Search Results (386)

Background/Objectives: The objective of this retrospective, multicenter cohort study was to compare the incidence of viral load blips between two-drug and three-drug antiretroviral therapy regimens in human immunodeficiency virus (HIV) patients. Methods: A total of 121 patients were included, with 44 receiving two-drug regimens (e.g., dolutegravir/lamivudine) and 77 receiving three-drug regimens (e.g., bictegravir/tenofovir alafenamide/emtricitabine) at the time of analysis. The primary outcome was the occurrence of viral blips, defined as transient HIV-RNA elevations ≥ 50 copies/mL; a sensitivity analysis used ≥20 copies/mL. Results: Generalized estimating equation models adjusted for clinical covariates showed no significant difference in the odds of blip occurrence comparing three-drug with two-drug regimens, both for blips ≥ 50 (odds ratio [OR]: 2.64; 95% confidence interval [CI]: 0.91–7.70; p = 0.075) and ≥20 (OR: 1.76; 95% CI: 0.76–4.08; p = 0.190). In the two- and three-drug groups, the predicted probabilities of blips were 1.4% and 3.7% (p = 0.075) for blips ≥ 50, and 6.9% and 11.5% (p = 0.190) for ≥20, respectively. No virologic failure was observed. Conclusions: These findings suggest that two-drug regimens provide virologic control comparable to three-drug regimens and may be a viable clinical option due to fewer drug interactions, lower toxicity, and reduced cost. Full article

Type I interferons (IFN-I) are pivotal effectors of innate immunity and constitute a central axis of host defense against pathogens. Sensing of exogenous or endogenous nucleic acids by pattern-recognition receptors—exemplified by Toll-like receptors—triggers transcriptional induction of IFN-I. Engagement of the heterodimeric IFN-I receptor on nucleated cells reprograms cellular states via canonical Janus kinase–signal transducer and activator of transcription (JAK–STAT) signaling as well as STAT-independent, noncanonical pathways. This axis is tempered by multilayered regulatory mechanisms, including epigenetic remodeling, and important aspects remain incompletely defined. Dysregulation of IFN-I activity underlies diverse autoimmune disorders, notably systemic lupus erythematosus, wherein IFN-responsive gene signatures stratify disease endotypes, reflect disease activity trajectories, and predict therapeutic responsiveness. In recent years, therapeutic strategies targeting this pathway are now available: anti-IFN-I receptor therapy for systemic lupus erythematosus (SLE) and JAK inhibition for rheumatoid arthritis (RA) and giant cell arteritis (GCA). Altogether, a refined understanding of the IFN-I axis furnishes a pragmatic framework for patient stratification, response prediction, and mechanism-informed therapy design across immune-mediated diseases. Full article

In this study, we propose a 2.5-dimensional (2.5-D) structure approach for insect-mimetic flapping-wing air vehicles (FWAVs). The proposed approach includes design and fabrication methods. To our best knowledge, this study is the first one that develops a flapping system for FWAVs without any post-assembly of structural components. The proposed structure consists of a transmission, a supporting frame, and elastic wings. The transmission transforms the small translational displacement produced by a piezoelectric bimorph into a large rotational displacement of the wings. The size is reduced using the proposed design method. Then, the 2.5-D structure is fabricated using the proposed polymer MEMS micromachining method. The presented micro flapping system flaps the wing with a stroke angle and flapping frequency comparable to those of actual small insects using resonance. The results confirm that the proposed approach can miniaturize FWAVs. Full article

