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Circular RNAs (circRNAs) are covalently closed RNA molecules widely expressed in eukaryotes and deregulated in several pathologies, including cancer. Many studies point to their activity as microRNAs (miRNAs) and protein sponges; however, we propose a function based on circRNA-mRNA interaction to regulate mRNA fate. We show that the widely tumor-associated circHIPK3 directly interacts in vivo with the BRCA1 mRNA through the back-splicing region in human cancer cells. This interaction increases BRCA1 translation by competing for the binding of the fragile-X mental retardation 1 protein (FMRP) protein, which we identified as a BRCA1 translational repressor. CircHIPK3 depletion or disruption of the circRNA-mRNA interaction decreases BRCA1 protein levels and increases DNA damage, sensitizing several cancer cells to DNA-damage-inducing agents and rendering them susceptible to synthetic lethality. Additionally, blocking FMRP interaction with BRCA1 mRNA with locked nucleic acid (LNA) restores physiological protein levels in BRCA1 hemizygous breast cancer cells, underscoring the importance of this circRNA-mRNA interaction in regulating DNA-damage response., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Abscisic acid (ABA), a phytohormone traditionally recognized for its role in plant stress responses, has recently emerged as a significant player in mammalian defense mechanisms. Like plants, various mammalian cell types synthesize ABA in response to specific health challenges, although the precise pathways remain not fully elucidated. ABA is associated with the regulation of inflammation and insulin signaling, prompting extensive research into its potential as a therapeutic agent for various diseases. ABA exerts its effects through its receptors, particularly PPAR-γ and LANCL-2, which serve as signaling hubs regulating numerous pathways. Through these interactions, ABA profoundly impacts mammalian health, and new ABA targets continue to be identified. Numerous studies in animal models demonstrate ABA's benefit in managing conditions such as neurological and psychiatric disorders, cancer, and malaria infections, all of which involve significant inflammatory dysregulation. In this manuscript we review the studies covering ABA synthesis and release in cell cultures, the signaling pathways regulated by ABA, and how these impact health in preclinical models. Furthermore, we highlight recent research suggesting that measuring ABA levels in human body fluids could serve as a useful biomarker for pathological conditions, providing insights into disease progression and treatment efficacy. This comprehensive review outlines the current understanding of ABA in mammalian pathophysiology, identifying gaps in knowledge, particularly concerning ABA biosynthesis and metabolism in mammals. In addition, this study emphasizes the need for clinical trials to validate the effectiveness of ABA-based therapies and its reliability as a biomarker for various diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Advisory Committee on Immunization Practices (ACIP) recommended that dengue pre-vaccination screening tests for Dengvaxia administration have at least 98% specificity and 75% sensitivity. This study evaluates the performance of commercial anti-DENV IgG tests to identify tests that could be used for pre-vaccination screening. First, for seven tests, we evaluated sensitivity and specificity in early convalescent dengue virus (DENV) infection, using 44 samples collected 7-30 days after symptom onset and confirmed by RT-PCR. Next, for the five best-performing tests and two additional tests (with and without an external test reader) that became available later, we evaluated performance to detect past dengue infection among a panel of 44 specimens collected in 2018-2019 from healthy 9- to 16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the four best-performing tests using 400 specimens from the same population. We used virus focus reduction neutralization test and an in-house DENV IgG ELISA as reference standards. Of seven tests, five showed ≥75% sensitivity in detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to the Zika virus. For the detection of previous DENV infections, the tests with the highest performance were the Euroimmun NS1 IgG ELISA (sensitivity 84.5%, specificity 97.1%) and CTK Dengue IgG rapid test R0065C with the test reader (sensitivity 76.2% specificity 98.1%). There are IgG tests available that can be used to accurately classify individuals with previous DENV infection as eligible for dengue vaccination to support safe vaccine implementation., Importance: The Advisory Committee on Immunization Practices (ACIP) has set forth recommendations that dengue pre-vaccination screening tests must exhibit at least 98% specificity and 75% sensitivity. Our research rigorously assesses the performance of various commercial tests against these benchmarks using well-characterized specimens from Puerto Rico. The findings from our study are particularly relevant given FDA approval and ACIP recommendation of Sanofi Pasteur's Dengvaxia vaccine, highlighting the need for accurate pre-vaccination screening tools., Competing Interests: The authors declare no conflict of interest.

This study presents the comprehensive design and performance validation of a wind tunnel specifically developed for advanced investigations into respirable dust deposition pertinent to coal mining environments. The design integrates a constant particle delivery system engineered to maintain uniform particle dispersion, which is critical for replicating real-world conditions in coal mines. Our methodology involved using ANSYS Fluent for the design and optimization of a blowing-type wind tunnel, with a focus on controlling turbulence levels and minimizing pressure drops, which are crucial for accurate dust behaviour simulation. The core of our research emphasizes the deployment of the Aerosol Lung Deposition Apparatus (ALDA) alongside a custom dust injection system to measure particle distributions within the test section. This setup enabled us to simulate the inhalation of coal dust particles, providing a realistic scenario for assessing potential hazards to miners. Validation of the tunnel's performance was achieved through extensive testing with dust sensors and a hot-wire anemometer, which verified the airflow velocity and turbulence against the initial design specifications. The findings affirm the wind tunnel's capability to effectively model dust deposition and its impacts, thereby offering opportunities for enhancing miner safety and health standards., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Head start (HS) programs are required to collect children's height and weight data. Programs also communicate these results to families. However, no standardized protocol exists to guide measurements or communicate results. The purpose of this article was to describe the development of a measurement toolkit and best practices for communication. Methods: HS programs contributed to the development and pilot testing of a toolkit for HS staff to guide child measurement. We used a three-phase iterative approach and qualitative methods to develop and test the toolkit, which included a video and handout. In addition, we convened an advisory group to draft best practices for communication. Results: HS program staff appreciated the toolkit materials for their simplicity and content. The advisory group highlighted the importance of weight stigma and the need to be cautious in the way that information is communicated to families. The group underscored the role of emphasizing health behavior change, instead of focusing solely on BMI. Best practices were organized into (1) Policies and procedures for communicating screening results, (2) training for HS program staff to improve communication related to screening and health behaviors, and (3) other best practices to promote health behaviors and coordinate data systems. Conclusions: Our toolkit can improve anthropometric measurements of HS to ensure that potential surveillance data are accurate. Advisory group best practices highlight opportunities for HS to develop and implement policies, procedures, and trainings across the country to improve communication with HS families. Future research should test the implementation of these best practices within HS.

Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease with a mean survival time of three years. The 97% of the cases have TDP-43 nuclear depletion and cytoplasmic aggregation in motor neurons. TDP-43 prevents non-conserved cryptic exon splicing in certain genes, maintaining transcript stability, including ATG4B, which is crucial for autophagosome maturation and Microtubule-associated proteins 1A/1B light chain 3B (LC3B) homeostasis. In ALS mice (G93A), Atg4b depletion worsens survival rates and autophagy function. For the first time, we observed an elevation of LC3ylation in the CNS of both ALS patients and atg4b -/- mouse spinal cords. Furthermore, LC3ylation modulates the distribution of ATG3 across membrane compartments. Antisense oligonucleotides (ASOs) targeting cryptic exon restore ATG4B mRNA in TARDBP knockdown cells. We further developed multi-target ASOs targeting TDP-43 binding sequences for a broader effect. Importantly, our ASO based in peptide-PMO conjugates show brain distribution post-IV administration, offering a non-invasive ASO-based treatment avenue for neurodegenerative diseases., (© 2024. The Author(s).)

