Search Results (48,919)

Recent studies have revealed a specific relationship between gut bacteria and inflammatory skin profiles. We aimed to perform a species-level comparative metagenomic analysis of the gut microbiome in patients with psoriasis, hidradenitis suppurativa (HS), and pemphigus foliaceus (PF). We included omnivorous nonsmokers and nondrinkers with psoriasis (n = 24), HS (n = 10), and PF (n = 11), as well as healthy controls (n = 10). We collected faecal samples from all patients for classic parasitological analysis. Gut microbiome analysis was conducted using shotgun next-generation sequencing. We used the Deseq2, Limma_voom, LinDA, and MaAMaAsLin 2 bioinformatics tools to evaluate concordance and differential abundance between patients. Thirteen patients (23.64%) were diagnosed with active intestinal parasitosis. The presence of intestinal parasitosis was significantly related to immunosuppression (p = 0.009). The most abundant microorganism species found in the faeces of the patients evaluated was Escherichia coli. Psoriasis patients presented a greater abundance of bacteria from the Veillonellaceae family, whereas PF patients presented a greater abundance of Firmicutes bacteria. Patients with PF showed increased E. coli virulence and antibiotic resistance functional markers. Immunosuppression significantly influenced the presence of intestinal parasitosis as well as increased the virulence of functional markers in patients with PF receiving systemic corticosteroid therapy. Full article

The global proliferation of plastics and their degradation into microplastics (<5 mm) have created a pervasive environmental crisis with severe ecological and human health consequences. Despite the exponential growth in microplastic research over the past decade, standardized protocols are still lacking. The absence of consistent sampling, analysis, and reporting methods limits data comparability, interoperability, and harmonization across studies. This study conducted a systematic bibliographic review of 355 peer-reviewed articles published between 2010 and 2022 that investigated microplastics in freshwater as well as marine water and sediment environments. The goal was to evaluate methodological consistency, sampling instruments, measurement units, reported characteristics, and data-sharing practices to identify pathways toward harmonized and FAIR (Findable, Accessible, Interoperable, and Reusable) microplastic data. Results show that 80.6% of studies focused on marine environments, 18% on freshwater, and 1.4% on both. This highlights persistent data gaps in freshwater systems, which function as key transport pathways for plastics to the ocean. Most studies targeted water (59%) rather than sediment (41%) and were mostly based on single-time sampling, limiting long-term analyses. Surface layers (<1 m) were predominantly sampled, while deeper layers remain understudied. Nets, particularly Manta, neuston, and plankton nets were the dominant tools for water sampling, whereas grabs, corers, and metallic receptacles were used for sediments. However, variations in mesh size and sampling depth introduce substantial biases in particle size recovery and reduce comparability across studies. The most common units were counts/volume for water and counts/g dry weight for sediments, but more than ten unit expressions were identified, complicating conversions. Only 35% of studies reported all four key microplastic characteristics (color, polymer type, shape, and size), and less than 20% made datasets publicly available. To advance harmonization, we recommend the adoption of consistent measurement units, mandatory reporting of key metadata, and wider implementation of open data practices aligned with the FAIR principles. These insights provide a foundation for developing robust monitoring strategies and evidence-based management frameworks. This is especially important for freshwater systems, where data remain scarce, and policy intervention is urgently needed. Full article

The Micangshan lead–zinc deposits, located in the northern margin of the Sichuan Basin, are classified as the Mississippi Valley-type (MVT) deposits. This study investigates the genetic linkage between Pb–Zn mineralization and paleo-oil reservoirs in the region, which is distinct from separate investigations on lead–zinc deposits or paleo-oil reservoirs. Through mineralogy, isotope, and fluid inclusion analyses, it is revealed that the direction of ore-forming fluid migration and the ore-forming process are closely related to the thermal cracking of paleo-oil reservoirs. The deposits show a characteristic clustered distribution along the southern part of the Micangshan area, with high-grade mineralization concentrated in the Nanmushu and Kongxigou Pb–Zn deposits. Rb–Sr isotopic dating indicates that mineralization occurred during the Late Cambrian to Early Ordovician (Nanmushu deposit 486.7 ± 3.1 Ma; Kongxigou deposit 472 ± 6.1 Ma), coinciding with the formation of the first-stage paleo-oil reservoirs. The study concludes that the MVT Pb–Zn mineralization in the Micangshan area is genetically linked to the first-stage paleo-oil reservoirs’ hydrocarbon generation and migration events. The organic-rich hydrothermal fluids facilitated the migration and precipitation of Pb–Zn minerals. Full article

