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FM3VCF: A software library for accelerating the loading of large VCF files in genotype data analyses

The increasing size of genotype data has led to the loading of VCF files becoming a computational bottleneck in various analyses, including imputation and genome-wide association studies (GWAS). To address this issue, we developed a software library, FM3VCF (fast M3VCF), that utilizes multiple CPU threads to accelerate this process and compress VCF files into the more compact M3VCF format. FM3VCF can convert VCF files into the exclusive data format of MINIMAC4 and M3VCF and can efficiently read and parse data from VCF files. Compared with m3VCFtools, FM3VCF exhibits a speed improvement of approximately 36-fold in the compression of VCF files to the M3VCF format. This acceleration addresses a limitation faced by MINIMAC4 when dealing with datasets containing millions of samples. Furthermore, FM3VCF is approximately 3 times faster than HTSlib, including decompressing and parsing, for reading compressed VCF files. FM3VCF is an effective tool for both compressing VCF files efficiently and accelerating the loading of large VCF files in genotype data analyses. By fully utilizing multiple CPU threads, FM3VCF can significantly reduce the computational burden of various genomic analyses.

Immediate and short-term effect of physical exercise on BDNF in multiple sclerosis patients: a systematic review and meta-analysis

A comparative study of various statistical and machine learning models for predicting restaurant demand in Bangladesh

Precise demand forecasting has become crucial for merchants due to the growing complexity of client behavior and market dynamics. This allows them to enhance inventory management, minimize instances of stock outs, and enhance overall operational efficiency. In Bangladesh, there is a significant lack of emphasis on demand forecasting to enhance corporate performance. In recognition of these difficulties, the study seeks to produce predictions by employing two statistical models and three machine learning models. The historical sales data was obtained from a restaurant in Bangladesh, and five specific products were chosen for the purpose of predicting sales. The models have been rated according to their average score of deviation from the optimal root mean squared error. The Multilayer Perceptron and Random Forest algorithms have attained the top two positions. Statistical models such as simple exponential smoothing and Croston’s method have exhibited superior performance compared to XGBOOST model. This study advances demand forecasting techniques in Bangladesh’s restaurant industry by providing valuable insights, comparing different approaches, and suggesting ways to improve forecast accuracy and operational efficiency, thereby demonstrating the practical relevance and applicability of the research to the reader.

Research on optimal scheduling of integrated energy system based on improved multi-objective artificial hummingbird algorithm

To accelerate energy efficiency improvement and green transition in industrial parks while addressing energy utilization and carbon reduction requirements, this study proposes a low-carbon economic dispatch model for integrated energy systems (IES) based on an enhanced multi-objective artificial hummingbird algorithm (MOAHA). The main contributions are threefold: First, we establish an optimized dispatch model incorporating combined cooling, heating and power (CCHP) systems, a refined two-stage power-to-gas (P2G) conversion process, and carbon capture technologies. Second, a stepwise carbon trading mechanism is introduced to further reduce carbon emissions from the IES. Third, a multi-strategy enhanced MOAHA is developed through three key improvements: 1) Logistic-sine fused chaotic mapping for population initialization to enhance distribution uniformity and solution quality; 2) Elite opposition-based learning and adaptive spiral migration foraging mechanisms to optimize individual positions and population diversity; 3) Simplex method integration to strengthen local search capabilities and optimization precision. Comprehensive case studies demonstrate the model’s effectiveness, achieving an 82.9% reduction in carbon emissions and 17.3% decrease in operational costs compared to conventional approaches. The proposed framework provides a technically viable solution for sustainable energy management in industrial parks, effectively balancing economic and environmental objectives.

