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Objective: The aim of this study was to establish the utility of the NIH Toolbox as a cognitive screener of executive functions in the clinical context. Additionally, we aimed to investigate whether age and time on transfusion were related to executive function performance. Method: Twenty-eight children and adolescents with sickle cell anemia (SCA) between 8 and 18 years (M = 13.28, SD = 3.05) on transfusion treatment were included. Participants completed five NIH Toolbox tasks (three executive function tasks and two non-executive function control tasks). Results: Mean scores on one of the three executive function measures (inhibitory control) fell below the average range (M = 81.36, SD = 14.01) with approximately 70% of children from both groups below the average range. Scores for processing speed (M = 86.82, SD = 22.01) and cognitive flexibility (M = 85.75, SD = 12.67) were low averages. As expected, scores on non-executive measures (language and memory) fell within the average range. No significant differences were observed between children with silent stroke and no stroke on executive function measures. Older age (p <.01) and length of time on transfusion (p <.05) predicted lower inhibitory control scores. Conclusions: Findings provide evidence for poor development of inhibitory control with age in this patient population. As the NIH Toolbox successfully highlighted expected deficits in this patient population, this study supports the use of this tool as a brief screening measure for children with SCD. The clinical and theoretical implications of the findings are discussed. [ABSTRACT FROM AUTHOR]

In this paper, we summarize findings from the Tenth International Workshop on Tropical Cyclones (IWTC-10) subgroup on operational track forecasting techniques and capability. The rate of improvement in the accuracy of official forecast tracks (OFTs) appears to be slowing down, at least for shorter lead times, where we may be approaching theoretical limits. Operational agencies continue to use consensus methods to produce the OFT with most continuing to rely on an unweighted consensus of four to nine NWP models. There continues to be limited use of weighted consensus techniques, which is likely a result of the skills and additional maintenance needed to support this approach. Improvements in the accuracy of ensemble mean tracks is leading to increased use of ensemble means in consensus tracks. Operational agencies are increasingly producing situation-dependent depictions of track uncertainty, rather than relying on a static depiction of track forecast certainty based on accuracy statistics from the preceding 5 years. This trend has been facilitated by the greater availability of ensemble NWP guidance, particularly vortex parameter files, and improved spread in ensembles. Despite improving spread-skill relationships, most ensemble NWP systems remain under spread. Hence many operational centers are looking to leverage "super-ensembles" (ensembles of ensembles) to ensure the full spread of location probability is captured. This is an important area of service development for multi-hazard impactbased warnings as it supports better decision making by emergency managers and the community in the face of uncertainty. [ABSTRACT FROM AUTHOR]

Article 12 of the United Nations Convention of the Rights of the Child (UNCRC) (1989) sets out the right for all children to be heard and for their opinions to be given due weight. However, the voices of children with disabilities often remain silenced as their perspectives are rarely consulted. This paper describes how a visual, participatory research method called Photovoice was used to elicit the voices of students with Intellectual Disabilities (ID) in mainstream post-primary schools in the Republic of Ireland. Thirteen students with ID in four schools across Ireland participated by taking photographs of aspects of their school life that were meaningful to them. Photographs focused on places, spaces, objects and examples of learning, including their role in decision making. This paper details the stages of the Photovoice method which was adapted to support students to participate in the research process. It provides guidance on how to address the ethical and methodological concerns which arise when researching with children. It outlines a two-step approach to analysis, where participating students interpreted and created meaning which was further developed by the Principal Investigator. Employing Photovoice repositions students in this study as co-researchers and co-creators of meaning. Its use operationalises Lundy's Model of Participation (2007) by providing space, voice, audience and influence which are necessary for children to express their views and have their voices heard in an ethical and inclusive manner. [ABSTRACT FROM AUTHOR]

As a heterogeneous disease, breast cancer (BC) has been characterized by the uncontrolled proliferation of mammary epithelial cells. The tumor microenvironment (TME) also contains inflammatory cells, fibroblasts, the extracellular matrix (ECM), and soluble factors that all promote BC progression. In this sense, the macrophage migration inhibitory factor (MIF), a pleiotropic pro-inflammatory cytokine and an upstream regulator of the immune response, enhances breast tumorigenesis through escalating cancer cell proliferation, survival, angiogenesis, invasion, metastasis, and stemness, which then brings tumorigenic effects by activating key oncogenic signaling pathways and inducing immunosuppression. Against this background, this review was to summarize the current understanding of the MIF pathogenic mechanisms in cancer, particularly BC, and address the central role of this immunoregulatory cytokine in signaling pathways and breast tumorigenesis. Furthermore, different inhibitors, such as small molecules as well as antibodies (Abs) or small interfering RNA (siRNA) and their anti-tumor effects in BC studies were examined. Small molecules and other therapy target MIF. Considering MIF as a promising therapeutic target, further clinical evaluation of MIF-targeted agents in patients with BC was warranted. [ABSTRACT FROM AUTHOR]

In this review, the process of extracting precise values for NMR interaction tensors from single crystal samples is systematically explored. Starting with a description of the orientation dependence of the considered interactions, i.e., chemical shift, dipolar, and quadrupole interaction, the techniques for acquiring and analysing single-crystal spectra are outlined. This includes the 'classical' approach, which requires the acquisition of three rotation patterns around three rotation axes that are orthogonal to each other, as well as more recent strategies aimed at reducing the number of required NMR spectra. One such strategy is the 'single-rotation method', which exploits the symmetry relations between tensors in the crystal structure to reduce the necessary amount of orientation-dependent data. This concept may be extended to additionally include the orientation of the goniometer axis itself in the data fit, which may be termed the 'minimal-rotation method'. Other, more exotic schemes, such as the use of specialised probe designs or the investigation of single crystals under magic-angle-spinning, are also briefly discussed. Actual values of NMR interaction tensors as determined from the various single-crystal methods have been collected and are provided in tables for spin I = 1 / 2 , I = 1 , and half-integer spins with I > 1 / 2 . [ABSTRACT FROM AUTHOR]

