For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

In 2012 the Open Geospatial Consortium published GeoSPARQL defining “an RDF/OWL ontology for [spatial] information”, “SPARQL extension functions” for performing spatial operations on RDF data and “RIF rules” defining entailments to be drawn from graph pattern matching. In the 8+ years since its publication, GeoSPARQL has become the most important spatial Semantic Web standard, as judged by references to it in other Semantic Web standards and its wide use for Semantic Web data. An update to GeoSPARQL was proposed in 2019 to deliver a version 1.1 with a charter to: handle outstanding change requests and source new ones from the user community and to “better present” the standard, that is to better link all the standard’s parts and better document & exemplify elements. Expected updates included new geometry representations, alignments to other ontologies, handling of new spatial referencing systems, and new artifact presentation. In this paper, we describe motivating change requests and actual resultant updates in the candidate version 1.1 of the standard alongside reference implementations and usage examples. We also describe the theory behind particular updates, initial implementations of many parts of the standard, and our expectations for GeoSPARQL 1.1’s use.

Tunnel-interchange connecting sections pose significant safety challenges on mountainous expressways due to their high incidence of accidents. Improving road safety necessitates a comprehensive understanding of driver behavior in such areas. This study explores the influences of road characteristics, signage information volume, and traffic conditions on drivers' car-following and lane-changing behavior in tunnel-interchange diverging areas. Utilizing driving data from 25 subjects of 72 simulated road models, driving performance is assessed using Friedman rank test and multivariate variance analysis. The results highlight the significant influence of both connection distance and signage information load on driving behavior. In tunnel-interchange scenarios, the reduction of velocity increased by 62.61%, and speed variability surged by 61.11%, indicating potential adverse effects on driving stability due to the environmental transitions. Decreased connection distances are associated with reduced lane-changing durations, larger steering angles, and increased failure rates. Furthermore, every two units increase in signage information leads to a 13.16% rise in maximum deceleration and a 5% increase in time headway. Notably, the signage information volume shows a significant interaction with connection distance (F=1.60, P=0.045) for most car-following indicators. Hence, the study recommends a maximum connection distance of 700 m and signage information not exceeding nine units for optimal safety and stability.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

(1) Background: The study aimed to investigate compressive strength for three computer-aided design/computer-aided manufacturing (CAD/CAM) dental materials: glassceramic IPS Empress CAD (IvoclarVivadent), hybrid ceramic Cerasmart (GC) and polymer-reinforced graphene G-CAM (Graphenano Dental). (2) Methods: 45 samples consisted of the molar crowns fabricated by three CAD/CAM materials were cemented adhesively on 3D printed abutments (Asiga DentalResin). The samples were divided into 3 groups (n=15) according to the crowns thickness; group 1 under the cusps/cervical margins - 0.6 mm/0.4 mm, group 2 - 1 mm/0.7 mm respectively, and group 3 - 1.5 mm/1 mm. Additionally, 20 cylindrical specimens fabricated by the three crowns and abutments material (n=5) were prepared by CAD/CAM technique. All samples and specimens were subjected to an axial compressive load by using a universal testing machine (Instron 3366-10kN, USA) until fracture. (3) Results: The compressive strength were for Empress CAD 1258 MPa, Cerasmart 501.3 MPa, G-CAM 435 MPa and Asiga resin 360 MPa. G-CAM crowns exhibited a higher maximum compressive load (1701.5-2011.8N) than both Cerasmart (1295.4-1642.9N) and Empress CAD (494.3-597.5N). (4) Conclusions: The CAD/CAM crown materials presented different mechanical behavior; Empress CAD and Cerasmart presented a fragile behavior, with a high compressive strength when compared to G-CAM and Asiga resins.

Introduction: Subtalar Arthroereisis (STA) is a surgical intervention for pediatric flexible flatfoot (PFF), primarily targeting hindfoot alignment by limiting excessive subtalar eversion. However, its effects on forefoot parameters remain underexplored. This study aims to investigate radiological changes following STA in pediatric patients. Materials and Methods: A retrospective analysis was conducted on consecutive patients treated with STA for PFF. First ray-related angles, including Hallux Valgus Angle (HVA) and Inter-Metatarsal Angle (IMA), alongside hindfoot radiological parameters such as Meary, Calcaneal Pitch, and Costa Bartani angles, were assessed. Subgroup analysis by gender was performed, and correlations between demographic and pre-operative radiological parameters were examined. Results: Forty-one patients (81 feet) with a mean age of 11.6 years were included, with a mean follow-up duration of 6.4 months. No significant differences were observed in first ray-related an-gles pre- and post-operatively, with mean IMA changing from 7.97° to 7.18° and mean HV angles from 9.51° to 8.66°. Noteworthy improvements were seen in flat foot angles, including Meary, Calcaneal Pitch, and Costa Bartani angles, postoperatively. Age subgroup analysis revealed similar trends in IMA and HVA changes between Group A (operated before peak growth) and Group B (operated later). Higher preoperative angles tended to improve, while lower preoperative IMA and HVA tended to worsen postoperatively, all remaining within normal ranges. Conclusion: STA showed positive radiological outcomes for PFF treatment, while negligible changes in first ray-related angles were observed. Age subgroup analysis indicated similar trends regardless of operation timing. Higher preoperative angles tended to improve, while lower preoperative angles tended to worsen postoperatively, despite all falling within non-pathological ranges. Further re-search is warranted to confirm this correlation.

This research deals with the possibility for construction of the database on the braking friction coefficient for actual roads from the viewpoint of traffic safety especially for automated driving such as level 4 or higher. In an automated driving such levels, the controller needs to control the vehicle, but the road surface condition, especially the road friction coefficient on wet roads, snowy or icy roads, changes greatly, and in some cases, changes by almost one order. Therefore, it is necessary for the controller to constantly collect environment information such as the road friction coefficients and prepare for emergencies such as obstacle avoidance. However, at present, the measurement of the road friction coefficients is not systemically performed, and a method for accurately measuring has not been established. In order to improve this situation, this study examines a method for continuously measurement for the road friction characteristics such as μ-s characteristics.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

This study aims to test a model linking destination image, perceived value, tourist satisfaction, and tourist loyalty. Based on a sample of 300 tourists travelling by car from the World Natural Heritage Site of Tianchi, China, a new model of destination image was explored and data were analysed using partial least squares structural equation modelling (PLS-SEM). The results show that perceived value and satisfaction are direct antecedents of destination loyalty. Above all, perceived value and tourist satisfaction mediate the relationship between destination image and loyalty. Finally, this study discusses the theoretical and management implications of the findings in order to boost the tourism industry in the context of car trips.

Immune checkpoint inhibitors (ICI’s) are in the forefront of advanced Non Small Cell Lung Cancer (NSCLC) treatment. Still, only 27- 46% of patients respond to initial therapy with ICI’s and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6-3.1 months and a Disease Control Rate (DCR) of 21.4%-41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75-81%, according to post-hoc analyses of several clinical trials. Future research of ICI rechallenge for NSCLC should focus on better patient stratification, to reflect the underlying biology of immunotherapy resistance more accurately.

The conversion of native habitats into anthropogenic ones compromises the original composition and configuration of the landscapes, influencing ecological dynamics and affecting biodiversity. Increasingly, landscape ecology has shown that these effects can only be understood if accessed at adequate spatial scales, as the scale which landscape structure is evaluated influences species responses. Here, we investigated how three variables of landscape composition (proportion of forest, coffee crop and pasture) and two of configuration (number of fragments and mean nearest neighbor distance) interfere in the richness and composition of medium and large-sized mammals considering a multiscale approach. We recorded medium and large-sized mammal species in 13 landscapes with predominantly matrices of coffee and pasture in Minas Gerais, Brazil. Then, we built distance-based linear models to identify the scale of effect of each landscape variable for both response variables considering eight scales (from 250 m to 2000 m). Finally, we verified the influence of the landscape on the richness and composition of mammals, considering the landscape variables in their respective scales of effect. We found 67% of the probable species occurring in the region. The scales of effect varied among landscape variables probably due to the different variables affect different aspects of organisms' ecological requirements. The proportion of pasture in the landscape explained the variation in species richness, while the proportion of forest explained the variation in species composition. In addition, the proportion of pasture in the landscape had a positive influence on species richness, indicating that this matrix may favor the presence of generalist species of habitat and/or this result is due to the higher concentration of species in the fragments immersed in this matrix. These results suggest that considering different responses to biodiversity is important to understand different aspects of the landscape's influence on biodiversity. In addition, the composition of the landscape is fundamental for the perpetuation of species and, therefore, both forest cover and types of matrices in the landscape must be considered to improve species conservation strategies. Finally, generalizing a spatial scale can lead to misinterpretations about the influence of the landscape on biodiversity.

Few prior works study self-driving cars by deep learning with IoT collaboration. SDC-Net, which is an end-to-end multitask self-driving car camera cocoon IoT-based system, is one of the research that tackles this direction. However, by design SDC-Net is not able to identify the accident locations, it only classifies if it is a crash scene or not. In this work, we introduce an enhanced design for the SDC-Net system by 1) replacing the classification network with a detection one, 2) adapting our benchmark dataset labels built on the CARLA simulator to include the vehicles bounding boxes while keeping the same training, validation, and testing samples, 3) modifying the shared information via IoT to include the accident location. We keep the same path planning and automatic emergency braking network, the digital automation platform, and the input representations to formulate the comparative study. SDC-Net++ system is proposed to 1) output the relevant control actions, especially in case of accidents: accelerate, decelerate, maneuver, and brake, and 2) share the most critical information to the connected vehicles via IoT, especially the accident locations. A comparative study is also conducted between SDC-Net and SDC-Net++ with the same input representations: front camera only, panorama and bird-eye views, and with single-task networks: crash avoidance only, and multitask networks. Multitask network with a BEV input representation outperforms the nearest representation in precision, recall, f1-score, and accuracy by more than 15.134%, 12.046%, 13.593%, and 5%, respectively. SDC-Net++ multitask network with BEV outperforms SDC-Net multitask with BEV in precision, recall, f1-score, accuracy, and average MSE by more than 2.201%, 2.8%, 2.505%, 2%, and 18.677% respectively.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

The objectives of this study was to assess the impact of a reproductive approach in high-yielding nulliparous and parous Holstein cows on the interestrus interval, estrus detection rates, conception rates, and pregnancy rates. The strategy involved giving GnRH on day 5 following artificial insemination (AI). For nulliparous cows, there appears to be no noticeable effect of GnRH therapy on the interestrus interval. In both groups, nearly all of the cows exhibited an 18–25-day cycle interval (P < 0.05). In the 18–25 day cycle period, the untreated multiparous cows exhibited the highest proportion (P < 0.05), while the treated group demonstrated the highest proportion (P < 0.05) in the 26–35 day cycle interval. The study found that the conception rate was higher in repeat breeder nulliparous and 3+ lactation treated Holstein cows compared with untreated ones. However, the cumulative heat detection rate, pregnancy rate and conception rates were similar in both groups (P > 0.05). Also, this study found that in the hottest months of the year, this therapeutic approach can't counteract the negative effect of heat stress in high-yielding dairy cows. Thus, it is not advised of using the hormonal method to create supplementary corpus luteum across the herd.

