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Bone marrow niches orchestrate stem-cell hierarchy and immune tolerance
Influences of footstrike patterns and overground conditions on lower extremity kinematics and kinetics during running: Statistical parametric mapping analysis
This study investigated lower extremity biomechanics when running on different surfaces among runners with different footstrike patterns. Thirty rearfoot strikers (RFSs) and non-rearfoot strikers (nRFSs) ran at 3.3 m/s on a specially designed indoor track covered with three surfaces: artificial grass, synthetic rubber, and concrete. A motion capture system with ten cameras combined a force plate was used to collect marker trajectory and ground reaction force (GRF) during the running stance phase. A two-way analysis of variance with statistical parametric mapping was employed to evaluate differences in the biomechanics of the lower extremities between footstrike patterns and among running surfaces. The nRFSs exhibited significantly greater ankle inversion angles and increased inversion and internal rotation moments at midstance compared to the RFSs. Conversely, the RFSs demonstrated significantly greater knee abduction moments in late stance. Running on stiffer surfaces was associated with greater vertical GRF in late stance, as well as increased knee and hip extension moments during midstance. Furthermore, running on stiffer surfaces was associated with increased knee abduction moments, hip abduction moments, and hip external rotation moments during late stance. These findings suggested that nRFSs endure more ankle loads, while RFSs face increased knee loads. However, regardless of the footstrike pattern, runners may benefit from selecting softer surfaces to reduce the risk of injury.
Brain-wide cell-type-specific transcriptomic signatures of healthy ageing in mice
Navigating the medical journey: Insights into medical students’ psychological wellbeing, coping, and personality
Background and aims In recent years, increased awareness of the psychological wellbeing of healthcare professionals and students has become a pressing public health issue affecting care delivery. Medical students undergo rigorous training programs that can affect their psychological wellbeing. Despite increased awareness of mental health issues among medical students, research often focuses on negative aspects, overlooking potential positive contributors to wellbeing. This study aims to explore both negative and positive factors influencing medical students’ psychological wellbeing, considering coping strategies and personality traits to inform targeted support measures for diverse student needs. Methods A mixed-methods approach was employed to investigate medical students’ psychological wellbeing, coping strategies, and personality traits. Quantitative data was gathered via self-report questionnaires and analysed using regression models. Additionally, qualitative insights were obtained from semi-structured interviews and analysed thematically to capture students’ perceptions and experiences. Results The analysis revealed moderate to high levels of stress, anxiety, and depression among medical students, along with decreased life satisfaction. Regression analysis showed that problem-focused coping positively impacted medical students’ psychological wellbeing, whereas emotion-focused and avoidance coping showed less favourable effects. Notably, problem-focused coping partially mediated the relationship between stress and depression. Furthermore, personality traits, particularly agreeableness and conscientiousness, played a pivotal role in shaping medical students’ coping strategies and mental health outcomes. Based on thematic analysis, codes gave rise to three overarching themes and corresponding subthemes. Conclusions The study underscores the significance of addressing both positive and negative factors impacting medical students’ wellbeing and highlights the need for tailored support considering individual personality traits that influence coping strategies and mental health. It also identifies challenges within medical education, emphasising the necessity for stress management programs, mental health support, and curricula promoting problem-solving skills. Prioritising medical students’ wellbeing may not only foster good mental health among future professionals but may also enhance future healthcare quality.
Medical students’ knowledge, attitudes, and motivation towards antimicrobial resistance efforts in Eastern Uganda
Introduction Learning beyond the classroom is important for holistic engagement in antimicrobial resistance(AMR) mitigation. Extracurricular interventions can catalyze multidisciplinary engagement and inspire innovative solutions. This study aimed to determine the knowledge, attitudes, and motivations influencing medical students’ engagement in AMR Club initiatives at Busitema University, Uganda. Methodology This was a descriptive cross-sectional study conducted at Busitema University among undergraduate students pursuing Bachelors of Medicine and Surgery, Bachelor of Science in Nursing, and Bachelor of Science in Anesthesia and Critical care. Data collection was performed using a semi-structured, pre-tested questionnaire and administered to the participants The Bloom’s cut-off method was used to analyse the knowledge of the participants, while bivariate analysis was conducted using the chi square test. Multivariable logistic regression analysis was used to identify factors independently associated with students’ engagement in AMR club activities. Results Of the 193 study participants, 71.5%(n) demonstrated sufficient knowledge about antimicrobial resistance (AMR), as determined using Bloom’s cutoff categories (≥60% classified as sufficient, <60% as insufficient), with an average knowledge score of 68.18% (SD ±16.12). Additionally, 90% of participants acknowledged the significance of incorporating AMR topics into their curriculum, while 87.5% emphasized the need for AMR training using a One Health approach. The major motivations for students to engage in extracurricular activities addressing AMR were peer influence (n = 42), university support (n = 35), and inspiration drawn from peer mentors’ work (n = 35). Conclusion The students demonstrated a high level of knowledge and positive attitudes towards AMR but highlighted the need for further in-depth training. Participation in extra-curricular activities such as involvement in an AMR Club, was found to significantly influence students’ engagement in AMR related interventions.
