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Incidence and determinants of extrapulmonary tuberculosis in Egypt: a retrospective cohort study
Abstract Tuberculosis (TB) is a significant global public health concern. The incidence of extrapulmonary tuberculosis (EPTB) is increasing; however, comprehensive data on its epidemiological and clinical characteristics remain limited, especially among populations who are co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). This study aimed to assess the incidence and predictors of EPTB in patients co-infected with HIV or HCV in Egypt. We conducted a retrospective cohort study on patients infected with TB who are treated in Egyptian chest hospitals from January 1 to December 31, 2023. Patients were categorized into pulmonary TB (PTB) and EPTB. Clinical data, including HIV or HCV co-infection status, were analyzed to identify risk factors and comorbidities associated with EPTB. Multilevel logistic regression was employed to examine predictors of EPTB. Among 7,245 TB patients, 42.5% were diagnosed with EPTB. Determinant of EPTB were HIV-positive (OR = 0.46, 95% CI: 0.30–0.71, p < 0.001), being male (OR = 0.31, 95% CI: 0.27–0.35, p < 0.001 ), age (particularly children under 5 years) (OR = 4.75, 95% CI: 2.29–9.84, p < 0.001 ), urban residency (OR = 1.05, 95% CI: 0.87–1.27, p < 0.05), and comorbidities (OR = 0.59, 95% CI: 0.35–0.98, p < 0.05). The most common sites for EPTB were the lymph nodes (27.10%) and pleural cavity/effusion (24.60%). EPTB represents a substantial proportion of TB cases in Egypt, particularly among younger individuals and females. Despite the low percentage of HIV or HCV co-infection in EPTB cases, further analysis and diagnostic testing of undiagnosed patients are required. These findings underscore the need for targeted interventions and comprehensive care models for TB patients, especially in the context of HIV co-infection.
Sickness absence among blue-collar workers in the retail and wholesale industry during the COVID-19 pandemic; a longitudinal cohort study
Abstract Sickness absence (SA) changed in various occupations during the COVID-19 pandemic. The aim was to investigate the prevalence of all-cause sickness absence (SA) during the COVID-19 pandemic in relation to in the preceding years, as well as factors associated with all-cause SA and SA due to COVID-19 and COVID-like diagnoses during the COVID-19 pandemic among blue-collar workers in the retail and wholesale industry. A population-based longitudinal cohort study using microdata linked from nationwide registers in Sweden. All 297 378 blue-collar employees aged 18–67 years in wholesale and retail in 2019 were followed during 2016–2021 regarding SA in spells > 14 days. Yearly prevalence rates were calculated for all-cause SA in sociodemographic and occupational groups. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for all-cause SA and SA due to COVID-19 or COVID-like diagnoses in 2020 and 2021. The annual prevalences of SA were 7.5-8% in 2016–2018, 10% in 2020, and 9% in 2021. The prevalence of SA due to COVID-19 or COVID-like diagnoses was 2.1% in 2020 and 1.6% in 2021. The OR was higher in the older age groups (OR age 55–64 = 2.38, 95% CI 2.20–2.57 compared to age 25–34). There were few significant occupational differences, however, warehouse and terminal staff had a higher OR (1.37, 1.27–1.48) than sales assistants, daily goods. While SA rates increased during the COVID-19 pandemic, the distribution of SA between sociodemographic or occupational groups did not change markedly. The distribution of SA due to COVID-19 and COVID-like diagnoses was similar to all-cause SA.
