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Evaluating therapeutic plasma exchange and protease inhibitors as mechanisms to reduce soluble mesothelin
Abstract Cell surface mesothelin (MSLN) can be solubilized and released into the systemic circulation. The resulting soluble MSLN (sMSLN) may interfere with therapies targeting surface MSLN. We investigated the effects of sMSLN on anetumab, an antibody-based therapy against MSLN, anetumab ravtansine, an antibody drug conjugate, and mechanisms to decrease sMSLN. Whole blood samples were collected before and after one plasma volume of therapeutic plasma exchange (TPE). sMSLN levels were measured with ELISA assays in matched pre- and post-TPE plasma samples, and anetumab-immunoprecipitated samples. We also used protease inhibitors (PIs) as a mechanism to stabilize surface MSLN, then evaluated the cytotoxic effects of anetumab ravtansine. Our findings indicate that sMSLN sequesters and may impair the efficacy of this anti-MSLN antibody based on results showing that anetumab decreases the concentration of MSLN in plasma (p < 0.05) and reduced cytotoxicity of anetumab ravtansine in the presence of recombinant MSLN in cell lines, a surrogate for sMSLN. TPE consistently reduced sMSLN (p < 0.05) with an average decrease of 43.6% (15.4 ng/mL). Surface MSLN stabilization was inconsistently observed with PIs. Overall, sMSLN could represent a predictive biomarker for MSLN directed therapies. TPE may be more reliable than PIs to reduce sMSLN and ultimately restore sensitivity to these therapies in patients with high sMSLN.
Polycyclic aromatics in the Chang’E 5 lunar soils
Abstract Polycyclic aromatics are ubiquitous in the interstellar medium and meteorites, yet the search for lunar polycyclic aromatics remains a significant challenge. Here, we analyze Chang’E-5 lunar soil samples, revealing polycyclic aromatic concentrations of 5.0–9.2 µg/g (average: 7.4 ± 1.4 µg/g). Their aromatic structures are highly condensed, comparable to ~4 nm graphene sheets, and distinct from terrestrial analogs, such as wood char, soot and kerogen. While meteorite impacts are the most likely sources, the stable carbon isotope composition of polycyclic aromatics in Chang’E-5 lunar soil (δ13C: −5.0 ± 0.6‰ to +3.6 ± 1.3‰) is more enriched in 13C compared to that in meteorites. This enrichment suggests a de novo formation mechanism during meteorite impacts, involving the conversion of non-aromatic organic matter—which is more enriched in δ13C—into polycyclic aromatics. This process may play a significant role in carbon accretion in lunar regolith, as the resulting polycyclic aromatics are more stable and resistant to degradation compared to smaller organic molecules (e.g., amino acids), which are largely destroyed during impact events.
Prevalence of impaired fasting glucose and associated risk factors among Malaysian adult population: Findings from the National Health and Morbidity Survey (NHMS) 2019
Impaired fasting glucose (IFG) is a condition when a person’s blood glucose level is above the normal range, but below the diagnostic cut-off for a formal diagnosis of diabetes mellitus. The objective of this study was to determine the prevalence of IFG among adults aged 18 years and older in Malaysia and its’ associated factors. Data were obtained as part of the National Health and Morbidity Survey (NHMS) 2019 [1]. It was a community-based, cross-sectional study that was conducted among a targeted population in both urban and rural areas in all 13 states and 3 federal territories in Malaysia, using a two stage stratified random sampling method. Adults aged 18 years and older with fasting capillary blood glucose (FBG) readings of ≤ 6.9 mmol/L were selected, except those known to have diabetes. IFG was defined according to World Health Organization (WHO) criteria as FBG between 6.1 and 6.9 mmol/L. The data were analyzed using SPSS Version 28.0. A total of 6183 respondents - 2842 men and 3341 women participated in this study. The overall prevalence of IFG was 22.6% (95% CI: 20.4, 24.9). Respondents aged 60 years and older had the highest percentage of IFG at about 30.2% (95% CI: 26.4, 34.4), followed by respondents with hypercholesterolemia at 29.2% (95% CI: 25.2, 33.6) and respondents with hypertension at 27.7% (95% CI: 24.3, 31.4). Multivariate analysis revealed that age of 60 years and above (aOR 1.51, 95% CI: 1.01, 2.06) and marriage (aOR 1.46, 95% CI: 1.16, 1.84) were significantly associated with IFG. The prevalence of IFG among Malaysian adults according to data obtained in 2019 was 22.6%, with an age of 60 and above and married being the associated factors. Policies need to be tailored for more vigorous screening among this group for prompt diagnosis and treatment to prevent complications.
