Browse Articles

Electrochemical deprotonation of halohydrins enables cascading reactions for CO2 capture and conversion into ethylene carbonate

Retrospective cohort of a decade of pediatric kidney transplant in a Brazilian state: Clinical profile, main complications, and outcomes

Pediatric kidney transplant is performed globally, although unevenly, with specific challenges in low-income countries with limited resources. We aimed to describe pediatric kidney transplantation in Bahia, a state located in one of the poorest regions in Brazil, and explore possible predictors of survival. This was a single-center retrospective cohort, and we included 101 pediatric kidney transplants performed between 2013 and 2022. There was no predominance of sex; the median age was 12 years old. Congenital anomalies of the kidney and urinary tract were the most common etiology of renal disease. 21 transplants were preemptive. Delayed graft function occurred in just over half of transplants. Patient survival rate was 96%, 96%, 89.1%, and 89.1% respectively at 1-year, 3-years, 5-years, and 10-years post-transplant. The overall graft survival rate was 80.2%, 76.9%, 66.8%, and 45.8% at 1-year, 3-years, 5-years, and 10-years post-transplant. Multivariate analysis of outcome predictors revealed that delayed graft function was a risk factor for graft survival in 5 years (adjusted HR 3.44 (1,18–10,05)). Pediatric kidney transplantation is a regionally feasible treatment, with good outcomes, although slightly inferior to those reported in the literature; efforts on reducing incidence in delayed graft function may improve graft survival.

Human autoimmunity at single cell resolution in aplastic anemia before and after effective immunotherapy

Abstract Severe immune aplastic anemia is a fatal disease due to the destruction of marrow hematopoietic cells by cytotoxic lymphocytes, serving as a paradigm for marrow failure syndromes and autoimmune diseases. To better understand its pathophysiology, we apply advanced single cell methodologies, including mass cytometry, single-cell RNA, and TCR/BCR sequencing, to patient samples from a clinical trial of immunosuppression and growth factor stimulation. We observe opposing changes in the abundance of myeloid cells and T cells, with T cell clonal expansion dominated by effector memory cells. Therapy reduces and suppresses cytotoxic T cells, but new T cell clones emerge hindering robust hematopoietic recovery. Enhanced cell-cell interactions including between hematopoietic cells and immune cells, in particular evolving IFNG and IFNGR, are noted in patients and are suppressed post-therapy. Hematologic recovery occurs with increases in the progenitor rather than stem cells. Genetic predispositions linked to immune activation genes enhances cytotoxic T cell activity and crosstalk with target cells.

Anesthesia isn’t sleep: The neuronal dynamics of immobility in isoflurane-anesthetized C. elegans differ from the activity patterns of previously established sleep-like quiescent states

Background C. elegans possesses a precisely defined pattern of neuronal activation associated with its quiescent sleep-like state. As for higher-order creatures, this state includes the induction of atonia and immobility. In C. elegans, activation of the GABAergic neuron ALA directly inhibits AVE, a crucial command motor interneuron. By comparing this stereotypical pattern of activation to the activity seen within this neuronal circuit during anesthesia, we may determine if the atonia and immobility observed in anesthetized C. elegans is recruited via the same neuronal mechanism as in quiescence. Methods Neuronal activity in C. elegans, as measured by fluorescence intensity of the calcium-indicator GCaMP6s, was captured using light-sheet microscopy under exposure to increasing depths of isoflurane anesthesia (n = 20). Neuronal identities were determined using the NeuroPAL nuclear labeling system. The activity of neurons in the sleep atonia pathway were identified for analysis. Neuronal traces were differentiated, and signal coherence between traces were calculated as Pearson correlation coefficients. Differences among conditions were assessed using ANOVA. Results During quiescence, we observe the characteristically strong activation of ALA and RIS, with suppression of other neurons. In the awake animal, neuronal activity in ALA and AVE remains moderately negatively correlated (r = -0.286). However, isoflurane anesthesia in C. elegans does not result in an increase in the negative correlation between these two neurons: we observe a progressive loss and inversion of this baseline negative correlation, resulting in a significantly different positive correlation when deeply anesthetized (r = 0.229: p = 0.003, Type III ANOVA). In comparison, isoflurane anesthesia suppresses the positive correlation between AVE and a strongly-connected key member of the command motor interneuron circuit, AVA (p = 0.007, Type III ANOVA). Conclusions Immobility is a fundamental characteristic of both anesthesia and naturally occurring sleep-states. However, we show that, in C. elegans, immobility in the anesthetized state is not produced by activating the innate neurological mechanism of quiescence.