Background: Fulminant idiopathic intracranial hypertension (IIH) is a rare and vision-threatening variant of IIH, characterized by rapid visual deterioration and a high risk of irreversible blindness. Urgent intervention is required to prevent permanent optic nerve damage. Cerebral transverse venous stenting (CTVS) has emerged as an effective treatment for medically refractory IIH, but data on its use in fulminant cases remain limited. Methods: A retrospective consecutive cohort study was conducted at a tertiary center and included all patients with fulminant IIH diagnosed by modified Dandy criteria, with bilateral transverse sinus stenosis > 50% and a trans-stenotic pressure gradient ≥ 8 mmHg on venography. Before stenting, patients received high-dose acetazolamide (up to 3000 mg/day) and IV methylprednisolone (1000 mg/day × 3). Neuro-ophthalmic assessment included BCVA, Ishihara color vision, pupillary exam, disc edema grading, Humphrey visual fields, and optical coherence tomography (OCT). Follow-up occurred at baseline (admission), 1 week, 1 month, 3 months, and 12 months. Results: Five young female patients underwent successful CTVS without peri- or post-procedural complications. Significant improvement in headache and stabilization or recovery of visual function were observed in all patients. OCT revealed early retinal nerve fiber layer thinning within one week, preceding clinical resolution of papilledema. Conclusions: Emergent CTVS appears to be a safe and effective vision-preserving procedure in fulminant IIH, offering rapid intracranial pressure reduction and early neuro-ophthalmologic improvement. OCT may serve as a useful early predictor of treatment success, supporting its role in post-procedural monitoring. Larger prospective studies are warranted. Full article

Background: Cefazolin is being increasingly used to treat central nervous system infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) to mitigate the side effects of existing anti-Staphylococcal drugs. This study aims to develop a cerebrospinal pharmacokinetic (PK) model to predict the cefazolin concentration in cerebrospinal fluid (CSF) and to individualize the dosing regimen for MSSA meningitis. Methods: A cerebrospinal PK model was developed based on the existing literature and used to estimate the probability of attaining PK/ pharmacodynamic (PD) targets. These targets were set as 100% time above the minimum inhibitory concentration (T > MIC) in CSF. The cerebrospinal PK/PD breakpoint was defined as the highest MIC at which target attainment probability in CSF was ≥90%. The mean CSF/serum ratio estimated from the literature was 0.0525 after a dose of 1–3 g (sampling time: 1–9 h after dose) in adult patients with suspected meningitis. This ratio was incorporated into this PK model based on a hybrid approach. Results: For patients with creatinine clearance (CL_cr) = 90 mL/min, the cerebrospinal PK/PD breakpoint MICs of continuous infusion regimens (6–12 g/day) reached 0.5 µg/mL, which can inhibit the growth of 90% of the MSSA population (MIC₉₀). Furthermore, for patients with renal dysfunction (CL_cr = 30 mL/min), a dose reduction (4 g/day) may be required to avoid excessive drug exposure. Conclusions: High-dose continuous infusion of cefazolin may be appropriate for MSSA meningitis in patients with normal renal function, while dose adjustments are needed for those with renal impairment. Full article

Ribosomal proteins have long been recognized as vital components of ribosomes that are involved in protein synthesis. However, emerging evidence indicates that some ribosomal proteins exhibit extraribosomal functions. In this study, we investigated the role of the ribosomal protein S4 X-linked (RPS4X) in the regulation of the Skp1–Cullin1–F-box (SCF) ubiquitin ligase complex and apoptosis. We found that RPS4X expression interfered with SCF complex formation by disrupting the interaction between Cullin1 and Skp1. This disruption suppressed ubiquitination of multiple SCF complex substrates, including the anti-apoptotic proteins myeloid cell leukemia 1 (MCL1) and HS1-associated protein X1 (HAX1). Stabilization of MCL1 and HAX1 by RPS4X led to increased resistance of HeLa cells to doxorubicin-induced apoptosis. These findings suggest that RPS4X contributes to the regulation of protein homeostasis and apoptotic pathways by modulating SCF complex activity, providing new insights into the extraribosomal roles of ribosomal proteins. Full article

Giant cell arteritis (GCA) is a form of large vessel vasculitis that primarily affects older adults and forms granulomatous inflammation in the aorta and its major branches. Recent advances in immunology and multi-omics technologies have elucidated several key mechanisms involved in the pathogenesis of GCA, including immune checkpoint dysregulation, clonal hematopoiesis, and age-associated immune dysfunction. From the perspective of immune cell subsets, a diverse range of immune cells—including tissue-resident memory T cells, stem-like T cells, macrophage subsets, B cells, and myofibroblasts—play distinct roles in sustaining vascular inflammation and tissue remodeling. This review summarizes the latest immunopathological and omics-based insights into GCA, proposes potential therapeutic targets, and discusses future directions for precision medicine aimed at achieving sustained remission. Full article

