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Oral administration of Limosilactobacillus reuteri VHProbi® M07 alleviates ovalbumin-induced allergic asthma in mice

Aims Asthma is characterized by chronic airway inflammation, persistent cough, wheezing, and dyspnea. This study aimed to evaluate the efficacy of Limosilactobacillus reuteri VHProbi® M07 (M07) administration in alleviate the asthma severity in a mice model. Methods and results In vitro studies confirmed that M07 can survive and proliferate within the gastrointestinal tract. BALB/c mice were administered M07 both before and after ovalbumin (OVA) challenge. Serum levels of OVA-specific immunoglobulin (Ig) E and IgG1, inflammatory cells and cytokines in bronchoalveolar lavage fluid were assessed, along with histopathological examination of lung tissue. Compared to the placebo (PLA) group, mice treated with M07 exhibited significantly lower levels of OVA-specific IgE and IgG1 (P < 0.01). The counts of eosinophils and neutrophils were also significantly reduced in both the pretreated (PRE) group and post-treated (POS) group compared with the PLA group (P < 0.01). Histological analysis of lung tissues verified the protective effects of M07 against inflammation, demonstrating reduced infiltration of inflammatory cells. Additionally, mice in the PRE and POS groups showed significantly increased levels of IL-10 (P < 0.01), and significantly decreased levels of IL-5, IL-13, MCP-1, eotaxin, and tumor necrosis factor-α (P < 0.01). Conclusions Oral administration of M07 mitigated key features of inflammatory responses in the OVA-induced mice asthma model. These findings suggest that M07 holds therapeutic potential for the treatment of allergic asthma.

Investigating amygdala nuclei volumes in military personnel with post-traumatic stress disorder, major depressive disorder, and adjustment disorder: A retrospective cross-sectional study using clinical routine data

Background Post-traumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD), and Adjustment Disorder (AdjD) are highly prevalent among military personnel, often presenting diagnostic challenges due to overlapping symptoms and reliance on self-reporting. The amygdala, particularly the basolateral complex involved in fear-related memory formation and extinction recall, plays a crucial role in emotional processing. Abnormalities in these amygdala nuclei are implicated in PTSD and may distinguish it from other disorders like MDD and AdjD, where these mechanisms are less central. Investigating structural differences in specific amygdala nuclei could enhance diagnostic precision and inform targeted interventions. Goal This study aimed to explore volumetric differences in amygdala nuclei among patients with PTSD, MDD, comorbid PTSD and MDD (PTSD+MDD), and AdjD using routine clinical MRI data. We hypothesized that patients with PTSD would exhibit distinct amygdala nuclei volumes compared to those with MDD or AdjD. Additionally, we examined the influence of symptom duration, prior medication, and psychotherapeutic experience on amygdala volumes. Methods We conducted a retrospective cross-sectional study with 185 military personnel (162 men, 23 women) diagnosed with PTSD (n = 50), MDD (n = 70), PTSD+MDD (n = 38), and AdjD (n = 27). High-resolution T1-weighted MRI scans were obtained using a 3T Siemens Skyra scanner. Amygdala subfields were automatically segmented and volumetrized using FreeSurfer software. Analysis of covariance (ANCOVA) models compared amygdala nuclei volumes across diagnostic groups, controlling for estimated total intracranial volume (eTIV), age, and gender. Exploratory analyses included symptom duration, medication use, and prior psychotherapy as additional covariates. Sensitivity analyses further examined the impact of depressive episode type (first vs. recurrent), severity (mild, moderate, severe), and AdjD symptom duration. Results The main analyses revealed no significant differences in the volumes of the basolateral and medial amygdala nuclei among the PTSD, MDD, PTSD+MDD, and AdjD groups. Exploratory analyses did not identify significant associations between amygdala volumes and symptom duration, medication use, or prior psychotherapy. Sensitivity analyses also showed no significant volumetric differences related to depressive episode type, severity, or AdjD symptom duration. Conclusion Our findings suggest that, within this military population, amygdala nuclei volumes measured using routine clinical MRI data do not significantly differ among patients with PTSD, MDD, PTSD+MDD, and AdjD. This indicates that structural amygdala volumetry alone may not suffice to distinguish between these stress-related disorders in clinical settings. The study highlights the complexity of diagnosing overlapping mental health conditions and underscores the need for comprehensive approaches that integrate neuroimaging with clinical assessments. Future research should include healthy control groups, consider additional brain regions and functional connectivity, and employ longitudinal designs to better understand the temporal dynamics of amygdala changes and their relation to symptomatology.

