Search Results (36)

The study of natural spontaneous fertile hybrids, whose parent species is Ae. trivialis Migusch. et Chak (2n = 42), is of great importance for expanding the genetic pool of the genus Triticum L., which is a crucial part of current and future breeding efforts. The number of wild relatives—potential sources of valuable disease resistance genes—is quite large for common wheat: these include species of the genera Tritium, Aegilops, Agropiron, Secale, Haynaldia, Villosa, and others. In addition to disease and pest resistance, wild species offer frost resistance, drought tolerance, salt tolerance, and increased protein quantity and quality. The primary objective of this study was to identify new, genetically diverse source material for common wheat breeding based on botanical and morphological studies, as well as to register new spontaneous Aegilops–wheat hybrids using electrophoretic analysis of storage proteins. To achieve the research objective, the following tasks were set and solved: Aegilops–wheat hybrids were studied and recorded using protein formulas; spontaneous fertile Aegilops–wheat hybrids were analyzed using laser microscopy and tandem mass spectrometry. In this study, we demonstrated differences between the studied spontaneous hybrids using metabolomic analysis and laser microscopy, as well as identified differences in the protein spectra of the spontaneous hybrids and their maternal form, K-1386. These spontaneous Aegilops–wheat hybrids will be used in further work to identify their paternal form. It should be noted that it is advisable to use the studied spontaneous Aegilops–wheat hybrids in future breeding to expand the gene pool of the genus Triticum L. and to obtain new heterogeneous forms. Full article

Soft rot disease caused by Pectobacterium carotovorum is a major postharvest problem in fruits and vegetables, particularly in East Asia. This systematic review and meta-analysis aimed to collate and critically evaluate studies on the biocontrol efficacy of microbial antagonists against P. carotovorum in East Asia, quantitatively estimate their effectiveness, and identify research gaps. A systematic search of PubMed, Web of Science, and Scopus databases was conducted following PRISMA guidelines and yielded 14 eligible studies (21 datasets) from East Asia. The overall pooled estimate of the relative reduction in disease incidence by microbial antagonists was 82% (95% CI: 74–88%; I² = 88.2%), indicating high but highly variable biocontrol efficacy across studies. Subgroup analyses revealed varying efficacy among different antagonists, with Chitosan-enhanced Lactobacillus pentosus and Leuconostoc fallax showing the highest potential (100% reduction), followed by Pseudomonas aeruginosa (90%), Bacillus velezensis (85.7%), and Lactobacillus paracasei WX322 (82.2%). Meta-regression identified BCA cell concentration, sample size, storage days, and storage temperature as significant sources of heterogeneity. Most studies were conducted in China, highlighting the need for more research in other East Asian countries. Microbial antagonists demonstrate substantial potential for reducing soft rot incidence, yet the high heterogeneity across studies warrants cautious interpretation of the pooled effect. While these findings are promising, further field validation and expanded geographical representation are needed. Full article

Dengue fever, with a high proportion of asymptomatic infections, poses a major global public health challenge that traditional surveillance systems frequently underestimate. Wastewater-based epidemiology (WBE) has emerged as a promising approach to monitoring infectious diseases beyond enteric viruses. Dengue virus is shed in urine, feces, and saliva, providing a biological basis for wastewater detection alongside clinical surveillance. This systematic review and meta-analysis synthesize current evidence on dengue virus (DENV) detection in wastewater and evaluate methodological factors influencing detection success in WBE. A systematic literature search using selected databases and predetermined keywords, followed by eligibility screening, resulted in ten studies being included, covering community surveillance and experimental trials. DENV ribonucleic acids (RNA) were most consistently detected and enriched in wastewater solids, indicating this matrix as the most reliable for surveillance. Among concentration methods, ultrafiltration achieved the highest viral recovery efficiency, while reverse transcription digital polymerase chain reaction (RT-dPCR) demonstrated superior sensitivity and precision compared to those of reverse transcription quantitative polymerase chain reaction (RT-qPCR), particularly at low viral concentrations. Storage at −80 °C was critical for preserving RNA integrity. The meta-analysis yielded a pooled DENV positivity rate of 24% (95% CI: 20–28%) after exclusion of outliers. Overall, solid-phase analysis combined with RT-dPCR represents the most sensitive methodological approach across the included studies. Harmonized protocols are needed to support future translation of dengue WBE into community surveillance as current evidence mainly demonstrates methodological feasibility and provides a technical foundation for future public health integration. Therefore, further longitudinal and multi-site validation is required to establish its broader applicability for dengue surveillance. Full article

