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Road traffic accidents are a global health concern. K-car vehicles, also known as "mini vehicles," are defined as those having an engine displacement <660 cc, vehicle length <3.4 m, width <1.48 m, and height <2.0 m. K-cars have become increasing popular not only in Japan but also in other countries. Compared with standard vehicles, the occupant space of a K-car vehicle is considerably smaller; thus, passengers may be more vulnerable to the external forces generated in a collision, which in turn can lead to deformation of the occupant space and less protection against injuries. However, data are scarce regarding whether K-car vehicles are related to poorer survival outcomes and severe trauma. We conducted a retrospective cohort study involving patients who were injured in four-wheeled vehicle accidents between 2002 and 2023 and admitted to a community teaching hospital in Japan. The vehicle configuration was divided into standard and K-car vehicles. The primary endpoint was in-hospital mortality. Other outcomes included severe trauma, defined as Injury Severity Score (ISS) >15, and anatomically specific severe injury of the head and neck, chest, abdomen, pelvis, and extremities, defined as Abbreviated Injury Scale score ≥3. Of 5331 eligible patients, 2384 (44.7%) were K-car vehicle occupants. In propensity score-matched analysis with 1947 pairs, we observed an increase for in-hospital mortality in the K-car vehicle group (2.6% vs. 4.0%, odds ratio 1.53, 95% confidence interval 1.07–2.19). Compared with standard vehicles, K-car vehicles were associated with a greater risk of severe trauma and serious injuries of the head and neck, chest, abdomen, pelvis, and extremities. These study data should be used to encourage vehicle occupants and automobile manufacturers to consider objective facts regarding the safety of vehicles in a traffic accident. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to identify new clinical phenotypes of microscopic polyangiitis (MPA) using a principal components analysis (PCA)-based cluster analysis. Methods: A total of 189 patients with MPA between May 2005 and December 2021 were enrolled from a multicenter cohort in Japan (REVEAL cohort). Categorical PCA and cluster analysis were performed based on clinical, laboratory, and radiological findings. Clinical characteristics and outcomes, including all-cause mortality, respiratory-related mortality, end-stage renal disease (ESRD), and relapse were compared between each cluster. Results: Eleven clinical variables were transformed into four components using categorical PCA and synthetic variables were created. Additionally, a cluster analysis was performed using these variables to classify patients with MPA into subgroups. Four distinct clinical subgroups were identified: Cluster 1 included the renal involvements and diffuse alveolar hemorrhage (DAH)-dominant group (N=33). Cluster 2 comprised the elderly onset systemic inflammation group (N=75). Cluster 3 included patients in the younger-onset limited-organ disease group (N=45). Cluster 4 was comprised of an ILD-predominant group without kidney involvement (N=36). 61 patients died during follow-up, with 32 dying of respiratory-related causes. Additionally, 19 patients developed ESRD and 70 relapsed. Cluster 1 showed the worst ESRD-free survival and relapse rates, whereas Cluster 2 showed the worst overall survival and respiratory-related death-free survival rates among the four groups. Conclusions: Our study identified four unique subgroups with different MPA outcomes. Individualized treatments for each subgroup may be required to improve the prognosis of MPA. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma, the most common primary bone malignancy, has a complex genetic basis and two incidence peaks. In younger patients, the standard treatment involves wide surgical resection combined with adjuvant chemotherapy; however, the role of chemotherapy in elderly patients remains controversial. The aims of this study were to investigate genetic differences between younger and elderly patients with osteosarcoma and to identify genetic signatures associated with chemotherapy response. Methods: Genetic alterations were analyzed using cancer genome profiling data for 204 patients with osteosarcoma obtained from the Center for Cancer Genomics and Advanced Therapeutics. Results: The mutation spectrum was consistent with previous results for osteosarcoma. CCNE1, MCL1, MYC, and RB1 alterations were significantly associated with a younger age, while CDK4, CDKN2A, CDKN2B, H3F3A, KMT2D, MDM2, RAC1, and SETD2 alterations were significantly associated with an older age. Age, unsupervised clustering of gene alterations, and MYC amplifications were significantly associated with the response to ifosfamide. Notably, both clustered mutation signatures and MYC amplification were correlated with age. Conclusions: These findings suggest that distinct oncogenic mechanisms contribute to differential sensitivity to chemotherapy in younger and elderly patients. Cancer genome profiling may aid in chemotherapy selection, and its early implementation is recommended to optimize treatment strategies. [ABSTRACT FROM AUTHOR]

Histological chorioamnionitis (HCA) is a form of maternal immune activation (MIA) linked to an increased risk of neurodevelopmental disorders in offspring. Our previous study identified neurodevelopmental impairments in an MIA mouse model mimicking HCA. Thus, this study investigated the role of CD11c+ microglia, key contributors to myelination through IGF-1 production, in this pathology. In the mouse model, the CD11c+ microglial population was significantly lower in the MIA group than in the control group on postnatal day 3 (PN3d). Furthermore, myelination-related protein levels significantly decreased in the MIA group at PN8d. In humans, preterm infants with HCA exhibited higher IL-6 and IL-17A cord-serum levels and lower IGF-1 levels than those without HCA, followed by a higher incidence of delayed myelination on magnetic resonance imaging at the term-equivalent age. In silico analysis revealed that the transient induction of CD11c+ microglia during early development occurred similarly in mice and humans. Notably, a lack of high CD11c+ microglial population has been observed in children with neurodevelopmental disorders. This study reports impaired induction of CD11c+ microglia during postnatal development in a mouse model of MIA associated with delayed myelination. Our findings may inform strategies for improving outcomes in infants with HCA.CD11c-positive microglia, which have an important role in myelination through IGF-1 production during early development, are poorly induced in infants with histological chorioamnionitis and this may be involved in the development of neurodevelopmental impairments. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring (TDM) is recommended during vancomycin (VCM) administration to adjust the dosage such that the area under the curve (AUC) remains between 400 and 600 µg·h/mL (minimum inhibitory concentration = 1 µg/mL). However, measuring the AUC requires frequent blood sampling, which increases the burden of added time and cost for testing on both patients and healthcare personnel. Therefore, we aimed to address these issues by developing a simple and rapid method for measuring urinary VCM levels using solid-phase extraction and fluorescence spectrometry. The developed method had a quantification range of 100–2,000 µg/mL, with an accuracy of 100.0%–108.5% for concentrations of 200, 1,000, and 2,000 µg/mL. The intra- and inter-day relative standard deviations were below 3.39% and 4.48%, respectively. Furthermore, to predict the AUC from urinary VCM concentrations, we calculated the slope of the urinary concentrations at 7–12 h post-VCM administration in six patients. The slope for one patient differed significantly from that for the others, and the AUC was obtained using practical AUC-guided TDM for vancomycin (PAT) ver. 3.0c for the patient whose value deviated from the recommended range. A negative correlation was observed between the slope and AUC, with a correlation coefficient of 0.65, suggesting the potential for predicting AUC from urinary concentration trends. The use of urine samples, which can be easily obtained, for VCM dose adjustment is expected to contribute to providing more appropriate drug therapy to patients and reduce the burden on healthcare professionals. [ABSTRACT FROM AUTHOR]