Life-cycle assessment of three biorefinery pathways across different generations
Abstract This study evaluated the ecological impacts of three generations of biorefineries using an integrated circularity-life cycle assessment (LCA) approach. In this context, LCA of three distinct biorefinery scenarios was conducted utilising the Greenhouse Gases, Regulated Emissions, and Energy use in Transportation (GREET®) model to compare their environmental impacts. Two third-generation scenarios, i.e., algae hydrothermal liquefaction (HTL)—pathway I and combined algae processing (CAP)—pathway II, and one second-generation scenario, i.e., palm fatty acid distillation (PFAD)—pathway III, were considered by following a well-to-wheel system framework. Pathway I and II exhibited very low emissions with negative net emissions in pathway I. On the contrary, pathway III had the highest emissions. Based on the results obtained from this study, exploitation of marine biomass (in the third-generation) might offer a sustainable solution to global energy demands with emerging green technologies, such as hydrothermal treatment, advanced fermentation, and green solvents that are essential for improving marine biorefineries. Policies must be formulated by setting standards prioritising renewable energy, resource efficiency, and waste reduction that are important in shaping the sustainability and efficiency of biorefineries across the globe.
A wheat CC-NBS-LRR protein Ym1 confers WYMV resistance by recognizing viral coat protein
Abstract Ym1 is the most widely utilized gene for wheat yellow mosaic virus (WYMV) disease control in worldwide wheat breeding. Here, we successfully isolated the responsible gene for Ym1 . It encodes a typical CC-NBS-LRR type R protein, which is specifically expressed in root and induced upon WYMV infection. Ym1 -mediated WYMV resistance is likely achieved by blocking viral transmission from the root cortex into steles, thereby preventing systemic movement to aerial tissues. Ym1 CC domain is essential for triggering cell death. Ym1 specifically interacts with WYMV coat protein, and this interaction leads to nucleocytoplasmic redistribution, a process for transitioning Ym1 from an auto-inhibited to an activated state. The activation subsequently elicits hypersensitive responses and establishes WYMV resistance. Ym1 is likely introgressed from the sub-genome X n or X c of polyploid Aegilops species. The findings highlight an exogenous-introgressed and root-specifically expressed R gene that confers WYMV resistance by recognizing the viral component.
Influence of artificial intelligence on ophthalmologists’ judgments in glaucoma
Purpose To examine the influence of artificial intelligence (AI) on physicians’ judgments regarding the presence and severity of glaucoma on fundus photographs in an online simulation system. Methods Forty-five trainee and expert ophthalmologists independently evaluated 120 fundus photographs, including 30 photographs each from patients with no glaucoma, mild glaucoma, moderate glaucoma, and severe glaucoma. A second trial was conducted at least one week after the initial trial in which photograph presentation order was randomized. During the second trial, 30% of the glaucoma judgments made by the AI system were intentionally incorrect. The evaluators were asked about their thoughts on AI in ophthalmology via a 3-item questionnaire. Results The percentage of correct responses for all images significantly improved (P < 0.001) from 48.4 ± 24.8% in the initial trial to 59.6 ± 20.3% in the second trial. The improvement in the correct response rate was significantly greater for trainees (14.2 ± 19.0%) than for experts (8.6 ± 11.4%) (P = 0.04). The correct response rate was 63.9 ± 20.6% when the AI response was correct, significantly greater than the 47.9 ± 26.6% when the AI response was incorrect (P < 0.0001). For trainees, the correct response rate was significantly greater when the AI’s response was correct than when it was incorrect. However, for experts, the effect was less pronounced. The decision time was significantly longer when the AI response was incorrect than when it was correct (P = 0.003). Conclusion In fundus photography-based glaucoma detection, the results of AI systems can influence physicians’ judgments, particularly those of physicians with less experience.
