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Background: Explicit funding and industry affiliation are believed to potentially impact medical research. There have been an increasing number of studies that have evaluated this relationship. The purpose of this study is to determine whether industry affiliation influences the outcomes of randomized controlled trials that investigate the effectiveness of platelet-rich plasma (PRP) in the treatment of lateral epicondylitis. Methods: A search of PubMed, SPORTDiscus, and SCOPUS was performed using the search terms “lateral epicondylitis” and “platelet-rich plasma” as well as “tennis elbow” and “platelet-rich plasma.” Only studies from 2010 to present were considered. Final texts were then analyzed for industry affiliation and treatment efficacy. When determining whether a study was industry-affiliated, explicit financial supporters of the study, stated conflicts of interest, American Academy of Orthopaedic Surgeons disclosures, and the Centers for Medicare and Medicaid Services open payments database were assessed. Study outcomes were categorized as favorable, analogous, or unfavorable based on achieving a statistically significant (P

Millet, a vital and nutritionally dense cereal extensively cultivated in Sub-Saharan Africa, plays a key role in ensuring food security. This study investigates the starch synthase (SS) gene family, which is crucial for starch biosynthesis and influences various plant functions and stress responses. While the specific roles of SS genes in millet under drought conditions are not fully elucidated, this research provides a thorough analysis of the SS gene family in millet. A total of twelve millet SS genes (SiSSs) were identified and classified into four subfamilies (I–IV) through gene structure and phylogenetic analysis. The SiSS genes were unevenly distributed across millet chromosomes, with cis-acting elements associated with plant growth and stress defense being identified. Quantitative PCR (qPCR) revealed dynamic and varied expression patterns of SiSSs in different tissues under drought stress. Millet plants subjected to drought conditions showed higher tissue starch content and increased starch synthase activity compared to controls. Importantly, the expression levels of the twelve SiSSs were positively correlated with both starch content and synthase activity, suggesting their significant role in drought tolerance. This study enhances our understanding of the millet SS gene family and highlights the potential of these genes in breeding programs aimed at developing drought-resistant millet varieties. Further research is recommended to validate these findings and delve deeper into the mechanisms underlying drought tolerance.

ABSTRACT Cryptococcal meningitis causes an estimated 112,000 global deaths per annum. Genomic and phenotypic features of the infecting strain of Cryptococcus spp. have been associated with outcomes from cryptococcal meningitis. Additionally, population-level pharmacokinetic variability is well documented in these patient cohorts. The relative contribution of these factors to clinical outcomes is unknown. Based in Malawi, we conducted a sub-study of the phase 3 Ambition-CM trial (ISRCTN72509687), collecting plasma and cerebrospinal fluid at serial time points during the first 14 days of antifungal therapy. We explored the relative contribution of pathogen genotype, drug resistance phenotype, and pharmacokinetics on clinical outcomes including lumbar opening pressure, pharmacodynamic effect, and mortality. We report remarkable genomic homogeneity among infecting strains of Cryptococcus spp., within and between patients. There was no evidence of acquisition of antifungal resistance in our isolates. Genotypic features of the infecting strain were not consistently associated with adverse or favorable clinical outcomes. However, baseline fungal burden and early fungicidal activity (EFA) were associated with mortality. The strongest predictor of EFA was the level of exposure to amphotericin B. Our analysis suggests the most effective means of improving clinical outcomes from HIV-associated cryptococcal meningitis is to optimize exposure to potent antifungal therapy.IMPORTANCEHIV-associated cryptococcal meningitis is associated with a high burden of mortality. Research into the different strain types causing this disease has yielded inconsistent findings in terms of which strains are associated with worse clinical outcomes. Our study suggests that the exposure of patients to potent anti-cryptococcal drugs has a more significant impact on clinical outcomes than the strain type of the infecting organism. Future research should focus on optimizing drug exposure, particularly in the context of novel anticryptococcal drugs coming into clinical use.

Abstract Bacteria have an extensive adaptive ability to live in close association with eukaryotic hosts, exhibiting detrimental, neutral or beneficial effects on host growth and health. However, the genes involved in niche adaptation are mostly unknown and their functions poorly characterized. Here, we present bacLIFE ( https://github.com/Carrion-lab/bacLIFE ) a streamlined computational workflow for genome annotation, large-scale comparative genomics, and prediction of lifestyle-associated genes (LAGs). As a proof of concept, we analyzed 16,846 genomes from the Burkholderia/Paraburkholderia and Pseudomonas genera, which led to the identification of hundreds of genes potentially associated with a plant pathogenic lifestyle. Site-directed mutagenesis of 14 of these predicted LAGs of unknown function, followed by plant bioassays, showed that 6 predicted LAGs are indeed involved in the phytopathogenic lifestyle of Burkholderia plantarii and Pseudomonas syringae pv. phaseolicola. These 6 LAGs encompassed a glycosyltransferase, extracellular binding proteins, homoserine dehydrogenases and hypothetical proteins. Collectively, our results highlight bacLIFE as an effective computational tool for prediction of LAGs and the generation of hypotheses for a better understanding of bacteria-host interactions.

Background: Preoperative assessment of risk for emergency laparotomy may enhance decision making with regards to urgency or perioperative critical care admission and promote a more informed consent process for patients. Accordingly, we aimed to assess the performance of risk assessment tools in predicting mortality after emergency laparotomy. Methods: PubMed, Embase, the Cochrane Library and CINAHL were searched to 12 February 2022 for observational studies reporting expected mortality based on a preoperative risk assessment and actual mortality after emergency laparotomy. Study screening, data extraction, and risk of bias using the Downs and Black checklist were performed in duplicate. Data on setting, operation undertaken, expected and actual mortality rates were extracted. Meta-analysis was planned but not possible due to heterogeneity. This study is registered with PROSPERO, CRD42022299227. Results: From 10,168 records, 82 observational studies were included. 17 risk assessment tools were described, the most common of which were P-POSSUM (42 studies), POSSUM (13 studies), NELA (12 studies) and MPI (11 studies). Articles were published between 1990 and 2022 with the most common country of origin being the UK (33 studies) followed by India (11 studies). Meta-analysis was not possible. Observed mortality and expected mortality based on risk assessment is reported for each study and generally shows most studies show accurate risk prediction. Conclusions: This review synthesises available literature to characterise the performance of various risk assessment tools in predicting mortality after emergency laparotomy. Findings from this study may benefit those undertaking emergency laparotomy and future research in risk prediction.

