The Deyang-Anyue rift trough is a key target for Lower Cambrian Qiongzhusi shale gas exploration in the Sichuan Basin, yet inorganic pore heterogeneity across structural positions remains poorly constrained. Shales from the fifth sublayer in intratrough and trough-margin settings were analyzed using an integrated large-scale Mosaic scanning electron microscopy (LAM-SEM)advanced mineral identification and characterization system (AMICS) workflow, enabling pixel-scale mineral-pore registration and quantitative characterization of inorganic pore types, area fraction, size distribution, and morphology. Intratrough shales, mainly organic-rich to organic-moderate quartz-rich felsic shales, exhibit low inorganic pore area fractions but larger average pore sizes with predominantly unimodal distributions. Their pores are elongated and irregular, showing high eccentricity and low circularity, and are mainly feldspar-hosted dissolution pores. In contrast, trough-margin shales display higher inorganic pore area fractions, smaller pore sizes, and particularly locally multimodal size distributions in organic-lean feldspar-rich shales. These pores are more equant and smoother, characterized by lower eccentricity and higher circularity. Mineral composition and TOC jointly control inorganic pore structures: quartz content is positively correlated with pore size, whereas feldspar content shows a negative correlation. Easily soluble minerals are positively correlated with pore circularity, whereas clay minerals show a negative correlation. In addition, TOC promotes heterogeneous dissolution, leading to decreased circularity and increased eccentricity. These findings reveal two contrasting inorganic pore development patterns within the rift trough and provide new insights into pore evolution mechanisms and reservoir quality variations in deeply buried marine shales, offering a basis for deep marine shale reservoir evaluation and exploration target optimization.
Gabapentin and duloxetine are common treatments for neuropathic pain in adults over 65, but data on their gastrointestinal (GI) bleeding risk are limited. We compared GI bleeding risk after starting gabapentin or duloxetine in this population. We used the TriNetX US Collaborative Network to conduct an active-comparator cohort study using target trial emulation. Patients aged 65 years and above with neuropathic pain diagnosed between January 2020 and December 2024 were included, excluding those with prior GI bleeding, major depressive disorder, or thrombocytopenia. Propensity score matching balanced key covariates. The main outcome was GI bleeding within 24 months, analyzed with Cox regression; secondary analyses included upper/lower GI bleeding, mortality, and hospitalization. Negative controls assessed confounding. The study analyzed 62,926 patients (55,236 gabapentin; 7,690 duloxetine) and matched 7,599 pairs. GI bleeding was less common with gabapentin initiators (1.22%) than duloxetine initiators (2.49%), showing an absolute risk reduction of 1.27% (HR 0.86, 95% CI 0.84-0.89, p < 0.0001), mainly for upper GI bleeding (HR 0.39, 95% CI 0.29-0.53). Lower GI bleeding results were not significant. Gabapentin also showed slightly lower all-cause mortality (HR 0.87, 95% CI 0.84-0.90). Negative control outcomes revealed no notable associations. In older adults with neuropathic pain, gabapentin initiation was associated with a lower risk of GI bleeding than duloxetine, especially for upper GI bleeding. As both drugs offer comparable analgesic efficacy, GI bleeding risk may be a relevant consideration when choosing between them. These findings are hypothesis-generating and should be confirmed in independent datasets and prospective comparative studies will confirm the data.