Unravelling the transcriptome of the human tuberculosis lesion and its clinical implications

Abstract The tuberculosis (TB) lesion is a complex structure, contributing to the overall spectrum of TB. We characterise, using RNA sequencing, 44 fresh human pulmonary TB lesion samples from 13 TB individuals (drug-sensitive and multidrug-resistant TB) undergoing therapeutic surgery. We confirm clear separation between the TB lesion and adjacent non-lesional tissue, with the lesion samples consistently displaying increased inflammatory profile despite heterogeneity. Using weighted correlation network analysis, we identify 17 transcriptional modules associated with TB lesion and demonstrate a gradient of immune-related transcript abundance according to spatial organization of the lesion. Furthermore, we associate the modular transcriptional signature of the TB lesion with clinical surrogates of treatment efficacy and TB severity. We show that patients with worse disease present an overabundance of immune/inflammation-related modules and downregulated tissue repair and metabolism modules. Our findings provide evidence of a relationship between clinical parameters, treatment response and immune signatures at the infection site.

Towards robust medical machine olfaction: Debiasing GC-MS data enhances prostate cancer diagnosis from urine volatiles

Prostate cancer (PCa) is a major, and increasingly global, health concern with current screening and diagnostic tools’ severe limitations causing unnecessary, invasive biopsy procedures. While gas chromatography–mass spectrometry (GC-MS) has been used to detect urinary volatile organic compounds (VOCs) associated with PCa, efforts to identify consistent molecular biomarkers have failed to generalize across studies. Inspired by the olfactory diagnostic capabilities of medical detection dogs, we do not reduce chromatograms to a list of compounds and concentrations. Instead, we deploy a machine learning approach that bypasses molecular identification: PCa “scent character" signatures are extracted from raw time series data transformed into image representations for classification via convolutional neural networks. To address confounding factors such as sample-source bias, we implement a multi-step pre-processing and debiasing pipeline, including empirical Bayes correction, baseline drift removal, and domain adversarial learning. The resulting model achieves classification performance on par with similarly trained canines, achieving a recall of 88% and an F1-score of 0.78. These findings demonstrate that, at least in the context of PCa detection from urine, machine learning-based scent signature analysis can serve as a fully non-invasive diagnostic alternative, with these early results being also relevant to the wider emergent field of medical machine olfaction.

Single-shot two-dimensional nano-size mapping of fluorescent molecules by ultrafast polarization anisotropy imaging

Abstract Molecular size plays a crucial role in determining the physical, chemical, and biological properties of substances. However, traditional fluorescence polarization anisotropy methods struggle to capture fast transient processes or provide plane-specific details. To overcome these limitations, we introduce Compressed Ultrafast Planar Polarization Anisotropy Imaging (CUP2AI). This approach combines femtosecond laser-sheet illumination, molecular rotational diffusivity, and compressed sensing to enable real-time, non-invasive, wide-field anisotropy measurements in both liquid and gas phases. CUP2AI captures 2D molecular size mapping in a single acquisition, granting unprecedented insights into dynamic events across various excitation modes (i.e. both one- and two-photon) and environmental conditions. It enables mapping of molecular volume (500 ų–80,000 ų) and hydrodynamic diameter (10 Å–50 Å) based on anisotropy lifetimes. We imaged fluorescein-conjugated dextran in water and polycyclic aromatic hydrocarbons in flames. CUP2AI holds transformative potential for applications ranging from molecular biology and drug design to nanoparticle formation.

