Browse Articles

Automated mapping of DNA replication fork progression in human cells with ForkML

Abstract Current approaches to mapping fork progression in the human genome suffer from drastically low throughput. Here, we introduce ForkML, a nanopore sequencing-based method automatically positioning thousands of individual fork velocities by tracking BrdU incorporation into replicating DNA after double pulse-labelling of asynchronous cells. ForkML recovers known human fork speed, accurately detects replication stress, and, crucially, connects replication dynamics to genomic and chromatin contexts, exposing fork slowdown in early-replicating transcribed regions.

Towards multi-modal and cross-modal integration in LiFi-based sensing

Exploring postnatal and newborn home care experiences of rural and remote mothers in Pakistan whose neonates were admitted to the hospital: A qualitative study

Background The neonatal mortality rate in Pakistan has been the second highest worldwide. Since mortality rate is higher in rural area than in urban area, to understand newborn care and response to progressing disease by rural families is vital to comprehend the background of poor neonatal outcomes. But in Pakistan research on newborn home care is scarce. This study aimed to understand the local context of neonatal morbidity derived from rural and remote Pakistan by exploring the postnatal and newborn home care experiences of mothers whose neonates required admission after being cared for at home. Methods This qualitative descriptive study conducted in-depth, individual, semi-structured interviews with 15 mothers and three family members with children admitted to the neonatal unit of a tertiary hospital from home. Seven pediatric and obstetric staff were also interviewed for data triangulation. Thematic analysis was used to extract themes and sub-themes, and to develop a thematic map. Results Lack of early initiation and exclusive breastfeeding, administration of prelacteals, and suboptimal bathing, wiping, wrapping, and umbilical cord care were identified; they were influenced by family experiences. Short postnatal stays, and lack of postnatal care and health education from facilities, left mothers with traditional care only. Very low birth weight neonates had been cared for at home. From the analysis, five themes were identified. They were gender roles, health literacy, health seeking behavior, lack of preventive care, and a high burden of low birth weight. Conclusion This study identified local newborn home care influenced by familial traditional norms that could make neonates susceptible to infection, dehydration, malnutrition, and hypothermia. Multiple healing approaches and health service quality may have affected families’ ability to seek timely medical attention. Strengthening facility preventive care, and families’ health literacy through culture-sensitive health education, is essential in antenatal and postnatal care, and during admission. Appropriate timing of home discharge, with newborn care counselling, is also vital, considering the high burden of preterm births and low birth weight.

The impact of K selection in K‑fold cross-validation on bias and variance in supervised learning models

Enhancing surveillance of sexually transmitted infections in England with gender identity and behavioural data: The GUMCAD STI Surveillance System

Background There has been an increasing trend in bacterial sexually transmitted infections (STIs) in England since the early 2000s. Since 2008, surveillance of STIs in England has been conducted using the Genitourinary Medicine Clinic Activity Dataset (hereafter referred to as ‘GUMCAD’), a depersonalised dataset of all attendances at all publicly-commissioned sexual health services (SHS). The aim of is this article is to describe and evaluate the piloting and rollout of an enhanced specification of GUMCAD at SHS in England. Methods GUMCAD was enhanced in 2019 to allow SHS to report the gender identity (whether cisgender, transgender, gender diverse) of service users, and selected behavioural information collected during routine sexual history-taking such as the number of recent sex partners (last 3 months). Results Feasibility and acceptability of reporting these new data were confirmed in the pilot stage. 2023 was the first year over which most SHS (93%, 224/241) submitted enhanced GUMCAD data. Of all 4,610,410 consultations at SHS in 2023, gender identity (96% of consultations) and data on whether this varied from the sex registered at birth (88% of consultations) were well reported. Transgender women, transgender men, and gender-diverse individuals (identifying as non-binary or in any other way) respectively comprised 0.4%, 0.4%, and 0.5% of all consultations in 2023. There was less complete reporting of recent sex partners but, where reported, gay, bisexual and other men who have sex with men were more likely to report multiple recent sex partners. Conclusions This enhancement provides novel insights into sexual health need relevant to targeting existing and novel preventative interventions for STIs such as 4CMenB vaccination for gonorrhoea and doxycycline post-exposure prophylaxis (doxyPEP) for syphilis in England. The reporting of these new STI surveillance data also raise new complexities in interpretation, and behavioural data completeness will require further support and development.

