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Machine learning for predicting metabolic-associated fatty liver disease including NHHR: a cross-sectional NHANES study
Objective Metabolic - associated fatty liver disease (MAFLD) is a common hepatic disorder with increasing prevalence, and early detection remains inadequately achieved. This study aims to explore the relationship between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and MAFLD, and to establish a predictive model for MAFLD using NHHR as a key variable. Methods All participants were selected from the NHANES cohort, spanning from 2017 to March 2020. Multiple linear regression models were employed to examine the relationship between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and the controlled attenuation parameter (CAP). To explore the non-linear association between NHHR and CAP, smooth curve fitting and restricted cubic splines (RCS) of the adjusted variables were utilized. Subgroup analyses were conducted to identify variations in the relationships between the independent and dependent variables across different populations. Finally, a metabolic - associated fatty liver disease (MAFLD) prediction model was developed using seven machine learning methods, including eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), Multilayer Perceptron (MLP), Random Forest, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), and logistic regression. The SHAP (SHapley Additive exPlanations) value was employed to interpret the importance of various features. Result Weighted multiple linear regression models revealed a significant positive correlation between the NHHR and the CAP (Beta = 7.42, 95% CI: 5.35-9.50, P < 0.001). Smooth curve fitting and RCS demonstrated a non-linear relationship between NHHR and CAP. Subgroup analyses indicated that this relationship was more pronounced in females. Among the seven machine learning predictive models incorporating NHHR, the XGBoost algorithm exhibited the highest predictive performance, with an area under the curve (AUC) of 0.828. Furthermore, NHHR was identified as the second most important feature in the SHAP analysis, following body mass index (BMI), highlighting its potential in predicting MAFLD. Conclusion A significant positive correlation was identified between the NHHR and the CAP. The inclusion of NHHR in the XGBoost predictive model for MAFLD demonstrated robust predictive capability, providing a valuable tool for the early detection of MAFLD with considerable clinical application potential.
Author Correction: Hybridisation of in silico and in vitro bioassays for studying the activation of Nrf2 by natural compounds
Eukaryotic phytoplankton drive a decrease in primary production in response to elevated CO <sub>2</sub> in the tropical and subtropical oceans
Ocean acidification caused by increasing anthropogenic CO 2 is expected to impact marine phytoplankton productivity, yet the extent and even direction of these changes are not well constrained. Here, we investigate the responses of phytoplankton community composition and productivity to acidification across the western North Pacific. Consistent reductions in primary production were observed under acidified conditions in the North Pacific Subtropical Gyre and the northern South China Sea, whereas no significant changes were found at the northern boundary of the subtropical gyre. While prokaryotic phytoplankton showed little or positive responses to high CO 2 , small (<20 µm) eukaryotic phytoplankton which are primarily limited by low ambient nitrogen drove the observed decrease in community primary production. Extrapolating these results to global tropical and subtropical oceans predicts a potential decrease of about 5 Pg C y −1 in primary production in low Chl- a oligotrophic regions, which are anticipated to experience both acidification and stratification in the future.
Towards developing brain-computer interfaces for people with Multiple Sclerosis
Background Multiple Sclerosis (MS) can be a severely disabling condition that leads to various neurological symptoms. A Brain-Computer Interface (BCI) may substitute some lost function; however, there is a lack of BCI research in people with MS. Present BCI designs have also overlooked the unique pathological changes associated with MS and have not considered needs of users within their home environments. To progress this research area effectively and efficiently, we aimed to evaluate user needs and assess the feasibility and user-centric requirements of a BCI for people with MS. We hypothesised that (i) people with MS would be interested in adopting BCI technology and (ii) those with reduced independence would prefer a higher-performing invasive BCI. Methods We conducted an online survey of people with MS to describe user preferences and establish the initial steps of user-centred design. The survey aimed to understand their interest in BCI applications, bionic applications, device preferences, and development considerations and related these to symptoms and assistance needs. Results We demonstrated widespread interest for BCI applications in all stages of MS, with a preference for a non-invasive (n = 12) or minimally invasive (n = 15) BCI over carer assistance (n = 6). Descriptive analysis indicated that level of independence did not influence preference towards the higher performing but highly invasive BCI. Conclusions The needs of end users reported in this study are crucial for efficient development of BCI systems that can be effectively translated into the home environment. Considering the potential to enhance independence and quality of life for people living with MS, the results emphasise the importance of user-centred design for future advancement of BCIs that account for the unique pathological changes associated with MS.