The dysfunction of TAR DNA-binding protein 43 (TDP-43) is implicated in various neurodegenerative diseases, though the specific contributions of its toxic gain-of-function versus loss-of-function effects remain unclear. This study investigates the impact of TARDBP loss on cellular metabolism and viability using human-induced pluripotent stem cell-derived motor neurons and HeLa cells. TARDBP silencing led to reduced metabolic activity and cell growth, accompanied by neurite degeneration and decreased oxygen consumption rates in both cell types. Notably, TARDBP depletion induced a metabolic shift, impairing ATP production, increasing metabolic inflexibility, and elevating free radical production, indicating a critical role for TDP-43 in maintaining cellular bioenergetics. Furthermore, TARDBP loss triggered non-apoptotic cell death, increased ACSL4 expression, and reprogrammed lipid metabolism towards lipid droplet accumulation, while paradoxically enhancing resilience to ferroptosis inducers. Overall, our findings highlight those essential cellular traits such as ATP production, metabolic activity, oxygen consumption, and cell survival are highly dependent on TARDBP function., Competing Interests: Declaration of competing interest To whom it may be of interest. On behalf of all the authors, I hereby confirm that the authors of "Loss of TDP-43 Induces ALS-Related Collapse of Cellular Homeostasis" have not declared or known conflicts of interest. And to confirm that I sign the present in Lleida, at June 4th, 2024., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS). Pharmacotherapy offers a potential treatment approach for EDS in OSA patients. This systematic review and meta-analysis aimed to assess the efficacy and safety of pharmacological interventions for alleviating EDS in patients with OSA. Following PRISMA guidelines, we included randomized controlled trials investigating pharmacological treatments for EDS in adult OSA until August 2023. We conducted meta-analysis, subgroup, and meta-regression analyses using a random effects model. Finally, a network meta-analysis synthesized direct and indirect evidence, followed by a comprehensive safety analysis. We included 32 articles in the meta-analysis (n = 3357). Pharmacotherapy showed a significant improvement in the Epworth Sleepiness Scale (ESS) score (Mean Difference (MD) -2.73, (95 % Confidence Interval (CI) [-3.25, -2.20], p < 0.01) and Maintenance of Wakefulness Test (MWT) score (MD 6.00 (95 % CI [2.66, 9.33] p < 0.01). Solriamfetol, followed by Pitolisant and modafinil, exhibited the greatest ESS reduction, while Danavorexton, followed by Solriamfetol and MK-7288, had the strongest impact on MWT. MK-7288 had the most total adverse events (AEs), followed by Danavorexton and armodafinil. Pharmacological Interventions significantly alleviate EDS in OSA patients but with heterogeneity across medications. Treatment decisions should involve a personalized assessment of patient factors and desired outcomes., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Although many studies analyse gender differences in the clinical expression of Attention-Deficit Hyperactivity Disorder (ADHD) and prevalence studies show that girls with ADHD are underdiagnosed, there are no instruments that are sensitive to the detection of girls with ADHD., Objective: The objective of this study is to develop a self-report early detection instrument for boys and girls with ADHD aged 7 to 16, which includes the gender perspective and is sensitive to the detection of girls with ADHD., Methods: The scale was developed and the items that comprised it were created from the thematic analysis of ADHD and its evaluation in children based on the diagnostic criteria of the DSM-5-TR. A modified e-Delphi method involving a three-round web survey was used to establish a consensus on the content of the scale. Ten experts were recruited to form a professional panel. The panel members were asked to assess the differential symptomatology of ADHD in boys and girls, the dimensions to be evaluated, and the importance of scale items to evaluate the content., Results: A consensus was reached regarding 13 total items distributed in three dimensions: inattention; hyperactivity/impulsivity; and, a third dimension, internalisation, which includes symptoms most present in the expression of ADHD in girls., Conclusions: To the best of our knowledge, the development of this scale using the Delphi method is the first specific scale used for identifying ADHD that also addresses the gender perspective and the differential symptomatology between boys and girls. However, we must proceed to the analysis of psychometric properties, as the scale requires an exhaustive study of its reliability and validity. We can anticipate that this scale will provide relevant and reliable information that can be used for the identification of ADHD in both boys and girls.

The liver has a unique ability to regenerate 1,2 ; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option 3-5 . Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2 + migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. Four-dimensional intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 reduces hepatocyte growth factor-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation that mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut-liver barrier may advance new areas of therapeutic discovery in regenerative medicine., (© 2024. The Author(s).)

Compressive hydrated nucleus pulposus extrusion (HNPE) is a sudden extrusion of hydrated, nondegenerated nucleus pulposus material with well-known characteristic MRI findings. The appearance of compressive HNPE during contrast-enhanced CT has already been described, but never its myelo-CT characteristics. The aim of this retrospective multicenter case series is to describe the myelo-CT findings in 15 dogs with compressive HNPE confirmed with gross surgical findings. A distinctive and consistent myelo-CT appearance of cervical compressive HNPE in dogs that included a focal extradural "seagull"-shaped extradural compression dorsal to the annulus fibrosus combined with a narrowing of the affected intervertebral disc space was found. The extruded material was hypoattenuating in the soft tissue algorithm. Myelo-CT could be a useful diagnostic tool and influence the clinical decision to address cervical compressive HNPE conservatively or surgically when MRI is not available., (© 2024 American College of Veterinary Radiology.)

Although science diplomacy has been gaining relevance in foreign policy to solve environmental challenges, critical questions concerning what different instruments mean under the term 'science diplomacy' and whether science diplomacy does contribute to the progress in solving environmental issues remain unanswered. We explore those questions by linking science diplomacy salient features through documentary analysis of international instruments addressing the plastics pollution in the ocean. We find that from a science diplomacy and multi-level governance perspective, the responsibilities and capabilities of emergent actors of cross-level governance are also important, leading to more attention being paid to changes in the role of national authorities, away from passive leadership to cross-cutting coalitions supported by the salient features of science diplomacy, and redefining dominant discursive approaches that have framed plastics waste., Points for Practitioners: As a result of the cost and limitations of the current international mechanisms, there is currently no incentive for individual countries to take action against marine plastic pollution.Science diplomacy and multi-level governance can contribute to international cooperation, foreign policy and national strategies.Leading efforts to engage countries with fewer scientific and technological capabilities could benefit countries' foreign policy., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2023.)

Hematopoietic stem cells (HSCs) produce all essential cellular components of the blood. Stromal cell lines supporting HSCs follow a vascular smooth muscle cell (vSMC) differentiation pathway, suggesting that some hematopoiesis-supporting cells originate from vSMC precursors. These pericyte-like precursors were recently identified in the aorta-gonad-mesonephros (AGM) region; however, their role in the hematopoietic development in vivo remains unknown. Here, we identify a subpopulation of NG2 + Runx1 + perivascular cells that display a sclerotome-derived vSMC transcriptomic profile. We show that deleting Runx1 in NG2 + cells impairs the hematopoietic development in vivo and causes transcriptional changes in pericytes/vSMCs, endothelial cells and hematopoietic cells in the murine AGM. Importantly, this deletion leads also to a significant reduction of HSC reconstitution potential in the bone marrow in vivo. This defect is developmental, as NG2 + Runx1 + cells were not detected in the adult bone marrow, demonstrating the existence of a specialised pericyte population in the HSC-generating niche, unique to the embryo., (© 2024. The Author(s).)