Background: Despite significant advancements in the development of anticancer therapies over the past few decades, the clinical management of colorectal cancer remains a challenging task. This study aims to investigate the inhibitory effects of cancer-targeting liposomes against colorectal cancer. Materials and Methods: Liposomes consisting of 3β-[N-(N′, N′-dimethylamino ethane)carbamoyl]-cholesterol (DC-CHOL), cholesterol (CHOL), and dioleoylphosphatidylethanolamine (DOPE) at a molar ratio of 1:1:0.5 were created and used as carriers to deliver an apoptosis-inducing plasmid encoding the tumor necrosis factor-related apoptosis-inducing ligand (pTRAIL) gene, along with the toll-like receptor (TLR7) agonist Rsiquimod (R848). The rationale behind this design is that pTRAIL can trigger cancer cell apoptosis by activating the DR4/5 receptor, while R848 can stimulate the immune microenvironment. Results: Experimental results demonstrated the synergistic effects of R848 and pTRAIL encapsulated by liposomes (RTL) in suppressing the proliferation of colorectal cancer cells. Moreover, further in vivo investigations revealed the strong anti-tumor efficacy of RTL in xenograft and orthotropic in situ models of colorectal cancer. Conclusions: These findings collectively highlight the therapeutic potential of R848/pTRAIL-loaded liposomes in the treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Apoptosis is an important cellular response to viral infection. In this study, we identified activating molecule in Beclin1-regulated autophagy protein 1 (AMBRA1) as a positive regulator of apoptosis triggered by double-stranded (ds)RNA. Depletion of AMBRA1 by gene editing significantly reduced dsRNA-induced apoptosis, which was largely restored by trans-complementation of AMBRA1. Mechanistically, AMBRA1 interacts with mitochondrial antiviralsignaling protein (MAVS), a key mitochondrial adaptor in the apoptosis pathway induced by dsRNA and viral infection. Further co-immunoprecipitation analysis demonstrated that the mitochondrial localization of MAVS was essential for their interaction. The impact of AMBRA1 on dsRNA-induced apoptosis relied on the presence of MAVS and caspase-8. AMBRA1 was involved in the stabilization of MAVS through preventing its dsRNA-induced proteasomal degradation. Consistently, AMBRA1 upregulated the apoptosis induced by Semliki Forest virus infection. Taken together, our work illustrated a role for AMBRA1 in virus-induced apoptosis through interacting with and stabilizing MAVS. [ABSTRACT FROM AUTHOR]

Copyright of Revista Colombiana de Ciencias Sociales is the property of Fondo Editorial Fundacion Universitaria Luis Amigo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Marek's disease (MD), caused by the Marek's disease virus, is a lymphoproliferative disease in chickens that can be controlled by vaccination. However, the current vaccines can limit tumor growth and death but not virus replication and transmission. The present study aimed to evaluate host responses following intramuscular injection of an mRNA vaccine encoding gB and pp38 proteins of the MDV within the first 36 h. The vaccine was injected in low and high doses using prime and prime-boost strategies. The expression of type I and II interferons (IFNs), a panel of interferon-stimulated genes, and two key antiviral cytokines, IL-1β and IL-2, were measured in spleen and lungs after vaccination. The transcriptional analysis of the above genes showed significant increases in the expression of MDA5, Myd88, IFN-α, IFN-β, IFN-γ, IRF7, OAS, Mx1, and IL-2 in both the spleen and lungs within the first 36 h of immunization. Secondary immunization increased expression of all the above genes in the lungs. In contrast, only IFN-γ, MDA5, MyD88, Mx1, and OAS showed significant upregulation in the spleen after the secondary immunization. This study shows that two doses of the MDV mRNA vaccine encoding gB and pp38 antigens activate innate and adaptive responses and induce an antiviral state in chickens. [ABSTRACT FROM AUTHOR]

Inflammasomes comprise a group of protein complexes with fundamental roles in the induction of inflammation. Upon sensing stress factors, their assembly induces the activation and release of the pro-inflammatory cytokines interleukin (IL)-1β and -18 and a lytic type of cell death, termed pyroptosis. Recently, CARD8 has joined the group of inflammasome sensors. The carboxy-terminal part of CARD8, consisting of a function-to-find-domain (FIIND) and a caspase activation and recruitment domain (CARD), resembles that of NLR family pyrin domain containing 1 (NLRP1), which is recognized as the main inflammasome sensor in human keratinocytes. The interaction with dipeptidyl peptidases 8 and 9 (DPP8/9) represents an activation checkpoint for both sensors. CARD8 and NLRP1 are activated by viral protease activity targeting their amino-terminal region. However, CARD8 also has some unique features compared to the established inflammasome sensors. Activation of CARD8 occurs independently of the inflammasome adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), leading mainly to pyroptosis rather than the activation and secretion of pro-inflammatory cytokines. CARD8 was also shown to have anti-inflammatory and anti-apoptotic activity. It interacts with, and inhibits, several proteins involved in inflammation and cell death, such as the inflammasome sensor NLRP3, CARD-containing proteins caspase-1 and -9, nucleotide-binding oligomerization domain containing 2 (NOD2), or nuclear factor kappa B (NF-κB). Single nucleotide polymorphisms (SNPs) of CARD8, some of them occurring at high frequencies, are associated with various inflammatory diseases. The molecular mechanisms underlying the different pro- and anti-inflammatory activities of CARD8 are incompletely understood. Alternative splicing leads to the generation of multiple CARD8 protein isoforms. Although the functional properties of these isoforms are poorly characterized, there is evidence that suggests isoform-specific roles. The characterization of the functions of these isoforms, together with their cell- and disease-specific expression, might be the key to a better understanding of CARD8's different roles in inflammation and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Polycystic Ovary Syndrome (PCOS) presents multifaceted challenges affecting women's reproductive, metabolic, and psychological systems, consequently impacting their psychological and emotional well-being. The utilization of meditation and mindfulness interventions (MMIs) is found to be increasing for the management of PCOS. This scoping review systematically explored the current literature to identify the type and application of MMIs for PCOS management. A systematic search of literature was conducted using CINAHL, PsycINFO, Scopus, MEDLINE, and PubMed databases for identifying studies conducted on the usage of MMIs in women diagnosed with PCOS, irrespective of age. The comprehensive search identified 14 trials (comprising 17 citations) meeting inclusion criteria, involving 723 participants across various age groups. Among these, nine were randomized controlled trials (RCTs), while the remaining comprised non-RCTs. Several types of MMIs, including Rajayoga of Brahmakumaris, Yoga Nidra, OM cyclic meditation, unspecified forms of meditation, mindfulness-based stress reduction programs, mindful yoga, and mindfulness-based activities, were used. Outcomes were predominantly assessed in psychological domains (n=11), followed by anthropometric (n=9), quality of life (n=7), and metabolic metrics (n=7). The review findings suggest the integration of meditation with conventional treatment modalities. Preliminary data indicate that MMIs have the potential to improve psychosocial well-being and quality of life among PCOS-affected women. However, adequately powered studies with extended follow-up periods are required to investigate the mechanisms and therapeutic efficacy of MMIs, particularly concerning reproductive outcomes and weight management. Furthermore, diligent monitoring and reporting of adverse events and adherence are essential for a comprehensive understanding of MMI utilization in PCOS management. [ABSTRACT FROM AUTHOR]

