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Hematopoietic stem cells (HSCs) drive cellular turnover in the hematopoietic system by balancing self-renewal and differentiation. In the adult bone marrow (BM), these cells are regulated by a complex cellular microenvironment known as "niche," which involves dynamic interactions between diverse cellular and non-cellular elements. During blood cell maturation, lineage branching is guided by clusters of genes that interact or counteract each other, forming complex networks of lineage-specific transcription factors. Disruptions in these networks can lead to obstacles in differentiation, lineage reprogramming, and ultimately malignant transformation, including acute myeloid leukemia (AML). Zinc Finger Protein 521 (Znf521/Zfp521), a conserved transcription factor enriched in HSCs in both human and murine hematopoiesis, plays a pivotal role in regulating HSC self-renewal and differentiation. Its enforced expression preserves progenitor cell activity, while inhibition promotes differentiation toward the lymphoid and myeloid lineages. Transcriptomic analysis of human AML patient samples has revealed upregulation of ZNF521 in AMLs with the t(9;11) fusion gene MLL-AF9. In vitro studies have shown that ZNF521 collaborates with MLL-AF9 to enhance the growth of transformed leukemic cells, increase colony formation, and activate MLL target genes. Conversely, inhibition of ZNF521 using short-hairpin RNA (shRNA) results in decreased leukemia proliferation, reduced colony formation, and induction of cell cycle arrest in MLL-rearranged AML cell lines. In vivo experiments have demonstrated that mZFP521-deficient mice transduced with MLL-AF9 experience a delay in leukemia development. This review provides an overview of the regulatory network involving ZNF521, which plays a crucial role in controlling both HSC self-renewal and differentiation pathways. Furthermore, we examine the impact of ZNF521 on the leukemic phenotype and consider it a potential marker for MLL-AF9 + AML., Competing Interests: Declarations. Ethics approval: Not applicable. Informed consent: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Dendritic cells (DC) are professional antigen-presenting cells involved in promoting and controlling immune responses. Different subsets of DC, named tolerogenic (tol)DC, play a critical role in the maintenance of tissue homeostasis and in fostering tolerance. These unique skills make tolDC especially attractive for strategies aimed at re-establishing/inducing tolerance in immune-mediated conditions. The generation of potent tolDC in vitro from peripheral blood monocytes has seen remarkable advancements. TolDC modulate T cell dynamics by favoring regulatory T cells (Tregs) and curbing effector/pathogenic T cells. Among the several methods developed for in vitro tolDC generation, IL-10 conditioning has been proven to be the most efficient, as IL-10-modulated tolDC were demonstrated to promote Tregs with the strongest suppressive activities. Investigating the molecular, metabolic, and functional profiles of tolDC uncovers essential pathways that facilitate their immunoregulatory functions. This Review provides an overview of current knowledge on the role of tolDC in health and disease, focusing on IL-10 production, functional characterization of in vitro generated tolDC, molecular and metabolic changes occurring in tolDC induced by tolerogenic agents, clinical applications of tolDC-based therapy, and finally new perspectives in the generation of effective tolDC., (© 2024 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Abstract: Immunosuppression, commonly accompanied by persistent inflammation, is a key feature in the later phase of sepsis. However, the pathophysiological mechanisms underlying this phenomenon remain unclear. Dendritic cells (DCs), specifically tolerogenic DCs (tolDCs), play a crucial role in this process by regulating immune responses through inducing T cell anergy and releasing anti-inflammatory cytokines. Nevertheless, the existing cell models are inadequate for investigating tolDCs during the immunosuppressive phase of sepsis. Therefore, this study aimed to develop a novel in vitro model to generate tolDCs under chronic inflammatory conditions. We have successfully generated tolDCs by exposing them to sublethal lipopolysaccharide (LPS) for 72 h while preserving cell viability. Considering that IL-10-induced tolDCs (IL-10-tolDCs) are well-established models, we compared the immunological tolerance between LPS-tolDCs and IL-10-tolDCs. Our findings indicated that both LPS-tolDCs and IL-10-tolDCs exhibited reduced expression of maturation markers, whereas their levels of inhibitory markers were elevated. Furthermore, the immunoregulatory activities of LPS-tolDCs and IL-10-tolDCs were found to be comparable. These dysfunctions include impaired antigen presenting capacity and suppression of T cell activation, proliferation, and differentiation. Notably, compared with IL-10-tolDCs, LPS-tolDCs showed a reduced response in maturation and cytokine production upon stimulation, indicating their potential as a better model for research. Overall, in comparison with IL-10-tolDCs, our data suggest that the immunological dysfunctions shown in LPS-tolDCs could more effectively elucidate the increased susceptibility to secondary infections during sepsis. Consequently, LPS-tolDCs have emerged as promising therapeutic targets for ameliorating the immunosuppressed state in septic patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

