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Successful first-pass reperfusion is associated with better functional outcomes after mechanical thrombectomy (MT) for acute ischemic stroke, but its treatment strategies remain unclear. We retrospectively recruited patients who underwent MT for M1 occlusion between December 2020 and May 2023 at our institution. The locations of susceptibility vessel sign (SVS) on magnetic resonance imaging were classified into M1 only, M1 to single M2 branch, or M1 to both M2 branches. Patients were included in the SVS tracing group when the stent retriever of the first pass covered the entire SVS length. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction scale 2b-3. Any intracranial hemorrhage detected at 24-hour postoperatively was included as a hemorrhagic complication. The SVS was detected in M1 only, M1 to single M2 branch, and M1 to both M2 branches in 8, 22, and 4 patients, respectively. Among the 34 patients, 27 were included in the SVS-tracing group. Successful first-pass reperfusion was significantly more frequent in the SVS-tracing group compared with the non-SVS tracing group (odds ratio, 14.4; 95% confidence interval, 2.0 − 101; P = 0.007). The procedural time was significantly reduced in the SVS tracing group (median, 29 [interquartile range, 22 − 49] minute vs. 63 [43 − 106] minute; P = 0.043). There was a trend toward less frequent hemorrhagic complications in the SVS tracing group (odds ratio, 0.17; 95% confidence interval, 0.029 − 1.0; P = 0.052). This study provides a thrombus imaging-based MT strategy to efficiently achieve first-pass reperfusion in M1 occlusion. [Display omitted] [ABSTRACT FROM AUTHOR]

While depression has been associated with alterations in the hypothalamic-pituitary adrenal (HPA) axis function, there is still controversy regarding the nature and extent of the dysfunction, such as in the debate about hypercortisolism vs. hypocortisolism. It may therefore be necessary to understand whether and how HPA axis function in depression is linked to mRNA expression of key genes regulating this system. We studied 163 depressed outpatients, most of whom were chronically ill, and 181 healthy controls. Blood mRNA expression levels of NR3C1 (including GRα , GRβ , and GR-P isoforms), FKBP4 , and FKBP5 were measured at baseline. HPA axis feedback sensitivity was measured by the dexamethasone (Dex)/corticotropin-releasing hormone (CRH) test. The association between mRNA expression levels and HPA axis feedback sensitivity was examined. Compared to controls, patients showed significantly higher expression of GRα and lower expression of FKBP5 , and higher post-Dex cortisol levels, even after controlling for age and sex. FKBP5 expression was significantly positively correlated with cortisol levels in patients, while GRα expression was significantly negatively correlated with cortisol levels in controls. Most patients were taking psychotropic medications. The large number of correlation tests may have caused type I errors. The tripartite relationship between depression, mRNA expression of GR and FKBP5 , and HPA axis function suggests that the altered gene expression affects HPA axis dysregulation and, as a result, impacts the development and/or illness course of depressive disorder. The combination of increased GRα expression and decreased FKBP5 expression may serve as a biomarker for chronic depression. • We examined blood mRNA expression of GR isoforms and FKBP4 / FKBP5 in depression. • Compared to controls, patients showed higher GRα and lower FKBP5 expression levels. • Compared to controls, patients had higher post-dexamethasone cortisol levels. • The differential gene expression was linked to altered HPA axis feedback sensitivity. • Gene expression affects HPA axis function, thereby possibly impacting depression. [ABSTRACT FROM AUTHOR]

To investigate the feasibility of cylindrical costal osteochondral graft transplantation as a novel regenerative treatment in growth arrest. The medial portion of the proximal tibial growth plate of 6-week-old male New Zealand White rabbits was resected to establish an experimental model of partial growth plate injury. The rabbits were divided into four groups: no-treatment, bone wax transplantation, costal chondral graft, and costal osteochondral graft groups. Radiographic and micro-computed tomography scan results were analyzed to evaluate angular deformity of the tibia and bony bridge formation at the injury site. In addition, repair of the injured growth plate cartilage was assessed histologically at 4, 8, and 12 weeks postoperatively. Radiographic examination revealed that bone wax transplantation continuously decreased the medial proximal tibial angle (MPTA) while the costal chondral graft implantation reduced the decrease of MPTA at 12 weeks postoperatively. The costal osteochondral graft implantation recovered the MPTA, close to the normal. Histologically, the costal osteochondral grafts retained the MPTA in the injured site compared to costal chondral grafts. Additionally, hypertrophic chondrocytes were observed at the graft site in the costal osteochondral graft group at 12 weeks, suggesting that endochondral ossification may occur at the graft site similar to normal ossification. The fluorescence in situ hybridization analysis of osteochondral grafts transplanted from male to female rabbits indicated that they were replaced by cells of host origin. The costal osteochondral graft can achieve regeneration without bony bridge formation in partial growth plate injury. [ABSTRACT FROM AUTHOR]

Edwardsiellosis is one of the most important bacterial diseases in fish, sometimes causing extensive economic losses in the aquaculture industry. Our previous studies demonstrated that the Cu,Zn-SOD (sod1) activity has significantly increased in Japanese flounder, Paralichthys olivaceus , hepatopancreas infected by causative bacteria of edwardsiellosis Edwardsiella tarda NUF251. In this study, NUF251 stimulated intracellular superoxide radical production in mouse macrophage RAW264.7 cells, which was reduced by N -acetylcysteine. This result suggests that NUF251 infection causes oxidative stress. To evaluate the regulatory mechanism of Jf sod1 at transcriptional levels under oxidative stress induced by NUF251 infection, we cloned and determined the nucleotide sequence (1124 bp) of the 5′-flanking region of the Jf sod1 gene. The sequence analysis demonstrated that the binding sites for the transcription factors C/EBPα and NF-IL6 involved in the transcriptional regulation of the mammalian sod1 gene existed. We constructed a luciferase reporter system with the 5′-flanking region (−1124/−1) of the Jf sod1 gene, and a highly increased transcriptional activity of the region was observed in NUF251 - infected RAW264.7 cells. Further studies using several mutants indicated that deletion of the recognition region of NF-IL6 (−272/−132) resulted in a significant decrease in the transcriptional activity of the Jf sod1 gene in NUF251-infected RAW264.7 cells. In particular, the binding site (−202/−194) for NF-IL6 might play a major role in upregulating the transcriptional activity of the 5′-flanking region of the Jf sod1 gene in response to oxidative stress induced by NUF251 infection. These results could be provided a new insight to understand the pathogenic mechanism of causative bacteria of edwardsiellosis. [Display omitted] • NUF251 infection caused oxidative stress in RAW264.7 cells. • 5′-flanking region of Jf sod1 gene was firstly sequenced and found some cis -elements. • Causative bacteria of edwardsiellosis infection upregulated transcription of Jf sod1. • NF-IL6 might play a role in activation of Jf sod1 transcription by NUF251 infection. [ABSTRACT FROM AUTHOR]

