Search Results (7,571)

Newborn screening (NBS) has evolved significantly since its inception, yet many treatable rare diseases remain unscreened due to technical limitations. The BabyDetect study used gene panel sequencing to expand NBS to treatable conditions not covered by conventional biochemical screening. We present here the analytical validation of this workflow, assessing sensitivity, precision, and reproducibility using dried blood spots from newborns. We implemented strict quality control thresholds for sequencing, coverage, and contamination, ensuring high reliability. Longitudinal monitoring confirmed consistent performance across more than 5900 samples. Automation of DNA extraction improved scalability, and a panel redesign enhanced the coverage and selection of targeted regions. By focusing on known pathogenic/likely pathogenic variants, we minimized false positives and maintained clinical actionability. Our findings demonstrate that gene panel sequencing-based NBS is feasible, accurate, and scalable, addressing critical gaps in current screening programs. Full article

When a navigation constellation depends exclusively on inter-satellite links for autonomous orbit determination, the absence of inertial frame orientation measurements can result in the accumulation of rotational errors across the entire constellation. To address these challenges, this study introduces inter-satellite orientation information in the inertial frame to provide the BeiDou satellite constellation with a stable inertial orientation reference. The results demonstrate that (1) incorporating space-based orientation observations with satellite-to-ground data significantly enhances orbit determination accuracy, reducing the three-dimensional orbit error from 2.604 m to 0.611 m. (2) Introducing a single orientation data point per epoch improves orbit determination accuracy from 2.604 m to 0.982 m. Compared to the scanning mode, the staring mode achieves higher performance. (3) When the error of space-based orientation data remains below 10 mas, the resulting spatial reference frame accuracy is better than 50 cm for the satellites. This research provides technical support for the construction of next-generation BDS. Full article

Grassland ecosystems, a major component of the global carbon (C) and nitrogen (N) cycles, are increasingly impacted by anthropogenic N addition. However, a comprehensive, integrated assessment of all three major greenhouse gas (GHG) responses in grasslands is lacking. Here, we present the first global meta-analysis to evaluate the effects of N addition on all three major GHGs (i.e., nitrous oxide (N₂O), methane (CH₄), and carbon dioxide (CO₂) fluxes) in grasslands. Our results show that N addition significantly and consistently stimulates N₂O emissions, a response primarily modulated by key drivers such as grassland type, management, N addition rate and forms, humidity index (HI), and soil pH, clay, and total nitrogen (TN) content. In contrast, N addition has a minimal and non-significant overall effect on soil CO₂ fluxes. For CH₄, N addition causes a context-dependent reduction in uptake, an effect that is exacerbated by high mean annual precipitation (MAP) and soil bulk density (BD) but alleviated by high soil organic carbon (SOC) content. Notably, both CO₂ and N₂O showed a dose-dependent effect, while soil CO₂ fluxes were unexpectedly suppressed by nitrate nitrogen (NO₃⁻) addition. Our findings indicate that the pronounced and consistent increase in N₂O emissions is the dominant factor in GHG-related impacts in grasslands, implying a net positive climate forcing in grasslands from N enrichment, even if there is insufficient data to calculate net climate forcing directly. Our study highlights the heterogeneous nature of grassland GHG responses and provides critical insights for developing sustainable N management strategies to mitigate climate change. Full article

Accurate spleen segmentation in abdominal CT scans remains a critical challenge in medical image analysis due to variable morphology, low tissue contrast, and proximity to similar anatomical structures. This paper presents an enhanced U-Net architecture that addresses these challenges through multi-slice contextual integration and interpretable deep learning. Our approach incorporates three-channel inputs from adjacent CT slices, implements a hybrid loss function combining Dice and binary cross-entropy terms, and integrates Grad-CAM visualization for enhanced model interpretability. Comprehensive evaluation on the Medical Decathlon dataset demonstrates superior performance, with a Dice similarity coefficient of 0.923 ± 0.04, outperforming standard 2D approaches by 3.2%. The model exhibits robust performance across varying slice thicknesses, contrast phases, and pathological conditions. Grad-CAM analysis reveals focused attention on spleen–tissue interfaces and internal vascular structures, providing clinical insight into model decision-making. The system demonstrates practical applicability for automated splenic volumetry, trauma assessment, and surgical planning, with processing times suitable for clinical workflow integration. Full article