3D micro-nano devices are expected to become the mainstay of multi-color solid-state lighting in the future because of their broad-band characteristic and the advantage of integrating the monolithic light-emitting diode on a single chip. In this work, InGaN/GaN micro-truncated pyramid arrays with six equivalent (10 1 ̄ 1) semi-polar facets and one (0001) polar facet were successfully prepared by the metal-organic chemical vapor deposition technology. The average diameter of the obtained uniform micro-truncated pyramids was 6.8 µm with a height of 2.4 µm. According to the results of micro-photoluminescence performed, the InGaN/GaN micro-truncated pyramid arrays can achieve multi-color emission from blue to red. The luminescent positions corresponding to different wavelengths were detected by the cathode luminescence spectrum. The multi-color emission was related to the quantum hybrid structures apart from the discrepancy of In composition in different positions. The developed microstructure can create multi-color emission by combining distinct luminescence modes, which can aid in the design of future optoelectronic devices. [ABSTRACT FROM AUTHOR]

Caspase (CASP) is a protease family that plays a vital role in apoptosis, development, and immune response. Herein, we reported the identification and characterization of two CASPs, AjCASPX1 and AjCASPX2, from the sea cucumber Apostichopus japonicus, an important aquaculture species. AjCASPX1/2 share similar domain organizations with the vertebrate initiator caspases CASP2/9, including the CARD domain and the p20/p10 subunits with conserved functional motifs. However, compared with human CASP2/9, AjCASPX1/2 possess unique structural features in the linker region between p20 and p10. AjCASPX1, but not AjCASPX2, induced marked apoptosis of human cells by activating CASP3/7. The recombinant proteins of AjCASPX2 and the CARD domain of AjCASPX2 were able to bind to a wide range of bacteria, as well as bacterial cell wall components, and inhibit bacterial growth. AjCASPX1, when expressed in Escherichia coli, was able to kill the host bacteria. Under normal conditions, AjCASPX1 and AjCASPX2 expressions were most abundant in sea cucumber muscle and coelomocytes, respectively. After bacterial infection, both AjCASPX1 and AjCASPX2 expressions were significantly upregulated in sea cucumber tissues and cells. Together, these results indicated that AjCASPX1 and AjCASPX2 were initiator caspases with antimicrobial activity and likely functioned in apoptosis and immune defense against pathogen infection. [ABSTRACT FROM AUTHOR]

In the modern world, dams and the artificial reservoirs behind them serve the increasing demand for water across diverse needs such as agriculture, energy production, and drinking water. As dams continue to proliferate, monitoring water availability influenced by reservoir operations is now of paramount importance. The Reservoir Assessment Tool (RAT) is a data-driven software platform that integrates satellite remote sensing with hydrological models, enabling the estimation of key reservoir parameters such as inflow, outflow, surface area, evaporation, and storage changes. The earliest version of RAT (version 1.0) was set up for 1598 reservoirs around the world with limitations in functional robustness, updating frequency, and scalability. Some of these limitations on updating frequency and functional robustness were addressed in version 2.0 that was later made operational for the intergovernmental agency of the Mekong River Commission. Recognizing the need for scalability to mobilize the global water management community to benefit from satellite remote sensing, we hereby introduce RAT version 3.0. This version is optimized for accelerating open collaboration among users for continuous improvement and customization of RAT to enable reservoir management breakthroughs. RAT 3.0 represents a wholesale overhaul from the previous versions to empower the global community of users and developers in the spirit of the open-source movement. RAT 3.0 allows reservoir monitoring advancements and new functional developments that can be freely exchanged and seamlessly integrated for continuous evolution of the software. A centralized web application has also been established to facilitate the storage and dissemination of global reservoir monitoring information along with comprehensive training resources. RAT 3.0 aspires to bridge the traditional practices of water management community with the capabilities of satellite remote sensing. The global impact of the software can be expected to increase as uptake spreads, enabling a more sustainable and equitable utilization of our planet's water resources. [ABSTRACT FROM AUTHOR]

In Australia, dental caries are observed in almost half of children starting school. Oral health promotion programs are being implemented in early childhood education and care (ECEC) settings to promote oral health. This study examined children's perceptions of one such program, the Bright Smiles Bright Futures (BSBF) program in ECEC settings in New South Wales, Australia. Data were collected using focus group discussions from 15 children aged 3–5 years, transcribed verbatim, and analysed through inductive thematic analysis. Three themes were identified as follows: (i) oral health knowledge of children, (ii) oral hygiene practices routine and skills development, and (iii) evaluation of the oral health promotion kit and opportunities for improvement. Children's perspectives highlight the BSBF program's success in communicating key messages to promote oral health. The integration of family-centric approaches, acknowledgement of children's preferences, and the use of interactive tools collectively enhance the overall effectiveness of the oral health promotion program. [ABSTRACT FROM AUTHOR]

Copyright of Pedagogy Studies / Pedagogika is the property of Vytautas Magnus University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The dry root of the soybean plant Astragalus membranaceus (Fisch) Bge. var. mongholicus (Bge) Hsiao or A. membranaceus (Fisch) Bge, Astragali Radix (AR) has a long medicinal history. Astragalus polysaccharide (APS), the natural macromolecule that exhibits immune regulatory, anti-inflammatory, antitumor, and other pharmacological activities, is an important active ingredient extracted from AR. Recently, APS has been increasingly used in cancer therapy owing to its anti-tumor ability as it prevents the progression of prostate, liver, cervical, ovarian, and non-small-cell lung cancer by suppressing tumor cell growth and invasion and enhancing apoptosis. In addition, APS enhances the sensitivity of tumors to antineoplastic agents and improves the body's immunity. This macromolecule has prospects for broad application in tumor therapy through various pathways. In this article, we present the latest progress in the research on the anti-tumor effects of APS and its underlying mechanisms, aiming to provide novel theoretical support and reference for its use in cancer therapy. [ABSTRACT FROM AUTHOR]

Lung cancer is often triggered by genetic alterations that result in the expression of oncogenic tyrosine kinases. Specifically, ALK, RET, and ROS1 chimeric receptor tyrosine kinases are observed in approximately 5–7%, 1–2%, and 1–2% of NSCLC patients, respectively. The presence of these fusion genes determines the response to tyrosine kinase inhibitors. Thus, accurate detection of these gene fusions is essential in cancer research and precision oncology. To address this need, we have developed a multiplexed RT-qPCR assay using xeno nucleic acid (XNA) molecular clamping technology to detect lung cancer fusions. This assay can quantitatively detect thirteen ALK, seven ROS1, and seven RET gene fusions in FFPE samples. The sensitivity of the assay was established at a limit of detection of 50 copies of the synthetic template. Our assay has successfully identified all fusion transcripts using 50 ng of RNA from both reference FFPE samples and cell lines. After validation, a total of 77 lung cancer patient FFPE samples were tested, demonstrating the effectiveness of the XNA-based fusion gene assay with clinical samples. Importantly, this assay is adaptable to highly degraded RNA samples with low input amounts. Future steps involve expanding the testing to include a broader range of clinical samples as well as cell-free RNAs to further validate its applicability and reliability. [ABSTRACT FROM AUTHOR]