Publisher Correction: Association of systemic immunity-inflammation index with type 2 diabetes and insulin resistance in NHANES 2005–2018
Cell type and region-specific transcriptional changes in the endometrium of women with RIF identify potential treatment targets
Recurrent implantation failure (RIF) is a devastating condition that leaves many undergoing fertility treatment childless. The human endometrium is receptive to a blastocyst for a brief period, the window of implantation. Critical knowledge underpinning biological processes leading to RIF, essential for effective treatment, is lacking. We employed spatial transcriptomics to define region- and cell-type-specific differences in endometrial gene expression in luteinizing hormone timed biopsies between women with RIF (n = 8) and fertile controls (FC) (n = 8). Differentially expressed genes (DEGs) were identified when comparing endometrial regions between FC and RIF (685 luminal epithelium, 293 glandular epithelium, 419 subluminal stroma, 264 functionalis stroma, 1,125 subluminal stromal CD45 + leukocytes, and 1,049 functionalis stromal CD56 + leukocytes). Only 57 DEGs were common to all subregions and cell types, which highlights that multiple DEGs are lost when the endometrium is examined as a single entity. When RIF-specific DEGs were leveraged against knowledge from mouse genetic models, genes associated with aberrant embryo implantation phenotypes were observed, mostly in immune cell populations. Dysregulated pathways in specific endometrial regions included the “WNT signaling pathway,” altered in the functionalis and subluminal stroma. “Response to estradiol” and “ovulation cycle” pathways were dysregulated in the subluminal stroma. In silico drug screening identified potential compounds that can reverse the RIF gene expression profile (e.g., raloxifene, bisoprolol). Our findings, in a well-characterized cohort, highly endorse consideration of each endometrial region and cell type as separate entities. Ignoring individual regions and composite cell populations will overlook important aberrations, forego potential treatment targets, and lead to research waste pursuing clinically irrelevant treatment options.
Multivariate prediction of temper outbursts in a sample of youth enriched for irritability using ecological momentary assessment data: A registered report
Irritability and temper outbursts are among the most common reasons youth are referred for psychiatric assessment and care. Identifying in vivo clinical variables that precede the onset of temper outbursts would provide valuable clinical utility. Here, we provide the rationale for a study testing the performance of a classifier trained to predict temper outbursts in a group of clinically-referred youth presenting with symptoms of irritability and temper outbursts. Due to the large sample sizes needed for multivariate classification studies, here, we demonstrated the feasibility of our approach using a relatively large preliminary dataset. Our preliminary data included digital based event sampling from an existing Ecological Momentary Assessment dataset consisting of n = 54 participants with a total of 932 time points. We used this data to develop a logistic regression-based classifier for predicting the temper outburst prospectively. Our initial evaluation provided encouraging evidence for the possibility of predicting the presence of a temper outburst based on individual’s momentary clinical responses (e.g., whether the participant is feeling grouchy, hungry, happy, sad, anxious, tired, etc.) prior to the outburst event, as well as external features (e.g., time of day, day of week). However, due to the risk of false positive discoveries and overfitting, these preliminary results are insufficient to conclusively establish the discovery of predictive rules for irritability in Ecological Momentary Assessment data. To more rigorously assess this classifier, we will collect a large confirmatory set, consisting of at least an additional 20 subjects with an expected total of 400 time points, in which will perform confirmatory analyses of the precision and recall of the classifier already fit using preliminary data. This work will potentially provide the foundation for the identification of features predictive of risk and future development of novel mobile-device-based interventions in youth affected with severe and impairing psychopathology.
Investigation of nitrate and nitrite in commercially available infant formulas and baby foods in Iran and estimation of human health risks
Periarteriolar niches become inflamed in aging bone marrow, remodeling the stromal microenvironment and depleting lymphoid progenitors
In early postnatal and young adult bone marrow, Leptin receptor–expressing (LepR + ) stromal cells and endothelial cells synthesize factors required for hematopoietic stem cell (HSC) maintenance, including Stem Cell Factor (SCF) and Cxcl12. However, little is known about how these stromal cells change during aging. We performed single-cell RNA sequencing of mouse bone marrow stromal cells at 2, 12, and 24 mo of age. We identified five transcriptionally distinct subsets of LepR + cells, all of which expressed the highest levels of Scf and Cxcl12 in bone marrow throughout adult life. In aging bone marrow, SCF from LepR + cells, but not endothelial cells, continued to be necessary for the maintenance of HSCs and early restricted progenitors. However, arteriolar endothelial cells and other periarteriolar cells expressed increasing levels of interferon during aging. This increased the numbers of periarteriolar Sca1 + Cxcl9 + LepR + cells with an inflammatory gene signature and depleted lymphoid progenitors, at least some of which are also periarteriolar. The periarteriolar environment thus became particularly inflamed during aging, remodeling the stromal microenvironment and depleting lymphoid progenitors in an interferon-dependent manner.