Insect bites are a common cause of skin irritation and can contribute to disease transmission through vector-borne pathogens. Early identification of the likely biting organism can assist preliminary guidance (e.g., monitoring for warning signs, considering exposure history) and may reduce complications through timely follow-up. This paper studies a compact attention-guided learning framework for multiclass insect-bite image classification under strict storage constraints. A teacher network (BiteAI-T) based on MobileNetV3-Small is trained with spatial attention pooling to emphasize lesion-relevant regions while maintaining an efficient backbone. A lightweight depthwise-separable student (BiteAI-S) is trained using multi-level knowledge distillation that combines softened-logit matching with intermediate supervision through attention-map alignment and pooled-feature matching. Model storage is further reduced through weight-only quantization-aware training using an LSQ-inspired learnable scaling factor; BatchNorm running statistics are frozen during quantization fine-tuning to improve stability. Experiments on an eight-class dataset (ants, bed bugs, chiggers, fleas, mosquitos, no bites, spiders, ticks) show that BiteAI-T reaches 93.75% test accuracy. For deployment, we export (i) a TorchScript Lite teacher artifact (BiteAI-T_Lite, 2.35 MB) and (ii) a weight-only int8 student artifact (BiteAI-S_int8, 0.992 MB). Comparative results are also reported for an SVD-compressed + fine-tuned FP16 variant (92.66% test accuracy, 2.84 MB), illustrating accuracy–size trade-offs across compression strategies. Full article

Kidney transplantation remains the ultimate treatment option for patients with end-stage renal disease. However, the global shortage in donor kidneys, exacerbated by challenges such as ischemia–reperfusion injury (IRI), reduces renal graft viability and negatively impacts post-transplant outcomes. Static cold storage, the gold standard of organ preservation, reduces metabolic demand but increases the risk of cold-induced mitochondrial dysfunction and IRI, especially in marginal kidneys. The introduction of machine perfusion techniques allows renal grafts and other solid organ grafts to be preserved at a wider range of temperatures. Organ preservation temperatures play an important role in determining post-transplant outcomes in the transplantation of the kidney and other transplantable solid organs. Therefore, determining the optimal preservation temperature may help increase organ utilization by avoiding unnecessary graft discards and increasing the safe use of marginal organs. This review discusses the impact of various preservation temperatures and methods of preservation on post-transplant outcomes in renal grafts and other organ grafts. Drawing from preclinical, clinical, and meta-analytic studies, we compare hypothermic (0–4 °C), moderate hypothermic (10 °C), subnormothermic (20–32 °C), normothermic (35–37 °C), and subzero preservation strategies, and cellular and molecular changes that occur in renal grafts and other solid organ grafts during preservation at these temperatures. Overall, temperature-controlled machine perfusion outperforms static preservation of renal grafts and other solid organ grafts from marginal and deceased donors, potentially expanding donor pools and improving long-term graft survival, and suggests the need for future research to determine optimal preservation temperature for renal grafts and other solid organ grafts to improve viability and post-transplant outcomes. Full article

