This article and accompanying video provide a comprehensive workflow for incorporating headset-mounted augmented reality (AR) navigation for minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). Consecutive patients undergoing a single level MIS-TLIF with AR navigation for degenerative spondylolisthesis were analyzed between January 2023-2025. Demographic, intraoperative, and postoperative outcomes were collected. The AR workflow features a wireless headset with projection of intraoperative navigation in the surgical field. MIS pedicle screw placement, facetectomy, disc preparation, and contralateral arthrodesis are carried out percutaneously though single line of sight using navigated instruments. A total of 138 consecutive patients underwent AR-assisted spinal fusion at our institution and 22 cases of single-level MIS TLIF met inclusion criteria. Mean age was 62.3 ± 15 years, 59% were females, mean BMI was 29.4±5.7 kg/m2, and mean CCI score was 2.1±1.5. The mean operative time from incision to closure for the entire cohort was 129±28 min, mean fluoroscopy time was 41±12 s, EBL was 51±33 ml, and the mean length of stay was 1.9±1.8 days. Two (9%) patients required reoperation at a mean 5 weeks. The AR protocol was safely implemented in all cases with improvement in back and leg pain and no persistent neurologic deficits at mean 163 day follow up. Headset-mounted AR navigation is a feasible and reproducible tool to provide visualization for MIS TLIF that can be successfully integrated into surgical workflow. In this initial case series, its use was associated with an acceptable early safety profile and consistent perioperative outcomes. However, given the limitations of this study, including its retrospective design and lack of a comparator cohort, further prospective and comparative studies are necessary to evaluate its impact on surgical efficiency, accuracy, and clinical outcomes.
A revision of Central African specimens of Rhipidoglossum has revealed two new species from the Cameroon Volcanic Line (CVL) and the lowland and peripheric forests of the Guineo-Congolian rainforest block. Rhipidoglossum acuminifolium sp. nov. is endemic to the CVL and is morphologically related to R. delepierreanum from the Western Rift Mountains. This disjunction may suggest historical connectivity or long-distance dispersal between these montane systems. Footage from Mount Cameroon recorded the settling moth Afroracotis cf. squalida (Lepidoptera, Erebidae) as a potential pollinator of R. acuminifolium, as well as numerous other plant-animal interactions, including only the second documented orchid-orthopteran interaction, involving nectaring by raspy crickets (Orthoptera, Gryllacrididae). Rhipidoglossum acuminifolium is preliminarily assessed here as Endangered (EN) under the IUCN Red List criteria. The morphologically allied R. delepierreanum is here newly recorded for Burundi, the Democratic Republic of the Congo (DRC), and Uganda. In turn, Rhipidoglossum falcatulum sp. nov. is described from the Central African Republic and the DRC, where it occurs in the Congolian and Central Zambezian regions, in Guineo-Congolian lowland forests and muhulu vegetation. It is preliminarily assessed as Endangered (EN), and it is also hypothesised to be phalaenophilous. These two novelties increase the species diversity of Rhipidoglossum up to 56 species in Tropical Africa and the Gulf of Guinea Islands.
Creating a dependable approach for identifying both the mass of a shuttle car and how material is distributed in it removes the need for equipment operators to manually engage the flight chain. The quantification of environmental and installation conditions and the extent of influence considering their combined contribution towards inaccurate or exclusive measurements are to that degree limited. This experimental study investigated how two different strain transducers-installed in a force-shunt configuration-respond to thermo-mechanical loads when used to determine load distribution and position. Initial observations indicated that thermal effects at the installation site contributed to measurement inaccuracies or exclusive readings. The investigation quantified the impact of environmental and installation variables on measurement accuracy and found this influence to be indirectly linked to the mechanical properties of the substrate to which the strain transducers were mounted. Mounting bolt torque was determined to exert a negligible effect on strain measurement accuracy for the custom-built strain transducers. Nonetheless, both transducers failed to consistently return to the selected baseline at the start of experiments since thermal dependence persisted at the balanced state following the first cycle of loading. The research indicated that the custom-built force-shunt strain transducers are an effective means for mapping the profile and location of coal in shuttle cars, provided that the systems are subjected to continuous and cyclic rebalancing to maintain accuracy.