Excitable neurons are intrinsically capable of firing action potentials (AP), yet a state of hyperexcitability is prevented in the central nervous system by powerful GABAergic inhibition. For this inhibition to be effective, it must occur before excitatory signals can initiate runaway activity, implying the existence of a proactive control system. To test for such proactive inhibition, we used Ca²⁺ imaging and patch-clamp recording to measure how hippocampal neurons respond to depolarization and glutamatergic agonists. In mature hippocampal cultures (14 days in vitro (DIV)) and acute brain slices from two-month-old rats, neurons exhibited non-simultaneous responses to various excitatory stimuli, including KCl, NH₄Cl, forskolin, domoic acid, and glutamate. We observed that the Ca²⁺ rise occurred significantly earlier in GABAergic neurons than in glutamatergic neurons. This delay in glutamatergic neurons was abolished by GABA(A) receptor inhibitors, suggesting a mechanism of preliminary γ-aminobutyric acid (GABA) release. We further found that these early-responding GABAergic neurons express calcium-permeable kainate and AMPA receptors (CP-KARs and CP-AMPARs). Application of domoic acid induced an immediate Ca²⁺ increase in neurons expressing these receptors, but a delayed response in others. Crucially, when domoic acid was applied in the presence of the AMPA receptor inhibitors NBQX or GYKI-52466, the response delay in glutamatergic neurons was significantly prolonged. This confirms that CP-KARs on GABAergic neurons are responsible for the delayed excitation of glutamatergic neurons. In hippocampal slices from two-month-old rats, depolarization with 50 mM KCl revealed two distinct neuronal populations based on their calcium dynamics: a majority group (presumably glutamatergic) exhibited fluctuating Ca²⁺ signals, while a minority (presumably GABAergic) showed a steady, advancing increase in [Ca²⁺]i. This distinction was reinforced by the application of domoic acid. The “advancing-response” neurons reacted to domoic acid with a similar prompt increase, whereas the “fluctuating-response” neurons displayed an even more delayed and fluctuating reaction (80 s delay). Therefore, we identify a subgroup of hippocampal neurons—in both slices and cultures—that respond to depolarization and domoic acid with an early [Ca²⁺]_i signal. Consistent with our data from cultures, we conclude these early-responding neurons are GABAergic. Their early GABA release directly explains the delayed Ca²⁺ response observed in glutamatergic neurons. We propose that this proactive mechanism, mediated by CP-KARs on GABAergic neurons, is a primary means of protecting the network from hyperexcitation. Furthermore, the activity of these CP-KAR-expressing neurons is itself regulated by GABAergic neurons containing CP-AMPARs. Full article

Background/Objectives: The latest National Comprehensive Cancer Network (NCCN) Central Nervous System (CNS) Guidelines recommend utilizing next-generation sequencing (NGS) to enable comprehensive genomic profiling (CGP) as the preferred approach for molecular characterization of central nervous system (CNS) malignancies. CNS malignancies present distinct challenges due to the infeasibility of tissue-based testing for many patients and the restrictive nature of the blood–brain barrier (BBB) making plasma-based liquid biopsy an ineffective alternative. Recent advances in liquid biopsy have extended molecular testing beyond plasma to include cerebrospinal fluid (CSF), which serves as a valuable source for tumor-derived nucleic acids. Methods: The Belay Summit™ 2.0 is a high-throughput CGP assay capable of detecting multiple variant types, including single nucleotide variants (SNVs) and small insertion and deletions (Indels), copy number variations (CNVs), gene fusions, splice variants, and immunotherapy biomarkers such as microsatellite instability (MSI) and tumor mutational burden (TMB). This study details the analytical and clinical validation of Summit™ 2.0 to assess its technical performance and clinical sensitivity. Analytical validation was conducted using 68 specimens, demonstrating robust and reproducible detection of all variant types with 15 ng of CSF-derived total nucleic acid (tNA). Results: The analytical sensitivity of the Belay Summit™ 2.0 assay for SNVs and Indels was determined to be 96.7% with a 100% limit of detection (LoD) at a variant allele frequency of 0.3%. Clinical validity was evaluated across a cohort of 118 CSF specimens, including both primary and metastatic CNS tumors, demonstrating 96% sensitivity and 98% specificity. Conclusions: These findings support the use of the Belay Summit™ 2.0 assay for accurate and reproducible genomic profiling of CNS tumors using tumor-derived nucleic acids from CSF in patients for whom tissue-based testing is considered infeasible, unsafe, or not deemed by the prescribing physician to be clinically appropriate. Full article