Background Mortality associated with HIV-associated cryptococcal meningitis remains high even in the context of clinical trials (24–45% at 10 weeks); mortality at 12-months is up to 78% in resource limited settings. Co-prevalent tuberculosis (TB) is common and preventable, and likely contributes to poor patient outcomes. Innovative strategies to increase TB preventative therapy (TPT) provision and uptake within this high-risk group are needed. Protocol The IMPROVE trial (Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease) is a nested open label, two arm, randomised controlled strategy trial to evaluate the safety (adverse events) and feasibility (adherence and tolerability) of two ultra-short course TPT strategies, in the context of recent diagnosis and treatment for cryptococcal meningitis. We will enrol 205 adults with HIV-associated cryptococcal meningitis from three hospitals in Uganda. Participants will be randomised to either inpatient initiation (early) or outpatient initiation (standard, week 6) of 1HP (one month of isoniazid and rifapentine). Participant follow-up is to include TB screening, 1HP pill counts and tolerability reviews on alternate weeks until week-18. The trial primary endpoint is TB-disease free 1HP treatment completion at 18-weeks, secondary endpoints: 1HP treatment completion, 1HP discontinuation, grade ≥3 adverse events and serious adverse events, drug-induced liver injury, incident active TB, 18-week survival; rifapentine, fluconazole and dolutegravir concentrations will be measured with intensive sampling in a pharmacokinetic sub-study of 15 eligible participants. Discussion The IMPROVE trial will provide preliminary safety and feasibility data to inform 1HP TPT strategies for adults with advanced HIV disease and cryptococcal meningitis. The potential impact of demonstrating that inpatient initiation of 1HP TPT is safe and feasible amongst this high-risk subpopulation with advanced HIV disease, would be to expand the range of clinical encounters in which clinicians can feasibly provide 1HP, and therefore increase the reach of TPT as a preventative intervention. ISRCTN registration ISRCTN18437550 (05/11/2021)

Background Radiofrequency has seen an increase in use in orthopedics including cartilage lesion debridement in the hip and knee as well as many applications in arthroscopic shoulder surgery. The purpose of this systematic review is to evaluate the safety and usage of radiofrequency in the shoulder. Methods This systematic review was registered with PROSPERO (international registry) and followed the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guidelines. Embase and PubMed were searched using: “shoulder,” “rotator cuff,” “biceps,” “acromion” AND “monopolar,” “bipolar,” “ablation,” “coblation,” and “radiofrequency ablation.” The title and abstract review were performed independently. Any discrepancies were addressed through open discussion. Results A total of 63 studies were included. Radiofrequency is currently utilized in impingement syndrome, fracture fixation, instability, nerve injury, adhesive capsulitis, postoperative stiffness, and rotator cuff disease. Adverse events, namely superficial burns, are limited to case reports and case series, with higher-level evidence demonstrating safe use when used below the temperature threshold. Bipolar radiofrequency may decrease operative time and decrease the cost per case. Conclusions Shoulder radiofrequency has a wide scope of application in various shoulder pathologies. Shoulder radiofrequency is safe; however, requires practitioners to be cognizant of the potential for thermal burn injuries. Bipolar radiofrequency may represent a more efficacious and economic treatment modality. Safety precautions have been executed by institutions to cut down patient complications from shoulder radiofrequency. Future research is required to determine what measures can be taken to further minimize the risk of thermal burns. Level of evidence IV.

Human amniotic membrane (hAM), the innermost placental layer, has unique properties that allow for a multitude of clinical applications. It is a common misconception that birth-derived tissue products, such as dual-layered dehydrated amnion–amnion graft (dHAAM), are similar regardless of the manufacturing steps. A commercial dHAAM product, Axolotl Biologix DualGraft™, was assessed for biological and mechanical characteristics. Testing of dHAAM included antimicrobial, cellular biocompatibility, proteomics analysis, suture strength, and tensile, shear, and compressive modulus testing. Results demonstrated that the membrane can be a scaffold for fibroblast growth (cellular biocompatibility), containing an average total of 7678 unique proteins, 82,296 peptides, and 96,808 peptide ion variants that may be antimicrobial. Suture strength results showed an average pull force of 0.2 N per dHAAM sample (equating to a pull strength of 8.5 MPa). Tensile modulus data revealed variation, with wet samples showing 5× lower stiffness than dry samples. The compressive modulus and shear modulus displayed differences between donors (lots). This study emphasizes the need for standardized processing protocols to ensure consistency across dHAAM products and future research to explore comparative analysis with other amniotic membrane products. These findings provide baseline data supporting the potential of amniotic membranes in clinical applications.

Presently, researchers’ and experts are currently dealing with ways to maintain and improve the best performance of several energy storage technologies. This review focuses on how adding carbon derivatives to lithium sulfur battery (LiSBs) electrodes can reduce capacity fade, resistance, breakdown and poor performance while also enabling the best possible use of LiSBs in a variety of devices. Their rate as regards specific capacitance, energy and power densities, life duration, lightweight, etc., are among these optimal performances. The global energy crisis focused more scientists’ attention on how to enhance the performance of LiSBs devices for the benefit of humanity. Numerous carbon derivatives, including GO, rGO, carbon nanotubes (CNTs), etc., have advantageous properties that raise the efficiency of energy storage technologies. This review looked at LiSBs and the impact of carbon derivatives addition on their storage capability, cycle stability, life span and durability.

There is an increasing need to improve the accuracy of extreme weather forecasts for life-saving applications and in support of various socioeconomic sectors in East Africa, a region with remarkable mesoscale systems due to its complex topography defined by sharp gradients in elevation, inland water bodies, and landuse conversions. This study sought to investigate the impacts of the Weather Research and Forecasting (WRF) model spatial resolution on resolving rainfall variability with topography utilizing nested domains at 12 and 2.4 km resolutions. The model was driven by the National Centers for Environmental Prediction (NCEP)-Global Data Assimilation System (GDAS) Global Forecast System (GFS) final (FNL) reanalysis to simulate the weather patterns over East Africa from 3rd April 2018 to 30th April 2018, which were evaluated against several freely available gridded weather datasets alongside rainfall data from the Kenya Meteorological Department (KMD) stations. The reference datasets and the model outputs revealed that the highlands had more rainfall events and higher maximum daily rainfall intensity compared to the surrounding lowlands, attributed to orographic lifting enhancing convection. Rainfall was inversely proportional to altitude from 500 m to 1,100 m above sea level (ASL) for both coarse and fine resolutions. The convection-permitting setup was superior in three aspects: resolving the inverse altitude-rainfall relationship for altitudes beyond 3000 m ASL, simulating heavy rainfall events over the lowlands, and resolution of the diurnal cycle of low-level wind. Although the coarse resolution setup reasonably simulated rainfall over large mountains, only the convection-permitting configuration could accurately resolve rainfall variability over contrasting topographical features. The study notes that high-resolution modeling systems and topography-sensitive bias correction techniques are critical for improving the quality of operational weather forecasts in East Africa.

Purpose: To determine the rate of reporting for sociodemographic variables in randomized controlled trials (RCTs) investigating femoral acetabular impingement (FAI) and hip arthroscopy. Methods: PubMed, Scopus, and Web of Science were queried for articles relating to FAI and hip arthroscopy. Articles included in final analysis were RCTs investigating operative management of FAI. Included RCTs were analyzed for reporting of age and sex or gender as well as the following sociodemographic variables: race, ethnicity, insurance status, income, housing status, work status, and education level in the results section or any section of the paper. Data was analyzed using χ2 and Fisher exact tests with significance defined as P < .05. Results: Forty-eight RCTs were identified from 2011 to 2023. Age was reported in 48 of 48 (100%) of included papers; sex or gender was reported in 47 of 48 (97.9%). Reporting of sociodemographic variables in any section respectively was: race (7/48, 14.6%), ethnicity (4/48, 8.33%), insurance status (0/48, 0%), income (1/48, 2.08%), housing status (0/48, 0%), work status (3/48, 6.25%), and education (2/48, 4.17%). There was no significant difference for reporting demographic variables with respect to journal or year of publication (P = .666 and P = .761, respectively). Sociodemographic variables (9/48) were reported significantly less frequently than age and sex or gender (48/48) (P < .001). Conclusions: This study found that sociodemographic variables in FAI and hip arthroscopy RCTs are reported with much lower frequency than age and sex or gender. These findings may demonstrate the need to include patient sociodemographic data in RCTs so that their results can be better generalized and applied to the appropriate patient population. Level of Evidence: Level II, systematic review of level I and II evidence.

