Miracle-dz/UniFAR-FTUs huggingface dataset:
Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma

Simple Summary This review explores the current trials using cellular immunotherapies in pediatric sarcoma and describes examples of promising new CAR T targets in sarcoma that are in preclinical development. We provide insights into the ways in which the immunosuppressive tumor immune microenvironment can impact on CAR T cell therapy, highlighting specific mechanisms by which the tumor microenvironment may limit CAR T efficacy. Appreciation of these mechanisms may lead to rational combinations of immunotherapies, for example, the combination of CAR T cells with checkpoint inhibitor drugs. We also describe innovations in CAR T cell generation and combination therapies that may pave the way to better clinical outcomes for these patients. Abstract Sarcomas are a diverse group of bone and soft tissue tumors that account for over 10% of childhood cancers. Outcomes are particularly poor for children with refractory, relapsed, or metastatic disease. Chimeric antigen receptor T (CAR T) cells are an exciting form of adoptive cell therapy that potentially offers new hope for these children. In early trials, promising outcomes have been achieved in some pediatric patients with sarcoma. However, many children do not derive benefit despite significant expression of the targeted tumor antigen. The success of CAR T cell therapy in sarcomas and other solid tumors is limited by the immunosuppressive tumor microenvironment (TME). In this review, we provide an update of the CAR T cell therapies that are currently being tested in pediatric sarcoma clinical trials, including those targeting tumors that express HER2, NY-ESO, GD2, EGFR, GPC3, B7-H3, and MAGE-A4. We also outline promising new CAR T cells that are in pre-clinical development. Finally, we discuss strategies that are being used to overcome tumor-mediated immunosuppression in solid tumors; these strategies have the potential to improve clinical outcomes of CAR T cell therapy for children with sarcoma.
The Influence of Celebrity Endorsement on Food Consumption Behavior

“Is consumer food behavior influenced by celebrity endorsement? ”. This question remains unsolved despite celebrities constantly recommending different products in their social media networks. Much of the literature on celebrity endorsement focuses on the characteristics of celebrities influencing consumers’ behavior, but there is scarce research about how celebrity endorsements about food and food products influence consumers’ behavior. In this context and based on the source credibility and source attractiveness models, as well as on the match-up theory, this study aims to examine whether consumers’ food purchase intention and consumers’ willingness to pay a premium price is influenced by celebrity endorsement. For this purpose, an empirical study is developed through Structural Equation Modeling (PLS-SEM) based on data gathered from 316 consumers who read celebrity recommendations. Findings report that consumers are most influenced in their food consumption behavior by the congruence between the celebrity endorsement and the product being recommended, and by the celebrity credibility. Interestingly, celebrity recommendations show a similar influencing pattern both for consumers’ food purchase intention and consumers’ willingness to pay a premium price for food. The major contribution of this research is to show that congruence is the main route by which celebrity endorsement influences food consumption behavior.
Preparation of Network-Structured Carbon Nanofiber Mats Based on PAN Blends Using Electrospinning and Hot-Pressing Methods for Supercapacitor Applications

In this work, we prepared network-structured carbon nanofibers using polyacrylonitrile blends (PAN150 and PAN85) with different molecular weights (150,000 and 85,000 g mol−1) as precursors through electrospinning/hot-pressing methods and stabilization/carbonization processes. The obtained PAN150/PAN85 polymer nanofibers (PNFs; PNF-73, PNF-64 and PNF-55) with different weight ratios of 70/30, 60/40 and 50/50 (w/w) provided good mechanical and electrochemical properties due to the formation of physically bonded network structures between the blended PAN nanofibers during the hot-processing/stabilization processes. The resulting carbonized PNFs (cPNFs; cPNF-73, cPNF-64, and cPNF-55) were utilized as anode materials for supercapacitor applications. cPNF-73 exhibited a good specific capacitance of 689 F g−1 at 1 A g−1 in a three-electrode set-up compared to cPNF-64 (588 F g−1 at 1 A g−1) and cPNF-55 (343 F g−1 at 1 A g−1). In addition, an asymmetric hybrid cPNF-73//NiCo2O4 supercapacitor device also showed a good specific capacitance of 428 F g−1 at 1 A g−1 compared to cPNF-64 (400 F g−1 at 1 A g−1) and cPNF-55 (315 F g−1 at 1 A g−1). The cPNF-73-based device showed a good energy density of 1.74 W h kg−1 (0.38 W kg−1) as well as an excellent cyclic stability (83%) even after 2000 continuous charge–discharge cycles at a current density of 2 A g−1.
Effect of Endogenic and Exogenic Oxidative Stress Triggers on Adverse Pregnancy Outcomes: Preeclampsia, Fetal Growth Restriction, Gestational Diabetes Mellitus and Preterm Birth

Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) in cells and tissues and the ability of a biological system to detoxify them. During a normal pregnancy, oxidative stress increases the normal systemic inflammatory response and is usually well-controlled by the balanced body mechanism of the detoxification of anti-oxidative products. However, pregnancy is also a condition in which this adaptation and balance can be easily disrupted. Excessive ROS is detrimental and associated with many pregnancy complications, such as preeclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM), and preterm birth (PTB), by damaging placentation. The placenta is a tissue rich in mitochondria that produces the majority of ROS, so it is important to maintain normal placental function and properly develop its vascular network to ensure a safe and healthy pregnancy. Antioxidants may ameliorate these diseases, and related research is progressing. This review aimed to determine the association between oxidative stress and adverse pregnancy outcomes, especially PE, FGR, GDM, and PTB, and explore how to overcome this oxidative stress in these unfavorable conditions.
A Review of the Clinical and Therapeutic Implications of Neuropathic Pain

Understanding neuropathic pain presents several challenges, given the various mechanisms underlying its pathophysiological classification and the lack of suitable tools to assess its diagnosis. Furthermore, the response of this pathology to available drugs is still often unpredictable, leaving the treatment of neuropathic pain still questionable. In addition, the rise of personalized treatments further extends the ramified classification of neuropathic pain. While a few authors have focused on neuropathic pain clustering, by analyzing, for example, the presence of specific TRP channels, others have evaluated the presence of alterations in microRNAs to find tailored therapies. Thus, this review aims to synthesize the available evidence on the topic from a clinical perspective and provide a list of current demonstrations on the treatment of this disease.
Intermittent Fasting and the Possible Benefits in Obesity, Diabetes, and Multiple Sclerosis: A Systematic Review of Randomized Clinical Trials

Intermittent fasting has become popular in recent years and is controversially presented as a possible therapeutic adjunct. A bibliographic review of the literature on intermittent fasting and obesity, diabetes, and multiple sclerosis was carried out. The scientific quality of the methodology and the results obtained were evaluated in pairs. Intermittent fasting has beneficial effects on the lipid profile, and it is associated with weight loss and a modification of the distribution of abdominal fat in people with obesity and type 2 diabetes as well as an improvement in the control of glycemic levels. In patients with multiple sclerosis, the data available are too scarce to draw any firm conclusions, but it does appear that intermittent fasting may be a safe and feasible intervention. However, it is necessary to continue investigating its long-term effects since so far, the studies carried out are small and of short duration.
3D Printing—A Cutting Edge Technology for Treating Post-Infarction Patients

The increasing complexity of cardiovascular interventions requires advanced peri-procedural imaging and tailored treatment. Three-dimensional printing technology represents one of the most significant advances in the field of cardiac imaging, interventional cardiology or cardiovascular surgery. Patient-specific models may provide substantial information on intervention planning in complex cardiovascular diseases, and volumetric medical imaging from CT or MRI can be translated into patient-specific 3D models using advanced post-processing applications. 3D printing and additive manufacturing have a great variety of clinical applications targeting anatomy, implants and devices, assisting optimal interventional treatment and post-interventional evaluation. Although the 3D printing technology still lacks scientific evidence, its benefits have been shown in structural heart diseases as well as for treatment of complex arrhythmias and corrective surgery interventions. Recent development has enabled transformation of conventional 3D printing into complex 3D functional living tissues contributing to regenerative medicine through engineered bionic materials such hydrogels, cell suspensions or matrix components. This review aims to present the most recent clinical applications of 3D printing in cardiovascular medicine, highlighting also the potential for future development of this revolutionary technology in the medical field.
Dry Period Heat Stress Impacts Mammary Protein Metabolism in the Subsequent Lactation