Photodiagnosis and photodynamic recognition of cervical cancer with SEM and AFM images
So far, the number of patients who die from cancer is quite high. Continuation of early detection research is important to reduce the number of deaths due to cancer. At the time of the literature review, images of the same patients taken from Scanning Electron Microscope (SEM) and Atomic Force Microscope (AFM) for early diagnosis of cervix cancer have not been addressed to date. This article, Photodiagnosis and Photodynamics with SEM and AFM images are valuable in recognizing cervical cancer and starting treatment early. Simultaneous examination of the, Photodiagnosis and Photodynamics with SEM and AFM cervix images of patients will provide us with a far more powerful solution than a one-way solution. Daubechies (db2, db3, db4, and db5), Coiflet (coif5, coif4, coif3, and coif2), Symlet (sym5, sym4, sym3, and sym2), and Biorthogonal (bior1.3, bior2.8, bior1.5, and bior3.3) 16 discrete wavelet transformation families (DWTF) have been applied to AFM and SEM images. One approximate and three detail coefficients have been obtained for each one AFM and SEM cervix images. Homogeneity, contrast, angular second moment, entropy, mean, standard deviation, correlation, cluster prominence, dissimilarity, and cluster shade values have been calculated for each of these one approximate and three detail coefficients. The classification rate found by the averages of the results obtained from the DWTF_JSD, DWTF_HD and DWTF_TD algorithms for AFM and SEM cervix images are 98.29% and 97.10%, respectively. According to these results, it has been determined that SEM images have lower classification rate than AFM images. It has been also observed that the surface roughness of the mAFM images was larger than nAFM and bAFM images. But, it was observed that the volume of particles of the mAFM images has been smaller than nAFM and bAFM images.
Impact of human body shape on free convection heat transfer
Understanding the thermal comfort and safety of diverse populations within indoor settings requires a quantitative understanding of the primary heat exchange pathways between occupants and their surroundings: radiation and free convection. Thus far, however, free convective heat transfer coefficients have only been determined for the average Western adult. To this end, we investigated how variation in body shape impacts free convection heat transfer using an experimentally validated numerical model. The multiphysics model was compared against experiments conducted using the thermal manikin ANDI ("Advanced Newton Dynamic Instrument") in a climate-controlled enclosure across five air-to-skin temperature differences ranging from 4.9 to 13.9°C. The difference between measured and simulated heat fluxes for the whole body, and per anatomical region, was typically <5%, occasionally reaching 15–20%, for some body regions due to physical features not modeled in the virtual ANDI model. Using the validated model, we simulated free convection around a family, or diverse group, of virtual manikins representing the 1st to 99th percentile body mass index (BMI) and height variation in the United States adult population. Our results show that the free convection heat transfer coefficient is independent of human sex and height but decreases slightly with increased BMI. However, the variation from the average manikin in the whole body and regional free convection coefficients with BMI was small, not exceeding 8% and 16%, respectively. Furthermore, our regression coefficients and exponents can be derived from the theorical correlation for free turbulent convection from a vertical plate, which also explains the observed independence of the heat transfer coefficient from the manikins’ height. Overall, these findings demonstrate the general applicability of using an average body shape in indoor thermal audits and/or overheating risk assessments to understand thermal comfort and heat stress. The results and valid application of the model support critical insights for human health, productivity, and well-being connected to heat and cooling in buildings.