• Activation of CGRP-positive (+) sensory neurons is crucial for tumor growth. • However, how CGRP (+) sensory neurons are activated requires elucidation. • TRPV1 contributes to activation of CGRP (+) sensory neurons as well as cancer pain. • TRPV1 can be a target for new treatments for cancer pain and cancer development. Activation of calcitonin gene-related peptide (CGRP)-positive sensory neurons in the tumor microenvironment has been shown to be involved in tumor growth. However, how CGRP-positive sensory neurons are activated requires elucidation. In this study, we focused on transient receptor potential vanilloid 1 (TRPV1) and examined the contribution of TRPV1 to tumor growth and cancer pain in a mouse cancer model in which Lewis lung carcinoma was subcutaneously inoculated in the left plantar region. Tumor inoculation gradually increased the volumes of the hind paws of wild type (WT) mice over time, but those of both αCGRP knockout mice and TRPV1 knockout mice were significantly smaller than those of WT mice after tumor inoculation. Both TRPV1 and CGRP are therefore suggested to be involved in tumor growth. In an immunohistochemical study, the percentage of phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB)-positive profiles in CGRP-positive dorsal root ganglion (DRG) neurons in WT mice was significantly increased after tumor inoculation. The percentage of p-CREB-positive profiles in CGRP-positive DRG neurons in TRPV1 knockout mice was also increased after tumor inoculation, but was significantly lower than that in WT mice, indicating the contribution of TRPV1 to activation of CGRP-positive DRG neurons. Cancer pain in TRPV1 knockout mice was significantly lower than that in WT mice. In conclusion, TRPV1 is involved in both tumor growth and cancer pain, potentially leading to a novel strategy for the treatment of cancer pain and cancer development. Cancer pain is also suggested to facilitate tumor growth. [ABSTRACT FROM AUTHOR]

This paper proposes a novel curve called the α - curve , which is specified by a variable shape parameter α and can be applied in curve reconstruction involving curve fairing, fitting, and segmentation. In contrast to classical log-aesthetic curves in which α is constant, this study contributes a novel formulation of α that varies monotonically within a specified segment. By introducing the variable α , the logarithmic curvature graph (LCG) becomes piecewise linear and parabolic, or any other function if necessary. Consequently, in comparison to conventional log-aesthetic curves that have limited field usage based on their rigidity, α -curves have various LCGs and flexible representations, thereby opening up many practical applications. Experimental results and comparative studies on curves created by CAD experts in the automotive industry demonstrate the theoretical and practical validity of α -curves. [Display omitted] • α -Curves are proposed by extending the mathematical framework of log-aesthetic curves • An α -curve is specified by a variable shape parameter • α -Curves have various log-curvature graphs (LCG) and flexible representations • α -Curves are applied to a new fairing, avoiding conventional issues of side effects [ABSTRACT FROM AUTHOR]

Noninvasive positive pressure ventilation (NIPPV) has been established as an effective treatment for heart failure. Positive airway pressure such as continuous positive airway pressure (CPAP) increases cardiac output (CO) in some patients but decreases it in others. However, the mechanism behind such unpredictable responses remains undetermined. We measured hemodynamic parameters of 38 cases using Swan-Ganz catheter before and after CPAP in chronic heart failure status. In those whose CO increased by CPAP, pulmonary vascular resistance (PVR) was significantly decreased and SpO2 significantly increased, but the other parameters were not changed. On the other hand, PVR was not changed, but systemic vascular resistance (SVR) was increased in those whose CO decreased by CPAP. To explain this phenomenon, we simulated the cardiovascular system using a cardiac model of time-varying elastance. In this model, it was indicated that CPAP decreases CO irrespective of cardiac function or filling status under constant PVR condition. However, when reduction of PVR by CPAP was taken into account, an increase in CO was expected especially in the hypervolemic and low right ventricle (RV) systolic function cases. CPAP would increase CO only where PVR can be reduced by CPAP therapy, especially in the case with hypervolemia and/or low RV systolic function. Understanding the underlying mechanism should help identify the patients for whom NIPPV would be effective. • Hemodynamic parameters were compared between CO increased/decreased cases by CPAP. • PVR was significantly decreased in the patients whose CO was increased by CPAP. • Theoretical analysis of the effect of CPAP using computer simulation were performed. • PVR plays an important role in the effect of CPAP on CO, while the mechanical effect of CPAP itself, the so-called transmural pressure, decrease CO. • The effects of CPAP on CO depend on the stressed volume and the RV systolic function. [ABSTRACT FROM AUTHOR]

The widespread dissemination of fake news on social media has substantial economic and social implications. Although traditional propagation-based methods employing graph neural networks show promise for fake news detection, they disregard the influence of confirmation bias in the spread of fake news between users with similar viewpoints. This paper presents a detection approach that accounts for opinion similarity between users by scrutinizing their stances toward news articles and users' post interactions. Using a graph transformer network, our method simultaneously extracts global structural information and interactions of similar stances. Furthermore, it addresses the challenges of stance analysis targeting microblogs while minimizing the effect of poorly represented stance features. We evaluated our approach using custom-crawled Twitter data and the benchmark FibVID dataset. It demonstrated a marked improvement in detection performance compared with conventional methods, including state-of-the-art methods. [Display omitted] • Propagation-based fake news detection considering stance similarity in interactions. • Fine-tunes BERT for stance analysis and assigns user stances as node feature vectors. • Uses GTN to compute attention as similarity of target and neighboring node features. • Enables detection of similar stance diffusion and obstructive stance feature removal. • Achieves best identification performance on PolitiFact and FibVID benchmark datasets. [ABSTRACT FROM AUTHOR]

• Proposal of photoelastic method for a stress analysis in granular terrains. • Visualization and observation of dynamic changes in internal stresses of a granular terrain beneath a traveling wheel. • Comparative investigation of force chain structures (stress propagation angles and propagated range) in granular terrains. • Quantitative evaluation of the force chains based on an orientational order. This paper presents a photoelastic method for the stress analyses of granular terrains beneath a traveling wheel. Recently, wheel terramechanics have been studied using various advanced techniques such as particle velocimetry and machine learning. However, the dynamic profiles of the stress distributions in soil have not been directly observed. In this paper, we propose a photoelastic method to experimentally demonstrate the two-dimensional stress analysis of a granular terrain. This method uses photoelastic disks as terrain particles; thus, the internal stress and propagation of the granular terrain can be visualized using the interference fringe of light. This study aimed to observe the dynamic behavior of grains, typically simulating circular or spherical objects of the granular terrain. To demonstrate the photoelastic method for simulated ground, we developed a single-wheel testbed using photoelastic materials. Moreover, the effects of mixing with non-photoelastic materials were investigated to simulate steady states with small and large wheel-slip conditions. This paper presents a force chain analysis of the photoelastic particles beneath a single traveling wheel. The force chain structure was geometrically compared with the propagation angle and length. In addition, the orientational orders of the force chains were quantitatively evaluated under both small and large wheel slip conditions. The experimental results confirmed that the photoelastic method can reveal dynamic changes in the internal stress structures of granular terrain beneath the wheel under various slip conditions. [ABSTRACT FROM AUTHOR]

