Miracle-dz/UniFAR-FTUs huggingface dataset:
Advantages of Porcine Xenograft over Autograft in Sinus Lift: A Randomised Clinical Trial

This study aimed to compare the performance of intra-oral autologous bone grafts versus porcine xenografts in a two-step lateral window sinus lift. This split-mouth randomised controlled trial sequentially enrolled 12 patients with a 6-month follow-up. For each patient, a simultaneous randomised bilateral maxillary sinus lift was performed and filled with autologous bone from the mandible (control) or a porcine xenograft (test). A bone biopsy sample was collected during the implant placement for histological and histomorphometric analysis. CT scans were performed at the beginning and at the end of the trial to assess radiological evolution. A comparison of initial and six-month CT scans indicated statistically significant increases in bone level for both materials (7.8 ± 2.4 mm for autologous and 8.7 ± 2.2 mm for xenograft, p < 0.05), and there were no significant differences between the performance of the two materials over time (p = 0.26). The histological analysis showed various stages of the remodelling process and no cells or other signs of inflammation or infection were visible in both groups. The porcine xenografts presented similar results for the studied variables when compared to autologous bone, being a reasonable alternative for a sinus lift.
Blockade of HVEM for Prostate Cancer Immunotherapy in Humanized Mice

Simple Summary Current immune checkpoint inhibitors have shown limitations for immunotherapy of prostate cancer. Thus, it is crucial to investigate other immune checkpoints to prevent disease progression in patients with prostate cancer. Here, we first show that the HVEM/BTLA immune checkpoint is associated with disease progression in patients. We then show that immunotherapy aimed at targeting HVEM reduced tumor growth twofold in vivo in a humanized mouse model of the pathology. The mode of action of the therapy was dependent on CD8+ T cells and is associated with improved T cell activation and reduced exhaustion. Finally, we demonstrated that HVEM expressed by the tumor negatively regulated the anti-tumor immune response. Our results indicate that targeting HVEM might be an attractive option for patients with prostate cancer. Abstract The herpes virus entry mediator (HVEM) delivers a negative signal to T cells mainly through the B and T lymphocyte attenuator (BTLA) molecule. Thus, HVEM/BTLA may represent a novel immune checkpoint during an anti-tumor immune response. However, a formal demonstration that HVEM can represent a target for cancer immunotherapy is still lacking. Here, we first showed that HVEM and BTLA mRNA expression levels were associated with a worse progression-free interval in patients with prostate adenocarcinomas, indicating a detrimental role for the HVEM/BTLA immune checkpoint during prostate cancer progression. We then showed that administration of a monoclonal antibody to human HVEM resulted in a twofold reduction in the growth of a prostate cancer cell line in NOD.SCID. gc-null mice reconstituted with human T cells. Using CRISPR/Cas9, we showed that the therapeutic effect of the mAb depended on HVEM expression by the tumor, with no effect on graft vs. host disease or activation of human T cells in the spleen. In contrast, the proliferation and number of tumor-infiltrating leukocytes increased following treatment, and depletion of CD8+ T cells partly alleviated treatment’s efficacy. The expression of genes belonging to various T cell activation pathways was enriched in tumor-infiltrating leukocytes, whereas genes associated with immuno-suppressive pathways were decreased, possibly resulting in modifications of leukocyte adhesion and motility. Finally, we developed a simple in vivo assay in humanized mice to directly demonstrate that HVEM expressed by the tumor is an immune checkpoint for T cell-mediated tumor control. Our results show that targeting HVEM is a promising strategy for prostate cancer immunotherapy.
Antimicrobial Activity and Protective Effect of Tuscan Bee Pollens on Oxidative and Endoplasmic Reticulum Stress in Different Cell-Based Models

