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Factorial structure of the patient health questionnaire-9, generalized anxiety disorder-7 and berger HIV stigma scale-short form among adolescents living with HIV in Ghana
Background Mental health issues and stigma experiences significantly affect adolescents living with HIV (ALHIV). While the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Berger HIV Stigma Scale-Short Form (HSS-SF) are widely used screening tools for mental health and stigma, their factorial validity among ALHIV in resource-limited settings such as Ghana remains understudied. This study investigated the factor structure, internal consistency, and correlations of the PHQ-9, GAD-7, and HSS-SF among ALHIV in Ghana. Methods A cross-sectional study was conducted among 105 ALHIV (aged 10−24 years) receiving care at three government hospitals in Eastern Ghana. Confirmatory factor analyses were conducted to examine the factor structure of the PHQ-9 and GAD-7 and HSS-SF. Results A two-factor structure showed the best fit for PHQ-9, with satisfactory internal consistency for cognitive/affective (α = 0.79) and somatic factors (α = 0.70). The GAD-7 demonstrated best fit as a unidimensional factor structure, with acceptable internal consistency (α = 0.88). The HSS-SF was found to be best represented by a three-factor structure, with internal consistency ranging from 0.76 to 0.95 across subscales. Conclusions The PHQ-9, GAD-7, and HSS-SF demonstrated acceptable factorial structure and internal consistency among Ghanaian ALHIV, supporting their utility as screening tools in this population.
‘Remarkable’ new enzymes built by algorithm with physics know-how
A genome-wide SNP-SNP interaction analysis exploring novel interacting loci associated with the risk of recurrence in colorectal cancer
Background Genetic factors can influence and predict patient outcomes. The association of interactions of germline SNPs with patient outcomes is an understudied area of prognostic research. In this study, we applied the first genome-wide SNP-SNP interaction analysis in relation to colorectal cancer outcomes. Objectives Our objective was to explore interacting SNP loci at the genome-wide level that predict the risk of local or distant recurrence (RMFS) in a cohort of stage I-III colorectal cancer patients from the Canadian province of Newfoundland and Labrador. Methods The patient cohort consisted of 430 unrelated Caucasian patients. Genetic and medical data was collected previously and the genetic data consisted of a total of 384,415 genotyped SNPs. The PLINK epistasis function was utilized to examine pairwise SNP interactions. Select interactions were assessed by multivariable Cox-regression models, adjusting for established clinical covariates. Genomic regions identified were explored for additional interactions. Published databases were utilized to retrieve biological information about the loci identified. Results After Bonferroni correction for multiple testing, no interaction remained significant. We present the top 20 interactions. The interaction p-values ranged from p = 1.37E-8 to p = 2.14E-9 in this set. Interactions were also tested by multivariable Cox regression models including established clinical covariates. Many of the SNPs were intronic and some of them were functional (e.g., expression quantitative expression loci). Analysis of the other SNPs in the same genomic regions as the interacting SNPs led to the identification of three additional interaction models. Conclusions We present the results of the first genome-wide SNP-SNP interaction analysis in colorectal cancer outcomes. While no SNP-SNP interaction remained significant after correction for multiple testing, our methodology emphasizes the additional knowledge that can be obtained using interaction analyses while studying prognostic markers.
Verification of emerging genomic mutations in Mycobacterium tuberculosis allows transmission chains to be distinguished in an epidemiological typing cluster extending over thirty years
Whole genome sequencing (WGS) is able to identify epidemiological links between Mycobacterium tuberculosis isolates. Recent clustering can be ruled out using a pre-defined single nucleotide polymorphism (SNP) threshold. If WGS clusters grow significantly over time limited genetic variability hampers epidemiological investigations. Newly emerging (informative) SNPs in isolates of an extended cluster growing for more than 30 years to >150 cases in the Netherlands were analysed. WGS data was analyzed from 61 sequencing files from 54 patients. Genomic positions that varied within the cluster isolates were carefully screened for minority populations in other isolates from the cluster. A transmission scheme was generated on the basis of WGS data alone then compared to the epidemiological information available. Fifty-two informative SNPs were identified, eight of which were also detected as mixed variants. One emerging SNP in dnaA (1199G > A R400H) has been observed in other transmitted strains and may be under selection. There was high concordance between the transmission chains suggested on basis of the newly emerging SNPs and scenarios identified using classical epidemiological cluster investigations. Analysis of filtered SNPs accumulating in the genome of M. tuberculosis in large clusters contains information on transmission dynamics and can be used to support epidemiological investigations.
