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Introduction: Deprescribing fall-risk increasing drugs (FRIDs) is promising for reducing the risk of falling in older adults. Applying appropriate deprescribing in practice can be difficult due to the outcome uncertainties associated with stopping FRIDs. The ADFICE_IT intervention addresses this complexity with a clinical decision support system (CDSS) that facilitates optimum deprescribing of FRIDs by using a fall-risk prediction model, aggregation of deprescribing guidelines, and joint medication management. Methods: The development process of the CDSS is described in this paper. Development followed a user-centered design approach in which users and experts were involved throughout each phase. In phase I, a prototype of the CDSS was developed which involved a literature and systematic review, European survey (n = 581), and semi-structured interviews with clinicians (n = 19), as well as the aggregation and testing of deprescribing guidelines and the development of the fall-risk prediction model. In phase II, the feasibility of the CDSS was tested by means of two usability testing rounds with users (n = 11). Results: The final CDSS consists of five web pages. A connection between the Electronic Health Record allows for the retrieval of patient data into the CDSS. Key design requirements for the CDSS include easy-to-use features for fast-paced clinical environments, actionable deprescribing recommendations, information transparency, and visualization of the patient's fall-risk estimation. Key elements for the software include a modular architecture, open source, and good security. Conclusion: The ADFICE_IT CDSS supports physicians in deprescribing FRIDs optimally to prevent falls in older patients. Due to continuous user and expert involvement, each new feedback round led to an improved version of the system. Currently, a cluster-randomized controlled trial with process evaluation at hospitals in the Netherlands is being conducted to test the effect of the CDSS on falls. The trial is registered with ClinicalTrials.gov (date; 7-7-2022, identifier: NCT05449470). [ABSTRACT FROM AUTHOR]

Hybrid immunity (vaccination + natural infection) to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. The mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed for T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera, reflected by smaller antigenic cartography distances. Transcriptomics post-infection reflects both vaccination status and disease course and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of high titers of neutralizing antibodies in the serum, correlates with recall of broadly reactive B- and T-cell responses. Author summary: Hybrid immunity to SARS-CoV-2, defined as the immunity provided by the combination of vaccination and natural infection has been shown to provide superior protection to re-infection. To assess the induction of hybrid immunity, we vaccinated hamsters with a single-dose of the mRNA BNT162b2 vaccine and challenged them with different SARS-CoV-2 variants of concern. This vaccine dose induced ELISA binding antibody titers against the virus spike, but these antibodies were not able to neutralize ancestral or drifted viruses. Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha variant but allowed breakthrough infections with the other antigenically more distant variants of concern. Nevertheless, vaccination primed for more cross-reactive B and T cell responses after infection. Whole lung transcriptomics after infection suggests a role for innate immune cells, such as interstitial macrophages, in vaccine-mediated protection. Our study sheds light on the early phases of induction of protective immune responses during infection with SARS-CoV-2 variants of concern in vaccinated hosts, even before the onset of neutralizing antibodies through recall of cross-reactive B- and T-cell responses. [ABSTRACT FROM AUTHOR]

Background: Falls are the leading cause of injury-related mortality and hospitalization among adults aged ≥ 65 years. An important modifiable fall-risk factor is use of fall-risk increasing drugs (FRIDs). However, deprescribing is not always attempted or performed successfully. The ADFICE_IT trial evaluates the combined use of a clinical decision support system (CDSS) and a patient portal for optimizing the deprescribing of FRIDs in older fallers. The intervention aims to optimize and enhance shared decision making (SDM) and consequently prevent injurious falls and reduce healthcare-related costs. Methods: A multicenter, cluster-randomized controlled trial with process evaluation will be conducted among hospitals in the Netherlands. We aim to include 856 individuals aged ≥ 65 years that visit the falls clinic due to a fall. The intervention comprises the combined use of a CDSS and a patient portal. The CDSS provides guideline-based advice with regard to deprescribing and an individual fall-risk estimation, as calculated by an embedded prediction model. The patient portal provides educational information and a summary of the patient's consultation. Hospitals in the control arm will provide care-as-usual. Fall-calendars will be used for measuring the time to first injurious fall (primary outcome) and secondary fall outcomes during one year. Other measurements will be conducted at baseline, 3, 6, and 12 months and include quality of life, cost-effectiveness, feasibility, and shared decision-making measures. Data will be analyzed according to the intention-to-treat principle. Difference in time to injurious fall between the intervention and control group will be analyzed using multilevel Cox regression. Discussion: The findings of this study will add valuable insights about how digital health informatics tools that target physicians and older adults can optimize deprescribing and support SDM. We expect the CDSS and patient portal to aid in deprescribing of FRIDs, resulting in a reduction in falls and related injuries. Trial registration: ClinicalTrials.gov NCT05449470 (7-7-2022). [ABSTRACT FROM AUTHOR]

Background: Acanthamoeba spp. are one of the free-living amoeba that spread worldwide causing keratitis. Owing to the increase in the use of lenses, whether for medical or cosmetic purposes, the incidence of disease increases every year. Contamination of the lenses with the Acanthamoeba trophozoites or cysts may lead to eye infection and cause sight-threatening keratitis in human. We isolated Acanthamoeba spp. from new lenses, used lenses, and contact lens disinfecting solutions and identified them based on morphological characteristics and molecular test. Methods: New and used lenses and contact lens disinfecting solutions were cultured on monogenic media. Light and scanning electron microscope was used to identify Acanthamoeba spp. morphological features. Genotype identification was also evaluated using PCR sequencing of 18S rRNA gene specific primer pair JDP1 and JDP2. Results: A hundred samples were examined, 29 (29%) were infected with Acanthamoeba spp. That belonged to two strains of Acanthamoeba (Acanthamoeba 41 and Acanthamoeba 68). 18S rRNA of the Acanthamoeba 41 had 99.69% sequence identity to Acanthamoeba castellanii clone HDU-JUMS-2, whereas Acanthamoeba 68 had 99.74% similar pattern to that of Acanthamoeba sp. isolate T4 clone ac2t4 that are morphologically identified as Acanthamoeba polyphaga. The obtained data revealed that the isolated strains belong to T4 genotype that was evolutionarily similar to strains isolated in Iran. Conclusions: Cosmetic lenses and disinfectant solutions are a major transmissible mode for infection. This genotype is common as the cause of Acanthamoeba keratitis. To avoid infection, care must be taken to clean the lenses and their preservative solutions and prevent contamination with the parasite. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Isolation and molecular characterization of novel glucarpidases: Enzymes to improve the antibody directed enzyme pro-drug therapy for cancer treatment." The notice states that the Data Availability statement in the article is incorrect and that the authors have provided the primary data for certain figures in supporting information files. It also mentions a spelling error in the second author's name and acknowledges the reuse of an image from the same group's later article, with the editors having no concerns about it. The supporting information files contain quantitative data, original images, CD spectra, and settings related to specific figures in the article. [Extracted from the article]

Background: There have been growing recommendations to include education in multi-disciplinary interventions targeting chronic pain management. However, effects of this strategy on short- and long-term self-management of chronic pain, remain largely unexplored. Objectives: 1. To provide an updated overview of studies that report on the impact of patient education in multi-disciplinary interventions, on self-management of chronic pain; 2. To explore associations between education and chronic pain self-management techniques; and 3. To identify the format and duration of suitable chronic pain interventions targeted at patient self-management. Methods: Design: Narrative systematic literature review of randomised or controlled study designs. Data Sources: PubMed, CINAHL, EMBASE, PsycINFO. Participants: Adult patients with chronic pain of any aetiology participating in multi-disciplinary programs that included education. Main outcome measures: Assessments of level of pain, function, quality of life, self-efficacy, self-management, and any other relevant assessments. Study Appraisal and Synthesis Methods: PRISMA guidelines, Cochrane Risk of Bias tool, and TIDieR model. Results: Database searching identified 485 potential papers. After removal of duplicates, and irrelevant articles by title and abstract, 120 full-text articles were reviewed and 27 studies were included in this systematic review. Studies were predominantly from the United States (n = 8; 29.6%). Over one hundred outcome measures were identified across all studies, with significant variation also observed in terms of how chronic pain duration was defined, and how education was delivered to participants. Overall, positive benefits of education were reported. Conclusions: Education, as part of multi-disciplinary programs, is likely to improve self-management and self-efficacy in people with chronic pain of any aetiology. Heterogeneity in terms of: chronic pain duration; educational resources; healthcare professionals; and outcome measures, were identified as limitations. Further research, in the form of Randomised Controlled Trials addressing these limitations, is recommended. [ABSTRACT FROM AUTHOR]