Mie-mediated edge-enhanced Raman scattering of vertically-stacking ge quantum-dots/Si-SiN array for enhancing photoluminescence and photodetection

Clinical proof of concept for small molecule mediated inhibition of IL-17 in psoriasis

Efficacious and well-tolerated systemic, oral treatments for psoriasis are needed. We report preclinical and phase 1c (NCT06808815) results for DC-806, a small molecule interleukin (IL)-17 inhibitor, for the treatment of mild-to-moderate psoriasis. Preclinical results demonstrated DC-806 targets IL-17AA and IL-17AF with secukinumab-like therapeutic efficacy. In the phase 1c trial, 32 patients consented to receive twice daily (BID) doses of placebo or DC-806 (200 mg or 800 mg) for 28 days. No serious adverse events (SAEs) or discontinuations due to treatment-related adverse events (TRAEs) occurred. In an exploratory analysis, adjusted mean percentage reductions from baseline in psoriasis area and severity indices (PASI) at Day 29 were 43.7%, 15.1%, and 13.3% for 800 mg BID, 200 mg BID, and placebo arms, respectively (800 mg BID vs placebo, P value = 0.0008). DC-806 was found to be well tolerated with an acceptable safety profile and preliminary signals of clinical efficacy in mild-to-moderate psoriasis. EudraCT Identifier: 2021-002888-21.

Frost resistance improvement of recycled powder concrete by chemical admixtures

Examining the role of social factors in the utilization of preventive cardiovascular clinical services: An analysis using Andersen’s behavioral health model

Background Cardiovascular disease (CVD) remains the leading cause of mortality in Saudi Arabia, mainly influenced by multiple lifestyle risk factors. Addressing this challenge requires a comprehensive evaluation of preventive services, particularly Preventive Cardiovascular Clinical Services (PCCS), which are essential for early detection and management. Hence, studying the utilization of PCCS is crucial to assess uptake and inform strategies to combat CVD burden. Methods A survey-based cross-sectional study was conducted at the largest primary healthcare center under the Armed Forces Healthcare Services (AFHS) in Riyadh, Saudi Arabia. We surveyed 384 respondents to assess predisposing, enabling, and need factors that influence the utilization of nine PCCS using Andersen’s Behavioral Model of Health Services Use. Descriptive statistics and logistic regression models were employed to explore predictors of service utilization. Results The study revealed a notably high prevalence of both positive family history (90%) and self-reported diagnosis (53%) of CVD among participants, highlighting significant disparities in the utilization of PCCS across different service types and participant characteristics. Predisposing factors, including sex, age, parenthood, and educational attainment, consistently influenced the utilization of various PCCS. Sex-specific disparities were observed, with female individuals engaging in more PCCS, while gaps persisted in services such as smoking-cessation counseling. Personal and organizational enabling factors, including vehicle ownership and proximity to the nearest primary healthcare center, were crucial in facilitating access to healthcare. Finally, need factors, such as family history of CVD, the presence of CVD risk factors, and perceived health status, strongly influenced individuals’ motivations for seeking PCCS. Conclusion The complex intertwining of multiple personal, structural, and contextual factors further underscores the need to enhance PCCS user experience by designing, implementing, and monitoring targeted interventions, particularly for high-risk groups, based on their predisposing, enabling, and need profiles.

Epidemic spread with asymptomatic infectious period in contact adaptive networks

Turning crisis into potential: Leveraging the skills of forced Ukrainian migrant women in Poland

The 2022 Russian invasion of Ukraine triggered a large influx of highly skilled Ukrainian women into Poland, presenting both challenges and opportunities for their effective economic integration. This study employs network analysis on firm-level data from the Orbis database to identify 32 key industries – including food manufacturing, textiles, business services, wholesale trade, and healthcare – where Ukrainian managerial talent can enhance Poland’s industry space. Guided by a conceptual framework of three mechanisms for integration – (1) Matching and Complementarities, (2) Diversification via Relatedness, and (3) Gendered Sectoral Constraints – we examine how sectoral skill alignment interacts with gendered barriers to shape integration outcomes. By examining industry specialisation patterns and gender dynamics, we assess how leveraging the expertise of these skilled migrant women can drive economic diversification, fill labour shortages, and stimulate innovation. Our findings underscore that these women can strengthen market competitiveness in industries where Poland has a specialisation advantage and contribute to economic diversification in emerging industries – provided that gender-specific barriers are addressed. This study contributes to the broader discourse on migration, gender, and industrial policy, offering an empirical framework for other host countries seeking to transform skilled refugee inflows into engines of economic growth. The findings emphasise the necessity of evidence-based policies that align skilled migration integration strategies with industrial and gender equity objectives to maximise economic benefits.