Background: Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate targeting HER2-positive gastric cancer or gastroesophageal junction cancer (GC/GEJC). Although effective, T-DXd has notable toxicities, including interstitial lung disease (ILD). This study evaluated the efficacy, safety, and prognostic factors associated with T-DXd for GC/GEJC. Methods: A retrospective observational study was conducted at our institution by reviewing medical records of patients treated with T-DXd until September 2023. Eligible patients had unresectable advanced or recurrent GC/GEJC, HER2 status of IHC 3 + or IHC 2 + /ISH-positive, and prior treatment with trastuzumab-containing regimen. Results: Among the 101 patients analyzed, the initial T-DXd dose was 6.4 mg/kg in 77 patients and 5.4 mg/kg in 24 patients. The objective response rate was 54.3%, with a median PFS of 5.4 months and a median OS of 11.4 months. The significant prognostic factors for shorter PFS and OS included ECOG PS ≥ 1, presence of primary lesion, and peritoneal metastasis but not the initial T-DXd dose. ILD occurred in 14.9% of patients. Notably, higher T-DXd dose and smaller tumor burden were associated with a higher incidence of ILD. Conclusions: Several factors were associated with prognosis after T-DXd treatment in patients with GC/GEJC. Tumor burden is a potential risk factor for T-DXd-related ILD. Further studies are needed to optimize dosing based on tumor burden and to improve the therapeutic index. [ABSTRACT FROM AUTHOR]

The appearances of Schisandrae Sphenantherae Fructus (SSF) and Schisandrae Chinensis Fructus (SCF) are very similar. Thus, being able to distinguish between SSF and SCF is useful for the quality control of these herbal medicines. In this study, two kinds of electrochemical fingerprint analyses using voltammetry or HPLC with electrochemical detection (HPLC-ECD) were developed in combination with multivariate analysis for discriminating between SSF and SCF. The data sets of the oxidation current values from voltammograms of SSF and SCF samples ranging from +0.5 to +1.0 V were applied to perform a partial least squares discriminant analysis (PLS-DA). Moreover, the data sets of the current heights of the characteristic target peaks on the chromatograms at an applied potential of +0.9 V were also applied to perform PLS-DA. In each PLS-DA obtained from the voltammograms and chromatograms, the scores for the SSF samples were plotted on a different region compared with the scores for the SCF samples. Considering the results of the cross-validation, the HPLC-ECD clearly discriminated between the SSF and SCF samples when compared with the voltammetry. In conclusion, our results show that the present electrochemical fingerprint analyses coupled with PLS-DA are useful as a means for discriminating between the SSF and SCF samples. [ABSTRACT FROM AUTHOR]

Lysophosphatidylethanolamine (LPE) is a bioactive lipid mediator involved in diverse cellular functions. In this study, we investigated the effects of three LPE species, 1-palmitoyl LPE (16:0 LPE), 1-stearoyl LPE (18:0 LPE), and 1-oleoyl LPE (18:1 LPE) on pre-osteoblast MC3T3-E1 cells. All LPE species stimulated cell proliferation and activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1/2. MAPK/ERK1/2 activation by 16:0 LPE and 18:1 LPE was inhibited by the Gq/11 inhibitor YM-254890, while activation by 18:0 LPE was blocked by the Gi/o inhibitor pertussis toxin. Intracellular Ca2+ transients were triggered by 16:0 LPE and 18:1 LPE but not by 18:0 LPE, with YM-254890 suppressing these responses. These results suggest that 16:0 and 18:1 LPE act via Gq/11-coupled G protein coupled receptors (GPCRs), and 18:0 LPE acts via Gi/o-coupled GPCRs. Furthermore, receptor desensitization experiments suggested that each LPE acts through distinct GPCRs. Interestingly, 18:0 LPE suppressed osteogenic differentiation, reducing mineralization, alkaline phosphatase activity, and osteogenic gene expression, whereas 16:0 LPE and 18:1 LPE had no such effects. These results suggest the physiological significance of LPEs in bone formation and indicate that different LPE species and their receptors play distinctive roles in this process. [ABSTRACT FROM AUTHOR]

Objective: Epitope spreading (ES), involving autoantibodies, plays a crucial role in the development and persistence of autoimmune reactions in various autoimmune diseases. This study aimed to investigate the relationship between ES of anti–RNA polymerase III (RNAP III) antibodies (ARAs) and the clinical manifestations of systemic sclerosis (SSc). Methods: We investigated whether intermolecular ES occurs in the subunits of the RNAP III complex and whether intramolecular ES targets the major antigen, RNA polymerase III subunit A (RPC1), in patients with SSc. To achieve this, we synthesized 17 full‐length subunit proteins of the RNAP III complex and 5 truncated forms of RPC1 in vitro using a wheat germ cell‐free translation system. Subsequently, we prepared antigen‐binding plates and measured autoantibodies in the serum of patients with SSc. Results: Autoantibodies against different RNAP III complex subunits were found in patients who were ARA‐positive with SSc. The intermolecular ES indicators significantly correlated with the modified Rodnan skin thickness score (mRSS) and surfactant protein‐D, a biomarker of interstitial lung disease. However, the extent of disease on high‐resolution computed tomography or pulmonary function tests did not show any significant correlation. Intramolecular ES indicator against RPC1 were significantly correlated with mRSS and renal crisis. Furthermore, longitudinal assessment of ES in RNAP III complex subunits correlated with mRSS and exhibited potential as a disease activity biomarker. Conclusion: Our findings indicate a correlation between ES levels and the severity of skin sclerosis or the risk of other complications in SSc. This study suggests that measuring ES in SSc serves as a novel biomarker for disease activity. [ABSTRACT FROM AUTHOR]