Accurate human immunodeficiency virus diagnosis is required to treat and prevent transmission. HIV western blot (MP-WB) has major drawbacks such as prolonged turnaround times, and high percentages of indeterminate results. To address these issues, the CDC in 2014 recommended the use of an immunological test capable of differentiating anti-HIV-1 antibodies from anti-HIV-2 antibodies for HIV diagnosis. The Geenius™ HIV 1/2 Confirmatory Assay/Bio-Rad is a rapid, single-use immunochromatographic test designed to confirm and differentiate HIV antibodies. This study, conducted at the Central Virology Laboratory of the Rabat Specialty Hospital, Morocco, evaluated the performance of the Geenius test as an alternative to MP-WB for confirming HIV-1 diagnoses over 24 months. 116 samples were included, 113 patient samples with repeatedly reactive HIV screening test (HIV Combo Ag/Ab) and 3 external quality evaluation programs. Samples were tested by Geenius™ HIV-1/2 confirmatory assay and MP-WB. A nucleic acid amplification test (NAAT) was performed for discordant cases. Geenius and MP-WB mostly agreed in 95% of the overall, with a Cohen's kappa coefficient at 0.728, indicating substantial agreement. Geenius also produced fewer indeterminate results compared with MP-WB (16.67% vs. 83.33%), mainly in low-reactive samples. At the band level, the highest performances were seen with Gp160 and Gp41, showing concordance rates of 97% and 99%, respectively, with Cohen's kappa coefficient of 0.866 and 0.955. In contrast, the p24 and p31 bands demonstrated lower performances. Among six discordant results, five had low HIV Combo index values and were NAAT confirmed negative. A single high screening ratio and positive NAAT discordant case was classified as acute HIV infection. Excluding indeterminate Geenius results, the Geenius assay displayed 99% sensitivity, 100% specificity, 100% PPV, and 90.9% NPV, which justifies its better diagnostic performance compared to MP-WB. The Bio-Rad Geenius HIV-1/2 confirmatory test represents a reliable, rapid, and less labor-intensive alternative to MP-WB, offering a simplified approach for confirming HIV diagnoses, with good sensitivity for gp41 and gp160 bands, and can be integrated into diagnostic algorithms.
Glass transition temperature (T g) is a key thermophysical property in polymer informatics, yet many machine learning (ML) studies focus on point prediction accuracy without explicitly evaluating reliability under chemical novelty. Here, we evaluate two established descriptor-based regressors, gradient-boosted trees (XGBoost) and support vector regression (SVR), on a 410-sample simulation-derived polymer data set using stratified, scaffold-based, and fingerprint-clustered validation regimes. We combine learning curves, applicability-domain diagnostics, split conformal prediction (SCP), subgroup coverage analysis, model-specific descriptor-importance analysis, and interval-aware triage metrics. Performance degraded and variability increased under novelty-enforcing splits, with SVR showing more stable point-prediction behavior than XGBoost in several regimes; this trend is interpreted as benchmark-specific, not as general model-class superiority. Conformal intervals maintained near-nominal marginal coverage but were often too wide for fine-grained candidate ranking, and subgroup diagnostics revealed local reliability limitations in low-similarity, high-T g, or chemistry-specific subsets. Thus, conformal intervals are best interpreted as conservative risk indicators for uncertainty-aware triage, not as high-resolution screening tools. Descriptor-importance analyses highlighted chemically plausible feature families related to topology, polarity, surface area, heteroatom content, and electronic-state descriptors, but these attributions are treated as model-level plausibility diagnostics, not physical validation of T g mechanisms. Overall, this work provides a reproducible reliability-assessment workflow for small-data polymer T g prediction against MD-derived labels, with experimental validation required before deployment against measured T g data.
Microdroplet technology is a cornerstone of modern biophysical analysis for applications such as single-cell studies, drug screening, and chemical synthesis. Many of these applications involve biological and chemical processes that require precise temperature control under physiologically relevant conditions. However, temperature not only influences these processes but also affects droplet formation by altering fluid properties, thereby changing droplet size and encapsulation efficiency. Despite growing interest in environmentally sustainable alternatives to fluorinated oils, the thermal behavior of such systems remains poorly understood. In this study, we introduce a novel experimental approach to investigate thermally controlled microdroplet generation using emu oil as a biocompatible continuous phase. By independently controlling the temperatures of the dispersed and continuous phases, we distinguish their individual contributions to droplet formation. The resulting changes in droplet morphology were quantitatively characterized across a thermal gradient, showing the distinct influence of phase-specific temperature control on droplet generation. Increasing temperature resulted in larger droplets and accelerated the transition from the squeezing to the jetting regime These findings provide practical guidance for temperature-sensitive microfluidic assays, where the aqueous sample and carrier oil are often prepared at different temperatures, and can improve the reproducibility of applications in different fields requiring precise thermal regulation.
