Browse Articles

Proximal and distal middle cerebral artery diameter ratio and lenticulostriate artery infarction

Background Lipohyalinotic degeneration (LD) and branch atheromatous disease (BAD) can contribute to subcortical infarctions in the lenticulostriate artery (LSA) territory. This study aimed to identify the association between the proximal and distal middle cerebral artery (MCA) diameter ratio and the two different pathomechanisms of LSA infarction. Methods Patients with acute LSA infarctions categorized as small vessel occlusive disease were included. Demographic and clinical data, along with MCA geometrical variables, were collected. LD and BAD were differentiated based on the length of the infarction diameter and number of axial slices. The proximal/distal M1 diameter ratio was calculated. MCA geometrics between LD and BAD were compared. Independent factors associated with LD were investigated. Computational fluid dynamics (CFD) analysis was used to evaluate hemodynamic parameters. Results A total of 117 patients were included, of whom 64 (54.7%) and 53 (45.3%) were classified as BAD and LD, respectively. LD was associated with hypertension and favorable prognosis. MCA geometric variables revealed that LD had a higher proximal/distal M1 diameter ratio, indicating a potential distinguishing factor. Multivariate analysis confirmed the independent association between LD and the proximal/distal M1 diameter ratio. The proximal/distal M1 diameter ratio also showed a positive correlation with the number of ipsilesional lacunes. CFD analysis showed that the LD model had faster, greater blood influx into LSAs and higher wall shear stress and pressure gradient compared with the BAD model. Conclusions This study suggests MCA geometry, particularly the proximal/distal M1 diameter ratio, may serve as an independent factor for identifying LD.

Development of conformation-selective antibodies targeting human SLC15A4

Prevalence and determinants of violent disciplinary practices for children in Bangladesh: Evidence from a nationally representative survey

Violent discipline, characterized by the use of physical force resulting in bodily pain, discomfort, or resorting to scolding and emotional abuse to correct children’s misbehavior, has gathered considerable attention due to its negative impact on children’s development. This study aims to identify the prevalence and factors associated with different violent disciplinary practices toward children of 1–14 years age in Bangladesh. Utilizing data from the Multiple Indicator Cluster Surveys (MICS) conducted in 2019, this analysis, based on interviews with parents of 70027 children, focuses on three dependent variables measuring violent disciplinary practices: psychological aggression, physical punishment and any violent discipline. The independent variables considered include the child’s age, sex, type of residence (rural or urban), division, education of mothers, child disability, ethnicity and wealth index. Logistic regression models were employed to find the relationships between these variables and different forms of violent discipline, including psychological aggression, physical punishment and any violent discipline (psychological aggression, physical punishment or both), among children in Bangladesh. The results reveal several significant associations with these disciplinary practices. Younger male children, with functional difficulties, those from urban residence and poorer households, residing in the central and southern regions of the country (Khulna, Chattogram), having primary educated mothers and belonging to the Bengali households are at higher risk of any form of violent discipline including psychological aggression, physical punishment. Significantly, our study unveils a strong correlation between any violent discipline and psychological aggression, highlighting that Bangladeshi parents predominantly employ psychological aggression as their primary mode of disciplinary practice. The findings underscore the importance of activating child protection laws and implementing continuous training programs for parents to promote positive parenting practices. To mitigate the use of violent discipline in Bangladesh, the study suggests focusing on improving parental education levels and addressing economic conditions.

Lipid-mediated gating of a miniature mechanosensitive MscS channel from Trypanosoma cruzi

Abstract The mechanosensitive channel of small conductance (MscS) from E. coli (EcMscS) has served as the prevailing model system for understanding mechanotransduction in ion channels. Trypanosoma cruzi, the protozoan parasite causing Chagas disease, encodes a miniature MscS ortholog (TcMscS) critical for parasite development and infectivity. TcMscS contains a minimal portion of the canonical EcMscS fold yet maintains mechanosensitive channel activity, thus presenting a unique model system to assess the essential molecular determinants underlying mechanotransduction. Using cryo-electron microscopy and molecular dynamics simulations, we show that TcMscS contains two short membrane-embedded helices that would not fully cross an intact lipid bilayer. Consequently, drastic membrane deformation is induced at the protein-lipid interface, resulting in a funnel-shaped bilayer surrounding the channel. Resident lipids within the central pore lumen block ion permeation pathway, and their departure driven by lateral membrane tension is required for ion conduction. Together with electrophysiology and mutagenesis studies, our results support a direct lipid-mediated mechanical gating transition. Moreover, these findings provide a foundation for the development of alternative treatment of Chagas disease by inhibition of the TcMscS channel.