To evaluate the causative and risk factors for optic neuropathy with mucocele via imaging studies. We included 21 patients with rhinogenous optic neuropathy with mucocele. We collected data on the sinus involved, age, sex, number of days from the onset of visual impairment to surgery, and computed tomography (CT) imaging findings (bone defects in the lamina papyracea, Onodi cell mucocele, exophthalmos, and optic nerve deviation). The results were compared between two groups, the one having nine patients with pre-operative visual acuity of <0.1 (the poor group) and the other having 12 patients with pre-operative visual acuity of ≥0.1 (the fair group). Whether or not there was a difference in pre-operative visual acuity between patients with and without Onodi cell mucocele was determined. After surgery, visual acuity improved in 16/21 (76.2%) patients, and a correlation analysis showed a significant positive correlation between pre-operative and post-operative visual acuity. In imaging, the causative sinuses accounted for 85.7% of both posterior ethmoid and sphenoid sinuses. Bone defects of the lamina papyracea at the optic canal and the vertical downward deviation of the optic nerve at each location, especially in 6/9 patients with Onodi cell mucocele, were characteristic in the poor group. In these conditions, increasing the contact areas of the optic nerve and mucocele can leads to more chances of direct downward compression of the optic nerve and infection occurring, and it may lead to severe pre-operative visual impairment. Imaging studies of optic neuropathy with mucocele help to determine the risk factors and perform early and precise diagnostic imaging and decision-making for surgery. [ABSTRACT FROM AUTHOR]

Women with Type 2 diabetes (T2D) face up to 50% higher risk of cardiovascular disease than men. This study evaluated the extent to which prediabetes and undiagnosed T2D are associated with a greater excess risk of cardiovascular disease in women versus in men. Data were pooled from 18,745 cardiovascular disease−free individuals from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. The risk of coronary heart disease, ischemic stroke, and atherosclerotic cardiovascular disease (coronary heart disease or stroke) associated with prediabetes or undiagnosed T2D was estimated using Cox models adjusting for sociodemographic factors, concomitant risk factors, medication use, and menopausal status. Data were collected in 2022, and the analysis was performed in 2023. During a median follow-up of 18.6 years, the associations between prediabetes and risk of atherosclerotic cardiovascular disease were only significant in women (hazard ratio=1.18, 95% CI=1.01, 1.34, p =0.03) but not in men (hazard ratio=1.08, 95% CI=1.00, 1.28, p =0.06) (p -interaction=0.18). The associations between undiagnosed T2D and cardiovascular disease outcomes were significant in both sexes, but the effect was more pronounced in women (coronary heart disease: hazard ratio=1.83, 95% CI=1.4, 2.41, p <0.0001 in women vs hazard ratio=1.6, 95% CI=1.38, 2.07, p =0.007 in men; stroke: hazard ratio=1.99, 95% CI=1.39, 2.72, p <0.0001 vs hazard ratio=1.81, 95% CI=1.36, 2.6, p <0.0001; atherosclerotic cardiovascular disease: hazard ratio=1.86, 95% CI=1.5, 2.28, p <0.0001 vs hazard ratio=1.65, 95% CI=1.4, 1.98, p <0.0001) (all p -interactions≤0.2). Both White and Black patients exhibit similar sex differences. Prediabetes or undiagnosed T2D was associated with a greater excess risk of cardiovascular disease in women than in men. The sex differential in cardiovascular disease risk among those without the T2D diagnosis suggests the need for sex-specific guidelines in T2D screening and treatment. [ABSTRACT FROM AUTHOR]

Combining the Malliavin calculus with Fourier techniques, we develop a high-order asymptotic expansion theory for general Wiener functionals. Our method gives an expansion of the characteristic functional and of the local density of a Wiener functional up to an arbitrary order. The asymptotic expansion is distributional. Except for the non-degeneracy of the limit covariance matrix, we do not assume any condition of non-degeneracy of the Malliavin covariance like a non-degeneracy condition for temporally local characteristic functions so far assumed in the theory for mixing processes, that corresponds to the Cramér condition in the classical setting. Moreover, our method does not require the Markovian property used in the mixing approach. An application to the stochastic wave equation with space–time white noise is discusses. [ABSTRACT FROM AUTHOR]

Soft tissue necrosis (STN) is a late toxicity after radiotherapy. Extensive tissue defects due to STN near the carotid artery, such as in the lateral oropharyngeal wall, may lead to infectious pseudoaneurysms associated with fatal bleeding. Such defects are usually treated with transcervical reconstructive surgeries, which are highly invasive and technically difficult. We report a case in which a buccal fat pad (BFP) flap was used for minimally invasive transoral repair of tissue defects due to radiation-induced STN in the lateral oropharyngeal wall. The BFP flap covered the tissue defect, and the wound epithelialized completely. The patient had no dysfunctional mouth opening, speech, or swallowing. The BFP flap can be easily harvested via a minimally invasive transoral approach and is expected to be further utilized for radiation-induced STN in the lateral oropharyngeal wall. [ABSTRACT FROM AUTHOR]

We have derived functions of the lowest possible degree that enable us to evaluate curvature monotonicity for any 2D and 3D rational Bézier curves. We proved that the degree of the function is at most 8 n − 12 for planar rational Bézier curves of degree n , and is at most 11 n − 18 for space rational Bézier curves of degree n. These functions are derived in the Bernstein basis, allowing for efficient checking of curvature monotonicity using subdivision or Bézier clipping. As an application, we present real-time visualization of the region of a particular control point that guarantees monotonic variation of curvature over the entire segment of the rational Bézier curve. This allows users to identify where to move the control point to ensure that the curvature changes monotonically. • Curvature Monotonicity Evaluation Functions (CMEFs) are derived for Bézier curves • These CMEFs cover polynomial/rational planar/space Bézier curves of any degree • Derived CMEFs have succinct structures in Bernstein basis • Exact degree reduction mechanism in the derivation process is clarified • CMEFs can be used to interactive curve design with monotonically varying curvature [ABSTRACT FROM AUTHOR]

This article discusses a retrospective cohort study that aimed to assess the feasibility of neoadjuvant chemoradiotherapy (NACRT) followed by minimally invasive esophagectomy (MIE) for borderline resectable esophageal squamous cell carcinoma (ESCC). The study included 33 patients with clinically borderline resectable T3 tumors, and the short- and mid-term oncological outcomes were assessed. The study found that NACRT followed by MIE was feasible and resulted in acceptable local control as mid-term oncological outcomes for cT3br ESCC. However, the study had limitations such as a small sample size and short follow-up period. [Extracted from the article]