(1) Background: The article gives us an insight into the key issues of the car-sharing and its impact on urban sustainability. (2) Methods: A selection of 314 articles published in peer-reviewed journals from the Scopus database were analysed using Leximancer 5.0 for Automated Content analysis. (3) Results: Seven themes were identified explaining the researched topic of the car-sharing situation in Europe, which are Sharing, Economy, Model, Systems, Electrical car-sharing, Policy and Travel. There are two ways of sharing owned cars in Europe, access to cars from the fleet of private organizations and P2P car-sharing. Sustainable environmental solutions in the context of the electrification of cars are used. Car-sharing usually takes place online and can be free or for a free as defined by The European Economic and Social Committee. (4) Conclusions: The article provides an overview of understanding the concept of urban car-sharing in Europe.

The work at hand focuses on an adaptive system aimed at improving the soundproof performance of car door seals at specific working regimes (cruise), without interfering with the conventional open-closure operations. The idea addresses the necessity of increasing the seal effectiveness, jeopardized by aerodynamic actions more and more important as the speed increase, generating a pressure difference between the internal and the external filed, in the direction of opening the door. To recover this effect, an expanding mechanism was integrated within the seal cavity, driven by an SMA actuator. The material was activated (heated) by Joule effect; its compactness, intrinsic of smart materials, contributed to arrive to a final system characterized by a high level of integrability (expanding cells). In this paper, the development process is described together with the verification activity, aimed at proving the functionality of the realized device. Starting from the industrial requirements, the most appropriate solution was identified highlighting the working principle and the main design parameters involved. Then, the envisaged system was designed and its executive digital mock up (CAD) was released. Prototyping and laboratory validation showed the reliability of the numerical models and the associated predictions. On this basis, the integration task within the actual reference car was faced. To demonstrate the isolation effect of the proposed system, an experimental campaign was finally organized in an anechoic room, achieving significant results on the concept value.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T and CAR-NK therapies; approaches to tailor the microenvironment and target neoantigens; and allogeneic approaches.

Due to the retrognathic mandible, an orthodontist frequently observes skeletal class II malocclusion in growing patients. The preferred technique for analyzing and monitoring the temporomandibular joint alterations caused by the functional device is magnetic resonance imaging [MRI]. The study aimed to assess and compare changes in the articular disc's dimension and location before and following the use of various class II correctors to correct the class II molar relation using MRI technology. Methods: 39 adolescent patients aged 15-23 years old [24 girls and 15 boys] who were diagnosed with skeletal Class II division 1 malocclusion based on clearly defined criteria underwent treatment with either the power scope II [PS], Sabbagh Advanced Repositioning Appliance [SARA] and or Dynaflex [DF] with fixed appliances. For fixed functional treatment, the average length of treatment was 5-7 months. The changes in the articular disc dimension and position and condylar position were assessed. The study was done at the Department of Orthodontics at the College of Dentistry, Hawler Medical University in Erbil City. Results: Group DF has a significant effect on the condylar position index and posterior joint space on the closed mouth and disc length on both open and close mouth techniques, and in the group SARA, disc position, and condylar position index on closed mouth technique have shown that significant differences were observed. Conclusion: Class II malocclusions can be effectively corrected by fixed functional appliances. The statistical significance forward movement of the condyle in the glenoid fossa and the posterior movement of the articular disc concerning the condylar head was observed. The mechanism of action of functional appliances appears to include the forward migration of the C-GF complex.

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.

The motivations for the move to electrified vehicles are discussed with reference to their improved energy efficiency, their potential for lower CO2 emissions (if the electricity system is decarbonized), their lower (or zero) NOx/particulate matter (PM) tailpipe emissions, and the lower overall costs for owners. Some of the assumptions made in life-cycle CO2 emissions calculations are discussed and the effect of these assumptions on the CO2 benefits of electric vehicles are made clear. A number of new tribological challenges have emerged, particularly for hybrid vehicles that have both a conventional internal combustion engine and a battery, such as the need to protect against the much greater number of stop-starts that the engine will have during its lifetime. In addition, new lubricants are required for electric vehicle transmissions systems. Although full battery electric vehicles (BEVs) will not require engine oils (as there is no engine) they will require a system to cool the batteries – alternative cooling systems are discussed, and where these are fluid based, the specific fluid requirements are outlined.

This last decade, chimeric antigen receptor (CAR) T-cell therapy has become a real treatment option for patients with B-cell malignancies, while multiple efforts are being made to extend this therapy to other malignancies and broader patient populations. However, several limitations remain, including those associated with the time-consuming and highly personalized manufacturing of autologous CAR-Ts. Technologies to establish “off-the-shelf” allogeneic CAR-Ts with low alloreactivity are currently being developed, with a strong focus on gene editing technologies. Although these technologies have many advantages, they have also strong limitations including double-strand breaks in the DNA with associated multiple safety risks as well as the lack of modulation. As an alternative, non-gene editing technologies provide an interesting approach to support the development of allogeneic CAR-Ts in the future, with possibilities of fine-tuning gene expression and easy development. Here we will review the different ways allogeneic CAR-Ts can be manufactured and discuss which technologies are currently used. The biggest hurdles for successful therapy of allogeneic CAR-Ts will be summarized and finally an overview of the current clinical evidence for allogeneic CAR-Ts in comparison to its autologous counterpart will be given.

Systemic autoimmune diseases (SAIDs) such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA) are fully related to the unregulated innate and adaptive immune systems involved in their pathogenesis. They have similar pathogenic characteristics including the interferon signature, loss of tolerance to self-nuclear antigens, and enhanced tissue damage like necrosis and fibrosis. Glucocorticoids and immunosuppressants, which have limited specificity and are prone to tolerance, are used as the first-line therapy. A plethora of novel immunotherapies have been developed including monoclonal and bispecific antibodies, and other biological agents to target cellular and soluble factors involved in disease pathogenesis such as B cells, co-stimulatory molecules, cytokines or their receptors, and signalling molecules. Many of these have shown encouraging results in clinical trials. CAR-T cell therapy is considered the most promising technique for curing autoimmune diseases, with recent successes in the treatment of SLE and SSc.

As machine learning and computer vision techniques and methods continue to advance, the collection of naturalistic traffic data from video feeds is becoming more and more feasible. That is especially true for the case of bicycles, for which the collection of naturalistic data is not achievable in the traditional vehicle approach. This study describes a research effort that aims to extract naturalistic cycling data from a video dataset for use in safety and mobility applications. The used videos come from a dataset collected in a previous Virginia Tech Transportation Institute study in collaboration with SPIN in which continuous video data at a non-signalized intersection on the Virginia Tech campus was recorded. The research team applied computer vision and machine learning techniques to develop a comprehensive framework for the extraction of naturalistic cycling trajectories. In total, this study resulted in the collection and classification of 619 bicycle trajectories based on their type of interactions with other road users. The results confirm the success of the proposed methodology in relation to extracting the locations, speeds, and accelerations of the bicycles at a high level of precision. Furthermore, preliminary insights into the acceleration and speed behavior of bicyclists around motorists are determined.

The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.

Free Floating Car Sharing (FFCS) services are a flexible alternative to car ownership. These transportation services show highly dynamic usage both over different hours of the day, and across different city areas. In this work, we study the problem of predicting FFCS demand patterns -- a problem of great importance to an adequate provisioning of the service. We tackle both the prediction of the demand i) over time and ii) over space. We rely on months of real FFCS rides in Vancouver, which constitute our ground truth. We enrich this data with detailed socio-demographic information obtained from large open-data repositories to predict usage patterns. Our aim is to offer a thorough comparison of several machine learning algorithms in terms of accuracy and easiness of training, and to assess the effectiveness of current state-of-art approaches to address the prediction problem. Our results show that it is possible to predict the future usage with relative errors down to 10%, and the spatial prediction can be estimated with relative errors of about 40%. Our study also uncovered the socio-demographic features that most strongly correlate with FFCS usage, providing interesting insights for providers opening service in new regions.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p&lt;0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

To drive safely, the driver must be aware of the surroundings, pay attention to the road traffic, and be ready to adapt to new circumstances. Most studies on driving safety focus on detecting anomalies in driver behavior and monitoring the cognitive capabilities of drivers. In our study, we proposed a classifier for basic activities in driving a car, based on a similar approach that could be applied to the recognition of basic activities in daily life, that is, using electrooculographic (EOG) signals and a one-dimensional convolutional neural network (1D CNN). Our classifier achieved an accuracy of 80% for the 16 primary and secondary activities. The accuracy related to primary activities in driving, including crossroad, parking, roundabout was 97.9%, 96.8%, 97.4%, and 99.5%, respectively. The F1 score for secondary driving actions (0.99) was higher than for primary driving activities (0.93–0.94). Furthermore, using the same algorithm, it was possible to distinguish four secondary activities related to activities of daily life and secondary when driving a car.

This purpose of the study presented in this article is to comparing different service quality measurements between Kano and TRIZ that plays the critical roles in the catering industrial. Data collected from a DINESERV questionnaire comprises service-quality standards to increase customer satisfaction of mobile dining car. Finally, the TRIZ is standardized measure designed to improve the idealization of strategy for selecting the most appropriate service quality model. In addition, the preferences of more than one decision maker are internally aggregated into the TOPSIS procedure. All these things provide several important theoretical and practical implications for developing a successful mobile catering app.

Gesture recognition has always been a technique to decrease the distance between the physical and the digital world. In this work, we introduce an Arduino based vehicle system which no longer require manual controlling of the cars. The proposed work is achieved by utilizing the Arduino microcontroller, accelerometer, RF sender/receiver, and Bluetooth. Two main contributions are presented in this work. Firstly, we show that the car can be controlled with hand-gestures according to the movement and position of the hand. Secondly, the proposed car system is further extended to be controlled by an android based mobile application having different modes (e.g., touch buttons mode, voice recognition mode). In addition, an automatic obstacle detection system is introduced to improve the safety measurements to avoid any hazards. The proposed systems are designed at lab-scale prototype to experimentally validate the efficiency, accuracy, and affordability of the systems. We remark that the proposed systems can be implemented under real conditions at large-scale in the future that will be useful in automobiles and robotics applications.

Good estimators are characterized as robust, unbiased, efficient, and consistent. However, the commonly used estimators are weak or lack one or more of these properties. In this article, eight (8) estimators for statistical and geometrical estimations of symmetry/asymmetry, similarity/dissimilarity, identity/unidentity, and feature transformation were proposed following Kabirian-based optinalysis and other operations. The proposed estimators are characterized as invariant (robust) under scaling, location shift, and rotation or reflection. A computing code was written in python language for each of the proposed estimators so that peers can have working codes for application and performance evaluation.

Infrared sensors are applied more and more widely in industrial production applications. Based on the theory of thermal radiation, this paper discusses the system design principle, temperature calibration method and thermal image analysis method in detail. The system has passed the measurement unit certification, showing that the field of view is 180°, the number of scanning points is 2048, the linear velocity is 10-100Hz, the spatial resolution is 2.5mrad, and the precision is ±1℃. On-line monitoring test has been done in the steelmaking plant of Bao Steel. The results show that the system has strong anti-interference ability, stability and reliability, and meets the application requirements of online monitoring.