Screening for variable drug responses using human iPSC cohorts

We have developed a laboratory-based drug screening platform that uses a cohort of human induced pluripotent stem cell (hiPSC) lines, derived from different donors, to predict variable drug responses of potential clinical relevance. This builds on recent findings that pluripotent hiPSC lines express a broad repertoire of gene transcripts and proteins, whose expression levels reflect the genetic identity of the donor. We demonstrate that a cohort of hiPSC lines from different donors can be screened efficiently in their pluripotent state, using high-throughput Cell Painting assays. Variable phenotypic responses between hiPSC lines were detected with a wide range of clinically approved drugs, in use across multiple disease areas. Furthermore, information on mechanisms of drug-cell interactions underlying the observed variable responses was derived by using quantitative proteomic analysis to compare sets of hiPSC lines that had been stratified objectively, based upon variable response, Cell Painting data. We propose that information derived from comparative drug screening, using curated libraries of hiPSC lines from different donors, can help to improve the delivery of safe new drugs suitable for a broad range of genetic backgrounds and sexual diversity within human populations.

The barite record of the past seawater oxygen isotope composition

Epidemiology of Traumatic brain injury in Ethiopia: A systematic review and meta-analysis of prevalence, mechanisms, and outcomes

Introduction Traumatic brain injury (TBI) is a major cause morbidity and mortality globally. In Ethiopia, the prevalence of TBI is high, driven by factors such as road traffic incidents (RTIs), assaults, and falls. However, comprehensive data regarding the epidemiology, causes, severity, and outcomes of TBI in Ethiopia remain limited. This scarcity hinders the formulation of evidence-based interventions and policies that are specifically tailored to this context. Therefore, this systematic review and meta-analysis was conducted to provide pooled estimates on the prevalence, causes, severity, complications, and outcomes associated with TBI. Method A comprehensive review of existing literature was carried out by searching through PubMed, Scopus, Web of Science and EMBASE to gather studies published until September 2024. The inclusion criteria were centered on studies that discussed the frequency, causes, risk factors and results of brain injury, in Ethiopia. The quality of the studies included in the review was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist. We utilized Stata 17 statistical software for analysis. To address the heterogeneity observed among the studies, random-effects models were employed. Results The pooled prevalence of TBI among patients presented with trauma was approximately 30.5%. The average age of the patients was 27.48 ± 2.047 years. The main causes for TBI were assaults 36% (CI: 0.28–0.44) road traffic incidents 35% (CI: 0.28–0.41) and falls 21% (CI: 0.15–0.27). Mild TBI made up 57% while moderate and severe TBI accounted for 25% and 18%, respectively. Complications, such as post-traumatic seizures and infections, were reported in 17% of cases. Additionally, the overall mortality rate was 12%. However, significant variability was observed among studies. Conclusion The meta-analysis underscores the impact of TBI, in Ethiopia with high mortality rates and associated challenges. The results underscore the pressing requirement for measures to decrease TBIs linked to accidents and violence while also enhancing emergency services access and strengthening neurosurgeons capabilities, in Ethiopian medical facilities.

Voltage-controlled magnetoelectric devices for neuromorphic diffusion process

Abstract Neuromorphic diffusion models have become one of the major breakthroughs in the field of generative artificial intelligence. Unlike discriminative models that have been well developed to tackle classification or regression tasks, diffusion models aim at creating content based upon contexts learned. However, the more complex algorithms of these models result in high computational costs using today’s technologies. Here, we develop a spintronic voltage-controlled magnetoelectric memory hardware for the neuromorphic diffusion process. The in-memory computing capability of our spintronic devices goes beyond current Von Neumann architecture, where memory and computing units are separated. Together with the non-volatility of magnetic memory, we can achieve high-speed and low-cost computing, which is desirable for the increasing scale of generative models in the current era. We experimentally demonstrate that the hardware-based true random diffusion process can be implemented for image generation and achieve comparable image quality to software-based training as measured by the Fréchet inception distance (FID) score, achieving ~103 better energy-per-bit-per-area over traditional hardware.