To prevent losses before consumption due to the rapid ripening of bananas, turning unripe bananas into flour and using it in bakery products can both enhance the functional properties of the product and transform bananas into a high-value product. In this study, it is aimed to enhance the functional properties of banana flour through fermentation, thereby investigating its potential use in the production of healthy snack biscuits which are widely consumed, especially by children and busy people. Different proportions (0%, 15%, and 30%) of unripe banana flour (UBF) and fermented unripe banana flour (FUBF) were added to biscuits, evaluating their impact on physical (color, diameter, thickness, spread ratio), textural (hardness), and functional properties (total phenolic content, antioxidant activity, dietary fiber, glycemic index). The effect of FUBF on biscuit spread ratio compared to UBF was positive (p < 0.05). The addition of UBF or FUBF significantly increased total phenolic content (TPC) and antioxidant activity (p < 0.05), with the highest TPC (1167.88 mg GAE/kg) observed in biscuits containing 30% FUBF (p < 0.05). Fermentation showed no significant effect on antioxidant activity of samples (p > 0.05). The glycemic index (GI) values were notably high across all samples, with the control at 78.59 and the 30% FUBF sample at 72.74 (p < 0.05), indicating all samples fell into the high GI food category. Biscuit hardness decreased significantly with UBF or FUBF addition (p < 0.05), while fermentation had no significant impact on hardness (p > 0.05). This study underscores the potential of UBF or FUBF to contribute to healthier snack options with improved functional characteristics., Competing Interests: Declarations Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The public release of ChatGPT in November 2022 sparked a boom and public interest in generative artificial intelligence (AI) that has led to journals and journal families hastily releasing generative AI policies, ranging from asking authors for acknowledgement or declaration to the outright banning of use., Results: Here, we briefly discuss the basics of machine learning, generative AI, and how it will affect scientific publishing. We focus especially on potential risks and benefits to the scientific community as a whole and journals specifically., Conclusion: While the concerns of editors, for example about manufactured studies, are valid, some recently implemented or suggested policies will not be sustainable in the long run. The quality of generated text and code is quickly becoming so high that it will not only be impossible to detect the use of generative AI but would also mean taking a powerful tool away from researchers that can make their life easier every day., Significance: We discuss the history and current state of AI and highlight its relevance for medical publishing and pain research. We provide guidance on how to act now to increase good scientific practice in the world of ChatGPT and call for a task force focusing on improving publishing pain research with use of generative AI., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Background: The cause of food allergy (FA) is still a mystery. Telomerases are involved in the regulation of immune responses. This study aims to gain an understanding of the contribution of telomerase reverse transcriptase (TERT) to the pathogenesis of FA., Methods: A murine FA model was established with ovalbumin as the specific antigen. The role of TERT in regulating dendritic cell (DC) immune tolerogenic functions was evaluated in this murine model., Results: We observed that the Tert promoter was at demethylation status and the Tert expression was elevated in DCs of FA mice. The Tert expression in DCs had a positive correlation with the FA response. TERT prevented the induction of Il10 expression in DCs. The immune tolerogenic functions of DCs were diminished by TERT. The immune tolerogenic functions of DC were restored by CpG by boosting the Tert promoter methylation. Administration of CpG promoted the therapeutic effects of allergen specific immunotherapy in FA mice., Conclusions: Low levels of Il10 expression and high levels of Tert expression were observed in intestinal DCs of FA mice. CpG exposure restored the expression of Il10 and increased the therapeutic benefits of allergen-specific immunotherapy., Competing Interests: Declarations Conflict of interest None to declare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: During total arch replacement (TAR) using frozen elephant trunk (FET) technique with Frozenix for true thoracic aortic aneurysm (tTAA), oversized FET tends to be chosen similar to the endovascular devise selection. However, the oversized FET is considered a risk factor for intimal injury. The appropriate size selection of FET remains insufficiently understood., Methods: Between October 2014 and March 2022, a total of 49 patients underwent TAR using Frozenix for tTAA. Out of 49 patients, four patients planned to staged surgery were excluded, 19 patients were operated on with an undersized Frozenix compared with the descending aorta (undersized FET group) and in 26 patients an equal or oversized Frozenix was used (oversized FET group). Clinical outcomes and postoperative diameter changes were investigated., Results: In-hospital mortality was 0%. The mean diameter of Frozenix and the descending aorta was 30.7 mm and 28.8 mm, respectively, in the oversized FET group, and 26.7 mm and 30.1 mm in the undersized FET group. Postoperative computed tomography (CT) demonstrated no endoleaks not only in the oversized FET group but also in the undersized FET group. CT also revealed that undersized FET had expanded more than the original diameter in all cases except for two, with an average of 2.47 ± 1.53 mm. Additionally, the descending aorta covered with Frozenix shrank in 10 patients (53%). Postoperative adverse aortic events were not observed., Conclusions: Undersized Frozenix tightly fit the descending aorta and resulted in complete sealing without endoleaks. Oversized FET is not strictly necessary considering the size-related adverse complications., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Wastewater-based epidemiology, during the COVID-19 pandemic years, has been applied as a complementary approach, worldwide, for tracking SARS-CoV-2 virus into the community and used as an early warning of the prevalence of COVID-19 infection. The present study presents the results of the 2-year surveillance project, in the city of Patras, Greece. The purpose of the study was to monitor SARS-CoV-2 and implement WBE as an early warning method of monitoring Public Health impact. The presence of SARS-CoV-2 was determined and quantified in 310 samples using RT-qPCR assays. For the years 2022 and 2023, 93.5% and 78.7% of samples were found positive, respectively. Comparison of detection methods have been conducted to select the method with the highest recovery of the viral load. A seasonal variation of the virus was recorded, showing a recession in summer months confirming the country's epidemiological data as indicated by positive correlation of wastewater viral load with registered cases of COVID-19 infections during these years (p < 0.05) and moreover sealed with a significant negative correlation observed with Daily Average (p < 0.01) and Daily Maximum Temperature (p < 0.01). More research was carried out to elucidate a possible association of physicochemical characteristics of wastewater with viral load showing positive correlation with Chlorides (p < 0.01) advocating possible increased use of chlorine-based disinfectants and Electrical Conductivity (p < 0.01) indicates that wastewater during periods of increased infections is more heavily loaded with ions from chemical and biological pollutants. No correlation found with rainfall and physicochemical indicators, such as COD, BOD 5 , Total Phosphorus, Total Nitrogen, and Total Suspended Solids. According to the findings, WBE represents a useful tool in the management of epidemics based on an environmental approach and it can also shed light on the interacting parameters that capture Public Health since any infections that may lead to epidemics lead to a parallel change in the use of pharmaceuticals, antimicrobials, disinfectants, and microbial load in urban wastewater., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

With rising consumer awareness of health and wellness, the demand for enhanced food safety is rapidly increasing. The generation of chemical contaminants during the thermal processing of food materials, including polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, and acrylamide happens every day in every kitchen all around the world. Unlike extraneous chemical contaminants (e.g., pesticides, herbicides, and chemical fertilizers), these endogenic chemical contaminants occur during the cooking process and cannot be removed before consumption. Therefore, much effort has been invested in searching for ways to reduce such thermally induced chemical contaminants. Recently, the addition of bioactive compounds has been found to be effective and promising. However, no systematic review of this practical science has been made yet. This review aims to summarize the latest applications of bioactive compounds for the control of chemical contaminants during food thermal processing. The underlying generation mechanisms and the toxic effects of these chemical contaminants are discussed in depth to reveal how and why they are suppressed by the addition of certain bioactive ingredients. Examples of specific bioactive compounds, such as phenolic compounds and organic acids, as well as their application scenarios, are outlined. In the end, outlooks and expectations for future development are provided based on a comprehensive summary and reflection of references., (© 2024 Institute of Food Technologists®.)

Some attorneys and legal scholars argue that medicalizing transgender plaintiffs (i.e., introducing plaintiff diagnoses and/or medical procedures) in discrimination cases will enhance favorable plaintiff outcomes. Research and theory linking biological essentialism (i.e., believing social groups reflect biologically-rooted, stable categories) to prejudice, however, suggests that medicalizing transgender plaintiffs might not help them win cases and might instead backfire and harm their case outcomes. To test these competing hypotheses, we coded all published cases involving alleged transgender discrimination (N = 124) from 1974 to 2021. Importantly, we addressed limitations of existing research that narrowly defined transgender plaintiff medicalization exclusively via diagnosis by documenting various other forms of medicalization beyond diagnosis. Contrary to legal scholars' claims and attorney intuitions, medicalization did not predict favorable outcomes for transgender plaintiffs. In fact, various forms of medicalization beyond diagnosis predicted negative plaintiff case outcomes. We discuss the implications of this research for informing scientific theory and legal practice., (© 2024 The Author(s). Behavioral Sciences & The Law published by John Wiley & Sons Ltd.)

The E2A-PBX1 gene fusion is a common translocation in B-cell acute lymphoblastic leukaemia. Patients harbouring the E2A-PBX1 fusion gene typically exhibit an intermediate prognosis. Furthermore, minimal residual disease has unsatisfactory prognostic value in E2A-PBX1 B-cell acute lymphoblastic leukaemia. However, the mechanism of E2A-PBX1 in the occurrence and progression of B-cell acute lymphoblastic leukaemia is not well understood. Here, we mainly review the roles of E2A and PBX1 in the differentiation and development of B lymphocytes, the mechanism of E2A-PBX1 gene fusion in B-cell acute lymphoblastic leukaemia, and the potential therapeutic approaches., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To determine the relation between pelvic symmetry, as measured by the cross-measurement technique, and patient-reported outcome measures (PROMs) in terms of functional status and health-related quality of life., Methods: In this prospective cohort study, X and Y measurements were taken according to the cross-measurement technique on AP radiographs of patients who were treated for an unstable pelvic ring injury in a level-1 trauma center. Patients completed PROMs at the time of admission (recalled pre-injury score) and one year following their injury, reporting their functional status with the Short Musculoskeletal Function Assessment (SMFA-NL), specifically the lower extremity dysfunction (LED), problems with daily activities (PDA) and mental and emotional problems (MEP) subscales, and quality of life with EuroQol-5D (EQ-5D). Subgroup analyses were also performed. PROMs were used to analyze the relation between pelvic symmetry and patient-reported outcome, using Spearman's Rank correlation coefficients., Results: A total of 130 patients (mean age 58 (SD18) years) with an unstable pelvic ring injury were included, of which 95 (73%) sustained type-B injuries and 35 (27%) type-C injuries. Sixty-three (49%) patients were treated operatively. The median pelvic symmetry ratio was 1.01 (IQR: 0.05). Weak or no correlations were found between the pelvic symmetry scores and the outcome measurements (Spearman's correlation coefficients: LED r = 0.09; PDA r = 0.11; MEP r=-0.02; and EQ-5D r=-0.08). Subgroup analyses revealed no correlations., Conclusions: No significant relation was found between pelvic symmetry, measured radiologically, and functional status and health-related quality of life, one year following an unstable pelvic ring injury., (© 2024. The Author(s).)

