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Long-term health consequences and costs of changes in alcohol consumption in England during the COVID-19 pandemic
Background and aims The COVID-19 pandemic led to changes in alcohol consumption in England. Evidence suggests that one-fifth to one-third of adults increased their alcohol consumption, while a similar proportion reported consuming less. Heavier drinkers increased their consumption the most and there was a 20% increase in alcohol-specific deaths in England in 2020 compared with 2019, a trend continuing through 2021 and 2022. This study aimed to quantify future health, healthcare, and economic impacts of changes in alcohol consumption observed during the COVID-19 pandemic. Methods This study used a validated microsimulation model of alcohol consumption and health outcomes. Inputted data were obtained from the Alcohol Toolkit Study, and demographic, health and cost data from published literature and publicly available datasets. Three scenarios were modelled: short, medium, and long-term, where 2020 drinking patterns continue until the end of 2022, 2024, and 2035, respectively. Disease incidence, mortality, and healthcare costs were modelled for nine alcohol-related health conditions. The model was run from 2020 to 2035 for the population of England and different occupational social grade groups. Results In all scenarios, the microsimulation projected significant increases in incident cases of disease, premature mortality, and healthcare costs, compared with the continuation of pre-COVID-19 trends. If COVID-19 drinking patterns continue to 2035, we projected 147,892 excess cases of diseases, 9,914 additional premature deaths, and £1.2 billion in excess healthcare costs in England. The projections show that the more disadvantaged (C2DE) occupational social grade groups will experience 36% more excess premature mortality than the least disadvantaged social group (ABC1) under the long-term scenario. Conclusions Alcohol harm is projected to worsen as an indirect result of the COVID-19 pandemic and inequalities are projected to widen. Early real-world data corroborate the findings of the modelling study. Increased rates of alcohol harm and healthcare costs are not inevitable but evidence-based policies and interventions are required to reverse the impacts of the pandemic on alcohol consumption in England.
The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions
Factors associated with knowledge and practice regarding oxygen administration: A cross-sectional study among registered nurses working in wards and ICUs at Muhimbili National Hospital in Dar es Salaam, Tanzania
Background Oxygen is a vital therapy approved by WHO, crucial for critically ill patients as a supplemental treatment. Nurses’ pivotal role in oxygen administration is poorly understood. This study aimed to assess factors associated with oxygen administration to critically ill patients among nurses at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania. Methods A descriptive cross-sectional study was conducted among 208 nurses using a simple random technique to recruit respondents. Data were collected in May 2022 via a self-administered questionnaire, designed and tested by the authors. Mean knowledge and practice scores were used to categorize knowledge and practice as high or low respectively. The Chi-square test and multiple logistic regression analyses were performed to evaluate factors associated with knowledge and practice regarding oxygen administration. Statistical significance was determined at a p-value less than 0.05. Results Of the 208 respondents, 96(46.2%) and 78(37.5%) had low knowledge and low practices regarding oxygen administration, respectively. Receiving in-service training on oxygen administration (AOR: 3.515; p<0.001) was positively associated with knowledge of oxygen administration. None of the factors showed a statistically significant association with the practice of oxygen administration. Conclusion A substantial proportion of nurses had inadequate knowledge and practices regarding oxygen administration. While none of the assessed factors were found to have a statistical association with practice on oxygen administration, it is important to note their clinical significance. Healthcare institutions can benefit from implementing regular in-service training programs to address these knowledge and skills gaps and ensure that nurses are well-prepared for proper oxygen administration. Additionally, ongoing monitoring and support are essential to help translate improved knowledge into effective clinical practices.
Joint speech and text machine translation for up to 100 languages
Tunning valence state of cobalt centers in Cu/Co-CoO1-x for significantly boosting water-gas shift reaction
Factors associated with quality of life of chronic spontaneous urticaria patients in a Vietnamese population
Objective Chronic spontaneous urticaria (CSU) is a challenging condition that significantly impacts the affected patients. This study aimed to evaluate the quality of life (QoL) among patients with CSU in Vietnam and identify factors associated with QoL. Methods A cross-sectional study was conducted at the Vietnam National Dermatology and Venereology Hospital from June 2023 to March 2024. A total of 358 CSU patients aged 16 years or older were recruited. Data were collected using a structured questionnaire covering demographic, clinical, and laboratory characteristics. The Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) and the Weekly Urticaria Activity Score (UAS7) were utilized to assess QoL and disease severity. Multivariate Tobit regression models were performed. Results The CU-Q2oL total score had a mean of 48.67 (SD = 16.90) and a median of 46 (IQR = 35–59). The scores for individual CU-QoL subscales were as follows: pruritus (5.42±2.02), swelling (2.86±1.54), life activities (13.89±6.00), sleep problems (11.12±4.96), limits (6.52±2.66), and looks (8.85±4.09). Higher UAS7 scores were associated with lower QoL, and angioedema in the eyes and lips were associated with increased swelling domain and poorer overall QoL. Longer disease duration was associated with higher pruritus scores, while a history of allergy was related to poorer total QoL, sleep, and looks. Severe itching further degraded sleep quality. Positive Autologous Serum Skin Test (ASST) was correlated with lower overall QoL, particularly in swelling and limits domains. Positive Basophil Histamine Release Assay (BHRA) status was linked to poorer sleep quality domain. Conclusion CSU significantly impairs the QoL of patients, affecting physical, emotional, and social dimensions. Regular QoL assessments should be integrated into clinical practice to ensure comprehensive and patient-centered treatment strategies.