Over the past two decades, immune–inflammatory dysregulation has emerged as a central paradigm in the biology of mood disorders. Patients with major depression (MDD) and bipolar disorder (BD) frequently display low-grade systemic inflammation. Elevated C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) identify clinically relevant subgroups of patients characterized by greater severity, cognitive impairment, and poor treatment response. Changes in the gut microbiota and disruptions of the blood–brain barrier (BBB) act as important gateways through which systemic immune activity can influence the brain. At the intracellular level, pattern-recognition receptors activate convergent hubs including NF-κB, JAK/STAT, and MAPK cascades, while the NLRP3 inflammasome integrates mitochondrial dysfunction and oxidative stress with IL-1β release and pyroptosis. These pathways converge on glial dysregulation, impaired BDNF/TrkB signaling, and kynurenine pathway (KP) alterations, fostering excitotoxicity and synaptic deficits. Translational studies demonstrate that elevated CRP and IL-6 predict poor antidepressant outcomes. Anti-inflammatory agents such as infliximab and celecoxib show efficacy in specific subgroups of patients. Emerging multi-omics approaches identify immuno-metabolic biotypes, supporting the rationale for biomarker-guided stratification. These findings define an ‘inflammatory biotype’ of mood disorders and highlight the need for biomarkers and precision-based trials to guide treatment. Full article

Mineral water content strongly depends on the geologic layer characteristics. Therefore, the aim of the present study is to make a comparison between two renowned mineral water sources in Romania, Borsec and Tusnad. Two public springs were selected from each location: Boldizsar (about 6600 L/day) and Lazar (about 500 L/day) from Borsec and Mikes (about 5000 L/day) and Young’s spring (about 600 L/day) from Tusnad. All investigated springs are naturally carbonated. Water properties were measured in situ and in laboratory for the collected samples; the results found that Borsec mineral water has a pH of about 7.5, while Tusnad mineral water is slightly acid (pH = 6.5). TDS strongly depends on the spring’s flow (for instance, Boldizsar has a TDS of about 900 mg/L, while Lazar has a TDS of about 1529 mg/L due to its high mineralization, while Young’s spring has a TDS of 165 mg/L due to its low mineralization, although it has low flow). Borsec mineral water has a lower salinity of about 1.22 PSU, while Tusnad water has a salinity of about 2 PSU, caused by a high amount of Na and Fe ions. Mineral waters dissolve ions from the geological layers, which react with carbonic acid during drying, generating specific crystallized compounds. The crystallized matter was investigated using XRD coupled with mineralogical optical microscopy (MOM); their microstructural features were observed using SEM coupled with elemental spectroscopy. Borsec water generates mainly Ca, Mg, and Na minerals like calcite, aragonite, pseudo-dolomite, natron, and traces of halite. Tusnad mineral waters have significant amounts of Ca, but also have Fe and much more Cl, since calcite and aragonite are mixed up with large amounts of halite and iron compounds. It looks like the presence of iron ions in the Tusnad mineral water collected from Mikes and Young’s spring explains the acidic pH. All these aspects are useful for further investigation regarding specific therapeutic purposes like chronic colitis and biliary lithiasis symptom amelioration (Boldizsar), chronic colitis, and enterocolitis symptoms (Lazar). Tusnad waters, like the water from Mikes spring, are recommended for anemia and neurasthenia, while Young’s spring is recommended for renal lithiasis amelioration. Full article

This study examines the impacts of climate change on fisheries and aquaculture in Bangladesh, one of the most climate-vulnerable countries in the world. The fisheries and aquaculture sectors contribute significantly to the national GDP and support the livelihoods of 12% of the total population. Using a Critical Literature Review (CLR) approach, peer-reviewed articles, government reports, and official datasets published between 2006 and 2025 were reviewed across databases such as Scopus, Web of Science, FAO, and the Bangladesh Department of Fisheries (DoF). The analysis identifies major climate drivers, including rising temperature, erratic rainfall, salinity intrusion, sea-level rise, floods, droughts, cyclones, and extreme events, and reviews their differentiated impacts on key components of the sector: inland capture fisheries, marine fisheries, and aquaculture systems. For inland capture fisheries, the review highlights habitat degradation, biodiversity loss, and disrupted fish migration and breeding cycles. In aquaculture, particularly in coastal systems, this study reviews the challenges posed by disease outbreaks, water quality deterioration, and disruptions in seed supply, affecting species such as carp, tilapia, pangasius, and shrimp. Coastal aquaculture is also particularly vulnerable to cyclones, tidal surges, and saline water intrusion, with documented economic losses from events such as Cyclones Yaas, Bulbul, Amphan, and Remal. The study synthesizes key findings related to climate-resilient aquaculture practices, monitoring frameworks, ecosystem-based approaches, and community-based adaptation strategies. It underscores the need for targeted interventions, especially in coastal areas facing increasing salinity levels and frequent storms. This study calls for collective action through policy interventions, research and development, and the promotion of climate-smart technologies to enhance resilience and sustain fisheries and aquaculture in the context of a rapidly changing climate. Full article