Developmental differences in perceiving arousal and valence from dynamically unfolding emotional expressions

The development of emotion perception has predominantly been studied using static, unimodal stimuli featuring the faces of young adults. Most findings indicate a processing advantage for positive emotions in children (positivity bias) and a negativity bias in adults, although these results are usually task-dependent. We created a new stimulus database comprising digital avatars from four age groups, dynamically expressing happiness, happy-surprise, anger, and sadness in visual (face only) and visual-verbal (face and voice) conditions. To determine whether previously found biases would re-emerge with this new database, we tested the arousal and valence perception of positive and negative emotions in 6- and 7-year-old children and young adults. Our results revealed high correlations between children’s and adults’ responses but also significant differences: children rated negative expressions as more arousing compared to adults and positive emotions as more positive than adults. Additionally, visual-verbal presentations were perceived as more arousing than visual across both age groups. In terms of valence, all participants found positive emotions as more positive in the visual condition, whereas negative emotions were perceived as more negative in the visual-verbal condition. As one of the first studies to employ dynamically multimodal emotional expressions, our findings underscore the relevance of studying developmental differences in emotion perception using naturalistic stimuli.

Real-time prediction of intensive care unit patient acuity and therapy requirements using state-space modelling

A qualitative study on barriers and facilitators of COVID-19 vaccination during pregnancy among pregnant women in Malaysia

Background COVID-19 vaccination is crucial for pregnant women to protect against severe complications during pregnancy. However, vaccine hesitancy and refusal can affect acceptance rates among this vulnerable group, posing risks to both maternal and fetal health. This research was conducted to explore the barriers and facilitators influencing COVID-19 vaccination among Malaysian pregnant women. Methods This qualitative study adopted a hermeneutic phenomenological design. Nineteen pregnant women receiving antenatal care at three clinics in Kelantan between February 2024 and June 2024 were purposively selected to participate in in-depth interviews. The interviews were audio-recorded, transcribed verbatim, and analyzed using NVivo software alongside manual coding. Thematic analysis, incorporating both inductive and deductive approaches, was conducted to identify key themes. Results Most pregnant women expressed hesitancy toward COVID-19 vaccination during pregnancy due to various concerns. Our findings identified four key themes as barriers to vaccination: (i) Fear of side effects, (ii) Negative social influences, (iii) Perception of returning to normalcy, and (iv) Vaccine scepticism and prejudice. Conversely, three themes emerged as facilitators of vaccine acceptance: (i) Concerns about the effects of COVID-19 infection, (ii) Trust in the vaccine, and (iii) Personal and shared vaccination experiences. Conclusion This study identified key factors influencing COVID-19 vaccine hesitancy. These findings highlight the importance of addressing both personal and social dimensions of vaccine hesitancy. Public health interventions should focus on building trust, countering misinformation, and leveraging positive community experiences to encourage vaccine uptake, particularly in populations where hesitancy remains a concern.

Development of a versatile chassis for the efficient production of diverse type II polyketides

Expression of human A53T alpha-synuclein without endogenous rat alpha-synuclein fails to elicit Parkinson’s disease-related phenotypes in a novel humanized rat model

Alpha-synuclein (aSyn) is linked to Parkinson’s disease (PD) through SNCA genetic mutations, phosphorylated aSyn in Lewy bodies and Lewy neurites, and most recently through evidence of aSyn aggregation in patient spinal fluid using the aSyn seed amplification assay. Therefore, understanding the biology of this protein and developing therapeutic interventions targeting pathological processing of aSyn are a key area of focus for novel treatments to slow or stop PD. Reliable preclinical models are imperative for these efforts. To this end, we developed a novel model using CRISPR/Cas9 to humanize the regions surrounding the naturally occurring threonine 53 amino acid in the Sprague Dawley rat to generate a humanized A53T aSyn rat model (aSyn A53T KI). We also generated an Snca knockout (aSyn KO) line to pair with the humanized A53T aSyn rat line to confirm that phenotypes were not due to loss of endogenous rat aSyn protein. A systematic phenotyping study was performed on these lines, assessing PD-related pathology and phenotypes at multiple timepoints. The aSyn KO rat line was profiled at 6 and 12 months of age, revealing successful aSyn protein knockout. The aSyn A53T KI model was profiled at 4, 8, 12, and 18 months of age for motor and non-motor phenotypes, nigrostriatal degeneration, and brain pathology. We confirmed the aSyn A53T KI rat expresses human aSyn while lacking endogenous rat aSyn. Motor function and non-motor function remain largely unaffected in this model, and no overt nigrostriatal degeneration or brain pathology are observed up to 18 months of age. Although the aSyn A53T KI rat lacks the ability to model PD pathology and phenotypes at baseline, it is an ideal model for investigating the impact of exogenous synuclein aggregates or environmental triggers on human aSyn in an in vivo model system.