Glucosamine induces hepatic FGF21 expression by activating the Akt/mTOR/p70S6K axis and driving PGC-1α activity
Dysregulation of N-terminal acetylation causes cardiac arrhythmia and cardiomyopathy
Latent profile analysis of psychological help-seeking stigma and influential factors among Hainan medical students
Objective Medical students frequently confront a range of psychological challenges inherent to their profession. Among these, the psychological help-seeking stigma (PHSS) is a crucial yet often neglected barrier, impeding medical students from obtaining necessary psychological support. This research aims to elucidate the characteristics of PHSS in medical students through latent profile analysis (LPA), examine its psycho-social determinants, and establish the threshold for PHSS using receiver operating characteristic (ROC) analysis. Methods A cross-sectional survey was conducted among 3650 medical students from three medical colleges in Hainan Province, China, between February and July 2023. The survey gathered data on demographic details, PHSS, family socioeconomic status, professional help-seeking attitude, mental health level, self-efficacy and family function. LPA was employed to categorize distinct stigma profiles. Univariate and multiple logistic regression analyses were utilized to investigate the factors influencing these PHSS profiles. ROC analysis was executed to determine the optimal cut-off value for PHSS. Results Three distinct PHSS profiles emerged among the participants: “low-level stigma” (23.2%), “moderate-level stigma” (53.2%), and “high-level stigma” (23.6%). Logistic regression analysis revealed that professional help-seeking attitude, mental health level, self-efficacy and family function were associated with PHSS. The ROC analysis determined that the optimal cut-off value for identifying PHSS was ≥ 19.5. Conclusion This study highlights the substantial variability in PHSS among medical students. The identification of key influencing factors underscores the need for bespoke mental health interventions tailored to this unique demographic.
Reliability assessment of accelerated MR sequences for the estimation of structural and vascular markers in dementia
An anisotropic strategy for developing polymer electrolytes endowing lithium metal batteries with electrochemo-mechanically stable interface
Abstract Developing versatile solid polymer electrolytes is a reasonable approach to achieving reliable lithium metal batteries but is still challenging due to the nonuniform lithium deposition associated with the sluggish Li+ kinetics and insufficient mechanical strength. Herein, the concept of developing anisotropic solid polymer electrolyte is realized via integrating polymer hosts with highly oriented polyacrylonitrile nanofibers modified by Li6.4La3Zr1.4Ta0.6O12 particles. The oriented composite structure is employed to homogenize Li+ flux, serving as a physical barrier to resist lithium dendrites, retarding the side reaction between the electrolyte and lithium, thus endowing a compatible interface for lithium negative electrode. Correspondingly, the Li | |LiFePO4 cells steadily operate over 1000 cycles, delivering durable capacity retention of 91% at 170 mA g-1. Furthermore, numerical modeling and density functional theory are combined to clarify the multiphysics interplay between the designed solid polymer electrolyte and lithium negative electrode. This work provides a perspective for constructing interface-friendly solid polymer electrolytes at an electrochemo-mechanical level.