Simple Summary Heat stress during the dry period of dairy cows reduces milk yield in the following lactation. Factors such as altered mammary metabolism could impact yields and alter milk composition, including milk protein. We sought to determine if exposure to dry period heat stress would influence mammary milk protein metabolism during the subsequent lactation. Objectives were to first determine the impact of dry period heat stress on milk protein yields and secondly characterize the amino acid and protein profiles in the mammary tissue, milk, and blood to elucidate potential carry-over impact of dry period heat stress on systems that participate directly in milk protein metabolism (i.e., mTOR). We found that heat stress during the dry period reduces milk yield, protein content, and protein yield in the subsequent lactation. The plasma amino acid profile and mammary amino acid transporters are altered in dry period heat-stressed cows, and mammary mTOR signaling proteins are differentially expressed as well. It appears that dry period heat stress impacts mammary metabolism with consequences on milk yield and protein content. The continuous production of high-quality and -quantity milk is vital as a sustainable source of protein in the face of rising global temperatures. Abstract Dry period heat stress impairs subsequent milk production, but its impact on milk protein content and yield is inconsistent. We hypothesize that dairy cow exposure to dry period heat stress will reduce milk protein synthesis in the next lactation, potentially through modified amino acid (AA) transport and compromised mTOR signaling in the mammary gland. Cows were enrolled into heat-stressed (dry-HT, n = 12) or cooled (dry-CL, n = 12) treatments for a 46-day dry period then cooled after calving. Milk yield and composition and dry matter intake were recorded, and milk, blood, and mammary tissue samples were collected at 14, 42, and 84 days in milk (DIM) to determine free AA concentrations, milk protein fractions, and mammary AA transporter and mTOR pathway gene and protein expression. Dry matter intake did not significantly differ between treatments pre- or postpartum. Compared with dry-CL cows, milk yield was decreased (32.3 vs. 37.7 ± 1.6 kg/day) and milk protein yield and content were reduced in dry-HT cows by 0.18 kg/day and 0.1%. Further, dry-HT cows had higher plasma concentrations of glutamic acid, phenylalanine, and taurine. Gene expression of key AA transporters was upregulated at 14 and 42 DIM in dry-HT cows. Despite minor changes in mTOR pathway gene expression, the protein 4E-BP1 was upregulated in dry-HT cows at 42 DIM whereas Akt and p70 S6K1 were downregulated. These results indicate major mammary metabolic adaptations during lactation after prior exposure to dry period heat stress.
Exercise and Sestrin Mediate Speed and Lysosomal Activity in Drosophila by Partially Overlapping Mechanisms

Chronic exercise is widely recognized as an important contributor to healthspan in humans and in diverse animal models. Recently, we have demonstrated that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits in flies and mice. Knockout of Sestrins prevents exercise adaptations to endurance and flight in Drosophila, and similarly prevents benefits to endurance and metabolism in exercising mice. In contrast, overexpression of dSestrin in muscle mimics several of the molecular and physiological adaptations characteristic of endurance exercise. Here, we extend those observations to examine the impact of dSestrin on preserving speed and increasing lysosomal activity. We find that dSestrin is a critical factor driving exercise adaptations to climbing speed, but is not absolutely required for exercise to increase lysosomal activity in Drosophila. The role of Sestrin in increasing speed during chronic exercise requires both the TORC2/AKT axis and the PGC1α homolog spargel, while dSestrin requires interactions with TORC1 to cell-autonomously increase lysosomal activity. These results highlight the conserved role of Sestrins as key factors that drive diverse physiological adaptations conferred by chronic exercise.
Thermal stability study of transition metal perovskite sulfides

Transition metal perovskite chalcogenides, a class of materials with rich tunability in functionalities, are gaining increased attention as candidate materials for renewable energy applications. Perovskite oxides are considered excellent n-type thermoelectric materials. Compared to oxide counterparts, we expect the chalcogenides to possess more favorable thermoelectric properties such as lower lattice thermal conductivity and smaller band gap, making them promising material candidates for high temperature thermoelectrics. Thus, it is necessary to study the thermal properties of these materials in detail, especially thermal stability, to evaluate their potential. In this work, we report the synthesis and thermal stability study of five compounds, α-SrZrS_3, β-SrZrS_3, BaZrS_3, Ba_2ZrS_4, and Ba_3Zr_2S_7. These materials cover several structural types including distorted perovskite, needle-like, and Ruddlesden–Popper phases. Differential scanning calorimeter and thermogravimetric analysis measurements were performed up to 1200 °C in air. Structural and chemical characterizations such as X-ray diffraction, Raman spectroscopy, and energy dispersive analytical X-ray spectroscopy were performed on all the samples before and after the heat treatment to understand the oxidation process. Our studies show that perovskite chalcogenides possess excellent thermal stability in air at least up to 550 °C.
Effects of Rural Restaurants’ Outdoor Dining Environment Dimensions on Customers’ Satisfaction: A Consumer Perspective

The catering industry is one of the important industries that promote rural tourism development. Hence, rural restaurants have high research value. However, few studies have examined rural restaurants and their outdoor dining environments (ODE). In this study, from the perspective of consumers and using exploratory factor analysis, three ODE dimensions (quality and facilities, image and atmosphere, and landscape elements) were proposed that affect customers’ satisfaction with rural restaurants. Moreover, the differences between different customer groups in terms of the various dimensions were analyzed. The research results provide management recommendations and fundamental knowledge for rural restaurant managers and rural restaurant designers and articulate different consumer groups’ expectations with regard to rural restaurants.
Genetic Analysis, Population Structure, and Characterisation of Multidrug-Resistant Klebsiella pneumoniae from the Al-Hofuf Region of Saudi Arabia