Background/Objectives: Longitudinal metabolomics analysis offers valuable insights into how metabolic pathways change according to age and health status. However, metabolite levels can fluctuate due to biological factors (e.g., age, diet, and health status) and technical factors (e.g., sample handling, storage times, and instrument performance), with some metabolites exhibiting greater sensitivity to these sources of variability than others. This study aimed to characterize the longitudinal and technical stability of untargeted plasma and cerebrospinal fluid (CSF) metabolites and to identify a subset that remains reliable over the extended time scales required for epidemiological research. Methods: Untargeted ultrahigh-performance liquid chromatography–mass spectrometry (LC-MS) metabolomic profiles were available from multiple visits in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and Wisconsin Alzheimer’s Disease Research Center (ADRC) studies. For this analysis, we constructed a subset of generally healthy participants with samples drawn at four time points (~2.5 years apart): two visits analyzed in 2017 and two visits analyzed in 2023, corresponding to two distinct analytical waves. We computed Rothery’s intraclass correlation coefficients (ICCs) to quantify intra-wave and inter-wave stability, evaluated pooled quality-control (QC) variation, classified metabolite stability by established thresholds, and developed a composite score integrating longitudinal stability and susceptibility to technical variance. Results: Across all metabolites, median stability was classified as ‘fair’ (Rothery’s ρ > 0.40 to ≤0.75) for both plasma and CSF. Although analytical batches were bridged using pooled QC samples, inter-wave stability was significantly lower than intra-wave stability, reflecting increased technical variability across waves. Using the composite score, we identified subsets of metabolites with ‘excellent’ stability and low susceptibility to batch effects in plasma and CSF. Stability patterns varied across biochemical super pathways. Conclusions: This work highlights metabolites suitable for long-term epidemiological studies and informs experimental design and analytical strategies for combining data across cohorts and analytical batches. Full article

Background: Fabry disease is a rare X-linked lysosomal storage disorder associated with progressive renal, cardiac, and neurological complications. Enzyme replacement therapy (ERT) has been the standard treatment for more than two decades, but its long-term impact on renal outcomes remains debated. Methods: We conducted a systematic review and meta-analysis of studies reporting renal outcomes in Fabry patients under long-term follow-up, including both ERT-treated and untreated cohorts. Electronic databases were searched up to October 2023. Data were extracted on estimated glomerular filtration rate (eGFR) slope, proteinuria, and clinical events. Random-effects models were used to calculate pooled effect sizes, and subgroup analyses were performed by treatment status and baseline risk factors. Results: Sixteen studies involving 2191 patients were included. Pooled analyses demonstrated a significant decline in eGFR over time across Fabry cohorts. Crucially, baseline proteinuria was identified as a significant prognostic factor; male patients with baseline UPCR > 0.5 g/g experienced a significantly faster decline in eGFR compared to those with UPCR < 0.5 g/g (p = 0.011). While direct comparisons between ERT and non-ERT groups did not consistently reach statistical significance, trends suggested a slower decline in ERT-treated patients, particularly in those with preserved renal function and lower proteinuria. Patients with baseline eGFR < 60 mL/min/1.73 m² had a significantly higher risk of clinical events compared with those with preserved renal function. Conclusions: Fabry patients experience progressive renal decline despite available therapies. Although direct comparisons between ERT and non-ERT groups did not consistently reach statistical significance, our quantitative analysis highlighted baseline proteinuria as a major determinant of renal trajectory. Patients with baseline UPCR > 0.5 g/g exhibited a significantly faster decline in eGFR, emphasizing the importance of early diagnosis and intervention before significant glomerular damage occurs. The limitations of the analysis include the small number of studies, heterogeneity in renal function definitions, exclusion of advanced kidney disease, and methodological constraints related to effect size reporting and risk-of-bias assessment. Full article

Introduction: Liver transplantation remains the definitive treatment for end-stage liver disease but faces critical challenges including organ shortages and preservation difficulties, particularly with extended criteria donor (ECD) grafts. Hypothermic machine perfusion (HMP) represents a promising alternative to traditional static cold storage (SCS). Methods: This retrospective study analyzed outcomes from 62 liver transplant recipients between 2016 and 2025, comparing 8 grafts preserved by HMP using the Liver Assist^® system and 54 grafts preserved by SCS. Parameters assessed included postoperative complications, hemodynamic stability, ischemia times, and survival outcomes. Results: HMP significantly reduced surgical (0% vs. 75.9%, p = 0.01) and biliary complications (0% vs. 34.4%, p = 0.004), improved hemodynamic stability post-reperfusion (∆MAP%: 1 vs. 21, p = 0.006), and achieved superior one-year survival rates (100% vs. 84.4%). Despite longer ischemia periods, grafts treated with HMP exhibited fewer adverse effects from ischemia-reperfusion injury. Discussion: These findings highlight the substantial benefits of HMP, particularly in improving graft quality from marginal donors and reducing postoperative morbidity. Further adoption of this technology could significantly impact liver transplantation outcomes by expanding the viable donor pool. Conclusions: The study underscores the effectiveness of hypothermic machine perfusion (HMP) as a superior preservation method compared to traditional static cold storage (SCS), HMP appears to be associated with improved short-term outcomes in liver transplantation. By substantially reducing postoperative complications and enhancing graft viability, HMP emerges as a pivotal strategy for maximizing the use of marginal donor organs. Further research and broader clinical implementation are recommended to validate these promising results and to fully harness the potential of HMP in liver transplantation. Full article