The discovery and development of new drugs is a lengthy, complex, and costly process, often requiring 10–20 years to progress from initial concept to market approval, with clinical trials representing the most resource-intensive stage. In recent years, Artificial Intelligence (AI) has emerged as a transformative technology capable of reshaping the entire pharmaceutical research and development (R&D) pipeline. The purpose of this narrative review is to examine the role of AI in drug discovery and development, highlighting its contributions, challenges, and future implications for pharmaceutical sciences and global public health. A comprehensive review of the scientific literature was conducted, focusing on published studies, reviews, and reports addressing the application of AI across the stages of drug discovery, preclinical development, clinical trials, and post-marketing surveillance. Key themes were identified, including AI-driven target identification, molecular screening, de novo drug design, predictive toxicity modelling, and clinical monitoring. The reviewed evidence indicates that AI has significantly accelerated drug discovery and development by reducing timeframes, costs, and failure rates. AI-based approaches have enhanced the efficiency of target identification, optimized lead compound selection, improved safety predictions, and supported adaptive clinical trial designs. Collectively, these advances position AI as a catalyst for innovation, particularly in promoting accessible, efficient, and sustainable healthcare solutions. However, substantial challenges remain, including reliance on high-quality and representative biomedical data, limited algorithmic transparency, high implementation costs, regulatory uncertainty, and ethical and legal concerns related to data privacy, bias, and equitable access. In conclusion, AI represents a paradigm shift in pharmaceutical research and drug development, offering unprecedented opportunities to improve efficiency and innovation. Addressing its technical, ethical, and regulatory limitations will be essential to fully realize its potential as a sustainable and globally impactful tool for therapeutic innovation. Full article

Herein, an electrochemically activated zinc–cobalt-layered double hydroxide/nickel–cobalt-sulfide (EA ZnCo-LDH/NCS) hierarchical composite electrode was fabricated in situ via coupled hydrothermal synthesis and electrodeposition. The influence of electrolyte concentration on the activation efficiency was systematically analyzed, and the corresponding effects of electrochemical activation on each component were elucidated. Benefiting from the introduction of the Zn component and subsequent electrochemical activation, the composite electrode exhibits a marked performance enhancement. The EA ZnCo-LDH/NCS electrode achieves a high areal specific capacitance (Cs) of 11.39 F cm⁻² at 4 mA cm⁻², maintains 70.15% of this value when the current density is increased ten-fold, and retains 80.05% of its initial capacity after 5000 cycles. Full article

Jacquemontia pentantha (Jacq.) G. Don. (Convolvulaceae): This is a plant with rich ethnobotanical uses, but its essential oil (EO) composition and overall biological properties remain largely uninvestigated. In this research, the J. pentantha EO (JPEO) is characterized in a thorough manner, with an evaluation of its in vitro antioxidant, antimicrobial, and cytotoxic properties, aiming to provide scientific support for ethnobotanical uses, as well as the definition of new potentialities. The EOs were isolated from the aerial part of the plant via hydrodistillation, and a qualitative analysis of the components was carried out via GC–MS. The biological properties were investigated by means of standard in vitro assays: namely, DPPH and ABTS for the measurement of antioxidant activity, the disk diffusion technique, and the microbroth dilution assay for the evaluation of antimicrobial activity against six bacterial species, as well as for the assessment of the activity against five species of Candida fungi, whereas the cytotoxic activity against MCF-7 and HepG2 cells was assessed using the MTT assay. Preliminary characterization of the EOs via GC/MS revealed a particular “chemical profile” with a high concentration of himachalene-type sesquiterpenes, namely, β-himachalene (6.47%) and (+)-α-himachalene (6.46%), together with phenolic monoterpenoids. The EOs showed significant antioxidant activity (IC₅₀ = 172.41 and 378.94 µg/mL, respectively), high phenolic content (97.34 mg GAE/g), and significant antibacterial activity (MIC = 4.68 µg/mL), especially against Pseudomonas aeruginosa, as well as against Candida albicans (MFC = 3.90 µg/mL), together with dose-dependent cytotoxic effects on the two cell lines, with IC₅₀ = 161.62 and 151.87 µg/mL, respectively. This research indicates that the EO of this plant is a potential source of a certain “chemical profile” with noteworthy antibacterial and cytotoxic properties, thus providing scientific support for its ethnobotanical use and highlighting its particular potential for developing pharmaceutical agents against infections and cancer. Full article