The performance of programmable voltage signals that exploit the quantum behavior of superconducting Josephson junctions continues to improve and enhance measurements in metrology, communications, and quantum control. We review advances in pulse-driven digital synthesis techniques with Josephson-junction-based devices. Quantum-based synthesis of voltage waveforms has been demonstrated at frequencies up to 3 GHz and rms amplitudes up to 4 V. Josephson pulse generators have also been used to control and characterize superconducting qubits., Competing Interests: Conflict of Interest The authors have no conflicts to disclose.

Broadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic hypermutation in bnAbs and the limited affinity of HIV Env proteins for bnAb germline precursors suggest that extended antigen exposure is necessary for their production. Consequently, HIV vaccine research is exploring complex sequential vaccination strategies to guide the immune response through maturation stages. In this context, the exploration of the factors linked to the generation of these antibodies across diverse age groups becomes critical. In this study, we assessed the anti-HIV-1 neutralization potency and breadth in 108 aviremic adults and 109 aviremic children under 15 years of age who were receiving ART. We used a previously described minipanel of recombinant viruses and investigated the factors associated with neutralization in these individuals. We identified individuals in both groups who were capable of neutralizing viruses from three different subtypes, with greater cross-neutralization observed in the adult group (49.0% vs. 9.2%). In both groups, we observed an inverse association between neutralization breadth and the CD4+/CD8+ ratio, as well as a direct association with the time to ART initiation. However, we found no association with time post-infection, cumulative ART duration, or CD8+ cell levels. The present study demonstrates that children receiving antiretroviral therapy generate broadly neutralizing responses to HIV-1, albeit with lower magnitude compared to adults. We also observed that neutralization breadth is associated with CD4+/CD8+ levels and time to treatment initiation in both children and adults living with HIV-1. Our interpretation of these results is that a delay in ART initiation could have prolonged the antigenic stimulation associated with viral replication and thus facilitate the capacity to elicit long-lasting broadly neutralizing responses. These results corroborate prior findings that show that HIV-1-neutralizing responses can persist for years, even at low antigen levels, implying an HIV-1 vaccine may induce lasting neutralizing antibody response.

Conventional dendritic cells (cDCs) are antigen-presenting cells (APCs) that play a central role in linking innate and adaptive immunity. cDCs have been well described in a number of different mammalian species, but remain poorly characterised in the chicken. In this study, we use previously described chicken cDC specific reagents, a novel gene-edited chicken line and single-cell RNA sequencing (scRNAseq) to characterise chicken splenic cDCs. In contrast to mammals, scRNAseq analysis indicates that the chicken spleen contains a single, chemokine receptor XCR1 expressing, cDC subset. By sexual maturity the XCR1 + cDC population is the most abundant mononuclear phagocyte cell subset in the chicken spleen. scRNAseq analysis revealed substantial heterogeneity within the chicken splenic XCR1 + cDC population. Immature MHC class II (MHCII) LOW XCR1 + cDCs expressed a range of viral resistance genes. Maturation to MHCII HIGH XCR1 + cDCs was associated with reduced expression of anti-viral gene expression and increased expression of genes related to antigen presentation via the MHCII and cross-presentation pathways. To visualise and transiently ablate chicken XCR1 + cDCs in situ , we generated XCR1 -iCaspase9-RFP chickens using a CRISPR-Cas9 knockin transgenesis approach to precisely edit the XCR1 locus, replacing the XCR1 coding region with genes for a fluorescent protein (TagRFP), and inducible Caspase 9. After inducible ablation, the chicken spleen is initially repopulated by immature CD1.1 + XCR1 + cDCs. XCR1 + cDCs are abundant in the splenic red pulp, in close association with CD8 + T-cells. Knockout of XCR1 prevented this clustering of cDCs with CD8 + T-cells. Taken together these data indicate a conserved role for chicken and mammalian XCR1 + cDCs in driving CD8 + T-cells responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Wu, Shih, Macdonald, Meunier, Hogan, Chintoan-Uta, Gilhooley, Hu, Beltran, Henderson, Sang, Stevens, McGrew and Balic.)

The absence of germinal centers (GCs) in cartilaginous fishes lies at odds with data showing that nurse sharks can produce robust antigen-specific responses and affinity mature their B cell repertoires. To investigate this apparent incongruity, we performed RNA sequencing on single nuclei, allowing us to characterize the cell types present in the nurse shark spleen, and RNAscope to provide in situ cellular resolution of key marker gene expression following immunization with R-phycoerythrin (PE). We tracked PE to the splenic follicles where it co-localizes with CXCR5 high  centrocyte-like B cells and a population of putative T follicular helper (Tfh) cells, surrounded by a peripheral ring of Ki67 +  AID +  CXCR4 +  centroblast-like B cells. Further, we reveal selection of mutations in B cell clones dissected from these follicles. We propose that the B cell sites identified here represent the evolutionary foundation of GCs, dating back to the jawed vertebrate ancestor., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of technical errors (TEs) on the outcomes after repair of femoral neck fractures in young adults., Design: Multicenter retrospective clinical study., Setting: 26 North American Level 1 Trauma Centers., Patients: Skeletally mature patients younger than 50 years of age with 492 femoral neck fractures treated between 2005 and 2017., Intervention: Operative repair of femoral neck fracture., Main Outcome Measurements: The association between TE (malreduction and deviation from optimal technique) and treatment failure (fixation failure, nonunion, malunion, osteonecrosis, malunion, and revision surgery) were examined using logistic regression analysis., Results: Overall, a TE was observed in 50% (n = 245/492) of operatively managed femoral neck fractures in young patients. Two or more TEs were observed in 10% of displaced fractures. Treatment failure in displaced fractures occurred in 27% of cases without a TE, 56% of cases with 1 TE, and 86% of cases with 2 or more TEs. TEs were encountered less frequently in treatment of nondisplaced fractures compared with displaced fractures (39% vs. 53%, P < 0.001). Although TE(s) in nondisplaced fractures increased the risk of treatment failure and/or major reconstructive surgery (22% vs. 9%, P < 0.001), they were less frequently associated with treatment failure when compared with displaced fractures with a TE (22% vs. 69% P < 0.001)., Conclusions: TEs were found in half of all femoral neck fractures in young adults undergoing operative repair. Both the occurrence and number of TEs were associated with an increased risk for failure of treatment. Preoperative planning for thoughtful and well-executed reduction and fixation techniques should lead to improved outcomes for young patients with femoral neck fractures. This study should also highlight the need for educational forums to address this subject., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The following authors reported a conflict of interest relating to the topic of this study: Walter Virkus receives royalties from GLW Orthopedics, Frank Liporace, Daniel Horwitz, and S. Andrew Sems receives royalties from Zimmer Biomet; Paul Tornetta III receives royalties from Smith & Nephew., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Spinal Muscular Atrophy (SMA) is a severe genetic neuromuscular disorder that occurs in childhood and is caused by misexpression of the survival motor neuron (SMN) protein. SMN reduction induces spinal cord motoneuron (MN) degeneration, which leads to progressive muscular atrophy and weakness. The link between SMN deficiency and the molecular mechanisms altered in SMA cells remains unclear. Autophagy, deregulation of intracellular survival pathways and ERK hyperphosphorylation may contribute to SMN-reduced MNs collapse, offering a useful strategy to develop new therapies to prevent neurodegeneration in SMA. Using SMA MN in vitro models, the effect of pharmacological inhibition of PI3K/Akt and ERK MAPK pathways on SMN and autophagy markers modulation was studied by western blot analysis and RT-qPCR. Experiments involved primary cultures of mouse SMA spinal cord MNs and differentiated SMA human MNs derived from induced pluripotent stem cells (iPSCs). Inhibition of the PI3K/Akt and the ERK MAPK pathways reduced SMN protein and mRNA levels. Importantly, mTOR phosphorylation, p62, and LC3-II autophagy markers protein level were decreased after ERK MAPK pharmacological inhibition. Furthermore, the intracellular calcium chelator BAPTA prevented ERK hyperphosphorylation in SMA cells. Our results propose a link between intracellular calcium, signaling pathways, and autophagy in SMA MNs, suggesting that ERK hyperphosphorylation may contribute to autophagy deregulation in SMN-reduced MNs., (© 2023. The Author(s).)

Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not a mere passenger in this structure, but instead plays a key role in the localization of cohesin to diverse biological processes and promotes loading of the complex at these sites. We show that in cells acutely depleted for RAD21, SA proteins remain bound to chromatin, cluster in 3D and interact with CTCF, as well as with a wide range of RNA binding proteins involved in multiple RNA processing mechanisms. Accordingly, SA proteins interact with RNA, and R-loops, even in the absence of cohesin. Our results place SA1 on chromatin upstream of the cohesin ring and reveal a role for SA1 in cohesin loading which is independent of NIPBL, the canonical cohesin loader. We propose that SA1 takes advantage of structural R-loop platforms to link cohesin loading and chromatin structure with diverse functions. Since SA proteins are pan-cancer targets, and R-loops play an increasingly prevalent role in cancer biology, our results have important implications for the mechanistic understanding of SA proteins in cancer and disease., Competing Interests: HP, YL, MN, MB, WV, LM, MC, DP, AB, SS, RJ, MC, SH No competing interests declared, (© 2023, Porter, Li et al.)

Sleepiness is one of the outcomes most used in randomized clinical trials (RCT) on the effect of treatments for obstructive sleep apnea (OSA). Furthermore, it is known that there is a placebo effect, especially in subjective measures. Therefore, given that sleepiness is a subjective measure, the objective of this systematic review with meta-analysis and three-level meta-regression was to assess the response to different placebos (pills and sham-CPAP) used in RCTs in OSA, both on subjective (Epworth Sleepiness Scale [ESS]) and objective (Multiple Sleep Latency Test [MSLT], Maintenance Wake Test [MWT], the Osler test and the Psychomotor Vigilance Task [PVT]). We observed a statistically significant placebo effect in both subjective and objective measures of hypersomnia, and in both sham-CPAP and pills. This placebo effect was greater, even clinically significant, in subjective measures (ESS: -2.84 points) and in those RCTs that used pills as a placebo. In the meta-regression, only a higher baseline value of the ESS and Osler test was related to the placebo effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Measurement of anti-pneumococcal capsular polysaccharides (anti-PnPs) IgG titers is an important tool in the immunologic assessment of patients with suspected immunodeficiency disorders (ID) to reduce the morbi-mortality and minimize severe infections. Retrospectively, we studied the relationship among anti-PnPs IgG response to 3 doses of Prevenar®13, levels of immune system components, leukocyte populations, and clinical data in children with ID. Serum samples were collected at least 4 weeks post vaccination. Subsequently, multi-serotype enzyme-linked immunosorbent assay (ELISA) was performed. Eighty-seven children (under 12 years) were enrolled. Primary immunodeficiency disorder (PID) was the most common disorder (45) followed by possible immunodeficiency disorder (POID) (19), secondary immunodeficiency disorder (SID) (15), and mixed immunodeficiency disorder (MID) (8). The median age was 3 (1.50-5.33) years, 65% of patients were male. Deficient production of anti-PnPs IgG (titer ≤ 50 mg/L) was detected in 47 patients (54%), especially in the MID group, all of them under immunosuppressive therapy. In PCV13 responders, the mean of leukocyte population levels was higher with statistically significance differences in CD4 + /CD8 + T lymphocytes (p = 0.372, p = 0.014) and CD56 + /CD16 + NK (p = 0.016). Patients with previous bone marrow transplantation were the worst PCV13 responders. Pneumococcal IgG antibody titers (post-vaccination) along with clinical and analytical markers represented., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Prenatal infections are associated with an increased risk of the onset of schizophrenia. Rodent models of maternal immune stimulation (MIS) have been extensively used in preclinical studies. However, many of these studies only include males, omitting pathophysiological features unique to females. The aim of this study is to characterize the MIS model in female rats using positron emission tomography (PET), structural magnetic resonance imaging (MR), and neuroplasticiy studies. Methods: In gestational day 15, Poly I:C (or Saline) was injected into pregnant Wistar rats to induce the MIS model. Imaging studies : [ 18 F]-fluoro-2-deoxy-D-glucose-PET scans of female-offspring were acquired at post-natal day (PND) 35 and PND100. Furthermore, T2-MR brain images were acquired in adulthood. Differences in FDG uptake and morphometry between groups were assessed with SPM12 and Regions of Interest (ROI) analyses. Ex vivo study : The density of parvalbumin expressing interneurons (PV), perineuronal nets (PNN), and parvalbumin expressing interneurons surrounded by perineuronal nets (PV-PNN) were evaluated in the prelimbic cortex and basolateral amygdala using confocal microscopy. ROIs and neuroplasticity data were analyzed by 2-sample T -test and 2-way-ANOVA analyses, respectively. Results: A significant increase in brain metabolism was found in all animals at adulthood compared to adolescence. MIS hardly modified brain glucose metabolism in females, highlighting a significant hypometabolism in the thalamus at adulthood. In addition, MIS induced gray matter (GM) enlargements in the pituitary, hippocampus, substantia nigra, and cingulate cortex, and GM shrinkages in some thalamic nuclei, cerebelar areas, and brainstem. Moreover, MIS induced white matter shrinkages in the cerebellum, brainstem and corpus callosum, along with cerebrospinal fluid enlargements in the lateral and 4th ventricles. Finally, MIS reduced the density of PV, PNN, and PV-PNN in the basolateral amygdala. Conclusion: Our work showed in vivo the differential pattern of functional and morphometric affectation in the MIS model in females, as well as the deficits caused at the synaptic level according to sex. The differences obtained highlight the relevance of including both sexes in psychiatric research in order to consider their pathophysiological particularities and successfully extend the benefits obtained to the entire patient population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Casquero-Veiga, Lamanna-Rama, Romero-Miguel, Rojas-Marquez, Alcaide, Beltran, Nacher, Desco and Soto-Montenegro.)