Dynamically weighted graph neural network for detection of early mild cognitive impairment

Alzheimer’s disease (AD) is a prevalent neurodegenerative disease that primarily affects the elderly population. The early detection of mild cognitive impairment (MCI) holds significant clinical importance for prompt intervention and treatment of AD. Currently, functional connectivity (FC) networks-based diagnostic methods for early MCI (eMCI) detection are widely employed. FC considers the interaction patterns between brain regions as a topological structure. Recently, graph neural network (GNN) approaches have been utilized for disease diagnosis using FC networks, leveraging their ability to extract features from topological structures. However, existing methods typically treat FC features as GNN node attributes, disregarding the fact that FC features represent the weights of connection edges in FC networks with topological characteristics. In this paper, we propose a dynamically weighted GNN-based approach for early eMCI detection. Our method takes into account the topological structure and dynamic properties of FC networks by utilizing temporal FC features as the weighted adjacency matrix for dynamic GNNs. Moreover, the weighted graph local clustering coefficient of brain regions is employed as the node feature for GNNs. We extensively evaluated our approach using the ADNI database and achieved accuracies of 91.67% and 78.33% on low- and high-order FC networks, respectively. These results demonstrate the effectiveness and superiority of our proposed method compared to existing approaches.

Male mice can grow female organs — if their mothers lack iron

Global burden and regional disparities of rheumatoid arthritis among the working-age population: A comprehensive analysis from 1990 to 2021 with projections to 2040

Objective To evaluate the age-standardized incidence (ASIR), prevalence (ASPR), death (ASDR), and disability-adjusted life year (DALY) rates of rheumatoid arthritis (RA) among the working-age population from 1990 to 2021. Methods The data is sourced from the Global Burden of Disease 2021. Estimated annual percentage change (EAPC) was utilized to assess temporal trends. Decomposition analysis was conducted to identify the driving factors underlying burden changes. The Slope Index of Inequality and the Concentration Index were employed to evaluate cross-country inequalities. Results In 2021, there were 11.88 million cases of RA in the working-age population globally and an ASPR of 222.68 per 100,000 population. The ASIR was 14.09 per 100,000 population (95% uncertainty interval [UI]: 8.97 − 20.19), while the ASDR was 0.13 per 100,000 population (95% UI: 0.11−0.15), with an EAPC of −1.59 (95% confidence interval [CI]: −1.73 to −1.45), indicating a sustained decline in RA ASDR. The age-standardized DALYs rate was 34.54 per 100,000 population (95% UI: 23.90 − 48.67), with an EAPC of 0.15 (95% CI: 0.10 to 0.20). Regionally, high Socio-Demographic Index (SDI) regions exhibited the highest ASPR, ASIR, and age-standardized DALYs rates, suggesting a greater overall burden of RA. Interestingly, middle SDI regions showed the highest ASDR, potentially indicating differences in disease management and access to care that impact mortality despite a lower overall burden compared to high SDI regions. Decomposition analysis identified population growth as the primary driver of the increasing RA burden. Cross-national inequality analysis revealed that RA burden remains concentrated in high SDI countries, though overall health inequality has declined. Conclusions The substantial global burden and regional disparities of RA in the working-age population necessitate targeted interventions. High SDI regions require strategies focusing on early diagnosis and optimal management to reduce the high burden. Elevated mortality in middle SDI regions demands improved access to effective treatment. These findings underscore the need for SDI-tailored public health approaches to address the specific challenges in each context.

Achieving green agricultural development: Analyzing the impact of agricultural non-point source pollution on food security and the regulation effect of environmental regulation

Food security is the lifeline of national security. It is not only an important cornerstone for world peace, stability, and development, but also the core driving force for promoting the green development of agriculture. This paper utilizes the empirical data of 30 provinces in China from 2010 to 2022 to explore how agricultural non-point source pollution (ANSP) affects food security (FS), and also discusses the moderating effect of environmental regulations (ER). Empirical research shows that the intensification of agricultural non-point source pollution will lead to a decline in the level of food security, especially in the western areas, grain-producing areas, and grain-balanced areas. Furthermore, environmental regulations have a positive moderating effect on the impact of agricultural non-point source pollution on food security. From the perspective of the spatial spillover effect, the inhibitory effect of agricultural non-point source pollution on food security has a spillover effect in space and will radiate to the development of food security in adjacent areas. The research suggests that the local government should enhance its attention and supervision over agricultural non-point source pollution, integrate agricultural technology with environmental supervision, optimize the allocation of agricultural resources, and attach importance to the protection of the agricultural ecological environment, so as to better ensure food security and achieve green agricultural development.