Perinatal intimate partner violence and breastfeeding practices: A systematic review and meta-analysis protocol
Background Intimate partner violence increases the risk of detrimental health, behaviors and psychological issues in mothers, affecting infant nutrition and development. However, the potential effects of maternal exposure to intimate partner violence on breastfeeding practices are understudied, and the results of individual studies are inconsistent and conflicting. The aims of this systematic review and meta-analysis are therefore to 1) estimate the prevalence of perinatal intimate partner violence and, 2) examine the relationship between perinatal intimate partner violence and breastfeeding outcomes. Methods and analysis This systematic review and meta-analysis will investigate the association between perinatal intimate partner violence and breastfeeding outcomes, including early initiation within 1 hour after giving birth, exclusive breastfeeding under six months, and continued breastfeeding at two years or beyond. Comprehensive searches will be conducted in PsycInfo, Scopus, Web of Science, Medline, Cochrane, JBI EBP, CINAHL, Informit, and PubMed electronic databases. Data extraction will be performed independently by two reviewers, with discrepancies resolved by a third reviewer. Statistical analysis will be conducted using STATA/SE version 17, employing random-effects models to calculate pooled effect sizes and assess heterogeneity with I2 and Chi-square tests. Subgroup analyses and meta-regression will explore potential sources of heterogeneity. Discussion and conclusion Evidence suggests that intimate partner violence is linked to poor breastfeeding outcomes. This systematic review and meta-analysis will update, compile, and critically review the evidence of the role of intimate partner violence on breastfeeding outcomes. This systematic review and meta-analysis will also inform effective strategies and interventions to support breastfeeding among IPV-affected women, thereby enhancing maternal and child health. Ethics and dissemination As this review and meta-analysis involves secondary analysis of existing data, ethical approval is not required. Findings will be disseminated through peer-reviewed publications and scientific conferences, aiming to inform strategies to support breastfeeding among women affected by intimate partner violence. Study registration This protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42024555048.
Rapid and scalable personalized ASO screening in patient-derived organoids
Abstract Personalized antisense oligonucleotides (ASOs) have achieved positive results in the treatment of rare genetic disease1. As clinical sequencing technologies continue to advance, the ability to identify patients with rare disease harbouring pathogenic genetic variants amenable to this therapeutic strategy will probably improve. Here we describe a scalable platform for generating patient-derived cellular models and demonstrate that these personalized models can be used for preclinical evaluation of patient-specific ASOs. We describe protocols for delivery of ASOs to patient-derived organoid models and confirm reversal of disease-associated phenotypes in cardiac organoids derived from a patient with Duchenne muscular dystrophy (DMD) with a structural deletion in the gene encoding dystrophin (DMD) that is amenable to treatment with existing ASO therapeutics. Furthermore, we designed novel patient-specific ASOs for two additional patients with DMD (siblings) with a deep intronic variant in the DMD gene that gives rise to a novel splice acceptor site, incorporation of a cryptic exon and premature transcript termination. We showed that treatment of patient-derived cardiac organoids with patient-specific ASOs results in restoration of DMD expression and reversal of disease-associated phenotypes. The approach outlined here provides the foundation for an expedited path towards the design and preclinical evaluation of personalized ASO therapeutics for a broad range of rare diseases.
FIRM image analysis: A machine learning workflow for quantifying extracellular matrix components from electron microscopy images
The extracellular matrix (ECM) is a complex network of biomolecules that plays an integral role in the structure, processes, and signaling mechanisms of cells and tissues. Identifying and quantifying changes in these matrix components provides insight into the mechanisms behind specific tissue remodeling processes; however, quantifying these changes is challenging due to difficult imaging conditions, complexity of the ECM, and the subtlety of these changes. Current imaging techniques allow us to visualize these critical remodeling events and developments in image analysis have employed a combination of analysis software and machine learning techniques to improve the efficiency and accuracy with which features are measured. Although image analysis has seen much improvement in recent years, there has been no technique developed to address ambiguity in feature edges in electron microscopy images. Presented here is a new machine learning-based workflow for the analysis of microscopy images named FIRM (Feature Identification from Raw Microscopy) that uses a random forest classifier to identify ECM features of interest and generate binary segmentation masks for quantification with ImageJ-FIJI. FIRM performed with an F1 score of 0.794 and greater than 80% accuracy for number and size of features detected. FIRM had similar deviation from the ground truth in the number of identified fibrils, fibril size, and size distributions when compared to human analyses. The results suggest that FIRM performs as well as manual analysis and requires a fraction of the time. This analysis technique is more efficient, eliminates user bias, and can be easily optimized to identify a variety of features, making it useful for any discipline requiring image analysis.
