Miracle-dz/UniFAR-FTUs huggingface dataset:
Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils

Background Myeloid dysfunction is an emerging hallmark of microenvironment changes occurring in multiple myeloma (MM). Our previous work showed that FcγRI/CD64 overexpression in neutrophils of newly diagnosed MM patients is associated to inferior outcomes, reduced oxidative bursts and phagocytosis, with an increased risk of bacterial infections. Pomalidomide is a novel immune-modulatory drug approved for relapsed/refractory patients (RRMM), with drug-related neutropenia as major limitation to treatment. Patients and methods Herein, we describe a prospective analysis of 51 consecutive RRMM patients treated with pomalidomide and dexamethasone (PomDex) from March 2015 through December 2016, associated with secondary prophylaxis with filgrastim (G-CSF) in case of neutrophil count <1500 cells/μL. Neutrophil function was investigated by flow cytometry, including the phagocytosis, oxidative bursts, and median fluorescence intensity of FcγRI-CD64. Controls included a group of newly diagnosed symptomatic MM (NDMM), asymptomatic (smoldering myeloma, MGUS) and healthy subjects referred to our Center in the same time-frame. Results Compared to controls, RRMM neutrophils had higher expression of FcγRI/CD64 and lower phagocytic activity and oxidative bursts. We maintained median leukocyte counts higher than 3.5 × 109/L for 6 cycles, and median neutrophil counts higher than 1.5 × 109/L, with only 6 (11%) patients developing grade 3–4 infections, without pomalidomide dose reduction. After 4 cycles of PomDex, FcγRI/CD64 was further increased in neutrophils, and phagocytic activity and oxidative bursts recovered independently from filgrastim exposure and the quality of hematological responses. Similarly, in NDMM patients, lenalidomide but not bortezomib upregulated FcγRI/CD64 expression, improving phagocytic activity and oxidative bursta as tested in vitro. Conclusions Our combined biological and clinical data provide new information on the ability of pomalidomide and lenalidomide to modulate the functional activity of neutrophils, despite their chronic activation due to FcγRI/CD64 overexpression.
Novel Biodegradable Composite of Calcium Phosphate Cement and the Collagen I Mimetic P-15 for Pedicle Screw Augmentation in Osteoporotic Bone

Osteoporotic vertebral fractures often necessitate fusion surgery, with high rates of implant failure. We present a novel bioactive composite of calcium phosphate cement (CPC) and the collagen I mimetic P-15 for pedicle screw augmentation in osteoporotic bone. Methods involved expression analysis of osteogenesis-related genes during osteoblastic differentiation by RT-PCR and immunostaining of osteopontin and Ca2+ deposits. Untreated and decalcified sheep vertebrae were utilized for linear pullout testing of pedicle screws. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA). Expression of ALPI II (p < 0.0001), osteopontin (p < 0.0001), RUNX2 (p < 0.0001), and osteocalcin (p < 0.0001) was upregulated after co-culture of MSC with CPC-P-15. BMD was decreased by 28.75% ± 2.6%. Pullout loads in untreated vertebrae were 1405 ± 6 N (p < 0.001) without augmentation, 2010 ± 168 N (p < 0.0001) after augmentation with CPC-P-15, and 2112 ± 98 N (p < 0.0001) with PMMA. In decalcified vertebrae, pullout loads were 828 ± 66 N (p < 0.0001) without augmentation, 1324 ± 712 N (p = 0.04) with PMMA, and 1252 ± 131 N (p < 0.0078) with CPC-P-15. CPC-P-15 induces osteoblastic differentiation of human MES and improves pullout resistance of pedicle screws in osteoporotic and non-osteoporotic bone.
The Impact of Repeated Attachment Priming on Paranoia, Mood and Help-Seeking Intentions in an Analogue Sample