What we know and don’t know about the antenatal care service utilization in Ethiopia: A scoping review of the literature

Introduction In Ethiopia, there has been considerable recent investment and prioritization in the maternal health program. However, coverage rates have been low and stagnant for a long time, indicating the existence of systemic utilization barriers. Therefore, it is fundamental to synthesize the current body of knowledge to successfully address these problems and enhance program effectiveness to increase antenatal care (ANC) uptake. Methods We conducted a scoping review of the literature. Using various combinations of search strategies, we searched Pubmed/Medline, WHO Library, ScienceDirect, Cochrane Library, Google Scholar, and Google for this review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) were used to conduct the review. We included studies that used any study design, data collection, and analysis methods related to antenatal care utilization. Results A total of 76 studies, national surveys, and estimates were included in this review. The analysis revealed that ANC utilization coverage varied considerably by region, from 27% in Somali to 90.6% in the Oromia region, with significant disparities in socioeconomic status, access to healthcare, and vaccination knowledge. Ten priority research areas covering various aspects of the national ANC services were identified through a comprehensive review of the existing body of knowledge led by experts using the Delphi method. Conclusion The barriers to recommended ANC service utilization differ depending on the context, suggesting that evidence-based, locally customized interventions must be developed and implemented. This review also identified evidence gaps, focusing on health system-related utilization barriers at the lower level, and identified additional research priorities in Ethiopia’s ANC service. The first step in developing and executing targeted program approaches could be identifying coverage of ANC services utilization among those with disadvantages.

Synthesis of chiral germanium center enabled by poly-deborylative alkylation and desymmetrization

The influence of the Big Five inventory on quality of life in people with Parkinson’s disease aged 50 and above: A Longitudinal Analysis from the Survey of Health, Aging and Retirement in Europe (SHARE)

Background Parkinson’s disease (PD) significantly reduces quality of life (QoL), particularly due to its complex interplay of motor and nonmotor symptoms. While personality traits influence QoL in chronic diseases, their longitudinal effects in people with PD (PwPD) remain underexplored. This study evaluates the longitudinal predictive influence of neuroticism, conscientiousness, and openness on QoL in PwPD over two waves of the Survey of Health, Aging, and Retirement in Europe (SHARE). Methods This study utilized longitudinal data from 100 PwPD participants in waves 7 and 8 of the Survey of Health, Aging, and Retirement in Europe (SHARE). QoL was assessed using the CASP-12 scale, while personality traits were measured with the Big Five Inventory (BFI-10). Linear regressions and generalized estimating equations (GEE) were used to examine cross-sectional and longitudinal associations between personality traits and QoL, controlling for sociodemographic, psychosocial, and health-related variables. Results Neuroticism was consistently associated with lower QoL across all analyses. Cross-sectional results showed neuroticism as the strongest predictor of QoL decline in wave 7 (beta = -0.33, p < 0.001), and longitudinal GEE analyses confirmed its predictive effect (beta = -0.03, p = 0.007). Conscientiousness and openness showed limited and inconsistent associations with QoL. Beyond personality traits, depressive symptoms and mobility limitations were found to substantially impact QoL, influencing the effects of neuroticism. Conclusions Neuroticism plays a pivotal role in predicting QoL decline in PwPD, highlighting its utility as a target for psychological interventions aimed at emotional regulation and resilience building. While depressive symptoms and mobility limitations also contribute, integrating personality assessments into care strategies may improve outcomes. These findings advocate for a multidimensional approach to managing PD that addresses both clinical and psychological factors.