The present study builds a regional urban resilience index model through ecological density, spatial distance, and social division based on the Density, Distance and Division (3D) theory of new economic geography. In total, 41 cities in the Yangtze River Delta, China, were used as the research object, and the characteristics of the urban resilience index and the driving effect of factors were investigated. The results show that: (1) the Yangtze River Delta urban agglomerations are at the primary level of resilience, which presents a spatial development pattern of one core and two belts; (2) there is a significant positive correlation between external resistance and internal restoration, and the restoration lags behind the resistance in most cities because of the lack of internal density effects; and (3) the driving effects of ecological density, spatial distance, and social division elements on the urban resilience level are different at the regional and district scales. Ecological density and social division are stronger at the district scale, and the spatial distance is stronger at the regional scale. [ABSTRACT FROM AUTHOR]

Longitudinal data from the Mexican Family Life Survey, in conjunction with aggregated vital statistics and census data, are used to examine how Mexican adults' experiences of violent victimization and perceptions of personal safety, as well as the homicide rate in their local community, are associated with the likelihood that they migrate to the USA. Multilevel logistic regression analyses provide suggestive evidence that Mexicans who report being recent victims of violence and who perceive a recent deterioration in their personal safety are more likely than others to migrate to the USA. The association between perceived deterioration in personal safety and the probability of migrating to the USA is particularly strong among residents of urban areas. We find no evidence that a generalized fear of crime or exposure to a high municipality-level homicide rate is associated with USA-bound migration. [ABSTRACT FROM AUTHOR]

Background: Effective pain control is crucial to optimise the success of medical procedures. Immersive virtual reality (VR) technology could offer an effective non-invasive, non-pharmacological option to distract patients and reduce their experience of pain. We aimed to evaluate the efficacy of Immersive virtual reality (VR) technology in reducing patient's pain perception during various medical procedures by conducting a systematic review and meta-analysis. Methods: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, and SIGLE until December 2022 for all randomised clinical trials (RCT) evaluating any type of VR in patients undergoing any medical procedure. We conducted a random effect meta-analysis summarising standardised mean differences (SMD) with 95% confidence intervals (CI). We evaluated heterogeneity using I2 and explored it using subgroup and meta-regression analyses. Results: In total, we included 92 RCTs (n = 7133 participants). There was a significant reduction in pain scores with VR across all medical procedures (n = 83, SMD − 0.78, 95% CI − 1.00 to − 0.57, I2 = 93%, p = < 0.01). Subgroup analysis showed varied reduction in pain scores across trial designs [crossover (n = 13, SMD − 0.86, 95% CI − 1.23 to − 0.49, I2 = 72%, p = < 0.01) vs parallel RCTs (n = 70, SMD − 0.77, 95% CI − 1.01 to − 0.52, I2 = 90%, p = < 0.01)]; participant age groups [paediatric (n = 43, SMD − 0.91, 95% CI − 1.26 to − 0.56, I2 = 87%, p = < 0.01) vs adults (n = 40, SMD − 0.66, 95% CI − 0.94 to − 0.39, I2 = 89%, p = < 0.01)] or procedures [venepuncture (n = 32, SMD − 0.99, 95% CI − 1.52 to − 0.46, I2 = 90%, p = < 0.01) vs childbirth (n = 7, SMD − 0.99, 95% CI − 1.59 to − 0.38, I2 = 88%, p = < 0.01) vs minimally invasive medical procedures (n = 25, SMD − 0.51, 95% CI − 0.79 to − 0.23, I2 = 85%, p = < 0.01) vs dressing changes in burn patients (n = 19, SMD − 0.8, 95% CI − 1.16 to − 0.45, I2 = 87%, p = < 0.01)]. We explored heterogeneity using meta-regression which showed no significant impact of different covariates including crossover trials (p = 0.53), minimally invasive procedures (p = 0.37), and among paediatric participants (p = 0.27). Cumulative meta-analysis showed no change in overall effect estimates with the additional RCTs since 2018. Conclusions: Immersive VR technology offers effective pain control across various medical procedures, albeit statistical heterogeneity. Further research is needed to inform the safe adoption of this technology across different medical disciplines. [ABSTRACT FROM AUTHOR]

Background: The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity as a negative regulator of NF- ĸB, and has been associated with regulation of proteins involved in inflammation. Expression of CARD8 mRNA and protein has been identified in human atherosclerotic lesions, and the truncated T30A variant (rs2043211) of CARD8 has been associated with lower C-reactive (CRP) and MCP-1 levels in myocardial infarction patients. The present study examines the role of a genetic variation in the CARD8 gene in relation to a selection of markers of inflammation. Methods: In a cross-sectional study of young healthy individuals (18.0–25.9 yrs, n = 744) the association between the rs2043211 variant in the CARD8 gene and protein markers of inflammation was assessed. Genotyping of the CARD8 C10X (rs2043211) polymorphism was performed with TaqMan real time PCR on DNA from blood samples. Protein levels were studied via Olink inflammation panel (https://olink.com/). Using linear models, we analyzed men and two groups of women with and without estrogen containing contraceptives separately, due to previous findings indicating differences between estrogen users and non-estrogen using women. Genotypes were analyzed by additive, recessive and dominant models. Results: The minor (A) allele of the rs2043211 polymorphism in the CARD8 gene was associated with lower levels of CCL20 and IL-6 in men (CCL20, Additive model: p = 0.023; Dominant model: p = 0.016. IL-6, Additive model: p = 0.042; Dominant model: p = 0.039). The associations remained significant also after adjustment for age and potential intermediate variables. Conclusions: Our data indicate that CARD8 may be involved in the regulation of CCL20 and IL-6 in men. No such association was observed in women. These findings strengthen and support previous in vitro data on IL-6 and CCL20 and highlight the importance of CARD8 as a factor in the regulation of inflammatory proteins. The reason to the difference between sexes is however not clear, and the influence of estrogen as a possible factor important for the inflammatory response needs to be further explored. [ABSTRACT FROM AUTHOR]