Introduction: Monovalent COVID-19 boosters lower the risk of COVID-19 disease, infection, hospitalization, and death. This study examined associations between exposure to a booster public education campaign (the booster campaign) and the increases in booster uptake and reduced length of time until booster uptake among U.S. adults. Methods: Data included a national survey panel of U.S. adults and booster campaign paid media (i.e., digital impressions and TV gross rating points) from September 2021 to May 2022. Multilevel logistic regression models examined the association between exposure to the booster campaign and the likelihood of booster uptake. A Cox proportional hazard model evaluated the association between the booster campaign and booster uptake timing. Interaction terms between the booster campaign media variables and first-dose COVID-19 vaccine date examined differential effects of the booster campaign based on when individuals received their first dose. Results: Interactions between first-dose vaccination date and the booster campaign were statistically significant for cumulative digital impressions (ß=4.75e-08; 95% CIs=5.93e-09, 8.90e-08) and TV gross rating points (ß = 4.62e-05; 95% CIs=5.09e-06, 8.73e-05), suggesting that booster uptake was strongest among those who received their first-dose COVID-19 vaccine later. Booster campaign cumulative digital impressions and TV gross rating points were associated with accelerated booster uptake among those with later first-dose vaccination dates (digital: ß=9.98e-08; 95% CIs=2.70e-08, 1.73e-07; TV: ß=0.0001; 95% CIs=2.80e-05, 0.0002), relative to those with earlier first-dose vaccination dates. Conclusions: The booster campaign may have increased monovalent booster uptake and reduced how long individuals waited until getting their booster. Public education campaigns show promise in stemming the tide of pandemic fatigue and increasing booster confidence.

Background Maridi County is an onchocerciasis-endemic area in South Sudan. Annual community-directed treatment with ivermectin (CDTi) was instituted in Maridi since the early 2000s, but with low coverage. In 2021, the CDTi programme was strengthened to a six-monthly programme. Additionally, the community-based vector control strategy “Slash and Clear” has been implemented since 2019 at the Maridi Dam, the only blackfly breeding site in the area. This study assessed the effect of these reinforced onchocerciasis elimination interventions on the Onchocerca volvulus seroprevalence among young children, an indicator of ongoing transmission. Methods Baseline and follow-up serosurveys were conducted in Maridi in 2019 (prior to strengthening onchocerciasis elimination efforts) and 2023, respectively. During both surveys, children aged three to nine years were recruited from five study sites situated at different distances from the Maridi Dam. Ov16 antibodies were detected via rapid diagnostic tests (RDTs) using whole blood obtained by finger-pricking the participants. Baseline and follow-up Ov16 prevalence rates were calculated and compared. Results In 2019, the Ov16 seroprevalence among children aged three to nine years was 24.5% compared to 30.6% in 2023 (p=0.22). Both surveys found a particularly high Ov16 seroprevalence in the study site closest to the Maridi Dam (35.0% in 2019 and 44.0% in 2023, p=0.52). The Ov16 seroprevalence had a non-significant decreasing trend in the three-year-old children, from 12.5% (3/24) in 2019 to 8.8% (3/34) in 2023 (p=0.65). Conclusion The persistent Ov16 RDT seropositivity among three-year-old children in 2023 indicates ongoing O. volvulus transmission. Therefore, further strengthening of the onchocerciasis elimination programme is required. The study highlights the utility of RDTs in monitoring onchocerciasis transmission in highly endemic settings.

ObjectivesThe potential impact of cumulative community-directed treatment with ivermectin (CDTI) on epilepsy epidemiology in Mvolo County, South Sudan, an onchocerciasis-endemic area with high epilepsy prevalence, was investigated. Annual CDTI was introduced in 2002 in Mvolo, with interruptions in 2016 and 2020.MethodsComprehensive house-to-house surveys in Mvolo (June 2020 and 2022) identified cases of epilepsy, including probable nodding syndrome (pNS). Community workers screened households in selected sites for suspected epilepsy, and medical doctors confirmed the diagnosis and determined the year of seizure onset. The incidence of epilepsy, including pNS, was analysed using 95% confidence intervals (CIs). Data on ivermectin intake and onchocerciasis-associated manifestations (itching and blindness) were collected.ResultsThe surveys covered 15,755 (2020) and 15,092 (2022) individuals, identifying 809 (5.2%, 95% CI: 4.8-5.5%) and 672 (4.5%, 95% CI: 4.1-4.8%) epilepsy cases, respectively. Each survey reported that a third of the surveyed population experienced skin itching, and 3% were blind. Epilepsy incidence per 100,000 person-years gradually declined, from 326.5 (95% CI: 266.8-399.1) in 2013-2015 to 96.6 (95% CI: 65.5-141.7) in 2019-2021. Similarly, pNS incidence per 100,000 person-years decreased from 151.7 (95% CI: 112.7-203.4) to 27.0 (95% CI: 12.5-55.5). Coverage of CDTI was suboptimal, reaching only 64.0% of participants in 2019 and falling to 24.1% in 2021 following an interruption in 2020 due to COVID-19 restrictions. Additionally, while 99.4% of cases had active epilepsy in 2022, less than a quarter of these had access to antiseizure medication.ConclusionsThe observed decrease in epilepsy incidence despite suboptimal CDTI coverage highlights the potential impact of onchocerciasis control efforts and underscores the need to strengthen these efforts in Mvolo County and across South Sudan. As a proactive measure, Mvolo and neighbouring counties are transitioning to biannual CDTI. Furthermore, the substantial epilepsy treatment gap in Mvolo should be addressed.

Background: Total ankle arthroplasty (TAA), first developed as an alternative to ankle arthrodesis, has become an increasingly popular management option for end-stage ankle arthritis. Prior studies have shown commercial insurance payers base their coverage criteria on limited and low level of evidence research. This study aims to quantify and describe the evidence insurance companies use to support TAA coverage policies. Methods: The top 11 national commercial health insurance payers for TAA were identified. A google search was performed to identify payer coverage policies. Policy documents were examined and cited references were classified by type of reference as well as reviewed for level of evidence (LOE). Specific coverage criteria for each individual payer were then extracted. Criteria were compared to assess for similarities among commercial payers. Finally, all references cited by each payer were examined to determine whether they mentioned the specific payer criteria. Results: Six of the 11 payers had accessible coverage policies. The majority of cited references were primary journal articles (145, 60.9%) and the majority of references cited (179, 75.2%) were level III or level IV evidence. We found significant homogeneity in coverage criteria among payers. In addition, cited sources inconsistently mentioned specific payer coverage criteria. Conclusion: This study demonstrates that commercial insurance payers rely on the relatively low level of currently available scientific evidence when formulating coverage policies for TAA use and adopt criteria that have not been thoroughly analyzed in the literature. More high level of evidence research is needed to help clinicians and insurance companies further refine indications for TAA so that patients who might benefit from the procedure are adequately covered. Level of Evidence: Level IV, review.