A 69-year-old female was admitted with a four-day history of unexplained fever. Lung examination revealed coarse breath sounds, and laboratory tests showed elevated inflammatory markers. She had no identifiable environmental or occupational exposure, and initial screening for common respiratory pathogens was negative. Chest computed tomography (CT) scan demonstrated patchy ground-glass opacities and reticular shadows distributed along the bronchovascular bundles in the right upper lobe and dorsal segments of both lower lobes, with lesions showing the reversed halo sign (RHS). Initial empirical antibiotic therapy was ineffective. Subsequent bronchoalveolar lavage (BAL) culture yielded heavy growth of Pseudomonas putida, with negative fungal and tuberculosis nucleic acid testing. Based on antimicrobial susceptibility testing, the treatment regimen was adjusted to a combination of ceftazidime and amikacin. Following this targeted therapy, the patient's symptomatic improvement occurred while imaging abnormalities persisted, indicating a clinical-radiological dissociation. The patient was discharged after a 15-day hospital stay. This case highlights the following: (1) In community-acquired pneumonia with atypical imaging features (such as the RHS) that is refractory to conventional therapy, the differential diagnosis should be expanded to include environmental opportunistic pathogens like P. putida; (2) The RHS is a non-specific imaging finding, and its diagnostic significance must be interpreted in conjunction with lesion distribution, dynamic changes, and the complete clinical context; (3) Obtaining microbiological evidence through minimally invasive techniques such as BAL is crucial for shifting from empirical to precise targeted therapy, thereby improving patient prognosis.
Various 3,5-disubstituted isothiazolo[4,3-b]pyridines were previously shown to be potent inhibitors of the lipid kinase PIKfyve, displaying broad-spectrum antiviral activity. To further study their structure-activity relationship and to discover novel skeletons as antivirally active PIKfyve inhibitors, a scaffold hopping strategy was applied yielding isothiazolo[4,5-b]pyridines, pyrazolo[4,3-b]pyridines and isothiazolo[3,4-b]pyrazines. Among the newly synthesized scaffolds, the isothiazolo[3,4-b]pyrazines were the most promising, displaying potent and selective PIKfyve inhibition in a biochemical assay, and, in addition, showing antiviral activity against SARS-CoV-2 (in the low μM range). Finally, molecular docking of the various scaffolds in the ATP-binding site of PIKfyve allowed to rationalize their differences in PIKfyve inhibitory activity.
The advancement of sustainable precision agriculture necessitates high-performance, accessible sensing platforms capable of in-field operation. Herein, a scalable, solvent-free Laser Direct Writing (LDW) strategy is reported for fabricating freestanding, seamlessly integrated electrochemical devices based on Laser-reduced Graphene Oxide/Sodium Carboxymethylcellulose (LrGO/CMC) biocomposites. Uniquely, the CMC acts not merely as a matrix but also chemically stabilizes GO sheets via hydrogen bonding, preventing restacking and enabling photothermal processing to selectively convert the film surface into an expanded, highly conductive LrGO architecture. Meanwhile, the unmodified bulk preserves the composite's mechanical integrity. This continuous architecture, in which the active electrode is chemically derived from the substrate itself, effectively eliminates interfacial delamination, thereby enabling flexibility under dynamic stress. Analytically, the device leverages the high electroactive surface area of the rough LrGO network. Using optimized Differential Pulse Voltammetry (DPV) coupled with a rapid electrochemical conditioning step, the sensor demonstrates sensitivity to the Paraquat herbicide (limit of detection of 5.7 ± 1.2 μmol L-1 and a limit of quantification of 18.7 ± 4.1 μmol L-1) and is suitable for field monitoring, while showing selectivity against complex matrix interferents. As a ″lab-on-a-fruit″ proof-of-concept, the flexible device was successfully applied to the rapid (<1 min), noninvasive detection of pesticide residues directly on orange peels using a hydrogel interface. This work establishes LrGO/CMC composites as a versatile and resource-efficient platform for next-generation wearable electronics.