Study Design: Prospective observational study. Background: Lumbar spinal stenosis (LSS) impairs balance and gait function, increasing fall risk and limiting quality of life. Although postoperative recovery of balance is clinically important, longitudinal data using multidimensional balance assessments are limited. Methods: A prospective cohort study was conducted in 101 patients (mean age 74.9 ± 6.9 years) undergoing surgery for LSS. The Brief Balance Evaluation Systems Test (Brief BESTest), Oswestry Disability Index (ODI), Modified Falls Efficacy Scale (MFES), Zurich Claudication Questionnaire (ZCQ), and Visual Analog Scales (VAS) for pain/numbness were evaluated preoperatively and at 6 and 12 months postoperatively. Changes over time and correlations between Brief BESTest and PROMs were analyzed. Results: The total Brief BESTest score significantly improved from 13.3 ± 5.3 preoperatively to 16.1 ± 5.1 at 6 months and 16.0 ± 5.1 at 12 months (p < 0.01). Subdomains including Anticipatory Adjustments, Postural Responses, Sensory Orientation, and Stability in Gait improved significantly, while Stability Limits did not. At 12 months postoperatively, ODI decreased by 19.1%, ZCQ symptom and function scores improved by 0.8 and 0.9 points, respectively, and VAS scores improved by 17.1 mm for low back pain, 26.5 mm for lower limb pain, and 19.5 mm for numbness, all showing marked improvements from baseline. MFES also increased significantly postoperatively. The Brief BESTest score correlated significantly with MFES and ZCQ-PFS at baseline, and with ODI, ZCQ, and VAS scores at 12 months. Conclusions: Balance ability in LSS patients improved after surgery, as measured by the Brief BESTest, with clinically meaningful changes maintained for 12 months. Improvements in balance were significantly associated with reductions in pain, disability, and fear of falling, suggesting the Brief BESTest is a comprehensive indicator of postoperative recovery. Full article

Background/Objectives: Pumpkin seed pulp from processing plants offers high nutritional value due to its rich β-carotene content, making it a potential functional feed ingredient. This study investigated the effects of pumpkin seed pulp, which has already been administered as livestock feed, on key physiological parameters in cattle, including the concentration of β-carotene in the blood measured during routine health monitoring. Methods: Here, pumpkin waste cultivated in various fields was processed into cattle feed (pumpkin seed pulp flakes, PSPFs) by grinding and drying, and residual pesticide (heptachlor) and β-carotene contents were measured. A pilot feeding trial was conducted with 13 cattle (7 in the treatment group and 6 in the control group) and blood component analysis was performed, and findings were contextualized with a literature review. Results: Heptachlor concentrations varied depending on the cultivation site of raw pumpkins. Among the six lots produced using raw materials sourced from fields not contracted by the Air Water Group—a collective of companies in which Air Water Inc. holds more than 51% ownership—three exceeded the regulatory limits for animal feed established in Japan. PSPFs contained high levels of β-carotene, as expected. Blood tests before and after the feeding trial indicated absorption of β-carotene in the cattle. Maintaining high plasma β-carotene concentrations in cattle has been associated with improved immune function and reproductive performance. Conclusions: Our study demonstrates that PSPFs are a promising, environmentally friendly, and natural β-carotene-rich feed ingredient. Tracing the cultivation fields of raw pumpkins can help ensure feed safety. Full article