Background: This study investigates the influence of emotional processing on flexor reflex responses in the upper limbs, focusing on cutaneomuscular reflexes (CMRs) and the cutaneous silent period (CSP) in patients with chronic neuropathic pain. The modulation of motor reflexes by emotions remains unclear. Methods: Fifty-one patients with chronic upper limb neuropathic pain (carpal tunnel syndrome, other neuropathies, post-burn hypertrophic scars) and twenty healthy controls underwent standardized electrodiagnostic signal acquisition. Neurophysiological assessments (CMRs, CSP, standard nerve conduction tests) and psychological evaluations (anxiety, depression, emotion processing) were conducted. Neurophysiological signal acquisition included median and ulnar nerve conduction studies recorded with an electrodiagnostic system (48 kHz sampling rate; 30–3000 Hz bandpass). CSP and CMRs were recorded from the abductor pollicis brevis using surface electrodes (bipolar belly–tendon montage) and were evoked by electrical stimulation delivered through ring electrodes, with individualized perceptual-threshold calibration. Statistical analyses examined correlations between neurophysiological and psychological measures. Results: Patients showed significantly longer duration and higher intensity of CMRs and CSP than controls (p < 0.01). CMR and CSP durations correlated positively with anxiety, depression, and alexithymia scores, and negatively with facial emotion recognition. General Linear Model analyses indicated these relations were mediated by tactile and pain perception thresholds. Conclusions: The findings support that spinal reflex responses in the upper limbs are modulated by emotional and cognitive-affective processes, especially in chronic pain contexts. This highlights the complex interaction between emotion regulation and motor control in neuropathic pain conditions. Full article

Background/Objectives: Transmission electron microscopy (TEM) is an essential tool for diagnosing renal diseases. It produces high-resolution visualization of glomerular and mesangial ultrastructural features. However, manual interpretation of TEM images is labor-intensive and prone to interobserver variability. In this study, we introduced and evaluated deep learning architectures based on YOLOv8-OBB for automated detection of six ultrastructural features in kidney biopsy TEM images: glomerular basement membrane, mesangial folds, mesangial deposits, normal podocytes, podocytopathy, and subepithelial deposits. Methods: Building on our previous work, we propose a modified YOLOv8-OBB architecture that incorporates three major refinements: a grayscale input channel, a high-resolution P2 feature pyramid with refinement blocks (FPRbl), and a four-branch oriented detection head designed to detect small-to-large structures at multiple image scales (feature-map strides of 4, 8, 16, and 32 pixels). We compared two pretrained variants: our previous YOLOv8-OBB model developed with a grayscale input channel (GSch) and four additional feature-extraction layers (4FExL) (Pretrained + GSch + 4FExL) and the newly developed (Pretrained + FPRbl). Results: Quantitative assessment showed that our previously developed model (Pretrained + GSch + 4FExL) achieved an F1-score of 0.93 and mAP@0.5 of 0.953, while the (Pretrained + FPRbl) model developed in this study achieved an F1-score of 0.92 and mAP@0.5 of 0.941, demonstrating strong and clinically meaningful performance for both approaches. Qualitative assessment based on expert visual inspection of predicted bounding boxes revealed complementary strengths: (Pretrained + GSch + 4FExL) exhibited higher recall for subtle or infrequent findings, whereas (Pretrained + FPRbl) produced cleaner bounding boxes with higher-confidence predictions. Conclusions: This study presents how targeted architectural refinements in YOLOv8-OBB can enhance the detection of small, low-contrast, and variably oriented ultrastructural features in renal TEM images. Evaluating these refinements and translating them into a web-based platform (Renal-AI) showed the clinical applicability of deep learning-based tools for improving diagnostic efficiency and reducing interpretive variability in kidney pathology. Full article