The objective of this study is to characterize the seroprevalence of anti-dengue (DENV) and anti-chikungunya (CHIKV) antibodies among blood donors residing in Qatar who are Middle East and North Africa (MENA) nationals and non-nationals. Sera were collected from adult blood donors in Qatar from 2013 to 2016 and tested for anti-DENV and anti-CHIKV IgG using commercial microplate enzyme-linked immunosorbent assays. Age-specific seroprevalence was summarized by region/nationality: Asia (India, Philippines), Middle East (Iran, Jordan, Lebanon, Pakistan, Palestine, Syria, Yemen), North Africa (Egypt, Sudan), Qatar. The adjusted odds of anti-DENV and anti-CHIKV IgG seropositivity was estimated by logistic regression. Among 1,992 serum samples tested, Asian nationals had higher adjusted odds of being seropositive for anti-DENV antibodies compared to nationals of the Middle East (aOR 0.05, 95% CI 0.04–0.07), North Africa (aOR 0.14, 95% CI 0.10–0.20), and Qatar (aOR 0.01, 95% CI 0.01–0.03). Asian nationals also had higher adjusted odds of being seropositive for anti-CHIKV antibodies compared to those from the Middle East (aOR 0.14, 95% CI 0.07–0.27), North Africa (aOR 0.50, 95% CI 0.26–0.96), and Qatar (aOR 0.38, 95% CI 0.15–0.96). The adjusted odds of being anti-DENV seropositive was higher among anti-CHIKV seropositive adults, and vice versa (aOR 1.94, 95% CI 1.09–3.44), suggesting co-circulation of these viruses. DENV and CHIKV exposure is lower in Qatar and MENA nationals compared to Asian nationals suggesting a lower burden of DENV and CHIKV disease in the MENA. Antibodies to both viruses were detected in nationals from most MENA countries, supporting the need to better understand the regional epidemiology of these viruses. [ABSTRACT FROM AUTHOR]

Repeated cycles of antibody-directed enzyme pro-drug therapy (ADEPT) and the use of glucarpidase in the detoxification of cytotoxic methotrexate (MTX) are highly desirable during cancer therapy but are hampered by the induced human antibody response to glucarpidase. Novel variants of glucarpidase (formal name: carboxypeptidase G2, CPG2) with epitopes not recognized by the immune system are likely to allow repeated cycles of ADEPT for effective cancer therapy. Towards this aim, over two thousand soil samples were collected and screened for folate hydrolyzing bacteria using folate as the sole carbon source. The work led to the isolation and the characterization of three new glucarpidase producing strains, which were designated as: Pseudomonas lubricans strain SF168, Stenotrophomonas sp SA and Xenophilus azovorans SN213. The CPG2 genes of Xenophilus azovorans SN213 (named Xen CPG2) and Stenotrophomonas sp SA (named Sten CPG2) were cloned and molecularly characterized. Both Xen CPG2 and Sten CPG2 share very close amino acid sequences (99%); we therefore, focused on the study of Xen CPG2. Finally, we demonstrated that a polyclonal antibody raised against our new CPG2, Xen CPG2, does not react with the CPG2 from Pseudomonas sp. strain RS-16 (Ps CPG2) that are currently in clinical use. The two enzymes, therefore could potentially be used consecutively in the ADEPT protocol to minimize the effect of the human antibody response that hampers current treatment with Ps CPG2. The identified novel CPG2 in this study will, therefore, pave the way for safer antibody directed enzyme pro-drug therapy for cancer treatment. [ABSTRACT FROM AUTHOR]

Drought stress is a recurring feature of world climate and the single most important factor influencing agricultural yield worldwide. Plants display highly variable, species-specific responses to drought and these responses are multifaceted, requiring physiological and morphological changes influenced by genetic and molecular mechanisms. Moreover, the reproducibility of water deficit studies is very cumbersome, which significantly impedes research on drought tolerance, because how a plant responds is highly influenced by the timing, duration, and intensity of the water deficit. Despite progress in the identification of drought-related mechanisms in many plants, the molecular basis of drought resistance remains to be fully understood in trees, particularly in poplar species because their wide geographic distribution results in varying tolerances to drought. Herein, we aimed to better understand this complex phenomenon in eastern cottonwood (Populus deltoides) by performing a detailed contrast of the proteome changes between two different water deficit experiments to identify functional intersections and divergences in proteome responses. We investigated plants subjected to cyclic water deficit and compared these responses to plants subjected to prolonged acute water deficit. In total, we identified 108,012 peptide sequences across both experiments that provided insight into the quantitative state of 22,737 Populus gene models and 8,199 functional protein groups in response to drought. Together, these datasets provide the most comprehensive insight into proteome drought responses in poplar to date and a direct proteome comparison between short period dehydration shock and cyclic, post-drought re-watering. Overall, this investigation provides novel insights into drought avoidance mechanisms that are distinct from progressive drought stress. Additionally, we identified proteins that have been associated as drought-relevant in previous studies. Importantly, we highlight the RD26 transcription factor as a gene regulated at both the transcript and protein level, regardless of species and drought condition, and, thus, represents a key, universal drought marker for Populus species. [ABSTRACT FROM AUTHOR]

Drug repositioning or repurposing, i.e. identifying new indications for existing drugs, has gained increasing attention in the recent years. This approach enables the scientists to discover “new targets” for known drugs in a cost and time efficient manner. Glycation, the non-enzymatic reaction of sugars with proteins or nucleic acids to form early glycation (Amadori or fructosamine) products, is a key molecular basis of diabetic complications. Inhibiting the process of non-enzymatic protein glycation is one of the key strategies to prevent glycation-mediated diabetic complications. The present study focuses on the anti-glycation activity of 18 drugs, commonly used for the treatment of gastrointestinal, central nervous system, inflammatory diseases, bacterial infections, and gout. This study was carried out by using two in-vitro protein anti-glycation assay models. Results revealed that nimesulide (3), a non-steroidal anti-inflammatory drug, possesses a good anti-glycation activity in in-vitro BSA-MG and BSA-glucose glycation models with IC50 values of 330.56 ± 2.90, and 145.46 ± 16.35 μM, respectively. Phloroglucinol dihydrate (11), a drug used for the treatment of gastrointestinal diseases, showed a weak activity in BSA-MG glycation model (IC50 = 654.89 ± 2.50 μM), while it showed a good activity in BSA-glucose assay (IC50 = 148.23 ± 0.15 μM). Trimethylphloroglucinol (9), a drug used for the treatment of pain related to functional disorders of the digestive and biliary tracts, also showed a good antiglycation activity in BSA-MG model (IC50 = 321.15 ± 1.26 μM), while it was found to be inactive in in-vitro BSA-glucose assay (IC50 = 12.95% inhibition). These activities of drugs were compared with the anti-glycation activity of the standard, rutin (IC50 = 294.5 ± 1.50 μM in BSA-MG glycation model, and IC50 = 86.94 ± 0.24 μM in BSA- glucose model). Rest of the drugs exhibited a relatively weak antiglycation activity. This study identifies nimesulide (3), and phloroglucinol dihydrate (11) as new inhibitors of in-vitro protein glycation for further investigations as potential anti-diabetic agents. [ABSTRACT FROM AUTHOR]

An understanding of how each individual 5q chromosome critical deleted region (CDR) gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs). Early Growth Response 1 (EGR1) is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell) quiescence as well as the master regulator of apoptosis—p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which myeloid malignancies arise. We evaluated radiation induced apoptosis of Egr1+/+ and Egr1-/- bone marrow cells in vitro and in vivo. EGR1 is not required for radiation induced apoptosis of murine bone marrow cells. Neither p53 mRNA (messenger RNA) nor protein expression is regulated by EGR1 in these cells. Radiation induced apoptosis of bone marrow cells by double strand DNA breaks induced p53 activation. These results suggest EGR1 dependent signaling mechanisms do not contribute to aberrant apoptosis of malignant cells in myeloid malignancies. [ABSTRACT FROM AUTHOR]