Drug repurposing can accelerate therapeutic development, yet existing computational approaches typically rely on a single evidence type and lack validation across biological scales. Here we present LinkD, an integrated framework combining structure-informed latent diffusion modeling for drug-target interaction prediction with entropy-aware selectivity scoring, large-scale cellular phenotype validation, and real-world clinical evidence from population-scale electronic health records (EHRs). LinkD comprises four modules. LinkD-DTI, a diffusion-based affinity prediction model, ranks first on 8 of 9 benchmarks spanning BindingDB, Davis, and KIBA (RMSE 0.447-0.699) under random and cold-start settings. LinkD-Select computes entropy-based selectivity scores that distinguish on-target from off-target interactions, recovering 95.3% of known selective drug-target pairs with concordant docking support. LinkD-Pheno validates predicted molecular effects through concordance of drug sensitivity and CRISPR gene-dependency profiles across 960 cancer cell lines. LinkD-Agent ( https://linkd-agent.onrender.com/ ) is an interactive AI system enabling transparent, multi-evidence hypothesis generation without programming expertise. Population-level analyses of 11.5 million individuals from Mount Sinai and UK Biobank EHR cohorts show that LinkD-prioritized drug-disease associations are enriched for protective clinical signals, including the beta-blockers carvedilol (OR: 0.66, 95% CI: 0.59-0.73) and propranolol (OR: 0.77, 95% CI: 0.61-0.97) associated with reduced prostate cancer risk-corroborated by ADRB2 docking and in vitro growth inhibition. These results establish LinkD as a scalable, multi-scale framework for systematic drug repurposing.
Perfluorooctanoic acid (PFOA) contamination in soils is of concern, stemming from its detrimental impact on ecosystem functions and human health at high levels. However, considering its actual pollution levels in cultivated soil, it is necessary to comprehensively evaluate its biological effects under environmental concentrations. Results on the effect of PFOA at levels of 10 and 20 μg/kg on the entire life cycle of soybeans (Glycine max L.) showed increased accumulation in the order of root > leaf > stem > pod > bean, ranging from 0.5 to 155.4 μg/kg. PFOA accumulated in beans (0.5-1.1 μg/kg) posed a potential health risk to the human body with an estimated daily intake (EDI) value at 0.008-0.18 ng/(kg body weight (bw)·day). Moreover, PFOA at such levels disrupted amino acid metabolism, especially decreasing the contents of l-4-hydroxyproline (Hyp), γ-aminobutyric acid (GABA) and l-tryptophan, thereby lowering the nutritional quality of soybeans. It also changed the relative abundance of soil microorganisms, reduced the production of flavonoids, and negatively impacted the biological nitrogen fixation of soybean. The findings unequivocally validate that even at the environmental concentrations, PFOA could reach a level hazardous to food safety and soil quality. This underscores the paramount importance of implementing stringent risk mitigation measures.
Metal mesh reflective surfaces are widely used in deployable antennas mounted on satellites where lightweight and stowability are required; however, quantitative characterization of reflective performance is difficult due to complex woven/knitted structures. This paper presents a modeling method that characterizes the reflection coefficient of complex mesh fabrics by combining a per-band effective wire radius reff estimation procedure with the Casey surface impedance model. The lattice spacing is fixed from the specimen geometry, the electrical conductivity is set to the material property of gold (σ = 45.2 MS/m), and reff is determined as a single parameter that minimizes the error against the measured reflection coefficient in each frequency band. For validation, waveguide-contact measurements were performed on three Atlas-series mesh specimens fabricated with gold-coated molybdenum wire (diameter: 30 μm), measuring each specimen across all three waveguide standards (WR-340, WR-90, WR-28) with nine repeated trials per configuration, totaling 162 measurement runs. The estimated reff ranged from 10.1 to 44.5 μm depending on band and polarization, with RMSE below 0.021 dB in all native-band fits. Even for the same specimen, directional reff values differed by up to 1.78× due to the anisotropy of the weave structure, confirming that polarization dependence must be considered in mesh reflector antenna design.