Static mixers are commonly used for process intensification in a wide range of industrial applications. For the design and selection of a static mixer, an accurate prediction of the hydraulic performance, particularly the pressure drop, is essential. This experimental study examines the pressure drop for turbulent single-phase and gas–liquid two-phase flows through a Komax triple-action static mixer placed on a horizontal pipeline. New values of friction factor and z-factor are reported for fully turbulent liquid single-phase flow (11,700 ≤ Re_L ≤ 18,700). For two-phase flow, the pressure drop for stratified and intermittent flows (0.07 m/s ≤ U_L ≤ 0.28 m/s and 0.46 m/s ≤ U_G ≤ 3.05 m/s) is modeled using the Lockhart–Martinelli approach, with a coefficient, C, correlated to the homogenous void fraction. Conversely, the analysis of power dissipation reveals a dependence on both liquid and gas superficial velocities. For conditions corresponding to intermittent flow upstream of the mixer, flow visualization revealed the emergence of a swirling flow in the Komax static mixer. It is interesting to note that an increase in slug frequency leads to an increase, followed by stabilization of the pressure drop. The results offer valuable insights for improving the design and optimization of Komax static mixers operating under single-phase and two-phase flow conditions. In particular, the reported correlations can serve as practical tools for predicting hydraulic losses during the design and scale-up. Moreover, the observed influence of the slug frequency on the pressure drop provides guidance for selecting operating conditions that minimize energy consumption while ensuring efficient mixing. Full article

Background: The aim of the present study is to compare the potential of a high-fat diet, a high-carbohydrate diet, and a high-fat, high-carbohydrate diet to induce liver injury and visceral obesity within a period of five weeks, identify the pattern and degree of hepatic changes at the tissue level, identify the earliest metabolic markers of specific liver changes induced by each type of diet, and to test the possible beneficial effects of steviol glycosides in a rat experimental model. Methods: Wistar rats (n = 56) were divided into seven groups as follows: group BD (before diet), group SD (standard diet), group HFD (high-fat diet), group HCHD (high-carbohydrate diet), group HFHCHD (high-fat high-carbohydrate diet), group SDS (standard diet supplemented with Stevia extract), and group HFDS (high-fat diet supplemented with Stevia extract). Results: Total cholesterol concentrations (2.02 ± 0.22 mmol/L) increased in the HFD group (2.56 ± 0.82 mmol/L) and in the HFDS group (2.89 ± 0.48 mmol/L). The VLDL values before diets were 0.27 ± 0.11 mmol/L and increased most significantly in the HFHCHD group—1.14 ± 0.62 mmol/L. The baseline ALT values (88.4 ± 10.6 U/L) increased in the HFD group (128.13 ± 19.5 U/L) and the HFDS group (127.00 ± 17.74 U/L). Similar increases were registered in the AST/ALT ratio and ALP. Total bilirubin (7.10 ± 1.39 μmol/L) increased in HFD group (27.86 ± 17.01 μmol/L). Serum NO had the lowest values in groups fed diets supplemented with steviol glycosides. All high-calorie diets induced hepatocellular injury. The mass of the perirenal fat depot and cross-sectional area of adipocytes were highest in HFD, HFHCHD, and HFDS groups. Conclusion: High-calorie diets have the potential to induce visceral obesity and hepatocellular injury within a very short period of time, which produces characteristic histological changes and specific biochemical profile. Steviol glycosides may alleviate some aspects of the inflammatory response, but findings about lipid profile parameters and liver enzymes are controversial. Full article