Pixel super-resolved virtual staining of label-free tissue using diffusion models

Abstract Virtual staining of tissue offers a powerful tool for transforming label-free microscopy images of unstained tissue into equivalents of histochemically stained samples. This study presents a diffusion model-based pixel super-resolution virtual staining approach utilizing a Brownian bridge process to enhance both the spatial resolution and fidelity of label-free virtual tissue staining, addressing the limitations of traditional deep learning-based methods. Our approach integrates sampling techniques into a diffusion model-based image inference process to significantly reduce the variance in the generated virtually stained images, resulting in more stable and accurate outputs. Blindly applied to lower-resolution auto-fluorescence images of label-free human lung tissue samples, the diffusion-based pixel super-resolution virtual staining model consistently outperforms conventional approaches in resolution, structural similarity and perceptual accuracy, successfully achieving a pixel super-resolution factor of 4-5×, increasing the output space-bandwidth product by 16-25-fold compared to the input label-free microscopy images. Diffusion-based pixel super-resolved virtual tissue staining not only improves resolution and image quality but also enhances the reliability of virtual staining without traditional chemical staining, offering significant potential for clinical diagnostics.

Efficacy and safety of botulinum toxin-A injection in the treatment of premature ejaculation: A systematic review and meta-analysis

Introduction Premature ejaculation (PE) is a common male sexual dysfunction, impacting sexual satisfaction and quality of life. Botulinum toxin-A (BoNT-A), known for its muscle-relaxing properties, has been proposed as a treatment for PE, but its efficacy and safety remain uncertain. Objectives To systematically evaluate the efficacy and safety of BoNT-A injection compared to placebo for treating PE. Methods A comprehensive search of PubMed, EMBASE, and Cochrane databases was conducted to identify randomized controlled trials comparing BoNT-A and placebo in treating PE. Primary outcomes included intravaginal ejaculatory latency time (IELT) and premature ejaculation profile (PEP), while sexual satisfaction score was a secondary outcome. Mean differences (MD) with 95% confidence intervals (CI) and odds ratios (OR) for adverse events were calculated using a random-effects model. Results Three studies were included in the analysis. BoNT-A significantly increased IELT and PEP at the 1-month follow-up (MD = 22.32; 95% CI = 10.83–33.82; P = 0.001 for IELT; MD = 0.91; 95% CI = 0.41–1.42; P < 0.001 for PEP), but no significant differences were observed at 3-month and 6-month follow-ups (P > 0.05). No significant improvements in sexual satisfaction were found (P = 0.32). BoNT-A was associated with a higher incidence of adverse events compared to placebo (OR = 5.90; 95% CI = 1.29–26.89; P = 0.02), but no significant differences were observed for drippling or erectile dysfunction (P > 0.05). Conclusion BoNT-A injections may be an effective short-term treatment for PE, significantly improving IELT and PEP at 1-month follow-up. However, the effects appear to diminish over time, and no significant improvement in sexual satisfaction was observed. BoNT-A is associated with a higher rate of adverse events, but does not increase the risk of drippling or erectile dysfunction. Further studies with longer follow-up periods are needed to assess long-term efficacy and safety.

Short-range order controlled amphoteric behavior of the Si dopant in Al-rich AlGaN

Abstract AlGaN alloys with high Al content offer the possibility to create deep ultraviolet light sources emitting at wavelengths ≤ 240 nm with enhanced quantum efficiency. However, increasing the band gap when the Al content surpasses  ~80% leads to problems with n -type doping of AlGaN alloys with the standard choice of Si donors, due to the formation of the so-called negative Si DX center. In this paper, we show that the amphoteric nature of the Si dopant in AlGaN alloys is fundamentally controlled by the local environment and the ordering of the Ga and Al atoms in the vicinity of the Si atom. Our conclusions are based on advanced characterization sensitive to the local environment of defects and impurities, complemented by electronic structure calculations. We propose that spatial ordering of Ga and Si atoms could allow efficient n -type doping at even higher Al contents, including AlN.

