and it represents a valuable tool for future control initiatives and for research. Still, the need for more studies remains, especially for further testing of potential hosts other than camelids and for the examination of their potential transmission vectors.

The plate heat exchanger (PHE) is a component that provides heat to be transferred from hot water to domestic cold water without mixing them with high efficiency. Over the lifetime of the PHE, cyclic pressures act on the brazing points and the plates, and this may lead to fatigue failure. The fatigue behaviour of the PHE, designed by using copper-brazed 316L stainless steel, was investigated in this study. First, the fatigue tests under the load ratio R = 0.1 were performed on the Vibrophore 100 testing machine to obtain the S-N curve of the analysed brazed joint. Based on the obtained experimental results, an appropriate material model of the analysed brazed joint has been created, which was validated with numerical calculation in the framework of a program code Ansys. A validated material model was then used for the subsequent numerical analysis of PHE. In order to carry out a numerical calculation using the finite element method (FEM), a 3D model of the heat exchanger was created based on the previous scanning of PHE-geometry. Thereafter, the geometry was parameterised, which allowed us to perform parametric simulations (monitoring different responses depending on the input geometry). Numerical simulations were carried out in the framework of the Ansys software, whereby the obtained results were analysed, and the responses were appropriately characterised according to previously determined load cases.

Trichothecene mycotoxin T-2 toxin is an important environmental pollutant and poses a global threat to human and animal health. T-2 toxin could induce nephrotoxicity, however, the precise molecular mechanism remains unclear. In this study, the mice were intraperitoneally administrated with a single dose of 2 mg/kg T-2 toxin. The kidney function and ultrastructural observation were also assessed and found T-2 toxin exposure could cause kidney damage. Transmission electron microscopy showed a significant swelling and vacuolization of the mitochondria of renal cell. A total of 1122, 58, and 391 differential expression genes (DEGs) that were predominantly expressed in kidney tissues at 1 d, 3 d, and 7 d after T-2 toxin exposure, respectively. Early transcriptomic changes at 1 d after exposure were down-regulation of DEGs involved in the cell cycle, p53 signaling pathway, and cellular senescence, while up-regulation of DEGs referred to the ribosome pathway. The temporal variations in gene expression pattern in T-2 toxin exposure in mice kidney were presented and cellular metabolism was disturbed at the exposure recovery period with 7 d. In conclusion, this study, for the first time, provided a comprehensive comparative transcriptomic analysis of gene regulation in T-2 toxin exposure-induced nephrotoxicity at different temporal periods and explored the nephrotoxicity mechanism of T-2 toxin at the mRNA level.

Ulcerative colitis is a chronic immune-mediated disease of unclear etiology, affecting people of different ages and significantly reducing the quality of life. Modern methods of therapy are mainly represented by anti-inflammatory drugs and are not aimed at a specific pathogenetic factor. In this study, we investigated the effect of transplantation of sterile stool filtrate from healthy donors on the induction of anti-inflammatory immune mechanisms. It was shown that performing such a procedure in patients with ulcerative colitis caused the appearance of T helper cells in the blood, which reacted to the content of sterile stool filtrates in an antigen-specific manner and produced IL10. At the same time, cells of the same patients before therapy in response to the addition of sterile stool filtrates were less reactive and predominantly produced IL4, indicating its pro-inflammatory skewing. The obtained data demonstrated the effect of an anti-inflammatory shift in the T-helper response after transplantation of sterile stool filtrate, which increased and persisted for at least three months after the procedure.

Abstract: Background: The main aim of the study was to assess the intensity and frequency of cervical spine pain in young people with temporomandibular disorders (TMD). Methods: The pilot study was conducted from June to July 2023. Inclusion criteria were: age (18-30 years), cervical spine pain (for at least 1 month) and consent to participate in the study. The study was conducted based on a physiotherapeutic examination and an original questionnaire. The pain level was assessed using the Visual Analogue Scale (VAS). Among 95 people with cervical spine pain, 51 people (53.7%) constituted the control group (without a history of temporomandibular disorders), while 44 (46.3%) people constituted the study group. Results: The mean age of people participating in the study was 22.2±2.2 years in the study group and 22.5±3.1 years in the control group. The largest group were people aged 21-25 (n=51 people, 53.7%). Patients from the study group more often experienced pain in the stomatognathic system during palpation (both in the muscle, joint and musculoskeletal groups) and had reduced mobility of the temporomandibular joints in every movement (p<0.001). People from the study group were characterized by also less mobility of the cervical spine (p<0.05), apart from extension movement (p>0.05). There was a significant relationship between temporomandibular disorders and cervical spine pain (p<0.05, chi2=10.118, df=1, rc=0.31). The level of back pain was significantly higher in people from the study group (p<0.001, chi2=45.765, df=4, rc=0.57). Conclusions: Our research has shown that the causes of cervical spine pain at a young age may be temporomandibular disorders, which are generally not recognized and properly treated.

Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially to those with co-morbidities, the elderly and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analysis of transcriptomic RNAseq and single-cell sequencing datasets comparing between severe and mild COVID-19 patients have demonstrated that the early expansion of myeloid-derived suppressor cells (MDSCs) could a key feature of severe COVID-19 progression. Besides serving as potential early prognostic biomarkers for severe COVID-19 progression, several studies have also indicated the functional roles of MDSCs in severe COVID-19 pathogenesis and possibly even long COVID. Given the potential links between MDSCs and severe COVID-19, we examined the existing literature summarizing the characteristics of MDSCs, the evidence of MDSCs in facilitating severe COVID-19 pathogenesis and discuss the potential therapeutic avenues that can be explored to reduce the risk and burden of severe COVID-19. We also provide a web app where users can visualise the temporal changes of specific genes or MDSC-related gene sets during severe COVID-19 progression and disease resolution at https://temporal-severe-covid.streamlit.app/, based on our previous study described by Ong et al., 2021.

Tumors are complex tissues of malignant cells surrounded by a diverse cellular micro-environment with which they interact. The molecular and cellular underpinnings of cancer cells have been increasingly understood during the last few decades. Nonetheless, a great deal remains unknown regarding the ways in which tumour cells modify their surroundings and impact the organisation and makeup of cells. This review aims to concentrate on recent advancements in molecular characterization of tumor cells and its immunology, provides recent and general insight into cancer immunity and immunotherapy, and discusses the immunobiology of human adaptive and innate immunity to malignant growth of cancer cells, the mechanisms that support human immune response from beneath, an up-to-date scientific development to cancer immunotherapy, and how tumor and host responses can Encircle as a military tactic effective anti-cancer immunity.

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.

We propose that the coexistence of gapless Fermi arcs with the metal-insulator crossover of in-plane resistivity in strongly underdoped cuprates can be explained by the FL* fractionalized Fermi liquid nature of these systems and it is not due simply to disorder effects. The particle excitations of this FL* system derived from variants of the t-J model are: the gapless holon carrying charge with small Fermi momentum proportional to the doping, the gapful spinon carrying spin 1/2, gauge fluctuations coupling them and the hole as a spinon-holon bound state or resonance due to gauge binding with a Fermi surface respecting the topological Luttinger theorem. In our proposal Fermi arcs are determined by the hole resonance, whereas the metal-insulator crossover is dominated by spinon-spinon (with subleading holon-holon) gauge interactions and this dichotomy is able to explain their coexistence.

One of the most common subgroups of cutaneous T-cell lymphomas is the that of primary cutaneous CD30 positive lymphoproliferative disorders. The group includes lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL), as well as some borderline cases. Recently, significant progress has been made in understanding the genetics and treatment of these disorders. This review article summarizes the clinical evidence supporting the current treatment options in these diseases. Recent years have seen the introduction of novel agents into clinical practice; most of these target CD30, such as anti-CD30 monoclonal antibodies and conjugated antibodies (brentuximab vedotin), bispecific antibodies and cellular therapies, particularly anti-CD30 CAR-T cells. This paper briefly reviews the biology of CD30 that makes it a good therapeutic target, and describes the anti-CD30 therapies that have emerged to date.

Background: This study retrospective evaluates patients with stage IV melanoma treated with Nivolumab and Ipilimumab combination therapy from two regional oncology centers from Romania between the years of 2019 up to the end of 2022. Methods: The data were analyzed in SAS for Windows, V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. Results: Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150-NA) and a median PFS of 211 days (95% CI: 113-430). 45.3% of the patients experienced adverse events during the Nivolumab + Ipilimumab treatment with some of them having multiple organ systems involved. Discussion: The OS values were lower than that reported in approval clinical trials, but the results show a marked improvement when comparing to results obtained by chemotherapy regimens previously used in these scenarios. Conclusion: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.

Mesothelioma is a cancer arising from mesothelial cells lining the thoracic (pleura) or the abdominal (peritoneum) cavities, and more rarely from transformed mesothelial cells of pericardium or tunica vaginalis testis. The development of mesothelioma has been related to the exposure to carcinogenic mineral fibers, mainly asbestos. Malignant mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. We here review all these aspects to underline the progress being made in investigation and to emphasise how much work remains to be done to improve prognosis and treatment.

In this note we consolidate and give a brief description of several recently published results in ring theory having disproof. These results have been published during 2016 to 2021 in the so called non-predatory reputed mathematical journals indexed in the well known database like Scopus. We have considered results on rings in which each element is a sum of two idempotents appeared in Canad. Math. Bull. (2016), weakly tripotent rings appeared in Bull. Korean Math. Soc. (2018) and Rendiconti Sem. Mat. Univ. Pol. Torino (2021), involution t-clean rings appeared in Eur. J. Pure Appl. Math (2022) and strongly 2-nil clean rings with units of order two appeared in Eur. J. Pure Appl. Math (2023).

Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T cell response, but far from all patients elicit a sufficient immunological response. This witnesses a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic healthy human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy showing E1-specific T cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors, and preferably in patient samples.

To improve the measurement accuracy of three-dimensional rotation angle of the spherical joint, a novel approach is proposed in this study, which combines the magnetic detection by Hall sensor and surface feature identification by eddy current sensor. Firstly, a permanent magnet is embedded in the ball head of spherical joint, and Hall sensors are set and distributed in the ball socket to measure the variation of magnetic flux density when spherical joint rotating, which are related to 3D rotation angle. In order to further improve measurement accuracy and robustness, we also set grooves on the ball head and use eddy current sensors to synchronously identify the rotation angle of the ball head. After the combination of two signals is adopted, a measurement model is established using the RBF neural network by training, and realized real-time measurement of the 3D rotation angle of spherical joint. The feasibility and superiority of this method are validated through experiments. The experimental results indicated that the measurement accuracy is promoted substantially compared to the preliminary measurement scheme based on spherical coding, the average measurement error of single axis is reduced by 9'9". The root mean square errors for the measurement of 3D rotation angles in this proposed method are as follows: the pitch angle α has an error of 1'8", the yaw angle β has an error of 2'15", and the roll angle γ has an error of 29'6".

Keywords: Agrobacterium 1; Xenorhabdus 2; NR-AMP 3 T-DNA keyword 4; TI-plasmid 5; Intact/Cured/T-DNA Deleted 6 Sensitive/Resistant 7; EMA_PF2 8; HPLC 9

By conjugating a radioantigen (o-quinone) with a protein - Esherichia coli endotoxin, a stable polyantigen complex-protein-quinoid radioantigen (BChA) - o-quinone imine (C6H10O-NH - protein) was obtained, including haptenic (o-quinone) and protein part of the antigenic complex (Esherichia coli endotoxin). Using the above components (hyperimmune antiradiotoxic serum, ethanol extract of the Vita-Force apiphitopreparation, metabolic products of Bifidobacterium bifidum, Bacillus subtilis and a highly dispersed fraction of bentonite), a polyfunctional composition «Polyapisogen» was compiled, including polyglobulins (500 cm3 per 1 L),500 cm3 of 4% ethanol extract of the Vita-Force apiphitopreparation, in which a highly dispersed fraction of bentonite (20 g), metabolism products (2 g powder) and Bacillus subtilis metabolism products (4 g) are dissolved. The polyfunctional preparation obtained by the above-described technology is used as an activator of the immune system against the background of its imbalance induced by agents of a radiogenic nature. It was found that a single subcutaneous injection of the drug at a dose of 25 mg / kg of live weight (dry matter basis) had a radioprotective effect increasing the survival rate of affected animals upto 75%. The studies carried out can serve as a basis for the creation of polyfunctional radioprotective, immunoprotective and bioprotective agents not only for isolated, but also for combined lesions of the body by agents of radiogenic and non-radiogenic nature using polyglobulins, convalescent serums, bee products, metabolic products of probiotic microorganisms and mineral sorbents.

Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8+ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest into the ability of radiation to modulate CD8+ T cell responses. Recent studies that carefully analyzed the CD8+ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials that evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are undergoing. In this review, we summarize the current status of knowledge regarding the changes of CD8+ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biologic mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.

In this research paper an algorithm for the derivation of methods based on theorems and axioms of fuzzy logic is presented, analyzed and applied. This new proposed procedure generates fuzzy methods and evaluates the value of fuzzy propositions through fuzzy implication. The new implications of the family should satisfy a number of axioms. Also, we denote the conditions in order to satisfy the maximum number of axioms. Moreover, authors state and prove theorems focusing on fuzzy implication, observing the rule: the fuzzy function of fuzzy implication is strong and that lead to fuzzy negation. In addition, the optimal number of repetitions is calculated according to the expected truth value. The formulas produced are verified through the use of temperature and humidity values over a certain period of time and in a certain geographical area in Greece. The basic steps of the methodology are the fuzzification of the data given ​​using four membership degree functions and the application of the membership degrees of temperature and humidity values on a new type of fuzzy implication. Finally, we observed that the isosceles trapezium gave the best results and the type of fuzzy implication can be effectively applied.

The new class of mRNA vaccines is studied extensively, leading to many novel prospects based on the pivotal success of vaccines against the SARS-Cov-2 virus. Many novel mechanisms of immune response discovered have led to the possibility of mutation-resistant vaccines by combining multiple conserved epitopes as antigens to manipulate the T-cell and B-cell responses; these antigens can also come from different organisms, providing protection against numerous diseases and of most tremendous significance is the utility of mRNA vaccines in preventing and treating more than 100 autoimmune disorders. This is a significant humanitarian breakthrough given the ease and faster and low cost of mRNA vaccines, being a chemical entity. This paper provides a prospective analysis of mRNA vaccines with much broader applications than anticipated when these vaccines entered treating SARS-Cov-2 infections.