Purpose: Traditional anesthesia for video-assisted thoracoscopy (VATS) such as double-lumen tracheal intubation (DLT) and one-lung ventilation (OLV), may lead to post-operative pulmonary complications (PPCs). Non-intubation VATS (NIVATS) is an anesthetic technique that avoided DLT and OLV, maybe avoiding the PPCs. So we hypothesized that NIVATS would non-inferiority to intubation VATS (IVATS) in the risk of developing PPCs and some safety indicators., Methods: This study is a randomised, controlled, double-blind, non-inferiority trial, 120 patients were randomly assigned to the NIVATS group and IVATS group according to 1:1. The primary outcome was the incidence of PPCs with a pre-defined non-inferiority margin of 10%. The second outcome was the safety indicators, including the incidence of cough/body movement, hypoxemia, malignant arrhythmia, regurgitation and aspiration, and transferring to endobronchial intubation intraoperatively (The malignant arrhythmia was defined as an arrhythmia that caused hemodynamic disturbances in a short period of time, resulting in persistent hypotension or even cardiac arrest in the patient)., Results: There was no significant difference in demographic indicators such as gender and age between the two groups. The incidence of PPCs in the NIVATS group was non-inferior to that in the IVATS group (1.67% vs. 3.33%, absolute difference: - 1.67%; 95%CI - 7.25 to 3.91). In additionan, no significant differences were found between the two groups for the incidence of cough/body movement (10.00% vs. 11.67%, p = 0.77), the incidence of hypoxemia (25% vs. 18.33%, p = 0.38), the incidence of malignant arrhythmia (1.67% vs. 6.67%, p = 0.36), the incidence of regurgitation and aspiration (0% vs. 0%, p > 0.999) and the incidence of transferring to endobronchial intubation intraoperatively (0% vs. 0%, p > 0.999)., Conclusion: We conclude that when using the non-intubation anesthesia for VATS, the incidence of PPCs was not inferior to intubation anesthesia. Furthermore, NIVATS had little effect on perioperative safety., (© 2024. The Author(s).)

This study aims to investigate how inert gas affects the partial pressure of alveolar and venous blood using a fast and accurate operator splitting method (OSM). Unlike previous complex methods, such as the finite element method (FEM), OSM effectively separates governing equations into smaller sub-problems, facilitating a better understanding of inert gas transport and exchange between blood capillaries and surrounding tissue. The governing equations were discretized with a fully implicit finite difference method (FDM), which enables the use of larger time steps. The model employed partial differential equations, considering convection-diffusion in blood and only diffusion in tissue. The study explores the impact of initial arterial pressure, breathing frequency, blood flow velocity, solubility, and diffusivity on the partial pressure of inert gas in blood and tissue. Additionally, the effects of anesthetic inert gas and oxygen on venous blood partial pressure were analyzed. Simulation results demonstrate that the high solubility and diffusivity of anesthetic inert gas lead to its prolonged presence in blood and tissue, resulting in lower partial pressure in venous blood. These findings enhance our understanding of inert gas interaction with alveolar/venous blood, with potential implications for medical diagnostics and therapies., (© 2024 John Wiley & Sons Ltd.)

Vitamin C (ascorbic acid) is a potent antioxidant and a cofactor for various enzymes including histone demethylases and methylcytosine dioxygenases. Vitamin C also exerts direct cytotoxicity toward selected tumor cells including colorectal carcinoma. Moreover, vitamin C has been shown to impact immune cell differentiation at various levels including maturation and/or functionality of T cells and their progenitors, dendritic cells, B cells, and NK cells. γδ T cells have recently attracted great interest as effector cells for cell-based cancer immunotherapy, due to their HLA-independent recognition of a large variety of tumor cells. While γδ T cells can thus be also applied as an allogeneic off-the-shelf product, it is obvious that the effector function of γδ T cells needs to be optimized to ensure the best possible clinical efficacy. Here we review the immunomodulatory mechanisms of vitamin C with a special focus on how vitamin C enhances the effector function of γδ T cells. We also discuss future directions of how vitamin C can be used in the clinical setting to boost the efficacy of adoptive cell therapies., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)

Background: Diminished muscle protein synthesis in cirrhosis leads to reduced strength and mass, impacting daily activities and overall quality of life., Aims: This study aimed to examine the effectiveness of exercise intervention in body composition, exercise capacity, fatigue, and quality of life in patients with liver cirrhosis., Methods: A systematic search of medical databases, including PubMed, Embase, Cochrane, and CINAHL, was executed from their inception to November 2022. The inclusion criteria were randomized controlled trials comparing exercise interventions with a control group that did not receive exercise interventions., Results: From the initially identified 2,565 articles, eight studies with a total of 220 patients were eligible for inclusion in this meta-analysis. According to the meta-analysis, exercise significantly improved the six-minute walk distance (6MWD) by 68.93 m (95% CI 14.29-123.57) compared to the control group. Furthermore, the subgroup analysis revealed that combing exercise with amino acid supplementation had a greater positive effect on the 6MWD (MD = 144.72, 95% CI 87.44-202.01). Exercise also significantly increased thigh circumference (MD = 1.26, 95% CI 0.12-2.39) and the thigh ultrasound average compression index (MD = 0.07, 95% CI 0.00-0.14). Moreover, exercise significantly decreased fatigue levels by 0.7 points in patients with liver cirrhosis (95% CI 0.38-1.03). However, no significant effects were observed on body mass index (BMI), fat mass, fat-free mass, and quality of life., Conclusions: Exercise can improve exercise capacity, thigh muscle thickness, and fatigue in patients with cirrhosis, but it does not have a significant impact on fat mass, BMI, or quality of life., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multiple myeloma (MM) is the second most common haematological malignancy and is characterized by a clonal proliferation of neoplastic plasma cells within the bone marrow. MM is the most frequent cancer involving the skeleton, causing osteolytic lesions, bone pain and pathological fractures that dramatically decrease MM patients' quality of life and survival. MM bone disease (MBD) results from uncoupling of bone remodelling in which excessive bone resorption is not compensated by new bone formation, due to a persistent suppression of osteoblast activity. Current management of MBD includes antiresorptive agents, bisphosphonates and denosumab, that are only partially effective due to their inability to repair the existing lesions. Thus, research into agents that prevent bone destruction and more importantly repair existing lesions by inducing new bone formation is essential. This review discusses the mechanisms regulating the uncoupled bone remodelling in MM and summarizes current advances in the treatment of MBD. LINKED ARTICLES: This article is part of a themed issue on The molecular pharmacology of bone and cancer-related bone diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc., (© 2019 The British Pharmacological Society.)