The expression of some genes is affected by age. To detect such age-related changes, their expression levels are related to constant marker genes. However, transcriptional noise increasing with advancing age renders difficult the identification of real age-related changes because it may affect the marker genes as well. Here, we report a selection procedure for genes appropriate to normalise the mouse liver transcriptome under various conditions including age. These genes were chosen from an initial set of 16 candidate genes defined based on a RNA-sequencing experiment and published literature. A subset of genes was selected based on rigorous statistical assessment of their variability using both RNA-sequencing and Nanostring hybridization experiments. The robustness of these marker genes was then verified by the analysis of 130 publicly available data sets using the mouse liver transcriptome. Altogether, a set of three genes, Atp5h, Gsk3β, and Sirt2 fulfilled our strict selection criteria in all assessments, while four more genes, Nono, Tprkb, Tspo, and Ttr passed all but one assessment and were included into the final set of marker genes to enhance robustness of normalisation against outliers. Using the geometric mean of expression of the genes to normalise Nanostring hybridization experiments we reliably identified age-related increases in the expression of Casein kinase 1δ and 1ϵ, and Sfpq, while the expression of the glucose transporter Glut2 decreased. The age-related changes were verified by real-time PCR and Western blot analysis. As conclusion, proper normalisation enhances the robustness of quantitative methods addressing age-related changes of a transcriptome. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is caused by defects in the survival motor neuron 1 (SMN1) gene that encodes survival motor neuron (SMN) protein. The majority of therapeutic approaches currently in clinical development for SMA aim to increase SMN protein expression and there is a need for sensitive methods able to quantify increases in SMN protein levels in accessible tissues. We have developed a sensitive electrochemiluminescence (ECL)-based immunoassay for measuring SMN protein in whole blood with a minimum volume requirement of 5μL. The SMN-ECL immunoassay enables accurate measurement of SMN in whole blood and other tissues. Using the assay, we measured SMN protein in whole blood from SMA patients and healthy controls and found that SMN protein levels were associated with SMN2 copy number and were greater in SMA patients with 4 copies, relative to those with 2 and 3 copies. SMN protein levels did not vary significantly in healthy individuals over a four-week period and were not affected by circadian rhythms. Almost half of the SMN protein was found in platelets. We show that SMN protein levels in C/C-allele mice, which model a mild form of SMA, were high in neonatal stage, decreased in the first few weeks after birth, and then remained stable throughout the adult stage. Importantly, SMN protein levels in the CNS correlated with SMN levels measured in whole blood of the C/C-allele mice. These findings have implications for the measurement of SMN protein induction in whole blood in response to SMN-upregulating therapy. [ABSTRACT FROM AUTHOR]

Higher body mass index (BMI) is a well-established risk factor for type 2 diabetes, and rates of obesity and type 2 diabetes are substantially higher among Mexican-Americans relative to non-Hispanic European Americans. Mexican-Americans are genetically diverse, with a highly variable distribution of Native American, European, and African ancestries. Here, we evaluate the role of Native American ancestry on BMI and diabetes risk in a well-defined Mexican-American population. Participants were randomly selected among individuals residing in the Houston area who are enrolled in the Mexican-American Cohort study. Using a custom Illumina GoldenGate Panel, we genotyped DNA from 4,662 cohort participants for 87 Ancestry-Informative Markers. On average, the participants were of 50.2% Native American ancestry, 42.7% European ancestry and 7.1% African ancestry. Using multivariate linear regression, we found BMI and Native American ancestry were inversely correlated; individuals with <20% Native American ancestry were 2.5 times more likely to be severely obese compared to those with >80% Native American ancestry. Furthermore, we demonstrated an interaction between BMI and Native American ancestry in diabetes risk among women; Native American ancestry was a strong risk factor for diabetes only among overweight and obese women (OR = 1.190 for each 10% increase in Native American ancestry). This study offers new insight into the complex relationship between obesity, genetic ancestry, and their respective effects on diabetes risk. Findings from this study may improve the diabetes risk prediction among Mexican-American individuals thereby facilitating targeted prevention strategies. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.

Wolbachia are intracellular bacterial symbionts that are able to protect various insect hosts from viral infections. This tripartite interaction was initially described in Drosophila melanogaster carrying wMel, its natural Wolbachia strain. wMel has been shown to be genetically polymorphic and there has been a recent change in variant frequencies in natural populations. We have compared the antiviral protection conferred by different wMel variants, their titres and influence on host longevity, in a genetically identical D. melanogaster host. The phenotypes cluster the variants into two groups — wMelCS-like and wMel-like. wMelCS-like variants give stronger protection against Drosophila C virus and Flock House virus, reach higher titres and often shorten the host lifespan. We have sequenced and assembled the genomes of these Wolbachia, and shown that the two phenotypic groups are two monophyletic groups. We have also analysed a virulent and over-replicating variant, wMelPop, which protects D. melanogaster even better than the closely related wMelCS. We have found that a ∼21 kb region of the genome, encoding eight genes, is amplified seven times in wMelPop and may be the cause of its phenotypes. Our results indicate that the more protective wMelCS-like variants, which sometimes have a cost, were replaced by the less protective but more benign wMel-like variants. This has resulted in a recent reduction in virus resistance in D. melanogaster in natural populations worldwide. Our work helps to understand the natural variation in wMel and its evolutionary dynamics, and inform the use of Wolbachia in arthropod-borne disease control. [ABSTRACT FROM AUTHOR]

Lentiviruses can infect non-dividing cells, and various cellular transport proteins provide crucial functions for lentiviral nuclear entry and integration. We previously showed that the viral capsid (CA) protein mediated the dependency on cellular nucleoporin (NUP) 153 during HIV-1 infection, and now demonstrate a direct interaction between the CA N-terminal domain and the phenylalanine-glycine (FG)-repeat enriched NUP153 C-terminal domain (NUP153C). NUP153C fused to the effector domains of the rhesus Trim5α restriction factor (Trim-NUP153C) potently restricted HIV-1, providing an intracellular readout for the NUP153C-CA interaction during retroviral infection. Primate lentiviruses and equine infectious anemia virus (EIAV) bound NUP153C under these conditions, results that correlated with direct binding between purified proteins in vitro. These binding phenotypes moreover correlated with the requirement for endogenous NUP153 protein during virus infection. Mutagenesis experiments concordantly identified NUP153C and CA residues important for binding and lentiviral infectivity. Different FG motifs within NUP153C mediated binding to HIV-1 versus EIAV capsids. HIV-1 CA binding mapped to residues that line the common alpha helix 3/4 hydrophobic pocket that also mediates binding to the small molecule PF-3450074 (PF74) inhibitor and cleavage and polyadenylation specific factor 6 (CPSF6) protein, with Asn57 (Asp58 in EIAV) playing a particularly important role. PF74 and CPSF6 accordingly each competed with NUP153C for binding to the HIV-1 CA pocket, and significantly higher concentrations of PF74 were needed to inhibit HIV-1 infection in the face of Trim-NUP153C expression or NUP153 knockdown. Correlation between CA mutant viral cell cycle and NUP153 dependencies moreover indicates that the NUP153C-CA interaction underlies the ability of HIV-1 to infect non-dividing cells. Our results highlight similar mechanisms of binding for disparate host factors to the same region of HIV-1 CA during viral ingress. We conclude that a subset of lentiviral CA proteins directly engage FG-motifs present on NUP153 to affect viral nuclear import. [ABSTRACT FROM AUTHOR]