Nanodiamonds (NDs) are an innovative material in biomedical applications based on their excellent biocompatibility, nanoscale dimensions, and high surface area. In this study, we evaluated the potential of ND-in-oil emulsion to induce potent antibody responses in animals immunized with cobra venom. NDs demonstrated the capacity to bind complex venom proteins as stable conjugates, well dispersed in aqueous solution. Immunization of mice with cobra venom incorporated with ND-in-oil emulsion adjuvant (ND/venom) elicited strong venom-specific antibody responses with titers comparable to those induced by venom formulation with conventional Freund’s adjuvants (FA/venom). IgG subclass analysis revealed that ND- and FA-based formulations induced a Th2-biased immune response in mice. Moreover, antibodies elicited by ND/venom or FA/venom immunization specifically recognized the epitopes of the lethal component of short-chain neurotoxin and conferred full protection against lethal cobra venom challenge (3LD₅₀). Further, ND/venom hyperimmunization was capable of inducing high levels of neutralizing antibodies in larger animals, rabbits, highlighting the potential for antivenom manufacturing. Notably, there were no obvious lesions at the injection sites of animals that received ND/venom, in contrast to those that received FA/venom. These findings indicated NDs as an effective and safe additive in venom formulation for antivenom production. Full article

Background: Antibody-drug conjugates (ADCs) have ushered in a new era of precision oncology by combining the targeting specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic drugs. However, the cellular and molecular mechanisms underlying their dose-limiting ocular toxicity remain unclear. Elahere™, the first FDA-approved ADC targeting folate receptor α (FRα), demonstrates remarkable efficacy in platinum-resistant ovarian cancer but causes keratitis and other ocular toxicities in some patients. Notably, FRα is not expressed in the corneal epithelium—the primary site of damage—highlighting the urgent need to elucidate its underlying mechanisms. The aim of this study was to identify the cell-type-specific molecular mechanisms underlying Elahere-induced ocular toxicity. Methods: Sprague-Dawley rats were treated with intravenous Elahere (20 mg/kg) or vehicle weekly for five weeks. Ocular toxicity was determined by clinical examination and histopathology. Corneal single-cell suspensions were analyzed using the BD Rhapsody single-cell RNA sequencing (scRNA-seq) platform. Bioinformatic analyses to characterize changes in corneal cell populations, gene expression, and signaling pathways included cell clustering, differential gene expression, pseudotime trajectory inference, and cell-cell interaction modeling. Results: scRNA-seq profiling of 47,606 corneal cells revealed significant damage to the ocular surface and corneal epithelia in the Elahere group. Twenty distinct cell types were identified. Elahere depleted myeloid immune cells; in particular, homeostatic gene expression was suppressed in phagocytic macrophages. Progenitor populations (limbal stem cells and basal cells) accumulated (e.g., a ~2.6-fold expansion of limbal stem cells), while terminally differentiated cells decreased in corneal epithelium, indicating differentiation blockade. Endothelial cells exhibited signs of injury and inflammation, including reduced angiogenic subtypes and heightened stress responses. Folate receptor alpha, the target of Elahere, was expressed in endothelial and stromal cells, potentially driving stromal cells toward a pro-fibrotic phenotype. Fc receptor genes were predominantly expressed in myeloid cells, suggesting a potential mechanism underlying their depletion. Conclusions: Elahere induces complex, multi-compartmental ocular toxicity characterized by initial perturbations in vascular endothelial and immune cell populations followed by the arrest of epithelial differentiation and stromal remodeling. These findings reveal a cascade of cellular disruptions and provide mechanistic insights into mitigating Elahere-associated ocular side effects. Full article

Aquaculture has rapidly become a vital sector for ensuring global food security by meeting the growing demand for animal protein. Bangladesh, one of the world’s leading aquaculture producers, recorded a production of 4.91 million MT in 2022–2023, largely driven by inland farming systems. Despite this remarkable growth, the sector is highly vulnerable to disease outbreaks, which are aggravated by different factors. Pathogens such as bacteria, viruses, fungi, and parasites cause significant losses, while conventional disease diagnosis in Bangladesh still depends mainly on visual assessment and basic laboratory techniques, limiting early detection. This narrative review highlights recent advances in diagnostics as molecular tools, immunodiagnostics, nanodiagnostics, machine learning, and next-generation sequencing (NGS) that are widely applied globally but remain limited in Bangladesh due to infrastructure gaps, lack of skilled manpower, and resource constraints. Current treatment strategies largely rely on antibiotics and aquaculture medicinal products (AMPs), often misused without proper diagnosis, contributing to antimicrobial resistance (AMR). Promising alternatives, including probiotics, immunostimulants, vaccines, and enhanced biosecurity, require greater adoption and farmer awareness. The near-term priorities for Bangladesh include standardized disease and AMR surveillance, prudent antibiotic stewardship, phased adoption of validated rapid diagnostics, and investment in diagnostic and human capacity. Policy-level actions, including a national aquatic animal health strategy, stricter antimicrobial regulation, strengthening diagnostic infrastructure in institution, are crucial to achieve sustainable disease management and ensure long-term resilience of aquaculture in Bangladesh. Full article