Newborn bloodspot screening for one or more lysosomal storage disorders (NBS-LSD) is currently performed by many public health NBS laboratories globally. The screening tests measure activities of selected lysosomal enzymes on dried blood spot (DBS) specimens collected from newborns by the heel stick method Because these assays measure enzyme activity, the quantitative results are dependent on the particular analytical method. DBS quality control (DBS QC) materials with assay-specific certified values that span the relevant range from typical to LSD-affected newborns are an important component of quality assurance in NBS laboratories. The Newborn Screening Quality Assurance Program (NSQAP) at the U.S. Centers for Disease Control and Prevention (CDC) provides public health NBS laboratories with DBS QC sets for NBS-LSD comprising four admixtures of pooled umbilical cord blood and a base pool made from leukodepleted peripheral blood and heat-inactivated serum. To evaluate the suitability of these materials for use with digital microfluidics fluorometry (DMF) assays which can currently measure the activity of four enzymes (acid α-galactosidase (GLA); acid β-glucocerebrosidase (GBA); acid α-glucosidase (GAA); and iduronidase (IDUA)), CDC collaborated with the Newborn Screening Unit at the Missouri State Public Health Laboratory (MSPHL). Using MSPHL criteria, we found that the certified results from each of two DBS QC lots collectively spanned the range from typical (screen negative) to enzyme deficient (screen positive) newborn DBS levels for each of the four lysosomal enzymes measured. The range included borderline results that would require repeat screening of the newborn under the MSPHL protocol. We conclude that these DBS QC preparations are suitable for use as external quality control materials for DMF assays used to detect LSDs in newborns. Full article

Background/Objectives: Fabry Disease (FD) is a multisystem X-linked lysosomal storage disorder that often manifests with nonspecific gastrointestinal (GI) symptoms, such as abdominal pain, diarrhea, and constipation. These symptoms may appear early in childhood, severely impacting quality of life and delaying diagnosis, and may be linked to nutritional challenges. This systematic review aims to evaluate the prevalence, characteristics, clinical relevance, and nutritional aspects of GI manifestations in pediatric FD patients to aid in early recognition and improve outcomes. Methods: A systematic literature search with meta-analysis adhering to PRISMA and MOOSE guidelines was conducted across PubMed, Web of Science, and Google Scholar from inception to November 2024 using fixed inclusion and exclusion criteria. Data were extracted by two reviewers independently. Disagreements were resolved by consensus; a third reviewer was consulted, when necessary. Pooled analysis was performed by a random-effects model; heterogeneity was assessed using the I² method. A quality assessment appraisal of the studies was carried out using the ROBINS-I tool. Results: The review encompassed 18 studies involving 736 pediatric patients. The evaluation of the pooled prevalence of GI symptoms in FD patients was 53% (95% CI 38–68%, I² 90%), with abdominal pain being the most frequent (pooled prevalence of 46% (95% CI 33–60%, I² 86%)). Symptoms often presented early, with a summarized standardized mean difference between the mean age of symptom onset and the mean age at FD diagnosis of 2.07 years (95% CI of 0.56–3.57, I² 42%, p < 0.01). Nutritional issues, including reduced food intake and potential malabsorption, were reported in cases with severe GI symptoms, contributing to growth impairments. Conclusions: GI symptoms frequently constitute the earliest clinical manifestation of FD in children. Their nonspecific nature underscores the importance of heightened clinical suspicion for timely diagnosis. Early intervention, including enzyme replacement therapy and tailored nutritional strategies, can alleviate symptoms, improve quality of life, and prevent disease progression. Multidisciplinary approaches are essential to optimize patient outcomes and further research into the pathophysiology and management of GI symptoms in FD is warranted. Full article