Multiple myeloma (MM) is tightly dependent on inflammatory bone marrow microenvironment. IL-17 producing CD4+ T cells (Th17) sustain MM cells growth and osteoclasts-dependent bone damage. In turn, Th17 differentiation relies on inflammatory stimuli. Here, we investigated the role of miR-21 in Th17-mediated MM tumor growth and bone disease. We found that early inhibition of miR-21 in naive T cells (miR-21i-T cells) impaired Th17 differentiation in vitro and abrogated Th17-mediated MM cell proliferation and osteoclasts activity. We validated these findings in NOD/SCID-g-NULL mice, intratibially injected with miR-21i-T cells and MM cells. A Pairwise RNAseq and proteome/phosphoproteome analysis in Th17 cells demonstrated that miR-21 inhibition led to upregulation of STAT-1/-5a-5b, STAT-3 impairment and redirection of Th17 to Th1/Th2 like activated/polarized cells. Our findings disclose the role of miR-21 in pathogenic Th17 activity and open the avenue to the design of miR-21-targeting strategies to counteract microenvironment dependence of MM growth and bone disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease globally, with a fast-growing prevalence. The etiology of PD exhibits a multifactorial complex nature and remains challenging. Herein, we described clinical, molecular, and integrative bioinformatics findings from a Brazilian female affected by Early-Onset PD (EOPD) harboring a recurrent homozygous pathogenic deletion in the parkin RBR E3 ubiquitin protein ligase gene (PRKN; NM&#95;004562.3:c.155delA; p.Asn52Metfs*29; rs754809877), along with a novel heterozygous variant in the synaptojanin 1 gene (SYNJ1; NM&#95;003895.3:c.62G > T; p.Cys21Phe; rs1486511197) found by Whole Exome Sequencing. Uncommon or unreported PRKN-related clinical features in the patient include cognitive decline, auditory and visual hallucinations, REM sleep disorder, and depression, previously observed in SYNJ1-related conditions. Moreover, PRKN interacts with endophilin A1, which is a major binding partner of SYNJ1. This protein plays a pivotal role in regulating the dynamics of synaptic vesicles, particularly in the context of endocytosis and recycling processes. Altogether, our comprehensive analyses underscore a potential synergistic effect between the PRKN and SYNJ1 variants over the pathogenesis of EOPD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Several pieces of evidence suggest immune dysregulation could trigger the onset and modulate sequelae of new onset refractory status epilepticus (NORSE), including its subtype with prior fever known as febrile infection-related epilepsy syndrome (FIRES). Consensus-driven recommendations have been established to guide the initiation of first- and second-line immunotherapies in these patients. Here, we review the literature to date on second-line immunotherapy for NORSE/FIRES, presenting results from 28 case reports and series describing the use of anakinra, tocilizumab, or intrathecal dexamethasone in 75 patients with NORSE. Among them, 52 patients were managed with anakinra, 21 with tocilizumab, and eight with intrathecal dexamethasone. Most had elevated serum or cerebrospinal fluid cytokine levels at treatment initiation. Treatments were predominantly initiated during the acute phase of the disease (92%) and resulted, within the first 2 weeks, in seizure control for up to 73% of patients with anakinra, 70% with tocilizumab, and 50% with intrathecal dexamethasone. Cytokine levels decreased after treatment for most patients. Anakinra and intrathecal dexamethasone were mainly initiated in children with FIRES, whereas tocilizumab was more frequently prescribed for adults, with or without a prior febrile infection. There was no clear correlation between the response to treatment and the time to initiate the treatment. Most patients experienced long-term disability and drug-resistant post-NORSE epilepsy. Initiation of second-line immunotherapies during status epilepticus (SE) had no clear effect on the emergence of post-NORSE epilepsy or long-term functional outcomes. In a small number of cases, the initiation of anakinra or tocilizumab several years after SE onset resulted in a reduction of seizure frequency for 67% of patients. These data highlight the potential utility of anakinra, tocilizumab, and intrathecal dexamethasone in patients with NORSE. There continues to be interest in the utilization of early cytokine measurements to guide treatment selection and response. Prospective studies are necessary to understand the role of early immunomodulation and its associations with epilepsy and functional outcomes., (© 2024 International League Against Epilepsy.)

Metabolomics, leveraging techniques like NMR and MS, is crucial for understanding biochemical processes in pathophysiological states. This field, however, faces challenges in metabolite sensitivity, data complexity, and omics data integration. Recent machine learning advancements have enhanced data analysis and disease classification in metabolomics. This study explores machine learning integration with metabolomics to improve metabolite identification, data efficiency, and diagnostic methods. Using deep learning and traditional machine learning, it presents advancements in metabolic data analysis, including novel algorithms for accurate peak identification, robust disease classification from metabolic profiles, and improved metabolite annotation. It also highlights multiomics integration, demonstrating machine learning's potential in elucidating biological phenomena and advancing disease diagnostics. This work contributes significantly to metabolomics by merging it with machine learning, offering innovative solutions to analytical challenges and setting new standards for omics data analysis., (© 2024 Wiley‐VCH GmbH.)

Children's testimonial learning often occurs in epistemic collaborations with others. In this paper, we will discuss ways in which cultural learning emerges in social and interpersonal contexts, and is intrinsically supported and guided by children's collaborative capacities. Much work in cultural learning has focused on children's examination of speaker and model characteristics, but more recent research has investigated the interactive aspects of testimonial exchanges. We will review evidence that children (1) participate in the interpersonal commitments that are shared in testimonial transactions by way of direct address and epistemic buck passing, (2) participate in social groups that affect their selective learning in nuanced ways, and (3) may detect epistemic harms by listeners who refuse to believe sincere and accurate speakers. Implications for conceptualizing children's testimonial learning as an interactive mechanism of collaboration will be discussed., (© 2023 The Authors. Topics in Cognitive Science published by Wiley Periodicals LLC on behalf of Cognitive Science Society.)

Purpose: This study aimed to determine the incidence of pelvic ring fractures and their associated epidemiological profile in Qatar., Methods: A retrospective cross-sectional study was performed at the only level I trauma centre in Qatar for patients diagnosed with pelvic ring fractures between January 2016 and December 2018. Age, sex, mechanism of injury, fracture classification and associated characteristics, mode of treatment, associated nerve injuries, and other complications were analyzed., Results: A total of 327 consecutive patients were included, with an average age of 32.6 years. Most of the included patients were males, 85% (279), with a male: female ratio of 6:1. The incidence of pelvic fractures was 3.887/100,000 across the three years. High-speed motor vehicle collisions (MVC) were the most common mechanism of injury (108, 33%), followed by falling from height (105, 32%). Young-Burgess lateral compression (LC) fracture type was the most frequent (224, 68.5%) and was associated with 25% of the entire mortalities. Nine (2.8%) cases were open fractures, and 12% (39) were deemed unstable. Around 29% of cases had associated injuries, with an overall mortality rate of 4.9% (16) observed. Most fractures were treated nonoperatively(n = 283,86.5%)., Conclusion: This study demonstrated the epidemiology of pelvic fractures in Qatar. MVC and work-related injuries were predominant in a younger cohort compared to the literature. Also, the mortality rate was lower than those reported in the literature. Therefore, well-trained surgeons and specialized trauma centres for treating these injuries are recommended., (© 2024. The Author(s).)