Accurate evaluation of the spatiotemporal variability of people's interest in seasons (i.e., their "sense of seasons") is required to deeply understand temporal changes in the relationship between people and landscape under climate and societal changes. To this end, it is useful to analyze the time series of relative search volume (RSV) for relevant search terms extracted from Google Trends (GT) for any target period and target area. We examined the presence and absence of 12-month seasonality of the time series of RSV for about 300 representative search terms for Hokkaido in Japan, which has vast natural resources and is visited year-round by many tourists from Japan and abroad. In the case of searchers in both all of Japan and Hokkaido alone, search terms categorized into the foods, leisure, natural scenic spots, and seafood fields showed a strong trend toward 12-month seasonality of the time series of RSV, whereas those categorized into the Ainu (indigenous people) and people fields had weak trends for 12-month seasonality. People's sense of seasons in all of Japan or Hokkaido alone was likely associated with tourism (search terms in the animals, festivals, foods, leisure, natural scenic spots, seafood, tourist spots, and vegetation fields), as well as with animal and plant phenology (terms in the animals and vegetation fields), provisioning ecosystem services (terms in the foods and seafood fields), climate (terms in the climate field), and cultural ecosystem services (terms in the animals, festival, foods, leisure, natural scenic spots, seafoods, and vegetation fields). However, search terms with no 12-month seasonality were included in the tourist spots fields: they included many tourist spots visited by tourists all year around. Despite the need to appropriately select a huge number of representative search terms to reduce the effect of GT limitations and the uncertainty caused by unexpected and rapid temporal changes in RSV, the GT analysis allowed us to evaluate the spatiotemporal variability of people's sense of seasons regarding various objects in the landscape, including those related to tourism, under climate and societal changes. [ABSTRACT FROM AUTHOR]

Background: Excessive exposure to adrenergic vasopressors may be harmful. Non-adrenergic vasopressors may spare adrenergic agents and potentially improve outcomes. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of non-adrenergic vasopressors in adult patients receiving vasopressor therapy for vasodilatory shock or perioperative vasoplegia. Methods: We searched PubMed, Embase, and Cochrane Library for RCTs comparing non-adrenergic vasopressors with adrenergic vasopressors alone or placebo in critically ill or perioperative patients. Each eligible study was categorized into septic shock, cardiac surgery, or non-cardiac surgery. Non-adrenergic vasopressors included vasopressin, terlipressin, selepressin, angiotensin II, methylene blue, and hydroxocobalamin. The primary outcome was mortality at longest follow-up. We conducted a random-effects meta-analysis. We registered the protocol in PROSPERO International Prospective Register of Systematic Reviews (CRD42024505039). Results: Among 51 eligible RCTs totaling 5715 patients, the predominant population was septic shock in 30 studies, cardiac surgery in 11 studies, and non-cardiac surgery in 10 studies. Cochrane risk-of-bias tool for randomized trials version 2 identified 17 studies as low risk of bias. In septic shock, mortality was significantly lower in the non-adrenergic group (960/2232 [43%] vs. 898/1890 [48%]; risk ratio [RR], 0.92; 95% confidence interval [95% CI], 0.86–0.97; P = 0.03; I2 = 0%), with none of the individual non-adrenergic vasopressors showing significant survival benefits. No significant mortality difference was observed in patients undergoing cardiac surgery (34/410 [8.3%] vs. 47/412 [11%]; RR, 0.82; 95% CI, 0.55–1.22; P = 0.32; I2 = 12%) or those undergoing non-cardiac surgery (9/388 [2.3%] vs. 18/383 [4.7%]; RR, 0.66; 95% CI, 0.31–1.41; P = 0.28; I2 = 0%). Conclusions: Administration of non-adrenergic vasopressors was significantly associated with reduced mortality in patients with septic shock. However, no single agent achieved statistical significance in separate analyses. Although the pooled effects of non-adrenergic vasopressors on survival did not reach statistical significance in patients undergoing cardiac or non-cardiac surgery, the confidence intervals included the possibility of both no effect and a clinically important benefit from non-adrenergic agents. These findings justify the conduct of further RCTs comparing non-adrenergic vasopressors to usual care based on noradrenaline alone. [ABSTRACT FROM AUTHOR]

Background: Tooth loss can lead to an increased risk of physical disease and a reduced quality of life. The current study investigated the association of the use of interdental cleaning devices with oral health outcomes such as tooth loss among employees as a healthier population. Method: Tooth loss was determined as the main outcome in 2017 in a company employee population (n = 845, average age = 47.76 years old, and 25.09% of female). Using the data of dental health examinations in the past 5-years from 2017, the years of use of interdental brushes (IDB) and dental floss (DF) were examined. The Community Periodontal Index (CPI) as of 5-years ago was also examined. The impact of years of use of IDB and DF on tooth loss was analyzed by a logistic regression model in stratifying the subjects into two groups by the maximum CPI (0–2 of CPI [< 4 mm] and 3–4 of CPI [≥ 4 mm]) in all periodontium. Results: In the group of maximum CPI < 3, a multivariate-adjusted odds ratio of the use of DF for 4–5 years on tooth loss was 0.42 versus for 0–1 year (reference). In the group of maximum CPI ≥ 3, the multivariate-adjusted odds ratio of the use of IDB for 4–5 years was 0.38 versus for 0–1 year (reference). Conclusion: A longer-term use of interdental cleaning devices could improve oral health outcomes in this population, while the impact could differ depending on the basis of periodontal status. These findings would be useful for making strategies for oral health promotion in healthier people as employees. [ABSTRACT FROM AUTHOR]

Fenestration has been reported to enhance Fontan hemodynamics in several cases of Fontan circulation. However, the indication criteria for fenestration remain under discussion. To assess the effectiveness of fenestration in Fontan circulation, we conducted a theoretical analysis using a computational model of the fenestrated Fontan circulation. The cardiac chambers and vascular systems were modeled using the time-varying elastance model and the modified Windkessel model, respectively. When the pulmonary vascular resistance index was 4.01 Wood units m2, fenestration significantly reduced central venous pressure from 18.0 to 16.1 mmHg and decreased stressed blood volume from 610 to 555 ml. However, in the models with reduced ventricular end-systolic elastance, increased ventricular stiffness constant, or heightened systemic vascular resistance, the advantages of fenestration were diminished. Thus, fenestration may effectively improve the hemodynamics of Fontan circulation in patients with elevated pulmonary vascular resistance. [ABSTRACT FROM AUTHOR]

In single-lined spectroscopic binaries (SB1s) where flux variations due to tidal deformation of the primary star (ellipsoidal variations, EVs) are detected, the binary mass can be determined by combining EVs with the primary's radial velocity (RV) variations from orbital motion and information about the primary's radius. This method has been used for mass estimation in close binaries including X-ray systems, but it has been pointed out that contaminating light from sources other than the primary star could introduce systematic errors in the mass and inclination estimates. Here, we focus on the apparent RV variations caused by asymmetric distortion of the absorption lines of the tidally deformed primary star (tidal RV). Because this signal contains information equivalent to that from photometric EVs, it enables mass estimation of the binary system using only the primary star's absorption lines from high-resolution spectroscopic data, providing a potentially more robust approach against contaminating light. We apply the method to the binary system V723 Monocerotis, where both photometric EV and tidal RV signals are detected and successfully determine the component masses using only the primary star's RVs and projected rotational velocity, without relying on absolute flux measurements or stellar evolutionary models. The masses derived from the tidal RV model shows a reasonable agreement with those obtained from EVs after carefully modeling the flux contamination from the secondary. This result demonstrates that tidal RVs provide a useful alternative means for mass estimation in SB1s. [ABSTRACT FROM AUTHOR]

