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The impact of political assassinations on turnout: Evidence from Colombia
Although a growing literature has investigated the effects of various types of civil war violence on political behavior, no study has examined the impact of assassinations targeting politicians. This is a critical omission, as violence against local politicians is prevalent across civil war contexts and may be the most consequential form of violence for political participation by affecting both candidate supply and voter demand. Using an original dataset of nearly 2,000 killings of Colombian local politicians between 1980 and 2023, we estimate the impact of this violence on voter turnout. Taking municipalities where assassination attempts failed as a comparison group, we find that political assassinations significantly decrease voter turnout in both the short and medium terms, with effects persisting in various elections even after the signing of a peace agreement. These findings contrast with many studies suggesting that other forms of civil war violence enhance political participation during the postconflict period or after a truce or peace agreement. Our results suggest that different forms of violence can have distinct effects on political behavior, underscoring the need to theorize how the targeting, nature, and context of violence condition its effects. This echoes calls for more nuanced studies on the behavioral impacts of violence. Our findings also have implications for understanding democracy amid rising violence against political leaders in countries affected by organized crime, such as Mexico and Brazil; polarized contexts, such as the United States; and weakly institutionalized democracies, such as South Africa, Indonesia, and the Philippines.
Individual participant data network meta-analysis of psychosocial interventions for survivors of intimate partner violence: Study protocol
Many systematic reviews and meta-analyses have been conducted in the field of Intimate Partner Violence (IPV) and the evidence shows small to moderate effect sizes in improving mental health outcomes. However, there is considerable heterogeneity due to variation in participants, interventions and contexts. It is therefore important to establish which participant and intervention characteristics affect the different psychosocial outcomes in different contexts. Individual Participant Network Meta-analysis (IPDNMA) is a gold-standard method to estimate moderating effects, compare the effectiveness of different interventions and thus answer the question of which intervention is best-suited for whom. We will conduct an IPDNMA of randomised controlled trials (RCTs) of psychosocial interventions for IPV survivors aimed at improving mental health, psychosocial outcomes such as self-efficacy and quality of life, reducing IPV and increasing safety-behaviours and dropout from the intervention (as an indication of intervention acceptability) compared to any type of control (PROSPERO registration number: CRD42023488502). We aim to establish collaborations with the authors of eligible RCTs, to obtain and harmonise the Individual Participant Data of the trials. We will conduct one-stage IPDNMA under a Bayesian framework using the multinma package in R, after testing which characteristics of the participants and interventions are effect modifiers. We anticipate that not all study authors will provide access to IPD, which is a limitation of IPDNMA. We aim to address this by combining studies with aggregate data and studies with IPD using Multi-Level Network Meta-Regression (ML-NMR) implemented in the multinma R package. This approach is novel in the field and makes full use of available evidence to inform clinical and policy-related decision making.
Research on the comprehensive dessert evaluation method in shale oil reservoirs based on fractal characteristics of conventional logging curves
Abstract The traditional logging evaluation of comprehensive sweet spots in shale oil reservoirs has problems such as complex explanatory parameters, incompatible quantitative characterization scales, and low-cost efficiency. A method based on the fractal characteristics of conventional logging curves is proposed to evaluate the comprehensive sweet spots of fractured horizontal wells in shale oil reservoirs. Firstly, the existing evaluation parameters and methods were reviewed, pointing out the limitations of traditional logging evaluation methods. Furthermore, we analyzed 63 fractured sections from three horizontal fractured wells in the Yingxiongling shale oil reservoir of the Qinghai Oilfield, using tracer monitoring data. By applying wavelet transform to reduce noise in high-frequency signals from conventional logging curves, we then used multifractal spectrum analysis and R/S analysis to extract the multifractal spectrum width (∆α) and fractal dimension (D) from four conventional logging attributes: natural gamma logging (GR), acoustic time difference logging (AC), density logging (DEN), and neutron logging (CNL). A multi-attribute comprehensive fractal evaluation index was developed by using the post-fracturing tracer monitoring profile as a constraint and applying the grey relational analysis method. This approach enabled a quantitative classification and evaluation of the key sweet spots in shale oil reservoirs after fracturing. The results show that the comprehensive fractal evaluation index of the high-yield well section after Class I layering is 0.75<∆ α‘<1, 0 < D‘<0.25; 0.35<∆ α‘<0.75, 0.25 < D‘<0.8 in the middle well section of Class II layer; Class III low production well Sect. 0<∆ α‘<0.35, 0.8<∆ α‘<1. Finally, a prediction model for physical property parameters characterized by fractals was introduced using machine learning algorithms, which is 31.9% more accurate than the conventional interpretation physical property parameter prediction model for the comprehensive sweet spot of fracturing. This evaluation method is a concise approach to comprehensively evaluate the sweet spot area based on the extraction of multifractal spectral characteristic parameters from conventional logging data. It is of great significance for characterizing the volume fracturing effect of shale oil and providing technical support for the effective development of shale on a large scale.