Obstetric admission and maternal mortality in the intensive care unit in Africa: A systematic review and meta-analysis
Background Obstetric complications are a major contributor to maternal morbidity and mortality worldwide, especially in low-resource settings such as many countries in Africa. Intensive care units offer specialized care for women with severe obstetric complications, which require advanced monitoring and therapeutic interventions. Despite the critical importance of ICU care, there is a paucity of comprehensive data on obstetric ICU admissions and outcomes in Africa. Therefore, this study aimed to assess the proportion of obstetric admissions and maternal mortality in the intensive care unit in Africa. Objective To assess the proportion of obstetric admissions and maternal mortality in the intensive care unit in Africa. Methodology The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA 2020) guidelines were followed in reporting the study’s findings. Articles searched; from PubMed, HINARI, Web of Science, Google Scholar, Repository, and African Journals Online were systematically searched for reports of obstetric admission in the intensive care unit, either pregnant or up to 6 weeks postpartum. The Joanna Briggs Institute (JBI) Critical Appraisal tool was used to evaluate each article’s quality. The Stata 17 software was used to compute the analysis. The heterogeneity of the studies was detected using the Cochran Q test and I2 test statistics, which were considered significant at p < 0.05. The random effect model of analysis was used with evidence of heterogeneity. Egger’s test at p < 0.05 was used to check the evidence of publication bias within the studies. Subgroup analysis and sensitivity analysis were done. Result Eleven studies were included in this study with a total of 10,190 mothers admitted to the intensive care unit. The overall pooled proportion of obstetric intensive care unit admissions in Africa was 17.22% (95% CI; 12.97–21.47; I2 = 97.63%). This translates to roughly 17 out of every 100 ICU admissions being for obstetric complications. Hypertensive disorders of pregnancy 42.96% (95% CI: 27.3, 58.56) and obstetric hemorrhage 24.15% (95% CI: 18.12, 30.18) were the common indications for obstetric admission in the intensive care unit.. Maternal mortality among ICU-admitted patients reached a concerning 30.69% (95% CI: 23.16, 38.22; I2= 93.34%). This means that, nearly one in three women admitted to the ICU for obstetric complications died. Conclusion In Africa, the proportion of obstetric admissions and maternal mortality in the intensive care unit is significant. This high percentage of obstetric admissions and maternal mortality in the ICU highlights the necessity to enhance emergency obstetric care services and invest in the development of well-equipped obstetric ICUs to reduce maternal mortality. Registration CRD42024516612.
The relationship between postoperative delirium and plasma amyloid beta oligomer
Abstract Postoperative delirium (POD) is a frequent complication in older people undergoing general anesthesia surgery. We investigated the potential link between Alzheimer’s disease and POD by comparing plasma amyloid-beta oligomer levels (measured using the multimer detection system, MDS-OAβ) in patients who developed POD after general anesthesia surgery with those who did not. A total of 104 eligible participants were screened daily for delirium for three days postoperatively. After propensity score matching based on the ApoE4 allele, the final analysis included 31 patients with POD and 31 without POD. In the ICU, patients with delirium underwent immediate assessment with the Korean version of the Delirium Rating Scale-98 (K-DRS-98) and plasma MDS-OAβ levels. The control group (those without POD) received the same tests on the third postoperative day. Patients with POD had significantly higher MDS-OAβ values compared to those without POD. Within the POD group, MDS-OAβ values positively correlated with K-DRS-98 scores (both severity and total scores). These findings suggest an association between POD in older people undergoing general anesthesia surgery and elevated plasma amyloid oligomer levels. To definitively establish causality, further prospective studies are necessary.