Background: The use of low-calorie menu items as optimal defaults and visual cues may nudge consumers to healthier choices at restaurants. However, little is known regarding their effects on emotions and behavioral intentions, particularly among people with different levels of health concern., Objective: Evaluate optimal defaults and visual cues' effect on anticipated pleasure and order intention depending upon consumers' health concern level., Design: Between-subjects randomized scenario-based experiment., Participants/setting: In all, 636 US adults recruited through an online crowdsourcing platform in July 2020., Intervention: Participants saw 1 of 6 menu boards in a fast-food drive-through simulation. Half the menu boards included meal photos with (1) menu items to be arranged as a combo by choice (ie, create-your-own combo); (2) traditional combos that included high-calorie default items; or (3) optimal combos that included low-calorie default items. The remaining 3 boards were identical without photos., Main Outcome Measures: Anticipated pleasure, order intention, and health concern were evaluated with 7-point Likert scales., Analysis: Statistical tests included multiple regression, Kruskal-Wallis, χ 2 , and analysis of variance. Education and sex were tested as potential confounders., Results: Optimal combos negatively affected anticipated pleasure (P = .003) and order intention (P < .001) compared with choice combos. Order intention reduction was the same for traditional and optimal combos (P = .128). The presence of photos changed order intention for optimal combos but varied by consumer's health concern level. When health concern was lower, photos decreased the likelihood of ordering the optimal combos (B = -3.06, P = .001), but when health concern was higher, photos enhanced ordering intention compared with the choice group (B = 0.60, P = .001). The photos did not affect anticipated pleasure for any level of health concern., Conclusions: The adverse effect of optimal defaults and how visual cues may reduce their negative effect should be considered in menu design., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Trauma exposure is widespread and linked to chronic physical and mental health conditions including posttraumatic stress disorder. However, there are major gaps in our knowledge of trauma exposure in Africa and on the validity of instruments to assess potentially life-threatening trauma exposure. Objective: The Life Events Checklist for the DSM-5 (LEC-5) is a free, widely used questionnaire to assess traumatic events that can be associated with psychopathology. As part of a case-control study on risk factors for psychosis spectrum disorders, we used the LEC-5 to examine the frequency of traumatic events and to assess the questionnaire's factor structure in South Africa ( N  = 6,765). Method: The prevalence of traumatic events was measured by individual items on the LEC-5 across the study sample, by case-control status, and by sex. Cumulative trauma burden was calculated by grouping items into 0, 1, 2, 3, and ≥4 traumatic event types. Psychometric properties of the LEC-5 were assessed through exploratory and confirmatory factor analyses. Results: More than 92% of the study sample reported experiencing ≥1 traumatic event; 38.7% reported experiencing ≥4 traumatic event types. The most endorsed item was physical assault (65.0%), followed by assault with a weapon (50.2%). Almost 94% of cases reported ≥1 traumatic event compared to 90.5% of controls ( p  < .001) and 94% of male participants reported ≥1 traumatic event compared to 89.5% of female participants ( p  < .001). Exploratory factor analysis revealed a 6-factor model. Confirmatory factor analyses of three models found that a 7-factor model based on the South African Stress and Health survey was the best fit (standardized root mean square residual of 0.024, root mean square error of approximation of 0.029, comparative fit index of 0.910). Conclusion: Participants reported very high exposure to traumatic events. The LEC-5 has good psychometric priorities and is adequate for capturing trauma exposure in South Africa.

Background: Low-calorie menu items as optimal defaults may encourage healthier choices when people eat out. Limited research has studied default effects from the restauranteurs' perspective, as well as the public health perspective., Objective: To examine the effects of optimal defaults on calories ordered, dietary autonomy, and visit intention in the context of a fast-food drive-through., Design: Between-subjects randomized scenario-based experiment., Participants/setting: In all, 377 adults who lived in the United States were recruited through a crowdsourcing platform in July 2020., Intervention: Participants were asked to visualize ordering a combo meal in a fast-food drive-through. They were randomly assigned to order from 1 of 3 menu boards: (1) menu items available for combos by customer choice, (2) combos that included traditional high-calorie default items, or (3) combos that included low-calorie optimal defaults., Main Outcome Measures: Differences in calories ordered among groups, dietary autonomy, and restaurant visit intention., Analysis: Statistical tests included multiple regression, Kruskal-Wallis, χ 2 , and 1-way analysis of variance. Covariates such as education and sex were tested in regression models as potential confounders., Results: Compared with the choice combo meals, optimal combo meals reduced calories ordered by consumers (-337 kcal, standard error = 19, P < .001), while traditional combos increased them (+132 kcal, standard error = 20, P < .001). No significant difference was found in visit intention. Dietary autonomy was affected by the optimal defaults (P = .025), even in participants with high health concern. Conversely, the traditional combo's effect on dietary autonomy was moderated by health concern (B = -0.26, P = .023), with only individuals with very high levels of health concern perceiving less autonomy., Conclusions: Optimal defaults provided a robust reduction in calories ordered but had implications for dietary autonomy., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disorder caused by reduction of the ubiquitously expressed protein Survival Motor Neuron (SMN). Low levels of SMN impact on spinal cord motoneurons (MNs) causing their degeneration and progressive muscle weakness and atrophy. To study the molecular mechanisms leading to cell loss in SMN-reduced MNs, we analyzed the NF-κB intracellular pathway in SMA models. NF-κB pathway activation is required for survival and regulates SMN levels in cultured MNs. Here we describe that NF-κB members, inhibitor of kappa B kinase beta (IKKβ), and RelA, were reduced in SMA mouse and human MNs. In addition, we observed that Gemin3 protein level was decreased in SMA MNs, but not in non-neuronal SMA cells. Gemin3 is a core member of the SMN complex responsible for small nuclear ribonucleoprotein biogenesis, and it regulates NF-κB activation through the mitogen-activated protein kinase TAK1. Our experiments showed that Gemin3 knockdown reduced SMN, IKKβ, and RelA protein levels, and caused significant neurite degeneration. Overexpression of SMN increased Gemin3 protein in SMA MNs, but did not prevent neurite degeneration in Gemin3 knockdown cells. These data indicated that Gemin3 reduction may contribute to cell degeneration in SMA MNs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miralles, Sansa, Beltran, Soler and Garcera.)

Background: In Central America, the COVID-19 pandemic coexists with a devastating epidemic of chronic kidney disease of unknown origin. The consequences of these overlapping health crises remain largely unknown., Methods: We assessed vulnerability to and impact of the first wave of COVID-19 on participants in a cohort study of chronic kidney disease (CKD) in El Salvador (n = 229). Participants were contacted by phone during August and September 2020. We queried changes to employment, healthcare access, household income and food security due to the pandemic (from March 2020 until the time of the interview) and COVID-19-associated symptoms during that time., Findings: We reached 94% of the cohort (n = 215). Nearly 40% of participants reported an unexpected change in employment or work activities and 8.8% reported new unemployment due to the pandemic. Participants with CKD (n = 27) had higher odds of reporting new income insecurity, food insecurity, and reductions in medical care access due to the pandemic. COVID-19-associated symptoms (an approximation of disease) were reported in 7.0% (n = 15). Participants with CKD were more likely to report COVID-19-associated symptoms compared to those without CKD, although these differences were not statistically significant., Conclusions: Overall, participants with CKD suffered greater economic consequences as a result of the pandemic and may have experienced higher incidence of COVID-19 disease, although laboratory diagnostics would be required to draw this conclusion. Longitudinal analyses are required to comprehensively evaluate the implications of the pandemic for individuals with CKD in Central America., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Alzheimer's Disease (AD) has currently no effective treatment; however, preventive measures have the potential to reduce AD risk. Thus, accurate and early prediction of risk is an important strategy to alleviate the AD burden. Neuroinflammation is a major factor prompting the onset of the disease. Inflammation exerts its toxic effect via multiple mechanisms. Amongst others, it is affecting gene expression via modulation of non-coding RNAs (ncRNAs), such as miRNAs. Recent evidence supports that inflammation can also affect long non-coding RNA (lncRNA) expression. While the association between miRNAs and inflammation in AD has been studied, the role of lncRNAs in neurodegenerative diseases has been less explored. In this review, we focus on lncRNAs and inflammation in the context of AD. Furthermore, since plasma-isolated extracellular vesicles (EVs) are increasingly recognized as an effective monitoring strategy for brain pathologies, we have focused on the studies reporting dysregulated lncRNAs in EVs isolated from AD patients and controls. The revised literature shows a positive association between pro-inflammatory lncRNAs and AD. However, the reports evaluating lncRNA alterations in EVs isolated from the plasma of patients and controls, although still limited, confirm the value of specific lncRNAs associated with AD as reliable biomarkers. This is an emerging field that will open new avenues to improve risk prediction and patient stratification, and may lead to the discovery of potential novel therapeutic targets for AD.