Attachment security priming effects therapeutic change in people with depression and anxiety. Preliminary studies indicate that visualising secure attachment memories also reduces paranoia in non-clinical and clinical groups, probably due to a decrease in cognitive fusion. Benefits to clinical populations depend on the sustainability of these effects and the impact on help-seeking behaviours. The combination of paranoia and an insecure-avoidant attachment style is likely to be a particular barrier to help seeking. We used a longitudinal experimental design to test the impact of repeated attachment priming on paranoia, mood and help-seeking intentions and whether cognitive fusion mediates these effects. Seventy-nine people with high levels of non-clinical paranoia, aged 18–50 years (M = 20.53, SD = 4.57), were randomly assigned to a secure or insecure-avoidant priming condition. Participants rehearsed the visualisation prime on four consecutive days and were assessed on standardised measures of paranoia, positive and negative affect, help-seeking intentions and cognitive fusion. A series of mixed-model analyses of variance showed that security priming decreases paranoia, negative affect and cognitive fusion and increases positive affect and help seeking, compared to insecure-avoidant priming. Examining the impact of primed attachment (rather than measured attachment style) allows us to draw conclusions about the causal processes involved; mediation analyses showed indirect effects of the primes on paranoia and negative affect through cognitive fusion. With a growing understanding of (1) the impact of security priming on paranoia, affect and help-seeking behaviours, (2) causal mechanisms and (3) sustainability of effects, security priming may be developed into a viable intervention for clinical populations.
Bucky Ball Is a Novel Zebrafish Vasa ATPase Activator

Many multicellular organisms specify germ cells during early embryogenesis by the inheritance of ribonucleoprotein (RNP) granules known as germplasm. However, the role of complex interactions of RNP granules during germ cell specification remains elusive. This study characterizes the interaction of RNP granules, Buc, and zebrafish Vasa (zfVasa) during germ cell specification. We identify a novel zfVasa-binding motif (Buc-VBM) in Buc and a Buc-binding motif (zfVasa-BBM) in zfVasa. Moreover, we show that Buc and zfVasa directly bind in vitro and that this interaction is independent of the RNA. Our circular dichroism spectroscopy data reveal that the intrinsically disordered Buc-VBM peptide forms alpha-helices in the presence of the solvent trifluoroethanol. Intriguingly, we further demonstrate that Buc-VBM enhances zfVasa ATPase activity, thereby annotating the first biochemical function of Buc as a zfVasa ATPase activator. Collectively, these results propose a model in which the activity of zfVasa is a central regulator of primordial germ cell (PGC) formation and is tightly controlled by the germplasm organizer Buc.
Anti-Allergic and Anti-Inflammatory Effects of Neferine on RBL-2H3 Cells

Mast cells play a very important role in skin allergy and inflammation, including atopic dermatitis and psoriasis. In the past, it was found that neferine has anti-inflammatory and anti-aging effects on the skin, but its effect on mast cells has not yet been studied in detail. In this study, we used mast cells (RBL-2H3 cells) and mouse models to study the anti-allergic and inflammatory effects of neferine. First, we found that neferine inhibits the degranulation of mast cells and the expression of cytokines. In addition, we observed that when mast cells were stimulated by A23187/phorbol 12-myristate-13-acetate (PMA), the elevation of intracellular calcium was inhibited by neferine. The phosphorylation of the MAPK/NF-κB pathway is also reduced by pretreatment of neferine. The results of in vivo studies show that neferine can improve the appearance of dermatitis and mast cell infiltration caused by dinitrochlorobenzene (DNCB). Moreover, the expressions of barrier proteins in the skin are also restored. Finally, it was found that neferine can reduce the scratching behavior caused by compound 48/80. Taken together, our results indicate that neferine is a very good anti-allergic and anti-inflammatory natural product. Its effect on mast cells contributes to its pharmacological mechanism.
Impact of Feeding Syngenta Enogen® Feed Corn Compared to Control Corn in Different Diet Scenarios to Finishing Beef Cattle