Preparing controlled low strength materials with cement-treated construction waste clay improved by sodium hexametaphosphate
To solve the disposal of large quantities of construction waste clay, this study proposes a new method for preparing controlled low strength materials (CLSM). Flow tests, unconfined compressive strength (UCS) tests, hydraulic conductivity tests and scanning electron microscope (SEM) analyses were performed on cement-treated construction waste clay with different additive content (e.g. sodium hexametaphosphate (SHMP), water glass, and phosphogypsum (PG)). The influence of additive content on the mechanical and microstructural properties of cement-treated clay-based CLSM was analyzed. The results indicated that the SHMP greatly enhanced the flowability of samples, adding 1%SHMP increased the fluidity of the sample by more than 80%, whereas 5% water glass had negligible effect. Additionally, the 10% PG improved the flowability retention, making it have higher flowability after 30 mins (more than 200 mm). SHMP interacted with Ca2+, significantly influencing the cement hydration; notably, 1% content resulted a notable reduction of samples from 167.5 kPa to 21.5 kPa at 1 day. Although increasing SHMP content improved the early strength, it led to a decrease in later strength, with the maximum late strength observed at 2% SHMP. Both PG and water glass also contributed to late strength enhancement, though higher SHMP levels diminished their effects. While SHMP markedly improved permeability resistance (less than 8 × 10−8 cm/s after 28d), hydraulic conductivity showed minimal variation with increased dosage. The combination of SHMP, PG and water glass effectively enhances the flowability and strength of clay-based CLSM at low water content, solving the contradiction between fluidity and strength. This promotes the sustainable development of green building materials.
Immune evasion through mitochondrial transfer in the tumour microenvironment
Influence of day and night temperature and carbon dioxide concentration on growth, yield, and quality of green butterhead and red oakleaf lettuce
Production of lettuce (Lactuca sativa) within vertical farms is an expanding segment of controlled environment agriculture—precise manipulation of environmental parameters including mean daily temperature (MDT) and carbon dioxide (CO2) concentration enables year-round production, alongside color, yield, and crop size regulation. Our objectives included 1) quantify how MDT and CO2 interact to influence lettuce growth, development, and quality; 2) model lettuce growth under several MDTs and CO2 concentrations. Green butterhead ‘Rex’ and red oakleaf ‘Rouxaï RZ’ seedlings were transplanted into hydroponic tanks under a photosynthetic photon flux density of 300 μmol·m‒2·s‒1 for 17-h·d‒1. CO2 concentrations of 500, 800, or 1200 μmol·mol−1 and day/night and MDT setpoints of 22/15°C (MDT 20°C), 25/18°C (23°C), or 28/21°C (26°C) were maintained within growth chambers. ‘Rex’ fresh mass increased linearly with MDT, increasing by 18% from 20 to 26°C. ‘Rouxaï RZ’ fresh mass increased quadratically with MDT, with a 32% increase from 20 to 23°C, then a 7% increase from 23 to 26°C. Elevating CO2 concentrations from 500 to 800 μmol·mol–1 increased ‘Rouxaï RZ’ and ‘Rex’ fresh mass by 33 and 16%, respectively, while fresh mass did not increase from 800 to 1200 μmol·mol–1. Both cultivars had the greatest dry mass at 800 μmol·mol–1 CO2 across temperatures. At a high MDT, ‘Rouxaï RZ’ foliage color became more light, vibrant, and green, while a low MDT induced darker, grayer, and redder foliage. Tipburn occurred on ‘Rex’ across treatments, while 25% of ‘Rouxaï RZ’ were afflicted at 500 μmol·mol−1 CO2 and 67% at 1200 μmol·mol−1. At the light intensity studied, we recommend growing ‘Rex’ and ‘Rouxaï RZ’ at an 800 μmol·mol−1 CO2 concentration and MDT of 23°C for greatest biomass and leaf number, and slightly redder foliage in ‘Rouxaï RZ’ than at a 26°C MDT.
Effect of the hour-1 bundle on clinical outcomes in patients with sepsis and septic shock: A protocol for systematic review and meta-analysis
Background According to the 2018 bundle guidelines of the Surviving Sepsis Campaign, many emergency departments and intensive care units currently adopt the hour-1 bundle as a standard practice for sepsis management. However, recent studies on the hour-1 bundle for sepsis treatment have yielded inconsistent results, raising questions and challenges about its clinical efficacy. Aim This study will conduct a systematic review and meta-analysis to compare the impact of the hour-1 bundle and non-hour-1 bundle on the clinical outcomes in patients with sepsis and septic shock. Methods The protocol was prepared according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocol (PRISMA-P) statement. The systematic review will be carried out in line with the statement of PRISMA. The following electronic databases will be searched: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. All clinical studies comparing the impact of the hour-1 bundle and non-hour-1 bundle on clinical outcomes in patients with sepsis and septic shock will be included. All stages of the literature search, study selection, data extraction, and quality assessment will be conducted independently by two reviewers. Any disagreements between the two reviewers will be resolved by discussion or arbitration by a third reviewer. The primary outcome will be short-term mortality, which involves in-hospital, 28-day, 30-day, and 90-day mortality corresponding to the definition used in each study. For quality assessment, the risk of bias specified by the Cochrane Collaboration and the methodological index for non-randomized studies will be used for randomized control trials (RCTs) and non-RCTs, respectively. Data synthesis will be performed via Review Manager 5.1.0. Expected results This systematic review will integrate all relevant studies to quantitatively estimate the effect size and clarify the role of the hour-1 bundle in sepsis management, contributing new evidence-based guidance to the field. Systematic review registration Protocol registration and reporting: PROSPERO CRD42024579314.