Brain tumors represent a heterogeneous group of neoplasms characterized by a high degree of aggressiveness and a poor prognosis. Despite recent therapeutic advances, the treatment of brain tumors, including glioblastoma (GBM), an aggressive primary brain tumor associated with poor prognosis and resistance to therapy, remains a significant challenge. Receptor tyrosine kinases (RTKs) are critical during development and in adulthood. Dysregulation of RTKs through activating mutations and gene amplification contributes to many human cancers and provides attractive therapeutic targets for treatment. Under physiological conditions, the Met RTK, the hepatocyte growth factor/scatter factor (HGF/SF) receptor, promotes fundamental signaling cascades that modulate epithelial-to-mesenchymal transition (EMT) involved in tissue repair and embryogenesis. In cancer, increased Met activity promotes tumor growth and metastasis by providing signals for proliferation, survival, and migration/invasion. Recent clinical genomic studies have unveiled multiple mechanisms by which MET is genetically altered in GBM, including focal amplification, chromosomal rearrangements generating gene fusions, and a splicing variant mutation (exon 14 skipping, METex14del). Notably, MET overexpression contributes to chemotherapy resistance in GBM by promoting the survival of cancer stem-like cells. This is linked to distinctive Met-induced pathways, such as the upregulation of DNA repair mechanisms, which can protect tumor cells from the cytotoxic effects of chemotherapy. The development of MET-targeted therapies represents a major step forward in the treatment of brain tumours. Preclinical studies have shown that MET-targeted therapies (monoclonal antibodies or small molecule inhibitors) can suppress growth and invasion, enhancing the efficacy of conventional therapies. Early-phase clinical trials have demonstrated promising results with MET-targeted therapies in improving overall survival for patients with recurrent GBM. However, challenges remain, including the need for patient stratification, the optimization of treatment regimens, and the identification of mechanisms of resistance. This review aims to highlight the current understanding of mechanisms underlying MET dysregulation in GBM. In addition, it will focus on the ongoing preclinical and clinical assessment of therapies targeting MET dysregulation in GBM. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is the most frequent and malignant primary tumor of the brain. Patient survival is dismal and personalized therapies are missing. In the diagnostic arena, the lack of an all-inclusive molecular subgroup classification for this tumor has delayed its personalized therapy. This study presents the validation of the first molecular subgroup classification of glioblastoma in a large patient cohort, and opens the avenue to rationalized therapeutic approaches. Preliminary comparative demographic studies between Caucasian/White and African American/Black patients offer the first comparative overview of the molecular diversity of glioblastoma. One molecular subgroup, G6/Multi-RTK, assembling several targetable gene fusions, is expanded and includes novel or rare examples of such events with associated tumorigenic mechanisms and cellular phenotypes. The bioinformatic analysis of the principal oncogenic pathways reveals important genetic associations and the extent of genomic heterogeneity at the populational level, offering the first organized molecular profiling of glioblastoma to be used as a foundation for therapy design, clinical practice and scientific research. Glioblastoma is the most frequent and malignant primary neoplasm of the central nervous system. In a recent breakthrough study on a prospective Discovery cohort, I proposed the first all-inclusive molecular classification of glioblastoma into seven subgroups, G1-G7, based on MAPK pathway activation. New data from a WHO-grade-4 diffuse glioma prospective Validation cohort offers, in this study, an integrated demographic–molecular analysis of a 213-patient Combined cohort. Despite cohort differences in the median age and molecular subgroup distribution, all the prospectively-acquired cases from the Validation cohort mapped into one of the G1-G7 subgroups defined in the Discovery cohort. A younger age of onset, higher tumor mutation burden and expanded G1/EGFR-mutant and G3/NF1 glioblastoma subgroups characterized the glioblastomas from African American/Black relative to Caucasian/White patients. The three largest molecular subgroups were G1/EGFR, G3/NF1 and G7/Other. The fourth largest subgroup, G6/Multi-RTK, was detailed by describing a novel gene fusion ST7–MET, rare PTPRZ1–MET, LMNA–NTRK1 and GOPC–ROS1 fusions and their overexpression mechanisms in glioblastoma. The correlations between the MAPK pathway G1-G7 subgroups and the PI3-kinase/PTEN, TERT, cell cycle G1 phase and p53 pathways defined characteristic subgroup pathway profiles amenable to personalized targeted therapy. This analysis validated the first all-inclusive molecular classification of glioblastoma, showed significant demographic and molecular differences between subgroups, and provided the first ethnic molecular comparison of glioblastoma. [ABSTRACT FROM AUTHOR]

Cambodia has made progress towards addressing Sustainable Development Goal 6.1. "By 2030, achieve universal and equitable access to safe and affordable drinking water for all", but challenges remain in fully realizing this target. We begin this paper by reviewing current country-wide access to safe and affordable water and subsequently report on the results of water sampling done for E. coli in a peri-urban area north of Phnom Penh that was conducted between 2018 and 2020. The sampling examined E. coli levels in source waters, including rivers, ponds, a large lake/wetland, wells, rainwater harvesting systems, piped water, and bottled water. Sampling from household storage containers and in-home drinking cups also was done to assess the effects that handling practices might have on exposure to E. coli. We show that country-wide, as well as in the peri-urban study area, there has been increased access to piped water. Piped water and commercially-available bottled water (0.5-1.5 L PET bottles) had the lowest E. coli levels in our study area, although such bottled water is not an affordable alternative for many peri-urban families. Surface pond water and the Tonle Sap River contained the highest E. coli levels and would pose the greatest risk associated with direct consumption. Handling practices may impact drinking water quality, as a significant difference (p=0.2) was found in E. coli levels between samples taken from commerciallyavailable 0.5-1.5 L PET bottles and from household cups into which the bottled water was poured. There also was a significant difference (p<0.05) in E. coli levels between piped water sampled directly from the tap and piped water stored in bulk household containers. T The geometric mean concentration of E. coli in large, covered, traditional outdoor storage jars used for rainwater harvesting was nearly 10 times lower than the same type of jars that were not covered, although due to the small sample size and variability in the data, the difference was not significant (p=0.5). Despite the increasing availability of piped water service in the study area, we found a diversity of water source practices, including use of rainwater harvesting, surface water, 20 L bottled water, and wells. These source waters can be safe, but must be routinely monitored. The study illustrates the advantages of field-based testing for effective screening of E. coli in peri-urban areas. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lung cancer is a major burden to global health and is still among the most frequent and most lethal malignant diseases. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in a variety of processes including tumorigenesis, formation of a tumor microenvironment and metastasis. It is therefore a potential prognostic biomarker in malignant diseases. OBJECTIVE: In this study, we investigated the applicability of MIF in serum samples as a biomarker in lung cancer. METHODS: In a retrospective approach, we analyzed the sera of 79 patients with non-small-cell lung cancer (NSCLC) and 14 patients with small-cell lung cancer (SCLC) before the start of chemotherapy, as well as before the second and third chemotherapy cycle, respectively. Serum MIF levels were measured using a sandwich immunoassay with a sulfo-tag-labelled detection antibody, while pro-gastrin releasing peptide (proGRP) levels were determined with an enzyme-linked immunosorbent assay. RESULTS: No difference in serum MIF levels between responders and non-responders to chemotherapy was observed at all time points, while proGRP levels were significantly lower in responders before the second chemotherapy cycle (p = 0.012). No differences in biomarker levels depending on the histopathological classification of NSCLC patients was found. Moreover, in ROC curve analyses MIF was not able to distinguish between responders and non-responders to therapy. proGRP could differentiate between responders and non-responders before the second chemotherapy cycle (p = 0.015) with sensitivities of 43% at 90% and 95% specificity, respectively. Likewise, proGRP yielded significantly longer survival times of patients with low proGRP concentrations before the second chemotherapy cycle (p = 0.015) in Kaplan-Meier analyses, yet MIF showed no significant differences in survival times at all time points. Comparison with the biomarkers CEA and CYFRA 21-1 in the same cohort showed that these established biomarkers clearly performed superior to MIF and proGRP. CONCLUSIONS: From the present results, there is no indication that serum MIF may serve as a biomarker in prognosis and monitoring of response to therapy in lung cancer. Limitations of this study include its retrospective design, the inclusion of a larger NSCLC and a smaller SCLC subgroup, the classical chemotherapeutic treatment, the use of a non-diagnostic immunoassay (RUO-test) for MIF measurement and the lack of a validation cohort. Strengths of the study are its highly standardized procedures concerning sample collection, preanalytic treatment, measurements and quality control of the laboratory assays. [ABSTRACT FROM AUTHOR]