Background: Sarcopenia is associated with adverse outcomes in cirrhosis. Branched-chain amino acids (BCAA) target several pathways that lead to muscle loss in this population., Aims: We aimed to evaluate the impact of BCAA supplementation on sarcopenia measures in patients with cirrhosis., Methods: We conducted a 12-month double-blinded, randomised, controlled trial of BCAA supplementation (30 g daily) compared to an equicaloric, equi-nitrogenous whey protein in volunteers with cirrhosis and reduced muscle strength. The primary endpoint was an increase in grip strength and upper limb lean mass measured on DEXA. Mean-adjusted differences (MAD, 95% CI) between groups at 6 and 12 months are reported as treatment effect using a linear mixed model for repeated measures., Results: A total of 150 volunteers entered the trial (74 BCAA, 76 control), with a median age of 58 years [IQR 48; 63] and MELD of 14 [12; 17]. At 12 months, 57% in the BCAA arm and 61% in the control arm met the primary endpoint (p = 0.80). No significant between-group difference was found in grip strength (MAD -0.15 kg [-0.37; 0.06], p = 0.29) or upper limb lean mass (1.7 kg [-0.2; 3.6], p = 0.22) at 12 months. No significant differences in other body composition parameters, physical performance, frailty, rates of hospitalisation or mortality were found between the BCAA and the control group. Fatigue improved across the entire cohort, without significant between-group differences. 15% of volunteers reported side effects, with distaste higher in the BCAA arm (p = 0.045)., Conclusion: BCAA supplementation did not improve measures of muscle strength, mass or performance or physical frailty compared to a whey protein supplement in a randomised controlled setting. ACTRN12618000802202., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Malnutrition, sarcopenia (low muscle mass), and physical frailty have gained increasing recognition in candidates for liver transplant (LT) as these conditions can impact postoperative functional capacity. Multidimensional prehabilitation programs have been proposed as a safe intervention in adults awaiting LT but the nutritional pillar of prehabilitation has been understudied. This review summarizes the nutritional recommendations for prehabilitation for individuals with cirrhosis awaiting LT. Three major aspects of nutritional prehabilitation are discussed: (1) Assess: Evaluate nutritional status and assess for malnutrition, sarcopenia, and frailty to guide the nutritional prehabilitation intervention intensity, increasing across universal, targeted, and specialist levels; (2) Intervene: Prescribe a nutritional prehabilitation intervention to meet established nutrition guidelines in cirrhosis with a targeted focus on improving nutritional status and muscle health; (3) Reassess: Follow-up based on the required intensity of nutritional care with as needed intervention adjustment. Topics covered in the review include nutritional care levels for prehabilitation, energy prescriptions across body mass index strata, detailed considerations around protein intake (amount, distribution, and quality), carbohydrate and fat intake, other nutritional considerations, and the potential role of dietary supplements and nutraceuticals. Future research is warranted to more accurately evaluate energy needs, evaluate emerging dietary supplementation strategies, and establish the role of nutraceuticals alongside food-based interventions. While the general principles of nutritional prehabilitation are ready for immediate application, future large-scale randomized controlled trials in this space will help to quantify the benefit that can be gained by transitioning the LT approach from passive "transplant waitlist time" to active "transplant preparation time.", (Copyright © 2024 American Association for the Study of Liver Diseases.)

The aim of this study is to conduct a systematic analysis of the SARS-CoV-2 levels in urban sewage and evaluate the associated positivity rates, thereby developing comprehensive insights into the epidemic situation and providing valuable inputs for the development of effective disease prevention and control strategies. The PubMed, Scopus, Embase, China National Knowledge Infrastructure, Wanfang Database, and VIP databases were systematically searched based on the predefined retrieval strategy. The literature published up to February 2023 was meticulously screened according to the predetermined inclusion and exclusion criteria, and the relevant data were extracted for subsequent integration. The quality assessment of the included studies adhered to the rigorous Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement guidelines. The meta-analysis was conducted using Stata 17.0 software. The meta-analysis included a total of 34 studies, encompassing 8429 municipal wastewater samples. A random effects model was employed for the analysis, revealing an overall SARS-CoV-2 positivity rate of 53.7% in the municipal wastewater samples. The subgroup analyses demonstrated significant regional variations in the SARS-CoV-2 positivity rate in municipal wastewater, with Africa exhibiting the highest rate at 62.5% (95% confidence interval [CI] 47.4 ~ 76.0%) and Oceania displaying the lowest at 33.3% (95% CI 22.0 ~ 46.3%). However, the subgroup analyses based on the sampling site, strain prevalence period, and laboratory testing method did not yield any statistically significant differences. The SARS-CoV-2 positivity rate in wastewater is relatively high globally, although it exhibits regional disparities. Regions with larger populations and lower economic levels demonstrate higher viral detection rates in sewage. Different types of wastewater sampling sites can be employed to monitor distinct aspects of the COVID-19 pandemic. Continuous surveillance of SARS-CoV-2 in wastewater plays a pivotal role in complementing clinical data, helping to track outbreak progression across diverse regions., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Observational learning is essential for the acquisition of new behavior in educational practices and daily life and serves as an important mechanism for human cognitive and social-emotional development. However, we know little about its underlying neurocomputational mechanisms from a developmental perspective. In this study we used model-based fMRI to investigate differences in observational learning and individual learning between children and younger adults. Prediction errors (PE), the difference between experienced and predicted outcomes, related positively to striatal and ventral medial prefrontal cortex activation during individual learning and showed no age-related differences. PE-related activation during observational learning was more pronounced when outcomes were worse than predicted. Particularly, negative PE-coding in the dorsal medial prefrontal cortex was stronger in adults compared to children and was associated with improved observational learning in children and adults. The current findings pave the way to better understand observational learning challenges across development and educational settings., (© 2024. The Author(s).)

Background: Neonatal colonization with multidrug-resistant (MDR) Enterobacter spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterococcus faecium (ESKAPE) and Candida spp. often precedes invasive hospital-acquired infections. We investigated the prevalence and dynamics of neonatal ESKAPE and Candida spp. colonization from hospital admission until discharge (or death) and followed up for invasive disease., Methods: Prospective longitudinal surveillance for neonatal ESKAPE and Candida spp. colonization was conducted over 6 months at a South African regional hospital. Neonates enrolled at birth had swabs (nasal, 2× skin and rectal) collected within 24 hours and every 48-96 hours thereafter, until discharge or death. ESKAPE and Candida spp. were cultured for and antimicrobial susceptibility was performed on bacterial isolates. Whole-genome sequencing was undertaken on paired samples with the same bacterial species from colonizing and invasive disease episodes in the same child., Results: Of 102 enrolled neonates, 79% (n = 81) were colonized by ≥1 ESKAPE organism by time of discharge or death. Forty-four percent (36/81) were colonized within 24 hours of birth. Common colonizers were K. pneumoniae (70%; n = 57) and Enterobacter spp. (43%; n = 35). Almost all MDR organisms (93%) were Gram-negative. Forty-two (45%, 42/93) newborns acquired Candida spp. (skin only) colonization, commonly Candida parapsilosis (69%; n = 29). For 2 children with K. pneumoniae colonization and sepsis, the bloodstream and colonizing isolates were genetically different, whereas the single A. baumannii colonizing and blood isolate pair were genetically identical., Conclusions: We report a high prevalence of MDR ESKAPE and Candida spp. colonization in a regional neonatal unit. Interventions to reduce the high incidence of hospital-acquired neonatal infections should include reducing high colonization rates., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This cross-sectional study aimed to investigate the prevalence and characteristics of supplement usage among cancer patients and explore its potential associations with anxiety, excessive daytime sleepiness, and overall quality of life., Methods: Cancer patients receiving specific care at Hôtel Dieu de France University Hospital, Beirut, were enrolled between April and June 2023. In face-to-face interviews, participants were asked to complete a questionnaire consisting of sociodemographic information, supplement usage details, and cancer-related variables. Three validated surveys (Epworth Sleepiness Scale, GAD-7, and EORTC-QLQ-C15-PAL) were employed to assess excessive daytime sleepiness, anxiety, and overall quality of life. Statistical analyses, including chi-square tests, t-tests, and multiple regression models, were conducted to examine associations between supplement use and other variables., Results: A total of 202 participants were interviewed. Fifty-two percent reported regular use of supplements following their cancer diagnosis, with vitamin D being the most commonly used supplement. Using multivariate logistic regression, supplement use was associated with being female, having lower educational levels, having a longer duration since cancer diagnosis, and having a poor overall quality of life. The multivariate logistic regression showed no significant correlation between supplement use and excessive daytime sleepiness and anxiety., Conclusion: This study highlights a high prevalence of supplement usage among cancer patients in Lebanon, indicating a rising interest in alternative therapies aimed at enhancing quality of life. Larger prospective studies are needed to assess the relation between supplement intake and excessive daytime sleepiness and anxiety and establish clear guidelines pertaining to supplement use in cancer patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Social cognition differs from general cognition in its focus on understanding, perceiving, and interpreting social information. However, we argue that the significance of domain-general processes for controlling cognition has been historically undervalued in social cognition and social neuroscience research. We suggest much of social cognition can be characterized as specialized feature representations supported by domain-general cognitive control systems. To test this proposal, we develop a comprehensive working model, based on an interactive activation and competition architecture and applied to the control of action. As such, we label the model "ICON" (interactive activation and competition model for the control of action). We used the ICON model to simulate human performance across various laboratory tasks. Our simulations emphasize that many laboratory-based social tasks do not require socially specific control systems, such as those that are argued to rely on neural networks associated with theory-of-mind. Moreover, our model clarifies that perceived disruptions in social cognition, even in what appears to be disruption to the control of social cognition, can stem from deficits in social representation instead. We advocate for a "default stance" in social cognition, where control is usually general, but representation is specific. This study underscores the importance of integrating social cognition within the broader realm of domain-general control processing, offering a unified perspective on task processing., (© 2024 The Authors. Cognitive Science published by Wiley Periodicals LLC on behalf of Cognitive Science Society (CSS).)