Herpesviruses mimic zygotic genome activation to promote viral replication
Abstract Zygotic genome activation (ZGA) is crucial for maternal to zygotic transition at the 2-8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In humans, ZGA is induced by DUX4, a pioneer factor that drives expression of downstream germline-specific genes and retroelements. Here we show that herpesviruses from all subfamilies, papillomaviruses and Merkel cell polyomavirus actively induce DUX4 expression to promote viral transcription and replication. Analysis of single-cell sequencing data sets from patients shows that viral DUX4 activation is of relevance in vivo. Herpes-simplex virus 1 (HSV-1) immediate early proteins directly induce expression of DUX4 and its target genes, which mimics zygotic genome activation. Upon HSV-1 infection, DUX4 directly binds to the viral genome and promotes viral transcription. DUX4 is functionally required for infection, since genetic depletion by CRISPR/Cas9 as well as degradation of DUX4 by nanobody constructs abrogates HSV-1 replication. Our results show that DNA viruses including herpesviruses mimic an embryonic-like transcriptional program that prevents epigenetic silencing of the viral genome and facilitates herpesviral gene expression.
Cellular senescence-associated genes in rheumatoid arthritis: Identification and functional analysis
Rheumatoid arthritis (RA), a long-term autoinflammatory condition causing joint damage and deformities, involves a multifaceted pathogenesis with genetic, epigenetic, and immune factors, including early immune aging. However, its precise cause remains elusive. Cellular senescence, a hallmark of aging marked by a permanent halt in cell division due to damage and stress, is crucial in aging and related diseases. In our study, we analyzed RA microarray data from the Gene Expression Omnibus (GEO) and focused on cellular senescence genes from the CellAge database. We started by selecting five RA datasets from GEO. Next, we pinpointed 29 differentially expressed genes (DEGs) linked to cellular senescence in RA, aligning them with genes from CellAge. We explored the roles of these DEGs in cellular senescence through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. We then pinpointed three key genes (DHX9, CYR61, and ITGB) using random forest and LASSO Cox regression machine learning techniques. An integrated diagnostic model was created using these genes. We also examined the variance in immune cell infiltration and immune checkpoint gene expression between RA and normal samples. Our methodology’s predictive accuracy was confirmed in external validation cohorts. Subsequently, RA samples were classified into three distinct subgroups based on the cellular senescence-associated DEGs, and we compared their immune landscapes. Our findings reveal a significant impact of cellular senescence-related DEGs on immune cell infiltration in RA samples. Hence, a deeper understanding of cellular senescence in RA could offer new perspectives for diagnosis and treatment.
Changes in event soil moisture-temperature coupling can intensify very extreme heat beyond expectations
The gender gap in STEM: (Female) teenagers’ ICT skills and subsequent career paths
Skills shortage in the fields of Sciences, Technology, Engineering, and Mathematics (STEM) poses a significant challenge for industries globally. To overcome shortage of STEM talent, the selection into STEM fields must be fully understood. We contribute to existing research on the selection of STEM careers by analysing the interplay between teenagers’ proficiency in Information and Communication Technology (ICT) and their career preferences in the STEM domain. Based on representative data for German teenagers, our study shows that female teenagers are less likely to choose a career in STEM unless they have strong ICT skills in secondary school. The relationship does not hold for male students. An increase in girls’ ICT skills by 10 percentage points in ninth grade is associated with an increase in the probability to choose a STEM career by 2.95 percentage points. Our findings can be explained with evidence that teenagers sort into occupations they believe to be good at and that female teenagers rather underestimate their true potential. Using different empirical approaches, we also show that ICT skills act as a moderator and not as a mediator in the gender-specific choice of training upon graduating from secondary school. By addressing the interplay between gender, ICT skills, and educational choices, the present study uncovers an additional lever of how to mitigate skills shortage in STEM.