Initiation of chromosomal replication requires dynamic nucleoprotein complexes. In most eubacteria, the origin oriC contains multiple DnaA box sequences to which the ubiquitous DnaA initiators bind. In Escherichia coli oriC, DnaA boxes sustain construction of higher-order complexes via DnaA-DnaA interactions, promoting the unwinding of the DNA unwinding element (DUE) within oriC and concomitantly binding the single-stranded (ss) DUE to install replication machinery. Despite the significant sequence homologies among DnaA proteins, oriC sequences are highly diverse. The present study investigated the design of oriC (tma-oriC) from Thermotoga maritima, an evolutionarily ancient eubacterium. The minimal tma-oriC sequence includes a DUE and a flanking region containing five DnaA boxes recognized by the cognate DnaA (tmaDnaA). This DUE was comprised of two distinct functional modules, an unwinding module and a tmaDnaA-binding module. Three direct repeats of the trinucleotide TAG within DUE were essential for both unwinding and ssDUE binding by tmaDnaA complexes constructed on the DnaA boxes. Its surrounding AT-rich sequences stimulated only duplex unwinding. Moreover, head-to-tail oligomers of ATP-bound tmaDnaA were constructed within tma-oriC, irrespective of the directions of the DnaA boxes. This binding mode was considered to be induced by flexible swiveling of DnaA domains III and IV, which were responsible for DnaA-DnaA interactions and DnaA box binding, respectively. Phasing of specific tmaDnaA boxes in tma-oriC was also responsible for unwinding. These findings indicate that a ssDUE recruitment mechanism was responsible for unwinding and would enhance understanding of the fundamental molecular nature of the origin sequences present in evolutionarily divergent bacteria. [ABSTRACT FROM AUTHOR]

Nualart and Yoshida (2019) presented a general scheme for asymptotic expansion of Skorohod integrals. However, when applying the general theory to a variation of a process related to a fractional Brownian motion, one repeatedly needs estimates of the order of L p -norms and Sobolev norms of functionals that are complicated as a randomly weighted sum of products of multiple integrals of the fractional Brownian motion. To resolve the difficulties, in this paper, we construct a theory of exponents based on a graphical representation of the structure of the functionals, which enables us to tell an upper bound of the order of functionals by a simple rule. We also show how the exponents change by the actions of the Malliavin derivative and its projection. The exponents are useful in various studies of limit theorems as well as in applications to asymptotic expansion. [ABSTRACT FROM AUTHOR]

The pneumococcal conjugate vaccine (PCV) was introduced to children in Japan in February 2010 for PCV7 and February 2013 for PCV13. This study aimed to investigate the changes in child pneumonia hospitalization in Japan, before and after the introduction of PCV. We utilized the JMDC Claims Database, an insurance claims database in Japan, with a cumulative population of approximately 10.6 million as of 2022. We extracted data of approximately 3.16 million children below 15 years of age from January 2006 to December 2019, and evaluated the number of pneumonia hospitalizations per 1,000 persons per year. The primary analysis was a comparison of three categories according to PCVs: before PCV7, before PCV13, and after PCV13 (2006–2009, 2010–2012, and 2013–2019). The secondary analysis was an interrupted time series (ITS) analysis, assessing the slope change in pneumonia hospitalizations per month, with PCV introduction as an intervening factor. The cases of pneumonia hospitalizations during the study period was 19,920 (0.6 %); 25 % of these were 0–1 years, 48 % were 2–4 years, 18 % were 5–9 years, and 9 % were 10–14 years. Pneumonia hospitalizations per 1000 population was 6.10 before PCV7 and 4.03 after PCV13, representing a 34 % decrease (p < 0.001). The reduction by age group was –30.1 % in 0–1 years, –20.3 % in 2–4 years, –41.7 % in 5–9 years, and –52.9 % in 10–14 years, significant reduction in all groups. ITS analysis showed a further reduction of –0.17 % per month after the introduction of PCV13 than that before PCV7 (p = 0.006). Our study estimated 4–6 pneumonia hospitalizations per 1000 pediatric population in Japan, with a 34 % decrease after the introduction of PCV. This study examined the nationwide effectiveness of PCV, further studies are needed in all age groups. [ABSTRACT FROM AUTHOR]

Aortic valve calcification (AVC) is a common valvular abnormality that predisposes to stenosis; AVC progression and factors associated with it remain unclear. We investigated the association of clinical factors and serum biomarkers with AVC progression in a population-based cohort of older adults. Participants enrolled in both the Cardiovascular Abnormalities and Brain Lesion study (CABL; years 2005–2010) and the Subclinical Atrial Fibrillation And Risk of Ischemic Stroke study (SAFARIS;2014–2019) represent the study cohort. AVC was defined as bright dense echoes >1 mm in size on ≥1 cusps; each cusp was graded on a scale of 0 (normal) to 3 (severe calcification) at baseline and follow up. Serum biomarkers were measured at the time of follow-up assessment. 373 participants (mean 68.1 ± 7.6 years of age, 146 M/ 227F) were included. 139 (37%) had AVC progression;93 (25%) had mild progression (1 grade), and 46 (12%) had moderate-severe progression (≥2 grades). The only significant clinical predictor of any progression was the use of anti-hypertensive medication which was associated with older age, higher BMI and more frequent hypertension, diabetes and hyperlipidemia. In multivariable analysis including biomarkers, transforming growth factor beta 1 (TGF-β1) was significantly associated with both all and moderate-severe AVC progression. A significant number of elderly subjects with AVC show progression of their valve disease; individual vascular risk factors are not associated with AVC progression, although a combined effect may exist. Higher levels of TGF-β1 are observed in individuals with AVC progression. [Display omitted] • Aortic valve calcification (AVC) is a common progressive valvular abnormality. • We measured AVC in elderly subjects at baseline and after a mean 8 year follow up. • Individual vascular risk factors are not associated with AVC progression. • Higher levels of transforming growth factor beta in subjects with AVC progression. [ABSTRACT FROM AUTHOR]

Biologists often study particular biological systems as models of a phenomenon of interest even if they already know that the phenomenon is produced by diverse mechanisms and hence none of those systems alone can sufficiently represent it. To understand this modeling practice, the present paper provides an account of how multiple model systems can be used to study a phenomenon that is produced by diverse mechanisms. Even if generalizability of results from a single model system is significantly limited, generalizations concerning specific aspects of mechanisms often hold across certain ranges of biological systems, which enables multiple model systems to jointly represent such a phenomenon. Comparing mechanisms that operate in different biological systems as examples of the same phenomenon also facilitates characterization and investigation of individual mechanisms. I also compare my account with two existing accounts of the use of multiple model systems and argue that my account is distinct from and complementary to them. [ABSTRACT FROM AUTHOR]