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

This paper establishes a prognosis of the long term environmental impact of various car subsidy concepts. The CO2 emissions of the German car fleet impacted by the purchase subsidies are determined. A balance model of the CO2 emissions of the whole car life cycle is developed. Consideration of production-, use- and End-of-Life processes are taken into account. The implementation of different subsidy scenarios directly affects the forecasted composition of the vehicle population and therefore the resulting life cycle assessment. All scenarios compensate the additional emissions required by the production pull-in within the considered period and hence reduce the accumulated CO2 emissions until 2030. The exclusive funding of BEVs is most effective with a break-even in 2025.

Traumatic brain injury (TBI) is a devastating event with severe long-term complications. TBI and its sequelae are one of the leading causes of death and disability in those under 50 years old. The full extent of secondary brain injury is still being intensely investigated; however, it is now clear that neurotrauma can incite chronic neurodegenerative processes. Chronic traumatic encephalopathy, Parkinson’s disease, and many other neurodegenerative syndromes have all been associated with a history of traumatic brain injury. The complex nature of these pathologies can make clinical assessment, diagnosis, and treatment challenging. The goal of this review is to provide a concise appraisal of the literature with focus on emerging strategies to improve clinical outcomes. First, we review the pathways involved in the pathogenesis of neurotrauma-related neurodegeneration and discuss the clinical implications of this rapidly evolving field. Next, because clinical evaluation and neuroimaging are essential to the diagnosis and management of neurodegenerative diseases, we analyze the clinical investigations that are transforming these areas of research. Finally, we briefly review some of the preclinical therapies that have shown the most promise in improving outcomes after neurotrauma.

Background/Objectives: To evaluate incidental findings in the mandible after the placement of dental implants using a new cone-beam computed tomography (CBCT) software. Methods: The initial sample consisted of 2,872 CBCT scans of patients of both sexes. The parameters evaluated in this study were the location of the implants in the mandible, implant length, anatomical relationship of the implant with the mandibular canal, presence or absence of damage to the adjacent teeth, presence or absence of implant fractures, and presence or absence of bone support. Fisher's exact test was performed to compare the variables. The significance level was set at p = 0.05. Results: Out of 2,872 CBCT scans, 214 images of patients with an average age of 44.5 years were included. The most frequent location of the implants was the posterior region (93.5%), with 54% of the implants having a length between 9 and 14 mm. It was found that 92% of the implants were positioned above the mandibular canal. Three damage to adjacent teeth was observed, with no correlation with the implant positioning (p = 0.999). In 100% of cases of implants in the anterior region, there was bone support. Fracture was observed in 1.7% of implants with a length between 9- and 14-mm. Conclusions: The installation of implants in the mandible occurs more frequently in the posterior region, with a high presence of bone support and a low incidence of damage to adjacent teeth, anatomical structures, and fractures.

The purpose of this study is to analyse the drivers and outcomes of the brand love derived from consumption experiences in the automobile retail sector. We examine the effects of consumers’ perceptions of perceived service quality and the trust they feel towards a car dealership (cognition) on emotions and brand love (affection), and the effects of brand love on consumers´ behavioural intentions (conation). This research provides insights into customer brand love in the automobile industry.

Multiple myeloma (MM) has witnessed improved patient outcomes through advancements in therapeutic approaches. Notably, allogeneic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have contributed to enhanced quality of life. Recently, a promising avenue has emerged with chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA), expressed widely on MM cells. To mitigate risks associated with allogenic T cells, we investigated the potential of BCMA CAR expression in natural killer cells (NKs), known for potent cytotoxicity and minimal side effects. Using the NK-92 cell line, we co-expressed BCMA CAR and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) employing the PiggyBac transposon system. Engineered NK cells (CAR-NK-92-TRAIL) demonstrated robust cytotoxicity against a panel of MM cell lines and primary patient samples, outperforming unmodified NK-92 cells with a mean difference in viability of 45,1% (± 26,1%, depending on the target cell line). Combination therapy was explored with the proteasome inhibitor bortezomib (BZ) and γ-secretase inhibitors (GSI), leading to a significant synergistic effect in combination with CAR-NK-92-TRAIL cells. This synergy was evident in cytotoxicity assays where a notable decrease in MM cell viability was observed in combinatorial therapy compared to single treatment. In summary, our study demonstrate the therapeutic potential of the CAR-NK-92-TRAIL cells for the treatment of MM. The synergistic impact of combining these engineered NK cells with BZ and GSI supports further development of allogeneic CAR-based products for effective MM therapy.

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T-cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B-cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T-cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

The reconstruction of traffic accidents has grown as an interdisciplinary field since the first accident occurred. Various methods have been developed over time, starting with primary data collected at the scene of the accident. In this work, I proposed a method by which the value of the force in the safety belt buckle can be determined when it is equipped with a pretensioning system with pyrotechnic trigger in the tube, PBP or PLP type. The anti-return system of the pretensioner mechanism, which prevents the passenger's body from moving forward, contains a set of balls that block the movement of the piston in the pretensioner tube after its activation. When limiting the movement, the force the human body exerts on the safety belt webbing is transformed into the deformation of the pretensioner tube by the balls of the anti-return system. Depending on the magnitude of the force, the marks left by the balls differ. I propose a relationship of dependence between the acting force and the deformation of the tube. An experimental test bench was created to perform shock traction tests on the pre-tensioning system, under similar conditions to those of the human body acting on the belt in case of a frontal collision. Following the tests, the force value of the seat belt buckle cable and the diameter of the spherical indentations that the balls left in the pretensioner tube were measured. A mathematical model was proposed to determine the normal force with which a ball from the anti-return system deforms the tube. The normal force was also determined by two other methods specific to contact mechanics and used in the specialized literature. By comparing the normal forces obtained by the three methods, a good correlation between the proposed mathematical model and the Komvopoulos-Ye method resulted, the "Hardness" method not being suitable for this study. The determined polynomial regression curve allows finding out the force in the cable of the closer depending on the size of the deformations produced by the balls in the tube. The forces in the belt webbing can be thus determined and biomechanics specialists can evaluate the injuries to the chest and abdomen of the occupants of a vehicle.

Chimeric Antigen Receptor (CAR)-T cell immunotherapy revolutionized cancer treatment and consists of the genetic modification of T lymphocytes with a CAR gene, aiming to increase their ability to recognize and kill antigen-specific tumor cells. The dynamics of CAR-T cell responses in patients presents a multiphasic kinetics with distribution, expansion, contraction, and persistence phases. The characteristics and duration of each phase depend on the tumor type, the infused product, and on patient-specific characteristics. We present a mathematical model which describes the multiphasic CAR-T cell dynamics resulting from the interplay between CAR-T and tumor cells, considering patient and product heterogeneities. The CAR-T cell population is divided into functional (distributed and effector), memory, and exhausted CAR-T cell phenotypes. The model is able to describe the diversity of CAR-T cell dynamic behaviors in different patients and hematological cancers as well as their therapy outcomes. Our results indicate that the joint assessment of the area under the concentration-time curve in the first 28 days and the corresponding fraction of non-exhausted CAR-T cells may be considered as potential markers to classify therapy responses. Overall, the analysis of different CAR-T cell phenotypes can be a key aspect for a better understanding of the whole CAR-T cell dynamics.

Multiple Myeloma (MM) is one of the incurable types of cancer in plasma cells. While immense progress has been made in the treatment of this malignancy, a large percentage of patients were unable to adapt to such therapy. Additionally, these therapies might be associated with significant diseases and are not always tolerated well in all patients. Since cancer in plasma cells has no cure, patients develop resistance to treatments, resulting in R/R MM. BCMA is primarily produced on mature B cells. Its up-regulation and activation are associated with multiple myeloma in both murine and human models, indicating that this might be an effective therapeutic target for this type of malignancy. Additionally, BCMA's predictive value, association with effective clinical trials, and capacity to be utilized in previously difficult to observe patient populations, imply that it might be used as a biomarker for multiple myeloma. Numerous kinds of BCMA-targeting medicines have demonstrated antimyeloma efficacy in individuals with refractory/relapsed MM, including CAR T-cell treatments, ADCs, bispecific antibody constructs. Among these medications, CART cell-mediated BCMA therapy has shown significant outcomes in multiple myeloma clinical trials. This review article outlines CAR T cell mediated BCMA medicines have the efficiency to change the therapeutic pattern for multiple myeloma significantly.

The use of chimeric antigen receptors (CAR-T cells) for the treatment of patients with malignant haematological diseases has become a well-established application, for conditions such as refractory or relapsed B cell acute lymphoblastic leukaemia (B-ALL), B cell lymphomas (BCL), and multiple myeloma (MM). Nearly 35,000 patients have received autologous CAR-T cells for the treatment of these conditions only in the USA. Since their approval by the Food and Drug Administration (FDA) in 2017, over 1200 clinical trials have been initiated globally and there are at least 10 different CAR-T cells with approval by different regulatory agencies around the globe. In the USA the Food and Drug Administration (FDA) has approved 6 commercial CAR-T cells that are widely distributed worldwide. At the time of this writing, several clinical trials have been performed in patients with solid tumours such as glioblastoma, renal and pancreatic cancer, as well as in patients with autoimmune conditions such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SS). There are also several studies showing the potential benefit of CAR-T cells for other non-malignant diseases such as asthma and even fungal infections. In this review, without pretending to cover all the current areas of treatments with CAR-T cells, we offer a brief summary of some of the most relevant aspects of the use of CAR-T cells for some of these conditions.

The purpose of this study is to investigate the failure mechanism and preventive strengthening methods of prefabricated full length small box girder (PSBG) under car explosion. After damage analysis during blast loads using the commercial software Autodyn, three strengthening methods are presented to improve the blast mitigation performance. The results show that the failure modes and bearing capacity are significantly different with various strengthening measures. Adhering U-shaped steel plate can effectively enhance the shear performance of PSBG under blast loads. Strengthening the bottom of the upper flange of box girder with steel plate can effectively mitigate the local bending failure, and enhance the overall flexural capacity during car explosion.

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: As long-lived organisms, urban trees often encounter development and redevelopment activities in close proximity during their lifespans. These activities can damage tree roots, often through methods like root severing during trenching or excavation. Methods: In 2017, we simulated trenching damage on mature Quercus virginiana Mill. trees at three different distances from the base (3x, 6x, and 12x the stem diameter). After five years, we revisited these trees to assess root regrowth based on the cut root's cross-sectional area (CSA) and distance from the base. Results: We observed regrowth in all but 38 (6.7%) of the 557 cut roots revisited. The lack of regrowth in some roots was not associated with our original treatments, the CSA of the roots at the time of trenching, or distance between the cut root end and the trunk (minimum P-value = 0.841). On average, the observed CSA of the regrowth was 22.2% of the original root's CSA. Only our original trenching treatments significantly predicted the level of regrowth observed five years after pruning (P-value = 0.024). Discoloration due to root pruning was minimal. Conclusion: In summary, our findings indicate that root systems require many years to recover from trenching damage. Increasing the distance between trenching activities and trees may have a minor effect on root regrowth but primarily helps reduce initial stress on the tree.