Hydrogels with programmed spatiotemporal mechanical cues for stem cell-assisted bone regeneration
Sensitivity of multi-parametric quantitative magnetic resonance imaging for multiple sclerosis pathology
Background In recent years, quantitative magnetic resonance imaging (MRI) made progress towards clinical applicability mainly through advances in acceleration techniques. In patients with multiple sclerosis (MS), objective quantitative MRI-based characterization of subtle pathological alterations in lesions, perilesion (PL), as well as normal-appearing (NA) white matter (NAWM) and grey matter (NAGM) would revolutionize clinical assessment. While numerous quantitative techniques have been applied in studies of MS patients, their diagnostic significance especially for individual patients with relatively short disease duration is unclear. Therefore, we investigated the sensitivity of several quantitative MRI parameters to focal and diffuse MS pathology in a clinical feasibility study with a small sample size. Methods In 13 MS patients with a mean disease duration of 8 years and a mean EDSS of 1.1 as well as 14 healthy age-matched controls (HC), we acquired nine (semi-)quantitative magnetic resonance (MR) biomarkers, namely myelin water fraction (MWF), magnetization transfer (MT) saturation (MTsat), inhomogeneous MT ratio (ihMTR), quantitative longitudinal relaxation time (qT1), intrinsic (qT2) and effective (qT2*) quantitative transverse relaxation times, proton density (PD), quantitative susceptibility mapping (QSM), and the ratio between T1-weighted and T2-weighted images (T1w/T2w). Four volumes of interest were automatically defined (NA/HC grey matter (GM), NA/HC white matter (WM), lesion, and PL), and biomarker values were analyzed between groups and tissue types. Results For all nine assessed biomarkers, mean values per patient were significantly different between lesion, PL, and NAWM (p < 0.05, FDR corrected). The lesion values of qT1, qT2, qT2 * , PD, and QSM were rather inhomogeneous. Furthermore, MWF, MTsat, and ihMTR were sensitive to diffuse WM pathology in MS with the largest absolute differences between NAWM and HCWM medians, albeit not statistically significant after correction for multiple testing. Discussion In our study, we successfully compared nine different quantitative MR parameters within the same subjects for tissue characterization of MS. Our study adds relevant aspects to the current debate on different sensitivities of various quantitative MR biomarkers to MS pathology. While all investigated MR biomarkers allowed characterizing lesions in individual patients, a separation of NAWM and HCWM could be most promising with the myelin-sensitive measures MWF, MTsat, and ihMTR.
The prophylactic anti-aging effect of aspirin (acetylsalicylic acid) on oxidative stress-induced damage in the buccal mucosa of D-galactose-induced aged rats
Abstract Most living organisms experience time-dependent functional deterioration as they age. To combat aging, aspirin was proposed as an already well-studied drug. However, its antiaging effect is neither well studied nor understood. So, this study intended to assess the proposed antiaging effect of aspirin. Three groups of seven adult male albino rats were established. The control group received saline, the aging model group got a daily single D-galactose subcutaneous injection (300 mg/kg), and the aspirin group consisted of D-galactose-induced aged rats that received a daily aspirin oral dose (60 mg/kg). Drugs were given for 8 weeks. Then, malondialdehyde (MDA) blood level was evaluated, and rats were euthanized. Buccal mucosa samples were obtained for inducible nitric oxide synthase (iNOS) gene expression, histopathological, ultrastructural, and comet analyses. MDA blood level, iNOS gene expression and DNA damage examined by comet assay displayed a significant reduction in the aspirin group when compared to the aging model group. Histopathological and ultrastructural results showed that aspirin ameliorated most of the degenerative signs caused by D-galactose. Thus, it was deduced that aspirin had promising results as an antiaging pharmaceutical agent. However, more studies are needed regarding its translation to human trials.
TRAPT: a multi-stage fused deep learning framework for predicting transcriptional regulators based on large-scale epigenomic data
The impact of clergy sexual abuse on spirituality and health: A systematic scoping review of the literature
Sexual abuse perpetrated by clergy or other Church leaders can cause harm to the spirituality of people who are subject to this abuse, which also has impacts on their overall health. We conducted a systematic scoping review to examine how Spiritual Harm in this context is operationalized in the literature with specific reference to the Catholic Church. Literature searches were conducted across Academic Search Complete, Informit Database, ProQuest, Web of Science and Google Scholar in 2022 and updated throughout 2023. Eligible studies were published between 2002–2022 and included peer reviewed empirical research, systematic reviews, discussion, or perspective papers that explored spiritual and/or religious harm and sexual abuse in a church context, and the psychological, emotional, and spiritual impact of the abuse. The review included 12 research articles. Data were analysed using qualitative approaches and presented as a narrative summary. Reporting follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews. Spiritual Harm in people who are subject to clerical sexual abuse is understood as a distinct condition or phenomena, comprising of complex spiritual, emotional and psychological components. However, it is not consistently defined. Understanding Spiritual Harm in a more comprehensive and consistent way is important in order to be able to adequately respond to the needs of victims, survivors, their families and wider communities.