Energy evolution mechanism of hard roof of working face adjacent to goaf after hydraulic fracturing and application

Real-world study: Assessing the impact of hemolysis on 48 biochemical and immunological analytes through big data analysis and its feasibility validation

Background This research utilizes clinical laboratory real-world data to explore the influence of in vitro hemolysis on 48 biochemical and immunological analytes, aiming to propose and validate the methods and tools based on big data for analysis of the impact of hemolysis on laboratory analytes. Methods This research initially employs univariate analysis to display the levels and distribution of 48 analytes across different H-index groups. Subsequently, it utilizes quantile regression models to analyze the impact of hemolysis on laboratory analytes, adjusting for age, gender, patient type, and PVD, with the magnitude of impact described using β values and 95% CIs, visualized through error bar graphs. Finally, the study compares its results with those obtained from homogenized experimental research using the same testing platforms and hemolysis assessment methods, validating the feasibility of conducting research based on big data. Results Adjusting for gender, age, patient type, and PVD, hemolysis showed a significant positive interference on ALT, Alb, TBil, GGT, AST, CK, LD, K, P, Mg, and FFA(P < 0.001)., and a significant negative interference on DBil, Na, Cl, TCO2, and Cr (P < 0.001). High hemolysis levels also negatively interfere UA, PA, and GA. No consistent pattern of significance was observed for other analytes. Our multivariate analysis, when compared to experimental data, revealed a 93.0% concordance, with discrepancies noted in GGT, ALP, and RF. Conclusions The impact of hemolysis on laboratory analytes can be effectively evaluated through comprehensive big data analysis, demonstrating a level of consistency comparable to that of homogeneous experimental research.

Neuroprotective potential of eugenol against acrylamide-induced brain toxicity by regulating Nrf2/NQO1/HO-1 and NLRP3/NF-κB/IL-1β signaling cascades

Abstract Acrylamide (ACR), a common environmental and dietary neurotoxicant, exerts profound deleterious effects on the central nervous system by triggering oxidative stress, neuroinflammation, apoptosis, and motor impairments. Eugenol (EU), a natural phenolic compound known for its antioxidant and anti-inflammatory properties, was evaluated for its neuroprotective efficacy in ACR-induced brain toxicity in rats. Male Wistar rats were orally administered ACR (20 mg/kg/day) for four weeks to induce neurotoxicity, with concurrent administration of EU at two doses (50 and 100 mg/kg/day). Behavioral assessments, including foot splay, gait score, and rotarod performance, were conducted to evaluate motor coordination and neuromuscular integrity. Biochemical analyses revealed that ACR significantly elevated markers of oxidative and nitrosative stress, suppressed antioxidant defense mechanisms. Furthermore, ACR induced significant upregulation of pro-inflammatory mediators (NLRP3, p-NF-κB, IL-1β), as well as apoptosis markers such as caspase-3, alongside prominent histopathological alterations and astrocyte activation (evidenced by increased GFAP expression). Treatment with EU resulted in a dose-dependent amelioration of these neurotoxic effects. Notably, EU restored motor function, attenuated oxidative/nitrosative damage, and reactivated the Nrf2/NQO1/HO-1 antioxidant pathway. Simultaneously, it significantly downregulated the expression of NLRP3, p-NF-κB, and IL-1β, indicating strong anti-inflammatory action. Histological analysis confirmed preservation of neuronal architecture, while immunohistochemistry showed reduced caspase-3 and GFAP expression in EU-treated groups. These findings suggest that EU exerts potent neuroprotective effects against ACR-induced brain toxicity, primarily through modulation of redox balance, suppression of neuroinflammation, and inhibition of apoptotic cell death, via targeting both the Nrf2-mediated antioxidant system and the NLRP3/NF-κB/IL-1β inflammatory cascade.

Intuitive or deliberative dishonesty: The effect of abstract versus concrete victim

There has been ongoing debate over whether people are intuitively honest or intuitively dishonest. A recent social harm account was proposed to address this debate: dishonesty is intuitive when cheating inflicts harm on an abstract other while honesty is intuitive when cheating inflicts harm on a concrete other. This pre-registered and well-powered study ( n  = 764) aims to directly test this account by using a time pressure manipulation. Specifically, we examined whether time pressure (versus self-paced conditions) would lead to increased cheating depending on whether the harmed party was concrete or abstract. The results showed no significant effect of time pressure on cheating behavior. However, the harm-type manipulation produced findings that contradicted those reported in previous studies. Given the low replication rates and reliance on controversial experimental manipulations in this area, our findings underscore the importance of further pre-registered research to rigorously evaluate the roles of time pressure and social harm in shaping intuitive (dis)honesty.