Each year, people spend less time reading and more time viewing images 1 , which are proliferating online 2-4 . Images from platforms such as Google and Wikipedia are downloaded by millions every day 2,5,6 , and millions more are interacting through social media, such as Instagram and TikTok, that primarily consist of exchanging visual content. In parallel, news agencies and digital advertisers are increasingly capturing attention online through the use of images 7,8 , which people process more quickly, implicitly and memorably than text 9-12 . Here we show that the rise of images online significantly exacerbates gender bias, both in its statistical prevalence and its psychological impact. We examine the gender associations of 3,495 social categories (such as 'nurse' or 'banker') in more than one million images from Google, Wikipedia and Internet Movie Database (IMDb), and in billions of words from these platforms. We find that gender bias is consistently more prevalent in images than text for both female- and male-typed categories. We also show that the documented underrepresentation of women online 13-18 is substantially worse in images than in text, public opinion and US census data. Finally, we conducted a nationally representative, preregistered experiment that shows that googling for images rather than textual descriptions of occupations amplifies gender bias in participants' beliefs. Addressing the societal effect of this large-scale shift towards visual communication will be essential for developing a fair and inclusive future for the internet., (© 2024. The Author(s).)

The detection of a protein analyte and use of this type of information for disease diagnosis and physiological monitoring requires methods with high sensitivity and specificity that have to be also easy to use, rapid and, ideally, single step. In the last 10 years, a number of DNA-based sensing methods and sensors have been developed in order to achieve quantitative readout of protein biomarkers. Inspired by the speed, specificity, and versatility of naturally occurring chemosensors based on structure-switching biomolecules, significant efforts have been done to reproduce these mechanisms into the fabrication of artificial biosensors for protein detection. As an alternative, in scaffold DNA biosensors, different recognition elements (e.g., peptides, proteins, small molecules, and antibodies) can be conjugated to the DNA scaffold with high accuracy and precision in order to specifically interact with the target protein with high affinity and specificity. They have several advantages and potential, especially because the transduction signal can be drastically enhanced. Our aim here is to provide an overview of the best examples of structure switching-based and scaffold DNA sensors, as well as to introduce the reader to the rational design of innovative sensing mechanisms and strategies based on programmable functional DNA systems for protein detection., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

What is more effective to guide behavior: The desire to gain or the fear to lose? Electroencephalography (EEG) studies have yielded inconsistent answers. In a systematic exploration of the valence and magnitude parameters in monetary gain and loss processing, we used time-domain and time-frequency-domain analyses to uncover the underlying neural processes. A group of 24 participants performed a monetary incentive delay (MID) task in which cue-induced anticipation of a high or low magnitude of gain or loss was manipulated trial-wise. Behaviorally, the anticipation of both gain and loss expedited responses, with gain anticipation producing greater facilitation than loss anticipation. Analyses of cue-locked P2 and P3 components revealed the significant valence main effect and valence × magnitude interaction: amplitude differences between high and low incentive magnitudes were larger with gain vs. loss cues. However, the contingent negative variation component was sensitive to incentive magnitude but did not vary with incentive valence. In the feedback phase, the RewP component exhibited reversed patterns for gain and loss trials. Time-frequency analyses revealed a large increase in delta/theta-ERS oscillatory activity in high- vs. low-magnitude conditions and a large decrease of alpha-ERD oscillatory activity in gain vs. loss conditions in the anticipation stage. In the consumption stage, delta/theta-ERS turned out stronger for negative than positive feedback, especially in the gain condition. Overall, our study provides new evidence for the neural oscillatory features of monetary gain and loss processing in the MID task, suggesting that participants invested more attention under gain and high-magnitude conditions vs. loss and low-magnitude conditions., (© 2023 Society for Psychophysiological Research.)

Liver transplantation (LT) has been indicated for smaller and more clinically severe patients in recent years. Small biliary atresia (BA) patients often show portal hypoplasia and sclerotic portal vein (PV), which may make PV reconstruction more difficult during the operation. Among PV complications, intraoperative PV thrombosis can be considered a disaster, and it is important to prevent this catastrophic event by the precise assessment of the PV structure and PVF using radiological imaging before and during LT. However, there are no objective parameters to indicate whether sufficient PVF can be obtained. PV pressure (PVP) and PV flow (PVF) have mainly been studied in adult living donor LT, for the purpose of preventing small-for-size syndrome, and PVP has been considered an objective parameter of graft inflow modulation (GIM). In the setting of pediatric LT, GIM is mainly performed to prevent hypoperfusion, and it must be performed before graft implantation. GIM to maximize the PVF of pediatric patients with potentially low PVF in LT consists of the interruption of collateral vessels, the assessment of the usability of the native PV, and technical modifications in PV reconstruction. Reliable objective parameters that represent sufficient PVF before graft implantation are desired. Our recent study proposed that a PVP of ≥25 mmHg before graft implantation can be considered an objective parameter to obtain sufficient PVF (cutoff value: 50 mL/min/100 g of graft weight). Further investigation is needed to determine the best strategy for successful PV reconstruction in pediatric LT., (© 2023 Wiley Periodicals LLC.)

Members of advantaged groups are more likely than members of disadvantaged groups to think, feel, and behave in ways that reinforce their group's position within the hierarchy. This study examined how children's status within a group-based hierarchy shapes their beliefs about the hierarchy and the groups that comprise it in ways that reinforce the hierarchy. To do this, we randomly assigned children (4-8 years; N = 123; 75 female, 48 male; 21 Asian, 9 Black, 21 Latino/a, 1 Middle-Eastern/North-African, 14 multiracial, 41 White, 16 not-specified) to novel groups that differed in social status (advantaged, disadvantaged, neutral third-party) and assessed their beliefs about the hierarchy. Across five separate assessments, advantaged-group children were more likely to judge the hierarchy to be fair, generalizable, and wrong to challenge and were more likely to hold biased intergroup attitudes and exclude disadvantaged group members. In addition, with age, children in both the advantaged- and disadvantaged-groups became more likely to see membership in their own group as inherited, while at the same time expecting group-relevant behaviors to be determined more by the environment. With age, children also judged the hierarchy to be more unfair and expected the hierarchy to generalize across contexts. These findings provide novel insights into how children's position within hierarchies can contribute to the formation of hierarchy-reinforcing beliefs. RESEARCH HIGHLIGHTS: A total of 123 4-8-year-olds were assigned to advantaged, disadvantaged, and third-party groups within a hierarchy and were assessed on seven hierarchy-reinforcing beliefs about the hierarchy. Advantaged children were more likely to say the hierarchy was fair, generalizable, and wrong to challenge and to hold intergroup biases favoring advantaged group members. With age, advantaged- and disadvantaged-group children held more essentialist beliefs about membership in their own group, but not the behaviors associated with their group. Results suggest that advantaged group status can shape how children perceive and respond to the hierarchies they are embedded within., (© 2023 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

Genetic variants in cell division cycle 42 (CDC42) can manifest with dysmorphic features, autoinflammation, hemophagocytic lymphohistiocytosis, and thrombocytopenia, whereas defective thymopoiesis is a rare disease manifestation. We report a novel CDC42 missense variant (c.46A > G, p.Lys16Glu) resulting in infection and HPV-driven carcinogenesis in the mosaic mother and impaired thymopoiesis and profound T cell lymphopenia in the heterozygous daughter identified through newborn screening for SCID. We found that surface expression of IL-7Rα (CD127) was decreased, consistent with reduced IL-7-induced STAT5 phosphorylation and accelerated apoptotic T cell death. Consistent with the vital role of IL-7 in regulating thymopoiesis, both patients displayed reduced T cell receptor CDR3 repertoires. Moreover, the CDC42 variant prevented binding to the downstream effector, p21-activated kinase (PAK)1, suggesting this impaired interaction to underlie reduced IL-7Rα expression and signaling. Here, we provide the first report of severely compromised thymopoiesis and perturbed IL-7Rα signaling caused by a novel CDC42 variant and presenting with diverging clinical and immunological phenotypes in patients., (© 2023. The Author(s).)