Reaction-induced regioselective reconstruction of Ni-doped Ce(OH)3/CeO2 enables exceptional activity and selectivity for reverse water-shift reaction

Teaching fish new tricks: Repeated exposure to a velocity barrier improves passage performance

Instream structures like culverts and dams can impede upstream fish migration, acting as environmental filters that only allow onward migration of individuals that can successfully pass them. Cognition and learning ability may be an important factor in determining if a fish can successfully traverse such structures. This study investigated the effect of repeated exposure on passage performance of juvenile Galaxias maculatus through an experimental raceway. Over five consecutive days, individual fish were subjected to the same high-speed (0.45–0.5 m s-1) conditions within the raceway, and performance on each day was recorded. The proportion of fish successfully passing the barrier increased significantly from 40% on Day 1–63% on Day 5. Time-to-event analysis further revealed that by Day 5, fish successfully passed the barrier at a significantly faster rate compared to Day 1. However, repeated exposure did not significantly improve approach or entry rates into the raceway. Fish length influenced approach rates, but not entry or passage rates. These findings suggest that cognition and spatial memory play a role in improving passage performance through velocity barriers, but other factors such as attraction flows may also play an important role in successful passage outcomes.

ATP allosterically regulates an acyl-CoA oxidase

Scenario-based Kaya identity analysis for city-level carbon dioxide emissions

Many countries worldwide have committed to reduce their carbon dioxide emissions in response to climate change. In China, cities are striving to achieve their 2030 peak carbon emission targets. In this study, we developed a scenario-based Kaya identity analysis methodology to explore the notable uncertainty inherent in future carbon dioxide emissions. Using the case of Changning City, Hunan province, China, we found that under the business-as-usual scenario, the city’s carbon dioxide emissions of 3,839.1 thousand tons in 2022 are projected to reach 4,674.3 thousand tons in 2031. Changning is unlikely to achieve its carbon peak target. In a more challenging future scenario of rapid economic growth, carbon dioxide emissions are expected to rise from 3,839.1 thousand tons in 2022–5,447 thousand tons in 2031. Under the environmentalist scenario, Changning could achieve its carbon peak target before 2030 (carbon dioxide emissions would peak at 3,922 thousand tons in 2028). Under a slowed economic development scenario, Changning could also achieve a carbon peak in 2028 (carbon dioxide emissions would peak at 3,980.2 thousand tons in 2028). However, without sufficient energy-saving and emissions-reduction measures, annual increases in carbon dioxide emissions are likely to resurge during periods of rapid economic development.

Uncovering hidden enhancers through unbiased in vivo testing

Abstract Chromatin signatures are widely used to identify tissue-specific in vivo enhancers, but their sensitivity and specificity remains unclear. Here we show that many developmental enhancers remain undetectable using currently available chromatin data. In an initial comparison of over 1200 developmental enhancers with tissue-matched chromatin data, 14% ( n  = 285) lacked canonical enhancer-associated chromatin signatures. To further assess the prevalence of enhancers missed by chromatin profiling approaches, we used a high-throughput transgenic enhancer assay to screen the regulatory landscapes of two key developmental genes at 5 kb resolution, spanning 1.3 Mb of mouse sequence in total. We observed that 23 of 88 (26%) in vivo enhancers discovered by this approach lacked enhancer-associated chromatin signatures in the respective tissue. Our findings suggest the existence of tens of thousands of enhancers that remain undiscovered by currently available chromatin data, underscoring the continued need for expanding resources for enhancer discovery.