Retraction: Implementation of organization and end-user computing-anti-money laundering monitoring and analysis system security control
Analytical design and test of a clip-based precision corn seed metering device using DEM-MBD coupling
Protein interactions, calcium, phosphorylation, and cholesterol modulate CFTR cluster formation on membranes
The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel whose dysfunction leads to intracellular accumulation of chloride ions, dehydration of cell surfaces, and subsequent damage to airway and ductal organs. Beyond its function as a chloride channel, interactions between CFTR, epithelium sodium channel, and solute carrier (SLC) transporter family membrane proteins and cytoplasmic proteins, including calmodulin and Na+/H+ exchanger regulatory factor-1 (NHERF-1), coregulate ion homeostasis. CFTR has also been observed to form mesoscale membrane clusters. However, the contributions of multivalent protein and lipid interactions to cluster formation are not well understood. Using a combination of computational modeling and biochemical reconstitution assays, we demonstrate that multivalent interactions with CFTR protein binding partners, calcium, and membrane cholesterol can induce mesoscale CFTR cluster formation on model membranes. Phosphorylation of the intracellular domains of CFTR also promotes mesoscale cluster formation in the absence of calcium, indicating that multiple mechanisms can contribute to CFTR cluster formation. Our findings reveal that coupling of multivalent protein and lipid interactions promotes CFTR cluster formation consistent with membrane-associated biological phase separation.
Biopsychosocial impact of high levels of trait anxiety on family caregivers in the end-of-life palliative care setting
Introduction Caring for a family member with a palliative diagnosis at home is physically and mentally stressful. This prospective study explores the emotional and physical burdens experienced by family caregivers in end-of-life palliative care settings, particularly focusing on those caregivers with high levels of pre-existing trait anxiety. The following hypotheses were examined: 1.) Family caregivers with high levels of trait anxiety suffer from high levels of anxiety, stress, burnout symptoms, insomnia, daytime sleepiness, physical complaints, health-related anxiety and resentments. 2.) Caregivers with a high level of trait anxiety are less resilient and receive less social support. They are more likely to use inappropriate strategies in the context of emotional regulation and work-related behavior. 3.) The support provided by the mobile palliative care team reduces stress and improves the quality of sleep of the caregiving relatives. Methods Forty-seven caregivers participated, with assessments conducted at two time points: before the mobile palliative care team’s intervention and six weeks later. Data collection included measures such as the State-Trait Anxiety Inventory (STAI), Whiteley Index (WI), Perceived Stress Scale (PSS-10), Maslach Burnout Inventory (MBI-HSS), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Giessen Complaints Questionnaire, Berner Bitterness Inventory (BVI), Brief Resilience Coping Scale, FEEL-E for emotional regulation, AVEM, and the MOS Social Support Survey. Results High levels of trait anxiety among caregivers were significantly associated with increased anxiety, stress, emotional exhaustion, depersonalization, insomnia, and feelings of resentment. Notably, maladaptive emotional regulation strategies were also prevalent. Intervention by the mobile palliative care team significantly reduced stress and insomnia, showing benefits across all levels of trait anxiety. Conclusion Family caregivers with high trait anxiety face significant challenges in end-of-life palliative care settings, indicating a crucial need for early identification and comprehensive biopsychosocial support to mitigate adverse emotional and physical health outcomes.