Ascorbic acid is a redox regulator in many physiological processes. Besides its antioxidant activity, many intriguing functions of ascorbic acid in the expression of immunoregulatory genes have been suggested. Ascorbic acid acts as a co-factor for the Fe +2 -containing α-ketoglutarate-dependent Jumonji-C domain-containing histone demethylases (JHDM) and Ten eleven translocation (TET) methylcytosine dioxygenasemediated epigenetic modulation. By influencing JHDM and TET, ascorbic acid facilitates the differentiation of double negative (CD4 - CD8 - ) T cells to double positive (CD4 + CD8 + ) T cells and of T-helper cells to different effector subsets. Ascorbic acid modulates plasma cell differentiation and promotes early differentiation of hematopoietic stem cells (HSCs) to NK cells. These findings indicate that ascorbic acid plays a significant role in regulating both innate and adaptive immune cells, opening up new research areas in Immunonutrition. Being a water-soluble vitamin and a safe micro-nutrient, ascorbic acid can be used as an adjunct therapy for many disorders of the immune system., (© 2023 Wiley Periodicals LLC.)

Background: Pomegranate is known for its beneficial properties due to its high content in antioxidants and might constitute a natural option for preventing and treatment of different pathologies including cancer. Since mitochondria are involved in tumorigenesis through ROS production and modulation of oxidative metabolism, we investigated the biological effects of pomegranate on cellular redox state, proliferation and metabolism in the breast cancer cell line MDA-MB-231 (MDA)., Methods: MDA were treated for 24 h with graded concentration of filtered Pomegranate juice (PJ) and tested for metabolic Flux Analysis with XFe96 Extracellular Flux Analyzer, for proliferation using the xCELLigence System Real-Time Cell Analyzer and for intracellular ROS content by Confocal Microscopy Imaging., Results: Cells-treatment with freshly prepared pomegranate juice (PJ) resulted in a significant reduction of the intracellular ROS content already at the lower concentration of PJ tested. Additionally, it enhanced mitochondria respiration, and decreased glycolysis at high concentrations, inhibiting at the same time cell proliferation. As pomegranate is a seasonal fruit, assessment of optimum storage conditions preserving its bio-active properties was investigated. Our results indicated that storage conditions under controlled atmosphere for 30 days was able to enhance mitochondrial respiration at the same extent than freshly extracted PJ. Conversely, freezing procedure, though retaining the antioxidant and cell-growth inhibitory property, elicited an opposite effect on the metabolic profile as compared with fresh extract., Conclusion: Overall, the results of our study, on the one hand, confirms the preventive/therapeutic potential of PJ, as well as of its post-harvested processing, for cancer management. On the other hand, it highlights the intrinsic difficulties in attaining mechanistic insights when a multiplicity of effects is elicited by a crude mixture of bio-active compounds., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Hepatic encephalopathy (HE) is a challenging complication of liver disease that is associated with substantial morbidity and mortality. Branched-chain amino acid (BCAA) supplementation in the management of HE is a debated topic. This narrative review aims to provide an up-to-date review of the topic and includes studies featuring patients with hepatocellular carcinoma. A review of the literature was performed using the online databases MEDLINE and EMBASE for studies between 2002 and December 2022. Keywords 'branched-chain amino acids', 'liver cirrhosis' and 'hepatic encephalopathy' were used. Studies were assessed for inclusion and exclusion criteria. Of 1045 citations, 8 studies met the inclusion criteria. The main outcomes reported for HE was changed in minimal HE (MHE) (n = 4) and/or incidence of overt HE (OHE) (n = 7). Two of the 4 studies reporting on MHE had improvement in psychometric testing in the BCAA group, but there was no change in the incidence of OHE in any of the 7 papers in the BCAA group. There were few adverse effects of BCAA supplementation. This review found weak evidence for BCAA supplementation for MHE, and no evidence for BCAAs for OHE. However, given the relative paucity and methodological heterogeneity of the current research, there is scope for future studies to examine the effects of varying timing, dosage, and frequency of BCAAs on outcomes such as HE. Importantly, research is also needed to examine BCAAs in conjunction with standard therapies for HE such as rifaximin and/or lactulose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Mesenchymal stem cells (MSCs) are drawing considerable attention in the field of regenerative medicine due to their differentiation capabilities. The miRNAs are among the most important epigenetic regulators of MSC differentiation. Our previous study identified miR-4699 as a direct suppressor of the DKK1 and TNSF11 gene expression. However, the precise osteogenic-related phenotype or mechanism caused by miR-4699 change has yet to be dealt with in depth., Material and Methods: In the present study, miR-4699 mimics were transfected into human Adipose tissue-derived mesenchymal stem cells (hAd-MSCs) and osteoblast marker gene expression (RUNX2, ALP, and OCN), was analyzed to investigate whether miR-4699 promotes osteoblast differentiation of hAd-MSCs through targeting the DKK-1 and TNFSF11. We further examined and compared the effects of recombinant human BMP2 with miR-4699 on cell differentiation. In addition to quantitative PCR, analysis of alkaline phosphatase activity, calcium content assay, and Alizarin red staining were used to explore osteogenic differentiation. To evaluate the effect of miR-4699 on its target gene (on protein level) we utilized the western blotting technique., Results: The overexpression of miR-4699 in hAd-MSCs resulted in the stimulation of alkaline phosphatase activity, osteoblast mineralization, and the expression of RUNX2, ALP, and OCN osteoblast marker genes., Conclusion: Our findings indicated that miR-4699 supported and synergized the BMP2-induced osteoblast differentiation of mesenchymal stem cells. We suggest, thereof, the utilization of hsa-miR-4699 for further in vivo experimental investigation to reveal the potential therapeutic impact of regenerative medicine for different types of bone defects., (© 2023. The Japanese Society Bone and Mineral Research.)