Simple Summary A pooled statistical analysis of seven experiments and 200 pen observations was performed to determine the impact of feeding Enogen® corn compared to conventional corn grain in beef cattle finishing diets. When the corn was compared as dry-rolled corn in diets with lower inclusion rates of distiller grains plus solubles (less than 20% of the diet), feeding Enogen® corn improved the efficiency of beef production. That response was a 4.8% improvement due to feeding Enogen® in a corn-based diet without distiller grains but was 1.8% in diets with 18 to 20% distiller grains. Feeding Enogen® corn improved the efficiency by 4.5% in diets with another common byproduct, Sweet Bran®. Cattle performance was similar for Enogen® and conventional hybrids when processed and fed as high-moisture corn. Feeding Enogen® corn improves the gain efficiency of finishing cattle compared with conventional corn when fed as dry-rolled corn in diets with less than 20% distillers or diets that include Sweet Bran® feeds. Abstract The objective of this pooled statistical analysis was to evaluate Syngenta Enogen® Feed Corn (EFC) versus conventional corn (CON) when fed as either dry-rolled corn (DRC) or high-moisture corn (HMC) for effects on finishing beef cattle performance and carcass characteristics. Corns were evaluated in diets with byproduct inclusion rates of 0, 15, 18, 20, and 30% distiller grains or 25 and 35% Sweet Bran® (a commercial corn gluten feed product). Seven trials (n = 1856) consisting of 200 pen means comparing 26 diet treatments were analyzed using regression in a pooled analysis. When EFC was processed as DRC, the gain efficiency (G:F) improved compared with CON, but the response to feeding EFC decreased from a 4.8% improvement to no improvement compared to CON as distiller grains increased from 0 to 30%, but was significantly improved due to feeding EFC in diets with 0 to 18% distiller grains. Feeding cattle EFC as DRC increased the average daily gain (ADG) and G:F by 4.5% compared with CON corn in diets containing Sweet Bran®. No improvements in animal performance were observed when cattle were fed EFC compared to CON when processed as HMC in any situation. Feeding Enogen® corn improved the gain efficiency of finishing cattle compared with conventional corn when processed as dry-rolled corn and fed in diets with less than 20% distillers or diets that include Sweet Bran®.
How Do Tougher Plastics Ban Policies Modify People’s Usage of Plastic Bags? A Case Study in China

This study analyzes people’s bag usage before and after the introduction of the tougher 2021 plastics ban policies by counting the number of charged carrier bags, inner bags, old plastic bags, and reusable bags used by consumers at the exits of the investigated supermarkets in Shanghai, China. The results indicate positive effects of the tougher 2021 measures by observing significantly decreased usage of charged carrier bags by 46%, and significantly increased usage of old plastic bags and reusable bags by 117% and 36%, respectively. Policy execution loopholes are found in some supermarkets which do not follow the tougher plastics ban measures. Fortunately, the spill-over effects from tougher-measure-executing supermarkets fix this issue to some extent. Additionally, the tougher 2021 measures fail to be the most powerful impacting factor on people’s usage of each type of bag. To produce better plastics reducing results, other bag-targeted measures are necessary.
Neuron-Derived Extracellular Vesicles Modulate Microglia Activation and Function

Simple Summary In this study we investigated how neuron-derived extracellular vesicles (NDEVs) mediate neuroimmune regulation in primary cell culture systems. Rat cortical neurons released EVs that improved microglial survival and inhibited the expression of activation markers on microglia. Furthermore, NDEVs reduced the LPS-induced proinflammatory response and promoted an anti-inflammatory response. Thus, neurons critically regulate microglia activity and control inflammation via EV-mediated neuron–glia communication. Abstract Microglia act as the immune cells of the central nervous system (CNS). They play an important role in maintaining brain homeostasis but also in mediating neuroimmune responses to insult. The interactions between neurons and microglia represent a key process for neuroimmune regulation and subsequent effects on CNS integrity. However, the molecular mechanisms of neuron-glia communication in regulating microglia function are not fully understood. One recently described means of this intercellular communication is via nano-sized extracellular vesicles (EVs) that transfer a large diversity of molecules between neurons and microglia, such as proteins, lipids, and nucleic acids. To determine the effects of neuron-derived EVs (NDEVs) on microglia, NDEVs were isolated from the culture supernatant of rat cortical neurons. When NDEVs were added to primary cultured rat microglia, we found significantly improved microglia viability via inhibition of apoptosis. Additionally, application of NDEVs to cultured microglia also inhibited the expression of activation surface markers on microglia. Furthermore, NDEVs reduced the LPS-induced proinflammatory response in microglia according to reduced gene expression of proinflammatory cytokines (TNF-α, IL-6, MCP-1) and iNOS, but increased expression of the anti-inflammatory cytokine, IL-10. These findings support that neurons critically regulate microglia activity and control inflammation via EV-mediated neuron–glia communication. (Supported by R21AA025563 and R01AA025591).
Tutorial: Guidelines for Single-Cell RT-qPCR