While cycling presents environmental benefits and promotes a healthy lifestyle, the risks associated with overtaking maneuvers by motorized vehicles pose significant hindrances for many potential cyclists. Large-scale analysis of overtaking maneuvers could inform traffic researches and city planners on how to reduce these risks by better understanding these maneuvers. Drawing from the fields of sensor-based cycling research and of LiDAR-based traffic data sets, this paper provides a step towards addressing these safety concerns by introducing the Salzburg Bicycle 3d (SaBi3d) data set, consisting of LiDAR point clouds capturing car-to-bicycle overtaking maneuvers. The data set, collected using a LiDAR-equipped bicycle, facilitates detailed analysis of a large quantity of overtaking maneuvers without the need for manual annotation through enabling automatic labeling by a neural network. Additionally, a benchmark result for 3d object detection using a competitive neural network is provided as a baseline for future research. The SaBi3d data set is structured identically to the nuScenes data set, and therefore offers compatibility with numerous existing object detection systems. This work provides valuable resources for future researchers to better understand cycling infrastructure and mitigate risks, thus promoting cycling as a viable mode of transportation.

This study explored drivers’ emotion-based impressions of car-borne central control platforms (CBCCPs) personal-use vehicles. Thus, this preference-based study examined experts’ and drivers’ opinions regarding CBCCPs’ appeal from the perspective of Miryoku engineering. To this end, this study analyzed data via the EGM (evaluation grid method (EGM) and quantification theory type I. Results: Drivers’ preferences for specific CBCCP design characteristics were categorized into the factors “legible,” convenient,” and “tasteful,” which comprised the core of the EGM semantic hierarchical diagram. In addition, the importance of CBCCPs’ appeal factors and characteristics was assessed through quantification theory type I.The findings of this study provide valuable insights for designers, manufacturers, and researchers interested in the design of CBCCPs. Additionally, the results of this study can contribute to research on applied psychology, human-computer interactions, and car interface design.

The used car market has a high global economic importance, with more than 35 million cars sold yearly. Accurately predicting prices is a crucial task for both buyers and sellers to facilitate informed decisions in terms of opportunities or potential problems. Although various Machine Learning techniques have been applied to create robust prediction models, a comprehensive approach has yet to be studied. This research introduces two datasets from different markets, one with over 300,000 entries from Germany to serve as a training base for deep prediction models and a second dataset from Romania containing more than 15,000 car quotes used mainly to observe local traits. As such, we include extensive cross-market analyses by comparing the emerging Romanian market versus one of the world’s largest and most developed car markets, Germany. Our study uses several neural network architectures that capture complex relationships between car model features, individual add-ons, and visual features to predict used car prices accurately. Our models achieved a high R2 score exceeding 0.95 on both datasets, indicating their effectiveness in estimating used car prices. Moreover, we experimented with advanced convolutional architectures to predict car prices based solely on visual features extracted from car images. This approach exhibited transfer-learning capabilities, leading to improved prediction accuracy, especially since the Romanian training dataset is limited. Our experiments highlight the most important factors influencing the price, while our findings have practical implications for buyers and sellers in assessing the value of vehicles. At the same time, the insights gained from this study enable informed decision-making and provide valuable guidance in the used car market.

In-wheel motor vehicles are gaining attention as a new type of electric vehicle due to their efficient power units located inside each wheel hub. However, they are more susceptible to wheel resonance due to the increase in unsprung mass caused by the motor's weight. This can result in decreased both the ride comfort and driving stability. To resolve this issue, this study aims to apply an optimal switching controller with a semi-active n actuator; magnetorheological (MR) damper. For the implementation of the optimal switching controller, a road type classification is also carried out. An acceleration sensor is used for road type classification, and control logics include a ride comfort controller; the linear quadratic regulator (LQR _Paved Road) and a wheel motion controller (LQR_Off Road) for improved driving stability. For paved roads, the LQR_Paved Road control input is applied to the MR damper. However, if a road type prone to wheel resonance is detected, the control logic switches to the LQR_Off Road. During the transition, a weighted average of both LQR_ Paved Road and LQR_Off Road control input is applied to the actuator. Computer simulations are undertaken to evaluate vibration control performance, including the ride comfort and driving stability at various road profiles.

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of tumor microenvironment, Nor-Adrenaline (NA) is poured-in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surface of cancer and immune cells and are often involved in activation of pro-tumoral signaling pathways. β2-adrenergic receptor (β2-AR) is an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate the regulatory immune cells and inhibit the effector immune cells. Blocking β2-AR increases activation, proliferation and cytokine release of T lymphocytes. Moreover β2-AR deficiency during metabolic reprograming of T cells increases mitochondrial membrane potential and biogenesis. In the view of available research data, immunosuppressive role of β2-AR in T cells presents it a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged contemporary knowledge about adrenergic stress mediated β2-AR activation on T lymphocytes inside tumor milieu.

In this paper, we address the problem of car detection from aerial images using Convolutional Neural Networks (CNN). This problem presents additional challenges as compared to car (or any object) detection from ground images because features of vehicles from aerial images are more difficult to discern. To investigate this issue, we assess the performance of two state-of-the-art CNN algorithms, namely Faster R-CNN, which is the most popular region-based algorithm, and YOLOv3, which is known to be the fastest detection algorithm. We analyze two datasets with different characteristics to check the impact of various factors, such as UAV's altitude, camera resolution, and object size. The objective of this work is to conduct a robust comparison between these two cutting-edge algorithms. By using a variety of metrics, we show that YOLOv3 yields better performance in most configurations, except that it exhibits a lower recall and less confident detections when object sizes and scales in the testing dataset differ largely from those in the training dataset.

In this paper, we address the problem of car detection from aerial images using Convolutional Neural Networks (CNN). This problem presents additional challenges as compared to car (or any object) detection from ground images because features of vehicles from aerial images are more difficult to discern. To investigate this issue, we assess the performance of two state-of-the-art CNN algorithms, namely Faster R-CNN, which is the most popular region-based algorithm, and YOLOv3, which is known to be the fastest detection algorithm. We analyze two datasets with different characteristics to check the impact of various factors, such as UAV’s altitude, camera resolution, and object size. The objective of this work is to conduct a robust comparison between these two cutting-edge algorithms. By using a variety of metrics, we show that none of the two algorithms outperforms the other in all cases.

Systematic traders employ algorithmic strategies to manage their investments. As a result of the deterministic nature of such strategies, it is possible to determine their exact responses to any conceivable set of market conditions. Consequently, sensitivity analysis can be conducted to systematically uncover undesirable strategy behavior and enhance strategy robustness by adding controls to reduce exposure during periods of poor performance / unfavorable market conditions or increase exposure during periods of strong performance / favorable market conditions. In this study, we formulate both a simple systematic trend-following strategy (i.e., trading model) to simulate investment decisions, and a market model to simulate the evolution of instrument prices. We then map the relationship between market model parameters under various conditions and strategy performance. We focus, in particular, on identifying the performance impact of changes in both serial dependence in price variability and changes in the trend. The long-range serial dependence of the true range worsens performance of the simple classic trend-following strategy. During periods of strong performance, the dispersion of trading outcomes increases significantly as long-range serial dependence increases.

Cardiac complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been well-identified since the beginning of the current coronavirus disease 2019 (COVID-19) pandemic. Such conditions can occur of various etiologies, such as respiratory failure and hypoxemia, direct cardiac tissue damage due to viral replication, indirect myocarditis as systemic inflammation, and the interaction of different medications. Recently, with the start of the COVID-19 vaccination programs, COVID-19 vaccine-associated cardiac adverse events (AEs) have emerged and are increasingly being reported. Although these AEs are usually mild and self-limited, they can sometimes cause severe, catastrophic outcomes. This review compares the pathophysiology, diagnosis, and treatment of the de novo SARS-CoV-2 infection-related and COVID-19 vaccine-related myocarditis and pericarditis.

Coseismic landslides have the potential to cause catastrophic disasters. Thus, it is of crucial importance to conduct a comprehensive regional assessment of susceptibility to coseismic landslides. This study rigorously interprets 13,759 coseismic landslides triggered by the 2022 Luding earthquake within the seismic zone. Employing the Newmark method, we systematically assess the susceptibility to coseismic landslides through the application of six distinct displacement regression models. The efficacy of these models is validated against the actual landslide inventory using the area under the curve. A hazard map of coseismic landslides is generated based on the displacement regression model with the highest degree of fit. The results show that Moxi Town, Detuo Town, the flanks of the Daduhe River, Wandonghe River, Hailuogou River, and Yanzigou River are high susceptibility areas for coseismic landslides. The study explores factors influencing model fit, revealing that the inclusion of both epicentral distance and the distance to seismogenic fault and in displacement prediction enhances model performance. Nevertheless, in close proximity to fault zones, the distance to seismogenic fault exerts a more significant influence on the spatial distribution density of coseismic landslides compared to the epicentral distance. Conversely, in regions situated further from fault zones, the epicentral distance has a greater impact on the spatial distribution density of coseismic landslides compared to the distance to seismogenic fault. These findings contribute to a nuanced understanding of coseismic landslide susceptibility and offer valuable insights for future Newmark method-based coseismic landslide displacement calculations.

This research focusing on the environmental impact of tire and brake pad wear constitutes a significant area of transport-related studies. These two key vehicle components are not only the most frequently worn, but also generate micro and nano pollutants (i.e., rubber, metal oxides) that potentially harm the environment. Over half of the globally produced natural and synthetic rubbers, which amounted to about 30 million tons in 2022, are used for tire production. According to Wagner et al.'s research, over 1.3 million tons of such particles are released due to wear and tear in the European Union alone. This work focuses on examining snow deposits from various locations in an urban agglomeration (Poznan, Poland) in the winter season. FT-IR and NMR spectroscopic studies, optical and electron scanning microscopy SEM-EDS, and particle size studies using the DLS technique were conducted for a detailed characterization of pollutants in the environment. The conducted particle separation methods allowed for the extraction of a fraction mainly containing gum residues with particle sizes less than 2 µm. The results of these studies are crucial for understanding the impact of vehicle part exploitation on the environment.

Obesity is associated with serious comorbidities and economic implications. Bariatric surgery, most commonly Roux-en-Y gastric bypass and sleeve gastrectomy, are effective options for weight loss and improvement of obesity-related comorbidities. With the growing obesity epidemic, there has been a concomitant rise in bariatric surgeries, particularly in sleeve gastrectomy, which has been the most widely performed bariatric surgery since 2013. Gastroesophageal reflux disease (GERD) is highly prevalent in obese individuals, can significantly impact quality of life and may lead to serious complications. Obesity and GERD both improve with weight loss. However, as the incidence of sleeve gastrectomy rises, recent data has revealed a risk of exacerbation of pre-existing GERD or the development of de novo GERD following sleeve gastrectomy. We performed a detailed review of GERD post-sleeve gastrectomy, including its overall incidence, pathophysiology and current treatment paradigms.