Bee pollen is an apiary product of great interest owing to its high nutritional and therapeutic properties. This study aimed to assess the cellular antioxidant activity and the antihemolytic effect of Castanea, Rubus, and Cistus bee pollens on human erythrocytes. We also tested the antimicrobial potential of each sample on selected Gram-negative and Gram-positive bacteria. Finally, the effect of Castanea bee pollen, showing the best phytochemical profile, was analyzed on human microvascular endothelial cells exposed to thapsigargin, used as endoplasmic reticulum (ER) stressor. Our results showed good biological activities of all bee pollen samples that, under oxidative conditions, significantly improved the erythrocytes’ antioxidant activity and limited cell lyses. Castanea and Cistus showed comparable antihemolytic activities, with higher % hemolysis inhibition than Rubus. All samples exerted antimicrobial activity with different selectivity among all the tested microorganisms with minimal inhibitory concentration values ranging from 5 to 10 mg/mL. Finally, Castanea bee pollen was effective in reducing gene over-expression and oxidation process arising from thapsigargin treatment, with a maximum protective effect at 10 µg/mL. In conclusion, bee pollen represents a potential natural antibacterial and a good nutraceutical product useful in the prevention of free radical and ER stress-associated diseases.
The Effects of Fasting or Ketogenic Diet on Endurance Exercise Performance and Metabolism in Female Mice

The promotion of ketone body (KB) metabolism via ketosis has been suggested as a strategy to increase exercise performance. However, studies in humans and animals have yielded inconsistent results. The purpose of the current study was to examine the effects of ketosis, achieved via fasting or a short-term ketogenic diet (KD), on endurance exercise performance in female mice. After 8 h of fasting, serum KB significantly increased and serum glucose significantly decreased in fasted compared to fed mice. When subjected to an endurance exercise capacity (EEC) test on a motorized treadmill, both fed and fasted mice showed similar EEC performance. A 5-week KD (90% calories from fat) significantly increased serum KB but did not increase EEC times compared to chow-fed mice. KD mice gained significantly more weight than chow-fed mice and had greater adipose tissue mass. Biochemical tissue analysis showed that KD led to significant increases in triglyceride content in the heart and liver and significant decreases in glycogen content in the muscle and liver. Furthermore, KD downregulated genes involved in glucose and KB oxidation and upregulated genes involved in lipid metabolism in the heart. These findings suggest that a short-term KD is not an effective strategy to enhance exercise performance and may lead to increased adiposity, abnormal endogenous tissue storage, and cardiometabolic remodeling.
The Effects of Soil pH on Sodium Balance in the Red-Backed Salamander, Plethodon cinereus, and Three Other Terrestrial Salamanders

The osmoregulatory response of the red-backed salamander, Plethodon cinereus, to acidic substrates was studied. In the laboratory, animals exposed to low pH exhibited elevated sodium eflux rate constants. The efflux rate constant was elevated in two other plethodontid species under acidic conditions but was not elevated in efts of the red-spotted newt. Red-backed salamanders maintained on substrate of low pH for 14 d had reduced body sodium and body water levels and lost more mass than did salamanders maintained on substrate of higher pH. These results are consistent with earlier studies that have linked field distributions of P. cinereus and other salamanders to soil pH. However, in the field, body sodium levels of red-backed salamanders were not correlated with soil pH of the collection microsite, suggesting greater complexity of field than of laboratory conditions. Disruption of sodium balance by acidic conditions is well documented for aquatic amphibians but has not been demonstrated previously for terrestrial forms.
The Effect of the Cultivar and Harvest Term on the Yield and Nutritional Value of Rhubarb Juice