Interocular agreement and differences of ocular growth in cataract patients

Formic acid-sulfide synergistic aging kinetics and nanometer titanium dioxide modification mechanism in oil-immersed transformer insulation system

This study investigates the synergistic aging effects of formic acid and sulfides on oil-immersed transformer insulation systems and explores the mitigating role of titanium dioxide (TiO₂) nanoparticles. A series of multi-factor coupled accelerated aging experiments were conducted under controlled ambient conditions (25 ± 3 °C) to monitor the mechanical strength of insulating paper and the dielectric breakdown voltage of insulating oil. Results show that formic acid is the dominant agent in early-stage degradation, causing a sharp 63.88% drop in tensile strength within 30 days due to catalytic hydrolysis, followed by partial recovery to 50% of the initial value through crosslinking of degradation products. Notably, the coexistence of formic acid and powdered sulfur causes severe synergistic corrosion, leading to an 82.3% strength reduction and a dramatic decline in breakdown voltage to 7.2 kV. Conversely, the formic acid–DBDS system exhibits a protective synergy, with tensile strength and breakdown voltage recovering to 206 kN/m and 30.2 kV, respectively. The introduction of nano-TiO₂ enhances these effects, especially in DBDS environments, by forming passivation layers and interfacial traps that suppress degradation. These findings provide insights into the nonlinear coupling of chemical corrosion, interfacial modification, and insulation performance evolution in transformer systems.

LED lighting (350-650nm) undermines human visual performance unless supplemented by wider spectra (400-1500nm+) like daylight

Abstract Life evolved under broad spectrum sunlight, from ultraviolet to infrared (300–2500 nm). This spectrally balanced light sculpted life’s physiology and metabolism. But modern lighting has recently become dominated by restricted spectrum light emitting diodes (350–650 nm LEDs). Absence of longer wavelengths in LEDs and their short wavelength dominance impacts physiology, undermining normal mitochondrial respiration that regulates metabolism, disease and ageing. Mitochondria are light sensitive. The 420–450 nm dominant in LEDs suppresses respiration while deep red/infrared (670–900 nm) increases respiration in aging and some diseases including in blood sugar regulation. Here we supplement LED light with broad spectrum lighting (400–1500 nm+) for 2 weeks and test colour contrast sensitivity. We show significant improvement in this metric that last for 2 months after the supplemental lighting is removed. Mitochondria communicate across the body with systemic impacts following regional light exposure. This likely involves shifting patterns of serum cytokine expression, raising the possibility of wider negative impacts of LEDs on human health particularly, in the elderly or in the clinical environment where individuals are debilitated. Changing the lighting in these environments could be a highly economic route to improved public health.

Attitude toward physical activity after total hip or knee replacement: A cross-sectional survey study of Dutch and Norwegian patients

Objective To gain insight into the attitude towards physical activity (PA) of Norwegian and Dutch patients after hip or knee replacement, possible differences in attitude between the countries and which factors explain a more positive or negative attitude. Methods A cross-sectional survey study investigating attitude toward PA 6–12 months after hip or knee replacement was conducted in Norway and the Netherlands. Patients received a questionnaire consisting of three parts: demography, received health service, and the survey about attitude toward PA consisting of 32 statements divided into four domains – quality of life, level of PA, function, and kinesiophobia. Attitude was scored on a 4-graded Likert scale. A high score indicated a positive attitude toward PA. Survey responses from the Norwegian and Dutch cohorts were compared using one-way ANOVA for group comparison. To identify factors explaining the outcome of the attitude survey, stepwise regressions were used. Results Data from 732 Norwegian patients and 575 Dutch patients was included in the analyses. Overall, the characteristics of the two cohorts were quite similar, although a significantly greater number in the Norwegian cohort had participated in “prehab”, while the participation in “rehab” was similar. In all four domains the attitude scores were generally high, indicating positive attitudes, with Norwegian patients scoring significantly higher. Higher participation in sports was the strongest explaining factor for a more positive attitude toward PA. Older age was the strongest independent variable explaining a less positive attitude towards PA. Conclusion Patients seem to have an overall positive attitude towards PA after hip or knee replacement. Norwegian patients had a more positive attitude compared to Dutch patients, which could be the result of more formalized and extensive education of the benefits of PA as part of the “prehab” in Norway.

Indirect effects of higher mean air temperature related to climate change on major life-history traits in a pulsed-resource consumer

Abstract Climate change is directly and indirectly affecting species. The degree of these effect types differs by species and context, with indirect effects likely to be stronger for consumers of pulsed resources. Here, we investigated how higher mean air temperature related to climate change affects masting, and in parallel, how this change affects life-history traits in edible dormice ( Glis glis ). We analysed 17 years of capture-recapture data from 2,530 individuals. We collected air temperature, and, as a measure of seed production, pollen data from European beech ( Fagus sylvatica ). Our results show that increasing mean air temperature was associated with a shift in beech pollen production, leading to a biannual mast cycle in recent years, with alteration of years with very high and very low seed availability. The changed cycle in mast events resulted in a significant reduction in overall yearling survival in dormice, while overall adult survival remained stable. In parallel, both age classes significantly increased their litter size in this timeframe. Furthermore, survival probabilities in the two age classes also differed depending on the beech mast status (mast, mast-failure). We show that the observed dramatic changes in seed production had complex effects on life-history traits in a pulsed resource consumer.