Earthquakes often entail alterations in the groundwater flow regime, in the phreatic level, in the surge and loss of springs, and discharge in brooks and springs. As for the latter, there are diverse feasible mechanisms, so there is a variety of theoretical approaches to elucidate the post-earthquake effects on spring discharge. This study adopts a conceptual approach, primarily presenting various methods for estimating water released by earthquakes by calculating discharge surpluses in springs. This study delves into refined techniques rooted in groundwater hydraulics, displaying applications of analytical and simulation methodologies to quantify seismic-induced groundwater discharge in springs. Investigating springs as natural indicators, this research applies mathematical precipitation-runoff models, specifically the CREC model, for simulating hydrographs in post-earthquake scenarios. We apply analytical procedures or mathematical simulation techniques employed in groundwater hydraulics for natural aquifer recharge calculations. Firstly, we briefly describe the methods based on the analysis of depletion curves of hydrographs in spring discharge. Additionally, certain mathematical rainfall-runoff models utilized in simulating hydrographs of karstic springs, along with derived analytical approximations, are adapted for this scenario. These hydraulic calculations involve the depletion coefficient and hydrodynamic volumes of aquifers, parameters that reveal certain aspects of the relation between groundwater and earthquakes, such as: a) Acknowledging faults as the primary geological structures in transmitting pore pressures due to earthquakes. b) Clarifying mechanisms of permeability enhancement during earthquakes. c) Highlighting the substantial volumes in motion within the Earth's interior, which, for instance, could constitute a significant source for the origin of mineral deposits. The findings highlight diverse features of the complex interplay between hydrogeological and tectonic processes at challenging spatial and temporal scales.

Cardiovascular diseases (CVDs) are the leading cause of death in the globally. Morbidity and disability related to non-fatal events are increasing exponentially. There are several symptoms that may arise after invasive therapeutic approaches such as coronary artery bypass graft (CABG), including chronic pain in anatomical areas connected to the mediastinum; these pains can be found not only initially after surgery, but also years later. We present a case where non-specific neck pain (NNP), in a patient undergoing CABG five years earlier, was approached with an osteopathic technique, working the pericardial area. To the knowledge of the Authors, it is the first case report where osteopathy is associated with a gentle treatment on the pericardial area to resolve a NNP.

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.

New technologies such as "connected" and "autonomous" vehicles are going to change the future of traffic signal control and management and possibly will introduce new traffic signal systems that will be based on floating car data (FCD). The use of floating car data to regulate, in real-time, traffic signal systems has the potential for an increased sustainability of transportation in terms of energy efficiency, traffic safety and environmental issues. However, research has never explored how not "connected" vehicles would benefit by the implementation of such systems. This paper explores the use of floating car data to regulate in real-time traffic signal systems in terms of cooperative-competitive paradigm between "connected" vehicles and conventional vehicles. In a dedicated laboratory, developed for testing regulation algorithms, results show that "invisible vehicles" for the system (which are not "connected") in most simulated cases also benefit when real time traffic signal settings based on floating car data are introduced. Moreover, the study estimates the energy and air quality impacts of signal regulation by evaluating fuel consumption and pollutant emissions. Specifically, the study demonstrates that significant improvements in air quality are possible with the introduction of FCD regulated traffic signals.

Background: Previous investigations have found a correlation between abnormal curvatures and a variety of patient complaints such as cervical pain and disability. However, no study has shown that loss of the cervical curve is a direct result of exposure to a motor vehicle collision (MVC). This investigation presents a retrospective consecutive case series of patients with both a pre-injury cervical lateral radiograph (CLR) and a post-injury CLR after exposure to a MVC. Computer analysis of digitized vertebral body corners on CLRs was performed to investigate the possible alterations in the geometric alignment of the sagittal cervical curve. Methods: Three spine clinic records were reviewed, over a 2-year period, looking for patients where both an initial lateral cervical x-ray and an examination were performed prior to the patient being exposed to a MVC; afterwards an additional exam and radiographic analysis were required. A total of 41 patients met the inclusion criteria. Examination records of pain intensity on numerical pain rating scores (NPRS) and neck disability index (NDI), if available, were analyzed. The CLRs were digitized and modeled in the sagittal plane using curve fitting and the least squares error approach. Radiographic variables included total cervical curve (ARA C2-C7), Chamberlain’s line to horizontal (skull flexion), horizontal translation of C2 relative to C7, segmental translations (retrolisthesis and anterolisthesis), and circular modelling radii. Results: There were 15 males and 26 females with an age range of 8-65 years. Most participants were drivers (28) involved in rear end impacts (30). The pre-injury NPRS was 2.7 while the post injury was 5.0; p &lt; 0.001. The NDI was available on 24 /41 (58.5%) patients and was found to increase following exposure to the MVC: 15.7% to 32.8%, p &lt; 0.001. An altered cervical curvature was identified following exposure to MVC, characterized by an increase in radius of curvature and an approximate 8° reduction of lordosis from C2-C7; p &lt; 0.001. The mid cervical spine (C3-C5) showed the greatest curve reduction with localized mild kyphosis at these levels on average. Several participants developed segmental translations that approached the instability value of translation &gt; 3.5mm. Conclusions: Abnormalities of cervical lordosis occurred following exposure to a MVC. The average loss of cervical curvature was 8° from C2-C7, with mild flexion of the mid cervical segments. Snap through type or dynamic buckling during the MVC may explain our findings. The primary contribution of this study to the motor vehicle collision literature is that altered cervical lordosis may result from MVC exposures and the consequences of an altered cervical alignment, in turn, may lead to future pain, disability and decreased health-related quality of life.

Simple summary This reassessment of the findings from our Phase I/II study seeks to evaluate the effectiveness of SBRT for treating local intermediate-high risk prostate cancer in the absence of androgen-deprivation therapy due to patient’s refusal, with a median follow-up of 6.5 years. Our primary focus is on analysing the treated areas compared to recurrence patterns in the seven patients who experienced local relapse. Additionally, we provide updated data on late toxicities of grade 2 or higher, both genitourinary and gastrointestinal. Abstract Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intraprostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intraprostatic recurrences occurred in 7 patients (21%), with ≥ 75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patient. Notably, 5 patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intraprostatic recurrences. Extended follow-up revealed grade 2 or higher late GU and GI toxicity in 18% (n=6) and 6% (n=2) of the patients. Conclusions: Among patients with intermediate-high risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: focal dose escalated prostate SBRT prevented recurrences in the dominant nodule, however extra-prostatic recurrence sites were frequent.

The severest form of muscular dystrophy (MD) termed Duchenne MD (DMD) remains to this day an incurable disease, hence the continued effort to further develop supportive therapies. Perturbation of autophagy, a degradative yet protective mechanism activated when tissues face severe and persistent stress, is critically involved in DMD, consequently, treatments harnessing autophagic capacities represent an amenable therapeutic strategy. We studied the effects of the protective osmolyte ectoine in the standard mouse model of DMD, the MDX, zooming in on the autophagy-related proteome. From birth, mice were treated with ectoine in the drinking water (150mg/kg) or through daily intraperitoneal injection (177mg/kg) until 5 weeks old. Hind limb muscles were dissected, performing western blotting for protein quantification and immunofluorescence to investigate tissue distribution. We report significant alterations of total levels of autophagy related 5 (ATG5), Ser366 phosphorylated sequestosome 1 (SQSTM1) and heat shock protein 70 (HSP70), and of activated microtubule-associated protein 1A/1B-light chain 3 (LC3 II) in mitochondrial fractions. Ectoine tends to restore the shifted balance between LC3 II and SQSTM1 levels observed in MDX muscle, and LC3 II upregulation was most pronounced on muscle fibers of MDX treated with ectoine in the drinking water. Findings from this explorative study support a possible beneficial effect of ectoine on the autophagic deficit in the MDX, which warrants its further exploration as a therapeutic supplement for DMD.

A 68-year-old man with malignant metastatic melanoma in complete remission after Pembrolizumab treatment, developed 10 months after Pembrolizumab cessation due a grade 3 diarrhea, confusion, altered mental status, progressive memory loss, gait disturbance. He was admitted to the neurologic department and comprehensive neurological workup, brain magnetic resonance imaging, cerebral fluid analysis, EEG, blood test allowed the diagnosis of autoimmune encephalitis. The patient was treated with plasmapheresis, high dose of intravenous steroids and intravenous immunoglobulins. The patient improved and he is now well with a performance status 1. This case is interesting since the AE developed approximately 10 months after the cessation of immunotherapy, the underlying cancer was in complete remission and the AE showed a good response to the treatment done.

This work communicates the connection of measured shadowgraphs from optically induced air breakdown with emission spectroscopy in selected gas mixtures. Laser-induced optical breakdown is generated using 850 mJ and 170 mJ, 6-ns pulses at a wavelength of 1064 nm, the shadowgraphs are recorded using time-delayed 5-ns pulses at a wavelength of 532 nm and a digital camera, and emission spectra are recorded for typically a dozen of discrete time-delays from optical breakdown by employing an intensified charge-coupled device. The symmetry of the breakdown event can be viewed as close-to spherical symmetry for time-delays of several 100 ns. Spectroscopic analysis explores well-above hypersonic expansion dynamics using primarily the diatomic molecule cyanide and atomic hydrogen emission spectroscopy. Analysis of the air breakdown and selected gas breakdown events permits the use of Abel inversion for inference of the expanding species distribution. Typically, species are prevalent at higher density near the hypersonically expanding shockwave, measured by tracing cyanide and a specific carbon atomic line. Overall, recorded air breakdown shadowgraphs are indicative of laser-plasma expansion in selected gas mixtures, and optical spectroscopy delivers analytical insight into plasma expansion phenomena.

Background/Objectives: The aim of the project is a longitudinal assessment of body image and mental health in scoliosis females pre-, postoperatively and in a follow-up, and implementation (one group-CBT scoliosis sample, CBTSS) or not (second group-control scoliosis sample, CSS) of CBT interventions. A healthy female sample (HFS) was also selected for comparative purposes. Methods. 36 in total AIS patients participated in the 1st and 2nd study phases, whereas 23 were eligible in the follow-up. Regarding HFS, 18 participants were included in the study. The CBT intervention took place pre- and postoperatively, during the patients' stay in hospital. Participants completed the Spinal Appearance Questionnaire (SAQ), Body Esteem Scale (BES) and Strengths and Difficulties Questionnaire-25 (SDQ-25). Body image was also assessed using a virtual reality-based application “Avatar Scoliosis 3D”. Results: The difference between the desired and objective, actual body shape is significant preoperatively both in the CBTSS and CSS at p

The coronavirus disease (COVID-19) is a respiratory tract infection caused by the new virus SARS-CoV-2. In March 2020, the World Health Organization (WHO) declared a worldwide COVID-19 pandemic. Since then, there has been a rush to find preventative or curative treatment. This arrived with the appearance of the COVID-19 vaccine, months after the declaration of the pandemic. In the setting of global COVID-19 immunization, there have been reports of rare skin immune-mediated diseases (IMD) after COVID-19 vaccination, particularly systemic sclerosis. Systemic sclerosis (SSc) is the most reported new onset IMD following messenger RNA (mRNA) COVID-19 vaccination. The pathogenesis of SSc is not fully understood, and the diagnosis is based on clinical symptoms. We report a 54-year-old male, with no prior history of autoimmune disorder, with rapid and progressive skin thickening (Modified Rodnan skin score 30/51), weeks after his mRNA COVID-19 vaccination. Antinuclear antibodies (ANA) showed a strongly positive nuclear fine-speckled pattern, but no SSc autoantibodies were found. The patient was diagnosed with SSc based on the persistence of autoantibodies and the clinical criteria according to the 2013 American College of Rheumatology/European League Against Rheumatism classification. Due to the proximity of the two events, we hypothesized a cross-reaction between COVID-19 vaccination and, in genetically predisposed patients, an emergence of systemic sclerosis. Our case suggests a potential relationship between the mRNA COVID-19 vaccine and new-onset autoimmune diseases. Physicians should be aware of this possible association.