1,3-butadiene (BD) is a volatile organic pollutant. Upon inhalation, it is metabolically activated to reactive epoxides which alkylate genomic DNA and form potentially mutagenic monoadducts and DNA–DNA crosslinks including N7-(1-hydroxyl-3-buten-1-yl)guanine (EB-GII) and 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD). While metabolic activation resulting in mutagenicity is a well-established mode of action for 1,3-butadiene, characterization of the extent of inter-individual variability in response to BD exposure is a gap in our knowledge. Previous studies showed that population-wide mouse models can be used to evaluate variability in 1,3-butadiene DNA adducts; therefore, we hypothesized that this approach can be used to also study variability in the formation and loss of BD DNA adducts across tissues and between sexes. To test this hypothesis, female and male mice from five genetically diverse Collaborative Cross (CC) strains were exposed to filtered air or 1,3-butadiene (600 ppm, 6 h/day, 5 days/week for 2 weeks) by inhalation. Some animals were kept for two additional weeks after exposure to study DNA adduct persistence. EB-GII and bis-N7G-BD adducts were quantified in liver, lungs and kidney using established isotope dilution ESI-MS/MS methods. We observed strain- and sex-specific effects on both the accumulation and loss of both DNA adducts, indicating that both factors play important roles in the mutagenicity of 1,3-butadiene. In addition, we quantified the intra-species variability for each adduct and found that for most tissues/adducts, variability values across strains were modest compared to default uncertainty factors. Full article

The paper proposes the use of Bag-of-Words classifiers for the reliable detection of tuberculosis infection from cough recordings. The effect of using both independent and combined distinct feature extraction procedures and encoding strategies is evaluated in terms of standard performance metrics such as the Area Under Curve (AUC), accuracy, sensitivity, and F1-score. Experiments were conducted on two distinct large datasets, using both the original recordings and extended versions obtained by augmentation techniques. Performances were assessed by repeated k-fold cross-validation and by employing external datasets. An extensive ablation study revealed that the proposed approach yields up to 0.77 accuracy and 0.84 AUC values, comparing favorably against existing solutions and exhibiting robustness against various combinations of the setup parameters. Full article

Considering the world’s growing interest in health-promoting phytochemicals, the current research investigated the development of a dual-captured Ginkgo Biloba and Green Tea Extract into Collagen-Nanostructured Lipid Nanocarriers (Col-NLC-GBil-GTE) for an enhanced therapeutic efficacy against hepatic, colon or breast cancer. NLC considerably reduced cell viability; the most advanced cytotoxicity profile was determined on human colon adenocarcinoma cells (LoVo) and liver cancer cells (HepG2), e.g., tumor cell viability was 21.81% in the presence of Col-NLC-GBil-GTE, similar to that determined for Cisplatin. Col-NLC exhibited apoptosis in HepG2 and LoVo cells and no significant apoptosis induction in normal HUVECs. A 20% increase in apoptosis for HepG2 cells was registered for 100 μg/mL NLC-GBil-GTE compared to Cisplatin (Cis-Pt), e.g., a 63.4% total apoptosis for NLC-GBil-GTE versus a 52.6 apoptosis induced by 100 μg/mL of a chemotherapeutic drug. According to the cell cycle outcomes, an accumulation of hepatocyte HepG2 tumor cells in the G0/G1 phase was detected upon treatment with 100 mg/mL of NLC- and Col-NLC-GBil-GTE, simultaneously with a drastic decrease in the S phase, which may indicate a cell number reduction that enters in the division cycle. The simultaneous delivery of GBil and GTE by synchronizing their bioactivities offers several advantages; Col-NLC-GBil-GTE can be viewed as a noteworthy strategy for consideration in connection with antitumor therapeutic protocols. Full article