Aging dimensions and markers as relative predictors of mortality in a longitudinal epidemiological sample
Measurement of aging is critical to understanding its causes and developing interventions, but little consensus exists on what components such measurements should include or how they perform in predicting mortality. The aim of this study was to identify factors of aging among a comprehensive set of indicators, and to evaluate their relative performance in predicting mortality. Measurements on 34 clinical, survey, and neuroimaging variables, along with epigenetic age markers, were obtained from two waves (2004–2021) of the Midlife in the United States (MIDUS) study. Mortality data was also available on 11875 participants, including 1908 twins. Factor analyses were used to identify aging factors, and these were used to predict mortality as of 2022. Twin data were used to model predictors of mortality within families. Factor analyses identified 9 major dimensions of aging: frailty, cognition, adiposity, glucose, blood pressure, inflammation, lipids, adaptive functioning, and neurological functioning. The strongest predictors of survival among the aging dimensions were cognition, adaptive functioning, and inflammation, and among the epigenetic markers, the decline-predictive markers (GrimAge and DunedinPACE). When entered in joint prediction models, cognition remained a significant predictor of mortality, but the epigenetic markers did not. Cognition, adaptive functioning, and inflammation remained significant predictors of mortality within twin pairs as well. Aging is a multidimensional construct, with cognition, adaptive functioning, and inflammation being the strongest predictors of survival among the aging dimensions examined. Their association with mortality is observed within families, suggesting that early developmental factors cannot entirely account for their association with survival. Interventions and assessments should prioritize cognition in measures of aging quality, along with adaptive functioning and inflammation.
Does geopolitical risks drive the extreme spillovers of bulk energy and chemical commodity
Geopolitical risks (GPR) can affect the prices of natural resources, which are crucial for survival and sustainable economies. Based on the TVP-VAR-BK models, this paper examines the asymmetric risk contagion between geopolitical risk, bulk energy, and chemical commodity from a time-frequency perspective. The results show that the risk contagion of geopolitical risks, bulk energy and chemical commodity markets has time-varying asymmetry and periodicity, and is susceptible to extreme events. Furthermore, the main driving factor is high-frequency spillover, which has “short-term fragility”, that is, the risk spillover in the short term is more significant than in the medium and long term, and network spillover is mainly caused by negative risk changes. In addition, the bulk energy market is the main risk transmitter, while the chemical commodity market is the main risk receiver. The risk contagion of crude oil on bitumen markets is the most significant. Finally, as a downstream market of the crude oil industry, the chemical commodity market not only directly accepts risk contagion from the crude oil market, but also transmits risks along the “bulk energy - geopolitical risk - chemical commodity” path. This evidence has important implications for governments and regulators in taking steps to prevent extreme spillover effects and a series of chain reactions from geopolitical risks.
For the future
Combinatorial discovery of microtopographical landscapes that resist biofilm formation through quorum sensing mediated autolubrication
Abstract Bio-instructive materials that intrinsically inhibit biofilm formation have significant anti-biofouling potential in industrial and healthcare settings. Since bacterial surface attachment is sensitive to surface topography, we experimentally surveyed 2176 combinatorially generated shapes embossed into polymers using an unbiased screen. This identified microtopographies that, in vitro, reduce colonization by pathogens associated with medical device-related infections by up to 15-fold compared to a flat polymer surface. Machine learning provided design rules, based on generalisable descriptors, for predicting biofilm-resistant microtopographies. On tracking single bacterial cells we observed that the motile behaviour of Pseudomonas aeruginosa is markedly different on anti-attachment microtopographies compared with pro-attachment or flat surfaces. Inactivation of Rhl-dependent quorum sensing in P. aeruginosa through deletion of rhlI or rhlR restored biofilm formation on the anti-attachment topographies due to the loss of rhamnolipid biosurfactant production. Exogenous provision of N-butanoyl-homoserine lactone to the rhlI mutant inhibited biofilm formation, as did genetic complementation of the rhlI, rhlR or rhlA mutants. These data are consistent with confinement-induced anti-adhesive rhamnolipid biosurfactant ‘autolubrication’. In a murine foreign body infection model, anti-attachment topographies are refractory to P. aeruginosa colonization. Our findings highlight the potential of simple topographical patterning of implanted medical devices for preventing biofilm associated infections.