Diversity and pathogenicity of pestalotioid fungi infecting Camellia oleifera in China
Simultaneously capturing excessive variations and smooth dynamics of the underlying neural activity using spatiotemporal basis expansion and multisubject fMRI data
Integrated multi-omics analysis and experimental verification reveal the involvement of the PI3K/Akt signaling pathway in myometrial fibrosis of adenomyosis
Targeting CD38 immunometabolic checkpoint improves metabolic fitness and cognition in a mouse model of Alzheimer’s disease
The nucleoid of rapidly growing Escherichia coli localizes close to the inner membrane and is organized by transcription, translation, and cell geometry
Abstract Bacterial chromosomes are spatiotemporally organized and sensitive to environmental changes. However, the mechanisms underlying chromosome configuration and reorganization are not fully understood. Here, we use single-molecule localization microscopy and live-cell imaging to show that the Escherichia coli nucleoid adopts a condensed, membrane-proximal configuration during rapid growth. Drug treatment induces a rapid collapse of the nucleoid from an apparently membrane-bound state within 10 min of halting transcription and translation. This hints toward an active role of transertion (coupled transcription, translation, and membrane insertion) in nucleoid organization, while cell wall synthesis inhibitors only affect nucleoid organization during morphological changes. Further, we provide evidence that the nucleoid spatially correlates with elongasomes in unperturbed cells, suggesting that large membrane-bound complexes might be hotspots for transertion. The observed correlation diminishes in cells with changed cell geometry or upon inhibition of protein biosynthesis. Replication inhibition experiments, as well as multi-drug treatments highlight the role of entropic effects and transcription in nucleoid condensation and positioning. Thus, our results indicate that transcription and translation, possibly in the context of transertion, act as a principal organizer of the bacterial nucleoid, and show that an altered metabolic state and antibiotic treatment lead to major changes in the spatial organization of the nucleoid.
Auto-sumoylation of the yeast Ubc9 E2 SUMO-conjugating enzyme extends cellular lifespan
Effect of girls’ education on cancer awareness and screening in a natural experiment in Lesotho
Abstract Breast and cervical cancers are important causes of disability and premature death among women in Sub-Saharan Africa. Previous research has linked girls’ education to cancer service access. Here, we examine the causal effect of girls’ educational attainment on cancer screening practices by means of a natural experiment in Lesotho. In particular, we exploit variation in educational attainment among women that was introduced by an educational policy (a school-entry age cut-off). Data on awareness towards breast cancer, knowledge of Pap smear, breast self-exam, breast clinical exam, and having received a Pap smear is extracted from the Lesotho Demographic and Health Surveys 2009-10 and 2014 (N = 7971). Each additional year of schooling caused by the education policy increases awareness of breast cancer by 4.7 percentage points (p = 0.014, 95% Confidence Interval [CI]: 1.0, 8.5), awareness of Pap smear by 5.9 percentage points (p = 0.001, 95% CI: 2.3, 9.5), and engagement in Pap smear by 3.5 percentage points (p = 0.004, 95% CI: 1.1, 5.8). We found no statistically significant effects on breast self-exam and breast clinical exam.
A dynamically phase-adaptive regulating hydrogel promotes ultrafast anti-fibrotic wound healing
A framework reforming personalized Internet of Things by federated meta-learning
PI3K-Akt signalling regulates Scx-lineage tenocytes and Tppp3-lineage paratenon sheath cells in neonatal tendon regeneration
Introspective access to value-based multi-attribute choice processes
Abstract People routinely choose between options varying on multiple attributes – homes to rent, movies to watch, and so on. Here, we test how much awareness people have of the mental processes underlying these choices. We develop a method to quantify awareness of value-based multi-attribute choice processes that accounts for diverse choice strategies. Across five studies, participants make choices and then report how they believe they made them. We use computational modeling to identify the process revealed in their choices, and compare it to their self-reports to quantify individuals’ accuracy about their choice process. While we observe substantial variation in accuracy, participants are often highly accurate about their choice process – more accurate than predicted by a sample of decision scientists – and more accurate than informed third-party observers, suggesting evidence for introspection. These results challenge notions that we are strangers to ourselves and instead suggest that people often know how they made value-based choices.
Structural characterization of antibody-responses following Zolgensma treatment for AAV capsid engineering to expand patient cohorts
Abstract Monoclonal antibodies are useful tools to dissect the neutralizing antibody response against the adeno-associated virus (AAV) capsids that are used as gene therapy delivery vectors. The presence of pre-existing neutralizing antibodies in large portions of the human population poses a significant challenge for AAV-mediated gene therapy, primarily targeting the capsid leading to vector inactivation and loss of treatment efficacy. This study structurally characterizes the interactions of 21 human-derived neutralizing antibodies from three patients treated with the AAV9 vector, Zolgensma®, utilizing high-resolution cryo-electron microscopy. The antibodies bound to the 2-fold depression or the 3-fold protrusions do not conform to the icosahedral symmetry of the capsid, thus requiring localized reconstructions. These complex structures provide unprecedented details of the mAbs binding interfaces, with many antibodies inducing structural perturbations of the capsid upon binding. Key surface capsid amino acid residues were identified facilitating the design of capsid variants with antibody escape phenotypes. These AAV9 capsid variants have the potential to expand the patient cohort to include those that were previously excluded due to their pre-existing neutralizing antibodies against the wtAAV9 capsid, and the possibly of further treatment to those requiring redosing.
