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Daily briefing: AI-designed proteins offer lifeline for treating snake bites

Novel methotrexate long-acting system using ambroxol coating and hydroxypropyl methylcellulose encapsulation for preferential and enhanced lung cancer efficiency

Methotrexate (MTX) is classified as an antimetabolite. It’s commonly used to treat lung cancer. MTX is an immunosuppressant following the above-mentioned mechanism of action due to its poor selectivity. The tricky move is to investigate the solid dispersions and coating using a co-delivery system of MTX and Ambroxol (ABL). ABL is known for its, anticancer and preferential pulmonary distribution after oral administration. The goals was development were the MTX physiochemical modulation for pulmonary enhanced distribution, MTX resistance modulation and long-acting system development using ABL middle coating and HPMC outer coating. The selection of the optimum MTX-ABL dispersion was done based on the FT-IR characterization. The MTX-release analysis results for the optimized MTX-ABL solid dispersion and the HPMC-coated MTX-ABL gel product were tested for release in the gastrointestinal simulated media to select the most optimum HPMC amounts to coat the MTX-ABL optimum solid dispersion. Moreover, different characterizations of FT-IR, X-ray diffraction and Scanning electron microscopy investigations were completed for the MTX, ABL, the ABL-MTX optimized solid dispersion and the optimum MTX-ABL-HPMC gel. The cytotoxicity assay and the ELISA to assess the levels of BAX, BCL-2, TGF-β and FR-ɑ after the MTX, ABL and the optimized MTX-ABL solid dispersion groups were tested against lung cancer cells, A549 cells, for 24 h. The sustained release character and HPMC-ABL encapsulation of MTX were confirmed. The MTX-ABL solid dispersion showed less MTX resistance without the need to use the high MTX concentrations in comparison to the MTX alone. The apoptotic, anti-metastatic, and MTX preferential lung cancer uptake profiles were higher using the MTX-ABL solid dispersion than in the MTX or ABL. The MTX-ABL-HPMC gel could serve as an alternative to the MTX-oral tablets available in the markets with enhanced efficacy and safety profile.

A CD26+ tendon stem progenitor cell population contributes to tendon repair and heterotopic ossification

Abstract Inadequate tendon healing and heterotopic bone formation result in substantial pain and disability, yet the specific cells responsible for tendon healing remain uncertain. Here we identify a CD26+ tendon stem/progenitor cells residing in peritendon, which constitutes a primitive stem cell population with self-renewal and multipotent differentiation potentials. CD26+ tendon stem/progenitor cells migrate into the tendon midsubstance and differentiation into tenocytes during tendon healing, while ablation of these cells led to insufficient tendon healing. Additionally, CD26+ tendon stem/progenitor cells contribute to heterotopic ossification and Tenascin-C-Hippo signaling is involved in this process. Targeting Tenascin-C significantly suppresses chondrogenesis of CD26+ tendon stem/progenitor cells and subsequent heterotopic ossification. Our findings provide insights into the identification of tendon stem/progenitor cells and illustrate the essential role of CD26+ tendon stem/progenitor cells in tendon healing and heterotopic bone formation.

Household food insecurity, living conditions, and individual sense of security: A cross-sectional survey among Burkina Faso refugees in Ghana

Food insecurity and achieving adequate nutrition is a major global challenge, especially in vulnerable groups such as refugee communities. In West Africa, thousands of Burkina Faso refugees have crossed the border into northern Ghana due to conflict and instability in their home country. We conducted a one-off cross-sectional survey to assess household food insecurity, living conditions, and sense of security among Burkina Faso refugees currently residing in the Upper East region of Ghana. Study data was collected over 14–21 October 2022 from 498 refugee households, via registered refugee households who were contacted with the help of the community refugee focal persons. We used the validated USAID household food insecurity questionnaire, analysed using Rasch modelling, with descriptive statistics, and linear regression analyses (with significance at p < 0.05) to assess food insecurity. Results revealed that 100% of households experienced food insecurity, with 95.2% defined as moderate or severe, and 70.4% as experiencing severe food insecurity. Refugees from rural areas were less insecure compared to urban refugees (β = -4.25 [CI: -5.79 –-2.71], p < .001). Refugees residing in host communities experienced lower food insecurity than those in designated refugee camps (β = -1.56 [CI: -2.74 –-0.39,] p = .009). Further, refugees who were dissatisfied with their accommodation size were more likely to experience food insecurity (β = 2.96 [CI: -0.06–2.47], p = .060). Most refugees (73.5%) felt safe and welcomed by host communities. Our results highlight the extremely high prevalence of moderate and severe food insecurity in this vulnerable refugee population. We provide evidence to support the need to improve food distribution logistics, prioritising suitable accommodation, and facilitating access to healthcare. Follow-up research, such as repeated community surveys, can track this evolving situation to continuously inform decision-making for refugee support.