Background: Survivors of physical and emotional trauma experience enduring occupational, psychological and quality of life impairments. Examining survivors from a large fire provides a unique opportunity to distinguish the impact of physical and emotional trauma on long-term outcomes. The objective is to detail the multi-dimensional long-term effects of a large fire on its survivor population and assess differences in outcomes between survivors with and without physical injury. Methods and Findings: This is a survey-based cross-sectional study of survivors of The Station fire on February 20, 2003. The relationships between functional outcomes and physical injury were evaluated with multivariate regression models adjusted for pre-injury characteristics and post-injury outcomes. Outcome measures include quality of life (Burn Specific Health Scale-Brief), employment (time off work), post-traumatic stress symptoms (Impact of Event Scale-Revised) and depression symptoms (Beck Depression Inventory). 104 fire survivors completed the survey; 47% experienced a burn injury. There was a 42% to 72% response rate range. Although depression and quality of life were associated with burn injury in univariate analyses (p<0.05), adjusted analyses showed no significant relationship between burn injury and these outcomes (p = 0.91; p = .51). Post-traumatic stress symptoms were not associated with burn injury in the univariate (p = 0.13) or adjusted analyses (p = 0.79). Time off work was the only outcome in which physical injury remained significant in the multivariate analysis (p = 0.03). Conclusions: Survivors of this large fire experienced significant life disruption, including occupational, psychological and quality of life sequelae. The findings suggest that quality of life, depression and post-traumatic stress outcomes are related to emotional trauma, not physical injury. However, physical injury is correlated with employment outcomes. The long-term impact of this traumatic event underscores the importance of longitudinal and mental health care for trauma survivors, with attention to those with and without physical injuries. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is a unique autoimmune disorder in which the genetic factors (DQ2/DQ8) and the environmental trigger (gluten) are known and necessary but not sufficient for its development. Other environmental components contributing to CD are poorly understood. Studies suggest that aspects of gluten intake might influence the risk of CD occurrence and timing of its onset, i.e., the amount and quality of ingested gluten, together with the pattern of infant feeding and the age at which gluten is introduced in the diet. In this study, we hypothesize that the intestinal microbiota as a whole rather than specific infections dictates the switch from tolerance to immune response in genetically susceptible individuals. Using a sample of infants genetically at risk of CD, we characterized the longitudinal changes in the microbial communities that colonize infants from birth to 24 months and the impact of two patterns of gluten introduction (early vs. late) on the gut microbiota and metabolome, and the switch from gluten tolerance to immune response, including onset of CD autoimmunity. We show that infants genetically susceptible to CD who are exposed to gluten early mount an immune response against gluten and develop CD autoimmunity more frequently than at-risk infants in which gluten exposure is delayed until 12 months of age. The data, while derived from a relatively small number of subjects, suggest differences between the developing microbiota of infants with genetic predisposition for CD and the microbiota from infants with a non-selected genetic background, with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes and microbiota that do not resemble that of adults even at 2 years of age. Furthermore, metabolomics analysis reveals potential biomarkers for the prediction of CD. This study constitutes a definite proof-of-principle that these combined genomic and metabolomic approaches will be key to deciphering the role of the gut microbiota on CD onset. [ABSTRACT FROM AUTHOR]

Cigarette smoke-induced release of pro-inflammatory cytokines including interleukin-8 (IL-8) from inflammatory as well as structural cells in the airways, including airway smooth muscle (ASM) cells, may contribute to the development of chronic obstructive pulmonary disease (COPD). Despite the wide use of pharmacological treatment aimed at increasing intracellular levels of the endogenous suppressor cyclic AMP (cAMP), little is known about its exact mechanism of action. We report here that next to the β2-agonist fenoterol, direct and specific activation of either exchange protein directly activated by cAMP (Epac) or protein kinase A (PKA) reduced cigarette smoke extract (CSE)-induced IL-8 mRNA expression and protein release by human ASM cells. CSE-induced IαBκ-degradation and p65 nuclear translocation, processes that were primarily reversed by Epac activation. Further, CSE increased extracellular signal-regulated kinase (ERK) phosphorylation, which was selectively reduced by PKA activation. CSE decreased Epac1 expression, but did not affect Epac2 and PKA expression. Importantly, Epac1 expression was also reduced in lung tissue from COPD patients. In conclusion, Epac and PKA decrease CSE-induced IL- 8 release by human ASM cells via inhibition of NF-κB and ERK, respectively, pointing at these cAMP effectors as potential targets for anti-inflammatory therapy in COPD. However, cigarette smoke exposure may reduce anti-inflammatory effects of cAMP elevating agents via down-regulation of Epac1. [ABSTRACT FROM AUTHOR]

Objective: Proper arterial and venous specification is a hallmark of functional vascular networks. While arterial-venous identity is genetically pre-determined during embryo development, it is unknown whether an analogous pre-specification occurs in adult neovascularization. Our goal is to determine whether vessel arterial-venous specification in adult neovascularization is pre-determined by the identity of the originating vessels. Methods and Results: We assessed identity specification during neovascularization by implanting isolated microvessels of arterial identity from both mice and rats and assessing the identity outcomes of the resulting, newly formed vasculature. These microvessels of arterial identity spontaneously formed a stereotypical, perfused microcirculation comprised of the full complement of microvessel types intrinsic to a mature microvasculature. Changes in microvessel identity occurred during sprouting angiogenesis, with neovessels displaying an ambiguous arterial-venous phenotype associated with reduced EphrinB2 phosphorylation. Conclusions: Our findings indicate that microvessel arterial-venous identity in adult neovascularization is not necessarily pre-determined and that adult microvessels display a considerable level of phenotypic plasticity during neovascularization. In addition, we show that vessels of arterial identity also hold the potential to undergo sprouting angiogenesis. [ABSTRACT FROM AUTHOR]

GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6x10-4 ) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry. [ABSTRACT FROM AUTHOR]

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious.

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10−6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10−8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10−8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10−8; RREB1: p = 5.7×10−8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.

Background: Survivors of physical and emotional trauma experience enduring occupational, psychological and quality of life impairments. Examining survivors from a large fire provides a unique opportunity to distinguish the impact of physical and emotional trauma on long-term outcomes. The objective is to detail the multi-dimensional long-term effects of a large fire on its survivor population and assess differences in outcomes between survivors with and without physical injury. Methods and Findings: This is a survey-based cross-sectional study of survivors of The Station fire on February 20, 2003. The relationships between functional outcomes and physical injury were evaluated with multivariate regression models adjusted for pre-injury characteristics and post-injury outcomes. Outcome measures include quality of life (Burn Specific Health Scale–Brief), employment (time off work), post-traumatic stress symptoms (Impact of Event Scale–Revised) and depression symptoms (Beck Depression Inventory). 104 fire survivors completed the survey; 47% experienced a burn injury. There was a 42% to 72% response rate range. Although depression and quality of life were associated with burn injury in univariate analyses (p<0.05), adjusted analyses showed no significant relationship between burn injury and these outcomes (p = 0.91; p = .51). Post-traumatic stress symptoms were not associated with burn injury in the univariate (p = 0.13) or adjusted analyses (p = 0.79). Time off work was the only outcome in which physical injury remained significant in the multivariate analysis (p = 0.03). Conclusions: Survivors of this large fire experienced significant life disruption, including occupational, psychological and quality of life sequelae. The findings suggest that quality of life, depression and post-traumatic stress outcomes are related to emotional trauma, not physical injury. However, physical injury is correlated with employment outcomes. The long-term impact of this traumatic event underscores the importance of longitudinal and mental health care for trauma survivors, with attention to those with and without physical injuries.