Transparent tetragonal ZrO 2 (3-mol% yttria-stabilized zirconia [3YTZ]) was fabricated by sinter forging of nanoparticles at 950 °C with applied stress of 200 MPa. In this study, the initial compact prepared by gel-casting had a densely packed structure of nanoparticles, and the calcined compact exhibited slight translucency. The grain size of the resulting dense sample was approximately 47 nm. In-line transmittance for a 0.9-mm-thick sample was 28% at a wavelength of 640 nm, representing 37% of the theoretic value. Meanwhile, the sample with the best transparency in this study was slightly whitish. This study demonstrated that combining nanoparticle gel-casting with external pressure to lower the sintering temperature is an effective method for obtaining transparent tetragonal zirconia. • Tetragonal zirconia with high birefringence is one of the most difficult materials to achieve transparency in. • A homogeneous green body with slight translucency was successfully prepared by gel-casting of tetragonal zirconia nanoslurry. • The sample sintered at 950 °C had a grain size of 47 nm and exhibited optical transparency. • In-line transmittance for a 0.9-mm-thick sample was 28% at a wavelength of 640 nm. [ABSTRACT FROM AUTHOR]

Objective: Recurrent otitis media and persistent otitis media with effusion in early childhood may cause an atelectatic eardrum and adhesive otitis media, which sometimes progress to pars tensa cholesteatoma. When and how children with adhesive otitis media should be operated on remain controversial. Therefore, this study aimed to analyze the clinical characteristics of children with adhesive otitis media and pars tensa cholesteatoma, and to determine the risk factors of progression to cholesteatoma.Methods: Seventeen ears of 15 children with adhesive otitis media (adhesive group) and 14 ears of 13 children with pars tensa cholesteatoma (tensa cholesteatoma group) who underwent tympanoplasty were included in this study. We analyzed the following clinical characteristics of children in both groups: medical and life history, associated diseases, sites of the adhesion, and development and aeration of mastoid air cells as shown by temporal bone computed tomography.Results: Most of the children in both groups had a history of recurrent otitis media and/or persistent otitis media with effusion. They showed a male predominance and a frequent association of allergic rhinitis. The number of ears showing undeveloped mastoid air cells in the tensa cholesteatoma group was significantly larger than that in the adhesive otitis media group (P=0.0068). A lack of aeration of the middle ear, including the eustachian tube, was more frequently found in ears with pars tensa cholesteatoma than in ears with adhesive otitis media (P=0.0012). Using multivariate logistic regression, the presence of otorrhea (odds ratio [OR], 14.847; 95% confidence interval [CI], 0.834-264.184), total adhesion (OR, 28.550; 95% CI, 0.962-847.508), and undeveloped mastoid air cells (OR, 19.357; 95% CI, 1.022-366.589) were related to pars tensa cholesteatoma.Conclusion: Children with adhesive otitis media should be carefully followed up in the outpatient setting. Ears with poor mastoid development may develop pars tensa cholesteatoma. Additionally, ears with middle ear effusion, total adhesion, and the presence of otorrhea tend to be at risk of pars tensa cholesteatoma. Tympanoplasty or tympanostomy tube insertion should be considered for children with adhesive otitis media who have these risk factors to prevent progression to pars tensa cholesteatoma. [ABSTRACT FROM AUTHOR]

Although oral frailty is independently associated with an increased risk of mortality, evidence for the usefulness of screening tools for oral frailty is less than that for physical frailty screening tools. We aimed to investigate the relationship between oral frailty and mortality in older adults. This prospective cohort study included 11,374 adults aged ≥65 years, who provided valid responses to a baseline mail survey questionnaire from the Kyoto-Kameoka study. Oral frailty status was evaluated using the Oral Frailty Index-8 (range, 0 [best] to 10 [worst]). Participants were classified into four categories according to the Oral Frailty Index-8: robust (score, 0–2), oral pre-frailty (score, 3), oral frailty (score, 4–6), and oral severe frailty (score ≥ 7). Physical and psychological frailty were evaluated using the validated frailty-screening index and defined as a score of ≥3 out of a possible 5 points. Mortality data were collected from 30 July 2011 to 30 November 2016. Hazard ratios (HR) for all-cause mortality were calculated using a multivariable Cox proportional hazards model. During the 5.3-year median follow-up period (57,157 person-years), 1184 deaths were recorded. After adjusting for confounders, including physical and psychological frailty, medical history, and lifestyle, in comparison with a robust oral status, oral pre-frailty (HR, 1.29; 95 % confidence interval [CI], 1.02–1.63), oral frailty (HR, 1.22; 95 % CI, 1.01–1.48), and oral severe frailty (HR, 1.43; 95 % CI, 1.16–1.76) were associated with higher HRs of mortality (p for trend = 0.002). Oral frailty is associated with mortality independent of physical and psychological frailty in older adults. The Oral Frailty Index-8 may be useful for identifying individuals at high risk of mortality. • Oral Frailty Index-8 has moderate diagnostic accuracy for oral frailty defined from objectively measured mixing ability. • Oral frailty was independently associated with all-cause mortality, even after adjusting for physical and psychological frailty in older adults. • Oral Frailty Index-8 score > 6 has positive log-linear relationship with mortality. [ABSTRACT FROM AUTHOR]

Lung cancer is a leading cause of cancer-related mortality and remains one of the most poorly prognosed disease worldwide. Therefore, it is necessary to identify novel molecular markers with potential therapeutic effects. Recent findings have suggested that dual-specificity tyrosine-regulated kinase 2 (DYRK2) plays a tumor suppressive role in colorectal, breast, and hepatic cancers; however, its effect and mechanism in lung cancer remain poorly understood. Therefore, this study aimed to investigate the tumor-suppressive role and molecular mechanism of DYRK2 in lung adenocarcinoma (LUAD) by in vitro experiments and xenograft models. The evaluation of DYRK2 expression was carried out using lung cancer cell lines and normal bronchial epithelial cells. Overexpression of DYRK2 was induced by an adenovirus vector, and cell proliferation was assessed through MTS assay and Colony Formation Assay. Cell cycle analysis was performed using flow cytometry. Additionally, proliferative capacity was evaluated in a xenograft model by subcutaneously implanting A549 cells into SCID mice (C·B17/Icr-scidjcl-scid/scid). Immunoblotting assays showed that DYRK2 was downregulated in most LUAD cell lines. DYRK2 overexpression using adenovirus vectors significantly suppressed cell proliferation compared with that in the control group. Additionally, DYRK2 overexpression suppressed tumor growth in a murine subcutaneous xenograft model. Mechanistically, DYRK2 overexpression inhibited the proliferation of LUAD cells via p21-mediated G1 arrest, which was contingent on p53. Taken together, these findings suggest that DYRK2 may serve as potential prognostic biomarker and therapeutic target for LUAD. • DYRK2 overexpression suppresses lung adenocarcinoma via p53 and p21 upregulation. • DYRK2 induces G1 arrest in lung adenocarcinoma cell lines. • DYRK2 expression may be a prognostic factor in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Intractable otitis media is resistant to antimicrobial therapy, tympanostomy ventilation tube insertion, and surgery. In children, intractable acute otitis media, pathological tympanic membrane due to prolonged otitis media with effusion (OME), tympanic membrane atelectasis, and adhesive otitis media are common. Contrarily, in adults, otitis media caused by drug-resistant pathogens, tuberculous otitis media, cholesterol granuloma, malignant otitis externa (skull base osteomyelitis), eosinophilic otitis media (EOM), and otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) are common and require differentiation. Among them, EOM is increasing along with eosinophilic upper respiratory tract diseases, such as bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps (CRSwNP). EOM is associated with adult-onset bronchial asthma and is characterized by viscous middle ear effusion and middle ear mucosa thickness with eosinophilic infiltration, which requires treatment with glucocorticoids according to disease activity and symptoms. Recently, OMAAV was proposed because of the similarities in clinical features and therapeutic effects. The clinical course of OMAAV is characterized by a relatively rapid increase in the bone conductive hearing threshold, which progresses over 1-2 months, without response to antimicrobial agents or tympanostomy ventilation tube insertion, and in some cases, is complicated by facial paralysis and hypertrophic pachymeningitis. This new concept may explain the pathogenesis and clinical presentation of many cases of intractable otitis media, the cause of which was previously unknown. Although making a diagnosis of OMAAV is relatively easy based on the clinical course, such as vascular dilatation of the tympanic membrane and positive ANCA titer, it is often difficult because the ANCA titer becomes negative with previous administration of glucocorticoids. In adults with intractable otitis media, ANCA titers must be measured before glucocorticoid administration. Treatment consisted of remission induction therapy with a combination of glucocorticoids and immunosuppressive drugs. [ABSTRACT FROM AUTHOR]

Otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV) has been proposed as a new type of otitis media. The hearing loss caused by OMAAV can be expected to improve with early detection and intervention, but if it continues to worsen and leads to deafness, it is challenging to recover the patient's hearing. When bilateral deafness occurs, cochlear implant (CI) surgery is the only way to improve hearing. Here, Case 1 showed unilateral cochlear calcification, and Case 2 showed bilateral cochlear calcification. In Case 1, CI surgery was performed on the ear lacking calcification, and in Case 2 it was performed on the ear with milder calcification. In Case 2, granulation was present from the tympanic space to the mastoid, the round window was closed, and the basal turn of the cochlea was narrowed. Such calcification of the cochlea caused by OMAAV has not been reported so far. It is essential to detect these changes by computed tomography scans at an early stage and to perform CI surgery at an appropriate time, because hearing improvements are not expected in patients who become deaf because of OMAAV. [ABSTRACT FROM AUTHOR]

Introduction: Women of reproductive age are less prone to cardiovascular disease than men. However, diabetes mellitus negates this female advantage. The prevalence change of prediabetes (prediabetes mellitus) and diabetes mellitus and diabetes mellitus‒associated cardiovascular risk factors have not been clearly described in women before menopause.Methods: Using National Health and Nutrition Examination Survey data (1999-2018), this study estimated the age-adjusted prevalence of prediabetes mellitus (2005-2018), diagnosed diabetes mellitus, and undiagnosed diabetes mellitus in premenopausal women. Logistic regression was used to examine cardiovascular risk factors, including obesity, central obesity, hypercholesterolemia, hypertension, and hypertriglyceridemia, associated with prediabetes mellitus, diagnosed diabetes mellitus, or undiagnosed diabetes mellitus in premenopausal women. The magnitude of the association among age-matched men and postmenopausal women was compared. The analysis was conducted in 2022.Results: Premenopausal women experienced an increased prevalence of prediabetes mellitus and undiagnosed diabetes mellitus, contrasting with steady trends in all U.S. adults over the last 2 decades. Premenopausal women with prediabetes mellitus or diabetes mellitus (versus those with normoglycemia) have significant obesity risk, and the risk is equivalent to that among age-matched men and higher than that among postmenopausal women. The association between prediabetes mellitus and hypercholesterolemia or hypertriglyceridemia was significant in premenopausal women only. Hypercholesterolemia and hypertension associated with undiagnosed diabetes mellitus were significant in premenopausal women and men of the same age, respectively. Diagnosed and undiagnosed diabetes mellitus was associated with hypertriglyceridemia in men and postmenopausal women, respectively.Conclusions: Premenopausal women had increased prediabetes mellitus and undiagnosed diabetes mellitus in the past 2 decades. They face a considerable cardiovascular risk burden associated with prediabetes mellitus and diabetes mellitus. Cardiometabolic risk screening and patient education should be improved in young and early middle-aged adults, particularly in women. [ABSTRACT FROM AUTHOR]

Early decompressive surgery within 24 hours improves the functional outcome of patients with traumatic spinal cord injury; however, little is known about the effect of early surgery for spontaneous spinal epidural hematoma (SSEH). In this study, we aimed to investigate the effectiveness of ultraearly hematoma evacuation (<12 hours) for SSEH. Patients with SSEH treated with surgical hematoma evacuation at our institution between January 2000 and July 2021 were retrospectively analyzed. Neurologic function was evaluated using the American Spinal Injury Association Impairment Scale (AIS). AIS grades A–C were defined as severe, and grades D and E as mild. AIS grades D and E at the final follow-up were considered favorable outcomes. Preoperative status and postoperative treatment results were compared between patients who had hematoma evacuation within 12 hours of onset and those who underwent surgery after 12 hours. Twenty-five consecutive patients were included in the analysis. Preoperatively, 23 patients (92.0%) had severe AIS. Fourteen (56.0%) patients underwent early surgery. At the final follow-up, 21 patients (84.0%) achieved favorable outcomes. Patients treated with ultraearly surgery had significantly better outcomes (100% vs. 63.6%, P = 0.03). Additionally, the time from onset to surgery was significantly shorter in patients with AIS improvement by 2 or more grades than that in patients with AIS improvement of 1 or less (median 8 hours vs. 14 hours, P = 0.0001). Ultraearly surgery within 12 hours for SSEH was associated with better functional outcomes. [ABSTRACT FROM AUTHOR]

Asymptotic expansion of a variation with anticipative weights is derived by the theory of asymptotic expansion for Skorohod integrals having a mixed normal limit. The expansion formula is expressed with the quasi-torsion, quasi-tangent and other random symbols. To specify these random symbols, it is necessary to classify the level of the effect of each term appearing in the stochastic expansion of the variable in question. To solve this problem, we consider a class L of certain sequences (I n) n ∈ N of Wiener functionals and give a systematic way of estimation of the order of (I n) n ∈ N. Based on this method, we introduce a notion of exponent of the sequence (I n) n ∈ N , and investigate the stability and contraction effect of the operators D u n and D on L , where u n is the integrand of a Skorohod integral. After constructed these machineries, we derive asymptotic expansion of the variation having anticipative weights. An application to robust volatility estimation is mentioned. [ABSTRACT FROM AUTHOR]