RNA guanine content and G-quadruplex structure tune the phase behavior and material properties of biomolecular condensates
Cross-reactivity of rPvs48/45, a recombinant Plasmodium vivax protein, with plasma from Plasmodium falciparum endemic areas of Africa
Background Ps48/45, a Plasmodium gametocyte surface protein, is a promising candidate for malaria transmission-blocking (TB) vaccine. Due to its relevance for a multispecies vaccine, we explored the cross-reactivity and TB activity of a recombinant P. vivax Ps48/45 protein (rPvs48/45) with plasma from P. falciparum-exposed African donors. Methods rPvs48/45 was produced in Chinese hamster ovary cell lines and tested by ELISA for cross-reactivity with plasma from Burkina Faso, Tanzania, Mali, and Nigeria. In addition, BALB/c mice were immunized with the rPvs48/45 protein formulated in Montanide ISA-51 and inoculated with a crude extract of P. falciparum NF-54 gametocytes to evaluate the parasite-boosting effect on rPvs48/45 antibody titers. Specific anti-rPvs48/45 IgG purified from African plasma was used to evaluate the ex vivo TB activity on P. falciparum, using standard mosquito membrane feeding assays (SMFA). Results rPvs48/45 protein showed cross-reactivity with plasma of individuals from all four African countries, in proportions ranging from 94% (Tanzania) to 40% (Nigeria). Also, the level of cross-reactive antibodies varied significantly between countries (p < 0.0001), with a higher antibody level in Mali and the lowest in Nigeria. In addition, antibody levels were higher in adults ( ≥ 17 years) than young children ( ≤ 5 years) in both Mali and Tanzania, with a higher proportion of responders in adults (90%) than in children (61%) (p < 0.0001) in Mali, where male (75%) and female (80%) displayed similar antibody responses. Furthermore, immunization of mice with P. falciparum gametocytes boosted anti-Pvs48/45 antibody responses, recognizing P. falciparum gametocytes in indirect immunofluorescence antibody test. Notably, rPvs48/45 affinity-purified African IgG exhibited a TB activity of 61% against P. falciparum in SMFA. Conclusion Plasma from African volunteers predominantly exposed to P. falciparum cross-recognized the rPvs48/45 protein. This, together with the functional activity of IgG, warrants further studies for the potential development of a P. vivax and P. falciparum cross-protective TB vaccine.
A novel deep sequential learning architecture for drug drug interaction prediction using DDINet
Uncovering the relationship between working memory and performance in the Jigsaw classroom
The Jigsaw classroom is a popular cooperative learning method based on resource interdependence, which requires students to work in small groups on complementary pieces of information, to achieve learning. However, Jigsaw classroom is characterized by contradictory findings and a lack of knowledge on its underlying cognitive mechanisms. The present study examined whether working memory capacity, a key executive function for academic achievement and learning, mediated or moderated the effects of Jigsaw classroom on individual performance. Undergraduate students (n == 342) attending French University took part in this study (Mage == 19.40, SD == 1.21, 60% female). Students worked in small groups on a critical thinking reasoning task, either in the Jigsaw condition or in a cooperative (control) condition without resource interdependence. Working memory was assessed twice, before and during the group activities, by using a complex working memory span task. We analyzed students’ individual score to a quiz on logical fallacies. Multilevel analyses revealed that working memory capacity moderated—but did not mediate—the effect of the Jigsaw classroom. That is, Jigsaw enhanced performance for students with low working memory capacities. These findings offer insight into the potential cognitive mechanisms implied in the success of the Jigsaw method and provide new recommendations for educators on how to redeem the deficit of low working-memory-capacity students on performance.
Determination of optimum extract conditions and evaluation of biological activity potential of Salvia cilicica Boiss
Gut microbiota signatures of the three Mexican primate species, including hybrid populations
Diversity of the gut microbiota has proven to be related with host physiology, health and behavior, influencing host ecology and evolution. Gut microbial community relationships often recapitulate primate phylogeny, suggesting phylosymbiotic associations. Howler monkeys (Alouatta) have been a model for the study of host-gut microbiota relationships, showing the influence of different host related and environmental factors. Differences in life-history traits and feeding behavior with other atelids, like spider monkeys, may reveal distinct patterns of bacterial gut communities, yet few wild populations have been studied; likewise, gut microbiota studies of hybrid populations are mostly lacking. We analyzed diversity and abundance patterns of the gut microbiota of wild populations of the three Mexican primates Ateles geoffroyi, Alouatta palliata and A. pigra from different regions across its distribution in the country, including sympatric localities and the Alouatta hybrid zone. Interspecific differences in gut microbial diversity were higher than intraspecific differences, concordant with phylosymbiosis. Ateles harbored the more differentiated diversity with a major presence of rare taxa, while differences were less strong between Alouatta species. Hybrids had a microbial diversity in-between their parental species, yet also showing unique microbe taxa. Genetic distances between Alouatta individuals correlated positively with their gut microbial dissimilarities. Results show that interspecific and intraspecific overall diversity, abundance and composition patterns are affected by environment, geographic distribution and host genetics. Our study provides the first comprehensive study of gut microbiota of the three Mexican primates and hybrid populations.