Objective: Adult spinal deformity (ASD) with osteoporotic vertebral fractures (OVF) often requires vertebral body resection and replacement. However, postoperative mechanical complications (MC) have been unsolved issues. This study retrospectively investigated the risk of MC following anterior-posterior spinal fusion (APF) with vertebral body resection and replacement for OVF with ASD. Methods: Among 91 cases undergoing APF with vertebral body resection and replacement, 43 cases met the deformity criteria. The mean age was 74.2 years, and the mean number of fused segments was 5.7. Pre and postoperative spinal alignments were measured, and the risk of MC occurrence, including PJK, DJK, and cage sinking, was determined through multivariate analysis. The AUC and cutoff values were calculated through ROC analysis. Results: The incidence of MC, PJK, and DJK were 28%, 12%, and 14%, respectively. Multivariate analysis for MC revealed postoperative PI-LL and operative time (cutoff: 40.5 degrees, 238 min) as significant risk factors, while postoperative PI-LL was a significant risk factor for PJK (cutoff: 42.4 degrees). Evaluation considering only thoracolumbar level showed postoperative local kyphosis as a significant MC risk factor (cutoff: 11 degrees). There was a positive correlation between operative time and preoperative local kyphosis, with a cutoff value of 238 min being equivalent to 21 degrees. Conclusion: The postoperative mismatch over 40 degrees and preoperative local kyphosis over 21 degrees were considered as a high risk for MCs. The postoperative kyphosis of 11 degrees was the risk factor of MC in the thoracolumbar level. The meticulous preoperative assessment, including local and global alignment, and local flexibility as well as detailed surgical planning of fixation range and the requirement of osteotomy, are crucial. [ABSTRACT FROM AUTHOR]

Background: It is mandatory to demonstrate the removal or inactivation of potential viral contaminants in the manufacturing processes of pharmaceuticals derived from biomaterials. Porcine-derived gelatin is used in various medical fields, including regenerative medicine, tissue engineering, and medical devices. However, the steps of virus inactivation in the gelatin manufacturing process are poorly defined. In this study we evaluated virus inactivation in two steps of the gelatin manufacturing process. Methods: Pig skin (4.5 g), including solid pieces as intermediate products, was spiked with model viruses, including CPV (canine parvovirus), BAV (bovine adenovirus), BPIV3 (bovine parainfluenza type 3), PRV (pseudorabies virus), BReoV3 (bovine reovirus type 3), and PPV (porcine parvovirus), and underwent chemical treatment with alkaline ethanol or heat treatment at 62 °C followed by inoculation in relevant cell cultures. Viral titers in the samples were calculated based on the Behrens-Kärber method. Results: Model viruses were inactivated at different rates; however, effective inactivation of all model viruses was demonstrated by an LRV (log reduction value) over 4 by both chemical and heat treatment, and chemical treatment demonstrated rapid inactivation compared to heat treatment. Conclusion: The chemical and heat treatment steps exhibited meaningful viral inactivation capacity. They are integrated parts in the extraction and manufacturing process of porcine-derived gelatin, ensuring virus safety for use in medical applications. [ABSTRACT FROM AUTHOR]

The local injection of therapeutic drugs, including cells, oncolytic viruses and nucleic acids, into different organs is an administrative route used to achieve high drug exposure at the site of action. However, after local injection, material backflow and side effect reactions can occur. Hence, this study was carried out to investigate the effect of gelatin on backflow reduction in local injection. Gelatin particles (GPs) and hydrolyzed gelatin (HG) were injected into tissue models, including versatile training tissue (VTT), versatile training tissue tumor-in type (VTT-T), and broiler chicken muscles (BCM), using needle gauges between 23 G and 33 G. The backflow material fluid was collected with filter paper, and the backflow fluid rate was determined. The backflow rate was significantly reduced with 35 μm GPs (p value <.0001) at different concentrations up to 5% and with 75 μm GPs (p value <.01) up to 2% in the tissue models. The reduction in backflow with HG of different molecular weights showed that lower-molecular-weight HG required a higher-concentration dose (5% to 30%) and that higher-molecular-weight HG required a lower-concentration dose (7% to 8%). The backflow rate was significantly reduced with the gelatin-based formulation, in regard to the injection volumes, which varied from 10 μL to 100 μL with VTT or VTT-T and from 10 μL to 200 μL with BCM. The 35 μm GPs were injectable with needles of small gauges, which included 33 G, and the 75 μm GPs and HG were injectable with 27 G needles. The backflow rate was dependent on an optimal viscosity of the gelatin solutions. An optimal concentration of GPs or HG can prevent material backflow in local injection, and further studies with active drugs are necessary to investigate the applicability in tumor and organ injections. [ABSTRACT FROM AUTHOR]

The 2024 Noto Peninsula Earthquake significantly affected the Noto Peninsula, Japan, where foreign nationals, mainly foreign technical intern trainees, reside. They represent a minority in Japanese society in terms of language and religion, which may render them vulnerable to disasters. Muslim communities centered in mosques have supported such minorities in past natural hazard-related disasters. However, in Japan, these activities have rarely been investigated immediately after a disaster event. This study aims to provide a prompt report on the initial responses of three mosques (1. Kanazawa Mosque, 2. Al-Faruq Mosque, and 3. Toyama Mosque) in Ishikawa and Toyama Prefectures, which were significantly affected by the 2024 Noto Peninsula Earthquake. To this end, we conducted interviews mainly with the (deputy) representatives of the target mosques until approximately two months after the earthquake. Consequently, all three mosques functioned as evacuation shelters for traveling or nearby affected Muslims in the immediate aftermath of the earthquake. In addition, both the Kanazawa Mosque and Al-Faruq Mosque provided relief supplies to foreign technical intern trainees (Indonesian Muslims) in the Noto Peninsula within approximately one week of the earthquake; they continued providing support thereafter. Al-Faruq Mosque also provided soup kitchens to Japanese individuals (non-Muslims) and the technical intern trainees. Such mosque functions and activities have been observed in past natural hazard-related disasters; thus, these findings are highly generalizable. These findings may be useful for the government and other stakeholders when considering how to support affected minorities in the future. [ABSTRACT FROM AUTHOR]

In both space and fusion plasmas, energetic ions with a ring-like velocity distribution are present in various ion species with different masses. We study how the nonlinear development of lower hybrid wave (LHW) instabilities, driven by the ring-like energetic ions, depends on the mass of the energetic ions, by using the electromagnetic particle-in-cell simulation with a model where the energetic ions are continuously injected into a plasma. As expected from linear theory, the initial growth of the LHWs slows down as the energetic-ion mass (M) increases. However, long-time simulations have revealed that as M increases, the LHWs eventually grow to larger amplitudes. This is because the velocity distribution of the energetic ions, influenced by spreading due to wave development and reformation due to injection, can maintain a steep gradient when M is large. As a result, in a large M plasma, a greater part of the injected energy is converted to the energies of the electric field and background ions. In addition, it has been found that a larger value of M leads to an increase in the amplitudes of the second and third harmonics of the LHWs because of enhanced nonlinear wave-wave coupling. [ABSTRACT FROM AUTHOR]