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) is a major public health problem that is globally associated with disease outbreaks and high mortality rates. As the world seeks solutions to such pathogens, global and regional surveillance is required. The aim of the present study was to examine the antimicrobial susceptibility pattern and clonal relatedness of Klebsiella pneumoniae isolates collected for a period of three years through pulse field gel electrophoresis (PFGE). Isolate IDs, antimicrobial assays, ESBL-production, and minimum inhibitory concentrations (MICs) were examined with the Vitek 2 Compact Automated System. IDs were confirmed by 16S rRNA gene sequencing, with the resulting sequences being deposited in NCBI databases. DNA was extracted and resistance genes were detected by PCR amplification with appropriate primers. Isolates were extensive (31%) and multidrug-resistant (65%). Pulsotype clusters grouped the isolates into 22 band profiles that showed no specific pattern with phenotypes. Of the isolates, 98% were ESBL-KP, 69% were carbapenem-resistant Enterobacteriaceae (CRE) strains, and 72.5% comprised the carriage of two MBLs (SIM and IMP). Integrons (ISAba1, ISAba2, and IS18) were detected in 69% of the MDR-KP. Additionally, OXA-23 was detected in 67% of the isolates. This study therefore demonstrates clonal diversity among clinical K. pneumoniae, confirming that this bacterium has access to an enormous pool of genes that confer high resistance-developing potential.
Nano-Drug Design Based on the Physiological Properties of Glutathione

Glutathione (GSH) is involved in and regulates important physiological functions of the body as an essential antioxidant. GSH plays an important role in anti-oxidation, detoxification, anti-aging, enhancing immunity and anti-tumor activity. Herein, based on the physiological properties of GSH in different diseases, mainly including the strong reducibility of GSH, high GSH content in tumor cells, and the NADPH depletion when GSSH is reduced to GSH, we extensively report the design principles, effect, and potential problems of various nano-drugs in diabetes, cancer, nervous system diseases, fluorescent probes, imaging, and food. These studies make full use of the physiological and pathological value of GSH and develop excellent design methods of nano-drugs related to GSH, which shows important scientific significance and prominent application value for the related diseases research that GSH participates in or responds to.
Pharmacogenomics: An Update on Biologics and Small-Molecule Drugs in the Treatment of Psoriasis

Pharmacogenomic studies allowed the reasons behind the different responses to treatments to be understood. Its clinical utility, in fact, is demonstrated by the reduction in adverse drug reaction incidence and the improvement of drug efficacy. Pharmacogenomics is an important tool that is able to improve the drug therapy of different disorders. In particular, this review will highlight the current pharmacogenomics knowledge about biologics and small-molecule treatments for psoriasis. To date, studies performed on genes involved in the metabolism of biological drugs (tumor necrosis factor inhibitors and cytokines inhibitors) and small molecules (apremilast, dimethyl fumarate, and tofacitinib) have provided conflicting results, and further investigations are necessary in order to establish a set of biomarkers to be introduced into clinical practice.
COL5A1 RS12722 Is Associated with Temporomandibular Joint Anterior Disc Displacement without Reduction in Polish Caucasians

Numerous reports describe the association between the single-nucleotide polymorphism (SNP) rs12722 and rs13946 in the COL5A1 gene and injuries, such as Achilles tendon pathology, anterior cruciate ligament (ACL) injuries, and tennis elbow. Hence, there were no studies investigating COL5A1 and temporomandibular joint (TMJ) pathology. The aim of this study is to evaluate the relationship between COL5A1 rs12722 and rs13946 SNPs and TMJ articular disc displacement without reduction (ADDwoR). In this case-control study, the study group consisted of 124 Caucasian patients of both sexes. Each patient had a history of ADDwoR no more than 3 months prior. The control group comprised 126 patients with no signs of TMD according to DC/TMD. Genotyping of the selected SNPs was performed by real-time PCR using TaqMan probes. The significance of the differences in the distribution of genotypes was analyzed using Pearson’s chi-square test. Logistic regression modeling was performed to analyze the influence of the 164 investigated SNPs on ADDwoR. The COL5A1 marker rs12722 turned out to be statistically significant (p-value = 0.0119), implying that there is a difference in the frequencies of TMJ ADDwoR. The distribution of rs12722 SNPs in the study group TT(66), CC(27), CT(31) vs. control group TT(45), CC(26), CT(51) indicates that patients with CT had an almost 2.4 times higher likelihood of ADDwoR (OR = 2.41) than those with reference TT (OR = 1), while rs13946 genotypes were shown to be insignificant, with a p-value of 0.1713. The COL5A1 rs12722 polymorphism is a risk factor for ADDwoR in the Polish Caucasian population.