Declining knee extensor strength (KES) is a recognized risk factor for musculoskeletal disorders including knee osteoarthritis. Regular self-assessment of knee extensor strength in older women is essential for prevention of the progression. This study aimed to clarify the relationship between the KES and parameters derived from shoe-based wearable sensors during natural walking. Thirty-seven older women participated in this study. Insole force sensors and shoe-mounted IMU sensors were used to obtain spatiotemporal, ground reaction force (GRF), and foot pitch angle parameters. The maximal isometric KES was measured, and simple and partial correlations (controlling for gait speed and age) were calculated. KES was significantly correlated with (1) percentages of the stance and double-stance phases (r = -0.58 to -0.46), (2) timing of the first peak of the vertical GRF (r = -0.57), and (3) foot pitch angle at toe-off (r = -0.56). Furthermore, these parameters remained significantly associated with the KES after controlling for gait speed and age. These findings may contribute to the development of wearable sensor-based systems to estimate and quantify knee extensor strength using daily walking data.
The wide-scale deployment of radars, distributed across a platform and across multiple platforms for reliable 360° situational awareness (SA), introduces the challenge of radar interference. Interference can broadly be categorised as self-interference (between radars mounted on the same platform) and mutual interference (signals received from radars on other platforms). Both types of interference impede the reliability of SA delivered by such systems, particularly in dense environments where numerous radars operate simultaneously within the same frequency band. This work presents a comprehensive evaluation of a multi-modal beamforming approach that combines unfocused synthetic aperture radar with the traditional Multiple-Input, Multiple-Output beamformer to enhance radar resolution and suppress interference. Additionally, various aspects of sensor configurations defining hardware and software capabilities of state-of-the-art radars are discussed, and a systematic analysis of signal-to-interference-plus-noise ratio at each step of the processing is presented. Extensive simulations and experimental results in both automotive and maritime environments are shown to validate the effectiveness of the proposed approach.
Microorganisms with dozens, hundreds, or thousands of proteins invade hosts. Whether the hosts simultaneously recognize all or a part of them is unknown. A total of 68 Escherichia coli recombinant outer membrane (OM) proteins were pooled to immunize mice, and the resulting antisera were analyzed using a protein microarray. Proteins recognized in each cycle were removed, and the remaining proteins were re-pooled for subsequent immunizations. Bioinformatics analysis of B cell epitope scores and GO functional categories was performed across the identified immunogen hierarchies. Among the 68 OM proteins, only 18 were recognized to generate antibodies, designated as the first hierarchy of immunogens. When the other 50 proteins were grouped to immunize mice, 15 were detected to have their corresponding antibodies, designated as the second hierarchy of immunogens. This procedure was repeated four times, leading to the identification of 16 and eight proteins as the third and the fourth hierarchy of immunogens, respectively, and 11 residual proteins as the fifth hierarchy of immunogens. Bioinformatics analysis showed a negative correlation of B cell epitope score with increasing hierarchies, suggesting that the score plays an essential role in hierarchy recognition. In addition, more proteins with transport and fewer proteins with metabolic process were found in the combination of the first, second, and third than the combination of the fourth and fifth hierarchies of immunogens. The host's immune system hierarchically recognizes antigens to mount antibody responses. This finding highlights the way in understanding differentially neutralizing antibodies during infections caused by different microorganisms.
Down syndrome (DS), caused by trisomy 21, confers a near-universal risk for Alzheimer's disease (AD), yet individuals exhibit marked variability in cognitive decline, suggesting the presence of cellular mechanisms that modulate vulnerability and resilience. However, these mechanisms remain poorly defined in the human brain. Here, we integrate matched single-nucleus RNA-seq and ATAC-seq profiles from the prefrontal cortex (PFC) and amygdala (AMY) of age-matched individuals with DS with and without AD (DSAD), enabling direct comparison within a shared genetic background. We identify basal astrocytes in the PFC as a selectively vulnerable cell state in DSAD, characterized by both reduced abundance and coordinated transcriptional and regulatory reprogramming. This state exhibits a shift away from homeostatic support functions, with decreased cytokine signaling and lipid-handling programs, alongside increased steroid- and nuclear receptor-associated activity. Concomitantly, chromatin accessibility profiling reveals reduced engagement of immune- and stress-responsive transcription factor programs, including AP-1, STAT, and BACH families, with linked regulatory perturbations at loci such as ABCA1, DAB2IP, and IL1RAP. Together, these findings define a previously unrecognized astrocyte state marked by epigenetic constraint and diminished responsiveness to stress and inflammatory signals, distinguishing it from classical reactive astrocyte phenotypes. Our results nominate PFC basal astrocytes as a key locus of vulnerability in DSAD and suggest that failure to mount appropriate astrocyte responses, rather than overt activation alone, may contribute to neurodegenerative progression.