Aim: This review aimed to synthesise the available reviews on the effects of nursing interventions on sleep quality among patients hospitalised in intensive care and non-intensive care units., Background: Poor sleep quality is a common fact in hospitalised patients. Nurses can contribute to the improvement of patients' sleep quality and duration., Design: A review of intervention reviews was carried out and reported following the PRISMA guidelines and checklist., Methods: We systematically searched for reviews published from January 2009 to December 2019 in PubMed, CINAHL Plus, Scopus, Institute for Scientific Information Web of Science, Joanna Briggs Database of Systematic Reviews and Cochrane Central Register of Controlled Trials databases. Searches were repeated at 24 November 2020 to include the most recent evidence. A narrative synthesis of the results was conducted., Results: Nine reviews (representing 109 original papers) met the selection criteria and were included for critical appraisal. Overall, nursing interventions and sleep quality were poorly defined. We grouped the interventions into 3 categories (environmental, barrier and internal interventions) to provide a more comprehensive overview and examine effects of nursing interventions on inpatients sleep quality. Inconsistent results were obtained and low quality of the original articles was reported, making it difficult to establish absolute conclusions., Conclusion: The impact of environmental changes on patients' sleep was positive but inconclusive, while use of earplugs and eye masks, music and acupuncture generally showed positive results with moderate quality of evidence, and no harmful effects were reported., (© 2022 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Introduction: Multiple myeloma (MM) is a malignancy of plasma cells with characteristic bone disease. Despite recent great strides achieved in MM treatment owing to the implementation of new anti-MM agents, MM is still incurable and bone destruction remains a serious unmet issue in patients with MM., Approach: In this review, we will summarize and discuss the mechanisms of the formation of bone disease in MM and the available preclinical and clinical evidence on the treatment for MM bone disease., Conclusions: MM cells produce a variety of cytokines to stimulate receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis and suppress osteoblastic differentiation from bone marrow stromal cells, leading to extensive bone destruction with rapid loss of bone. MM cells alter the microenvironment through bone destruction where they colonize, which in turn favors tumor growth and survival, thereby forming a vicious cycle between tumor progression and bone destruction. Denosumab or zoledronic acid is currently recommended to be administered at the start of treatment in newly diagnosed patients with MM with bone disease. Proteasome inhibitors and the anti-CD38 monoclonal antibody daratumumab have been demonstrated to exert bone-modifying activity in responders. Besides their anti-tumor activity, the effects of new anti-MM agents on bone metabolism should be more precisely analyzed in patients with MM. Because prognosis in patients with MM has been significantly improved owing to the implementation of new agents, the therapeutic impact of bone-modifying agents should be re-estimated in the era of these new agents., (© 2023. The Japanese Society Bone and Mineral Research.)

People intuitively view some social groups (such as Black people, Muslims, and women) as having biological underpinnings and discrete boundaries. Essentialist beliefs about social groups shape how people view themselves and others, leading to a number of negative social consequences. Whereas previous research has demonstrated variations in social essentialism within some Western societies, less is known about how social essentialism manifests in East Asian cultures that have well-documented differences in social values and cognitive styles from Western cultures. The current research investigated cultural variations in social essentialist thinking in the United States and China to reveal how cultural ideologies and social belief systems shape people's basic representations of the social world. Analyses revealed several cultural and social correlates of social essentialism both between and within the cultures and demonstrated the mediating role of collectivistic values in predicting cultural differences in essentialist beliefs about group coherence., (© 2022. The Psychonomic Society, Inc.)

Purpose: An animal model of laparoscopic hepatectomy showed that bleeding from the hepatic vein is influenced by airway pressure. However, there are little research reports on how airway pressure leads to risks in clinical practice. The main objective of this study was to investigate the impact of preoperative forced expiratory volume % in 1 s (FEV1.0%) on intraoperative blood loss in laparoscopic hepatectomy., Methods: All patients who underwent pure laparoscopic or open hepatectomy from April 2011 to July 2020 were classified into two groups by preoperative spirometry: those with obstructive ventilatory impairment (obstructive group; FEV1.0% < 70%) and those with normal respiratory function (ormal group; FEV1.0% ≥ 70%). Massive blood loss was defined as 400 mL for laparoscopic hepatectomy., Results: In total, 247 and 445 patients underwent pure laparoscopic and open hepatectomy, respectively. Regarding laparoscopic hepatectomy group, blood loss was significantly greater in the obstructive group (122 vs. 100 mL, P = 0.042). Multivariate analysis revealed that high IWATE criteria which classify the surgical difficulty of laparoscopic hepatectomy (≥ 7, odds ratio (OR): 4.50, P = 0.004) and low preoperative FEV1.0% (< 70%, OR: 2.28, P = 0.043) were independent risk factors for blood loss during laparoscopic hepatectomy. In contrast, FEV1.0% did not affect the blood loss (522 vs. 605 mL, P = 0.113) during open hepatectomy., Conclusion: Obstructive ventilatory impairment (low FEV1.0%) may affect the amount of bleeding during laparoscopic hepatectomy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Research linking genetic differences with human social and behavioural phenotypes has long been controversial. Frequently, debates about the ethical, social and legal implications of this area of research centre on questions about whether studies overtly or covertly perpetuate genetic determinism, genetic essentialism and/or genetic reductionism. Given the prominent role of the '-isms' in scientific discourse and criticism, it is important for there to be consensus and clarity about the meaning of these terms. Here, the author integrates scholarship from psychology, genetics and philosophy of science to provide accessible definitions of genetic determinism, genetic reductionism and genetic essentialism. The author provides linguistic and visual examples of determinism, reductionism and essentialism in science and popular culture, discusses common misconceptions and concludes with recommendations for science communication., (© 2022. Springer Nature Limited.)

Although the incidence and death rates of gastric cancer (GC) are decreasing, approximately one million new cases and 800,000 GC-related deaths were reported worldwide in 2018. Currently, the oncogenesis of GC remains unclear, and the demand for novel treatment options are unmet. Here, we explored the role of aldo-keto reductase family 1 member B (AKR1B1) in the progression of GC. The proliferation, migration, and invasion of GC cells were evaluated by CCK-8 assay, wound healing assay, and transwell assay, respectively. The interaction between EBF transcription factor 1 (EBF1) and the promoter region of AKR1B1 was determined by luciferase reporter assay and chromatin immunoprecipitation (ChIP). Gene expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting assay. The expression of AKR1B1 was elevated in GC cells, resulting in increased cell proliferation, migration, and invasion. Meanwhile, EBF1 was a negative regulator of AKR1B1; its overexpression suppressed AKR1B1 expression and GC progression. Furthermore, knockdown of ZNF521 induced EBF1 expression, thus suppressing AKR1B1 expression and resulting in attenuated GC growth and invasiveness. Notably, knockdown of ZNF521 attenuated GC progression and was rescued by overexpression of AKR1B1. Our current study revealed a novel ZNF521/EBF1/AKR1B1 axis in GC and elaborated its important role in promoting GC progression, providing potential therapeutic targets for anti-GC treatments., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Introduction: James Baldwin (1924-1987) was a prolific African American author and activist whose writing centered primarily on race, sexuality, and religion. Baldwin's lived experiences and breadth of knowledge provided him with a unique perspective of the Black experience in America, a theme he frequently revisited in his work and the impetus for his involvement in the Civil Rights Movement METHOD: This article presents a psychobiographical application of Queering Black Racial Identity Development to conceptualize the life story of James Baldwin., Results: This study explores the life of James Baldwin, highlights his influence as a historical figure and agent of social change, and explores the "why" of his life and behavior. Specifically, his decision to return to the United States during the Civil Rights Movement and possible reasons he avoided politicizing his sexuality in the same way he did his racial identity., Conclusion: As an African American, nonheterosexual, male author and Civil Rights activist, Baldwin's intersectional identities played a significant role in his decision to dedicate his life to writing and activism. Limitations of the study are discussed., (© 2022 Wiley Periodicals LLC.)

Competing Interests: All the authors are employees of the Instituto Nacional de Pediatria. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Our neonatal intensive care unit (NICU) saw an increase in Staphylococcus aureus (SA) infections-methicillin-resistant SA (MRSA) infections increased from 2.1/10,000 patient days (PD) to 5.1/10,000 PD, and methicillin-sensitive SA (MSSA) infections from 1.2/10,000 PD to 3.9/10,000 PD. This quality improvement project aimed to decrease the rates of SA infections to less than 2.0/10,000 PD, and to determine the rate of SA decolonization., Methods: Infection prevention interventions targeted patient factors (SA surveillance, patient cohorting, decolonization protocol), provider factors (provider cohorting, enhanced hand hygiene) and environmental factors (room structure, equipment optimization)., Results: The rates of MRSA and MSSA infections decreased to 0.6/10,000 PD and 0.7 infections/10,000 PD respectively. Persistent decolonization of SA was successful in 67% of colonized patients., Conclusions: Specific interventions targeting patient, provider, and environmental factors, including the implementation of a SA decolonization protocol, were successful in decreasing the incidence of SA infections in neonates., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)