The development of rapid and reliable point-of-care testing (POCT) devices requires optical platforms capable of combining fast readout, sensitivity, and robustness. In this work, a fully integrated optoelectronic platform for fluorescence detection in multichannel microfluidic chips is presented, based on a parallel optical interrogation strategy. The platform employs a diffractive optical element (DOE) to achieve simultaneous excitation of multiple microchannels and an array of waveguide absorption filters (WAFs) for parallel fluorescence collection and efficient rejection of excitation light. This configuration eliminates mechanical scanning and enables optical interrogation within a few seconds. The platform is integrated with a microfluidic handling system and dedicated control software, allowing automated execution of immunoassays. Stability and reproducibility were demonstrated through repeated chip loading experiments, showing low variability across microchannels. As a proof of concept, a fluorescence sandwich immunoassay for C-reactive protein (CRP) was implemented in plasma, achieving a limit of detection of 0.32 µg mL⁻1 with good intra- and inter-chip reproducibility. The proposed approach demonstrates the potential of parallel optical architectures for the development of rapid, scalable, and reliable fluorescence-based POCT platforms.
Astringency in red wine is associated with lubrication changes driven by tannin-saliva interactions, yet the physicochemical basis of astringency subqualities remains unclear. Focusing on drying, a key quality-related subquality, we examined whether wine-saliva aggregates can contribute to lubrication stability rather than only increasing friction. Red wines spanning non-drying to highly drying profiles were mixed 1:1 with unstimulated human saliva. Film thickness and friction were measured under controlled, oral-inspired sliding conditions, and mixtures were centrifuged to obtain soluble (supernatant) and insoluble (pellet) fractions characterized for colloidal stability, interfacial wetting, turbidity, viscosity, and macromolecular composition. Lower drying was associated with thicker films and lower friction, with more stable, entrainable supernatants showing more negative zeta potential, smaller colloids, higher suspended turbidity, and greater polysaccharide support. Overall, the results support a supernatant-centric view in which aggregate functionality and morphology relate to drying subquality, suggesting routes to soften mouthfeel without necessarily reducing phenolics.
Comparative post-marketing safety evidence across commonly used antiglaucoma drug classes remains limited. We conducted a real-world pharmacovigilance study to compare adverse event reporting patterns associated with 6 major classes of glaucoma medications using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). FAERS reports from 2004 to 2024 were analyzed for 6 antiglaucoma drug classes. Baseline characteristics were summarized descriptively. Safety signals were identified using 4 disproportionality methods: reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson Shrinker. Time-to-onset was compared across drug classes. A total of 13,703 prostaglandin analog, 7,108 adrenergic agonist, 3,149 carbonic anhydrase inhibitor, 399 β-blocker, 149 cholinergic agonist, and 424 fixed-combination cases were identified. Ocular events were most frequently reported, but each class showed distinct safety signals. Prostaglandin analogs showed prominent signals for madarosis and eyelid pigmentation; adrenergic agonists for flushing, skin burning sensation, and rash macular; carbonic anhydrase inhibitors for eye allergy, ocular irritation-related events, hypoacusis, dysgeusia, and a systemic signal of interest for metabolic acidosis; β-blockers for bradycardia, arrhythmia, and atrioventricular block; and cholinergic agonists for vitreous detachment, vitreous opacity, and retinal detachment. Compound preparations showed signals including punctate keratitis, cataract, retinal detachment, eye pain, and visual acuity reduced. Among date-complete reports, time-to-onset differed across drug classes, with cholinergic agonists showing the shortest mean onset time and β-blockers the longest. This FAERS-based study compared post-marketing adverse event reporting patterns across 6 major antiglaucoma medication classes. Most signals were ocular, periocular, or visual-function related, with selected nonocular signals also observed. These findings are hypothesis-generating and warrant further clinical validation.