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

Despite the popularity of theraphosids, detailed reports on bite symptoms are still limited to few geographic regions and subfamilies. We therefore examined 363 published bite reports and noticed muscles cramps caused by theraphosids from nearly all continents and subfamilies. Symptoms are mostly locally restricted and mild, but 12.7% of victims experience pronounced cramps with highest incidence rates by Poecilotheriinae, Harpactirinae and Stromatopelminae subfamilies. We discuss how variations in venom quantity correlate with muscle cramp prevalence.

The effect of embryo reinsertion immediately after embryo flushing was studied to determine its effect on luteal function, pregnancy outcome, endometrial bacterial contamination, and embryo morphology. In Experiment 1, eight mares were used during 32 cycles (8 cycles in each group): for the first two groups, inseminated mares were flushed 8 days after ovulation and prostaglandin F2α was not administered: in group EF-ET (embryo flushing and embryo transfer) the embryo was reinserted in the same donor mare, while in the EF group, no further procedure was performed. In the third group (ET), non-inseminated mares (recipients) received a Day 8 embryo 5 to 8 days after ovulation. Progesterone concentration was measured before EF/ET and 72 h after in the 3 groups. Pregnancy diagnosis was performed within 6 days of transfer. In Experiment 2, twelve mares were used during 17 cycles in two groups: EF-ET (n=11) and ET (n=6), as in Experiment 1, except that every mare was flushed 24 h after embryo transfer to retrieve the embryo. Fewer pregnancies resulted after transfer in EF-ET cycles (0(8, 0%) than in the ET group (6/8, 75%). Progesterone concentration decreased significantly (p=0.05) 72 h after EF-ET, but not in EF or ET cycles (p>0.1). Three mares from the EF-ET showed full luteolysis and signs of endometritis. In Experiment 2, more (5/6; p=0.08) grade I embryos were recovered in the ET compared to the EF-ET group (3/7); 4 embryos were graded III-IV (were broken or had signs of degeneration) in the EF-ET group, but none in the ET group. In both groups, capsule fragments were obtained as indicative of the presence of a recently destroyed embryo in the EF-ET (n=3) and ET (n=1) groups. Positive bacterial cultures were obtained in 2/11 and 1/6 embryo flushes from the EF-ET and ET groups, respectively.

In the modern power grid, characterized by the increased penetration of power electronics and extensive utilization of renewable energy, inverters-based power plants play a pivotal role as the principal interface of renewable energy sources (RESs) and the grid. Considering the stability characteristics of grid-following (GFL) inverters when the grid is relatively weak, the application of grid-forming (GFM) controls becomes imperative to enhance the stability of the entire power plant. Thus, there is an urgent need for suitable and effective models to study the interaction and stability of the paralleled inverters employing GFL and GFM controls. Thus, the small-signal modeling with full-order state space model and eigenvalues analysis is presented in this paper. First, the small-signal state-space model of the individual GFL and GFM inverters is obtained considering the control loop, interaction, reference frame, transmissions, and time delays. Then, the models of the individual inverter are extended to the hybrid inverters to study the effects of the GFM inverters on the small- signal stability of the entire system. And, the impacts of the inertia and damping are analyzed by the eigenvalues of the state-transition matrix. Case comprising three parallel GFL inverters and two GFL inverters with one GFM inverter, respectively, are studied to examine the effectiveness and accuracy of the model. Finally, the stability margin obtained from the eigenvalue analysis of the entire system is verified by time-domain simulations.

Hematopoietic stem cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation have been critical in our fundamental understanding of HSC biology and developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone marrow (BM) niches. Various signaling molecules and growth factors secreted by HSCs and the niche microenvironment play critical roles in homing and engraftment of the transplanted cells. The sustained equilibrium of these chemical and biologic factors ensures that engrafted HSCs generate healthy and durable hematopoiesis. Transplanted healthy HSCs compete with residual host cells to repopulate stem cell niches in the marrow. Stem cell niches, in particular, can be altered by the effects of previous treatments, aging, and paracrine effects of leukemic cells that create inhospitable bone marrow niches that are unfavorable for healthy hematopoiesis. More work to understand how stem cell niches can be restored to favour normal hematopoieis may be key to reducing leukemic relapses following transplant.

Hydrogen sulfide (H2S) is an environmental toxicant of health concern. The brain is a major target in acute H2S poisoning. This study was to test the hypothesis that acute and subchronic ambient H2S exposures alter the brain metabolome. Male 7-8 week-old C57BL/6J mice were exposed by whole-body inhalation to 1000 ppm H2S for 45 min and euthanized at 5 min or 72 h for acute exposure. For subchronic study, mice were exposed to 5 ppm H2S 2 h/day, 5 days/week for 5 weeks. The brainstem was removed for metabolomic analysis. Enrichment analysis showed the metabolomic profiles in acute and subchronic H2S exposures matched with those of cerebral spinal fluid from patients with seizures or Alzheimer’s disease. Acute H2S exposure decreased excitatory neurotransmitters, aspartate and glutamate, while the inhibitory neurotransmitter, serotonin, was increased, which may explain H2S-induced loss of consciousness. Branched-chain amino acids and glucose were increased by acute H2S exposure. Subchronic H2S exposure within OSHA guideline surprisingly decreased serotonin altering central nervous system. In subchronic H2S exposure, glucose was decreased while polyunsaturated fatty acids, inosine, and hypoxanthine were increased. Collectively, these results provide important mechanistic clues of acute and subchronic ambient H2S poisonings and show that H2S alters brainstem metabolome.

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female WT mice were treated with Paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones including estrogen. RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by Paclitaxel but reversed the cardioprotection was observed in females after radiotherapy. Conversely, rhoB deficiency protected males from radiation toxicity. In sum, rhoB was identified as a molecular determinant driving estrogen dependent cardioprotection in female mice, whereas neuroprotection was not sex-hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.

Cancer-associated fibroblasts (CAF) form the basis of tumor microenvironment and possess immunomodulatory functions by interacting with other cells surrounding tumor, including T lymphocytes, macrophages, dendritic cells and natural killer cells. Ionizing radiation is a broadly-used method in radiotherapy to target tumors. In mammalian cells, ionizing radiation induces various types of DNA damages and DNA damage response. Being unspecific, radiotherapy affects all the cells in tumor microenvironment, including the tumor itself, CAFs and immune cells. CAFs are extremely radio-resistant and do not initiate apoptosis even at high doses of radiation. However, following radiation, CAFs become senescent and produce a distinct combination of immunoregulatory molecules. Radiosensitivity of immune cells varies depending on the cell type due to inefficient DNA repair in, for example, monocytes and granulocytes. In this minireview, we are summarizing recent findings on the interaction between CAF, ionizing radiation and immune cells in the tumor microenvironment.

This study is based on the BP neural network regression model optimised by genetic algorithm and dedicated to predicting the amount of car purchase, this study is important for all parties in the automotive industry. By plotting the violins of six indicators, including gender, age, annual salary, credit card debt, net worth, and car purchase amount, we found that, except for gender, the other data showed a trend of dense in the middle gradually decreasing to the upper and lower sides, with an overall normal distribution. The correlation analysis shows that the amount of car purchase has a high positive correlation with age (0.63), followed by annual income (0.62), the correlation between net worth and the amount of car purchase is 0.49, while the correlation between credit card debt and the amount of car purchase is low (0.03). In the experimental part, we analyse the predicted-actual values of the training and test sets in comparison and find that the model predicted values are very close to the actual values. The RMSE of the training set is 11.559 and the RMSE of the test set is 11.4835, which is not much different from each other, indicating that the model has good generalisation ability. In addition, the R2 of both the training and test sets is 1, indicating that the model fits well. The MAE of the training set is 8.2512 and the MAE of the test set is 9.578; the MBE of the training set is -4.3035 and the MBE of the test set is -2.4547.These metrics indicate that the model performs well in predicting the amount of car purchase. In conclusion, this study provides an effective and reliable method to predict the amount of car purchase, creating a useful bridge between car manufacturers, dealers and consumers.

The link between the world of communication and the world of racing is provided by telemetry systems in electric racing cars. These systems send real-time data about the vehicle’s behavior and systems to enable informed decisions during the race. The aim of this research was to integrate telemetry into the battery bank of a racing electric vehicle to find the optimal values of current and voltage that optimize the charging process, thus improving the vehicle’s performance in competition using Response Surface Analysis. Particularly, the telemetry system consisted of an Arduino Mega, a digital wattmeter, and temperature sensors, all installed in the vehicle. Once the telemetry data was obtained, a response surface design was adapted with current, voltage, and temperature as factors, varying from low to high values, with the objective function being to minimize the battery’s charging time. Applying the response surface methodology and the steepest descent algorithm, it was found that all factors significantly affect the charging time, with the minimum charge time being 6961 seconds, obtained with a current of 2.4 amps and voltages of 50.5 volts and 43.6 volts.

CAR-T therapy has achieved considerable treatment success in hematologic tumors by using patient derived autologous αβ T cells. There is an impetus to broaden the applicability of this approach by using a third-party donor derived CAR-T cell product which has a potent anti-tumor function but a constrained GVHD property. In this study, CAR-T cells were prepared from Vγ9Vδ2 T cells expanded by using a novel prodrug PTA and their anti-tumor functions were assessed in conjunction with persistency, localization, and phenotype. γδ T cells were successfully transduced with a CAR specific to CEA with signaling domains of CD3ζ and CD28 (CEA.CAR-γδ T cells), and exhibited potent tumor killing function in vitro. In a xenograft mouse model, CEA.CAR-γδ T cells suppressed CEA+ tumor growth though a limited time window. CEA.CAR-γδ T cells persisted and accumulated in the tumor even after tumor progression, however, ex vivo analysis revealed that those recovered at different time points from PBMC, spleen and tumors gradually lost tumor reactivity as assessed by IFN-γ production. Provision of GITR co-stimulation enhanced anti-tumor function of CEA.CAR-γδ T cells, the result of which imposes additional measurers to be adopted in CAR-γδ T cells for an allogeneic adoptive immunotherapy.

Direct yaw moment control (DYC) is an effective way to alter the behaviour of electric cars with independent drives. Controlling the torque applied to each wheel can improve the handling performance of a vehicle making it safer andfaster on a race track. The state-of-the-art literature covers the comparison of various controllers (PID, LPV, LQR, SMC, etc.) using ISO manoeuvres. However, more advanced comparison on important characteristics of the controllers performance is missed, such as the robustness of the controllers under changes in the vehicle model, steering behaviour, use of the friction circle and, ultimately, lap time on a track. In this study, we have compared the controllers according to some of the aforementioned parameters on a modelled race car. Interestingly, best lap times are not provided by perfect neutral or close-to-neutral behaviour of the vehicle, but rather by allowing certain deviations from the target yaw rate. In addition, a modified PID controller showed that its performance is comparable to other more complex control techniques such as MPC.