Investigating the effect of butanol isomers on combustion and emissions in port injection dual fuel diesel engines: an experimental study
The present study examines the effects of substituting alternative fuels for diesel fuel and employing a dual fuel approach on diesel engine combustion characteristics and emissions. Various butanol isomers, namely ıso-butanol, n-butanol, tert-butanol, and sec-butanol, were chosen as novelty alternative fuels. In dual fuel combustion strategy, diesel fuel was injected directly into the cylinder, while butanol isomers as a secondary fuel were introduced into the cylinder at the beginning of the intake period using a port injection technique. The tests were repeated for 15%, 30%, and 45% premixing ratios (Rp) of butanol isomers. This study presents detailed combustion parameters and pollutant emission findings produced in diesel engines employing a dual fuel strategy with butanol isomers. In general, an increase within in cylinder pressure and heat release rate was observed. Especially at a premixing ratio of 45%, an increase of 50% within heat release rate was observed. Use of all butanol isomers increased the ignition delay and shortened combustion duration. Brake thermal efficiency remained at acceptable levels, and ringing intensity was below the knock limit. In addition to an increase in CO and HC emissions, NOX emissions were also up at other premixing ratios but declined at 15%. High levels of decreased smoke opacity were recorded. Especially at a premixing ratio of 45% iso-butanol, a decrease up to 90% is remarkable. In conclusion, the combustion characteristics and pollutant emission results obtained from the experimental engine are discussed in detail according to the operating parameters. The obtained findings provide important information about the performance and emission profiles of alternative fuels and dual fuel systems and provide guidance for future research.
Phenotypic plasticity co-varies with elevational range in two avian species of elevational migrants in the Himalayas
Association between the Body Roundness Index and osteoarthritis: A population-based study
Background Obesity is recognized as an independent risk factor for the development of osteoarthritis (OA). The Body Roundness Index (BRI) represents a novel metric for assessing obesity, yet its connection to OA remains unclear. This research aims to explore the potential association between BRI and OA. Methods We analyzed data from 20,564 participants who were part of the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. The association between BRI and the prevalence of OA was examined using multifactorial logistic regression and restricted cubic spline (RCS) analysis. To ensure the reliability of the findings, we conducted a stratified analysis. Results The average BRI among the participants was 5.18 (0.03), with an OA prevalence of 11.98%. Following adjustment for all covariates, continuous BRI exhibited a significant positive association with OA (OR: 1.19, 95% CI: 1.15–1.24, P < 0.0001). Participants in the top quartile of BRI showed a 153% higher prevalence of OA relative to individuals in the lowest quartile (OR: 2.53, 95% CI: 2.01–3.19, P < 0.0001). The RCS curve demonstrated a linear relationship between BRI and OA. Subgroup analysis examined that the observed relationship was significant exclusively among individuals with a BMI ≥ 30 kg/m². This association remained unaffected by variables such as race, age, gender, hypertension, cardiovascular disease (CVD), or diabetes. Conclusion An increased BRI is associated with a higher prevalence of OA, particularly in obese populations. BRI is expected to become a valuable indicator for identifying individuals at high risk of OA.