Taybi-Linder syndrome (TALS) is a rare autosomal recessive disorder characterized by severe microcephaly with abnormal gyral pattern, severe growth retardation and bone abnormalities. It is caused by pathogenic variants in the RNU4ATAC gene. Its transcript, the small nuclear RNA U4atac, is involved in the excision of ~850 minor introns. Here, we report a patient presenting with TALS features but no pathogenic variants were found in RNU4ATAC, instead the homozygous RTTN c.2953A>G variant was detected by whole-exome sequencing. After deciphering the impact of the variant on the RTTN protein function at centrosome in engineered RTTN-depleted RPE1 cells and patient fibroblasts, we analysed neuronal stem cells (NSC) derived from CRISPR/Cas9-edited induced pluripotent stem cells and revealed major cell cycle and mitotic abnormalities, leading to aneuploidy, cell cycle arrest and cell death. In cortical organoids, we discovered an additional function of RTTN in the self-organisation of NSC into neural rosettes, by observing delayed apico-basal polarization of NSC. Altogether, these defects resulted to a marked delay of rosette formation in RTTN-mutated organoids, thus impeding their overall growth and shedding light on mechanisms leading to microcephaly., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Guguin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Stress-related disorders are common diagnoses for sickness absence (SA) and disability pension (DP) in many Western countries. Knowledge on future SA/DP trajectories among those starting such a SA spell is limited. The aims were to identify future SA/DP days trajectories among individuals starting an SA spell due to stress-related disorder and investigate socio-demographic and morbidity characteristics associated with specific trajectories., Methods: Using microdata from nationwide registers, we established two cohorts of all living in Sweden who started a new SA spell >14 days due to stress-related disorder in 2011 (N = 32,417) or in 2018 (N = 65,511), respectively. Group-based trajectory models were used to identify trajectories of monthly average SA/DP days during the following 13 months, separate for each cohort. We used multinomial logistic regression to investigate the associations between sociodemographic and morbidity-related predictors and trajectory membership., Results: We identified six SA/DP trajectories in the two cohorts: steep drop (30.6% and 35.9% of all included in 2018 and 2011); constant fluctuating (8.7%, 11.2%); fast decrease (25.5%, 24.4%); medium decrease (18.1%, 13.1%); slow decrease (10.8%, 7.3%), and constant high (6.2%, 8.0%). The distributions of sociodemographic factors, multi-morbidity, and history of SA/DP differed between the trajectory groups. For example, compared to the steep drop trajectory, individuals in the other trajectories were more likely to be a woman, older, having had prior SA/DP or specialized outpatient healthcare visits., Conclusions: In these two explorative, population-wide cohorts, we identified six different trajectories of SA/DP days among all with a new SA spell with stress-related disorders. The trajectory groups differed regarding both sociodemographic and health-related covariates., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gémes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the era of precision medicine, it is necessary to understand heterogeneity among patients with complex diseases to improve personalized prevention and management strategies. Here, we introduce ClustAll, a Bioconductor package designed for unsupervised patient stratification using clinical data. ClustAll is based on the previously validated methodology ClustAll, a clustering framework that effectively handles intricacies in clinical data, including mixed data types, missing values, and collinearity. Additionally, ClustAll stands out in its ability to identify multiple patient stratifications within the same population while ensuring their robustness. The updated implementation of ClustAll features S4 classes, parallel computing for enhanced computational efficiency, and user-friendly tools for exploring and comparing stratifications against clinical phenotypes. The performance of ClustAll has been validated using two public clinical datasets, confirming its effectiveness in patient stratification and highlighting its potential impact on clinical management. In summary, ClustAll is a powerful tool for patient stratification in personalized medicine., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ortega-Legarreta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: To present a study protocol for the development of an intervention to enhance safe insulin use for older or frail adults undergoing a surgical admission to hospital., Design: Following the United Kingdom's Medical Research Council and National Institute for Health and Care Research Frameworks for development and evaluation of complex interventions; this qualitative study will use a co-design approach using design thinking, to develop a theoretical model for the intervention., Methods: Non-participatory observations, interviews and co-design workshops will be conducted with older or frail individuals with diabetes, their caregivers and healthcare staff responsible for their care during surgical admissions at a single National Health Service hospital in England. We will utilise their experiences and perspectives to establish priorities and generate ideas for the development of a conceptual model aimed at supporting the insulin safety review process in hospitals. Data will be analysed using framework analysis. People with diabetes were involved in the design of this study. The protocol was approved by the East-Midlands-Derby Research Ethics Committee (24/EM/0022). Study registered on Open Science Framework: https://osf.io/4wvu5., Results: Results of this study will be shared with study participants and disseminated through presentations at conferences/meetings and peer-reviewed publications., Conclusion: This article outlines the methodology for the planned study which will employ a novel methodology to tackle the problem of hospital insulin safety. Its findings will contribute to a better understanding of the multiple interacting components implicated in hospital insulin use (patient, staff, context) and support further work around system-based strategies to enhance insulin safety resilience in hospital., Competing Interests: Christina Lange Ferreira; Sara Donetto; Jyothish Govindan; Angus Forbes; Kirsty Winkley: no known conflicts of interest. Hellena Habte-Asres: received speaker honoraria from AstraZeneca and Bayer., (Copyright: © 2024 Lange Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Understanding the growth patterns and developmental trajectories of teeth during early life stages provides valuable insights into the ontogeny of individuals, particularly in archaeological populations where such information is scarce. This study focuses on first deciduous molars, specifically investigating crown formation times and daily secretion rates, through histological analysis. A total of 34 teeth from the Early Medieval necropolises of Casalmoro and Guidizzolo (Mantua, Lombardy, northern Italy) were analysed assessing growth parameters and identifying possible differences between sites and between sexes, which are determined through proteomic analysis. Furthermore, a robust linear regression model relating prism length and secretion time was built to estimate growth rates also in teeth in which the finest incremental markings are not visible. The daily secretion rates (DSR) in inner enamel showed a high homogeneity between dental arches, sexes and the two sites. Values fall within the known range reported in the literature for the same tooth class in archaeological populations. However, a difference in DSR was observed when compared with modern sample published values. Crown formation times and age at crown completion differ between dental arches, with maxillary first molars initiating their matrix apposition earlier than mandibular molars as formerly reported. However, no significant differences were highlighted in association with sex. This study expands our understanding of the growth and development of the first deciduous molars in a medieval population, providing valuable insights into growth trajectories specific to the dental arch. These findings highlight the need for extensive investigations using similar methodologies to attain more accurate and comprehensive information about the developmental patterns of first deciduous molars. Additionally, proteomic analysis improves the capability to conduct sex-specific histological assessments of immature individuals, thanks to this method's application in determining their sex., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: three of the authors (LB, FL and AN) are academic editors for Plos One. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Magri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Evolution is an important part of biology education, but many college biology students do not accept important components of evolution, like the evolution of humans. Practices that reduce perceived conflict between religion and evolution have been proposed to increase student evolution acceptance. This study investigates college student experiences of conflict reducing practices in evolution education and how these experiences are related to their gains in acceptance of human evolution during evolution instruction. We measured the natural variation in student experiences of conflict reducing practices among 6,719 college biology students in 55 courses and 14 states including (1) their experiences of an instructor demonstrating religion-evolution compatibility by presenting examples of religious leaders and scientists who accept evolution and (2) their experiences of an instructor emphasizing students' autonomy in their own decision to accept evolution or not. We also measured student acceptance of human evolution before and after instruction so that we could test whether any changes in evolution acceptance were associated with student experiences of the conflict reducing practices. Linear mixed models showed that highly religious Christian students accepted evolution more when they perceived more compatibility practices. Further, students from all religious and non-religious affiliations accepted human evolution more after instruction when they perceived more autonomy practices. These results indicate that integrating examples of religion compatibility in evolution education will positively impact Christian students' views on evolution and that emphasizing students' autonomy over their decision to accept evolution may be important for students more broadly. If instructors incorporate practices that emphasize compatibility and one's personal choice to accept or not accept evolution, then these results suggest that students will leave their college biology classes accepting evolution more. Perhaps by using more conflict reducing practices, instructors can help increase evolution acceptance levels that have remained low in the United States for decades., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Prolonged gaps in care of >12-months are frequent among people with cystic fibrosis (pwCF) and are associated with reduced lung function. Comprehensive analysis of patient-level predictors of visit frequency is needed to optimize protocols for stable pwCF and identify subgroups at high risk of gaps and poor outcomes, promoting equitable treatment for all pwCF., Objective: To determine sociodemographic and disease-related factors predictive of visit frequency in pwCF and to assess how these effects vary across the lifespan., Methods: We conducted an observational cohort study using data from 2004-2016 for pwCF aged 6-60 years in the US