This study aimed to investigate the relaxant effects of doxazosin (an α₁-adrenergic receptor blocker) and vardenafil (a phosphodiesterase type 5 inhibitor) on rabbit ureteral smooth muscle using an in vitro organ-bath model, and to determine whether sequential administration enhances relaxation, particularly in different ureteral segments. Ureteral segments (middle and distal) were obtained from 15 adult male New Zealand White rabbits and mounted in organ baths containing oxygenated Krebs-Henseleit solution at 37 °C. Each ureteral segment (middle and distal) obtained from the animals was treated as an independent experimental unit. Thus, a total of 15 middle and 15 distal ureteral segments were analyzed (n = 15 per group). Contractions were induced by 60 mmol/L KCl, and relaxation responses to doxazosin and vardenafil-applied separately or sequentially-were recorded isometrically. The degree of relaxation was expressed as a percentage of the initial KCl-induced contraction. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test. Both doxazosin and vardenafil produced significant relaxation in KCl-precontracted tissues (p < 0.001). In the middle ureter, relaxation responses were 47.3 ± 3.6% for doxazosin and 33.7 ± 3.5% for vardenafil. In the distal ureter, relaxation increased to 54.6 ± 2.2% and 40.8 ± 2.2%, respectively. Sequential administration of doxazosin followed by vardenafil yielded the greatest relaxation (84.1 ± 3.9% in middle, 88.4 ± 3.1% in distal segments; p < 0.001), whereas the reverse order produced a lower but still significant response (57.4 ± 4.8% and 80.5 ± 4.4%, respectively). Overall, distal segments exhibited greater pharmacologic sensitivity than middle ones. Doxazosin and vardenafil both exert potent relaxant effects on ureteral smooth muscle, with enhanced efficacy when administered sequentially-especially in distal segments. These findings provide mechanistic insight into the synergistic interaction between α₁-adrenergic blockade and PDE5 inhibition and support the rationale for combination therapy in facilitating distal ureteral stone passage.
Objective: This study investigates the influence of selecting three thermoplastics as raw materials (PLA, PETG, and ABS) on dimensional accuracy, defect formation, and slicer-based mass prediction reliability in FFF 3D-printed UAV micro-frames. Methods: A factorial experimental design combining three materials, two micro-frame geometries, and two infill levels was implemented. Print quality was assessed through structured visual inspection of common FFF defects, while manufacturing reliability was evaluated by comparing slicer-predicted and experimentally measured mass. Dimensional fidelity was quantified at critical motor mount features using repeated micrometric measurements and dedicated accuracy and uniformity indices. Results: The results reveal strong material-dependent behaviour. PLA exhibited the highest dimensional consistency and near-zero mean mass prediction error, PETG showed intermediate performance, and ABS presented significant warping, together with a pronounced positive mass prediction bias. These findings indicate systematic discrepancies between predicted and measured mass values and highlight the need for material-dependent calibration of slicing software. Conclusions: Material selection and process calibration strongly affect dimensional fidelity and manufacturing reliability in FFF-printed UAV micro-frames. The findings provide practical guidance for material choice and slicing parameter adjustment in UAV fabrication and similar small-scale FFF applications.