A randomized block experiment was conducted to investigate combined effects of planting density and biostimulants on sorghum performance and saline-alkali soil properties. Treatments included two densities (S, C) and three biostimulant applications: CK (control), sole γ-aminobutyric acid (T1), and γ-aminobutyric acid plus microbial inoculants (T2). The findings demonstrated that density-biostimulant interactions significantly affected sorghum agronomic traits and soil physicochemical properties. CT2 reduced soil pH, electrical conductivity by 18.30%, and bulk density by 16.46%, while increasing soil organic matter by 19%. Soil enzyme (N-acetyl-β-D-glucosaminidase, β-glucosidase, Leucine aminopeptidase, Alkaline phosphatase) activities showed distinct temporal dynamics: CT2 peaked at grain filling, whereas CK dominated at maturity stage. Furthermore, compared with CK, CT2 markedly increased plant height by 18.99%, stem diameter by 35.10%, leaf area by 67.49%, total dry matter by 25.86%, and dry matter partitioning to spikes by 37.03%. It also raised thousand-kernel weight by 33.49% and grains per spike by 51.65%, thereby improving grain yield by 6.00%. By comparison, ST1 yielded a striking 55.02% increment in grain yield. Altogether, these findings implied that under saline-alkali stress, dual biostimulants at low density benefit soil and single plants, and γ-aminobutyric acid at high density boosts population yield, showing individual-population yield tradeoffs. This study presents a novel investigation into the “coupling effects of planting density and combined biostimulant application” (γ-aminobutyric acid (GABA) and a microbial inoculant) on sorghum growth and soil amelioration in saline-alkaline conditions. While previous research has often focused on the individual application of such biostimulants or their combination with organic fertilizers, their synergistic use under different planting patterns in saline-alkali soils remains largely unexplored.Our work uniquely demonstrates that:The interaction between planting density and biostimulant type significantly influences both sorghum yield components and key soil physicochemical properties.Low planting density combined with the dual biostimulant (GABA + microbes) optimally ameliorates saline-alkali soil (significantly reducing pH, EC, and bulk density while increasing organic matter) and enhances individual plant productivity (e.g., dry matter accumulation, 1000-grain weight).High planting density coupled solely with GABA application maximizes population-level yield despite offering minimal soil improvement, revealing a crucial tradeoff between individual plant enhancement and population yield in this system.“Yield was more strongly linked to improved nitrogen availability” facilitated by the treatments “rather than directly to microbial-mediated stress resistance mechanisms”, providing new insight into the primary drivers of yield under these conditions.This research provides a new strategic framework for managing saline-alkali soils, offering two distinct pathways—either for rapid yield generation or for sustained soil improvement—based on the synergy between planting density and specific biostimulant combinations.
The cortical activity of preterm human infants is highly discontinuous, comprising transient high-amplitude bursts separated by periods of relative quiescence. While the functional significance of these bursts is well established, the underlying mechanism remains unclear. This burst-quiescence pattern could arise from a transient refractoriness within excitatory recurrent cortical networks following spontaneous activation. To assess this possibility, we tested whether such activation is followed by a transient reduction in excitability by evaluating whether externally evoked tactile responses are attenuated when somatosensory circuits have recently been active. We recorded electroencephalographic (EEG) responses to tactile stimulation of hands and feet in 35 preterm infants (40% female), with a median postmenstrual age of 32 weeks. This stimulation elicited wideband increases in EEG power, showing two distinct peaks: one in the delta range (1 Hz) and another in the alpha-beta range (~13 Hz). Low-frequency activity showed a single, broadly distributed peak across the scalp, whereas faster high beta-gamma responses were more confined to somatotopically specific regions, suggesting engagement of both widespread (tangential) and localized (columnar) cortical circuits. Importantly, the magnitude of the evoked response was significantly reduced when the activity immediately preceding stimulation resembled the spectro-spatial pattern of the somatosensory evoked response, indicating prior spontaneous activation of the somatosensory network. Stimulus-evoked EEG power changes decreased by 3.2 and 2.5 dB following hand and foot stimulation, respectively, for every 1.0-degree increase in the similarity between pre-stimulus activity and the spectro-spatial pattern of the somatosensory evoked response (scale 0-5). This effect was the strongest and most temporally sustained at slower frequencies. These results suggest that when somatosensory networks are spontaneously active, they become temporarily less responsive to stimulation-a form of refractoriness-preventing immediate reactivation. The extent of this refractory-like modulation is not uniform but depends on the spatial scale of the underlying networks, as indexed by their dominant frequency of activation. This mechanism may explain the cyclical pattern of bursting and quiescence neural activity observed in the preterm brain.