Since scientific interest in rhubarb from a culinary point of view is a relatively new issue, the aim of this study was to test five edible cultivars of Rheum rhabarbarum L. (‘Poncho’, ‘Canadian Red’, ‘Valentine’, ‘Red Champagne’, and ‘Victoria’) from a specific culinary perspective, i.e., processing into juice. Total yields (t/ha) were established in six harvests during a two-year field experiment. For juice production and subsequent laboratory analysis, rhubarb petioles from two different harvest terms were used (i.e., harvest term A (HTA) and harvest term B (HTB)). Analyses of total sugar, glucose, fructose, total soluble solids (TSS), total acidity, malic acid, and pH level were determined by FT-IR spectrophotometer. Total yields of petioles varied between 28.77 t/ha (‘Canadian Red’) and 45.58 t/ha (‘Red Champagne’) at a density of 11,000 pl/ha. ‘Red Champagne’ significantly (p < 0.05) reached the highest juice yield potential (85%) and the highest values of glucose (9.97 g/L), total soluble solids (4.37 g/L), and total sugars (54.96 g/L).
Psychological Impact of COVID-19 Outbreak on Families of Children with Autism Spectrum Disorder and Typically Developing Peers: An Online Survey

Background: When COVID-19 was declared as a pandemic, many countries imposed severe lockdowns that changed families’ routines and negatively impacted on parents’ and children’s mental health. Several studies on families with children with autism spectrum disorder (ASD) revealed that lockdown increased the difficulties faced by individuals with ASD, as well as parental distress. No studies have analyzed the interplay between parental distress, children’s emotional responses, and adaptive behaviors in children with ASD considering the period of the mandatory lockdown. Furthermore, we compared families with children on the spectrum and families with typically developing (TD) children in terms of their distress, children’s emotional responses, and behavioral adaptation. Methods: In this study, 120 parents of children aged 5–10 years (53 with ASD) participated. Results: In the four tested models, children’s positive and negative emotional responses mediated the impact of parental distress on children’s playing activities. In the ASD group, parents reported that their children expressed more positive emotions, but fewer playing activities, than TD children. Families with children on the spectrum reported greater behavioral problems during the lockdown and more parental distress. Conclusions: Our findings inform the interventions designed for parents to reduce distress and to develop coping strategies to better manage the caregiver–child relationship.
Risk Analysis of Needle Injury to the Long Thoracic Nerve during Ultrasound-Guided C7 Selective Nerve Root Block

Background and Objectives: Ultrasound (US)-guided cervical selective nerve root block (SNRB) is a widely used treatment for upper limb radicular pain. The long thoracic nerve (LTN) passes through the middle scalene muscle (MSM) at the C7 level. The needle trajectory of US-guided C7 SNRB pierces the MSM, therefore indicating a high probability of injury to the LTN. We aimed to identify the LTN and to investigate the risk of needle injury to the nerve during US-guided C7 SNRB. Materials and Methods: This retrospective observational study included 30 patients who underwent US-guided SNRB at the C7 level in a university hospital. We measured the maximal cross-sectional diameter (MCSD) of the LTN and cross-sectional area (CSA) of the C7 nerve root and assessed the injury risk of LTN during US-guided C7 SNRB by simulating the trajectory of the needle in the ultrasound image. Results: The LTN was detectable in all the cases, located inside and outside the MSM in 19 (63.3%) and 11 (36.7%) of cases, respectively. The LTN’s mean MCSD was 2.10 mm (SD 0.13), and the C7 root’s CSA was 10.78 mm2 (SD 1.05). The LTN location was within the simulated risk zone in 86.7% (26/30) of cases. Conclusion: Our findings suggest a high potential for LTN injury during US-guided C7 SNRB. The clear visualization of LTNs in the US images implies that US guidance may help avoid nerve damage and make the procedure safer. When performing US-guided C7 SNRB, physicians should take into consideration the location of the LTN.
Mechanical and Electrical Properties of Epoxy Composites Modified by Functionalized Multiwalled Carbon Nanotubes