COVID-19 vaccine hesitancy has been a major limiting factor to the widespread uptake of COVID-19 vaccination in the United States. A range of interventions, including mass media campaigns, have been implemented to encourage COVID-19 vaccine confidence and uptake. Such interventions are often guided by theories of behavior change, which posit that behavioral factors, including beliefs, influence behaviors such as vaccination. Although previous studies have examined relationships between vaccination beliefs and COVID-19 vaccination behavior, they come with limitations, such as the use of cross-sectional study designs and, for longitudinal studies, few survey waves. To account for these limitations, we examined associations between vaccination beliefs and COVID-19 vaccine uptake using data from six waves of a nationally representative, longitudinal survey of U.S. adults (N = 3,524) administered over a nearly 2-year period (January 2021–November 2022). Survey-weighted lagged logistic regression models were used to examine the association between lagged reports of vaccination belief change and COVID-19 vaccine uptake, using five belief scales: (1) importance of COVID–19 vaccines, (2) perceived benefits of COVID-19 vaccination, (3) COVID-19 vaccine concerns and risks, (4) normative beliefs about COVID-19 vaccination, and (5) perceptions of general vaccine safety and effectiveness. Analyses controlled for confounding factors and accounted for within-respondent dependence due to repeated measures. In individual models, all vaccination belief scales were significantly associated with increased COVID-19 vaccine uptake. In a combined model, all belief scales except the benefits of COVID-19 vaccination were significant predictors of vaccine uptake. Overall, belief scales indicating the importance of COVID-19 vaccines and normative beliefs about COVID-19 vaccination were the strongest predictors of COVID-19 vaccine uptake. Findings demonstrate that changes in vaccination beliefs influence subsequent COVID-19 vaccine uptake, with implications for the development of future interventions to increase COVID-19 vaccination.

Introduction: Reference ranges for determining pathological versus normal postoperative return of bowel function are not well characterised for general surgery patients. This study aimed to characterise time to first postoperative passage of stool after general surgery; determine associations between clinical factors and delayed time to first postoperative stool; and evaluate the association between delay to first postoperative stool and prolonged length of hospital stay. Methods: This study included consecutive admissions at two tertiary hospitals across a two-year period whom underwent a range of general surgery operations. Multivariable logistic regression analyses were conducted to determine associations between the explanatory variables and delayed first postoperative stool, and between delayed first postoperative stool and length of hospital stay. The previously specified explanatory variables were used, with the addition of the dichotomised ≥4-day delay to first postoperative stool. Prolonged length of hospital stay was considered ≥7 days. Results: 2,212 general surgery patients were included. Median time to first postoperative stool was 2.28 (IQR 1.06–3.96). Median length of stay was 7.19 (IQR 4.50–12.01). Several operative characteristics and medication exposures were associated with delayed first postoperative stool. There was a statistically significant association between delayed first postoperative stool (≥4 days) and prolonged length of stay (≥7 days) (OR 4.34, 95 %CI 3.27 to 5.77, p

Abstract In a population-based representative sample of adults residing in 22 communities in Botswana, a southern African country with high HIV prevalence, 1 in 4 individuals had high blood pressure. High blood pressure was less prevalent in adults with HIV than without HIV. Sixty percent of persons with high blood pressure had not previously been diagnosed. Among individuals with a prior diagnosis of high blood pressure who reported being prescribed anti-hypertension medications, almost half had elevated blood pressure, irrespective of HIV-status. One-third of adults in this setting (mainly men) declined free non-invasive blood pressure assessments in their households. In conclusion, our study highlights alarmingly high hypertension rates in the community, with low levels of awareness and control, emphasizing the urgent need for community level BP screening and active management to reach recommended targets.

Abstract Background Exposure to repetitive head impacts (RHI) in American football players can lead to cognitive impairment and dementia due to neurodegenerative disease, particularly chronic traumatic encephalopathy (CTE). The pathognomonic lesion of CTE consists of perivascular aggregates of hyper-phosphorylated tau in neurons at the depths of cortical sulci. However, it is unclear whether exposure to RHI accelerates amyloid-β (Aβ) plaque formation and increases the risk for Alzheimer’s disease (AD). Although the Aβ neuritic plaques characteristic of AD are observed in a minority of later-stage CTE cases, diffuse plaques are more common. This study examined whether former professional and college American football players, including those with cognitive impairment and dementia, have elevated neuritic Aβ plaque density, as measured by florbetapir PET. Regardless of cognitive and functional status, elevated levels of florbetapir uptake were not expected. Methods We examined 237 men ages 45–74, including 119 former professional (PRO) and 60 former college (COL) football players, with and without cognitive impairment and dementia, and 58 same-age men without a history of contact sports or TBI (unexposed; UE) and who denied cognitive or behavioral symptoms at telephone screening. Former players were categorized into four diagnostic groups: normal cognition, subjective memory impairment, mild cognitive impairment, and dementia. Positive florbetapir PET was defined by cortical-cerebellar average SUVR of ≥ 1.10. Multivariable linear regression and analysis of covariance (ANCOVA) compared florbetapir average SUVR across diagnostic and exposure groups. Multivariable logistic regression compared florbetapir positivity. Race, education, age, and APOE4 were covariates. Results There were no diagnostic group differences either in florbetapir average SUVR or the proportion of elevated florbetapir uptake. Average SUVR means also did not differ between exposure groups: PRO-COL (p = 0.94, 95% C.I. = [− 0.033, 0.025]), PRO-UE (p = 0.40, 95% C.I. = [− 0.010, 0.029]), COL-UE (p = 0.36, 95% CI = [0.0004, 0.039]). Florbetapir was not significantly associated with years of football exposure, cognition, or daily functioning. Conclusions Cognitive impairment in former American football players is not associated with PET imaging of neuritic Aβ plaque deposition. These findings are inconsistent with a neuropathological diagnosis of AD in individuals with substantial RHI exposure and have both clinical and medico-legal implications. Trial registration NCT02798185.

Abstract Background Cancer immunotherapies including immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T-cell therapy have shown variable response rates in paediatric patients highlighting the need to establish robust biomarkers for patient selection. While the tumour microenvironment in adults has been widely studied to delineate determinants of immune response, the immune composition of paediatric solid tumours remains relatively uncharacterized calling for investigations to identify potential immune biomarkers. Methods To inform immunotherapy approaches in paediatric cancers with embryonal origin, we performed an immunogenomic analysis of RNA-seq data from 925 treatment-naïve paediatric nervous system tumours (pedNST) spanning 12 cancer types from three publicly available data sets. Results Within pedNST, we uncovered four broad immune clusters: Paediatric Inflamed (10%), Myeloid Predominant (30%), Immune Neutral (43%) and Immune Desert (17%). We validated these clusters using immunohistochemistry, methylation immune inference and segmentation analysis of tissue images. We report shared biology of these immune clusters within and across cancer types, and characterization of specific immune cell frequencies as well as T- and B-cell repertoires. We found no associations between immune infiltration levels and tumour mutational burden, although molecular cancer entities were enriched within specific immune clusters. Conclusions Given the heterogeneity of immune infiltration within pedNST, our findings suggest personalized immunogenomic profiling is needed to guide selection of immunotherapeutic strategies.