Background: Axillary lymph node (ALN) metastasis is a critical prognostic determinant in breast cancer (BC) that informs surgical management. However, surgically clearing the axilla carries morbidity, so less invasive methods of risk-stratifying patients are needed. ALN fine needle aspiration (FNA) is currently used to detect BC metastases, but these samples also contain immune cells. Methods: Cells obtained via FNA from BC-patient-derived ALNs were analysed using flow cytometry. Results: FNA acquires sufficient leukocytes for comprehensive immunophenotyping of reactive, patient-derived ALNs. All CD4⁺ and CD8⁺ T-cell subsets (naïve, terminal effector, central memory, and effector memory) and rarer (<2%) natural killer (NK) and plasmacytoid dendritic cell (pDC) populations are represented. Importantly, the immune-cell profile of one reactive ALN appears to reflect the immune status of the patient’s axilla. Furthermore, FNA captures immune differences between patients with ≤1 or ≥2 metastatic ALNs. Increased numbers of naïve CD4⁺ T cells, but fewer terminal effector, central memory, and effector memory subpopulations, were obtained from patients with ≥2 metastatic ALNs. Moreover, despite their sparse distribution pattern on whole-section immunohistochemistry (WSI), FNA revealed that CD56⁺ NK cell activation receptors were decreased in patients with ≥2 metastatic ALNs. Finally, FNA captured a decrease in pDCs in patients with ≤1 metastatic ALNs, despite their clustered distribution pattern on WSI. Conclusions: FNA is not only feasible for sampling leukocytes from reactive, patient-derived ALNs, but also identifies immune-cell profiles that reflect axillary tumour burden in BC. Thus, this technique could be used to risk-stratify BC patients in the future. Full article

Even though environmental health and climate change are rapidly intensifying the severity of determinants of disease and inequity, training for health professionals in these areas remains fragmented across Europe. To address this gap, the European Medical Association (EMA), in collaboration with the European Network on Climate and Health Education (ENCHE), the International Network on Public Health and Environment Tracking (INPHET) and University College London, convened a one-day hybrid roundtable in London on 17 September 2025, focused on “Preparing Health Professionals for Environmental Health and Climate Change: A Challenge for Europe”. The programme combined keynote presentations on global and European policy, health economics and curriculum design with three disease-focused roundtables (respiratory, cardiovascular and neurological conditions), each examining the following topics: (A) climate and environment as preventable causes of disease; (B) healthcare as a source of environmental harm; and (C) capacity building through education and training. Contributors highlighted how environmental epidemiology, community-based prevention programmes and sustainable clinical practice can be integrated into teaching, illustrating models from respiratory, cardiovascular, surgical and neurological care. EU-level speakers outlined the policy framework (European Green Deal, Zero Pollution Action Plan and forthcoming global health programme) and tools through which professional and scientific societies can both inform and benefit from European action on environment and health. Discussions converged on persistent obstacles, including patchy national commitments to decarbonising healthcare, isolated innovations that are not scaled and curricula that do not yet embed sustainability in examinable clinical competencies. The conference concluded with proposals to develop an operational education package on environmental and climate health; map and harmonise core competencies across undergraduate, postgraduate and Continuing -professional-development pathways; and establish a permanent EMA-led working group to co-produce a broader position paper with professional and scientific societies. This conference report summarises the main messages and is intended as a bridge between practice-based experience and a formal EMA position on environmental-health training in Europe. Full article