Dear Donald Trump: A letter from Nature on how to make science thrive

A shallow-water oxygen minimum zone in an oligotrophic Tonian basin

Integrating post-validation surveillance of lymphatic filariasis with the WHO STEPwise approach to non-communicable disease risk factor surveillance in Niue, a study protocol

Background Lymphatic filariasis (LF), a mosquito-borne parasitic disease caused by three species of filarial worms, was first detected in Niue, a small Pacific Island nation of approximately 1,600 people, in 1954. After extensive efforts involving multiple rounds of Mass Drug Administration, Niue was validated by the World Health Organization (WHO) as having e4liminated LF as a public health problem in 2016. However, no surveillance has been conducted since validation to confirm infection rates have remained below WHO’s elimination threshold. WHO has encouraged an integrated approach to disease surveillance and integrating LF post-validation surveillance (PVS) with existing surveys is an anticipated recommendation of the upcoming WHO LF-PVS guidelines. This paper describes a protocol for the implementation of an integrated approach to LF-PVS in Niue as cost-efficient and operationally feasible means of monitoring the disease in the population. Methods The LF-PVS will be implemented as part of a planned national population-based WHO STEPwise approach to non-communicable disease (NCD) risk factor surveillance (STEPS) in Niue. Integration between the LF-PVS and STEPS will occur at multiple points, including during pre-survey community awareness raising and engagement, when obtaining informed consent, during the collection of demographics, risk factor, and location data, and when collecting finger-prick blood samples (for glucose as part of the STEPS survey and LF as part of the LF-PVS). The primary outcome measure for LF transmission will be antigen positivity. Microfilaria slides will be prepared for any antigen-positive cases. Dried blood spots will be prepared for all participants for Multiplex Bead Assays-based analysis to detect anti-filarial antibodies. We estimate a total sample size of 1,062 participants aged 15–69, representing approximately 66% of the population. Conclusions The results of this study will provide insight into the status of LF in Niue and evaluate the advantages, challenges, and opportunities offered by integrated approaches to disease surveillance.

RSK1 is an exploitable dependency in myeloproliferative neoplasms and secondary acute myeloid leukemia

Spatial epidemiological analysis based on township scale and analysis of influencing factors of pulmonary tuberculosis cure of Changshu city from 2015 to 2022

Objective This study aimed to enhance the prevention and control of pulmonary tuberculosis (PTB) and provide more effective and accurate methods in Changshu City. Methods The PTB patients’ information came from the China Information System for Disease Control and Prevention (CISDCP). The demographic data for Changshu city and towns came from the Suzhou Statistical Yearbook and the LandScan platform. ArcGIS was used for global spatial autocorrelation analysis and local spatial autocorrelation analysis. Univariate logistic regression and multivariate logistic regression were used to analyze the influencing factors of cured PTB patients. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to analyze the predictive efficacy and clinical benefit of the indicators. XGBoost analysis was performed to explore the feature importance of key metrics for PTB outcome. Results A total of 3943 PTB cases were included. The annual incidence rate of new PTB in Changshu city was 27.081 per 100,000. Changshu High-tech Industrial Development Zone in Jiangsu Province and Shajiabang town were the high-high aggregation areas and hot spot areas. Diagnosis delay, TB strain types, and drug sensitivity were independent predictors of the cure of new PTB patients. Conclusion The central and southern areas of Changshu were the high-high cluster areas and hot spots for PTB. Shorter diagnosis delay days and mycobacterium tuberculosis (MTB) promote the cure of tuberculosis, while drug sensitivity was a risk factor for its cure.

Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function

Analysis of entropy on the European markets of energy and energy commodities prices

The paper analyzes the problem of entropy in the moments of transition from a normal economic situation (2015–2019) to the Pandemic period (2020–2021) and the period of Russia’s attack on Ukraine (2022–2023). The research in the article is based on the analysis of electricity, oil, coal, and gas prices in 27 countries of the European Union and Norway. The daily data cover the period from January 1, 2015, to March 30, 2023, and were analyzed using two-dimensional sets of electricity and commodity prices. The work uses the time dependent James-Stein estimator of the Shannon informational entropy.

TRIM28 is an essential regulator of three-dimensional chromatin state underpinning CD8+ T cell activation

Correction: Genetic polymorphisms of muscular fitness in young healthy men

Reduced contribution of sulfur to the mass extinction associated with the Chicxulub impact event

Abstract The Chicxulub asteroid impact event at the Cretaceous-Paleogene (K-Pg) boundary ~66 Myr ago is widely considered responsible for the mass extinction event leading to the demise of the non-avian dinosaurs. Short-term cooling due to massive release of climate-active agents is hypothesized to have been crucial, with S-bearing gases originating from the target rock vaporization considered an important driving force. Yet, the magnitude of the S release remains poorly constrained. Here we empirically estimate the amount of impact-released S relying on the concentration of S and its isotopic composition within the impact structure and a set of terrestrial K-Pg boundary ejecta sites. The average value of 67 ± 39 Gt obtained is ~5-fold lower than previous numerical estimates. The lower mass of S-released may indicate a less prominent role for S emission leading to a milder impact winter with key implications for species survival during the first years following the impact.

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.