Reverse transcription quantitative PCR (RT-qPCR) has delivered significant insights in understanding the gene expression landscape. Thanks to its precision, sensitivity, flexibility, and cost effectiveness, RT-qPCR has also found utility in advanced single-cell analysis. Single-cell RT-qPCR now represents a well-established method, suitable for an efficient screening prior to single-cell RNA sequencing (scRNA-Seq) experiments, or, oppositely, for validation of hypotheses formulated from high-throughput approaches. Here, we aim to provide a comprehensive summary of the scRT-qPCR method by discussing the limitations of single-cell collection methods, describing the importance of reverse transcription, providing recommendations for the preamplification and primer design, and summarizing essential data processing steps. With the detailed protocol attached in the appendix, this tutorial provides a set of guidelines that allow any researcher to perform scRT-qPCR measurements of the highest standard.
Technology Acceptance and Leadership 4.0: A Quali-Quantitative Study

With the rapid advancement of Industry 4.0, new technologies are changing the nature of work and organizations. Nevertheless, technology acceptance is still an open issue and research, and practice interventions should investigate its antecedents and implement actions in order to reduce the risks of resistance and foster acceptance and effective usage of the new tools and systems. This quali-quantitative study was aimed at exploring perceptions about Industry 4.0 and its transformations and investigating job antecedents of technology acceptance. Whilst not many studies in the literature on technology acceptance have considered workers’ well-being, in this study, its association with work engagement has also been examined. The qualitative study used focus groups to collect perceptions of 14 key roles in a company that was implementing Industry 4.0. In the same company, the quantitative study involved 263 employees who filled in a questionnaire. The results confirmed that both job resources, namely supervisor support and role clarity, were antecedents of technology acceptance, which, in turn, was associated with work engagement. This study provides useful suggestions for interventions aimed at foster technology acceptance and workers’ well-being in companies that are facing Industry 4.0 transformations. Particularly, investments in both leadership 4.0 development and communication programs are essential.
Assessment of Arabian Gulf Seaweeds from Kuwait as Sources of Nutritionally Important Polyunsaturated Fatty Acids (PUFAs)

The fatty acid (FA) compositions of ten seaweeds representative of Chlorophyta, Rhodophyta, and Ochrophyta from Kuwait in the Arabian Gulf region were determined and are discussed in the context of their potential nutritional perspectives for seaweed valorization. All the seaweeds had higher saturated fatty acid (SFA) and lower monounsaturated (MUFA) and polyunsaturated fatty acid (PUFA) contents than those typical of tropical environments. Palmitic, myristic, stearic, oleic, linoleic, α-linolenic, and stearidonic acids were the major FAs detected. Arachidonic, eicosapentaenoic, and docosahexaenoic acids were detected in minor amounts. Conserved fatty acid patterns revealed phylogenetic relationships among phyla, classes, and orders matching the molecular phylogenies at higher taxonomic ranks. Hierarchical clustering analyses clearly segregated different seaweeds (except Codium papillatum and Iyengaria stellata) into distinct groups based on their FA signatures. All but one species (Chondria sp.) had health-beneficial n6/n3 PUFAs (0.33:1–2.94:1) and atherogenic (0.80–2.52) and thrombogenic indices (0.61–5.17). However, low PUFA/SFA contents in most of the species (except Ulva spp.) may limit their utilization in the formulation of PUFA-rich functional foods. Ulva spp. had substantially high PUFAs with PUFA/SFA > 0.4, n6/n3 (0.33–0.66) and atherogenic (0.80–1.15) and thrombogenic indices (0.49–0.72), providing substantial potential for their utilization in food and feed applications.
Effects of Individual Discount Rate and Uncertainty Perception on Compliance with Containment Measures during the COVID-19 Pandemic

Anti-contagion measures restricting individual freedom, such as social distancing and wearing a mask, are crucial to contain the COVID-19 pandemic. Decision-making patterns and attitudes about uncertainty can highly influence the adherence to these restrictive measures. Here we investigated the relationship between risky behavior and individual preferences for immediate vs. delayed reward, as indexed by temporal discounting (TD), as well as the association between these measures and confidence in the future, perceived risk and confidence in the containment measures. These measures were collected through an online survey administered on 353 participants at the end of the more restrictive phase of the first Italian lockdown. The results showed an unexpected inverse relationship between the individual pattern of choice preferences and risky behavior, with an overall greater adherence to containment measures in more discounter participants. These findings were interpreted in terms of a reframing process in which behaviors aimed at protecting oneself from contagion turn into immediate gains rather than losses. Interestingly, an excessive confidence in a better future was correlated with a higher tendency to assume risky behavior, thereby highlighting the downside of an overly and blindly optimistic view.
The Modulation of Gut Microbiota Composition in the Pathophysiology of Gestational Diabetes Mellitus: A Systematic Review