“It’s like a book in the palm of my hand”: Adapting the Safe Delivery App for Papua New Guinea to improve quality of maternal and newborn care

Background Health workers in many low- and middle-income countries are not adequately trained to provide quality antenatal and intrapartum care. The freely available Safe Delivery App (the App) provides health care professionals with direct and instant access to evidence-based, up-to-date clinical guidelines equipping them with an on-the-job reference guide, even in the most remote areas. In this paper we describe the uptake and acceptability and the process to align the App in Papua New Guinea (PNG). Methods Between June 2022 and December 2024, quantitative and qualitative methods were used to explore the usage and acceptability of the App among health care workers in PNG, re-designing images and aligning clinical content with PNG national clinical guidelines. Dissemination of the App took place through formal and informal networks, including a training of trainers’ program in one province. Results The App was seen as an acceptable and useful tool among midwives and nurses working clinically, particularly those in remote areas and midwifery educators. There was an increase in the use of the App, from 354 registered users in 2022 to 1304 in 2024. The majority of users were midwives and nurses, working in primary health care facilities and nursing and midwifery establishments. Participants reported that the App has led to changes in practice, supporting and encouraging staff to follow evidence-based guidelines, improving their clinical management. Conclusion The Safe Delivery App is seen as a useful tool, supporting clinical practice, knowledge and skills, providing users with more confidence in their ability to provide quality maternal and newborn health care. Wider implementation of the App across PNG may be a potential way to support health care workers in the remote settings, providing up to date evidence based clinical guidance in the absence of skilled midwives and doctors.

Human cytomegalovirus induces neuronal gene expression through IE1 for viral maturation

Presymptomatic microRNA-based biomarker signatures for the prognosis of localized radiation injury in mice

The threat of nuclear or radiological events requires early diagnostic tools for radiation induced health effects. Localized radiation injuries (LRI) are severe outcomes of such events, characterized by a latent presymptomatic phase followed by symptom onset ranging from erythema and edema to ulceration and tissue necrosis. Early diagnosis is crucial for effective triage and adapted treatment, potentially through minimally invasive biomarkers including circulating microRNAs (miRNAs), which have been correlated with tissue injuries and radiation exposure, suggesting their potential in diagnosing LRI. In this study, we sought to identify early miRNA signatures for LRI severity prognosis before clinical symptoms appear. Using a mouse model of hindlimb irradiation at 0, 20, 40, or 80 Gy previously shown to lead to localized injuries of different severities, we performed broad-spectrum plasma miRNA profiling at two latency stages (day 1 and 7 post-irradiation). The identified candidate miRNAs were then challenged using two independent mouse cohorts to refine miRNA signatures. Through sparse partial least square discriminant analysis (sPLS-DA), signatures of 14 and 16 plasma miRNAs segregated animals according to dose groups at day 1 and day 7, respectively. Interestingly, these signatures shared 9 miRNAs, including miR-19a-3p, miR-93-5p, miR-140-3p, previously associated with inflammation, radiation response and tissue damage. In addition, the Bayesian latent variable modeling confirmed significant correlations between these prognostic miRNA signatures and day 14 clinical and functional outcomes from unrelated mice. This study identified plasma miRNA signatures that might be used throughout the latency phase for the prognosis of LRI severity. These results suggest miRNA profiling could be a powerful tool for early LRI diagnosis, thereby improving patient management and treatment outcomes in radiological emergency situations.

Physical and chemical niche of human growth plate for polarized bone development

Automatic modulation classification for interrupted sampling proximity detector signals using time–frequency reconstruction network and polynomial chirplet transform

Mendelian randomization analysis: The causal relationship between C-reactive protein and amyloidosis and between C-reactive protein and atherosclerosis

Background A number of studies have shown that elevated CRP is linked to AS and reduced CRP is linked to amyloidosis. However, the exact mechanism explaining this connection is not known. Methods We used genomic pooled data from the Genome-Wide Association Study (GWAS) in a two-sample, two-way Mendelian randomization (MR) analysis study. Methods used included inverse variance weighting (IVW), weighted median (WM), MR-Egger method, Cochran’s Q, MR-PRESSO, MR-Egger intercept test, and leave-one-out sensitivity analysis. To investigate the specific causal relationship between C-reactive protein and amyloidosis and between C-reactive protein and atherosclerosis (coronary, cerebral, aortic, and peripheral atherosclerosis). The study procedure was performed with the STROBE-MR checklist. Results There was a inverse association between C-reactive protein and amyloidosis and an positive causal relationship between C-reactive protein and aortic atherosclerosis. The development of aortic atherosclerosis was positively correlated with C-reactive protein levels (IVW:p = 0.003, OR=1.203,95% CI:1.066–1.358). Whereas amyloidosis onset was associated with reduced C-reactive protein levels (IVW:p = 0.022, OR=0.582,95% CI:0.366–0.924). Reverse Mendelian randomization analysis found no evidence of reverse causality. Conclusion We verified the existence of a negative association between C-reactive protein and amyloidosis and a positive association between C-reactive protein and atherosclerosis by Mendelian randomization, which may provide some reference value for subsequent studies and treatment in the clinic.