Polypyrimidine tract binding proteins PTBP1 and PTBP2 associate with distinct proteins and have distinct post-translational modifications in neuronal nuclear extract

RNA binding proteins play an important role in regulating alternative pre-mRNA splicing and in turn cellular gene expression. Polypyrimidine tract binding proteins, PTBP1 and PTBP2, are paralogous RNA binding proteins that play a critical role in the process of neuronal differentiation and maturation; changes in the concentration of PTB proteins during neuronal development direct splicing changes in many transcripts that code for proteins critical for neuronal differentiation. PTBP1 can compensate for the loss of PTBP2 in some developmental contexts but not others signifying the paralogs have distinct functions. How two highly structurally similar proteins regulate different sets of neuronal exons is unclear and if known, will reveal how gene families evolved to achieve tissue-specific splicing and in turn, gene expression patterns. Here, we incubated PTBP1 and PTBP2 under splicing reaction conditions containing neuronal WERI retinoblastoma nuclear extract and probed for interacting partner proteins and chemical modifications via mass spectrometry. Our results reveal key differences in the kinds of proteins and processes the paralogs associate with under these conditions. Our data also highlight the presence of novel and distinct chemical modifications on the paralogs when incubated with neuronal nuclear extracts. Collectively, our study suggests a role for chemical modifications in regulating PTBP function in neuronal vs non-neuronal cells.

Nutritional status of healthcare professionals in primary health and social care

Balanced nutrition is crucial for healthcare workers’ health and performance. Despite extensive knowledge of healthy eating, they face organizational and behavioral barriers leading to suboptimal diets. This study aimed to compare anthropometric status and dietary intake among male physicians, female physicians, and nurses in primary healthcare, and to identify deficiencies or excesses of key nutrients. A descriptive cross-sectional study was conducted in six clinics in Karaganda (2023–2024), involving 202 participants (22 male physicians, 67 female physicians, and 113 nurses). Body composition (weight, fat percentage, muscle mass, bone mass, metabolic age) was assessed via Tanita BC-418MA bioelectrical impedance. Dietary intake was measured using repeated 24-hour recalls for proteins, fats, carbohydrates, fiber, vitamins, and minerals. Statistical analysis included nonparametric methods (Kruskal–Wallis, Dunn’s test) and the Wilcoxon signed-rank test. Results showed insufficient intake of proteins, carbohydrates, dietary fiber, calcium, potassium, magnesium, phosphorus, and vitamins B₁, B₂, PP, and C. Sodium intake was excessive in all groups, whereas iron deficiency was observed only in women. Male physicians had higher body weight, muscle mass, and bone mass than female groups, but there were no significant differences in BMI, metabolic age, or overall dietary composition among the groups. Female physicians consumed slightly more vitamin C than nurses. In conclusion, gender and professional role minimally influenced dietary patterns among primary healthcare workers. Despite mostly normal BMI values, the pervasive lack of essential nutrients, coupled with high sodium and fat consumption, emphasizes the need for institutional measures such as structured schedules and healthier food options.

Adaptation of PCR-based library preparation for MGI platform for cancer mutation testing in clinical setting

MGI platforms hold promise to become a widespread instrument for various clinical next-generation sequencing applications, from whole genome sequencing to COVID-19 genotyping. However, in the clinical oncology setting it is still restricted to large panel sequencing limiting capacity for routine biomarker screening. In this article, we describe our experience of tailoring amplicon-based library construction for the MGI platform. Illumina compatible reagents served as a prototype in order to introduce platform specific adapters. Elaborated reagent kits were used for BRCA1/2 or 34 oncogenes testing both with whole blood and FFPE-derived DNA. Our data show that amplicon-based DNBSEQ-tailored library preparation demonstrates sufficient analytical efficiency in terms of coverage uniformity (average MAPD 1.08 and 1.19 for ABC plus and Atlas plus panels) and amplicon drop-out rate (ranging from 0.3% to 2.5%). Additionally, it shows efficiency in terms of single sample sensitivity, maintaining 99% sensitivity compared to 99% for the Illumina prototype. We show that it also outreaches expected diagnostic parameters of MGI exome sequencing (99% vs 95% for WES). Per-amplicon coverage of sticky-end libraries sequenced on Illumina and MGI were highly correlated demonstrating that the platform itself does not introduce any bias to amplicon coverage. Across three tested variations of library preparation protocol, discordances were related to ligation mix component composition and resulted in underrepresentation of GC-low and GC-high amplicons and low uniformity as a result. Overall, we outline the successful adaptation of PCR-based library preparation for MGI signifying the importance of tailoring component composition of reagent kit for uniform coverage.