Bone scintigraphy is a sensitive nuclear medicine imaging technique widely used to detect skeletal metastases in cancer patients. Although minimally invasive, anticipation of scan results and concerns regarding disease progression may provoke psychological distress. Understanding anxiety prior to bone scintigraphy is important for improving patient-centered care in nuclear medicine practice. Therefore, this study aimed to evaluate pre-scan state and trait anxiety among cancer patients undergoing bone scintigraphy and to identify demographic factors associated with increased anxiety. A cross-sectional study was conducted among 228 cancer patients undergoing bone scintigraphy at a tertiary care university hospital in Thailand. Anxiety was assessed using the State-Trait Anxiety Inventory, which includes 20 items each for state and trait anxiety. Descriptive statistics were used to summarize demographic characteristics and anxiety levels. Group differences were analyzed using the Mann-Whitney U test and Kruskal-Wallis test, while Spearman's rank correlation was used to examine associations between age and anxiety scores. Most participants demonstrated low anxiety levels, with 67.4% exhibiting low state anxiety and 67.9% showing low trait anxiety. Moderate anxiety was observed in approximately one-third of patients, whereas high anxiety was not identified. Gender, educational level, occupation, and marital status were not significantly associated with anxiety scores (p > 0.05). However, age demonstrated a significant negative correlation with both state anxiety (p < 0.001) and trait anxiety (p = 0.001), indicating higher anxiety levels among younger patients. Patients undergoing bone scintigraphy generally experienced low anxiety levels. Younger age was significantly associated with higher pre-scan anxiety, highlighting the importance of supportive communication and patient-centered care in nuclear medicine practice. Pre-procedural education may help reduce anxiety, particularly among younger patients.
The potential cardiac toxicity of glutamate is debated and has been suggested by some epidemiological and experimental studies. To our knowledge, none investigated the links between both naturally occurring and food additive glutamate and cardiovascular disease (CVD) risk. Our objective was to assess the associations between intakes of total, food additive and naturally occurring glutamate, and the risk of CVD, including cerebrovascular (CVA) and coronary heart (CHD) diseases, in a large population-based study. Participants (n= 108,932, NutriNet-Santé prospective cohort, 2009-2023, France, mean age=42.4y (SD=14.5), 79.3% females) completed repeated 24h-dietary records (mean = 21 (SD=18), up to 84), including brands of industrial food consumed. Exposure to food additive glutamate was evaluated through multiple composition databases and ad-hoc laboratory assays in food matrices. Associations between time-dependent continuous exposures to total, naturally occurring and food additive glutamate and risk of CVD, CVA, and CHD were investigated using multivariable Cox models. During follow-up (median=7.92y), 2397 CVD, 1113 CVA, and 1284 CHD cases were diagnosed. Higher intakes of food additive glutamate (Hazard Ratioper 200mg/d=1.05, 95%Confidence Interval (1.01, 1.09), p-value=0.02), naturally occurring glutamic acid (HR3000mg/d=1.13(1.03, 1.25), p-value=0.009), and total glutamate (HR3000mg/d=1.15(1.05, 1.26), p-value=0.004) were associated with higher risks of CHD. For CVD, corresponding HRs were 1.03(1.00, 1.06; p-value=0.07), 1.09(1.01, 1.18; p-value=0.02) and 1.10(1.02, 1.18; p-value=0.01). No association was detected for CVA (all p-values≥0.5). Residual confounding cannot be entirely ruled out, and causality cannot be established based on this single observational study. This large prospective study showed positive linear associations between higher glutamate intakes and increased risks of CVD. In particular, food additive glutamate, naturally occurring glutamic acid, and total glutamate intakes were all associated with higher CHD risk. This adds to previous experimental data showing a role of glutamate in regulating heart functioning at physiological doses, while also suggesting heart rate dysfunction at higher exposures. ClinicalTrials.gov NCT03335644.