High signal intensity (HSI) on T2-weighted or fat-suppressed magnetic resonance imaging (MRI) around the shoulder is often observed in patients who have a rotator cuff tear, and is generally recognized as an indicator of shoulder pain, especially pain at night. We hypothesized these HSI volumes are reduced after improvement of symptoms. We sought to compare HSI before and after conservative treatment, and to determine if HSI is associated with the patient's pain status over time. We enrolled 55 patients (average age 65 years) into the study. All the patients complained of pain at night (University of California, Los Angeles (UCLA) pain score ≤2, Japanese Orthopedic Association (JOA) pain score ≤10) at their initial visits and underwent conservative treatment. MRI was obtained at their initial visit and after improvement of pain when their initial UCLA pain score was ≥6 points or JOA pain score was ≥20 points. The mean time between the MRI examinations was 11.8 months (SD 7.7) (range 2.5–39). HSI was assessed at the location of the subacromial–subdeltoid bursa, glenohumeral joint, subcoracoid bursa, and sheath of the long head of the biceps tendon, and graded. Factors correlating with the improvement of MRI findings were evaluated retrospectively. HSI had improved in 30 shoulders in all or some of the locations (I-group). There was no change in 25 shoulders for any location or aggravation in one or more locations (N-group). Multivariate logistic regression analysis found that the time from pain improvement until the second MRI was the only independent factor related to the improvement in HSI (p =.045). Improvement of shoulder symptoms is not directly associated with MRI findings. Improvement in HSI followed symptom improvement after a delay; the changes varied for each shoulder location. [ABSTRACT FROM AUTHOR]

A nanometric Rh overlayer exhibits excellent three-way catalytic activity under stoichiometric conditions. However, dynamic changes in the air-to-fuel (A/F) ratio under experimental conditions deteriorates the catalytic activity caused by the lack of oxygen storage/release capability of Rh. In this study, we first report that the surface modification of the Rh overlayer by a small amount of Ce using a sequential metal deposition technique based on the pulsed arc-plasma method enhances its three-way catalytic activity under A/F perturbation conditions. X-ray photoelectron spectroscopy and X-ray absorption fine structure measurements revealed that the redox behavior of the surface Ce contributed to an oxygen storage/release and buffered the A/F change. The Ce-modified Rh overlayer with a metal honeycomb structure exhibited high activity for the three-way catalytic reaction even under A/F perturbation conditions at high space velocity. This novel catalytic converter is expected to be significantly process and energy saving compared to the conventional catalytic converter. Thus, the oxygen storage/release performance, heat resistance, and low-temperature activity can be improved by controlling the surface composition. [Display omitted] • Sequential metal deposition technique based on pulsed arc-plasma method. • Surface of the Rh overlayer was modified by a small amount of Ce. • Redox behavior of the Ce contributed to an oxygen storage/release. • Ce-modified Rh overlayer exhibited high activity for three-way catalytic reaction. [ABSTRACT FROM AUTHOR]

To improve synthetic media for protein expression in Escherichia coli , a strategy using deep neural networks (DNN) and Bayesian optimization was performed in this study. To obtain training data for a deep learning algorithm, E. coli harvesting a plasmid pRSET/emGFP, which introduces the green fluorescence protein (GFP), was cultivated in 81 media designed using a Latin square in deepwell-scale cultivation. The media were composed of 31 components with three levels. The resultant GFP fluorescence intensities were evaluated using a fluorescence spectrometer, and the intensities were in the range 2.69–7.99 × 103. A deep neural network model was used to estimate the GFP fluorescence intensities from the culture media compositions, and accuracy was evaluated using cross-validation with 15% test data. Bayesian optimization using the best DNN model was used to calculate 20 representative compositions optimized for GFP expression. According to the validating cultivation, the simulated GFP expression levels included large errors between the estimated and experimental data. The DNN model was retrained using data from the validating cultivation, and secondary estimations were performed. The secondary estimations fit the corresponding experimental data well, and the best GFP fluorescence intensity was 1.4-fold larger than the best of the initial test composition. • A deep neural network and Bayesian optimization improved synthetic media. • Two cycles of learning-optimization improved the estimating accuracy. • Improved protein expression increased 1.4-folds larger than that of initial dataset. • Scalability of the optimal media was confirmed at different culture scales. [ABSTRACT FROM AUTHOR]

Support Vector Machines (SVMs) are one of the most popular supervised learning models to classify using a hyperplane in an Euclidean space. Similar to SVMs, tropical SVMs classify data points using a tropical hyperplane under the tropical metric with the max-plus algebra. In this paper, first we show generalization error bounds of tropical SVMs over the tropical projective torus. While the generalization error bounds attained via Vapnik–Chervonenkis (VC) dimensions in a distribution-free manner still depend on the dimension, we also show numerically and theoretically by extreme value statistics that the tropical SVMs for classifying data points from two Gaussian distributions as well as empirical data sets of different neuron types are fairly robust against the curse of dimensionality. Extreme value statistics also underlie the anomalous scaling behaviors of the tropical distance between random vectors with additional noise dimensions. Finally, we define tropical SVMs over a function space with the tropical metric. • We obtain generalization error bounds of tropical SVMs via the VC dimensions. • We demonstrate that the tropical SVMs are robust against the curse of dimensionality. • We define tropical SVMs over a function space to enable the classification of curves. [ABSTRACT FROM AUTHOR]

To ensure efficient photosynthesis, chloroplast proteins need to be flexibly regulated under fluctuating light conditions. Thiol-based redox regulation plays a key role in reductively activating several chloroplast proteins in a light-dependent manner. The ferredoxin (Fd)/thioredoxin (Trx) pathway has long been recognized as the machinery that transfers reducing power generated by photosynthetic electron transport reactions to redox-sensitive target proteins; however, its biological importance remains unclear, because the complete disruption of the Fd/Trx pathway in plants has been unsuccessful to date. Especially, recent identifications of multiple redox-related factors in chloroplasts, as represented by the NADPH-Trx reductase C, have raised a controversial proposal that other redox pathways work redundantly with the Fd/Trx pathway. To address these issues directly, we used CRISPR/Cas9 gene editing to create Arabidopsis mutant plants in which the activity of the Fd/Trx pathway was completely defective. The mutants generated showed severe growth inhibition. Importantly, these mutants almost entirely lost the ability to reduce several redox-sensitive proteins in chloroplast stroma, including four Calvin-Benson cycle enzymes, NADP-malate dehydrogenase, and Rubisco activase, under light conditions. These striking phenotypes were further accompanied by abnormally developed chloroplasts and a drastic decline in photosynthetic efficiency. These results indicate that the Fd/ Trx pathway is indispensable for the light-responsive activation of diverse stromal proteins and photoautotrophic growth of plants. Our data also suggest that the ATP synthase is exceptionally reduced by other pathways in a redundant manner. This study provides an important insight into how the chloroplast redox-regulatory system operates in vivo. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the distribution of human papillomavirus 16 (HPV16) variants that contribute to the development of HPV-related oropharyngeal carcinoma (HPV-OPC) in the Japanese population and to evaluate genetic variations in the sequence encoding the L1 antigen region of the viral outer shell that is targeted by existing vaccines and is relevant for designing a prevention strategy to combat the exponential increase in HPV-OPC cases in Japan.Methods: Seventy Japanese HPV-OPC patients treated at Tohoku University Hospital were included in the study. DNA was extracted from formalin-fixed, paraffin-embedded tissue samples. Polymerase chain reaction and direct nucleotide sequencing were performed to determine the nucleotide polymorphisms necessary for the classification of HPV16 variants and to assess genetic diversity in the HPV16 L1 antigen region, including the BC, DE, EF, FG, and HI loops.Results: The most common variant of HPV16 was the A4 sublineage (88.6%), conventionally called the Asian type, followed by the A1/2/3 (10.0%) sublineage, classified as the European type. The only nonsynonymous substitution detected in the L1 antigen loop region was p.N181T in the EF loop, which was found in 28/70 (40%) cases. In contrast, no nonsynonymous substitutions were observed in the DE, FG, and HI loops, which are particularly important regions in the antigen loop targeted by existing HPV vaccines.Conclusion: The most common HPV16 variant in Japanese HPV-OPC patients was the A4 subtype. The L1 antigen region is highly conserved, suggesting sufficient efficacy of existing HPV vaccines. These findings provide important information that will aid in the design of an HPV16 infection control strategy using existing HPV vaccines to prevent the spread of HPV-OPC in Japan. [ABSTRACT FROM AUTHOR]