Common variable immunodeficiency (CVID) constitutes a heterogenic group of primary immunodeficiency disorders with a wide-ranging clinical spectrum. CVID-associated non-infectious morbidity constitutes a major challenge requiring a full understanding of its pathophysiology and its clinical importance and global variability, especially considering the broad clinical, genetic, and regional heterogeneity of CVID disorders. This work aimed to develop a nationwide, multicenter, retrospective study over a 3-year period describing epidemiological, clinical, laboratory, therapeutic, and prognostic features of 250 CVID patients in Spain. The mean diagnostic delay was around 10 years and most patients initially presented with infectious complications followed by non-infectious immune disorders. However, infectious diseases were not the main cause of morbimortality. Non-infectious lung disease was extraordinarily frequent in our registry affecting approximately 60% of the patients. More than one-third of the patients in our cohort showed lymphadenopathies and splenomegaly in their follow-up, and more than 33% presented immune cytopenias, especially Evans' syndrome. Gastrointestinal disease was observed in more than 40% of the patients. Among biopsied organs in our cohort, benign lymphoproliferation was the principal histopathological alteration. Reaching 15.26%, the global prevalence of cancer in our registry was one of the highest reported to date, with non-Hodgkin B lymphoma being the most frequent. These data emphasize the importance of basic and translational research delving into the pathophysiological pathways involved in immune dysregulation and diffuse lymphocytic infiltration. This would reveal new tailored strategies to reduce immune complications, and the associated healthcare burden, and ensure a better quality of life for CVID patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cabañero-Navalon, Garcia-Bustos, Nuñez-Beltran, Císcar Fernández, Mateu, Solanich, Carrillo-Linares, Robles-Marhuenda, Puchades-Gimeno, Pelaez Ballesta, López-Osle, Torralba-Cabeza, Bielsa Masdeu, Diego Gil, Tornador Gaya, Pascual Castellanos, Sánchez-Martínez, Barragán-Casas, González-García, Patier de la Peña, López-Wolf, Mora Rufete, Canovas Mora, Forner Giner and Moral Moral.)

We report here the first implementation of chemically specific imaging in the exhaust plume of a gas turbine typical of those used for propulsion in commercial aircraft. The method used is chemical species tomography (CST) and the target species is C , absorbing in the near-infrared at 1999.4 nm. A total of 126 beams propagate transverse to the plume axis, along 7 m paths in a coplanar geometry, to probe a central region of diameter ≈1.5 O 2 , absorbing in the near-infrared at 1999.4 nm. A total of 126 beams propagate transverse to the plume axis, along 7 m paths in a coplanar geometry, to probe a central region of diameter ≈1.5 m . The C O 2 absorption spectrum is measured using tunable diode laser spectroscopy with wavelength modulation, using the second harmonic to first harmonic (2f/1f) ratio method. The engine is operated over the full range of thrust, while data are recorded in a quasi-simultaneous mode at frame rates of 1.25 and 0.3125 Hz. Various data inversion methodologies are considered and presented for image reconstruction. At all thrust levels a persistent ring structure of high C O 2 concentration is observed in the central region of the measurement plane, with a raised region in the middle of the plume assumed to be due to the engine's boat tail. With its potential to target various exhaust species, the CST method outlined here offers a new approach to turbine combustion research, turbine engine development, and aviation fuel research and development.

We demonstrate Josephson arbitrary waveform synthesizers (JAWS) with increased operating temperature range for temperatures below 4 K. These JAWS synthesizers were fabricated with externally-shunted Nb/ a -Si/Nb junctions whose critical current exhibits improved temperature stability compared to the self-shunted Nb/Nb 0.15 Si 0.85 /Nb junctions typically used. Vertical stud resistors made of 230 nm of PdAu were developed to provide the milliohm shunt resistance required for junction overdamping while maintaining a small footprint suitable for high-density series arrays embedded in a coplanar waveguide. We evaluated the performance of these resistors from 3.8 K down to 20 mK. We designed, fabricated and tested a JAWS circuit with 4650 externally shunted Nb/ a -Si/Nb JJs with a critical current density ( J c ) of 0.12 mA ∕ μ m 2 and critical current ( I c ) of 3 mA. This circuit was designed to be mounted to the 3 K stage of a dilution refrigerator and used to control and calibrate a qubit mounted at the 10 mK stage. To increase the circuit density of the JAWS circuits we made arrays of two-junction vertical stacks. Current-voltage ( I - V ) curves of this JAWS circuit with stacked junctions under microwave excitation show Shapiro steps with quantum-locking ranges similar to those of JAWS circuits used for qubit control.

Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requires HSC specification signals from the surrounding microenvironment. In zebrafish, PDGF-B/PDGFRβ signaling controls hematopoietic stem/progenitor cell (HSPC) generation and is required in the HSC specification niche. Little is known about murine HSPC specification in vivo and whether PDGF-B/PDGFRβ is involved. Here, we show that PDGFRβ is expressed in distinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and its deletion impairs hematopoiesis. We demonstrate that PDGFRβ + cells play a dual role in murine hematopoiesis. They act in the aortic niche to support HSPCs, and in addition, PDGFRβ + embryonic precursors give rise to a subset of HSPCs that persist into adulthood. These findings provide crucial information for the controlled production of HSPCs in vitro., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Although there is a federal mandate to collect anthropometric data in Head Start (HS), little is currently known about the processes used to collect the height and weight measurements across programs and how the results are communicated to parents/guardians. The goal of this study was to understand anthropometric data collection and dissemination procedures in a sample of HS programs serving children 3-5 years. Methods: A convenience sample of HS Health or Nutrition managers were recruited via personal contacts and HS state directors to complete an electronic survey. Quantitative data were analyzed using descriptive statistics (means, standard deviations and frequencies). Open-ended questions were coded using thematic analysis. All protocols and procedures were approved by the Institutional Review Board at Miami University. Results: Approximately half of the programs reported that they have a protocol in place to guide measurements (57.1%) and those measurements are primarily taken by HS staff (64.5%). Most programs explain measurements to parents (82.3%) and report that collecting height/weight data is helpful in supporting children's health (76.0%). Most programs (80.3%) provide resources to parents of children with overweight or obesity. Four themes emerged from open-ended responses: (1) Role of Community Partners (e.g., providing information that conflicts with others); (2) Communicating Children's Weight Status with Families (e.g., using sensitive communication methods); (3) Challenges Measuring Children's Weight Status (e.g., accuracy of data, children's awareness); and (4) Family Reaction to Weight Status Communication (e.g., positive or negative experiences). Conclusion: Opportunities for quality improvement include wider use of standardized, written protocols and policies on data collection and enhanced communication practices to share information with parents.

Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 (H3K27me3) to maintain gene repression and is essential for cell differentiation. In low-grade endometrial stromal sarcoma (LG-ESS), the PRC2 subunit SUZ12 is often fused with the NuA4/TIP60 subunit JAZF1. We show that JAZF1-SUZ12 dysregulates PRC2 composition, genome occupancy, histone modification, gene expression, and cell differentiation. Loss of the SUZ12 N terminus in the fusion protein abrogates interaction with specific PRC2 accessory factors, reduces occupancy at PRC2 target genes, and diminishes H3K27me3. Fusion to JAZF1 increases H4Kac at PRC2 target genes and triggers recruitment to JAZF1 binding sites during cell differentiation. In human endometrial stromal cells, JAZF1-SUZ12 upregulated PRC2 target genes normally activated during decidualization while repressing genes associated with immune clearance, and JAZF1-SUZ12-induced genes were also overexpressed in LG-ESS. These results reveal defects in chromatin regulation, gene expression, and cell differentiation caused by JAZF1-SUZ12 that may underlie its role in oncogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Jumping to conclusions (JTC) and impaired social cognition (SC) affect the decoding, processing, and use of social information by people with psychosis. However, the relationship between them had not been deeply explored within psychosis in general, and in first-episode psychosis (FEP) in particular. Our aim was to study the relationship between JTC and SC in a sample with FEP. We conducted a cross-sectional study with 121 patients with FEP, with measures to assess JTC (easy, hard, and salient probability tasks) and SC (emotional recognition, attributional style, and theory of mind). We performed Student's t-test and logistic regression in order to analyse these associations.We found a statistically significant and consistent relationship of small-moderate effect size between JTC (all three tasks) and impaired emotional recognition. Also, our results suggest a relationship between JTC and internal attributions for negative events. Relationships between JTC and theory of mind were not found. These results highlight the importance of psychological treatments oriented to work on a hasty reasoning style and on improving processing of social information linked to emotional recognition and single-cause attributions., (© 2022. The Author(s).)

Circular RNAs (circRNAs) are expressed and are regulated in many biological processes but little is known about their ability to directly control mRNA homeostasis. We show that circRNA zinc finger protein 609 (circZNF609) interacts with several mRNAs increasing the final protein levels, which in the case of the cytoskeleton-associated protein 5 (CKAP5) leads to a stabilized microtubule cytoskeleton and an enhanced tumor cell proliferation., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: The renin-angiotensin system is highly conserved across vertebrates, including zebrafish, which possess orthologous genes coding for renin-angiotensin system proteins, and specialized mural cells of the kidney arterioles, capable of synthesising and secreting renin., Methods: We generated zebrafish with CRISPR-Cas9-targeted knockout of renin ( ren -/- ) to investigate renin function in a low blood pressure environment. We used single-cell (10×) RNA sequencing analysis to compare the transcriptome profiles of renin lineage cells from mesonephric kidneys of ren -/- with ren +/+ zebrafish and with the metanephric kidneys of Ren1 c -/- and Ren1 c +/+ mice., Results: The ren -/- larvae exhibited delays in larval growth, glomerular fusion and appearance of a swim bladder, but were viable and withstood low salinity during early larval stages. Optogenetic ablation of renin-expressing cells, located at the anterior mesenteric artery of 3-day-old larvae, caused a loss of tone, due to diminished contractility. The ren -/- mesonephric kidney exhibited vacuolated cells in the proximal tubule, which were also observed in Ren1 c -/- mouse kidney. Fluorescent reporters for renin and smooth muscle actin ( Tg(ren:LifeAct-RFP; acta2:EGFP )), revealed a dramatic recruitment of renin lineage cells along the renal vasculature of adult ren -/- fish, suggesting a continued requirement for renin, in the absence of detectable angiotensin metabolites, as seen in the Ren1 YFP Ren1 c -/- mouse. Both phenotypes were rescued by alleles lacking the potential for glycosylation at exon 2, suggesting that glycosylation is not essential for normal physiological function., Conclusions: Phenotypic similarities and transcriptional variations between mouse and zebrafish renin knockouts suggests evolution of renin cell function with terrestrial survival.

Introduction: Patients with severe COVID-19 develops an acute respiratory distress syndrome (ARDS), requiring admission to the intensive care unit. COVID-19 also reports an increased prevalence of comorbidities, similar to patients with Sleep disorder breathing (SDB)., Objectives: To evaluate the association between undiagnosed SDB and the risk of ARDS and pulmonary abnormalities in a cohort of patients' survivors of COVID-19 between 3 and 6 months after diagnosis., Methods: Prospective cohort study of patients who developed ARDS during hospitalization due to COVID-19 compared with a control group of patients who had COVID-19 with mild to moderate symptoms. All patients were evaluated between the 12th and 24th week after SARS-CoV-2 infection. The evaluation includes persistent symptoms, lung diffusing capacity of carbon monoxide (DLCO), chest CT scan and home sleep apnea test. SDB was diagnosed by the respiratory disturbance index ≥5 ev/h. The association between SDB and ARDS, the hazards of lung impairment and the hazard ratios (HR) were analyzed., Results: A total of 60 patients were included (ARDS: 34 patients, Control: 26 patients). The mean follow-up was 16 weeks (range 12-24). ARDS reported a high prevalence of SDB (79% vs. 38% in control group). A total of 35% reported DLCO impairment, and 67.6% abnormal chest CT. SDB was independently associated to ARDS, OR 6.72 (CI, 1.56-28.93), p < 0.01, and abnormal Chest CT, HR 17.2 (CI, 1.68-177.4, p = 0.01). Besides, ARDS, days in mechanical ventilation, male gender were also associated with an increased risk of abnormal chest CT., Conclusion: Undiagnosed SDB is prevalent and independently associated with ARDS. In addition, undiagnosed SDB increased the hazard of abnormal Chest CT in the midterm., Study Register: ISRCTN16865246., Competing Interests: Conflict of interest The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: https://doi.org/10.1016/j.sleep.2021.02.029. Authors declare no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) at diagnosis is associated with superior long-term outcomes compared to non-GCB-DLBCL in patients treated with conventional chemo-immunotherapy. Whether cell of origin (COO) by Hans algorithm retains its prognostic significance in patients with (R/R) relapsed/refractory DLBCL undergoing autologous hematopoietic cell transplant (auto-HCT) is not well established. Three hundred and fifty-seven patients underwent auto-HCT between 2005 and 2018. The COO status was determined in 284 patients and these were included in the analysis. One hundred ninety-four patients had GCB-DLBCL while 90 had non-GCB-DLBCL. Median follow up was 1.7 (0-13) years. The GCB-DLBCL was associated with inferior 5-year overall survival at 44% (95%CI, 36-52) versus 64% (95%CI, 54-77) (P = .004) and a higher relapse incidence at 67% (95%CI, 58-74) versus 49% (95%CI, 35-60) (P = .01) in the non-GCB-DLBCL. The difference between GCB and non-GCB-DLBCL remained statistically significant in multivariate analysis. Additionally, response at the time of transplant was an independent prognostic factor. GCB-DLBCL was enriched in double-hit and triple hit phenotype based on available fluorescence in situ hybridization data. These results suggest an enrichment of high-risk genetic rearrangements in R/R GCB-DLBCL resulting in limited efficacy of auto-HCT., Competing Interests: Disclosure MAK-D reports consultancy for Daiichi Sankyo., (Copyright © 2021. Published by Elsevier Inc.)

A prion's pathogenic character is enciphered in its conformation, which also defines the chemical environments of its amino acids. Differences in chemical environments influence the reactivity of amino acid side chains, in a conformation-dependent manner. Chemical oxidation of susceptible methionines would identify those methionines on the surface of a prion, which would reveal conformation-dependent information. We identified a set of methionine-containing peptides derived from the tryptic, chymotryptic, or tryptic/chymotryptic digestion of recombinant prion protein and the Sc237 strain of hamster-adapted scrapie. We developed a multiple reaction monitoring-based method of quantifying the extent of the methionine oxidation in those peptides. This approach can be used to define a prion's conformation and to distinguish among prion strains, which is an important component of food safety., Competing Interests: The authors declare no competing financial interest., (Not subject to U.S. Copyright. Published 2022 by American Chemical Society.)

Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609/CKAP5 mRNA interaction might have a potent output in tumor growth and drug response., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The international expansion of higher education has intensified in recent decades with a rapidly growing number of international branch campuses appearing on the scene. This study investigates the economic, cultural and institutional, and educational determinants of transnational higher education on both the extensive margin (number of international branch campuses), and the intensive margin (the total number of educational programmes offered). Using the gravity equation, we applied fixed-effect empirical methods to a panel dataset that combined and extended the raw data from campuses and master's programmes in 33 source countries and 76 host countries in the period from 1948 to 2016. Estimates reveal that although cultural, economic and institutional ties foster cross-border educational relationships, their effect differs significantly from one margin to another. The study highlights the relevance of globalisation, research activities, and aggregate demand in international higher education., (© The Author(s) 2022.)

Dupuytren's disease (DD) is a common, progressive fibroproliferative disease affecting the palmar fascia of the hands, causing fingers to irreversibly flex toward the palm with significant loss of function. Surgical treatments are limited; therefore, effective new therapies for DD are urgently required. To identify the key cellular and molecular pathways driving DD, we employed single-cell RNA sequencing, profiling the transcriptomes of 35,250 human single cells from DD, nonpathogenic fascia, and healthy dermis. We identify a DD-specific population of pathogenic PDPN + /FAP + mesenchymal cells displaying an elevated expression of fibrillar collagens and profibrogenic genes. In silico trajectory analysis reveals resident fibroblasts to be the source of this pathogenic population. To resolve the processes governing DD progression, genes differentially expressed during fibroblast differentiation were identified, including upregulated TNFRSF12A and transcription factor SCX. Knockdown of SCX and blockade of TNFRSF12A inhibited the proliferation and altered the profibrotic gene expression of cultured human FAP + mesenchymal cells, demonstrating a functional role for these genes in DD. The power of single-cell RNA sequencing is utilized to identify the major pathogenic mesenchymal subpopulations driving DD and the key molecular pathways regulating the DD-specific myofibroblast phenotype. Using this precision medicine approach, inhibition of TNFRSF12A has shown potential clinical utility in the treatment of DD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Routine medical testing is not recommended before cataract surgery, but no consensus exists about preoperative testing before general ophthalmologic surgery. We aimed to assess the impact of preoperative testing on patients undergoing ophthalmologic surgery by analyzing their surgical outcomes and complications., Methods: We retrospectively reviewed electronic health records of patients who had preoperative evaluations before cataract or noncataract ophthalmologic surgery at a tertiary care center from January 1, 2015, through December 31, 2019., Results: The cohort consisted of 2268 patients (1270 [56.0%] women). The most frequent ophthalmologic procedure was cataract extraction (n = 1450 [63.9%]). Laboratory tests results were available for 489 patients (33.7%) in the cataract group; of these, 275 results (56.2%) had abnormal values, and 18 patients (6.5%) required preoperative interventions. Preoperative test results were available for 772 out of 818 patients (94.4%) having noncataract procedures. Of these, 384 results (49.7%) had abnormal values, and 10 patients (2.6%) required additional intervention. No significant differences were observed for the rate of surgery cancellations between the cataract and noncataract patient groups (0.6% vs 1.0%; P = .24). Of the 12 patients (0.5%) who had complications, all had undergone preoperative testing., Conclusions: No differences in outcomes and complications were observed among patients who underwent cataract or noncataract surgery. It is reasonable to consider avoiding preoperative testing in patients undergoing ophthalmologic surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Both early life aversive experiences and intrinsic alterations in early postnatal neurodevelopment are considered predisposing factors for psychiatric disorders, such as schizophrenia. The prefrontal cortex and the hippocampus have protracted postnatal development and are affected in schizophrenic patients. Interestingly, similar alterations have been observed in the retrosplenial cortex (RSC). Studies in patients and animal models of schizophrenia have found alterations in cortical parvalbumin (PV) expressing interneurons, making them good candidates to study the etiopathology of this disorder. Some of the alterations observed in PV+ interneurons may be mediated by perineuronal nets (PNNs), specialized regions of the extracellular matrix, which frequently surround these inhibitory neurons. In this study, we have used a double hit model (DHM) combining a single perinatal injection of an NMDAR antagonist (MK801) to disturb early postnatal development and post-weaning social isolation as an early life aversive experience. We have investigated PV expressing interneurons and PNNs in the hippocampus and the RSC of adult male mice, using unbiased stereology. In the CA1, but not in the CA3 region, of the hippocampus, the number of PNNs and PV + PNN+ cells was affected by the drug treatment, and a significant decrease of these parameters was observed in the groups of animals that received MK801. The percentage of PNNs surrounding PV+ cells was significantly decreased after treatment in both hippocampal regions; however, the impact of isolation was observed only in CA1, where isolated animals presented lower percentages. In the RSC , we observed significant effects of isolation, MK801 and the interaction of both interventions on the studied parameters; in the DHM, we observed a significantly lower number of PV+, PNNs, and PV+PNN+cells when compared to control mice. Similar significant decreases were observed for the groups of animals that were just isolated or treated with MK801. To our knowledge, this is the first report on such alterations in the RSC in an animal model combining neurodevelopmental alterations and aversive experiences during infancy/adolescence. These results show the impact of early-life events on different cortical regions, especially on the structure and plasticity of PV+ neurons and their involvement in the emergence of certain psychiatric disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Klimczak, Rizzo, Castillo-Gómez, Perez-Rando, Gramuntell, Beltran and Nacher.)

A number of regulatory factors are recruited to chromatin by specialized RNAs. Whether RNA has a more general role in regulating the interaction of proteins with chromatin has not been determined. We used proteomics methods to measure the global impact of nascent RNA on chromatin in embryonic stem cells. Surprisingly, we found that nascent RNA primarily antagonized the interaction of chromatin modifiers and transcriptional regulators with chromatin. Transcriptional inhibition and RNA degradation induced recruitment of a set of transcriptional regulators, chromatin modifiers, nucleosome remodelers, and regulators of higher-order structure. RNA directly bound to factors, including BAF, NuRD, EHMT1, and INO80 and inhibited their interaction with nucleosomes. The transcriptional elongation factor P-TEFb directly bound pre-mRNA, and its recruitment to chromatin upon Pol II inhibition was regulated by the 7SK ribonucleoprotein complex. We postulate that by antagonizing the interaction of regulatory proteins with chromatin, nascent RNA links transcriptional output with chromatin composition., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Significant and persistent racial and ethnic disparities exist related to infant mortality and other birth outcomes. Few models exist that aim to prepare organizations to implement essential features, such as community engagement or intervening on social determinants of health., Methods: Between 2013 and 2015, teams from seven local health departments participated in the Institute for Equity in Birth Outcomes (EI) with the goals of building capacity and implementing changes to address equity in birth outcomes. Four of the teams enrolled in the first cohort (2013-2015), and three enrolled in cohort two (2014-2015). To examine the EI effort and its impact on capacity and implementation of changes, two types of assessments were completed. Capacities of the teams in specific key areas were assessed using "Best Change Process" instruments at the completion of participation in the EI. Teams also documented on an ongoing basis implementation of interventions. The data were analyzed using descriptive statistics and Pearson Correlation tests., Results: Best Change Process capacity scores were higher in the first cohort than in the second and were highly correlated with implementation of changes (Pearson's Correlation = 0.838, p = 0.037). Collectively, the teams implemented about 32 new programs, policies, practices, and systems changes aimed at addressing equity in birth outcomes. Most interventions were based on scientific recommendations and local epidemiologic data., Discussion: The results of the study suggest the EI is a promising approach that may result in strong capacity and ability to implement interventions aimed at addressing equity in birth outcomes.