Integrated information theory (IIT) makes two predictions about the role of inactive neurons in consciousness. According to the silent brain (SB) prediction, rendering all active neurons inactive ("silent") in the physical substrate of consciousness (the "main complex") does not eliminate the presence of consciousness, because the neurons are still able to spike. According to the disabled neuron (DN) prediction, rendering a subset of silent neurons in the main complex no longer able to spike ("disabled") can impact the qualitative character of experiences "nonconventionally" associated with those neurons. Bartlett (2022) argues that these predictions are untestable, because evidence for either prediction would imply that the testing conditions were not met. In this paper, we provide a detailed analysis of both silent neuron predictions, showing how they can in fact be tested. For the SB case, we clarify how a neural mechanism outside of the main complex can yield the required report of consciousness while maintaining the SB state. For the DN case, we distinguish between two ways of explaining how a neural mechanism could casually interact with the main complex: an IIT-inspired "dispositionalist" explanation, and a more conventional "actualist" explanation. Drawing on the work of Imre Lakatos, we conclude with a discussion of how the distinction between the two explanations sheds light on why it is so difficult to resolve theoretical disputes about consciousness. Despite these difficulties, we provide a framework that can lead to concrete progress for consciousness science.
This study aimed to identify steroid metabolism-related molecular subtypes, investigate the gene expression patterns of these subtypes, and construct a prognostic risk model as well as predict therapeutic response in gastric cancer. We analyzed 410 TCGA-STAD and 483 GSE84437 gastric cancer samples. Unsupervised consensus clustering based on steroid metabolism-related genes identified molecular subtypes. Differential expression and functional enrichment analyses (GO, KEGG, GSEA) were performed. Prognostic genes were intersected with survival-associated genes, and a Lasso-Cox regression model was used to build a seven-gene risk score. Immune infiltration, tumor mutational burden (TMB), immune checkpoint expression, and drug sensitivity were evaluated. Two steroid metabolism-related gastric cancer subtypes were identified, with steroid-metabolism-poor prognosis subtype showing poorer overall survival. Differential expression analysis revealed 1,709 genes enriched in immune regulation, calcium signaling, cell adhesion, and extracellular matrix remodeling. Seven key genes (PRICKLE1, SERPINE1, APOD, RIMS1, GLP2R, CDH19, GRP) were used to construct a risk score, which correlated with advanced stage, steroid-metabolism-poor prognosis subtype subtype, and worse survival, and was an independent prognostic factor. High-risk and steroid-metabolism-poor prognosis subtype tumors displayed higher immune infiltration and immune scores, lower TMB, and upregulated immune checkpoint genes, indicating an immunosuppressive microenvironment. Drug sensitivity differed across subtypes and risk groups, suggesting potential implications for personalized therapy. Steroid metabolism defines molecular heterogeneity, immune features, and prognosis in gastric cancer. The seven-gene risk model provides a reliable tool for survival prediction and may guide personalized therapeutic strategies.