To identify structural alterations of Descemet's membrane (DM) in bullous keratopathy (BK) and to explore their association with intracellular dark endothelial spots (IDESs) observed by specular microscopy. This multicenter, retrospective, observational study included 75 eyes that underwent endothelial keratoplasty for corneal endothelial dysfunction. Based on preoperative clinical diagnosis, eyes were classified as having Fuchs endothelial corneal dystrophy (FECD)-related or non-FECD BK. DM specimens were collected during endothelial keratoplasty and analyzed as flat-mounted preparations using phase-contrast microscopy. IDESs were evaluated preoperatively by masked assessment using specular microscopy. Among the 75 eyes, 25 were clinically diagnosed with FECD. Of the remaining 50 eyes with BK, 15 showed no characteristic histological abnormalities, 11 exhibited guttae-like changes, and 24 demonstrated a distinct and previously unrecognized DM alteration, termed dome-shaped protrusions (DSPs). Specular microscopy images suitable for IDES evaluation were available in a subset of cases. IDESs were detected in 10 of 18 DSP-positive eyes and in 1 of 10 DSP-negative eyes, indicating a significant association between DSPs and IDESs (odds ratio 11.25; P < 0.05). DSPs represent a distinct structural alteration of the DM in non-FECD BK and are significantly associated with IDESs observed by specular microscopy. These findings provide insight into the heterogeneity of endothelial failure in BK and suggest a link between clinical imaging findings and underlying DM morphology. Dome-shaped protrusions provide a histopathological correlate for intracellular dark endothelial spots observed by specular microscopy and may support improved phenotyping of endothelial dysfunction in non-Fuchs endothelial corneal dystrophy bullous keratopathy.
The retinal microvasculature is one of the few sites where the microcirculation can be directly and non-invasively visualized in vivo, offering a unique window into ocular disease and systemic health. In this study we developed and validated a novel imaging platform integrating a custom-built one-lead electrocardiogram (ECG) with laser Doppler holography (LDH), a high-speed imaging technique that captures Doppler-induced phase shifts, for real-time cardiac cycle-resolved assessment of retinal hemodynamics. Twenty-five healthy adults were imaged (five images per eye), with 563 cardiac cycles meeting analysis quality criteria. Internal system latency combined with synchronization offset amounted to less than 5 ms. LDH-derived beat-to-beat intervals closely tracked ECG R-R intervals, with small mean differences (~ 3 ms), demonstrating excellent temporal stability without measurable drift. ECG-retina latencies, defined as time from the ECG R-peak to LDH peak systolic velocity (R-PSV), maximal systolic upslope (R-MaxSlope), and 50% PSV amplitude (R-PSV½), were measured. R-PSV½ mean ± SD was 128 ± 18 ms and showed the highest repeatability (ICC = 0.78, median CV = 4.8%). ECG-retina latencies were moderately associated with age and heart rate, in exploratory analyses. This integrated ECG-LDH platform provides repeatable, synchronized, high-speed, cardiac-resolved retinal hemodynamic measurements and establishes a quantitative framework for studying the eye-heart relationship.
Background/Objective: Buccal delivery offers a potential route to circumvent gastrointestinal degradation and hepatic first-pass metabolism, but hydrophilic peptides typically exhibit limited mucosal permeation. Nanostructured lipid carriers (NLCs) have been proposed as delivery platforms capable of modulating interfacial interactions and improving mucosal transport. This study aimed to quantitatively evaluate the ex vivo buccal permeation of angiotensin II (Ang II), used as a hydrophilic peptide model, when associated with NLCs compared with free peptide under matched Franz diffusion cell conditions. Methods: Ang II-associated NLCs were prepared by melt emulsification combined with a low-energy injection technique. Particle size, polydispersity index, and zeta potential were determined by dynamic light scattering and laser Doppler electrophoresis. Association efficiency and drug loading were quantified by indirect spectrofluorometric analysis. Ex vivo permeation studies were conducted using porcine buccal mucosa mounted in Franz diffusion cells, and cumulative permeation, steady-state flux, and apparent permeability coefficients were calculated. Results: The NLCs exhibited nanometric size, moderate polydispersity, and association efficiency above 80%, and remained colloidally stable at 4 °C for 28 days. In ex vivo experiments, Ang II-associated NLCs showed measurable cumulative permeation, reaching approximately 9% after 2 h, whereas free Ang II was not detected in the receptor compartment under the tested conditions. Conclusions: This work provides a quantitative ex vivo buccal transport comparison of a hydrophilic peptide model delivered as NLC-associated versus free peptide under matched Franz cell conditions. The findings support further investigation of NLC-based approaches for buccal delivery of vasoactive peptides and provide a rational basis for future in vivo evaluation of mucosal delivery performance and systemic exposure.