Abstract Purpose Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as “masqueraders of uveitis”. Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty. Methods An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes. Results We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs). Conclusion This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis.

Abstract Morphology and molecules are important data sources for estimating evolutionary relationships. Modern studies often utilise morphological and molecular partitions alongside each other in combined analyses. However, the effect of combining phenomic and genomic partitions is unclear. This is exacerbated by their size imbalance, and conflict over the efficacy of different inference methods when using morphological characters. To systematically address the effect of topological incongruence, size imbalance, and tree inference methods, we conduct a meta-analysis of 32 combined (molecular + morphology) datasets across metazoa. Our results reveal that morphological-molecular topological incongruence is pervasive: these data partitions yield very different trees, irrespective of which method is used for morphology inference. Analysis of the combined data often yields unique trees that are not sampled by either partition individually, even with the inclusion of relatively small quantities of morphological characters. Differences between morphology inference methods in terms of resolution and congruence largely relate to consensus methods. Furthermore, stepping stone Bayes factor analyses reveal that morphological and molecular partitions are not consistently combinable, i.e. data partitions are not always best explained under a single evolutionary process. In light of these results, we advise that the congruence between morphological and molecular data partitions needs to be considered in combined analyses. Nonetheless, our results reveal that, for most datasets, morphology and molecules can, and should, be combined in order to best estimate evolutionary history and reveal hidden support for novel relationships. Studies that analyse only phenomic or genomic data in isolation are unlikely to provide the full evolutionary picture.

Abstract Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI), but the components of RHI exposure underlying this relationship are unclear. We create a position exposure matrix (PEM), composed of American football helmet sensor data, summarized from literature review by player position and level of play. Using this PEM, we estimate measures of lifetime RHI exposure for a separate cohort of 631 football playing brain donors. Separate models examine the relationship between CTE pathology and players’ concussion count, athletic positions, years of football, and PEM-derived measures, including estimated cumulative head impacts, linear accelerations, and rotational accelerations. Only duration of play and PEM-derived measures are significantly associated with CTE pathology. Models incorporating cumulative linear or rotational acceleration have better model fit and are better predictors of CTE pathology than duration of play or cumulative head impacts alone. These findings implicate cumulative head impact intensity in CTE pathogenesis.

Purpose: To describe the incidence and types of spin in systematic reviews of platelet-rich plasma (PRP) injections for hip osteoarthritis (OA) and to determine whether patterns in study characteristics could be identified among studies with identifiable spin. Methods: The PubMed, Scopus, and SPORTDiscus databases were queried. Inclusion criteria were systematic reviews or meta-analyses that included an assessment of intra-articular PRP injections as a stand-alone treatment for hip OA. Two authors independently assessed the presence of spin in the included studies and recorded general study characteristics. The prevalence of the 15 different categories of spin was quantified using descriptive statistics. Results: Fifteen studies met inclusion criteria for this study. All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 (“Failure to report a wide confidence interval of estimates”), which was observed in 10 studies. The second most common type of spin was type 13 (“Failure to specify the direction of the effect when it favors the control intervention”), found in 6 studies. Conclusions: Spin is highly prevalent in abstracts of systematic reviews of PRP in the treatment of hip OA. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration. When present, spin in the abstracts of reviewed studies tended to favor the use of PRP in hip osteoarthritis. Clinical Relevance: It is important to understand the prevalence of spin in published abstracts, especially in areas of great impact or interest, so authors and readers can have a greater awareness of this potential form of bias.

The distribution and intensity of viral diseases transmitted by Aedes aegypti mosquitoes, including dengue, have rapidly increased over the last century. Here, we study dengue virus (DENV) transmission across the ecologically and demographically distinct regions or Ecuador. We analyzed province-level age-stratified dengue incidence data from 2000-2019 using catalytic models to estimate the force of infection of DENV over eight decades. We found that provinces established endemic DENV transmission at different time periods. Coastal provinces with the largest and most connected cities had the earliest and highest increase in DENV transmission, starting around 1980 and continuing to the present. In contrast, remote and rural areas with reduced access, like the northern coast and the Amazon regions, experienced a rise in DENV transmission and endemicity only in the last 10 to 20 years. The newly introduced chikungunya and Zika viruses have age-specific distributions of hospital-seeking cases consistent with recent emergence across all provinces. To evaluate factors associated with geographic differences in DENV transmission potential, we modeled DENV vector risk using 11,693 Aedes aegypti presence points to the resolution of 1 hectare. In total, 56% of the population of Ecuador, including in provinces identified as having increasing DENV transmission in our models, live in areas with high risk of Aedes aegypti, with population size, trash collection, elevation, and access to water as important determinants. Our investigation serves as a case study of the changes driving the expansion of DENV and other arboviruses globally and suggest that control efforts should be expanded to semi-urban and rural areas and to historically isolated regions to counteract increasing dengue outbreaks.

ABSTRACTThe Anopheles symbiont, Microsporidia MB, is maternally inherited and has a strong malaria transmission-blocking phenotype in Anopheles arabiensis. Microsporidia MB is also vertically transmitted, sexually transmitted, and avirulent. These characteristics are expected to promote its spread through mosquito populations, enhancing the potential of Microsporidia MB as a candidate for the development of a symbiont-mediated malaria transmission-blocking strategy. We found that the patterns of Microsporidia MB localization over the development of An. arabiensis indicate accumulation in tissues linked to its transmission, specifically the male and female gonadal tissues. Transovarial vertical transmission of Microsporidia MB occurs in the female An. arabiensis ovary when Microsporidia MB becomes localized to the cytoplasm of the developing oocyte. In male An. arabiensis, Microsporidia MB is localized in the testis and vas deferens. Notably, a high intensity of Microsporidia MB can also be observed in the An. arabiensis adult but not larval gut. The levels of Microsporidia MB found in the female ovary are linked to the progression of oogenesis, increasing after blood feeding initiates the development of eggs. There was a significant change in Microsporidia MB levels in female and male An. arabiensis gonads, where intensity tended to decrease as mosquitoes aged. However, the intensities did not significantly change in the male or female guts. Altogether, the high specificity of Microsporidia MB tissue localization patterns and changes in infection prevalence and intensity suggest adaptation to maximize transmission and avirulence in Anopheles arabiensis.IMPORTANCEMicrosporidia MB is a symbiont with a strong malaria transmission-blocking phenotype in Anopheles arabiensis. It spreads in mosquito populations through mother-to-offspring and sexual transmission. The ability of Microsporidia MB to block Plasmodium transmission, together with its ability to spread within Anopheles populations and its avirulence to the host, makes it a very attractive candidate for developing a key strategy to stop malaria transmissions. Here, we report tissue tropism and localization patterns of Microsporidia MB, which are relevant to its transmission. We find that Microsporidia MB accumulates in Anopheles arabiensis tissues, linked to its sexual and vertical transmission. Its prevalence and intensity in the tissues over the mosquito life cycle suggest adaptation to maximize transmission and avirulence in Anopheles arabiensis. These findings provide the foundation for understanding the factors that may affect Microsporidia MB transmission efficiency. This will contribute to the development of strategies to maximize Microsporidia MB transmission to establish and sustain a high prevalence of the symbiont in Anopheles mosquito populations for malaria transmission blocking.