This paper investigates the effect of multiwalled carbon nanotubes on the mechanical and electrical properties of epoxy resins and epoxy composites. The research concerns multiwalled carbon nanotubes obtained by catalytic chemical vapor deposition, subjected to purification processes and covalent functionalization by depositing functional groups on their surfaces. The study included the analysis of the change in DC resistivity, tensile strength, strain, and Young’s modulus with the addition of carbon nanotubes in the range of 0 to 2.5 wt. %. The effect of agents intended to increase the affinity of the nanomaterial to the polymer on the aforementioned properties was also investigated. The addition of functionalized multiwalled carbon nanotubes allowed us to obtain electrically conductive materials. For all materials, the percolation threshold was obtained with 1% addition of multiwalled carbon nanotubes, and filling the polymer with a higher content of carbon nanotubes increased its conductivity. The use of carbon nanotubes as polymer reinforcement allows higher values of tensile strength and a higher strain percentage to be achieved. In contrast, Young’s modulus values did not increase significantly, and higher nanofiller percentages resulted in a drastic decrease in the values of the abovementioned properties.
Robust LSPR Sensing Using Thermally Embedded Au Nanoparticles in Glass Substrates

The poor adhesion and chemical and thermal stability of plasmonic nanostructures deposited on solid surfaces are a hindrance to the longevity and long-term development of robust localized surface plasmon resonance (LSPR)-based systems. In this paper, we have deposited gold (Au) nanolayers with thicknesses above the percolation limit over glass substrates and have used a thermal annealing treatment at a temperature above the substrate’s glass transition temperature to promote the dewetting, recrystallization, and thermal embedding of Au nanoparticles (NPs). Due to the partial embedding in glass, the NPs were strongly adherent to the surface of the substrate and were able to resist to the commonly used cleaning procedures and mechanical adhesion tests alike. The reflectivity of the embedded nanostructures was studied and shown to be strongly dependent on the NP size/shape distributions and on the degree of NP embedding. Strong optical scattering bands with increasing width and redshifted LSPR peak position were observed with the Au content. Refractive index sensitivity (RIS) values between 150 and 360 nm/RIU (concerning LSPR band edge shift) or between 32 and 72 nm/RIU (concerning LSPR peak position shift) were obtained for the samples having narrower LSPR extinction bands. These robust LSPR sensors can be used following a simple excitation/detection scheme consisting of a reflectance measurement at a fixed angle and wavelength.
Granulomatous Inflammation in ANCA-Associated Vasculitis

ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163+ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites.
High-Throughput Chlorophyll and Carotenoid Profiling Reveals Positive Associations with Sugar and Apocarotenoid Volatile Content in Fruits of Tomato Varieties in Modern and Wild Accessions

Flavor and nutritional quality has been negatively impacted during the course of domestication and improvement of the cultivated tomato (Solanum lycopersicum). Recent emphasis on consumers has emphasized breeding strategies that focus on flavor-associated chemicals, including sugars, acids, and aroma compounds. Carotenoids indirectly affect flavor as precursors of aroma compounds, while chlorophylls contribute to sugar production through photosynthesis. However, the relationships between these pigments and flavor content are still unclear. In this study, we developed a simple and high-throughput method to quantify chlorophylls and carotenoids. This method was applied to over one hundred tomato varieties, including S. lycopersicum and its wild relatives (S. l. var. cerasiforme and S. pimpinellifolium), for quantification of these pigments in fruits. The results obtained by integrating data of the pigments, soluble solids, sugars, and aroma compounds indicate that (i) chlorophyll-abundant varieties have relatively higher sugar accumulations and (ii) prolycopene is associated with an abundance of linear carotenoid-derived aroma compounds in one of the orange-fruited varieties, “Dixie Golden Giant”. Our results suggest the importance of these pigments not only as components of fruit color but also as factors influencing flavor traits, such as sugars and aroma.
Asparagine: A Metabolite to Be Targeted in Cancers