A hollow TFG condensate spatially compartmentalizes the early secretory pathway
Abstract In the early secretory pathway, endoplasmic reticulum (ER) and Golgi membranes form a nearly spherical interface. In this ribosome-excluding zone, bidirectional transport of cargo coincides with a spatial segregation of anterograde and retrograde carriers by an unknown mechanism. We show that at physiological conditions, the Trk-fused gene (TFG) self-organizes to form a hollow, anisotropic condensate that matches the dimensions of the ER–Golgi interface and is dynamically regulated across the cell cycle. Regularly spaced hydrophobic residues in TFG control the condensation mechanism and result in a porous condensate surface. We find that TFG condensates act as a molecular sieve capable of allowing access of anterograde coats (COPII) to the condensate interior while restricting retrograde coats (COPI). We propose that a hollow TFG condensate structures the ER–Golgi interface to create a diffusion-limited space for anterograde transport. We further propose that TFG condensates optimize membrane flux by insulating secretory carriers in their lumen from retrograde carriers outside TFG cages.
Postural analysis of children with muscle retraction after six-month exercise or heel cup interventions in a randomized trial
Abstract Balance and proprioception are crucial in children, especially in sports. The ankle joint plays a key role in postural control, and triceps surae retraction is common in active children. This study aimed to analyze the effects of stretching exercises versus heel cups on postural control in children aged 8 to 12 with triceps surae retraction. A six-month randomized controlled trial was conducted with 150 children assigned to either stretching exercises (n = 76) or heel cups (n = 74). The study was registered at ClinicalTrials.gov under the identification number NCT05902949 (first posted on 06/15/23). The area of oscillation was measured using the Gyko system under four conditions: eyes open/closed and firm ground/foam. A linear mixed regression model was applied to analyze the effects of the treatments, adjusting for sex, age, and physical activity. Stretching exercises were associated with significant reductions around oscillation across all conditions (p < 0.001 at six months). In contrast, heel cups were linked to significant increases around oscillation in all conditions (p < 0.001 at six months), indicating a negative effect on balance. Additionally, higher levels of physical activity and female sex were associated with better postural control (p < 0.001). In conclusion, stretching exercises significantly improved postural control in children with triceps surae retraction, whereas heel cups worsened this essential motor-performance ability. Further research is needed, but these findings support the incorporation of stretching exercises and regular physical activity in the management of these patients. Clinical trial registration number: NCT05902949.
Trends and projections of the global and regional burden of multiple myeloma in adults aged 40 and over, 1990–2044
Abstract The objective is to examine the data from the global burden of disease (GBD) 2021 to report on the global, regional, and national trends and rates related to the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) for multiple myeloma in adults aged 40 and above. Data from the GBD 2021 was used in this study to evaluate the rates of incidence, prevalence, mortality, and DALYs related to multiple myeloma across global, regional, and national scales. To analyze these trends, joinpoint regression was applied to calculate the average annual percentage changes (AAPC). Further, the analysis was divided according to age, gender, region, and socio-demographic index (SDI). Projections extending to 2044 were also generated using the Nordpred model. From 1990 to 2021, an upward trend has been observed globally in the incidence, prevalence, mortality, and DALYs of multiple myeloma among adults aged 40 and older, with average annual percentage changes (AAPCs) of 0.53 (95% CI 0.41–0.64), 1.2 (95% CI 1.07–1.33), 0.19 (95% CI 0.07–0.31), and 0.15 (95% CI 0.04–0.26), respectively. Notably, middle SDI countries exhibited the most accelerated disease progression, demonstrating a 2.34 (95% CI 2.19–2.48) annual increase in age-standardized incidence rate (ASIR)—over fourfold higher than the global average. The increasing global burden of multiple myeloma in adults aged 40 and older, especially in areas and nations with lower SDI levels, underscores the pressing requirement for customized public health initiatives and policies to tackle this escalating issue.