Research with children is influenced by researcher's own perspectives and the diverse constructions including socio cultural perspectives of childhood. Are young children respected and cared for or overlooked by the practitioner or researcher's personal goals in research? Are issues, related to ethics in relation to children's consent and participation in research lost in translation especially in terms of expectations and interpretation in different cultural contexts. This paper explores the diverse perspectives of issues around ethics related to research with young children in early years settings. It questions the perceived tensions around adults' decisions about children's participation in research. The issues related to children's voice, gatekeepers of consent, participation, power, and children's rights will be discussed and the extent to which they influence the decisions which adults make about children's participation in any research. [ABSTRACT FROM AUTHOR]

Community engagement in research enhances a community's ability to address its own needs and challenges while ensuring that researchers understand community priorities. Some confusion exists about the definition of community engagement in the context of veteran research. The purpose of this study was to search the literature to identify common applications of community engagement in U.S. veterans' research and to determine how and at what stage veterans were involved in the research process. A systematic scoping review was conducted using CINAHL Plus, Wiley Cochrane Library, Education Source, ERIC, APA PsycInfo, National Library of Medicine PubMed, ProQuest Social Services Abstracts, and SocIndex by two independent investigators. Forty-two of 1,977 studies from initial searches were included in this review. From these studies, we identified two aspects of veterans' involvement in research characterized as "community engagement": (a) veterans as participants and (b) veterans as partners in the research process. There is a need to encourage veterans' engagement and to standardize reporting of their engagement in the various phases of the research process. [ABSTRACT FROM AUTHOR]

Minor changes to complex structures can exert major influences on synthesis strategy and functional properties. Here we explore two parallel series of picrotoxinin (PXN, 1) analogs and identify leads with selectivity between mammalian and insect ion channels. These are the first SAR studies of PXN despite its >100-year history and are made possible by advances in total synthesis. We observe a remarkable stabilizing effect of a C5 methyl, which completely blocks C15 alcoholysis via destabilization of an intermediate twist-boat conformer; suppression of this secondary hydrolysis pathway increases half-life in plasma. C5 methylation also decreases potency against vertebrate ion channels (γ-Aminobutyric acid type A (GABAA) receptors) but maintains or increases antagonism of homologous invertebrate GABA-gated chloride channels (resistance to dieldrin (RDL) receptors). Optimal 5MePXN analogs appear to change the PXN binding pose within GABAARs by disruption of a hydrogen bond network. These discoveries were made possible by the lower synthetic burden of 5MePXN (2) and were illuminated by the parallel analog series, which allowed characterization of the role of the synthetically simplifying C5 methyl in channel selectivity. These are the first SAR studies to identify changes to PXN that increase the GABAA-RDL selectivity index. Minor changes to complex structures can exert major influences on synthesis strategy and functional properties but synthetic difficulties can obstruct the exploration of natural product function. Here the authors explore two parallel series of picrotoxinin analogs and identify leads with selectivity between mammalian and insect ion channels. [ABSTRACT FROM AUTHOR]

This paper analyzes the literature data on the role of cytokines in the pathogenesis of malignant neoplasms. Cytokines are biologically active, hormone-like proteins that regulate a wide range of processes occurring in the body. Cytokines determine the type and duration of the immune response, stimulation or suppression of cell growth, and their differentiation and functional activity. The complex of cytokines produced in the tumor microenvironment play an important role in the pathogenesis of malignant neoplasms. The spectra of biological activities of cytokines in most cases overlap. The same process in a cell can be stimulated by more than one cytokine, creating a favorable environment for the initiation and progression of cancer. The immune system can recognize transformed cells. Various cytokines correspond to specific pathways activated by receptors on the cell surface, which, in turn, induce intracellular signaling cascades that affect targeted cellular functions. Cytokine genes are mutually associated with oncogenes. Cytokines that are released in response to infection or inflammation or in the course of an immune response to an antigen can suppress tumor development. In turn, cytokines that attenuate apoptosis and promote invasion and metastasis promote tumor growth. Cytokines are involved in the initiation, development, and metastasis of malignant neoplasms through various mechanisms. [ABSTRACT FROM AUTHOR]

Sickle Cell Anemia (SCA) is the most common genetic disease worldwide caused by a single mutation in the gene HBB. The disease severity is very variable and depends on many factors. We evaluated the clinical and biological profile of sickle cell anemia children in rural Central Africa. This cross-sectional study was conducted in the Hôpital Saint Luc de Kisantu, located 120 km away from Kinshasa-DR Congo in an area of 35 km around Kisantu with a population of roughly 80 000 individuals. We included SCA patients aged 6 months to 18 years. We collected clinical and hematological data. The SCA scoring system proposed by Adegoke et al. in 2013 was applied to determine the disease severity. We searched for factors associated to the disease severity. This study included 136 patients, 66 males and 70 females (sex-ratio M/F 0.94). The mean severity score was 8.21 ± 5.30 (ranges 0–23). Fifty-nine (43.4%) children had mild disease, 62 (45.6%) moderate and 15 (11%) severe disease. Girls had higher levels of HbF than boys (p = 0.003). An inverse correlation was observed between fetal hemoglobin and the disease severity (p = 0.005, r −0.239, IC95% −6.139; −1.469). Some factors such age influence the occurrence of certain chronic complications such as avascular bone necrosis. In conclusion, the disease severity of SCA depends on multiple factors. In this study, fetal hemoglobin was the main modulator of the disease severity. These data may also serve as a baseline to initiate HU treatment in this setting. [ABSTRACT FROM AUTHOR]