The article presents investigations of rail vehicle bogie of Y25 type. The Y25 bogie family is one of the most commonly used freight car bogie designs. In addition to several significant advantages characterising this design, it also has several disadvantages observed since the beginning of more than fifty years of operation in several types of cargo vehicles. One of these defects observed in real systems is "unsatisfactory running stability", particularly at long straight tracks. The article used commercial engineering software VI-Rail to create a model of the gondola car (type 412W Eaos) with two Y25 bogies. The car model was tested empty and loaded (maximum permissible load). Motion along straight and curved tracks with different radii values was analysed. The vehicle velocity was changed from a few m/s to the maximum values for which stable solutions of the model existed. For each route, a non-linear critical velocity was determined, defining the maximum operating velocity of the modelled car. The model solutions were recorded, while just one was selected to present the results - the first wheelset lateral displacement ylw. The opinion about the "imperfect running quality" in curved tracks was confirmed. The possible appearance of self-exciting wheelset vibrations in the modelled car's operating velocity range in the laden state was also observed. The research results on the impact of the bogie suspension parameters change on the vehicle model stability are presented. The crucial parameter in the bogie suspension was indicated. Reducing its value by several percent about the nominal value increases the critical velocity of the car to values higher than the maximum operating velocity of the modelled vehicle.

Preterm infants have increased body adiposity at term equivalent age and risk for adverse metabolic outcomes. The aim of the study was to define how nutrient intake may impact body composition (BC) of very low birth weight infants fed with early progressive enteral feeding and standard fortification. Eighty-six infants with

Introduction: Transportation logistics play a pivotal role in facilitating both individual mobility and supply chain operations on a global scale. However, conventional transportation systems have contributed significantly to urban congestion and environmental degradation. In response to these challenges, there is a growing momentum towards the adoption of intelligent transportation systems (ITS) and sustainable transportation solutions. This research aims to explore the potential of renewable energy sources to power electric vehicles (EVs) and flying automobiles, thereby accelerating the transition towards a low-carbon future. Objectives: The primary objectives of this research are as follows: - Investigate the role of renewable fuels in powering both EVs and flying cars to reduce reliance on fossil fuels and mitigate carbon emissions. - Analyze the dynamic growth and sustainability implications of advancements in battery technology and alternative renewable energy sources, such as Hydrogen Fuel Cells. - Evaluate the challenges and opportunities associated with the integration of flying vehicles into existing transportation infrastructure, focusing on safety, airspace control, and infrastructure development. - Review insights and guidance to stakeholders on promoting sustainable transportation solutions for EVs and flying cars through the utilization of renewable energy sources and the reduction of carbon emissions from the literature. Methodology: This research employs a mixed-method approach, combining literature review, and causal loop diagram analysis. The literature review provides a comprehensive understanding of current trends, challenges, and opportunities in sustainable transportation and renewable energy technologies. A causal loop diagram is utilized to visualize the dynamic interactions between various factors influencing the adoption of EVs and flying cars, including technological advancements, policy interventions, and market dynamics. Results and Discussion: The findings of this research highlight the significant potential of renewable energy sources, such as solar, wind, and hydrogen, in powering both EVs and flying cars. Advances in battery technology and hydrogen fuel cells are identified as key drivers in accelerating the transition towards sustainable transportation systems. However, challenges remain in terms of infrastructure development, safety regulations, and airspace management for flying vehicles. Nevertheless, there is a noticeable advancement in reducing carbon emissions and reliance on fossil fuels with the widespread adoption of EVs. By harnessing renewable energy and implementing effective policy measures, stakeholders might able to promote the widespread adoption of sustainable transportation solutions, thereby contributing to environmental protection and societal well-being. Conclusion: Literally, this research underscores the importance of sustainable transportation solutions in addressing urban congestion, environmental pollution, and energy security concerns. By leveraging renewable energy sources and embracing technological advancements, such as EVs and flying cars, stakeholders pave the way for a more sustainable and resilient transportation system. However, concerted efforts are needed to overcome existing challenges and ensure the successful integration of these technologies into existing infrastructure. Through collaborative partnerships and innovative initiatives, a low-carbon future for transportation logistics can be achieved, benefiting both the environment and society as a whole.

B-1 cells, a subtype of B lymphocytes, are found in lymphoid tissues and peritoneal and pleural cavities. They play diverse roles, releasing cytokines, generating antibodies, regulating the immune response, engaging in phagocytosis, and moving to inflammatory sites. However, their physiology remains partially understood, especially in stressful conditions like sleep restriction. This study aimed to investigate murine B-1 cell activation and differentiation under sleep restriction. Male C57BL/6J mice underwent an 18-hour sleep restriction for 21 days, followed by Candida albicans or Paracoccidioides brasiliensis infection. Purified peritoneal B-1 cells were evaluated for activation markers, microbicidal molecules, cytokine gene expression, Toll-like receptors, and commitment factors. Results showed that sleep restriction minimally influenced activation marker expression in B-1 cells across infection models. However, under sleep restriction, microbicidal molecule production increased in P. brasiliensis (NO) and C. albicans (ROS) infections. Gene expression revealed elevated TLR-2 and cytokines (IL-12, IL-6, TNF-α) in sleep-restricted animals. Lineage commitment analysis indicated myeloid polarization in sleep-restricted B-1 cells for all infection models. These findings underscore the impact of sleep restriction on B-1 cell activation and differentiation, with outcomes varying based on infection type. This study highlights the importance of investigating immunological changes resulting from sleep restriction.

Cardiac hypertrophy typically follows myocardial damage, a process known to involve members of the Krüppel-Like Factors (KLFs) which have pro-hypertrophic and anti-hypertrophic roles. Our study delved into the molecular mechanisms underlying KLFs-cardiac hypertrophy interplay post myocardial infraction. We induced myocardial dam-age in rats using isoproterenol. Total RNA was extracted from the left ventricle and Quantitative Real Time RT-PCR was conducted to assess the expression of KLFs, cardiac commitment genes, inflammatory markers, and certain conduction-related genes. We devel-oped a computational approach to construct a proteomic network centered on KLFs. Initial results revealed early expression (2-3 days post-induction) of KLF3, KLF4 and KLF6, followed by the subsequent expression of KLF11 and KLF15 (5-8 days after induction). In the maturation stage, KLF12 and KLF13 regulators were found upregulated. IL-6 was gradually found to be upregulated through. Interaction analysis revealed KLF3, KLF8 and KLF12 interacted with cardiac electrical functions. RT-PCR confirmed up-regulation in cardiac genes linked to electrical function and scar maturation. Our findings underscore the central role of KLFs during the modulation of the cardiac hypertrophic response. Dysregulation of KLF expression resulted in damaged myocardium, participating in the progression of abnormal hypertrophy, highlighting their potential as therapeutic targets for heart diseases.

The key to ensuring the sustainability of transportation operations on the roads is to manage traffic flows homogeneously. By homogenizing the behavior of various drivers, traffic operation can be optimized, and traffic safety can be improved. However, the advent of autonomous vehicles is expected to have a major impact on the homogeneity of sustainable transportation operations. In this study, a method of driving in harmony with surrounding vehicles was studied to minimize the impact of autonomous vehicles on current traffic operation. In particular, in this study, a methodology was developed to optimize the driving behavior of autonomous vehicles by analyzing the driving behavior of following vehicles using spectrum analysis. Specifically, a method for calculating three indicators that can analyze the driving behavior of a following vehicle, such as reaction time, stimulus adaptation index, and collision risk avoidance index, was proposed. These indices produced consistent and robust results for all traffic conditions. If these indicators are used, it is expected that sustainable traffic management will be possible even when autonomous vehicles and human drivers are mixed on the road.

Introduction: The rapid emergence of COVID-19 as a global crisis has led to the approval of many vaccinations, which were unfortunately associated with high complication rates due to a lack of sufficient safety studies. Objectives: The following manuscript focuses on discussing the demyelinating disorders that were noticed after COVID vaccine administration. Methods: We conducted a retrospective study using anonymous medical records from the US vaccine adverse events reporting system, complications retrieved included Acute disseminated encephalomyelitis (ADEM), Guillain Barre syndrome (GBS), and Multiple sclerosis (MS), outcome parameters were age, sex and the dose after which this complication was observed. Patients younger than 18 years-old were excluded as some of the vaccines, namely Janssen (JNJ-78436735) is not yet approved below this age. Results: Our analysis showed that demyelinating disorders were more likely to occur in patients over the age of 50 compared to other age groups, regardless of the type of vaccination, except for MS and ADEM occurrences after the Jansen vaccine. In addition, demyelinating complications were more likely to occur after the first dose of vaccination. Conclusion: Further research and observation of demyelinating diseases in different vaccinations, as well as additional in vitro studies, are recommended to further explain the pathogenesis of demyelinating disorder occurrence.

Myocardial infarction (MI) remains the leading cause of death in the western world. Although medical advancements have been made in interventional revascularization technologies, a large percentage of patients are not candidates for them due to co-morbidities or lack of local resources. Thus, there remains a need for the development of novel non-invasive strategies to treat MI. Approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been shown to be effective in animal models but not in humans likely due to its short half-life and systemic toxicity. We previously showed that a small peptide (PR1P) we developed stabilizes VEGF in its active dimer state, increases VEGF binding to its receptors and potentiates VEGF activity. Here we show that systemic PR1P treatment targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium following left coronary artery surgery in mice and rats. Targeted VEGF upregulation led to augmentation of heart function at two weeks following surgery. We conclude that PR1P is a potential candidate therapeutic for MI.

CAR-T cell therapy has emerged as a groundbreaking approach in cancer treatment, leveraging the immune system to target and eliminate cancer cells. While currently focused on hematologic malignancies, the future holds promise for expanding CAR-T cell therapy to diverse cancers, enhancing its efficacy, and improving safety profiles. Recent advances in tumor immunology have propelled CAR-T cell therapy as a game-changer in treating diseases such as relapsed/refractory B-cell acute lymphocytic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). Six CAR-T cell products have received FDA approval for treating R/R B cell malignancies. However, challenges persist, including complications like cytokine release syndrome (CRS), coagulopathy, and cytopenias. Strategies to mitigate these complications involve targeting distinct antigens with dual- or multi-targeted CAR-T cells and enhancing immunogenicity. Additionally, γδ CAR-T cells show promise in recognizing antigen- negative leukemia cells in an MHC-independent manner while reducing the risk of inducing graft-versus-host disease (GVHD). As CAR-T cell therapy continues to evolve through innovation and discovery, it holds the potential to revolutionize cancer treatment, offering new hope to patients and reshaping the landscape of oncology with its precision and efficacy.