Divergence in a eukaryotic transcription factor’s co-TF dependence involves multiple intrinsically disordered regions
Abstract Combinatorial control by transcription factors (TFs) is central to eukaryotic gene regulation, yet its mechanism, evolution, and regulatory impact are not well understood. Here we use natural variation in the yeast phosphate starvation (PHO) response to examine the genetic basis and species variation in TF interdependence. In Saccharomyces cerevisiae , the main TF Pho4 relies on the co-TF Pho2 to regulate ~28 genes, whereas in the related pathogen Candida glabrata , Pho4 has reduced Pho2 dependence and regulates ~70 genes. We found C. glabrata Pho4 (CgPho4) binds the same motif with 3–4 fold higher affinity. Machine learning and yeast one-hybrid assay identify two intrinsically disordered regions (IDRs) in CgPho4 that boost its activation domain’s activity. In ScPho4, an IDR next to the DNA binding domain both allows for enhanced activity with Pho2 and inhibits activity without Pho2. This study reveals how IDR divergence drives TF interdependence evolution by influencing activation potential and autoinhibition.
Long-term anti-SARS-CoV-2 antibody trajectories after neutralizing monoclonal antibody treatment
Background Neutralizing monoclonal antibodies (nMAbs) have been used to treat COVID-19 and are increasingly being used to treat other infections. However, there is concern that by neutralizing the SARS-CoV-2 virus, nMAbs may decrease the availability of antigens to the immune system, potentially impairing the endogenous polyclonal immune response and decreasing long-term immune protection. Methods We compared 28 and 90-day anti-SARS-CoV-2 spike protein neutralization activity and anti-SARS-CoV-2 nucleocapsid response for patients hospitalized with COVID-19 infection randomized to receive nMAbs or placebo in the large platform ACTIV-3/TICO trials. We pooled results from four trials of anti-spike nMAbs. For most tested agents, measurements of the spike protein response reflect both the therapeutic and endogenous immune response. Anti-nucleocapsid levels reflect only the endogenous immune response. Data are summarized as mean differences in percent binding inhibition (anti-spike) and signal-to-cutoff (S/C) ratio (anti-nucleocapsid). Linear mixed effects models were fit to compare the longitudinal trajectory between treatment and placebo groups. Results Of 2,254 participants in the ACTIV-3/TICO trials modified intention-to-treat population, 2,149 (95.3%) had antibody measures at baseline and at least 1 follow-up day (day 1, 3, or 5) and were included in this analysis. Antibody measures were available for 1,556 (72.4%) participants at day 28 and 1,429 (66.5%) participants at day 90. In participants who received nMAbs, anti-spike neutralization activity was higher at day 28 (mean difference in percent binding inhibition: 7.1% [95%CI: 5.3, 8.9], p < 0.001) and day 90 (mean difference in percent binding inhibition: 7.2% [95% CI: 5.4, 9.0], p < 0.001). Anti-nucleocapsid response was similar at day 28 (mean difference in S/C ratio: 0.02 [95%CI: −0.11, 0.15], p = 0.75) and day 90 (mean difference in S/C ratio: 0.08 [95% CI: −0.05, 0.21], p = 0.22). Similar patterns were observed in all trials. Conclusions In patients hospitalized with COVID-19, treatment with nMAbs did not decrease long-term anti-nucleocapsid response compared to placebo, suggesting neutralizing therapies do not suppress the endogenous humoral immune response in this population.
Equity and reliability of public electric vehicle charging stations in the United States
Abstract Equitable coverage and reliable operation of electric vehicle charging stations (EVCSs) are crucial for a just transition to a carbon-free future. Yet, a comprehensive national analysis of public EVCSs across different communities is lacking in the United States. Here, we utilize real-world reviews (n = 470,142) from a user-generated content platform to analyze public EVCSs at the census tract level. We find that disadvantaged communities (DACs) have 64% fewer public EVCSs per capita than non-DACs. This disparity rises to 73% when considering renters in multi-dwelling units. Additionally, EVCS users in DACs and urban areas experience significantly more reliability issues compared to those in non-DACs and rural areas, primarily related to hardware and technical failures. Given the limited access to home charging in DACs and their underserved public infrastructure, these findings highlight critical equity concerns and call for targeted investment in EVCS infrastructure and reliability improvements, particularly in DACs.