In this work, we studied p-i-n InGaN/GaN core-shell microrod (μrod) LEDs using confocal microscopy with a spatial resolution below 500 nm in all three dimensions. At low excitation conditions, the devices emit in the red spectral range, while green and blue emissions become more prominent with increasing driving current. 3D photoluminescence (PL) maps demonstrate that the red emission originates from the apex of the tip area, while the green emission stems from the corners between m- and r-planes and the dominant blue emission from the m-plane. Analyzing individual μrods of the LED chip in a closed circuit configuration, a pronounced photocurrent is found for quasi-resonant laser excitation, indicating charge carrier tunneling losses out of the quantum well. This hypothesis is confirmed by applying an external voltage in the forward direction, where a characteristic blueshift of the single μrod PL signal is observed due to a modified band alignment, and a nonlinear increase in the PL intensity proves suppressed tunneling losses. [ABSTRACT FROM AUTHOR]

Friendship is a central focus in children's lives and is important for healthy development. During the Covid‐19 pandemic, children experienced restrictions on their interactions with friends. This research heard the voices of 10 children (7–11 years) in England regarding their friendships, drawing on data collected through creative participatory methods including drawings, photography and collages, and accompanying unstructured interviews. Findings provide new insights into how children endeavoured to maintain their friendships through virtual interactions, street/doorstep visits, and artwork, and how friendship disruption affected their well‐being. This paper argues for educators to heed the implications for the period of 'Covid recovery'. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the head and neck (HNSCC) is a malignant cancer disease in humans and animals. There is ample evidence that the high plasticity of cancer cells, i.e., their ability to switch from an epithelial to a mesenchymal, endothelial, and stem cell-like phenotype, chiefly contributes to progression, metastasis, and multidrug resistance of human HNSCCs. In feline HNSCC, the field of cancer cell plasticity is still unexplored. In this study, fourteen feline HNSCCs with a known feline papillomavirus (FPV) infection status were subjected to histopathological grading and subsequent screening for expression of epithelial, mesenchymal, and stem cell markers by immunohistochemistry (IHC) and immunofluorescence staining (IF). Irrespective of the FPV infection status, all tumors except one corresponded to high-grade, invasive lesions and concurrently expressed epithelial (keratins, E-cadherin, β-catenin) and mesenchymal (vimentin, N-cadherin, CD146) proteins. This finding is indicative for partial epithelial-mesenchymal transition (pEMT) events in the lesions, as similarly described for human HNSCCs. IF double staining revealed the presence of CD44/CD271 double-positive cells notably within the tumors' invasive fronts that likely correspond to cancer stem cells. Taken together, the obtained findings suggest that feline HNSCCs closely resemble their human counterparts with respect to tumor cell plasticity. [ABSTRACT FROM AUTHOR]

The Jensen, Jensen–Mercer, and Hermite–Hadamard inequalities have been key in advancing convex inequalities for scalars and operators, with several applications in fields like mathematical physics, operator theory and mathematical inequalities. This paper presents a new argument leading to interesting refinements of these celebrated inequalities. Applications that include entropy and operator inequalities will be presented. [ABSTRACT FROM AUTHOR]

Background: Dolomiaea costus (syn: Saussurea costus; Family Asteraceae) occupies an important place in the traditional Chinese medicinal plants and is prescribed for a wide range of disorders. The current study aimed to tentatively identify the phytoconstituents of D. costus extract and to explore antiproliferative activity against human breast cancer cells and its possible apoptotic mechanism along with antiviral activity against human adenovirus 5 (Adv-5). Methods: The phytoconstituents of 70% ethanol extract of D. costus were assessed using HPLC/ESI-MS/MS technique. The cell viability was investigated against breast cancer cell line (MCF-7) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Mechanistically, the apoptotic effects on the Bax, Bcl2 and Caspase 3 were determined via quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). Further, the antiviral activity was assessed against Adv-5 based on virucidal and adsorption mechanisms. Results: The HPLC/MS analysis of the extract revealed tentative identification of twenty compounds of polyphenolic nature, mainly flavonoids, lignans, coumarins, and anthocyanidins. The plant extract showed a cytotoxic effect against MCF-7 and Vero cells with IC50 values of 15.50 and 44 µg/ml, respectively, indicating its aggressiveness against the proliferation of breast cancer cells as confirmed by apoptotic genes expression which revealed upregulation of Bax and Caspase 3 but further insight analysis is needed to explore exact mechanistic pathway. Antiviral activity against Adv-5 was observed at a non-toxic concentration of the tested extract. Conclusions: Such observations against human breast cancer and viral replication supported further studies for nanoformulations in drug delivery systems as targeting therapy and in vivo studies before biomedical applications. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a metabolic disease wherein chronic hyperglycemia triggers various renal cell dysfunctions, eventually leading to progressive kidney failure. Rosa laevigata Michx. is a traditional Chinese herbal medicine. Many studies have confirmed its antioxidative, anti-inflammatory, and renoprotective effects. However, the effects and mechanisms of Rosa laevigata Michx. polysaccharide (RLP) in DN remain unclear. In this study, a DN mouse model was established to investigate the therapeutic effect of RLP on DN mice. Then, nontargeted metabolomics was used to analyze the potential mechanism of RLP in the treatment of DN. Finally, the effects of RLP on ferroptosis and the PI3K/AKT pathway were investigated. The results demonstrated that RLP effectively alleviated renal injury and reduced inflammation and oxidative stress in the kidney. In addition, nontargeted metabolomic analysis indicated that RLP could modulate riboflavin metabolism and tryptophan metabolism in DN mice. Notably, ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney were also ameliorated following RLP treatment. In conclusion, this study confirmed that RLP had a significant therapeutic effect on DN mice. Furthermore, RLP treatment modulated tryptophan metabolism and inhibited ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney. [ABSTRACT FROM AUTHOR]

Executive function and processing speed difficulties are observed in children living with sickle cell anemia (SCA). The influence of processing speed on executive function is not well understood. We recruited 59 children living with SCA and 24 matched controls aged 8–18 years between 2010 and 2016 from clinics in the UK. Children completed tests in processing speed and cognitive flexibility, subdomains of executive function. MRI scans were conducted within one year of testing; oxygen saturation was obtained on the day of testing. Hemoglobin levels were obtained from medical records. Caregivers completed the executive function questionnaire. Hierarchical linear regressions found that hemoglobin, oxygen saturation, age, infarct status, and processing speed were not independent predictors for any model. However, for all cognitive flexibility tests, there was a significant interaction between infarct status and processing speed; children without silent cerebral infarction (SCI) with faster processing speed had better cognitive flexibility. Our findings indicate that, when interpreting executive function difficulties, it is important to account for the relationship between SCI status and processing speed. More research is needed to elucidate the mechanisms, but clinically, including executive function testing as part of clinic visits by embedding psychologists within the healthcare team would appear to be a critical step. [ABSTRACT FROM AUTHOR]