Cystic Fibrosis Foundation Patient Registry. We modeled the relationship between patient-level characteristics and between-visit interval (BVI) using multivariable longitudinal semiparametric regression. BVI was defined as the number of days from the index encounter to the previously recorded visit., Results: The study included 28,588 pwCF with 859,568 encounters. Overall, 55% of visits occurred within 90 days of the prior visit, adhering to national guidelines. On average, adults without common CF-complications attended clinic approximately every 4 months, with a BVI ≥ 110 days from age 23-56. Males attended clinic less frequently than females (9.8% longer BVI; 95% CI 9.1%, 10.5%; p<0.001), as did non-white individuals (3.6% longer BVI than whites; 95% CI 2.2%, 5.0%; p<0.001), with the greatest differences seen in young adults. Those with public and private insurance largely adhered to current guidelines (maximum average BVI of 90 and 95 days, respectively). In contrast, uninsured individuals over age 25 had a mean BVI ≥ 30 days longer than the insured., Conclusions: Frequent visits in those with CF-complications likely reflects higher need, while less frequent visits in male, non-white, and uninsured individuals may reflect patient-preference or structural barriers to care. Risk factors for gaps in care should inform changes to CF care recommendations going forward., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hinton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Colorectal cancer (CRC), with a growing incidence trend, is one of the most diagnosed cancers and the second cause of cancer-related deaths worldwide. The literature has frequently focused attention on the correlation between the gut microbiota imbalance and CRC. The genera Lactobacillus and Bifidobacterium have recently received increasing attention because of their potential in restoring alterations in the gut microflora. Therefore, this study aimed to quantitatively evaluate the presence of lactobacilli and bifidobacterial strains in the fecal samples of CRC patients compared to healthy volunteers., Methods: From 2018 to 2019, 25 confirmed CRC patients and 25 age- and gender-matched control subjects were enrolled in the study. Bacterial DNA was extracted from the fecal samples and the presence of lactobacilli and bifidobacterial strains were quantitatively determined using quantitative real-time PCR using genus-specific 16S rDNA primers., Results: A significant decline in the abundance of bifidobacteria in CRC patients compared to healthy individuals (p value<0.003) was observed; however, no significant difference was observed between the two groups regarding the abundance of lactobacilli (p value<0.163). Correlation analysis showed a positive association between the lack of genetic history of CRC and the numbers of gut bifidobacteria and lactobacilli., Conclusion: As a putative gut probiotic, depletion of bifidobacteria showed significant correlation to the development and progression of CRC; therefore, therapeutic use of these probiotic bacteria could be considered a possible adjuvant approach in disease management through modulation of the microbiota., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Esfandiari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Over 9.5 million confirmed cases of COVID-19 infection have been recorded in Africa. The syndrome of post-acute sequelae of SARS-CoV-2 infection (PASC) affects an estimated 32% to 87% of COVID patients globally. Data regarding prevalence and impact of PASC in Botswana are limited. This study used a cross-sectional survey design to query healthcare workers in Kweneng District, Botswana about perceived PASC prevalence, duration, symptoms, impact, and management strategies. The survey was disseminated to participants via pre-existing WhatsApp groups and paper copy. Descriptive statistics were used to analyse quantitative data, including demographic data. 72 respondents consented and completed the survey, from an estimated 650 staff meeting eligibility criteria; 63% were female and 36% were male. The majority (90%) were nurses, with doctors and "other" accounting for 6% and 4% of respondents, respectively; no administrators responded. Over half (72%) worked at primary care facilities and 28% worked in hospitals. Nearly all (93%) indicated seeing patients with PASC on a weekly basis, though the majority (61%) identified these patients as comprising <10% of total patients. The most frequently reported PASC symptom was persistent cough (64%), followed by shortness of breath (54%) and fatigue (49%). A substantial minority of respondents were unsure how to manage common PASC symptoms, with 29% and 36% indicating uncertainty regarding management of persistent cough and fatigue, respectively. Findings indicate that PASC symptoms are frequently encountered in clinical practice in Botswana with significant overlap with acute COVID-19, influenza-like illnesses, and tuberculosis, likely placing increased burden on existing health system processes. Providers reported uncertainty in managing presumed PASC, and current practice patterns may contribute to unintended adverse effects. Clear clinical algorithms for PASC screening, diagnosis, and management should be developed and disseminated in Botswana to mitigate the effects of PASC symptoms and improve the quality of life of COVID-19 survivors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mamalelala et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Long Covid is the continuation or development of symptoms related to a SARSCoV2 infection. Those with Long Covid may face epistemic injustice, where they are unjustifiably viewed as unreliable evaluators of their own illness experiences. Media articles both reflect and influence perception and subsequently how people regard children and young people (CYP) with Long Covid, and may contribute to epistemic injustice. We aimed to explore how the UK media characterises Long Covid in CYP through examining three key actor groups: parents, healthcare professionals, and CYP with Long Covid, through the lens of epistemic injustice. A systematic search strategy resulted in the inclusion of 103 UK media articles. We used an adapted corpus-assisted Critical Discourse Analysis in tandem with thematic analysis. Specifically, we utilised search terms to locate concordances of key actor groups. In the corpus, parents highlighted minimisation of Long Covid, barriers to care, and experiences of personal attacks. Mothers were presented as also having Long Covid. Fathers were unmentioned. Healthcare professionals emphasised the rarity of Long Covid in CYP, avoided pathologising Long Covid, and overemphasised psychological components. CYP were rarely consulted in media articles but were presented as formerly very able. Manifestations of Long Covid in CYP were validated or invalidated in relation to adults. Media characterisations contributed to epistemic injustice. The disempowering portrayal of parents promotes stigma and barriers to care. Healthcare professionals' narratives often contributed to negative healthcare experiences and enacted testimonial injustice, where CYP and parents' credibility was diminished due to unfair identity prejudice, in their invalidation of Long Covid. Media characterisations reveal and maintain a lack of societal framework for understanding Long Covid in CYP. The findings of this study illustrate the discursive practices employed by journalists that contribute to experiences of epistemic injustice. Based on our findings, we propose recommendations for journalists., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Sammie Mcfarland is the founder and CEO of Long Covid Kids. Nisreen A. Alwan is a Long Covid Kids Charity Champion, a scientific advisor to the Long Covid Support Charity, and has contributed in an advisory capacity to WHO and the EU Commission’s Expert Panel on effective ways of investing in health meetings in relation to post-COVID-19 condition. Nisreen A. Alwan is also co-investigator on the NIHR-funded STIMULATE ICP study. Sara Mckelvie is funded by NIHR Clinical Lectureship CL-2021-26-001. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Connor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As a new computing resources distribution platform, cloud technology greatly influenced society with the conception of on-demand resource usage through virtualization technology. Virtualization technology allows physical resource usage in a way that will enable multiple end-users to have similar hardware infrastructure. In the cloud, many challenges exist on the provider side due to the expectations of clients. Resource scheduling (RS) is the most significant nondeterministic polynomial time (NP) hard problem in the cloud, owing to its crucial impact on cloud performance. Previous research found that metaheuristics can dramatically increase CC performance if deployed as scheduling algorithms. Therefore, this study develops an evolutionary algorithm-based scheduling approach for makespan optimization and resource utilization (EASA-MORU) technique in the cloud environment. The EASA-MORU technique aims to maximize the makespan and effectively use the resources in the cloud infrastructure. In the EASA-MORU technique, the dung beetle optimization (DBO) technique is used for scheduling purposes. Moreover, the EASA-MORU technique balances the load properly and distributes the resources based on the demands of the cloud infrastructure. The performance evaluation of the EASA-MORU method is tested using a series of performance measures. A wide range of comprehensive comparison studies emphasized that the EASA-MORU technique performs better than other methods in different evaluation measures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 K. Karim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hearing impairment alters the sound input received by the human auditory system, reducing speech comprehension in noisy multi-talker auditory scenes. Despite such difficulties, neural signals were shown to encode the attended speech envelope more reliably than the envelope of ignored sounds, reflecting the intention of listeners with hearing impairment (HI). This result raises an important question: What speech-processing stage could reflect the difficulty in attentional selection, if not envelope tracking? Here, we use scalp electroencephalography (EEG) to test the hypothesis that the neural encoding of phonological information (i.e., phonetic boundaries and phonological categories) is affected by HI. In a cocktail-party scenario, such phonological difficulty might be reflected in an overrepresentation of phonological information for both attended and ignored speech sounds, with detrimental effects on the ability to effectively focus on the speaker of interest. To investigate this question, we carried out a re-analysis of an existing dataset where EEG signals were recorded as participants with HI, fitted with hearing aids, attended to one speaker (target) while ignoring a competing speaker (masker) and spatialised multi-talker background noise. Multivariate temporal response function (TRF) analyses indicated a stronger phonological information encoding for target than masker speech streams. Follow-up analyses aimed at disentangling the encoding of phonological categories and phonetic boundaries (phoneme onsets) revealed that neural signals encoded the phoneme onsets for both target and masker streams, in contrast with previously published findings with normal hearing (NH) participants and in line with our hypothesis that speech comprehension difficulties emerge due to a robust phonological encoding of both target and masker. Finally, the neural encoding of phoneme-onsets was stronger for the masker speech, pointing to a possible neural basis for the higher distractibility experienced by individuals with