Patient safety culture in public hospitals of Ethiopia: A systematic review and meta-analysis

Background Patient safety is a major health care challenge and is an issue of global concern. Poor healthcare system in Ethiopia, alongside increasing concerns for safety and patient safety culture, prompted to this systematic review and meta-analysis. Our systematic review and meta-analysis aims to determine the pooled prevalence of patient safety culture among healthcare providers in Ethiopia from studies that administered Hospital Survey on Patient Safety Culture (HSOPSC) tool. Method This study employed a systematic review and meta-analysis and followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. We carried out a comprehensive search for studies in Science Direct, Medline, African Journals Online (AJOL), Excerpta Medical Database (EMBASE), Scopus and Google Scholar to identify relevant observational studies published in the English language. Data sources were searched on the 10th of October 2024 and updated the search on the 29th of March 2025. All selected articles met the inclusion criteria according to the Participants, Intervention, Comparison and Outcome (PICOS) criteria.. Random effects model meta-analysis using STATA version 15 statistical software was conducted to estimate the pooled prevalence with 95% confidence intervals (CI). Funnel plot and I2 test were used to check publication bias and heterogeneity between studies, respectively. Subgroup analysis and leave-out-one sensitivity analysis was done. Results Searches retrieved a total of 667. After removing duplicates, 610 remained. 138 studies were reviewed in full, but only 14, which included 5,901 health care providers, were considered in the final meta-analysis. The pooled prevalence of patient safety culture among health care providers in public hospitals of Ethiopia was 45.52% (95% CI: 41.27, 49.76; I2 = 91.3; p-value<0.001). Conclusion and Implications Patient safety culture among health care providers in Ethiopia remained poor. These findings underscore the need for increased focus on education and training, development of guidelines and policies for patient safety to integrate a patient safety culture into the existing health system. Additionally, integrating patient safety education and training topics early in pre-service curricula is crucial. Registration Registered in PROSPERO database with registration number of CRD42023407601

Shear performance evaluation of sustainable concrete beams containing rice husk ash and carbon nanotubes as cement replacement

The utilization of rice husk ash (RHA) as a cement substitute in concrete can mitigate the environmental issues caused by concrete production. This study is the first investigated the effect of different concentrations of multiwall carbon nanotubes (MWCNTs) on the shear behaviour of RHA-reinforced concrete (RC) beams. Three RHA RC beams incorporating different MWCNTs concentrations (0%, 0.1%, and 0.2%) were subjected to shear failure tests, with shear behaviour evaluated based on load-deflection capacity, failure load, strain distribution, and crack development morphology. The results indicate that the incorporation of well-dispersed MWCNTs (0.1%) significantly enhances the shear resistance of RHA RC beams. Specifically, with the addition of 0.1% MWCNTs, the first crack load, initial stiffness, and ultimate shear capacity increased by 34.78%, 38.4%, and 4.76%, respectively, while midspan deflection and ductility improved by 23.19% compared to the control specimen. However, excessive MWCNTs incorporation negatively impacted shear capacity, as the inclusion of 0.2% MWCNTs led to an 8.57% reduction in the ultimate shear capacity of the RHA RC beam. Additionally, the experimental results were compared with predictions from several models, including the ACI 318 model, Eurocode 2–05 model, Canadian standard, Bazant and Kim, Zsutty, and Collins and Kuchma models. The comparison revealed that the Eurocode 2–05 model, Canadian standard, and Zsutty models provide reliable predictions of the shear behaviour of RHA RC beams, with an error margin within 20%. The findings suggested that well-dispersed MWCNTs can play a role in improving the initial stiffness and ductility of RHA RC beams, enhancing the shear resistance of the beams, delaying shear failure, and preventing brittle failure of the beams. Furthermore, the improvement of the performance of RHA sustainable concrete components by MWCNTs contributes to the sustainable development of the construction industry.