Ribosome biogenesis is an important regulator of skeletal muscle hypertrophy induced by repeated bouts of resistance exercise (RE). Hot-water immersion (HWI), a widely used post-exercise recovery strategy, activates the mechanistic target of rapamycin (mTOR) signaling, a key regulator of ribosome biogenesis in skeletal muscle. However, the effect of HWI on skeletal muscle ribosome biogenesis is not well understood. Here, we aimed to investigate the effects of HWI and post-exercise HWI on ribosome biogenesis using a rat RE model. Male Sprague-Dawley rats were randomly assigned to HWI and non-HWI groups. In both groups, the right leg was isometrically exercised using transcutaneous electrical stimulation, while the left leg was used as an internal non-RE control. Following RE, both limbs were immersed in hot water (41.2 ± 0.03°C) for 20 min under isoflurane anesthesia in the HWI group and the gastrocnemius muscles were sampled at 3- and 24-h post-exercise. HWI significantly increased mTOR signaling and c-Myc mRNA expression, whereas post-exercise HWI significantly increased transcription initiation factor-IA mRNA expression. However, neither HWI nor post-exercise HWI enhanced 45S pre-rRNA expression, ribosomal RNA, or ribosomal protein content. In addition, HWI tended to decrease 28S rRNA and 18S rRNA content, widely used markers of ribosome content. These results suggest that HWI as a post-exercise recovery is not effective in activating ribosome biogenesis. NEW & NOTEWORTHY: Ribosome biogenesis is crucial in resistance exercise (RE)-induced skeletal muscle hypertrophy. This study examined the effects of hot-water immersion (HWI) on ribosome biogenesis after RE. HWI and post-exercise HWI increased c-Myc and transcription initiation factor-IA mRNA but did not alter ribosomal RNA transcription or ribosomal protein content. HWI tended to decrease 28S and 18S ribosomal RNA. These findings suggest that HWI, as a recovery strategy, does not effectively promote ribosome biogenesis or muscle protein synthesis. [ABSTRACT FROM AUTHOR]

Background: The actual status of comprehensive genomic profiling (CGP) applications in Japan has not been clarified. We conducted a multicenter study to investigate the real-world application of CGP in gynecological malignancies. Methods: Nine designated cancer hospitals participated in this study. Patients who underwent CGP in 2020–2021 were assigned to the CGP group (n = 134). For the population that would have been eligible for CGP, patients who received initial treatment in 2015–2016 and were either alive with disease or died of disease at 5 years follow up were included in the control group (n = 316). We compared clinicopathological characteristics including tumor type (cervix, corpus, ovary, and others including sarcoma) and age. We also investigated the context of CGP-recommended treatment. Results: The CGP group had significantly fewer cervical cases and more others cases (cervix/corpus/ovary/others: CGP, 22/44/56/12; control, 89/79/142/6; p = 0.0003). The CGP group was significantly younger than the control group (median: CGP, 54.0; control, 65.0; p < 0.0001). Subgroup analyses revealed that patients with cervical and ovarian cancers were significantly younger in the CGP group. Among the CGP group, 17 patients (12.7%) received CGP-recommended treatments, 15 of which were not covered by public insurance. The survival time after CGP in 17 patients was longer than in the other 117 cases (median 21 vs. 11 months). Conclusion: There was significant selection bias in tumor type and age for the application of CGP for gynecological malignancies in clinical practice in Japan. While CGP often recommended drugs not covered by public insurance, prognosis can be improved by use of CGP. [ABSTRACT FROM AUTHOR]

Catheter ablation therapy, which is a treatment for atrial fibrillation (AF), has a higher recurrence rate as AF duration increases. Compared to paroxysmal AF (PAF), sustained AF is known to cause progressive anatomic remodeling of the left atrium, resulting in enlargement and shape changes. In this study, we used contrast-enhanced computed tomography (CT) to classify atrial fibrillation (AF) into paroxysmal atrial fibrillation (PAF) and long-term persistent atrial fibrillation (LSAF), which have particularly different recurrence rates after catheter ablation. Contrast-enhanced CT images of 30 patients with PAF and 30 patients with LSAF were input into six pretrained convolutional neural networks (CNNs) for the binary classification of PAF and LSAF. In this study, we propose a method that can recognize information regarding the body axis direction of the left atrium by inputting five slices near the left atrium. The classification was visualized by obtaining a saliency map based on score-class activation mapping (CAM). Furthermore, we surveyed cardiologists regarding the classification of AF types, and the results of the CNN classification were compared with the results of physicians' clinical judgment. The proposed method achieved the highest correct classification rate (81.7%). In particular, models with shallow layers, such as VGGNet and ResNet, are able to capture the overall characteristics of the image and therefore are likely to be suitable for focusing on the left atrium. In many cases, patients with an enlarged left atrium tended to have long-lasting AF, confirming the validity of the proposed method. The results of the saliency map and survey of physicians' basis for judgment showed that many patients tended to focus on the shape of the left atrium in both classifications, suggesting that this method can classify atrial fibrillation more accurately than physicians, similar to the judgment criteria of physicians. [ABSTRACT FROM AUTHOR]

People read human characteristics into the design of social robots, a visual process with socio-cultural implications. One factor may be nationality, a complex social characteristic that is linked to ethnicity, culture, and other factors of identity that can be embedded in the visual design of robots. Guided by social identity theory (SIT), we explored the notion of "mukokuseki," a visual design characteristic defined by the absence of visual cues to national and ethnic identity in Japanese cultural exports. In a two-phase categorization study (\(n=212\)), American (\(n=110\)) and Japanese (\(n=92\)) participants rated a random selection of nine robot stimuli from America and Japan, plus multinational Pepper. We found evidence of made-in and two kinds of mukokuseki effects. We offer suggestions for the visual design of mukokuseki robots that may interact with people from diverse backgrounds. Our findings have implications for robots and social identity, the viability of robotic exports, and the use of robots internationally. [ABSTRACT FROM AUTHOR]

Dysregulation of the renin–angiotensin–aldosterone-system (RAAS) in sepsis is a complex and early phenomenon with a likely significant contribution to organ failure and patient outcomes. A better understanding of the pathophysiology and intricacies of the RAAS in septic shock has led to the use of exogenous angiotensin II as a new therapeutic agent. In this review, we report a multinational and multi-disciplinary expert panel discussion on the role and implications of RAAS modulation in sepsis and the use of exogenous angiotensin II. The panel proposed guidance regarding patient selection and treatment options with exogenous angiotensin II which should trigger further research. [ABSTRACT FROM AUTHOR]