Objectives: This multicenter study aimed to clarify the recurrence patterns; treatment outcomes; and prognostic factors of thymic carcinoma, a rare cancer. Methods: We analyzed 101 patients with thymic carcinoma who underwent multidisciplinary treatment, including radiotherapy. The median age was 62 years, with 27 patients in stage I–II; 44 in stage III; and 30 in stage IV by the TNM classification. Seventy-two patients underwent surgery with radiotherapy; and 29 patients underwent definitive radiotherapy. Image-guided radiotherapy (IGRT) and elective nodal irradiation (ENI) were used for 35 and 23 patients, respectively. Local recurrence-free survival (LRFS); progression-free survival (PFS); and overall survival (OS) were calculated, and univariate and multivariate analyses were performed. Results: With a median follow-up of 68 months, we observed 17 local recurrences; 27 regional recurrences; and 35 distant metastases. The 5-year LRFS; PFS; and OS were 82%, 41%, and 76%, respectively. Multivariate analysis revealed that stage was the only factor associated with LRFS; PFS; and OS (p = 0.040; p < 0.0001; and p = 0.048, respectively), while treatment modality was associated with only LRFS (p = 0.015). IGRT and ENI were also associated with LRFS (p = 0.002 and 0.013, respectively). PFS and OS of stage IV patients were comparable between the surgery with radiotherapy and definitive radiotherapy groups (p = 0.99 and 0.98, respectively). Conclusions: Our results suggest the importance of stage-specific treatment strategies rather than resectability, especially for stage IV patients. These results should be validated in a prospective study. Our results also suggest that radiotherapy methods influence recurrence Full article

Background/Objectives: As high-acuity vision is limited to a very small visual angle, examination of a scene requires multiple fixations. Simultanagnosia, a disorder wherein elements of a scene can be perceived correctly but cannot be integrated into a coherent whole, has been parsed into dorsal and ventral forms. In ventral simultanagnosia, limited visual integration is possible. This case study was the first to record gaze during the presentation of a series of visual stimuli, which required the processing of local and global elements. We hypothesised that gaze patterns would differ with successful processing and that feature integration could be disrupted by distractors. Methods: The patient received a neuropsychological assessment and underwent CT and MRI. Eye movements were recorded during the following tasks: (1) famous face identification, (2) facial emotion recognition, (3) identification of Ishihara colour plates, and (4) identification of both local and global letters in Navon composite letters, presented either alone or surrounded by filled black circles, which we hypothesised would impair global processing by disrupting fixation. Results: The patients identified no famous faces but scanned them qualitatively normally. The only emotion to be consistently recognised was happiness, whose scanpath differed from the other emotions. She identified none of the Ishihara plates, although her colour vision was normal on the FM-15, even mapping an unseen digit with fixations and tracing it with her finger. For plain Navon figures, she correctly identified 20/20 local and global letters; for the “dotted” figures, she was correct 19/20 times for local letters and 0/20 for global letters (chi-squared NS for local, p < 0.0001, global), with similar fixation of salient elements for both. Conclusions: Contrary to our hypothesis, gaze behaviour was largely independent of the ability to process global stimuli, showing for the first time that normal acquisition of visual information did not ensure its integration into a percept. The core defect lay in processing, not acquisition. In the novel Navon task, adding distractors abolished feature integration without affecting the fixation of the salient elements, confirming for the first time that distractors could disrupt the processing, not the acquisition, of visual information in this disorder. Full article