Electrochromism via reversible electrodeposition of solid iodine
Single-cell and bulk RNA sequencing analysis reveals CENPA as a potential biomarker and therapeutic target in cancers
Background Cancer remains one of the most significant public health challenges worldwide. A widely recognized hallmark of cancer is the ability to sustain proliferative signaling, which is closely tied to various cell cycle processes. Centromere Protein A (CENPA), a variant of the standard histone H3, is crucial for selective chromosome segregation during the cell cycle. Despite its importance, a comprehensive pan-cancer bioinformatic analysis of CENPA has not yet been conducted. Methods Data on genomes, transcriptomes, and clinical information were retrieved from publicly accessible databases. We analyzed CENPA’s genetic alterations, mRNA expression, functional enrichment, association with stemness, mutations, expression across cell populations and cellular locations, link to the cell cycle, impact on survival, and its relationship with the immune microenvironment. Additionally, a prognostic model for glioma patients was developed to demonstrate CENPA’s potential as a biomarker. Furthermore, drugs targeting CENPA in cancer cells were identified and predicted using drug sensitivity correlations and protein-ligand docking. Results CENPA exhibited low levels of gene mutation across various cancers. It was found to be overexpressed in nearly all cancer types analyzed in TCGA, relative to normal controls, and was predominantly located in the nucleus of malignant cells. CENPA showed a strong association with the cancer cell cycle, particularly as a biomarker for the G2 phase. It also emerged as a valuable diagnostic and prognostic biomarker across multiple cancer types. In glioma, CENPA demonstrated reliable prognostic potential when used alongside other prognostic factors. Additionally, CENPA was linked to the immune microenvironment. Drugs such as CD-437, 3-Cl-AHPC, Trametinib, BI-2536, and GSK461364 were predicted to target CENPA in cancer cells. Conclusion CENPA serves as a crucial biomarker for the cell cycle in cancers, offering both diagnostic and prognostic value.
Striving for open-source and equitable speech-to-speech translation
Gypsum heterogenous nucleation pathways regulated by surface functional groups and hydrophobicity
Abstract Gypsum (CaSO4·2H2O) plays a critical role in numerous natural and industrial processes. Nevertheless, the underlying mechanisms governing the formation of gypsum crystals on surfaces with diverse chemical properties remain poorly understood due to a lack of sufficient temporal-spatial resolution. Herein, we use in situ microscopy to investigate the real-time gypsum nucleation on self-assembled monolayers (SAMs) terminated with −CH3, −hybrid (a combination of NH2 and COOH), −COOH, −SO3, −NH3, and −OH functional groups. We report that the rate of gypsum formation is regulated by the surface functional groups and hydrophobicity, in the order of −CH3 > −hybrid > −COOH > −SO3 ≈ − NH3 > − OH. Results based on classical nucleation theory and molecular dynamics simulations reveal that nucleation pathways for hydrophilic surfaces involve surface-induced nucleation, with ion adsorption sites (i.e., functional groups) serving as anchors to facilitate the growth of vertically oriented clusters. Conversely, hydrophobic surfaces involve bulk nucleation with ions near the surface that coalesce into larger horizontal clusters. These findings provide new insights into the spatial and temporal characteristics of gypsum formation on various surfaces and highlight the significance of surface functional groups and hydrophobicity in governing gypsum formation mechanisms, while also acknowledging the possibility of alternative nucleation pathways due to the limitations of experimental techniques.
The diagnostic accuracy of umbilical cord procalcitonin in predicting early-onset neonatal infection
Introduction To determine the threshold of umbilical cord blood procalcitonin for early-onset neonatal infection diagnosis. Method This prospective study was conducted on 126 neonates in the neonatal care unit of Hue University of Medicine and Pharmacy Hospital, Vietnam, from June 01, 2023 to August 31, 2024. All neonates showed signs at birth or risk factors for early-onset infection (EOI) and were divided into two groups: EOI group and non-EOI group. Umbilical cord blood samples were collected for procalcitonin analysis immediately after birth. Results The median procalcitonin (PCT) levels in umbilical cord blood were significantly higher in the EOI group (0.154 ng/ml [0.092–0.197]) compared to the non-EOI group (0.097 ng/ml [0.082–0.134]; p < 0.001). Receiver operating characteristic (ROC) curve determined the optimal threshold value of PCT of 0.142 ng/ml with an AUC 0.751 (95% CI: 0.661–0.841, p<0.001) in the total population. At this cut-off, the Se, Sp, PPV, and NPV were 68.2%, 76.8%, 61.2%, and 81.8%, respectively. The optimal cut-off value for preterm neonates was 0.122 ng/ml (AUC: 0.785, 95% CI: 0.658–0.911, p<0.001) corresponding a Se of 79.2%, Sp of 74.1%, PPV of 73.1%, and NPV of 80.0%. In term group, the optimal cut-off value was 0.150 ng/ml (AUC: 0.726, 95% CI: 0.583–0.860, p<0.01), with a Se of 60.0%, Sp of 80.4%, PPV of 52.2%, and NPV of 84.9%. Conclusions Umbilical cord blood PCT concentration were elevated in neonates with EOI. PCT could be a valuable marker for the early diagnosis of EOI.
Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2
Abstract Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis. Here, we use a combination of cryo-electron microscopy, immunofluorescence, in vitro binding and in vivo S1P export assays, and molecular dynamics simulations to probe SPNS2’s substrate binding and transport. These results reveal the transporter’s binding mode to its native substrate S1P, the therapeutic FTY720-P, and the reported SPNS2-targeting inhibitor 33p. Further capturing an inward-facing apo state, our structures illuminate the protein’s mechanism for exchange between inward-facing and outward-facing conformations. Finally, using these structural, localization, and S1P transport results, we identify how pathogenic mutations ablate the protein’s export activity and thereby lead to hearing loss.
A facial expression recognition network using hybrid feature extraction
Facial expression recognition faces great challenges due to factors such as face similarity, image quality, and age variation. Although various existing end-to-end Convolutional Neural Network (CNN) architectures have achieved good classification results in facial expression recognition tasks, these network architectures share a common drawback that the convolutional kernel can only compute the correlation between elements of a localized region when extracting expression features from an image. This leads to difficulties for the network to explore the relationship between all the elements that make up a complete expression. In response to this issue, this article proposes a facial expression recognition network called HFE-Net. In order to capture the subtle changes of expression features and the whole facial expression information at the same time, HFE-Net proposed a Hybrid Feature Extraction Block. Specifically, Hybrid Feature Extraction Block consists of parallel Feature Fusion Device and Multi-head Self-attention. Among them, Feature Fusion Device not only extracts the local information in expression features, but also measures the correlation between distant elements in expression features, which helps the network to focus more on the target region while realizing the information interaction between distant features. And Multi-head Self-attention can calculate the correlation between the overall elements in the feature map, which helps the network to extract the overall information of the expression features. We conducted a lot of experiments on four publicly available facial expression datasets and verified that the Hybrid Feature Extraction Block constructed in this paper can improve the network’s recognition ability for facial expressions.
Hydroclimatic extremes threaten groundwater quality and stability
Abstract Heavy precipitation, drought, and other hydroclimatic extremes occur more frequently than in the past climate reference period (1961–1990). Given their strong effect on groundwater recharge dynamics, these phenomena increase the vulnerability of groundwater quantity and quality. Over the course of the past decade, we have documented changes in the composition of dissolved organic matter in groundwater. We show that fractions of ingressing surface-derived organic molecules increased significantly as groundwater levels declined, whereas concentrations of dissolved organic carbon remained constant. Molecular composition changeover was accelerated following 2018’s extreme summer drought. These findings demonstrate that hydroclimatic extremes promote rapid transport between surface ecosystems and groundwaters, thereby enabling xenobiotic substances to evade microbial processing, accrue in greater abundance in groundwater, and potentially compromise the safe nature of these potable water sources. Groundwater quality is far more vulnerable to the impact of recent climate anomalies than is currently recognized, and the molecular composition of dissolved organic matter can be used as a comprehensive indicator for groundwater quality deterioration.
Beyond burnout: A comprehensive investigation of burnout, resilience, and career continuity among Palestinian lawyers in a complex socio-political environment
This article investigates burnout among lawyers and proposes systemic changes to reduce pressure and stress in the legal profession while enhancing resilience among lawyers. The article focuses on factors influencing career continuity among Palestinian lawyers within a socio-politically complex environment. It discusses elements contributing to resilience, including a positive mindset, a strong support system, training, and social support. The study reveals exceptional resilience among Palestinian lawyers. A quantitative cross-sectional study was used; the goals of the study involved 323 participants from different places in Palestine. Data analysis employed Smart PLS4 to build a regression model. Challenging conventional notions, the study provides valuable insights for state strategies, legal firms, educational institutions, and policymakers to address challenges and improve lawyer retention and job satisfaction in an environment marked by unstable economic and political conditions. Additionally, it examines gender-specific career intentions, notably women lawyers displaying a stronger inclination to stay, potentially linked to socio-economic responsibilities. This study contributes significantly to existing literature by providing a unique case study on career continuance determinants within economic and political instability. It sets a precedent for further study and strategic improvements in lawyer retention and job satisfaction within high-stress professions in an economically and politically complex environment.