“Kids and Girls”: Parents convey a male default in child-directed speech
Adults tend to view men (more so than women) as default people , with numerous real-world consequences for gender equity. In the United States, the tendency to center men in concepts of people develops across middle childhood, yet the specific mechanisms that contribute to it remain unknown. Here, we investigate one subtle but potentially powerful social mechanism: the category labels that parents use to describe boys/men and girls/women in conversations with their children. Across two studies ( N = 822 parent–child dyads, predominantly from the United States), parents used gender-neutral labels like “kid” or “person” more often to describe boys/men than girls/women and, conversely, used gender-specific labels (e.g., “girl”) more often to describe girls/women than boys/men. These patterns emerged when parents were shown gender-stereotypical girls/women and boys/men (e.g., a girl painting her nails, a boy digging for worms); when parents viewed counterstereotypical stimuli (e.g., a boy painting his nails, a girl digging for worms), the patterns reversed. Our findings illuminate parents’ category label usage as a critical social mechanism that may undergird the development of a male default in a US cultural context, informing efforts to intervene on this process.
Comparative analysis of translatomics and transcriptomics in the longissimus dorsi muscle of Luchuan and Duroc pigs
IMF (Intramuscular fat) content is a crucial indicator of meat quality in the livestock industry. However, the molecular mechanisms underlying IMF deposition remain unclear in pigs. In this study, we conducted RNC-seq (ribosome nascent-chain complex-bound RNA sequencing) and RNA-seq (RNA sequencing) analyses on the longissimus dorsi muscle of Duroc pigs (a lean breed) and Luchuan pigs (a fat breed) to uncover the genetic basis for the divergent IMF content. The results show that the overall translation level of Luchuan pigs is significantly higher than Duroc pigs, while there is no significant difference in the transcription level. Enzymes related to fatty acid synthesis and elongation, such as ACACA, FASN, and ELOVL5, are significantly up-regulated at the translation level, while enzymes associated with fatty acid degradation, namely ALDH1B1 and ALDH2, are significantly down-regulated. However, there is no significant difference in their transcription levels. qRT-PCR and Western Blotting experiments for ELOVL5 confirm the reliability of the sequencing results. Additionally, the translation initiation factor eIF4A1, known to positively regulate gene translation, displayed higher expression in Luchuan pigs rather than in Duroc pigs and the 5’UTR structural features of genes involved in translation up-regulation matched the mRNA selectivity of eIF4A1. In conclusion, these findings suggest the up-regulation of the eIF4A1 gene expression in Luchuan pigs may elevate the translation levels of genes related to lipid synthesis through translational regulation, further resulting in an increase in IMF content.
Independent genetic basis of meiotic crossover positioning and interference in domestic pigs
Abstract Meiotic crossover patterning shows huge variation within and between chromosomes, individuals, and species, yet the molecular and evolutionary causes and consequences of this variation remain poorly understood. A key step is to understand the genetic architecture of the crossover rate, positioning, and interference to determine if these factors are governed by common or distinct genetic processes. Here, we investigate individual variation in autosomal crossover count, crossover position (measured as both intra-chromosomal shuffling and distance to telomere), and crossover interference in a large breeding population of domestic pigs (N = 82,474 gametes). We show that all traits are heritable in females at the gamete (h2 = 0.07–0.11) and individual mean levels (h2 = 0.08–0.41). In females, crossover count, and interference are strongly associated with RNF212, but crossover positioning is associated with SYCP2, MEI4, and PRDM9. Our results show that crossover positioning and rate/interference are driven by distinct genetic processes in female pigs and have the capacity to evolve independently.