Background/Objectives: Dietary patterns vary with age and sex. The aim of this study was to clarify the differences in dietary patterns among young and middle-aged Japanese individuals by age group and sex via statistical methods such as alpha diversity and beta diversity analyses. Methods: Using data from a dietary survey of 10 food items during health checkups of 2743 Fujita Health University employees, we examined the effects of age and sex on alpha diversity (Shannon index) and beta diversity (nonmetric multidimensional scaling (NMDS) and RDA). Unlike principal component analysis which assumes linear relationships, redundancy analysis (RDA) incorporates explanatory variables to directly assess how external factors shape multivariate patterns. Results: The Shannon index increased with age and was greater in males across age groups. Type III ANOVA revealed significant main effects of age (p < 0.001) and sex (p < 0.001), and the effect of the interaction between age and sex approached significance (p = 0.08). Visualization of the NMDS data revealed that women aged 20–29 years and women aged 30 years and older and men aged 20–39 years and men aged 50–59 years have different dietary patterns. The RDA model accounted for 2.01% of the variance (adjusted R² = 1.94%), with age and sex contributing 56.7% and 43.3%, respectively. RDA1 and RDA2 were correlated with age (r = 0.26, −0.14) and sex (r = 0.15, 0.21). The RDA1 values increased with age and were greater in females, whereas the RDA2 values decreased with age and were greater in females. RDA1 (1.41% of the total variance in food group intake, 70.1% of the constrained variance) was positively associated with fruits, milk, and seaweed and negatively associated with meat and eggs. In RDA2 (0.60% of total variance, 29.9% contribution), fruits, potatoes, and vegetables had positive effects, whereas fish had negative effects. Conclusions: Dietary patterns vary by age and sex, with meat, fish, eggs, and fruit as key determinants. Nutritional guidance must account for variations in dietary patterns influenced by age and sex. Full article

Formaldehyde vapor (HCHO) is a harmful chemical substance and a potential air contaminant, with a permissible level in indoor spaces below 0.08 ppm (80 ppb). Thus, highly sensitive gas sensors for the continuous monitoring of HCHO are in demand. The electrical conductivity of semiconducting nanomaterials (e.g., single-walled carbon nanotubes (SWCNTs)) makes them sensitive to chemical substances adsorbed on their surfaces, and a variety of portable and highly sensitive chemiresistive gas sensors, including those capable of detecting HCHO, have been developed. However, when monitoring low levels of vapors (<1 ppm) found in ambient air, most chemiresistive sensors face practical issues, including false responses to interfering effects (e.g., fluctuations in room temperature and humidity), baseline drift, and the need to apply a purge gas. Here, we report an actuator-driven, purge-free chemiresistive gas sensor that is capable of reliably detecting 0.05 ppm of HCHO in the air. This sensor is composed of an HCHO→HCl converter (powdery hydroxylamine salt, HA), an HCl detector (a SWCNT-based chemiresistor), and an HCl blocker (a thin plastic plate). Upon exposure to HCHO, the HA emits HCl vapor, which diffuses onto the adjacent SWCNTs, increasing their electrical conductivity through p-doping. Meanwhile, inserting a plastic plate between HA and SWCNTs makes the conductivity of SWCNTs insensitive to HCHO. Thus, via periodic actuation (insertion and removal) of the plastic plate, HCHO can be detected reliably over a wide concentration range (0.05–15 ppm) with excellent selectivity over other volatile organic compounds. This actuator-driven system is beneficial because it does not require a purge gas for sensor recovery or baseline correction. Moreover, since the response to HCHO is synchronized with the actuation timing of the plate, even small (~0.8%) responses to 0.05 ppm of HCHO can be clearly separated from larger noise responses (>1%) caused by interfering effects and baseline drift. We believe that this work provides substantial insights into the practical implementation of nanomaterial-based chemiresistive gas sensors. Full article

Creating grayscale images from a color reality has been an inherent human practice since ancient times, but it became a technological challenge with the advent of the first black-and-white televisions and digital image processing. Decolorization is a process that projects visual information from a three-dimensional feature space to a one-dimensional space, thus reducing the dimensionality of the image while minimizing the loss of information. To achieve this, various strategies have been developed, including the application of color channel weights and the analysis of local and global image contrast, but there is no universal solution. In this paper, we propose a bio-inspired approach that combines findings from neuroscience on the architecture of the visual system and color coding with evidence from studies in the psychology of art. The goal is to simplify the decolorization process and facilitate its control through color-related concepts that are easily understandable to humans. This new method organizes colors in a scale that links activity on the retina with a system of opponent and complementary channels, thus allowing the adjustment of the perception of warmth and coolness in the image. The results show an improvement in chromatic contrast, especially in the warmth and coolness categories, as well as an enhanced ability to preserve subtle contrasts, outperforming other approaches in the Ishihara test used in color blindness detection. In addition, the method offers a computational advantage by reducing the process through direct pixel-level operation. Full article