Growth dynamics and protein-expression of Escherichia coli serotypes O26:H11, O111:H8 and O145:NM in the bovine rumen

To adapt to the ruminal environment, Shiga toxin-producing Escherichia coli (STEC) O157:H7 (O157) expresses proteins involved in survival rather than virulence. Additionally, STEC O157 strains exhibit distinct in vitro but shared in vivo survival patterns in rumen fluids that sets them apart from non-STEC, commensal E. coli. To determine if similar responses would be observed with other STEC, we evaluated three non-O157 serotypes, O26:H11, O111:H8 and O145:NM, along with a non-STEC E. coli, under the growth conditions used for STEC O157: (i) anaerobically, in vitro, in rumen fluid from cattle on a lactation (low fiber, high protein) or maintenance (high fiber, low protein) diet, at 39oC for 48 hr and (ii) in vivo for 48 hr within the rumen of cattle on the same diets using a non-terminal, rumen-fistulated animal model that allows for introduction of bacteria without ruminal contamination. On the lactation diet, the ruminal pH was acidic ranging from 5.2–6.0 and the total volatile fatty acids (VFA) concentration, 141–230 μM/ml. On the maintenance diet, the ruminal fluid pH was close to neutral ranging from 6.0–7.0, with a total VFA of 87–190 μM/ml. Unlike STEC O157, the three non-O157 serotypes demonstrated survival patterns similar to each other and the control non-STEC E. coli. A greater reduction in viable STEC counts was observed in vitro in rumen fluid from cattle fed the lactation diet than in vivo, corroborating previous reports that in vitro conditions cannot mimic those observed in vivo. Like STEC O157, the non-O157 serotypes mainly expressed proteins supporting ruminal adaptation although not all proteins matched those expressed by STEC O157, and included the virulence protein, intimin. Explorative studies such as this could provide insights into common conditions/ targets that may have application in broader STEC control in cattle. Importance of this study This study demonstrates that non-O157 serotypes O26:H11, O111:H8, O145:NM have similar survival and protein expression patterns in rumen fluid with variations being influenced primarily by rumen fluid composition associated with diet. Unlike STEC O157, under in vivo conditions, the growth dynamics of the non-O157 serotypes were comparable to that of non-STEC, commensal E. coli. Hence, exploring bacterial protein expression within the host is critical in discerning therapeutic targets, unique to/shared between STEC, for broad control strategies. In addition, this study further validates the value of using a non-terminal animal model for rumen studies that reduces number of animals used for an experiment.

The third intracellular loop of Drosophila Lilipod is required for protein function in vivo and can mediate protein-protein interactions in vitro

The evolutionarily conserved Lipocalin-Interacting Membrane Receptor (LIMR) family (InterPro: IPR006876) consists of transmembrane (TM) proteins characterized by 9 TM domains (TMDs). Their reported biological functions are diverse and remain poorly understood. In previous work, we showed that the fly family member Lilipod (Lili) impacts biological processes regulated by the fly BMP/TGF-β ligand Decapentaplegic (Dpp), including germline stem cell self-renewal in the Drosophila ovary, dorsal closure during embryonic development and wing vein formation at the pupal stage. Based on this genetic evidence, Lili directly or indirectly enhances bone morphogenetic protein (BMP) signaling. In the ovary, Lili functions between the activated type I BMP receptor and the SMAD intracellular transducer. To gain insight into Lili function at the cellular and molecular levels, we probed the functional significance of its largest intracellular loop, Intracellular Loop 3 (ICL3). Through mutational analysis, we mapped sequences critical for Lili function in vivo to the evolutionarily conserved regions of ICL3. Additionally, we showed that fly-human chimeric proteins in which Lili ICL3 is replaced with the ICL3 of its human homologs, LMBR1 and LMBR1L, can rescue lili null-mutant phenotypes. Using ICL3 as bait in an unbiased Yeast 2-Hybrid (Y2H) screen, we identified putative interactors, including the BMP signaling cascade components Mad, Sara, Nup93 and Nup358, and further Y2H analyses identified distinct regions on ICL3 as potentially important for protein binding. Taken together, our work has identified ICL3 as a region that is critical for Lili protein function, most likely via its mediation of protein-protein interactions (PPIs).