Human stem cells with in vivo high plasticity generated by cell–cell communication
Stem cells possess inherent properties of self-renewal and differentiation, and thus hold significant promise for regenerating damaged tissues or replacing lost cells. Unless their therapeutic effects are solely mediated by paracrine, transplanted stem cells need to be highly plastic to adapt to the host tissue environment and differentiate into constituent tissue-specific cells for tissue repair. Stem cells used in current cell-based therapies either have limited differentiation potential or are pluripotent but must be strictly restricted to avoid tumorigenicity risk in vivo. Here, we describe the derivation of human adult high-plasticity stem cells, which we call guide-integrated adult stem cells (giaSCs), from the interaction of blood-derived guide cells and umbilical cord tissue–derived mesenchymal stromal cells (UC-MSCs). The guide cells are a cell population derived from the peripheral blood of human adults. Unidirectional transfer through nanotube-like structures of granular substances from the guide cells into the recipient UC-MSCs gave rise to giaSCs. Topical application of human giaSCs into full-layer excisional wounds of wild-type mice led to reconstitution of skin tissue. Systemically administered human giaSCs migrated to and reside in mouse small intestinal tissue damaged by lipopolysaccharides and then differentiated into small intestinal epithelial cells for tissue repair. These transplantation experiments demonstrated that giaSCs have in vivo high plasticity. Additional in vivo and in vitro data showed that giaSCs have low immunogenicity and are nontumorigenic. These data indicate that giaSCs offer a highly promising approach to stem cell therapy.
Predicting dietary management intention of patients with chronic kidney disease using protection motivation theory
Background Psychological determinants underlying the dietary management intention (DMI) of Chinese patients with chronic kidney disease (CKD) are not well understood. This hinders the development of theory-informed dietary interventions targeting this population. The aim of this study was to identify factors influencing DMI of Chinese patients with CKD through the lens of Protection Motivation Theory (PMT). Methods 500 patients with CKD from a nephrology ward of a large teaching hospital in China completed a survey including measures of PMT constructs (i.e., perceived vulnerability, perceived severity, intrinsic and extrinsic rewards, self-efficacy, response efficacy, and response cost) using validated scales adapted from previous studies. Data were analyzed using confirmatory factor analysis and multiple linear regression. Results Three PMT constructs, namely perceived severity [B = 0.198, P < 0.001], response efficacy [B = 0.331, P < 0.001], and self-efficacy [B = 0.325, P < 0.001], two demographic variables, namely single status [B = -0.180, P = 0.028] and education level [B = 0.080, P = 0.007], and a disease-related variable, namely CKD stage [B = .056, P = 0.001], predicted 39.3% of the variance of the CKD DMI. No significant effect on CKD DMI was observed for other predictor variables (P > 0.05). Conclusions Applying the PMT, significant predictors of DMI in Chinese patients with CKD were identified, which should be targeted in behavior change initiatives aimed at promoting dietary management.
Neutrophil elastase binds at the central domain of extracellular Toll-like receptor 4: AI prediction, docking, and validation in disease model
Pattern separation and pattern completion in early childhood
Pattern separation, or distinguishing similar experiences from one another, and pattern completion, in which components of an experience prompt retrieval or forgetting of an event pattern as a unit, are essential components of episodic memory. However, these two components are sometimes described as opposite ends of a continuum and sometimes described as independent processes. Here, we examined the relations between the two processes for the same events in children between 4 and 7 y. Mnemonic discrimination (the behavioral signature of pattern separation) improved with age; holistic recollection (the behavioral signature of pattern completion) did not change in this age range. Crucially, the two behaviors were unrelated, controlling for the effect of age, and even when examining their relations at the fine-grained level of memory for individual events.
A Swedish genome-wide haplotype association analysis identifies novel candidate loci associated with endometrial cancer risk
Genome-wide association studies [GWAS] have identified a limited number of endometrial cancer risk loci by analyzing single nucleotide polymorphisms [SNPs]. We hypothesized that analyzing haplotypes rather than SNPs could provide novel and more detailed information on genetic cancer susceptibility loci. To examine the association of a SNP or haplotype with endometrial cancer risk we performed a two-stage haplotype GWAS. The discovery GWAS included a sub-cohort of 1,116 Swedish endometrial cancer cases and 5,021 controls from previously published GWAS data. A sliding window analysis was employed with window sizes of 1-25 SNPs using a logistic regression model. The Swedish haplotype analysis identified 15 novel candidate risk loci (2q31.1, 4p16.1, 4p15.31, 6q13, 7p21.1, 9p13.3, 10q26.3, 11q21, 12q13.11, 13q12.11, 15q13.3, 16q24.3, 19q13.32, 20p12.3 and 22q13.2) with OR ranging from 1.6 to 3.3 and p-values from 4.25 × 10−8 to 9.86 × 10−15. A second replication haplotype analysis of the Swedish novel loci was performed using two cohorts from Belgium and Germany. In spite of small sample sizes in the replication cohorts, there was still support for most loci with positive ORs. In addition, the findings in the two European cohorts motivates further studies to search for founder haplotypes. These novel findings suggested that endometrial cancer loci, identified through haplotype analysis, conferred a higher risk compared to previous single-variant GWAS.