Background The response rate to immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) receptor is 13%–18% for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Detailed understanding of the tumor immune microenvironment (TIME) is crucial in order to explain and improve this response rate. HNSCCs arise at various anatomical locations including the oral cavity, hypopharynx, larynx and oropharynx. Studies directly comparing immune infiltration between anatomical sites are scarce. Since the distinct locations could drive deviating microenvironments, we questioned whether the immune composition varies across these HNSCC sites.Methods Here, we characterized the TIME of 76 fresh tumor specimens using flow cytometry and performed single-cell RNA-sequencing on nine head and neck tumor samples.Results We found major differences in the composition of the TIME between patients. When comparing anatomical sites: tumors originating from the oral cavity had higher T cell infiltrates than tumors from other anatomical sites. The percentage of tumor-infiltrating T-lymphocytes positive for the immune checkpoint PD-1 varied considerably between patients, with the highest fraction of PD-1+ T cells found in larynx squamous cell carcinomas (SCCs). While we had hypothesized that the anatomical sites of tumor origin would drive sample clustering, our data showed that the type of TIME was more dominant and was particularly driven by the fraction of T cells positive for PD-1. Moreover, a high proportion of PD-1+ CD8+ T cells associated with an improved overall survival. Using single-cell RNA-sequencing, we observed that PD-1 expression was highest in the CD8-ENTPD1 tissue resident memory T cell/exhausted T cell and CD4-CXCL13 type 1 T helper cell clusters.Conclusions We found that oral cavity SCCs had the highest frequencies of T cells. We also observed considerable interpatient heterogeneity for PD-1 on T cells, with noticeably higher frequencies of PD-1+ CD4+ T helper cells in larynx SCCs. Within the entire cohort, a higher fraction of CD8+ T cells positive for PD-1 was linked to improved overall survival. Whether the fraction of PD-1+ T cells within the TIME enables immune checkpoint inhibitor response prediction for patients with head and neck cancer remains to be determined.

Background A high prevalence of onchocerciasis-associated epilepsy (OAE) has been observed in onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission. However, the pathogenesis of OAE remains to be elucidated. We hypothesise that the O. volvulus virome could be involved in inducing epilepsy. With this study, we aim to describe the O. volvulus virome and identify potential neurotropic viruses linked to OAE. Methods In Maridi County, an onchocerciasis endemic area in South Sudan with a high prevalence of OAE, we will conduct an exploratory case-control study enrolling 40 persons aged 12 years and above with palpable onchocerciasis nodules. Cases will be participants with OAE (n=20), who will be age- and village-matched with controls without epilepsy (n=20). For each study participant, two skin snips at the iliac crest will be obtained to collect O. volvulus microfilariae, and one nodulectomy will be performed to obtain adult worms. A viral metagenomic study will be conducted on microfilariae and adult worms, and the O. volvulus virome of persons with and without OAE will be compared. The number, size, and localisation of onchocerciasis nodules in persons with and without OAE will be described. Moreover, the pre- and post-nodulectomy frequency of seizures in persons with OAE will be compared. Ethics and dissemination The protocol has been approved by the Ethics Committee of the University of Antwerp and the Ministry of Health of South Sudan. Findings will be disseminated nationally and internationally via meetings and peer-reviewed publications. Registration ClinicalTrials.gov registration NCT05868551 (https://clinicaltrials.gov/study/NCT05868551). Protocol version 1.1, dated 09/05/2023.

Background: Emergency laparotomy (EL) is associated with high mortality rates and is performed on a heterogenous patient population. Pre-operative risk assessment is one tool which can assist with EL patient care. We aimed to characterise rates of pre-operative risk assessment for EL patients in South Australia. Methods: A retrospective audit of all patients undergoing EL over one year in six participating hospitals in South Australia was undertaken. Patient demographics, operation details, risk assessments (e.g. NELA, POSSUM, ACS-NSQIP) and outcomes were recorded. Results: 422 ELs were audited. Preoperative risk assessments were recorded for 42 (10 %) operations. The 30-day mortality rate was 9 %. There was no difference in mortality rates for patients with or without a risk assessment documented. Hospital participation in the Australia and New Zealand Emergency Laparotomy Audit (ANZELA) was associated with increased rates of risk assessment. Increasing patient age and then presence of certain comorbidities were also associated with increased rates of risk assessment. Conclusions: This audit shows poor uptake of recommendations for preoperative risk assessment in EL patients in South Australia. Comparable mortality rates to previously published Australian and international data are demonstrated. Factors associated with increased risk assessment rates are identified and are relevant to future quality improvement activities.

Purpose: To identify the quantity and types of spin present in systematic reviews and meta-analyses of ulnar collateral ligament reconstruction (UCLR) outcomes and to characterize the studies with spin to determine if any patterns exist. Methods: This study was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In August 2022, PubMed, Scopus, and SportDiscus databases were searched using the terms “ulnar collateral ligament reconstruction” AND “systematic review” OR “meta-analysis.” Each abstract was assessed for the presence of the 15 most common types of spin derived from a previously established methodology. General data that were extracted included study title, authors, publication year, journal, level of evidence, study design, funding source, reported adherence to PRISMA guidelines, preregistration of the study protocol, and methodologic quality per A Measurement Tool to Assess Systematic Reviews Version 2 (AMSTAR 2). Results: In total, 122 studies were identified during the preliminary search, of which 19 met the inclusion criteria. Each study had at least 1 form of spin. The most common type of spin identified was type 5 (“The conclusion claims the beneficial effect of the experimental treatment despite a high risk of bias in primary studies”) (7/19, 36.8%). AMSTAR type 9 (“Did the review authors use a satisfactory technique for assessing the RoB [risk of bias] in individual studies that were included in the review?”) was associated with both a lower Clarivate Impact Factor (P = .001) and a lower Scopus CiteScore (P = .015). Studies receiving external funding were associated with the failure to satisfy AMSTAR type 3 (“Did the review authors explain their selection of the study designs for inclusion in the review?”) (P = .047). Conclusions: Spin is highly prevalent in the abstracts of systematic reviews and meta-analyses that investigate the outcomes of UCLR. Clinical Relevance: Spin has been identified in peer-reviewed articles published on various topics, including many in orthopaedics. Systematic reviews and meta-analyses contain the most comprehensive evidence regarding a clinical question, so it is important to identify spin that may be included in these reports. Greater efforts are needed to ensure that the abstracts of papers accurately represent the results in the full text.

HIV-associated cryptococcal meningitis remains a key driver of AIDS-related mortality. Mortality is twice as high in those who present later to care and with severe symptoms such as confusion. We embedded a qualitative methods study within a randomised controlled trial in Gaborone, Botswana and Kampala, Uganda with the aim of understanding pathways to care. We conducted in-depth interviews with trial participants and surrogate decision makers and analysed data thematically. Between January 2020 and June 2021 we interviewed 58 individuals. Pathways to care were prolonged because headaches were disregarded by participants and healthcare workers as a common occurrence with a broad differential diagnosis of predominantly benign aetiologies. There was also a lack of awareness of cryptococcal meningitis, and it was often after HIV was diagnosed or disclosed that the pathway accelerated, resulting in hospital admission. We outline key recommendations to reduce mortality and argue for the integration of social and behavioural interventions within differentiated service delivery models for advanced HIV disease.