Reasons for declining to participate in a trial of online cognitive behavioural therapy following orthopaedic trauma: A mixed methods study

The timely enrollment of study participants is critical to the success of clinical trials. Understanding factors that contribute to patients’ decision to participate in trials involving online cognitive behavioural therapy for pain management should prove helpful to optimize the design of study protocols. Fracture patients from an orthopaedic clinic who declined to participate in the Cognitive behavioural therapy to Optimize Post-operative rEcovery (COPE) trial were asked to complete a Research Participation Questionnaire that asked them about their previous experiences with clinical research and mental health therapy and their reasons for declining to participate in the COPE trial. At the end of the questionnaire, a subset of participants was offered the opportunity to participate in a telephone interview to further discuss why they declined to participate in the COPE trial. Sixty-four patients who declined to participate in the COPE trial completed the questionnaire and twenty of these participants agreed to take part in a telephone interview (31%). Twenty-two participants (34%) had previous experience with clinical research and six participants (9%) had received cognitive behavioural therapy (CBT) in the past. Excessive time commitment (41%) was the most commonly selected reason for not participating in the COPE trial, followed by a disinclination to participate in clinical research (19%). Four themes emerged from the interviews with participants: 1) belief that they could overcome mental health challenges after their fracture without external help; 2) belief that CBT might be helpful for some fracture patients, but not for themselves; 3) preference for online or in-person CBT; and 4) concerns regarding time commitment. To maximize enrollment, trials exploring the role of psychotherapy in recovery from orthopedic trauma should optimize time commitment of psychotherapy. Providing information in the patient consent process regarding evidence for psychotherapy and recovery from orthopedic trauma may also prove helpful in promoting patient enrollment.

Championing queer scientists of colour: ‘I don’t think we’ve scratched the surface on systemic exclusion’

A recurrence model for non-puerperal mastitis patients based on machine learning

Objective Non-puerperal mastitis (NPM) is an inflammatory breast disease affecting women during non-lactation periods, and it is prone to relapse after being cured. Accurate prediction of its recurrence is crucial for personalized adjuvant therapy, and pathological examination is the primary basis for the classification, diagnosis, and confirmation of non-puerperal mastitis. Currently, there is a lack of recurrence models for non-puerperal mastitis. The aim of this research is to create and validate a recurrence model using machine learning for patients with non-puerperal mastitis. Methods We retrospectively collected laboratory data from 120 NPM patients, dividing them into a non-recurrence group (n = 59) and a recurrence group (n = 61). Through random allocation, these individuals were split into a training cohort and a testing cohort in a 90%:10% ratio for the purpose of building the model. Additionally, data from 25 NPM patients from another center were collected to serve as an external validation cohort for the model. Univariate analysis was used to examine differential indicators, and variable selection was conducted through LASSO regression. A combination of four machine learning algorithms (XGBoost、Logistic Regression、Random Forest、AdaBoost) was employed to predict NPM recurrence, and the model with the highest Area Under the Curve (AUC) in the test set was selected as the best model. The finally selected model was interpreted and evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, Decision curve analysis (DCA), and Shapley Additive Explanations (SHAP) plots. Results The logistic regression model emerged as the optimal model for predicting recurrence of NPM with machine learning, primarily utilizing three variables: FIB, bacterial infection, and CD4+ T cell count. The model showed an AUC of 0.846 in the training cohort and 0.833 in the testing cohort. The calibration curve indicated excellent calibration of the model. DCA revealed that the model possessed favorable clinical utility. Furthermore, the model effectively achieved in the external validation group, with an AUC of 0.825. Conclusion The machine learning model developed in this study, serving as an effective tool for predicting NPM recurrence, aids doctors in making more individualized treatment decisions, thereby enhancing therapeutic efficacy and reducing the risk of recurrence.

Environmental maternal exposures and the risk of premature birth and intrauterine growth restriction: The Generation Gemelli study protocol of newborn exposome

Background The study of women exposures and child outcomes occurring in the first 1,000 days of life since conception enhances understanding of the relationships between environmental factors, epigenetic changes, and disease development, extending beyond childhood and spanning the entire lifespan. Generation Gemelli is a recently launched case-control study that enrolls mother-newborns pairs in one of the largest university hospitals in Italy, in order to examine the association between maternal environmental exposures and intrauterine growth restriction (IUGR) and the risk of premature birth. The study will also evaluate the association of maternal exposures and the health and growth of infants and children up to 24 months of age. Methods The study entails the set-up of a case-control study within a birth cohort. With approximately 4,000 annual deliveries, we aim to enroll 140 cases (newborns with IUGR and premature birth) and 280 controls per year, from September 2022. A comprehensive questionnaire will be used to gather information about various types of maternal environmental exposures before and during pregnancy. We will collect biological samples from both mothers and newborns (including vaginal swab, placenta sample, blood, saliva, meconium, and bronchoalveolar lavage fluid) at birth and within the early hours of the newborn’s life. We will perform laboratory examinations including dosage of heavy metals and essential elements, investigation of placental distress and fetal brain damage of biomarkers, analysis of microbiota and of DNA methylation profile. We will conduct clinical follow-up assessments in both cases and controls at months 12 and 24 and we will collect anthropometric data, feeding types with particular reference to breastfeeding and its duration, pediatric emergency room visits, hospitalizations, medication usage, known allergies, and neuropsychological development. Discussion The Generation Gemelli case-control study holds the promise of significantly enhancing our comprehension of how maternal environmental exposures relate to the health of children and the broader population. The study of the exposome will provide insights into the relationships between environmental exposures, epigenetic changes and health outcomes during the first 1000 days of life and onward.

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.