Two stage multiobjective topology optimization method via SwinUnet with enhanced generalization
Enhancement of mitochondrial calcium uptake is cardioprotective against maladaptive hypertrophy by retrograde signaling uptuning Akt
Regulation of mitochondrial Ca 2+ uptake is critical in cardiac adaptation to chronic stressors. Abnormalities in Ca 2+ handling, including mitochondrial uptake mechanisms, have been implicated in pathological heart hypertrophy. Enhancing mitochondrial Ca 2+ uniporter (MCU) expression has been suggested to interfere with maladaptive development of heart failure. Here, we addressed whether MCU modulation affects the cardiac response to pressure overload. MCU content was quantified in human and murine hearts at different phases of myocardial hypertrophy. Cardiac function/structure were analyzed after Transverse Aortic Constriction (TAC) in mice undergone viral-assisted overexpression or downregulation of MCU. In vitro and ex vivo assays determined the effect of MCU modulation on mitochondrial Ca 2+ uptake, cellular phenotype and hypertrophic signaling. In human and murine hearts MCU levels increased in the adaptive phase of myocardial hypertrophy and declined in the failing stage. Consistently, modulation of MCU had a cell-autonomous effect in cardiomyocyte/heart adaptation to chronic overload. Indeed, upon TAC MCU-downregulation accelerated development of contractile dysfunction, interstitial fibrosis and heart failure. Conversely, MCU-overexpression prolonged the adaptive phase of hypertrophic response, as, in advanced stages upon TAC, hearts showed preserved contractility, absence of fibrosis and intact vascularization. In vitro and ex vivo analyses indicated that enhancement in mitochondrial Ca 2+ uptake in cardiomyocytes entails “mitochondrion-to-cytoplasm” signals leading to ROS-mediated activation of Akt, which may explain the protective effects towards heart response to TAC. Enhanced mitochondrial Ca 2+ uptake affects the compensatory response to pressure overload via retrograde mitochondrial-Ca 2+ /ROS/Akt signaling, thus uncovering a potentially targetable mechanism against maladaptive myocardial hypertrophy.
Retraction: Design and development of human resource management computer system for enterprise employees
Identifying novel risk factors for aneurysmal subarachnoid haemorrhage using machine learning
Abstract Aneurysmal subarachnoid haemorrhage (aSAH) is a type of stroke with high mortality and morbidity. This study aimed to identify novel aSAH risk factors by combining machine learning (ML) and traditional statistical methods. Using the UK Biobank, we identified aSAH cases via hospital-based ICD codes and analysed 618 baseline variables covering demographics, lifestyle, medical history, and physical measurements. The CatBoost ML algorithm and Shapley Additive Explanations (SHAP) identified the top 25 variables most influential in predicting aSAH. Logistic regression further described these variables while adjusting for established aSAH risk factors. Among 501,847 participants, 893 aSAH cases were identified. ML identified 214 variables with non-zero SHAP values. Logistic regression of the top 25 variables revealed four potential novel aSAH risk factors. Increased aSAH risk was associated with mean sphered cell volume (OR 1.02, 95% CI 1.00-1.03) and tea intake (OR 1.03, 95% CI 1.01–1.05). Decreased aSAH risk was associated with peak expiratory flow (OR 0.80, 95% CI 0.66–0.96), and haematocrit percentage (OR 0.97, 95% CI 0.95-1.00). Future research should validate these findings and explore the potential non-linear relationships and interactions indicated by the ML models.
Dual mRNA nanoparticles strategy for enhanced pancreatic cancer treatment and β-elemene combination therapy
Pancreatic ductal adenocarcinoma (PDAC) is notoriously immune-resistant, limiting the clinical efficacy of single-agent immune modulators and thereby necessitating the exploration of multimodal immunotherapy combinations. Traditional approaches combining conventional immune checkpoint inhibitors with neoantigen vaccines have shown some promise in treating PDAC but are often compromised by intratumoral T lymphocyte exhaustion and systemic toxicity. Hence, novel approaches are needed to address these challenges. Herein, we demonstrate that mRNA polymeric nanoparticles encoding anti-PD-1 antibodies in situ at the tumor site enhance the therapeutic efficacy of neoantigen-based mRNA vaccine for PDAC. This mRNA-based, in situ anti-PD-1 antibody production strategy also protects tumor-infiltrating T cells from PD-1 inhibition, potentially reducing the toxicities induced by systemic checkpoint inhibition. Our study may provide an innovative dual mRNA nanoparticle strategy for effective tumor neoantigen immunotherapy, as well as an mRNA cancer combination therapy strategy with other clinically approved drugs (e.g., β-elemene).