Background: Polygenic risk scores for Alzheimer's disease (AD), organized by gene networks shared between the blood and brain, may provide insights into underlying disease mechanisms common to both tissues. Methods: We derived a blood-brain network-based polygenic risk score (nbPRS) from AD-associated genetic variants for three blood-brain networks, selected by the preservation of blood and brain gene co-expression networks, and AD association. Participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 1109), Framingham Heart Study (FHS, n = 8310), the Religious Orders Study Memory Aging Project (ROSMAP, n = 1215), and Mount Sinai Brain Bank (MSBB, n = 323) were stratified into low- and high-nbPRS subgroups, then profiled using longitudinal and cross-sectional data. We compared the conversion from normal cognition to AD between nbPRS subgroups. Genes differentially expressed among low- and high-nbPRS individuals were profiled with classical neuropathological markers and we investigated potential biologically relevant pathways for the genes significantly expressed in high-risk individuals. Results: Individuals with high nbPRS in three AD-associated networks (M2, M6, M14) demonstrated significant impairment in executive function and memory performance, whereas high-risk individuals in networks M2 and M14 had significantly reduced hippocampal volume. We observed high-risk individuals in M2 and M14 developed AD at twice the rate of low-risk individuals in these networks. HLA genes were differentially expressed with transcriptome-wide significance among low- and high-nbPRS individuals in M14 and associated with neuroinflammatory and tau pathology. Conclusions: Polygenic risk scores derived from blood and brain networks can differentiate individuals with a high risk of AD conversion.
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To examine whether early vasopressin use was associated with major adverse kidney events in patients requiring vasopressor support after cardiac surgery. A multicenter retrospective cohort study using inverse probability of treatment weighting with overlap weights. Four intensive care units in Queensland, Australia (2015-2021). A total of 3,753 adults admitted after cardiac surgery (coronary artery bypass grafting, valve surgery, or combined procedures) requiring 6 or more consecutive hours of vasopressor support within the first 24 hours. Patients receiving extracorporeal membrane oxygenation were excluded. Vasopressin use within 24 hours of intensive care unit admission versus no vasopressin. The primary outcome was major adverse kidney events at 30 days, a composite of death, new renal replacement therapy, or creatinine doubling. Of 3,753 patients, 603 (16.1%) received vasopressin. After weighting, vasopressin was not associated with major adverse kidney events at 30 days (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.76-1.38, p = 0.88). No differences were observed for 30-day mortality (OR 1.12, 95% CI 0.69-1.82), acute kidney injury within 7 days (OR 1.04, 95% CI 0.85-1.28), or new renal replacement therapy (OR 1.19, 95% CI 0.80-1.76). A significant interaction was observed for illness severity (p = 0.004), with a trend toward benefit in the highest-severity tertile. Adjunctive vasopressin use was not associated with major adverse kidney events or mortality in patients requiring vasopressors after cardiac surgery. Heterogeneity of treatment effect by illness severity warrants prospective evaluation.
Hybrid cognitive behavioral therapy (CBT), combining group and individual sessions, for treating obsessive-compulsive disorder (OCD) has rarely been examined in routine clinical practice. This prospective observational study preliminarily evaluated the feasibility and acceptability of a hybrid CBT program implemented in Japan. The program consisted of one pre-treatment individual session, eight group sessions, and one post-treatment individual session. Feasibility and acceptability were assessed using dropout rates and written questionnaire feedback. Twenty-eight individuals (mean age = 36.1 ± 14.0 years) participated, with two dropouts. Seven participants reported that the program duration was too short, whereas the remaining participants considered it appropriate. Nineteen participants indicated their willingness to participate in a similar program. Open-ended feedback highlighted the importance of group composition and program content. Self-Rating Yale-Brown Obsessive Compulsive Scale scores decreased at Session 8 (estimate = -2.74, p = 0.002) and post-treatment (estimate = -4.16, p < 0.001) according to a linear mixed-effects model. Reductions were also observed in Sheehan Disability Scale, State-Trait Anxiety Inventory, and Clinical Global Impressions Scale scores, whereas Center for Epidemiologic Studies Depression Scale scores showed no significant change. These findings suggest the feasibility and acceptability of the program and may inform future program development.