HI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Carta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The prevalence of constant light exposure and high-fat diet in modern society raises concerns regarding their impact on maternal and offspring health outcomes. In rodents, exposure to maternal high-fat diet or continuous light negatively program metabolic and stress response outcomes of offspring. A 2x3 factorial study was conducted to investigate the impact of diet (control-CON, 10% fat, or high fat-HF, 60% fat) and exposure to different lighting conditions: regular 12-hour light-dark cycles (LD), continuous dim light (L5), or continuous bright light (L100) on female ICR mice daily patterns of time in and out of the nest, feed intake, and fecal corticosterone levels during gestation and lactation. Our previous analysis of these mice found HF diet decreased number of pups born, but increased litter growth rate to postnatal (PN) d12. Whereas continuous light increased gestation length and tended to increase PN litter growth. Here we report that patterns of grams of feed intake, an indicator of feeding activity, were affected by light, diet, period of the day (day versus night) and physiological state (gestation and lactation), with significant interactions among all these variables (P<0.05). HF diet and light treatment increased fecal corticosterone output (P<0.05) during lactation. Dams exhibited significant 12 h and 24 h rhythms of activity out of the nest in the first 48 h postnatal, with time outside of the nest greater in the second 24 h period. L100 treatment and HF diet attenuated rhythms and shifted phase of rhythms relative to LD and CON, respectively (P<0.05). Alterations in behavior affect maternal physiology, including level and timing of release of corticosteroids. Elevated fecal corticosterone levels due to high-fat diet and continuous light may have potential implications on maternal-offspring health, and potentially underlie some of the adverse effects of modern lifestyle factors on maternal and offspring health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Reis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Non-steroidal anti-inflammatory drugs (NSAID) are not recommended for use against pneumonia in humans, but are commonly utilised against bovine respiratory disease. This study aimed to determine if the use of NSAIDs in the early phase of bovine respiratory syncytial virus (BRSV)-infection limits pulmonary inflammation. Four to nine-week old calves were infected with BRSV by aerosol and were treated with either meloxicam intravenously on day (D)4 (n = 5, MEL), acetylsalicylat-DL-lysin intravenously on D4 and D5 (n = 5, ASA), or were left untreated as controls (n = 5, CTR). Clinical signs were monitored daily until necropsy on D7, BRSV-RNA was detected in nasal swabs and bronchoalveolar lavage (BAL) by RT-qPCR, inflammatory cells and proteins were identified in BAL by cytology and label-free quantitative mass spectrometry-based proteomics, respectively, and oxylipids were quantified in BAL and plasma by liquid chromatography tandem mass spectrometry with triple quadrupole mass detectors. The calves developed mild to moderate signs of respiratory disease and, with the exception of one MEL-treated and one ASA-treated calf, limited lung lesions. None of the treatments had a significant effect on virus replication, clinical signs or lung lesion extent. Relative to controls, both treatments initially induced a downregulation of proteins in BAL. Immunoglobulin (Ig)-related proteins, such as the Ig kappa and lambda locus and the joining chain of IgA and IgM, were downregulated in MEL-treated calves compared to controls. In addition, meloxicam induced an increased neutrophil influx in BAL in response to BRSV, possibly related to a reduction in plasma prostaglandin, and to a downregulation of The Liver X Receptor/ Retinoid X Receptor (LXR/RXR), the Farnesoid X Receptor (FXR)/RXR and the 24-Dehydrocholesterol Reductase (DHC24) signalling pathways in the lung. The risk of NSAIDs to increase neutrophil activity during stimulation with BRSV or other toll-like receptor 4 agonists needs to be investigated further. Since augmented neutrophil responses can be detrimental, the results of the present study do not support the use of NSAIDs to prevent the clinical expression of BRSV-infection., Competing Interests: Dr. Timsit is an Innovation Scientist at Ceva Animal Health and is responsible for early phases of drug discovery. This article reflects the views of the authors and should not be construed as representing the views of Ceva Sante Animale. None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Hägglund et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The objective of this scoping review is to provide an overview of the available evidence on the effectiveness of web-based interventions for fear of cancer recurrence (FCR) and a discussion of drawbacks and possible improvements for web-based interventions identified in the reviewed studies. These steps fulfil the aim of this review, which is to offer suggestions for developing future web-based interventions based on the reviewed studies., Methods: Five databases (PubMed, MEDLINE, EMBASE, SCOPUS and Web of Science) were searched. Original peer-reviewed articles, written in English, on web-based interventions for FCR were included for review. The data from the included studies was synthesised thematically., Results: We included 34 papers reporting on 28 interventions. Most of the studies in the papers were quantitative and mixed quantitative studies with a qualitative element, e.g. an interview post-intervention. Interventions were most commonly trialled with women breast cancer patients. Top three countries where studies were conducted were USA, Australia and the Netherlands. The most common theoretical framework for interventions is cognitive behavioural therapy (CBT), followed by mindfulness-based and mixed CBT, mindfulness, acceptance and commitment therapy (ACT), relaxation approaches. FCR was the primary focus/measure in 19 Studies, in 9 studies FCR was a secondary/related outcome/measure. Overall, the evidence of efficacy of web-based interventions on FCR is mixed., Conclusions: The existing research suggests several key points for producing more robust evidence about the effectiveness of web-based interventions for FCR. First, the studies suggest that it is a priority to better define eligibility criteria to proactively include people with higher levels of FCR. Second, there is a need for longer-term follow-up and outcome measuring period. Third, research examining the reasons for dropout from web-based interventions for FCR is critical to improve the effectiveness of web-based interventions. Fourth, while web-based interventions do not involve the costs of transportation, traveling time, space, equipment, cleaning, and other expenses, further cost utility analyses should be performed. Finally, future studies should assess how intervention accessibility, adherence, and effectiveness can be improved across different intervention designs, varying from intensive synchronous individual therapist-assisted web-based programme to blended designs combining the advantages of face-to-face and internet-based elements, to entirely self-managed programmes., Implications for Cancer Survivors: Developing and evaluating more accessible FCR treatments have been identified among top international FCR research priorities (Shaw et al. 2021). While there is some evidence that web-based interventions can be as effective as face-to-face interventions, currently there is a dearth of systematic data about the ways in which the web-based modality specifically can enhance supportive care for FCR. Developing knowledge about effective web-based interventions has implications for cancer survivors as they can be presented with more accessible, low-cost and low-burden options for managing fear of cancer recurrence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zibaite et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Algeria like other North African countries is experiencing recurrent episodes of West Nile Virus (WNV) emergences and new health threats associated with the introduction of Aedes albopictus in 2010 are to be feared. To improve the surveillance of mosquito-borne pathogens, we performed a study using innovative tools based on multiplex molecular methods., Methods: We combined two approaches: a high-throughput chip based on the BioMark Dynamic array system to detect arboviruses in mosquitoes, and a set of immunologic methods (ELISA, microsphere immunoassays (MIA) and virus microneutralization tests (MNT)) for serological surveys in animal hosts. We investigated two distinct regions: a first zone located in the coastal humid region and a second one in the Saharan desert region., Principal Findings: We collected a total of 1,658 mosquitoes belonging to nine different species and found predominantly Culex pipienss. l. (56.5%) and Cx. perexiguus (27.5%). From 180 pools of 10 mosquitoes, we detected four arboviruses: Banna virus (BAV), chikungunya virus (CHIKV), Sindbis virus (SINV), and Usutu virus (USUV). Moreover, we examined 389 blood samples from equids and poultry and found that 52.4% were positive for flavivirus antibodies in ELISA, while 30.8% were positive for WNV and two chickens and two equids were positive for USUV by MNT and MIA respectively., Conclusions: To our knowledge, this is the first report of five arboviruses circulating in Algeria, with three reported for the first time (CHIKV, BAV, and USUV). Our study brings evidence that reinforcing surveillance using more discriminant tools may help in anticipating future emergences and propose adapted control measures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Boubidi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Vaginitis is a prevalent clinical disorder associated with several adverse health consequences, prompting women to seek medical care. In this study we evaluate the Vaginal Panel Real-Time PCR kit (qPCR test) against routinely used diagnostics for detection of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and trichomoniasis. A total of 1011 vaginal swab specimens were analyzed. The routinely diagnostic methods for BV was Gram stain-based Nugent score. VVC presence was detected by culture, and Candida species were identified using MALDI-TOF MS. Trichomonas vaginalis was identified by culture in a selective medium. Molecular analyses were conducted on the MagXtract® 3200 System and analyzed using the CFX96™ Real-Time PCR Detection System. The sensitivity, specificity, positive predictive value, and negative predictive value of the qPCR test compared to the reference method for BV diagnosis was 93.1%, 88.8%, 90.1% and 92.2%, respectively, with a Kappa value of 0.82. For Candida species, sensitivity, specificity, positive predictive value, and negative predictive value were 96.0%, 98.4%, 95.3%, and 98.7%, respectively. The qPCR test detected 32 additional positive samples for Candida not reported by the routinely used diagnostics. For trichomoniasis, the qPCR test identified T. vaginalis in fifteen specimens, despite no microscopic detection in cultured specimens. Our results demonstrate that the Vaginal Panel Real-Time PCR kit shows optimal concordance with routinely used diagnostics for diagnosing vaginitis. Furthermore, enhancing detection of T. vaginalis. However, further validation studies are necessary to confirm its full diagnostic accuracy. The use of nucleic acid amplification tests (NAATs) provides rapid and accurate diagnosis, crucial for early detection and treatment of vaginitis., Competing Interests: The funder provided support in the form of salaries for authors IA, SUP and PM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Amor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