Liver transplantation is the preferred treatment for end-stage liver disease. Emerging evidence suggests a potential role for liver transplantation in treating liver tumors such as colorectal liver metastases and cholangiocarcinoma. However, due to a limited donor pool, the use of marginal grafts from donation after circulatory death (DCD) donors is increasing to meet demand. Machine perfusion is crucial in this context for improving graft acceptance rates and reducing ischemia–reperfusion injury. Few studies have evaluated the role of machine perfusion in the context of transplant oncology. Perfusion machines can be utilized in situ (normothermic regional perfusion—NRP) or ex situ (hypothermic and normothermic machine perfusion), either in combination or as a complement to conventional in situ cold flush and static cold storage. The objective of this analysis is to provide an up-to-date overview of perfusion machines and their function in donation after circulatory death with particular attention to their current and likely potential effects on transplant oncology. A literature review comparing standard cold storage to machine perfusion methods showed that, so far, there is no evidence that these devices can reduce the tumor recurrence rate. However, some evidence suggests that these innovative perfusion techniques can improve graft function, reduce ischemia–reperfusion injury, and, based on this mechanism, may lead to future improvements in cancer recurrence. Full article

Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine–Tryptophan–Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes. Full article

Polyphosphate (polyP) is an evolutionary ancient inorganic molecule widespread in biology, exerting a broad range of biological activities. The intracellular polymer serves as an energy storage pool and phosphate/calcium ion reservoir with implications for basal cellular functions. Metabolisms of the polymer are well understood in procaryotes and unicellular eukaryotic cells. However, functions, regulation, and association with disease states of the polymer in higher eukaryotic species such as mammalians are just beginning to emerge. The review summarises our current understanding of polyP metabolism, the polymer’s functions, and methods for polyP analysis. In-depth knowledge of the pathways that control polyP turnover will open future perspectives for selective targeting of the polymer. Full article

Liver transplantation (LT) is the only definitive treatment for end-stage liver disease, yet the UK has seen a 400% increase in liver disease-related deaths since 1970, constrained further by a critical shortage of donor organs. This shortfall has necessitated the use of extended criteria donor organs, including those with evidence of steatosis. The impact of hepatic steatosis (HS) on graft viability remains a concern, particularly for donor livers with moderate to severe steatosis which are highly sensitive to the process of ischaemia-reperfusion injury (IRI) and static cold storage (SCS) leading to poor post-transplantation outcomes. This review explores the pathophysiological predisposition of steatotic livers to IRI, the limitations of SCS, and alternative preservation strategies, including novel organ preservation solutions (OPS) and normothermic machine perfusion (NMP), to mitigate IRI and improve outcomes for steatotic donor livers. By addressing these challenges, the liver transplant community can enhance the utilisation of steatotic donor livers which is crucial in the context of the global obesity crisis and the growing need to expand the donor pool. Full article

Fabry Disease (FD) is one of the most prevalent lysosomal storage disorders, resulting from mutations in the GLA gene located on the X chromosome. This genetic mutation triggers glo-botriaosylceramide (Gb-3) buildup within lysosomes, ultimately impairing cellular functions. Given the role of lysosomes in immune cell physiology, FD has been suggested to have a profound impact on immunological responses. During the past years, research has been focusing on this topic, and pooled evidence strengthens the hypothesis that Gb-3 accumulation potentiates the production of pro-inflammatory mediators, revealing the existence of an acute inflammatory process in FD that possibly develops to a chronic state due to stimulus persistency. In parallel, extracellular vesicles (EVs) have gained attention due to their function as intercellular communicators. Considering EVs’ capacity to convey cargo from parent to distant cells, they emerge as potential inflammatory intermediaries capable of transporting cytokines and other immunomodulatory molecules. In this review, we revisit the evidence underlying the association between FD and altered immune responses and explore the potential of EVs to function as inflammatory vehicles. Full article