The association between oral health and risk behaviours of university students
Background Young adults are exposed to a variety of risk-related behaviours such as alcohol, smoking, and changes in dietary habits, which may result in unknown outcomes in their oral health. There is limited evidence on whether different risk behaviours are associated with oral health behaviours in the university student population. This study gathers data on the behaviours of students in their first year of university, which will inform the future development of oral health behaviour change interventions for this population. Method This longitudinal quantitative survey involved 205 first-year students aged 18-24 at the University of Manchester. Students completed online questionnaires at baseline and again at a 6-month follow-up interval, providing information regarding self-reported oral health status, hygiene routines, and risk behaviours (e.g., diet, smoking, alcohol). Results The findings showed associations between oral health behaviours with risk behaviours, including links with oral care routines, bleeding gums, brushing frequency, with exercise, vaping, and unhealthy food and drink intake. Significant changes over the two-time points were also observed, including the worsening of the self-reported condition of the teeth (p < 0.001), a reduction in the self-reported condition of the gums (p = 0.004), a decrease in brushing frequency (p = 0.003), fewer regular dental visits (p = 0.013), more students intending to visit their previous dentist rather than finding a new dentist at university (p = 0.026), and greater consumption of unhealthy non-alcoholic drinks (p = 0.003). Positive changes over time included reduced frequency and units of alcohol consumption (p = 0.030 and p = 0.001), fewer instances of binge drinking (p = 0.014), and less frequent consumption of unhealthy foods (p = 0.034). Conclusion The findings highlighted the complex relationship between oral health and risk behaviours in this demographic. Poorer oral health behaviours were linked to engagement in risk behaviours. Thus, oral health behaviours should be targeted alongside other risk behaviours, and tailored interventions should be developed to improve behaviours among university students.
Diagnostic accuracy of screening and diagnostic tests used in a state-wide tuberculosis prevalence survey in India
Bacterial motility depends on a critical flagellum length and energy-optimized assembly
The flagellum is the most complex macromolecular structure known in bacteria and is composed of around two dozen distinct proteins. The main building block of the long, external flagellar filament, flagellin, is secreted through the flagellar type-III secretion system at a remarkable rate of several tens of thousands of amino acids per second, significantly surpassing the rates achieved by other pore-based protein secretion systems. The evolutionary implications and potential benefits of this high secretion rate for flagellum assembly and function, however, have remained elusive. In this study, we provide both experimental and theoretical evidence that the flagellar secretion rate has been evolutionarily optimized to facilitate rapid and efficient construction of a functional flagellum. By synchronizing flagellar assembly, we found that a minimal filament length of 2.5 μm was required for swimming motility. Biophysical modeling revealed that this minimal filament length threshold resulted from an elasto-hydrodynamic instability of the whole swimming cell, dependent on the filament length. Furthermore, we developed a stepwise filament labeling method combined with electron microscopy visualization to validate predicted flagellin secretion rates of up to 10,000 amino acids per second. A biophysical model of flagellum growth demonstrates that the observed high flagellin secretion rate efficiently balances filament elongation and energy consumption, thereby enabling motility in the shortest amount of time. Taken together, these insights underscore the evolutionary pressures that have shaped the development and optimization of the flagellum and type-III secretion system, illuminating the intricate interplay and cost-benefit tradeoff between functionality and efficiency in assembly of large macromolecular structures.
Single image de-raining by multi-scale Fourier Transform network
Removing rain streaks from a single image presents a significant challenge due to the spatial variability of the streaks within the rainy image. While data-driven rain removal algorithms have shown promising results, they remain constrained by issues such as heavy reliance on large datasets and limited interpretability. In this paper, we propose a novel approach for single-image de-raining that is guided by Fourier Transform prior knowledge. Our method utilises inherent frequency domain information to efficiently reduce rain streaks and restore image clarity. Initially, the rainy image is decomposed into its amplitude and phase components using the Fourier Transform, where rain streaks predominantly affect the amplitude component. Following this, data-driven algorithms are employed separately to process the amplitude and phase components. Enhanced features are then reconstructed using the inverse Fourier Transform, resulting in improved clarity. Finally, a multi-scale neural network incorporating attention mechanisms at different scales is applied to further refine the processed features, enhancing the robustness of the algorithm. Experimental results demonstrate that our proposed method significantly outperforms existing state-of-the-art approaches, both in qualitative and quantitative evaluations. This innovative strategy effectively combines the strengths of Fourier Transform and data-driven techniques, offering a more interpretable and efficient solution for single-image de-raining (Code: https://github.com/zhengchaobing/DeRain).