Among the explored solutions to reduce the environmental impact of the transport sector, Vehicle Integrated Photovoltaics. Thus, we developed a simulation tool of the distance covered by VIPV. It considers various usage patterns and vehicle types, several characteristics of the PV system and all the losses that may decrease energy yield. Focusing on passenger car, simulations indicate the order of influence of the parameters on the outputs of the model: geographic locality, shading, thresholds due to extra-consumption to charge the vehicle battery from PV and frequency of recharge with the grid. With projections of the technology in 2030, with 30 % shading, VIPV cover up to 1444 km yearly distance. This represents up to 12 % of the driven mileage. For the best month, it can get up to 14 km/day. For average Europe and worst-case conditions, VIPV cover only 293 km per year. Life Cycle Assessment (LCA) of solarized passenger car shows negative balance for low-carbon electricity mix and average solar irradiance. In favorable conditions, the carbon footprint is up to 489 kg CO₂-equivalent avoided emissions on 13 years lifespan. Beyond km and LCA focus, VIPV may provide useful functions in non-interconnected zones and for resilience in disaster zones.

Despite advances in the understanding of its molecular pathophysiology, prostate cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate specific membrane antigen (PSMA), a glycoprotein that is overexpressed in prostate cancer, which expression involves neovasculature of several tumor entities, thus envisaging an additional antiangiogenic effect. To optimize the CAR design, we compared two CARs with signaling domains containing one or two T cell costimulatory elements, in addition to CD3ζ. Conversely, what has been described for other CARs, a third-generation CAR (containing CD28 and 41BB co-signaling domains) induced a potent antitumor effect similar to a second-generation CAR (containing CD28 co-signaling domain), though we observed a detrimental effect of the additional costimulatory domain that was attributed to increased activation-induced cell death (AICD). This “super-stimulation” resulted in exhaustion of cells, higher frequencies of cell death and, more importantly, the impossibility of sufficiently expanding the CAR cells to obtain the minimum number of cells requested for in vivo therapies. While the superiority of 2nd and 3rd generation over 1st generation CAR T cells has been clearly shown in both preclinical and clinical studies, the optimal combination of costimulatory domains for 3rd generation CAR-T cells must still be defined and should be evaluated case-by-case in order to fine-tune immunotherapy approaches.

Prostate cancer (PCa) has become the most common tumor among males in Europe and the USA. Adoptive immunotherapy appears as a promising strategy to control the advanced stages of the disease by specific targeting the tumor, in particular through chimeric antigen receptor T (CAR-T) cell therapy. Despite the advancements of CAR-T technology in the treatment of hematological malignancies, solid tumors still represent a challenge. To overcome current limits, other cellular effectors than T lymphocytes are under study as possible candidates for CAR-engineered cancer immunotherapy. A novel approach involves the NK-92 cell line, which mediates strong cytotoxic responses against a variety of tumor cells but has no effect on non-malignant healthy counterparts. Here, we report a therapeutic approach against PCa based on engineering of NK-92 cells with a CAR recognizing the human prostate-specific membrane antigen (PSMA), which is overexpressed in prostatic neoplastic cells. Upon CAR transduction, NK-92/CAR cells acquired high and specific lytic activity against PSMA-expressing prostate cancer cells in vitro, and also underwent degranulation and produced high levels of IFN-γ in response to antigen recognition. Lethal irradiation of the effectors, a safety measure requested for the clinical application of retargeted NK-92 cells, fully abrogated replication but did not impact on phenotype and short-term functionality. PSMA-specific recognition and antitumor activity were retained in vivo, as adoptive transfer of irradiated NK-92/CAR cells in prostate cancer-bearing mice restrained tumor growth and improved survival. Anti-PSMA CAR-modified NK-92 cells represent a universal, off-the-shelf, renewable and cost-effective product endowed with relevant potentialities as a therapeutic approach for PCa immunotherapy.

Background: The incidence of spinal metastatic disease has risen with improved cancer survivorship. Separation surgery, the current standard surgical treatment, does not fully address spinal deformity. Advances in operative management warrant reevaluating maximal tumor resection and anterior column reconstruction with corpectomy. Methods: An IRB-approved retrospective single-center review of 63 patients was performed. Demographics, tumor characteristics, clinical and radiographic data, treatments, and neurological and survival outcomes were analyzed. Results: The mean age at presentation was 63.5 ± 9.6 years (range, 37-84 years) and 28 patients (44.4%) were female. Functional outcomes, measured by KPS, RAND-36 survey scores and Oswestry Disability Index all improved postoperatively (pre- vs postop: 70 to 80 (p=0.0056), 26.5 to 46.4 (p=0.0081), and 28.9 to 16.9 (p=0.0613), respectively). Spinal alignment also improved, with Cobb angle measurements showing a reduction in spinal kyphosis from -5 to 0 (p=0.021). Nine patients (14.5%) had non-fatal postoperative complications. The median OS for this cohort was 14.4 months (range, 0.6-145.0 months) with median follow-up time of 15.5 months. Conclusion: In oligometastatic spinal disease patients with good functional status, corpectomy for decompression of neural elements, deformity correction, and spinal stabilization is associated with improvements in pain and functional outcomes without overwhelming morbidity.

(1) Importance of problem: Breast cancer accounted for 685.000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor beside gender and age-group. During last 4 decades we see a reduction by 40% of age-standardized breast cancer [1], which in turn means that the number of mastectomies performed for younger women increased, raising the need for adequate breast reconstructive surgery. Advances in oncological treatment have made it possible to limit the extent of what represents radical surgery for breast cancer, yet in the past decade, we see a marked trend toward mastectomy in breast conserving surgery eligible patients [2]. Prophylactic mastectomy has also registered an upward trend [3,4]. This trend together with new indication for breast reconstruction like chest feminization in transgender patients [5] have increased the need for breast reconstruction surgery. (2) Purpose: The purpose of this study is to analyze the types of reconstructive procedures, their indications, their limitations, their functional results and the safety profiles when used during the integrated treatment plan of the oncologic patient; (3) Methods: We conducted an extensive literature review of the main reconstructive techniques, especially the autologous procedures, summarized the findings and presented a few cases from our own experience for exemplification of the usage of breast reconstruction in oncologic patients. (4) Conclusions: Breast reconstruction has become a necessary step in the treatment of most breast cancers and many reconstructive techniques are now routinely practiced. Microsurgical techniques are considered the "gold standard", but they are not accessible to all services, from a technical or financial point of view, so pediculated flaps remain the safe and reliable option, along with alloplastic procedures, to improve the quality of life of these patients.

Acute chemical ablation of lateral line hair cells is an important tool to understand lateral line-mediated behaviors in free-swimming fish larvae and adults. However, lateral line-mediated behaviors have not been described in fish larvae prior to swim bladder inflation, possibly because single doses of ototoxin do not effectively silence lateral line function at early developmental stages. To determine if ototoxins can effectively silence the lateral line during early development, we repeatedly expose zebrafish larvae to the ototoxin neomycin during a 36-hour period from 3-4 days post-fertilization (dpf). We use simultaneous transgenic and vital dye labeling of hair cells to compare 6- hour and 12-hour repeated treatment timelines and neomycin concentrations between 0–400 µM in terms of larval survival, hair cell death, regeneration, and functional recovery. Following exposure to neomycin, we find that the emergence of newly functional hair cells outpaces cellular regeneration, likely due to the maturation of ototoxin-resistant hair cells that survive treatment. Furthermore, hair cells of 4 dpf larvae exhibit faster recovery compared to 3 dpf larvae. Our data suggest that the rapid functional maturation of ototoxin-resistant hair cells limits the effectiveness of chemical-based methods to disrupt lateral line function. Furthermore, we show that repeated neomycin treatments can continually ablate lateral line hair cells between 3–4 dpf in larval zebrafish.

Ecdysterone is a phytosteroid widely discussed for its various pharmacological, growth-promoting and anabolic effects mediated by activation of estrogen receptor beta (ERbeta). Performance-enhancement in sports was demonstrated recently, and ecdysterone was consequently included in the Monitoring Program to detect potential patterns of misuse in sport. Only few studies on the pharmacokinetics of ecdysterone in humans have been reported so far. In this study, post-administration urines in twelve volunteers (single dose of 50 mg of ecdysterone) were analyzed using dilute-and-inject liquid chromatography-tandem mass spectrometry. Identification and quantitation of ecdysterone and of two metabolites, 14-deoxy ecdysterone and 14-deoxy poststerone was achieved. Ecdysterone was the most abundant analyte present in post-administration urines, detected for more than 2 days with a maximum concentration (Cmax) in the 2.8-8.5 h urines (Cmax = 4.4-30.0 µg/mL). The metabolites 14-deoxy ecdysterone and 14-deoxy poststerone were detected later reaching the maximum concentrations at 8.5-39.5 h (Cmax = 0.1-6.0 µg/mL) and 23.3-41.3 h (Cmax = 0.1-1.5 µg/mL), respectively. Cumulative urinary excretion yielded average values of 18%, 2.3% and 1.5% for ecdysterone, 14-deoxy ecdysterone and 14-deoxy poststerone, respectively. Ecdysterone and 14-deoxy ecdysterone were excreted following first order kinetics with half-lives calculated with three hours, while pharmacokinetics of 14-deoxy poststerone needs further evaluation.

The pharmacokinetics of salicylic acid (SA) in sheep was evaluated following intravenous (IV) and oral administration of sodium salicylate (sodium salt of salicylic acid) at different doses. Six healthy sheep were administered sodium salicylate (SS) IV at doses of 10, 50, 100 and 200 mg/kg body weight and another six sheep were drenched with 100 and 200 mg/kg of SS orally. Both studies were randomised crossover trials. A one-week washout period between each treatment was allowed in both studies. Blood samples were collected at 0, 15, 30 minutes and 1, 2, 4 and 6 hours after IV and oral SS administrations. Plasma SA concentrations were determined using high performance liquid chromatography with diode array detection method. Pharmacokinetic variables were calculated in a non-compartmental model. The elimination half-life (T_{1/2 el}) of SA after IV administration of 200 mg/kg SS was 1.16 ± 0.32 hours. Mean bioavailability of SA was 64%, and mean T_{1/2 el} was 1.90 ± 0.35 hours, after 200 mg/kg of oral SS. The minimum plasma SA concentration (16.8 µg/mL) required to produce analgesia in humans was achieved after IV administration of 100 and 200 mg/kg SS in sheep for about 0.17 hour in this study. Experiments on pharmacokinetic-pharmacodynamics modelling are required to determine the actual effective plasma concentration range of SA in sheep.

There are no studies that have investigated the characteristics of car use across THA patients, including those who do not drive. This study aimed to evaluate, in THA patients, (1) postoperative car usage, (2) comfort while entering and exiting a car, and (3) whether lower limb muscle strength affects action comfort. One hundred seventy-two post-THA patients completed the questionnaire in 2020, along with assessments of hip abductor and knee extensor muscle strength before surgery and at discharge. Patients whose overall comfort level was judged as “comfortable” were defined as the “comfort” group; others were placed in the “discomfort” group. Of the 172 patients, 161 reported car usage at a mean of 5.6 years after THA. Of these, 114 and 47 patients were placed in the "comfort" and "discomfort" groups, respectively. Patients in the "discomfort" group were three times more likely to experience discomfort using the contralateral side door than the surgical side door, and about twice as many patients experienced discomfort when entering as when exiting. Lower preoperative contralateral hip abductor muscle strength was the only independent predictor for discomfort. The take-home messages were that prevention of contralateral-side weakness may improve comfort during the action after THA.