Simple Summary Recent studies have placed a great deal of emphasis on the importance of the microbiome, especially the link between the alteration of gut microbiota and multiple associated diseases. Gut microbiota changes in pregnancy have a significant impact on metabolic function and may contribute to gestational diabetes mellitus (GDM). Although GDM carries long-term health risks that affect women, there are also significant short- and severe long-term consequences for the offspring. Regardless, there is a notable lack of research focusing on the impact of prominent microorganisms involved in the development of GDM. A comprehensive review was conducted to gather relevant data on the types of microorganisms that have been associated with GDM. The review found that certain microorganisms impact the onset and progression of GDM during pregnancy. Several bacterial strains associated with GDM are influenced by a diet high in fat and low in fiber. Therefore, integrating the idea of a microbiome-based individualized dietary intervention into gestational diabetes management may be incredibly beneficial. Abstract General gut microbial dysbiosis in diabetes mellitus, including gestational diabetes mellitus (GDM), has been reported in a large body of literature. However, evidence investigating the association between specific taxonomic classes and GDM is lacking. Thus, we performed a systematic review of peer-reviewed observational studies and trials conducted among women with GDM within the last ten years using standard methodology. The National Institutes of Health (NIH) quality assessment tools were used to assess the quality of the included studies. Fourteen studies investigating microbial interactions with GDM were found to be relevant and included in this review. The synthesis of literature findings demonstrates that Bacteroidetes, Proteobacteria, Firmicutes, and Actinobacteria phyla, such as Desulfovibrio, Ruminococcaceae, P. distasonis, Enterobacteriaceae, Collinsella, and Prevotella, were positively associated with GDM. In contrast, Bifidobacterium and Faecalibacterium, which produce butyrate, are negatively associated with GDM. These bacteria were associated with inflammation, adiposity, and glucose intolerance in women with GDM. Lack of good diet management demonstrated the alteration of gut microbiota and its impact on GDM glucose homeostasis. The majority of the studies were of good quality. Therefore, there is great potential to incorporate personalized medicine targeting microbiome modulation through dietary intervention in the management of GDM.
Quercetin Completely Ameliorates Hypoxia–Reoxygenation-Induced Pathophysiology Severity in NY1DD Transgenic Sickle Mice: Intrinsic Mild Steady State Pathophysiology of the Disease in NY1DD Is Also Reversed

The vaso-occlusive crisis (VOC) is a major complication of sickle cell disease (SCD); thus, strategies to ameliorate vaso-occlusive episodes are greatly needed. We evaluated the therapeutic benefits of quercetin in a SCD transgenic sickle mouse model. This disease model exhibited very mild disease pathophysiology in the steady state. The severity of the disease in the NY1DD mouse was amplified by subjecting mice to 18 h of hypoxia followed by 3 h of reoxygenation. Quercetin (200 mg/kg body weight) administered to hypoxia challenged NY1DD mice in a single intraperitoneal (i.p.) dose at the onset of reoxygenation completely ameliorated all hypoxia reoxygenation (H/R)-induced pathophysiology. Additionally, it ameliorated the mild intrinsic steady state pathophysiology. These results are comparable with those seen with semisynthetic supra plasma expanders. In control mice, C57BL/6J, hypoxia reoxygenation-induced vaso-occlusion was at significantly lower levels than in NY1DD mice, reflecting the role of sickle hemoglobin (HbS) in inducing vaso-occlusion; however, the therapeutic benefits from quercetin were significantly muted. We suggest that these findings represent a unique genotype of the NY1DD mice, i.e., the presence of high oxygen affinity red blood cells (RBCs) with chimeric HbS, composed of mouse α-chain and human βS-chain, as well as human α-chain and mouse β-chain (besides HbS). The anti-anemia therapeutic benefits from high oxygen affinity RBCs in these mice exert disease severity modifications that synergize with the therapeutic benefits of quercetin. Combining the therapeutic benefits of high oxygen affinity RBCs generated in situ by chemical or genetic manipulation with the therapeutic benefits of antiadhesive therapies is a novel approach to treat sickle cell patients with severe pathophysiology.