Male mice can grow ovaries if their pregnant mums are iron deficient

Retraction: Determining the appropriate level of farmyard manure biochar application in saline soils for three selected farm tree species

“I’ve not been knocked out, so I’ll probably be fine:” Amateur Rugby players do not know the risks they are taking

Concussion is prevalent in British amateur Rugby and there is currently contradicting evidence of the attitudes and knowledge of concussion in Rugby players. As such this study aimed to investigate the reasons for the variance in attitudes and knowledge of concussion in British amateur Rugby. As concussion is a lived experience within sport, we utilised qualitative interviews using reflexive thematic analysis to assess data obtained from nine amateur Rugby players that had sustained over three concussions to understand if they are aware of the known risks associated with such injuries. Our findings show that poor duty of care from those around the player with suspected concussion was prevalent, and that this poor duty of care enables poor attitudes toward and limited knowledge of concussion. It was also discovered that a lack of education could explain this poor duty of care that is offered to Rugby players by non-players. Poor duty of care and lack of education encourage continued participation from the player with suspected concussion. When there are examples of World Rugby failing in their duty of care of the best players in the world, it is unsurprising that players and non-players in the amateur game follow suit. Therefore, the education of both players and non-players in amateur Rugby matches is paramount, as well as World Rugby improving their concussion practices, in tackling the poor attitudes and knowledge base that we see in the amateur Rugby game.

Enhancing time synchronization between host and node stations using a fuzzy proportional-integral approach for EtherCAT-based motion control systems

Real-time synchronization for the servo system becomes one of the most popular themes in the Industry 4.0 era. Each connected agent publishes its data and mutual information in the shared protocol while host station plays a role as coordinator among them. In the existing works, it reveals several drawbacks owing to low adaptability and inestimable redundancy. Hence, our study presents a novel method to synchronize between host and slaves by using the modified EtherCAT-based Type-2 Fuzzy-Proportional-Integral (mET2FuPI) control scheme. To serve our purpose, a custom platform of EtherCAT host is investigated to maintain the powerful resource in both data exchange and theoretical computation. The experimental validations of our system including one host station and three node stations are tested to measure the synchronized performance. From these results, it can be obviously seen that our approach is effective and feasible to deploy in the real-world applications.

Conservation of fish diversity in protected sites and adjacent fishing areas of the Southern Mexican Pacific Ocean

The global decline in marine biodiversity is accelerating, prompting Mexico’s government to establish marine protected areas to regulate human activities. The objective of this study was to test whether there were differences in fish taxonomic and functional diversity among protected reef sites within Parque Nacional Huatulco and adjacent non-protected (NP) zones, as well as whether the temporal trends in fish diversity, density, and biomass of commercial and non-commercial species differed in relation to these human use levels. It was hypothesized that fish functional diversity would be similar among protected and NP sites, given that fishing and tourism activities persist at protected sites. Concurrently, taxonomic and functional diversity decline was predicted, associated with decreasing commercial species due to increasing human activities in both zones. We collected data from underwater monitoring conducted by SCUBA divers (2006–2020) at 20 coral and rocky reef sites to calculate taxonomic and functional diversity metrics based on six biological traits. Functional diversity metrics were employed to analyze the resemblance among human use levels. Additionally, ecological indicators were incorporated as response variables in linear models to assess temporal changes. The results demonstrated functional diversity resemblance among human use levels, as well as temporal stability in Simpson’s dominance index and significant increases in fish species richness and density at both zones. For protected sites, significant changes in fish functional diversity (increase in functional richness and decrease in divergence and originality), could indicate positive effects of protection, such as functional redundancy increases and the capacity to maintain reef functions over time. Commercial and non-commercial species exhibited stability or increase in density and biomass at both protected and NP sites.