Tracheostomy in COVID-19: A retrospective cohort study of outcomes and mortality predictors in a specialized infectious disease hospital in Brazil
Background The COVID-19 pandemic profoundly impacted critical care practices, leading to a significantly increase in tracheostomies for patients with respiratory failure. This study aimed to investigate prognostic factors associated with mortality in COVID-19 patients undergoing tracheostomy for respiratory failure in the intensive care unit of a specialized infectious disease hospital in Brazil. Research Question What is the impact of the timing of tracheostomy on the outcome of COVID-19 patients?. Materials and methods This retrospective cohort study analyzed 356 COVID-19 patients who underwent tracheostomy at the Evandro Chagas National Institute of Infectious Diseases (INI) in Brazil between May 2020 and December 2023. Data on demographics, comorbidities, illness severity, surgical factors, and outcomes were extracted from medical records. Multivariate logistic regression was performed to identify factors associated with hospital mortality. Results The overall hospital mortality rate was 68%. Independent factors associated with mortality included age over 60 years, chronic pulmonary disease, diabetes, lack of COVID-19 vaccination, hemodialysis on the day of surgery, and a PaO2/FiO2 ratio lower than 200 on the day of surgery. The timing of tracheostomy (after 21 days of mechanical ventilation) was not associated with mortality. Conclusions This study offers valuable insights into the complex factors influencing mortality in critically ill COVID-19 patients. Our findings underscore the importance of assessing both patient characteristics and illness at the time of tracheostomy to predict outcomes which is more critical than basing the decision solely on the duration of endotracheal intubation or mechanical ventilation.
Daily briefing: The most-energetic molecule ever made
Author Correction: Focal liver lesion diagnosis with deep learning and multistage CT imaging
Influence of openings on the snowdrift characteristics of cubes
Snow drifts and accumulates under wind actions, leading to a complex distribution of snow around and on the surface of structures with openings, which in turn has a detrimental influence on the structures. There is no relevant code provision for this situation. Therefore, a wind tunnel study was carried out to experimentally investigate how opening size and vertical location (for cubes with single openings) and how the relative positions of different openings (for cubes with multiple openings) influenced the wind-induced snowdrifts around and on the surface of cubes with openings. A roughness coefficient was introduced to characterize the snow around cubes. It was found that snow accumulation at the side of the cube produced a greater uneven snow load. The number and vertical location of openings were the main factors influencing the roughness of the snow. The snow depth coefficient (Cs) around and on the surface of a cube is approximately negatively correlated with opening size and approximately positively correlated with opening vertical location. The simultaneous existence of openings on the windward, side and top faces of a cube adversely affected the safety of the surroundings of the cube. The variation pattern of fractal characteristic of particles, D, was similar to that of Cs when the snow was fully eroded at the windward corner of the cube. These findings will help improve the accuracy of snow distribution pattern prediction and enhance the safety and rationality of the structural design of buildings.
Reversible proliferative arrest induced by rapid depletion of RNase MRP
Abstract Cellular quiescence is a state of reversible proliferative arrest that plays essential roles in development, resistance to stress, aging, and longevity of organisms. Here we report that rapid depletion of RNase MRP, a deeply conserved RNA-based enzyme required for rRNA biosynthesis, induces a long-term yet reversible proliferative arrest in human cells. Severely compromised biogenesis of rRNAs along with acute transcriptional reprogramming precede a gradual decline of the critical cellular functions. Unexpectedly, many arresting cells show increased levels of histone mRNAs, which accumulate locally in the cytoplasm, and S-phase DNA amount. The ensuing proliferative arrest is entered from multiple stages of the cell cycle and can last for several weeks with uncompromised cell viability. Strikingly, restoring expression of RNase MRP leads to a complete reversal of the arrested state with resumed cell proliferation at the speed of control cells. We suggest that targeting rRNA biogenesis may provide a general strategy for rapid induction of a reversible proliferative arrest, with implications for understanding and manipulating cellular quiescence.