Antimicrobial resistance and the overuse of antimicrobials have driven the search for innovative therapies, particularly those based on natural compounds and medicinal plant derivatives, aiming to develop new drugs. This study aimed to investigate the antimicrobial and antibiofilm activities of crude ethanolic extract of O. campechianum (CEE-OC), and commercial (AgNPs-C), non-commercial (AgNPs-NC), and Ocimum campechianum-biosynthesized (AgNPs-OC) silver nanoparticles, against 21 Staphylococcus spp. isolates. Antimicrobial activity of rosmarinic acid (RA) against six isolates was also determined. The minimum inhibitory concentration (MIC) of CEE-OC ranged from 6,250 to 781.25 µg/mL, showing the highest antimicrobial activity among the substances evaluated. AgNPs-OC exhibited MIC values approximately fourfold lower than those of CEE-OC. In contrast, AgNPs-C and AgNPs-NC showed no antimicrobial activity at the concentrations tested. CEE-OC and AgNPs-OC inhibited biofilm formation but had no effect on established biofilms. Molecular docking analysis suggested a potential interaction between RA and the NorA efflux pump protein. The results indicated that O. Campechianum extract and biosynthesized silver nanoparticles may represent promising antimicrobial alternatives, although further studies are needed to elucidate the mechanisms underlying their activity.
Radioactive aerosol size classification is important for exposure assessment and decommissioning operations, particularly at the Fukushima Daiichi Nuclear Power Plant decommissioning site, where airborne particles may be generated or resuspended during remote inspection and debris retrieval. This study presents the development of a two-stage 3D-printed virtual impactor, called μSPLIT, designed to separate aerosols into three aerodynamic diameter classes (>10 μm, 1-10 μm, and <1 μm) while enabling direct postcollection analysis on integrated filters. The objective is to develop a virtual impactor that can be fabricated at a reduced cost and be disposed of easily after usage by incineration, without generating any hazardous human exposure during cleaning and decontamination activities, and free from metallic wastes that are not easily disposed of. The flow path was designed and optimized by computational fluid dynamics and Lagrangian particle tracking, and prototypes were fabricated by stereolithography. Numerical simulations predicted cutoff diameters of 9.0 and 1.3 μm for the first and second stages, respectively, with relatively sharp separation in both cases. The simulations also identified limitations of the current geometry, including small-particle contamination in the minor flow and large-particle contamination in the major flow of the second stage. Dimensional measurements of printed prototypes revealed contraction and corner rounding in the internal channels, confirming the need for fabrication compensation and quality control. Experimental tests with incense smoke provided a preliminary functional check, showing that submicrometric particles were mostly collected in the <1 μm particle class. Additional tests with Rn-progeny-bearing NaCl particles, characterized by a geometric mean aerodynamic diameter of 1.70 μm, produced the highest α activity on the middle filter (1-10 μm particle class), consistent with the expected classification. These results demonstrate the proof of concept of a lightweight and low-cost impactor for simultaneous aerosol size classification and direct radioactive particle analysis, while also identifying key areas requiring further optimization, particularly the second-stage geometry, quantitative wall loss assessment, and validation with standardized aerosols.
Parkinson's disease (PD) and sensorineural hearing loss (SNHL) are both prevalent conditions among older adults. Although increasing number of studies have investigated SNHL as a risk factor for PD, it is not well known how diagnosed PD affects the likelihood of SNHL diagnosis. To evaluate the temporal changes in the amount of SNHL diagnoses in relation to PD diagnosis. This nationwide register-based study included 22,189 community-dwelling persons who received a clinically verified PD diagnosis in 1996-2015 in Finland and a 1:1 matched comparison cohort. PD diagnoses were identified from the Special Reimbursement Register and SNHL diagnoses were extracted from Care Register for Healthcare. Incidences of the diagnoses were calculated per 100 person-years (PY) for each six-month period from ten years before to ten years after PD diagnosis. Before PD diagnosis the incidence of SNHL diagnosis was higher among people with PD (0.65/100 PY) than in the comparison cohort (0.58/100 PY, hazard ratio, 95% CI 1.11, 1.05-1.18) and increased similarly in both groups. After PD diagnosis the incidence was lower among people with PD (1.00 and 1.28/100 PY, hazard ratio, 95% Cl 0.78, 0.74-0.83) and declined shortly after PD diagnosis whereas it continued to increase in the comparison group. After PD diagnosis, the incidence of SNHL appears to decline compared to the control group, suggesting a possible deprioritization of hearing care. Our findings are also consistent with previous research showing an association between SNHL and PD, with a higher incidence of SNHL observed in individuals with PD.