Perspectives of a mobile intervention for kidney transplant seekers: Post-intervention qualitative results from the KidneyTIME study

Objective Mobile health education could expand accessibility, but limited research has explored attitudes about such products among kidney transplant (KT) seekers. This study aimed to assess KT-seeker’s attitudes about the learning and donor search intervention in the KidneyTIME study, which examined the effectiveness of a web-based intervention leveraging animated video education, video viewing and sharing, and use-reminders compared to usual care video alone. Methods Among 56 unique intervention-arm patients (54% non-Hispanic White, 58% no college degree, 46% total annual household income ≤ $30,000), we conducted semi-structured individual interviews with 31 patients and collected open-box survey comments from 36 patients. Using content analysis, we analyzed transcripts of the interviews to identify key concepts related to patient experience and usage of the mobile program as well as suggested improvements. Results Most patients found the online program to be convenient and easy to access on any device, although a few recommended technological enhancements or availability earlier in the transplant process. The video content was helpful to learn and reduce anxiety about kidney transplantation and donation; additional topics were suggested and that it could be more personalized. Videos were shared to put others at ease, prepare them, and elicit possible donors. Some could have benefitted from sharing instructions or assistance or wanted other outreach modalities. The digital reminders to use the resource prevented forgetting and prompted watching. Conclusion Patients had positive feelings about KidneyTIME, including receiving information from animated videos, sharing videos with their social network, and receiving email or text reminders. Findings provide insights about patients’ experience with this innovative approach for providing self-education and empowering patients’ social network outreach about kidney transplantation and donation, including future enhancements to consider.

Asian summer monsoon variability across Termination II and implications for ice age terminations

Abstract The detailed anatomy of Termination I (TI) is well depicted, but whether changes across Termination II (TII) resemble TI remains controversial. Here we present high-resolution Asian monsoon records covering TII using Shima Cave stalagmites from China. Correlating marine and ice-core records to our U/Th-dated records via millennial-scale variabilities, we find an initial CO2 rise from 139 ± 1 ka BP concordant with boreal summer insolation increase, which was followed by a major rise phase of CO2 between 135.7 ± 1 and 129 ± 1 ka BP. The major rise phases of CO2 were comparable during TI and TII, but the initial CO2 rise before TII was distinct from CO2 behavior before TI, likely forced by the Earth’s internal variabilities, in particular an ice-sheet collapse event and a 50% reduction in southern hemisphere dust flux. Here, we show that ~4000–5000-year-long gradual changes in CO2, along with insolation rise, preconditioned glacial terminations, supporting the “tipping point” theory.

Association of predicted lean body mass and fat mass with prognosis in patients with heart failure preserved ejection fraction

Background Previous studies have shown that body composition influences the prognosis of heart failure patients; however, the prognostic value of lean body mass and fat mass in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. This study aimed to investigate the association of lean body mass index and fat mass index with the prognostic outcomes in patients with HFpEF. Methods We performed a post hoc analysis of data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial to assess the relationship between Lean BMI and FMI with the adverse events. The primary endpoint was defined as a composite of cardiovascular death, aborted cardiac arrest, or heart failure hospitalization. Results A total of 3,320 patients were included, with a median follow-up of 3.3 years. Among them, 624 occurred a primary endpoint event, and 503 died. Lean BMI was not associated with the primary endpoint (HR 0.98, 95% CI 0.82–1.16) but was found to reduce the risk of all-cause mortality (HR 0.74, 95% CI 0.61–0.91). In contrast, FMI was associated with an increased risk of both the primary endpoint (HR 1.29, 95% CI 1.09–1.55) and all-cause mortality (HR 1.46, 95% CI 1.19–1.79). Conclusion In patients with HFpEF, a higher FMI was strongly associated with increased risks of both the primary endpoint and all-cause mortality, while an elevated LBMI was associated with a reduced risk of mortality.