The use of Internet tools virtually increases the work connectivity behavior after-hours (WCBA), is becoming increasingly common. Previous studies have found that WCBA has a double-edged sword effect on turnover intention (TI), but the configuration effect had been ignored. To investigate the configuration effect of WCBA, internal factors (i.e., psychological capital and mindfulness), and external factors (i.e., family-to-work conflict and social support), on TI. A total of 305 participants have been collected using convenience sampling. A questionnaire that covers six personal and contextual scales of the WCBA, psychological capital (PsyCap), mindfulness, family-to-work conflict (FWC), social support (SS), and TI, was used to gather data. Adhering to configurational theory, the study was conducted using fuzzy-set qualitative comparative analysis (fsQCA). it was revealed that seven antecedent configurations could achieve high TI, among them, WCBA existed in S4 and S6 but was absent in S5 and S7. Moreover, WCBA can exist and be absent in S1-S3 simultaneously; and for the 13 configurations that achieve low level of TI, WCBA can exist or not. Therefore, although the achievement of low level of TI is to some extent influenced by WCBA, it relies more on the influence of other factors (i.e., PsyCap, mindfulness, ∼ FWC, and SS). The study proves that WCBA has a double-edged effect on TI. The absence of FWC and existence of SS, PsyCap, and mindfulness are critical variables to buffer the loss of psychological resources caused by WCBA and recover psychological resources in time. These results may be helpful to recognize the negative effect of WCBA existence, accompanied with the absence of mindfulness on TI; also, the absence of SS was as crucial as the existence of FWC in the process of achieving high level of TI. Plain Language Summary: The configurational effect of work connectivity behavior on turnover intention This study investigates the double-edged sword effect of WCBA on TI from a configuration perspective. A questionnaire survey was conducted on 324 enterprise employees, and the results showed that: (a) Seven configurations achieve high level of TI. When WCBA exists, for the internal factor, compared with PsyCap, the absence of mindfulness was a more critical factor leading to TI; for the external factor, the absence of SS was as crucial as the existence of FWC in the process of achieving high level of TI. (b) 13 configurations achieve low level of TI, which can be divided into seven categories based on the existence of core conditions. When WCBA exists, as long as FWC does not exist or PsyCap or SS exists, low level of TI can be achieved. (c) The absence of mindfulness is the critical cause of high level of TI, but the existence of mindfulness is not the critical cause of low level of TI. The existence of PsyCap is a critical factor in achieving low level of TI, but the absence of PsyCap is not the critical factor leading to high level of TI. [ABSTRACT FROM AUTHOR]

HIV-1 has evolved a plethora of strategies to overcome the cytoskeletal barrier (i.e., actin and intermediate filaments (AFs and IFs) and microtubules (MTs)) to achieve the viral cycle. HIV-1 modifies cytoskeletal organization and dynamics by acting on associated adaptors and molecular motors to productively fuse, enter, and infect cells and then traffic to the cell surface, where virions assemble and are released to spread infection. The HIV-1 envelope (Env) initiates the cycle by binding to and signaling through its main cell surface receptors (CD4/CCR5/CXCR4) to shape the cytoskeleton for fusion pore formation, which permits viral core entry. Then, the HIV-1 capsid is transported to the nucleus associated with cytoskeleton tracks under the control of specific adaptors/molecular motors, as well as HIV-1 accessory proteins. Furthermore, HIV-1 drives the late stages of the viral cycle by regulating cytoskeleton dynamics to assure viral Pr55Gag expression and transport to the cell surface, where it assembles and buds to mature infectious virions. In this review, we therefore analyze how HIV-1 generates a cell-permissive state to infection by regulating the cytoskeleton and associated factors. Likewise, we discuss the relevance of this knowledge to understand HIV-1 infection and pathogenesis in patients and to develop therapeutic strategies to battle HIV-1. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is an inherited monogenic disorder with high prevalence throughout sub-Saharan Africa, the Mediterranean basin, the Middle East, and India. Sources of SCD epidemiology remain scarce and fragmented. A systematic literature review (SLR) to identify peer-reviewed studies on SCD epidemiology was performed, with a search of bibliographic databases and key conference proceedings from 1 January 2010 to 25 March 2022 (congress abstracts after 2018). The SLR followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Meta-analyses, using a binomial normal random-effects model, were performed to estimate global and regional prevalence and birth prevalence. Of 1770 journal articles and 468 abstracts screened, 115 publications met the inclusion criteria. Prevalence was highest in Africa (~800/100,000), followed by the Middle East (~200/100,000) and India (~100/100,000), in contrast to ~30/100,000 in Europe. Birth prevalence was highest in Africa (~1000/100,000) and lowest in North America (~50/100,000) and Europe (~30/100,000). This SLR confirmed that sub-Saharan and North-East Africa, India, the Middle East, and the Caribbean islands are global SCD hotspots. Publications including mortality data were sparse, and no conclusions could be drawn about mortality. The identified data were limited due to gaps in the published literature for large parts of the world population; the inconsistent reporting of SCD genotypes, diagnostic criteria, and settings; and a sparsity of peer-reviewed publications from countries with assumed high prevalence. This SLR demonstrated a lack of systematic knowledge and a need to provide uniform data collection on SCD prevalence and mortality. [ABSTRACT FROM AUTHOR]

This article uses the concept of literacy‐as‐event to explore the embodied meaning‐making of a young child during small world play. Recent developments in literacy research, influenced by relational thinking, have led to a reconsideration of how meaning‐making unfolds in home and school settings. The concept of literacy‐as‐event suggests that meaning‐making is unpredictable and dynamic, responding to novel socio‐material interactions between texts, people, objects and moments. This view suggests that there is a need to ensure children have opportunities to engage with embodied and material meaning‐making beyond shared reading events. In this article, small world play after a shared reading event is positioned as enabling socio‐material meaning‐making through embodied and material encounters with people and objects. A single episode of small world play is presented for analysis. A multimodal analytical approach is used, drawing attention to the embodied interactions between a child, her adult and objects. Analysis of the data shows that the young child's meaning‐making involved moments of physical and material almost‐hiatus, followed by erratic movements. These often unexpected fluctuations, between stillness and motion, created generative tensions between the child and her adult, enabling creative swerves in engagement between narrative action, character traits and story themes. [ABSTRACT FROM AUTHOR]