Objective: To test whether inpatient electrical muscle stimulation (EMS) using Russian current (5 kHz carrier, 50 Hz modulation; 4 s ON/6 s OFF) improves mobility and balance in elderly people with chronic cerebral ischaemia. Design: Prospective single-centre controlled observational pilot, embedded in routine inpatient rehabilitation; no concealed randomisation (EMS + standard care; sham EMS + standard care; standard care only (control)). Methods: A single-centre controlled observational study with three groups was conducted (EMS n = 27, control n = 10, sham n = 7) with 3–9 sessions over 2 weeks (20 min; quadriceps and calves). Pre/Post Outcomes: Tinetti (balance/gait), Rivermead Mobility Index, Timed Up and Go (TUG), ankle extensor maximal voluntary force (MVF), stabilography (statokinesiogram path length (L), mean velocity of COP (V), sway area (S), and myotonometry; ANOVA, α = 0.05). Ethics approval and informed consent were obtained. Between-group differences in change scores were evaluated descriptively, and no formal hypothesis-testing was planned. Results: EMS showed significant gains versus control/sham—higher Tinetti total and Rivermead scores, faster TUG, higher MVF, and improved stabilography in the eyes-closed condition (reduced L, V, and S), with good tolerability and no serious adverse events (SAEs). Conclusions: Short-course Russian-current EMS is feasible and associated with clinically meaningful improvements in balance, gait, and strength in elderly patients with chronic cerebral ischaemia; however, larger randomised trials are warranted. Full article

Sympatric species are closely related taxa that coexist within the same habitat through niche partitioning, and kingfishers serve as an ideal group for studying such ecological mechanisms. The present study examined the perch height in relation to foraging behaviour and hunting success of five kingfisher species: Common Kingfisher (Alcedo atthis), White-throated Kingfisher (Halcyon smyrnensis), Pied Kingfisher (Ceryle rudis), Stork-billed Kingfisher (Pelargopsis capensis), and Black-capped Kingfisher (Halcyon pileata). The study was conducted between 2021 and 2023, across seven habitat types in Kerala, India (Kadalundi–Vallikkunnu Community Reserve (KVCR) mangroves, Kallampara mangroves, Vadakkumpad mangroves, Vazhakkad agroecosystem, Mavoor wetland, Sanketham wetland, and Elathur beach). A generalized linear mixed model (GLMM) with a binomial distribution and logit link function was used to analyze hunting success across species. The model indicated that the effect of perch height on hunting success varied among species, though neither perch height nor species identity alone had a significant effect. Most species favored mid-height perches (2–5 m) for foraging, with the Common Kingfisher exhibiting moderate success across all heights and habitats. The Pied Kingfisher showed significantly reduced success at higher perches, while the Stork-billed Kingfisher achieved the highest success at mid-heights (2–5 m). The White-throated Kingfisher showed a non-significant negative association with capture success, whereas the Black-capped Kingfisher exhibited a neutral to positive relationship across perch heights. Among all variables tested, prey availability emerged as the sole significant predictor of hunting success, indicating that prey abundance is the principal determinant of foraging efficiency in tropical wetlands, rather than environmental conditions. Our findings confirm a pattern of vertical stratification in resource partitioning among sympatric kingfisher species and underscore the importance of conserving habitats that retain natural perch sites of varying heights. Full article

Silica-based sorbents covalently modified with polyhedral boron clusters represent a promising platform for highly selective separation materials, yet robust and synthetically accessible immobilization protocols remain underdeveloped. In this work, novel sorbents based on commercially available silica gels functionalized with closo-dodecaborate anions were synthesized and systematically characterized. Two immobilization strategies were compared: direct nucleophilic addition of surface aminopropyl groups to the nitrilium derivative (Bu₄N)[B₁₂H₁₁NCCH₃] and sol–gel condensation of a pre-formed boron-containing APTES-derived silane. Covalent attachment via amidine bond formation was confirmed by solution and MAS ¹¹B NMR spectroscopy, IR spectroscopy, elemental analysis/ICP-OES, and SEM. The direct grafting route afforded a boron loading of 4.5 wt% (≈20% of the theoretical capacity), with the efficiency limited by electrostatic repulsion between anionic amidine fragments on the negatively charged silica surface, whereas the APTES route gave lower absolute loading (0.085 mmol/g) due to the low specific surface area of the coarse silica support. Despite the moderate degree of functionalization, the resulting boron cluster–modified silica gels are attractive candidates for specialized chromatographic applications, where the unique hydrophobic and dihydrogen-bonding properties of closo-dodecaborates may enable selective retention of challenging analytes and motivate further optimization of surface morphology and immobilization conditions. Full article