All organisms sense and respond to pathogenic challenge. Tissue-specific responses are required to combat pathogens infecting distinct cell types. Cyclic dinucleotides (CDNs) are produced endogenously downstream of pathogen recognition or by pathogens themselves which bind to STING to activate NF-kB-dependent antimicrobial gene expression programs. It remains unknown whether there are distinct immune responses to CDNs in Drosophila tissues. Here, we investigated tissue specific CDN-STING responses and uncovered differences in gene-induction patterns across tissues that play important roles in viral infections. Using tissue-and cell-specific genetic studies we found that dSTING in the fat body controls CDN-induced expression of dSTING-regulated gene 1 (Srg1) but not dSTING-regulated gene 2 (Srg2) or 3 (Srg3). In contrast, the gastrointestinal tract largely controls expression of Srg2 and Srg3. We found that Srg3 is antiviral against the natural fly pathogen Drosophila C virus and the human arthropod-borne Rift Valley Fever virus (RVFV), but not other arthropod-borne viruses including Sindbis virus and dengue virus. Furthermore, we found that Srg3 has an important role in controlling RVFV infection of the ovary which has important implications in understanding vertical transmission of viruses and RVFV in mosquitoes. Overall, our study underscores the importance of tissue-specific responses in antiviral immunity and highlights the complex tissue regulation of the CDN-STING pathway., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Segrist et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Quality and timely antenatal care is a vital component of pregnancy care for the well-being of mothers and babies. The aim of this study of to assess self-reported obstetricians' adherence to national and international antenatal care guidelines in Lebanon. This cross-sectional study approached all obstetricians registered with the Lebanese Society of Obstetrics and Gynecology and the Lebanese Order of Physicians to participate in an online and telephone-based survey. The study tool included all of the items from the World Health Organization and national guidelines for antenatal care. Obstetricians' self-reported adherence was assessed across five modules including dietary interventions, dietary supplements, antenatal care assessment, fetal growth assessment, and antenatal care preventive measures. A total of 134 obstetricians completed the survey. Overall, adherence was high for most antenatal care guidelines except for providing nutrition services to undernourished pregnant women, screening for intimate partner violence, and providing tetanus vaccines. The number of recommended antenatal care visits (≥8 vs. <8 visits) was higher among obstetricians in Mount Lebanon or Beirut compared to other areas in Lebanon (72.7%vs.48.6%; p-value <0.01). Provision of tetanus or diphtheria, tetanus, and pertussis (DTP) vaccination was lower for obstetricians who provide care for women who pay out-of-pocket compared to obstetricians who provide care to women who use other payment methods (25.3%vs.45.7%; p-value = 0.024). Group B streptococcus screening test and the provision of at least five ultrasounds were higher among obstetricians who provide care in private clinics or clinics in private hospitals compared to clinics in public hospitals or primary healthcare centers (88.8%vs.66.7%; p-value = 0.023) and (83.6%vs.55.6%; p-value = 0.011), respectively. Reinforcing the adherence to all antenatal care guidelines by continuous monitoring of health facilities is crucial for best practice. Subsidies for essential services may be required for those who are unable to afford components of antenatal care., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Khoury et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: In the neurological emergency room (nER), timely electroencephalography (EEG) diagnostic is often crucial in patients with altered state of consciousness as well as in patients presenting with a first seizure. Yet, routine-EEG (rEEG) is often not available, especially during off-hours., Methods: We analyzed the value of a commercially available, simplified wireless eight-channel EEG recording (swEEG, CerebAir® EEG headset, Nihon Kohden), applied by non-EEG-specialized medical students, in patients presenting in our nER with (suspicion of) epileptic seizures and/or loss of or altered state of consciousness between 08/2019 and 08/2022. We evaluated the feasibility and validity compared to a standard rEEG (21 electrodes according to the international 10/20 system) and also included the clinical follow-up of the patients., Results: 100 patients were included in our analysis (mean age 57.6 ± 20.4 years; 61 male). Median time of electrode application was 7 minutes (range 4-20 minutes), with significantly longer duration in patients with altered level of consciousness (median 8 minutes, p = 0.035). Electrode impedances also differed according to state of consciousness (p = 0.032), and were higher in females (p<0.001). 55 patients received additional rEEG, either during their acute nER stay (25) and/or during the next days (38). Considering normal EEG findings vs. pathological slowing vs. epileptiform activity, swEEG matched first rEEG results in 48/55 cases (87.3%). Overall, swEEG detected the same or additional pathological EEG patterns in 52/55 cases (94.5%). In 7/75 patients (9.3%) who did not receive rEEG, or had their rEEG scheduled to a later time point during their hospital stay, swEEG revealed important additional pathological findings (e.g. status epilepticus, interictal epileptiform discharges), which would have triggered acute therapeutic consequences or led to further diagnostics and investigations., Conclusion: The introduced swEEG represents a practicable, valuable technique to be quickly applied by non-EEG-specialized ER staff to initiate timely diagnostic and guide further investigations and treatment in the nER. Moreover, it may help to avoid under-diagnostic with potentially harmful consequences caused by skipped or postponed regular 10/20 EEG examinations, and ultimately improve the outcome of patients., Competing Interests: “S. Gollwitzer received personal fees from Desitin, UCB, outside the submitted work. J.D. Lang served on the speakers’ bureau of Eisai and Destin. M.I. Sprügel reports grants from IZKF, Marohn Foundation, Doktor Robert Pfleger Foundation and German Society for Neurointensive Care and Emergency Medicine (DGNI) outside submitted work. H.M. Hamer has served on the scientific advisory boards of Arvelle, Bial, Corlieve, Eisai, GW, Novartis, Sandoz, UCB Pharma and Zogenix. He has served on the speakers’ bureaus of or received unrestricted grants from Amgen, Ad-Tech, Alnylam, Bracco, Desitin, Eisai, GW, Nihon Kohden, Novartis, Pfizer, and UCB Pharma. The remaining authors have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials”., (Copyright: © 2024 Welte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)