Amino acids play central roles in cancer progression beyond their function as building blocks for protein synthesis. Thus, targeting amino acid acquisition and utilization has been proved to be therapeutically beneficial in various pre-clinical models. In this regard, depletion of circulating asparagine, a nonessential amino acid, by L-asparaginase has been used in treating pediatric acute lymphoblastic leukemia (ALL) for decades. Of interest, unlike most solid tumor cells, ALL cells lack the ability to synthesize their own asparagine de novo effectively. However, only until recently, growing evidence suggests that solid tumor cells strive to acquire adequate amounts of asparagine to support tumor progression. This process is subjected to the regulation at various levels, including oncogenic signal, tumor-niche interaction, intratumor heterogeneity and dietary accessibility. We will review the literature on L-asparaginase-based therapy as well as recent understanding of asparagine metabolism in solid tumor progression, with the hope of shedding light into a broader cancer therapeutic strategy by perturbing its acquisition and utilization.
Pitfalls in the Diagnosis of Nodular Lymphocyte Predominant Hodgkin Lymphoma: Variant Patterns, Borderlines and Mimics

Simple Summary Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma containing infrequent tumor cells (LP cells) in a background of non-neoplastic cells. Some cases of NLPHL can recur or progress to a more aggressive lymphoma, such as diffuse large B-cell lymphoma. Awareness of the different appearances of NLPHL and its overlap with other lymphomas are important for the appropriate diagnosis, classification and research. This article discusses the conceptual framework and guidelines for the diagnosis of NLPHL, and how NLPHL can be best separated from its mimics. Emerging data in the field point to genetic changes in LP cells that are shaped by immune mechanisms. In addition, non-neoplastic cells in the background of LP cells also appear to play an important role. Further investigation is necessary to fully understand the biology of NLPHL and personalize cancer care for patients affected by this lymphoma. Abstract Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) represents approximately 5% of Hodgkin lymphoma and typically affects children and young adults. Although the overall prognosis is favorable, variant growth patterns in NLPHL correlate with disease recurrence and progression to T-cell/histiocyte-rich large B-cell lymphoma or frank diffuse large B-cell lymphoma (DLBCL). The diagnostic boundary between NLPHL and DLBCL can be difficult to discern, especially in the presence of variant histologies. Both diagnoses are established using morphology and immunophenotype and share similarities, including the infrequent large tumor B-cells and the lymphocyte and histiocyte-rich microenvironment. NLPHL also shows overlap with other lymphomas, particularly, classic Hodgkin lymphoma and T-cell lymphomas. Similarly, there is overlap with non-neoplastic conditions, such as the progressive transformation of germinal centers. Given the significant clinical differences among these entities, it is imperative that NLPHL and its variants are carefully separated from other lymphomas and their mimics. In this article, the characteristic features of NLPHL and its diagnostic boundaries and pitfalls are discussed. The current understanding of genetic features and immune microenvironment will be addressed, such that a framework to better understand biological behavior and customize patient care is provided.
Single-Oocyte Gene Expression Suggests That Curcumin Can Protect the Ovarian Reserve by Regulating the PTEN-AKT-FOXO3a Pathway

A better understanding of the mechanism of primordial follicle activation will help us better understand the causes of premature ovarian insufficiency (POI), and will help us identify new drugs that can be applied to the clinical treatment of infertility. In this study, single oocytes were isolated from primordial and primary follicles, and were used for gene profiling with TaqMan array cards. Bioinformatics analysis was performed on the gene expression data, and Ingenuity Pathway Analysis was used to analyze and predict drugs that affect follicle activation. An ovarian in vitro culture system was used to verify the function of the drug candidates, and we found that curcumin maintains the ovarian reserve. Long-term treatment with 100 mg/kg curcumin improved the ovarian reserve indicators of AMH, FSH, and estradiol in aging mice. Mechanistic studies show that curcumin can affect the translocation of FOXO3, thereby inhibiting the PTEN-AKT-FOXO3a pathway and protecting primordial follicles from overactivation. These results suggest that curcumin is a potential drug for the treatment of POI patients and for fertility preservation.