Abstract Background Depression is the leading cause of global disability and can develop following the change in body image and functional capacity associated with stoma surgery. However, reported prevalence across the literature is unknown. Accordingly, we performed a systematic review and meta-analysis aiming to characterise depressive symptoms after stoma surgery and potential predictive factors. Methods PubMed/MEDLINE, Embase, CINAHL and Cochrane Library were searched from respective database inception to 6 March 2023 for studies reporting rates of depressive symptoms after stoma surgery. Risk of bias was assessed using the Downs and Black checklist for non-randomised studies of interventions (NRSIs), and Cochrane RoB2 tool for randomised controlled trials (RCTs). Meta-analysis incorporated meta-regressions and a random-effects model. Registration: PROSPERO, CRD42021262345. Results From 5,742 records, 68 studies were included. According to Downs and Black checklist, the 65 NRSIs were of low to moderate methodological quality. According to Cochrane RoB2, the three RCTs ranged from low risk of bias to some concerns of bias. Thirty-eight studies reported rates of depressive symptoms after stoma surgery as a proportion of the respective study populations, and from these, the median rate across all timepoints was 42.9% 42.9% (IQR: 24.2–58.9%). Pooled scores for respective validated depression measures (Hospital Anxiety and Depression Score (HADS), Beck Depression Inventory (BDI), and Patient Health Questionnaire-9 (PHQ-9)) across studies reporting those scores were below clinical thresholds for major depressive disorder according to severity criteria of the respective scores. In the three studies that used the HADS to compare non-stoma versus stoma surgical populations, depressive symptoms were 58% less frequent in non-stoma populations. Region (Asia–Pacific; Europe; Middle East/Africa; North America) was significantly associated with postoperative depressive symptoms (p = 0.002), whereas age (p = 0.592) and sex (p = 0.069) were not. Conclusions Depressive symptoms occur in almost half of stoma surgery patients, which is higher than the general population, and many inflammatory bowel disease and colorectal cancer populations outlined in the literature. However, validated measures suggest this is mostly at a level of clinical severity below major depressive disorder. Stoma patient outcomes and postoperative psychosocial adjustment may be enhanced by increased psychological evaluation and care in the perioperative period.

Abstract Data on long-term outcomes and biological drivers associated with depth of remission after BCL2 inhibition by venetoclax in the treatment of chronic lymphocytic leukemia (CLL) are limited. In this open-label parallel-group phase-3 study, 432 patients with previously untreated CLL were randomized (1:1) to receive either 1-year venetoclax-obinutuzumab (Ven-Obi, 216 patients) or chlorambucil-Obi (Clb-Obi, 216 patients) therapy (NCT02242942). The primary endpoint was investigator-assessed progression-free survival (PFS); secondary endpoints included minimal residual disease (MRD) and overall survival. RNA sequencing of CD19-enriched blood was conducted for exploratory post-hoc analyses. After a median follow-up of 65.4 months, PFS is significantly superior for Ven-Obi compared to Clb-Obi (Hazard ratio [HR] 0.35 [95% CI 0.26–0.46], p

Abstract Background The incidence of cryptococcosis amongst HIV-negative persons is increasing. Whilst the excellent performance of the CrAg testing in people living with HIV is well described, the diagnostic performance of the CrAg LFA has not been systematically evaluated in HIV-negative cohorts on serum or cerebrospinal fluid. Methods We performed a systematic review to characterise the diagnostic performance of IMMY CrAg® LFA in HIV-negative populations on serum and cerebrospinal fluid. A systematic electronic search was performed using Medline, Embase, Global Health, CENTRAL, WoS Science Citation Index, SCOPUS, Africa-Wide Information, LILACS and WHO Global Health Library. Studies were screened and data extracted from eligible studies by two independent reviewers. A fixed effect meta-analysis was used to estimate the diagnostic sensitivity and specificity. Results Of 447 records assessed for eligibility, nine studies met our inclusion criteria, including 528 participants overall. Amongst eight studies that evaluated the diagnostic performance of the IMMY CrAg® LFA on serum, the pooled median sensitivity was 96% (95% Credible Interval (CrI) 68–100%) with a pooled specificity estimate of 96% (95%CrI 84–100%). Amongst six studies which evaluated the diagnostic performance of IMMY CrAg® LFA on CSF, the pooled median sensitivity was 99% (95%CrI 95–100%) with a pooled specificity median of 99% (95%CrI 95–100%). Conclusions This review demonstrates a high pooled sensitivity and specificity for the IMMY CrAg® LFA in HIV-negative populations, in keeping with findings in HIV-positive individuals. The review was limited by the small number of studies. Further studies using IMMY CrAg® LFA in HIV-negative populations would help to better determine the diagnostic value of this test.

Abstract Inference and analysis of gene regulatory networks (GRNs) require software that integrates multi-omic data from various sources. The Network Zoo (netZoo; netzoo.github.io) is a collection of open-source methods to infer GRNs, conduct differential network analyses, estimate community structure, and explore the transitions between biological states. The netZoo builds on our ongoing development of network methods, harmonizing the implementations in various computing languages and between methods to allow better integration of these tools into analytical pipelines. We demonstrate the utility using multi-omic data from the Cancer Cell Line Encyclopedia. We will continue to expand the netZoo to incorporate additional methods.

Auxetics are materials, metamaterials or structures which expand laterally in at least one cross-sectional plane when uniaxially stretched, that is, have a negative Poisson’s ratio. Over these last decades, these systems have been studied through various methods, including simulations through finite elements analysis (FEA). This simulation tool is playing an increasingly significant role in the study of materials and structures as a result of the availability of more advanced and user-friendly commercially available software and higher computational power at more reachable costs. This review shows how, in the last three decades, FEA proved to be an essential key tool for studying auxetics, their properties, potential uses and applications. It focuses on the use of FEA in recent years for the design and optimisation of auxetic systems, for the simulation of how they behave when subjected to uniaxial stretching or compression, typically with a focus on identifying the deformation mechanism which leads to auxetic behaviour, and/or, for the simulation of their characteristics and behaviour under different circumstances such as impacts.

BackgroundYaws is a disease caused by the bacteria Treponema pallidum subspecies pertenue, which is most commonly seen among children below 15 years. In the twentieth century yaws was endemic in Nigeria but eradication strategies markedly reduced the disease burden. Currently there is minimal data on the ongoing transmission of yaws in Nigeria, despite reports of confirmed yaws cases in neighbouring West African countries.MethodsWe conducted both community and school-based active yaws case search among school-aged children in southeast Nigeria. Children were screened by trained community volunteers. Suspected yaws cases were clinically reviewed and tested using rapid diagnostic serological tests.ResultsBetween February and May 2021, up to 28 trained community volunteers screened a total of 105,015 school children for yaws. Overall, 7,706 children with various skin lesions were identified. Eight (8) suspected cases of yaws were reported, reviewed and screened, but none was confirmed using rapid diagnostic tests. The four most common skin conditions identified were scabies (39%), papular urticaria (29%), tinea corporis (14%) and tinea capitis (12%).ConclusionsNo case of yaws was confirmed in this large population of children in south-east Nigeria. Continuous community awareness and yaws case finding activities have been recommended across Nigeria.