The synchronous activity of neuronal networks is considered crucial for brain function. However, the interaction between single-neuron activity and network-wide activity remains poorly understood. This study explored this interaction within cultured networks of rat cortical neurons. Employing a combination of high-density microelectrode array recording and optogenetic stimulation, we established an experimental setup enabling simultaneous recording and stimulation at a precise single-neuron level that can be scaled to the level of the whole network. Leveraging our system, we identified a network burst-dependent response change in single neurons, providing a possible mechanism for the network-burst-dependent loss of information within the network and consequent cognitive impairment during epileptic seizures. Additionally, we directly recorded a leader neuron initiating a spontaneous network burst and characterized its firing properties, indicating that the bursting activity of hub neurons in the brain can initiate network-wide activity. Our study offers valuable insights into brain networks characterized by a combination of bottom-up self-organization and top-down regulation. The synchronous activity has a crucial for brain function. Here, the authors established an experimental setup enabling simultaneous recording and stimulation at a single-neuron level in cultured neuronal networks and explored interaction between single-neuron activity and network-wide activity. [ABSTRACT FROM AUTHOR]

Introduction: Exogenous haptoglobin administration may enhance plasma-free hemoglobin (pfHb) clearance during hemolysis and reduce its end-organ damage: we systematically reviewed and summarized available evidence on the use of haptoglobin as a treatment for hemolysis of any cause. Methods: We included studies describing haptoglobin administration as treatment or prevention of hemolysis-related complications. Only studies with a control group reporting at least one of the outcomes of interest were included in the quantitative synthesis. Primary outcome was the change in pfHb concentration 1 h after haptoglobin infusion. Results: Among 573 articles, 13 studies were included in the review (677 patients, 52.8% received haptoglobin). Median initial haptoglobin intravenous bolus was 4,000 (2,000, 4,000) IU. Haptoglobin was associated with lower pfHb 1 h (SMD −11.28; 95% CI: −15.80 to −6.75; p < 0.001) and 24 h (SMD −2.65; 95% CI: −4.73 to −0.57; p = 0.001) after infusion. There was no difference in all-cause mortality between haptoglobin-treated patients and control group (OR 1.41; 95% CI: 0.49–4.95; p = 0.520). Haptoglobin was associated with a lower incidence of acute kidney injury (OR 0.64; 95% CI: 0.44–0.93; p = 0.020). No adverse events or side effects associated with haptoglobin use were reported. Conclusions: Haptoglobin administration has been used in patients with hemolysis from any cause to treat or prevent hemolysis-associated adverse events. Haptoglobin may reduce levels of pfHb and preserve kidney function without increase in adverse events. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to evaluate the predictors of deterioration of the Child‐Pugh classification 1 month after transcatheter arterial chemo‐embolization (TACE) in patients with treatment‐naive hepatocellular carcinoma (HCC). Methods: Between 2010 and 2020, consecutive patients who underwent conventional TACE using epirubicin as the initial treatment were enrolled. Patients with Barcelona Clinic Liver Cancer stage‐0, A or B and Child‐Pugh class A were included. The Child‐Pugh score was evaluated before treatment and 1 month after TACE. The following variables were analyzed by univariate and multivariate analyses as predictors of deterioration of the Child‐Pugh class from A to B: age, sex, etiology, serum albumin, bilirubin, prothrombin time (PT), encephalopathy, ascites, largest tumor diameter, tumor number, tumor location, α‐fetoprotein, protein induced by vitamin K absence or antagonist‐II, epirubicin dosage, ethiodized oil dosage, and number of treated liver segments. Results: A total of 152 patients were retrospectively enrolled. The deterioration rate of the Child‐Pugh class from A to B was 8.6%. Multivariable analysis showed that serum albumin ≤ 3.8 g/dL, PT ≤ 80%, and largest tumor diameter ≥ 3.8 cm were predictors of deterioration of the Child‐Pugh class. The deterioration rate to Child‐Pugh class B was 0% in patients with up to one of these factors, 14.3% in those with two factors, and 70% in those with three factors. Conclusions: A combination of serum albumin ≤ 3.8 g/dL, PT ≤ 80%, and largest tumor diameter ≥ 3.8 cm can predict the immediate deterioration of the Child‐Pugh classification from A to B following TACE. [ABSTRACT FROM AUTHOR]

Studies have suggested that the administration of epidural analgesia (Epi) and oxytocin (OT) during labor affects offspring outcomes. However, the effects of their combined use remain unclear. This article aimed to review the outcomes of offspring exposed to Epi and OT, identify research gaps, and discuss future research directions. We searched the MEDLINE/PubMed, Web of Science, and Cochrane Library databases to identify studies describing offspring outcomes in the Epi, OT, Epi-OT, and control groups. We included one systematic review, six cohort studies, and one case-control study. The offspring outcomes at birth did not differ between the Epi-OT and Epi groups. In the first hour of life, the pre-feeding and sucking behaviors of the Epi-OT group showed an inverse correlation. At 2 days of age, the breastfeeding behavior and skin temperature patterns differed significantly between the Epi-OT and other groups. At 4 days of age, hyperbilirubinemia was more prevalent in the Epi-OT versus control group. Behavioral scores at 1 month differed little among the Epi-OT, Epi, and control groups. No eligible studies examined 1 month to 1 year of life. From 1 to >13 years of age, the risk of autism spectrum disorder was higher in the Epi and Epi-OT groups versus the control group. Most eligible studies were small and observational without randomization, and the results were inconsistent. Additional large cohort studies of various aspects of offspring development are required to assess the long-term effects of Epi-OT administration. [ABSTRACT FROM AUTHOR]

Objective: Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes. Methods: This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups. Results: Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose. Conclusion: Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections. [ABSTRACT FROM AUTHOR]

Aim: Prenatal maternal depression is known to affect the neurodevelopment of offspring. This study aimed to investigate the profile of umbilical cord serum in mothers with major depressive disorder (MDD). Methods: Liquid chromatography–tandem mass spectrometry (LC–MS) was conducted using umbilical cord serum from mothers with MDD (n = 5) and controls (control, n = 5). The levels of several differentially expressed proteins in umbilical cord serum were compared between the MDD (n = 10) and control groups (n = 10) by enzyme‐linked immunosorbent assay. Results: The proteomic profiles in the umbilical cord serum were different between the MDD and control groups, including the pathways of regulation of plasma lipoprotein particle levels, and synapse organization. Only apolipoprotein A4 (APOA4) was significantly higher in the cord blood of MDD group. APOA4 levels in maternal serum were also significantly higher in the MDD group than those in the control group. The APOA4 levels in the umbilical cord serum were higher than that in the maternal serum. Conclusions: The levels of APOA4, a biomarker of depression, in the umbilical cord serum at birth were elevated in the neonates of MDD mothers. It is, therefore, likely that fetuses of MDD mothers were exposed to higher APOA4 levels in utero and this could have developmental and mental health implications for the offspring. [ABSTRACT FROM AUTHOR]