Adaptive enhancement of shoulder x-ray images using tissue attenuation and type-II fuzzy sets
Shoulder X-ray images typically have low contrast and high noise levels, making it challenging to distinguish and identify subtle anatomical structures. While existing image enhancement techniques are effective in improving contrast, they often overlook the enhancement of sharpness, especially when amplifying blurring and noise. These techniques may improve detail contrast but fail to maintain overall image clarity and the distinction between the target and the background. To address these issues, we propose a novel image enhancement method aimed at simultaneously improving both the contrast and sharpness of shoulder X-ray images. The method integrates automatic tissue attenuation techniques, which enhance the image contrast by removing non-essential tissue components while preserving important tissues and bones. Additionally, we apply an improved Type-II fuzzy set algorithm to further optimize image sharpness. By simultaneously enhancing contrast and sharpness, the method significantly improves image quality and detail distinguishability. When tested on certain images from the MURA dataset, the proposed method achieved the best or second-best results, outperforming five no-reference image quality assessment metrics. In comparative studies, the method demonstrated significant performance advantages over 10 contemporary X-ray image enhancement algorithms and was validated through ablation experiments to confirm the effectiveness of each module.
A scalable system using mini-organs to test personalized RNA therapy
Chronic kidney disease among people living with HIV on TDF based regimen: A systematic review and meta-analysis
Introduction Chronic kidney disease is a major public health concern among people living with human immunodeficiency virus (PLWHIV) who are taking tenofovir disoproxil fumarate-based regimen. Despite the available evidence showing a high prevalence of CKD in this population, comprehensive pooled estimate of CKD among PLWHIV receiving TDF based regimen across the globe is lacking. Hence, the present systematic review aimed to provide a global pooled prevalence estimate of CKD. Method We conducted a systematic review of literatures published between January 2000 and May 2024. Articles and grey literature were searched from the following databases and search engine: PubMed, EMBASE, Scopus, Web of science, The Cumulative Index to Nursing and Allied Health Literature (CINHAL), and Google Scholar. We included eligible studies that report magnitude of CKD in TDF based regimen. We executed the pooled CKD, subgroup analysis, and funnel plot using random effect model. All statistical analysis including sensitivity analysis were made using Stata 17 software. Results Sixty-nine studies with 88299 participants included in this meta-analysis. The pooled prevalence of CKD was 7% (95% CI:6–8). CD4 count less than 200 copies per milliliter, and being female were associated with CKD. Conclusion We concluded that the magnitude of CKD across the globe is high in people living with HIV who have received TDF based regimen. Early identification of CKD by considering regular renal function monitoring, and risk factors especially low CD4 count, and female gender at birth are essential. Trial registration The protocol has been prospectively registered with PROSPERO ((CRD42020136813).
Applying a quantitative fire risk assessment method in hospital settings: Case study
Understanding and mitigating fire risks in healthcare settings are crucial for ensuring the safety of individuals, especially during the current pandemic, which has increased the use of oxygen-supply equipment and potentially raised fire hazards. This case study, conducted in two university hospitals in Semnan, Iran, examined fire risk factors in healthcare facilities using a developed fire risk assessment method. A total of 28 wards and 74 compartments were assessed. Data collection included topographical structure analysis, building usage evaluation, and process documentation review. The FRAME method, validated in previous studies, was used to calculate fire risk levels for buildings, contents, occupants, and activities. The fire risk assessment revealed varying risk levels across different wards and compartments in the two hospitals. Hospital A exhibited higher fire risk levels compared to Hospital B, with several wards in Hospital A classified as "High" or "Very High" risk. Factors contributing to higher risk levels included building design, occupancy density, and the presence of flammable materials. Occupants in certain wards, particularly those with high occupancy rates and limited evacuation routes, were identified as being at increased risk. Activities such as the storage and handling of flammable materials were also found to contribute to elevated risk levels in specific areas. The study emphasizes the importance of implementing targeted fire safety measures, especially regarding oxygen-supplying equipment, high-density ventilators, and limited escape routes, to mitigate risks effectively in healthcare settings. This comprehensive assessment can guide best practices in fire safety management in hospitals.