IntroductionStress is one of the highest-ranked work-related injuries worldwide and has become almost universal among the Nigerian workforce. English as a Second Language (ESL) teachers face enormous work-related threats that lead to occupational stress. When ESL teachers are stressed, students' language development and entire educational progress are at risk. This is mostly underscored as English, though a second language, serves as the language of instruction in Nigerian schools. As a result, managing occupational stress is particularly important for ESL teachers, as it is among the definitive ways of improving ESL learning and overall educational outcomes. This study examined the effectiveness of online cognitive behavioral intervention (o-CBI) in lowering occupational stress among ESL teachers.MethodESL teachers with at least 1 year of experience were among the participants (N = 89). Participants were divided into two groups: the intervention group (N = 44) and the control group (N = 45). For 9 weeks, the experimental group engaged in nine sessions of 2 h of the o-CBI program. The Single Item Stress Questionnaire (SISQ), the Satisfaction with Therapy and Therapist Scale-Revised (STTS–R), and the Teachers' Stress Inventory (TSI) were the measures used to collect primary and secondary data. Four sets of data were collected at baseline, post-test, and follow-up 1 and 2 evaluations. The data were analyzed using mean, standard deviation, t-test statistics, repeated measures ANOVA, and bar charts.Results and discussionCompared to the control group, the o-CBT group had significantly lower TSI scores at the post-test (Time 2) and follow-up evaluations (Times 3 and 4). Between pre-, post-, and follow-up 1 and 2 measurements, there were no significant differences in occupational stress index scores in the control group. It was concluded that o-CBI is effective in job-stress treatment among ESL teachers. In addition, implications for school health policy are discussed. The o-CBI for occupational stress was well received by the participants, showing high acceptability among ESL teachers.

Abstract Introduction This study examined plasma glial fibrillary acidic protein (GFAP) as a biomarker of cognitive impairment due to Alzheimer's disease (AD) with and against plasma neurofilament light chain (NfL), and phosphorylated tau (p‐tau)181+231. Methods Plasma samples were analyzed using Simoa platform for 567 participants spanning the AD continuum. Cognitive diagnosis, neuropsychological testing, and dementia severity were examined for cross‐sectional and longitudinal outcomes. Results Plasma GFAP discriminated AD dementia from normal cognition (adjusted mean difference = 0.90 standard deviation [SD]) and mild cognitive impairment (adjusted mean difference = 0.72 SD), and demonstrated superior discrimination compared to alternative plasma biomarkers. Higher GFAP was associated with worse dementia severity and worse performance on 11 of 12 neuropsychological tests. Longitudinally, GFAP predicted decline in memory, but did not predict conversion to mild cognitive impairment or dementia. Discussion Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel to detect in vivo AD.

Abstract Background Research into life-threatening illnesses which require emergency hospitalisation is essential. This group of patients is unique in that they are experiencing an unfolding emergency when they are approached, enrolled, and followed up in a research study. We aimed to synthesise qualitative data from trial participants and surrogate decision-makers to deepen our understanding and inform the design and conduct of future clinical trials for life-threatening illnesses. Methods We conducted a critical interpretive synthesis of qualitative data from trial participants and surrogate decision-makers related to the experience of participating in a clinical research study when suffering from a life-threatening illness. A scoping review informed a systematic review of published data. We searched research databases and reviewed papers for inclusion. Primary data and interpretations of data were extracted from each paper. Data were analysed using reciprocal translational analysis, refutational synthesis, and lines of argument synthesis to develop a synthetic construct. Results Twenty-two papers were included. Most individuals had no previous knowledge or experience with clinical research. Individuals making decisions were directly experiencing or witness to an unfolding emergency which came with a myriad of physical and psychological symptoms. It was difficult to differentiate clinical research and routine care, and understanding of core concepts around research, particularly randomisation and equipoise, was limited. We found that this led to an underestimation of risk, an overestimation of benefit, and an expectation of being allocated to the intervention arm. The decision-making process was heavily influenced by trust in the research team. Individuals suggested that abbreviated information, presented in different ways and continuously throughout the research process, would have increased knowledge and satisfaction with the research process. Conclusion Individuals suffering from a life-threatening illness who are being invited to participate in clinical research need to be managed in a way that adapts to the severity of their illness and there is a need to tailor research processes, including informed consent, accordingly. We provide suggestions for further research and implementation work around research participation for individuals suffering from a life-threatening illness. Trial registration PROSPERO CRD42020207296

Brachial plexus tumors are rare and pose challenges for neurosurgeons due to their anatomical complexity. Retrosternal extension of a tumor makes it more difficult for the surgeons as well as for the anesthesiologists to secure a definitive airway. A cardiopulmonary bypass would be lifesaving in the event of acute cardiorespiratory decompensation. Multidisciplinary collaboration and cooperation between the neurosurgeon, oncosurgeon, cardiothoracic surgeon, and anesthesiologist are imperative to ensure good patient outcomes. Meticulous preoperative evaluation and operative planning are essentially the key factors in anesthetic management. Here we report a successful management of a 49-year-old male patient presented with a large painless mass arising from his right supraclavicular region and compressing the roots of the brachial plexus, trachea, and esophagus and extending up to the apex of the lungs, posted for mini sternotomy and excision of the mass.

Background and Aims: Emergence agitation is a significant clinical issue during recovery from general anesthesia. Patients after intracranial operations are even more vulnerable to the stress resulting from emergence agitation. Due to the limited data available in neurosurgical patients, we evaluated the incidence, risk factors, and complications of emergence agitation. Material and Methods: 317 consenting eligible patients undergoing elective craniotomies were recruited. The preoperative Glasgow Coma Scale (GCS)) and pain score were recorded. Bispectral Index (BIS) guided balanced general anesthesia was administered and reversed. Immediate postoperatively, the GCS and the pain score were noted. The patients were observed for 24 hours following extubation. The levels of agitation and sedation were evaluated by the Riker's Agitation-Sedation Scale. Emergence Agitation was defined as Riker's Agitation score of 5 to 7. Results: In our subset of the patient population, the incidence was 5.4%, mildly agitated in the first 24 hours and none required sedative medication as therapy. The sole risk factor identified was prolonged surgery beyond 4 hours. None of the patients in the agitated group had any complications. Conclusion: Early objective assessment of risk factors in the preoperative period with objective validated tests and shorter duration of surgery maybe the way forward in patients at high risk for emergence agitation, to reduce the incidence and mitigate the undesirable consequences.

Abstract Background Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players. Methods One hundred seventy male former football players (n=111 professional, n=59 college; 45–74 years) completed a neuropsychological test battery. Raw scores were converted to T-scores using age, sex, and education-adjusted normative data. A T-score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests. Results Most football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%]) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent. Conclusions In this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain.

Liposomes are widely used in pharmaceuticals yet trade-offs between uniform size and mass production, limit production and application. Here, the authors report on the design of a microfluidic vortex focusing microfluidic technique which can mass produce liposomes with controlled size and low variability.