Background: Tailored axillary surgery (TAS) is a new approach for selective removal of metastatic lymph nodes. This study evaluated the safety and utility of TAS using a breast biopsy clip inserted into a metastatic lymph node and a point marker consisting of a short hook wire and nylon thread to remove the clipped lymph node. Methods: Patients with breast cancer and clinically confirmed metastases to one-to-three axillary lymph nodes were included in this study. A breast biopsy clip was inserted into the metastatic lymph nodes before neoadjuvant chemotherapy. TAS was performed in patients with ycN0 disease after neoadjuvant chemotherapy. The lymph nodes containing the clips were removed using a point marker. The success criteria for TAS were the removal of the lymph node into which the clip was inserted using a point marker and the identification of the sentinel lymph node. The false-negative rate was calculated for cases in which TAS and axillary lymph node dissection were performed. Results: Thirty individuals from two institutions were enrolled between May 2021 and November 2022, of whom 20 underwent TAS. Ten patients had clinically positive axillary lymph nodes and underwent axillary lymph node dissection. No adverse events were observed in any patient using the clips or point markers. TAS was successful in 18 of the 20 patients (90%). Seven patients underwent TAS and axillary lymph node dissection with a false-negative rate of 0%. Conclusion: The use of clips and point markers to perform TAS is clinically feasible. [ABSTRACT FROM AUTHOR]

Background/Objectives: Fatty acids are involved in some hepatic disorders. The proprotein convertase subtilisin kexin 9 (PCSK9) inhibits the uptake of low-density lipoproteins (LDLs), which contain lipids, into the liver and may thus be associated with nonalcoholic fatty liver disease (NAFLD), a cardiovascular disorder (CVD) risk. Statins reduce blood LDL–cholesterol (LDL-C) levels and CVD risk and can attenuate the development of NAFLD while increasing blood PCSK9 levels. Methods: We investigated the correlation between PCSK9 and liver conditions in patients with familial hypercholesterolemia (FH), a CVD risk population with elevated blood LDL-C levels, under statin treatment. Blood tests for lipids, PCSK9, and liver function (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were performed in patients with FH taking statins (n = 25, mean age = 57 years, 12% of males). The ALT:AST ratio was used as a marker of NAFLD risk. Results: The mean LDL-C level was 3.38 mmol/L, and the median PCSK9 level was 312 ng/mL. The median ALT:AST ratio was 0.88. A significant negative correlation was observed between the PCSK9 and ALT:AST ratio (β = −0.67, p < 0.05). Conclusions: Their negative correlation might give a hypothetical insight into the effect of statin treatment on the development of NAFLD, in relation to PCSK9 behavior, in patients with FH. [ABSTRACT FROM AUTHOR]

Mechanical circulatory support is a potential treatment for failing Fontan patients. In this study, we performed a theoretical analysis using a computational model to clarify the effects of systemic ventricular assist device (VAD) in failing Fontan patients. Cardiac chambers and vascular systems were described using the time-varying elastance model and modified Windkessel model, respectively. A VAD was simulated as a nonlinear function. In systolic and diastolic ventricular dysfunction and atrioventricular valve regurgitation models, systemic VAD increased the cardiac index and decreased the central venous pressure (CVP). However, in the high pulmonary vascular resistance model, CVP became extremely high above 15 mmHg to maintain the cardiac index when the pulmonary vascular resistance index (PVRI) was above 5 Wood units m2. In Fontan patients with ventricular dysfunction or atrioventricular valve regurgitation, systemic VAD efficiently improves the hemodynamics. In Fontan patients with PVRI of > 5 Wood units m2, systemic VAD seems ineffective. [ABSTRACT FROM AUTHOR]

Background: Mepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings. Objectives: This study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM). Results: After PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose ≤ 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses ≤ 4 mg/day at the last observation. In all models, achieving a GC dose ≤ 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012). Conclusion: Mepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients. [ABSTRACT FROM AUTHOR]

Top-down visual attention is a fundamental cognitive process that allows individuals to selectively attend to salient visual stimuli in the environment. Recent empirical findings have revealed that gamma oscillations participate in the modulation of visual attention. However, computational studies face challenges when analyzing the attentional process in the context of gamma oscillation due to the unstable nature of gamma oscillations and the complexity induced by the layered fashion in the visual cortex. In this study, we propose a layer-dependent network-of-networks approach to analyze such attention with gamma oscillations. The model is validated by reproducing empirical findings on orientation preference and the enhancement of neuronal response due to top-down attention. We perform parameter plane analysis to classify neuronal responses into several patterns and find that the neuronal response to sensory and attention signals was modulated by the heterogeneity of the neuronal population. Furthermore, we revealed a counter-intuitive scenario that the excitatory populations in layer 2/3 and layer 5 exhibit opposite responses to the attentional input. By modification of the original model, we confirmed layer 6 plays an indispensable role in such cases. Our findings uncover the layer-dependent dynamics in the cortical processing of visual attention and open up new possibilities for further research on layer-dependent properties in the cerebral cortex. [ABSTRACT FROM AUTHOR]

Top-down visual attention is a fundamental cognitive process that allows individuals to selectively attend to salient visual stimuli in the environment. Recent empirical findings have revealed that gamma oscillations participate in the modulation of visual attention. However, computational studies face challenges when analyzing the attentional process in the context of gamma oscillation due to the unstable nature of gamma oscillations and the complexity induced by the layered fashion in the visual cortex. In this study, we propose a layer-dependent network-of-networks approach to analyze such attention with gamma oscillations. The model is validated by reproducing empirical findings on orientation preference and the enhancement of neuronal response due to top-down attention. We perform parameter plane analysis to classify neuronal responses into several patterns and find that the neuronal response to sensory and attention signals was modulated by the heterogeneity of the neuronal population. Furthermore, we revealed a counter-intuitive scenario that the excitatory populations in layer 2/3 and layer 5 exhibit opposite responses to the attentional input. By modification of the original model, we confirmed layer 6 plays an indispensable role in such cases. Our findings uncover the layer-dependent dynamics in the cortical processing of visual attention and open up new possibilities for further research on layer-dependent properties in the cerebral cortex. [ABSTRACT FROM AUTHOR]

Background: Mepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in realworld settings. Objectives: This study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM). Results: After PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose = 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses = 4 mg/day at the last observation. In all models, achieving a GC dose = 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012). Conclusion: Mepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients. [ABSTRACT FROM AUTHOR]

Objectives To identify and characterize undescribed systemic sclerosis (SSc)-specific autoantibodies targeting nucleolar antigens and to assess their clinical significance. Methods We conducted proteome-wide autoantibody screening (PWAS) against serum samples from SSc patients with nucleolar patterned anti-nuclear antibodies (NUC-ANAs) of specific antibodies (Abs) unknown, utilizing wet protein arrays fabricated from in vitro human proteome. Controls included SSc patients with already-known SSc-specific autoantibodies, patients with other connective tissue diseases and healthy subjects. The selection of nucleolar antigens was performed by database search in the Human Protein Atlas. The presence of autoantibodies was certified by immunoblots and immunoprecipitations. Indirect immunofluorescence assays on HEp-2 cells were also conducted. Clinical assessment was conducted by retrospective review of electronic medical records. Results PWAS identified three candidate autoantibodies, including anti-nuclear valosin-containing protein-like (NVL) Ab. Additional measurements in disease controls revealed that only anti-NVL Abs are exclusively detected in SSc. Detection of anti-NVL Abs was reproduced by conventional assays such as immunoblotting and immunoprecipitation. Indirect immunofluorescence assays demonstrated homogeneous nucleolar patterns. Anti-NVL Ab-positive cases were characterized by significantly low prevalence of diffuse skin sclerosis and interstitial lung disease, compared with SSc cases with NUC-ANAs other than anti-NVL Abs, such as anti-U3-RNP and anti-Th/To Abs. Conclusion Anti-NVL Ab is an SSc-specific autoantibody associated with a unique combination of clinical features, including limited skin sclerosis and lack of lung involvement. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the agreement of three different automated methods of identifying force-onset (40 N, 5 SDs, and 3 SDs) with manual identification, during the isometric mid-thigh pull (IMTP). Fourteen resistance-trained participants with >6 months experience training with the power clean volunteered to take part. After three familiarisation sessions, the participants performed five maximal IMTPs separated by 1 min of rest. Fixed bias was found between 40 N and manual identification for time at force-onset. No proportional bias was present between manual identification and any automated threshold. Fixed bias between manual identification and automated was present for force at onset and F150. Proportional but not fixed bias was found for F50 between manual identification and all automated thresholds. Small to moderate differences (Hedges g = −0.487- −0.692) were found for F90 between all automated thresholds and manual identification, while trivial to small differences (Hedges g = −0.122—−0.279) were found between methods for F200 and F250. Based on these results, strength and conditioning practitioners should not use a 40 N, 5 SDs, or 3 SDs threshold interchangeably with manual identification of force-onset when analysing IMTP force–time curve data. [ABSTRACT FROM AUTHOR]

For fish oil-free aquafeed development, a photoautotrophic microalga Tisochrysis lutea is believed to be the candidate source of n-3 highly unsaturated fatty acid (n-3 HUFA) because of its docosahexaenoic acid (DHA) biosynthesis. While DHA contents of T. lutea vary during the cultivation periods depending on algal growth phase, little is mentioned about how this dependence should be taken into consideration when evaluating the suitability of microalgae as an alternative to fish oil-formulated diets. Here, we compared nutritionally maximized cells of deceleration growth phase T. lutea and fish oils-formulated product (n-3 HUFA-enriched Chlorella) as a rotifer enrichment diet for enhancement in Japanese flounder Paralichthys olivaceus larviculture. T. lutea had higher concentrations of DHA in the polar lipids than those for enriched Chlorella. Such higher concentrations of T. lutea were estimated only in the deceleration growth phase (not in the logarithmic growth or stationary phase). When deceleration growth phase T. lutea were fed to Brachionus plicatilis rotifers previously cultured on unenriched Chlorella, the DHA of the rotifers was boosted up to the level in those fed with enriched Chlorella. Furthermore, use of T. lutea-fed rotifers for initial feeding of fish larvae enhanced the growth, survival, n-3 HUFA levels, and final juvenile productivity of the larvae as much as feeding the larvae with enriched Chlorella-fed rotifers. We propose that T. lutea in the deceleration growth phase are efficacious, fish oil-free sources of n-3 HUFA for marine fish larviculture. Highlights: Polar lipid DHA % was high in the deceleration growth phase of Tisochrysis lutea. DHA % was high in rotifers fed either T. lutea or fish oil-enriched Chlorella. Rotifers enriched with T. lutea improved marine fish larviculture performance. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major complication of rheumatoid arthritis (RA), but effective treatment remains an unmet need in its management. Our aim was to evaluate the therapeutic efficacy of abatacept for RA-ILD. Methods: This observational retrospective study included patients with RA-ILD treated with abatacept between 2012 and 2021. Indices of RA disease activity and interstitial lung disease (Disease Activity Score in 28 joints using C-reactive Protein [DAS28-CRP], Simplified Disease Activity Index [SDAI], Clinical Disease Activity Index [CDAI], serum Krebs von den Lungen-6 levels, % forced vital capacity [%FVC], and semi-quantified chest high-resolution computed tomography scores) were evaluated before and 1 year after the start of abatacept administration. Results: Overall, 38 patients were included. DAS28-CRP, SDAI, and CDAI were significantly improved (all with p < 0.0001). Total ground-glass opacity scores were decreased in both patients with usual interstitial pneumonia (UIP)-like patterns and with non-UIP-like patterns (p = 0.008 and <0.002, respectively). Total fibrosis scores were also decreased in the UIP-like pattern group (p < 0.042). The %FVC remained stable. Conclusions: Abatacept significantly improves RA disease activity and reduces pulmonary inflammation in patients with RA-ILD. [ABSTRACT FROM AUTHOR]

Precision medicine has drastically changed cancer treatment strategies including KRAS-mutant cancers which have been undruggable for decades. While intrinsic or acquired treatment resistance remains unresolved in many cases, epigenome-targeted therapy may be an option to overcome. We recently discovered the effectiveness of blocking small ubiquitin-like modifier (SUMO) signaling cascade (SUMOylation) in MYC-expressing KRAS-mutant cancer cells using a SUMO-activating enzyme E inhibitor TAK-981 that results in SUMOylation inhibition. Interestingly, TAK-981 promoted the degradation of MYC via the ubiquitin–proteasome system. Moreover, combination therapy with TAK-981 and MEK inhibitor trametinib remarkably regressed xenografted KRAS-mutant tumors by accumulating DNA damage and inducing apoptosis. Whereas our recent study revealed immune-independent antitumor efficacy, we evaluated the immune responses of cancer cells and immune cells in this study. We found that TAK-981-induced MYC downregulation promoted the activation of STING followed by Stat1 and MHC class I in KRAS-mutant cancer cells. Activation of dendritic cells or T cells treated with TAK-981 was also verified by upregulated activation markers in dendritic cells or skew-toward effector-like phenotypes in T cells. Furthermore, the enhanced immune-dependent antitumor efficacy of the combination therapy with TAK-981 and trametinib was confirmed by infiltration of immune cells into tumor tissues and immunodepleting-test using immunodepleting antibodies in syngeneic immunocompetent mouse models. Together with our recent study and here, the findings support that combination inhibition of SUMOylation and MEK comprehensively conquers MYC-expressing KRAS-mutant cancers by both immune-dependent and immune-independent antitumor responses. [ABSTRACT FROM AUTHOR]