The impact of body mass index (BMI) on hospital mortality in patients with acute heart failure has been well documented in Asian populations. However, the relationship between BMI, hospital-associated disability (HAD), and hospitalization costs in patients with heart failure is poorly understood. This study aimed to explore the impact of BMI on HAD and hospitalization costs for acute heart failure in Japan. From April 2012 to March 2020, the Japanese Registry of All Cardiac and Vascular Disease Diagnosis Procedure Combination (JROAD-DPC) database was used to identify patients with acute heart failure. All patients were categorized into five groups according to the World Health Organization Asian BMI criteria. The hospitalization costs and HAD were evaluated. Among the 238,160 eligible patients, 15.7% were underweight, 42.2% were normal, 16.7% were overweight, 19.3% were obese I, and 6.0% were obese II, according to BMI. The prevalence of HAD was 7.43% in the total cohort, and the risk of HAD increased with a lower BMI. Restricted cubic spline analysis showed a U-shaped relationship between BMI and hospitalization costs for all ages. Furthermore, developing HAD was associated with greater costs compared with non-HAD, regardless of BMI category. We found that the lower the BMI, the higher the incidence of HAD. A U-shaped association was confirmed between BMI and hospitalization costs, indicating that hospitalization costs increased for both lower and higher BMI regardless of age. BMI could be an important and informative risk stratification tool for functional outcomes and economic burdens. [Display omitted] • This study revealed that the prevalence of HAD was 7.43% in heart failure patients. • The risk of HAD increased in proportion to thinness. • A U-shaped relationship was found between BMI and hospitalization costs at all ages. • BMI is a risk stratification tool for functional outcomes and economic burdens. [ABSTRACT FROM AUTHOR]

The centromere is an essential chromosomal structure for faithful chromosome segregation during cell division. No protein-coding genes exist at the centromeres, but centromeric DNA is actively transcribed into noncoding RNA (ncRNA). This centromeric transcription and its ncRNA products play important roles in centromere functions. We previously reported that the transcriptional regulator ZFAT (zinc-finger protein with AT hook) plays a pivotal role in ncRNA transcription at the centromere; however, it was unclear how ZFAT involvement was regulated. Here, we show that the death domain-associated protein (DAXX) promotes centromeric localization of ZFAT to regulate ncRNA transcription at the centromere. Coimmunoprecipitation analysis of endogenous proteins clearly reveals that DAXX interacts with ZFAT. In addition, we show that ectopic coexpression of ZFAT with DAXX increases the centromeric levels of both ZFAT and ncRNA, compared with ectopic expression of ZFAT alone. On the other hand, we found that siRNA-mediated depletion of DAXX decreases the centromeric levels of both ZFAT and ncRNA in cells ectopically expressing ZFAT. These results suggest that DAXX promotes the centromeric localization of ZFAT and ZFAT-regulated centromeric ncRNA transcription. Furthermore, we demonstrate that depletion of endogenous DAXX protein is sufficient to cause a decrease in the ncRNA levels at the centromeres of chromosomes 17 and X in which ZFAT regulates the transcription, indicating a physiological significance of DAXX in ZFAT-regulated centromeric ncRNA transcription. Taken together, these results demonstrate that DAXX regulates centromeric ncRNA transcription through ZFAT. [ABSTRACT FROM AUTHOR]

Chloroplast FoF1-ATP synthase (CFoCF1) uses an electrochemical gradient of protons across the thylakoid membrane (ΔμH+) as an energy source in the ATP synthesis reaction. CFoCF1 activity is regulated by the redox state of a Cys pair on its central axis, that is, the γ subunit (CF1-γ). When the ΔμH+ is formed by the photosynthetic electron transfer chain under light conditions, CF1-γ is reduced by thioredoxin (Trx), and the entire CFoCF1 enzyme is activated. The redox regulation of CFoCF1 is a key mechanism underlying the control of ATP synthesis under light conditions. In contrast, the oxidative deactivation process involving CFoCF1 has not been clarified. In the present study, we analyzed the oxidation of CF1-γ by two physiological oxidants in the chloroplast, namely the proteins Trx-like 2 and atypical Cys-His-rich Trx. Using the thylakoid membrane containing the reduced form of CFoCF1, we were able to assess the CF1-γ oxidation ability of these Trx-like proteins. Our kinetic analysis indicated that these proteins oxidized CF1-γ with a higher efficiency than that achieved by a chemical oxidant and typical chloroplast Trxs. Additionally, the CF1-γ oxidation rate due to Trx-like proteins and the affinity between them were changed markedly when ΔμH+ formation across the thylakoid membrane was manipulated artificially. Collectively, these results indicate that the formation status of the ΔμH+ controls the redox regulation of CFoCF1 to prevent energetic disadvantages in plants. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of the fragility fractures of the pelvis (FFPs) has been increasing in recent years. Operative treatment is effective in patients who are unable to ambulate due to pain. Anterior subcutaneous internal fixation (ASIF) is a minimally invasive and stable fixation used to treat the FFPs, with few reported vascular complications. However, we experienced a case in which the rod directly pressed the common femoral artery (CFA).Objectives: The purpose of this study was to examine the relationship between the rod position as defined by ASIF and the CFA in the FFPs patients, and between BMI and the rod-to-CFA distance.Materials and Methods: Pelvic measurements were performed in 47 patients with FFPs using trauma CT. We identified the anterior inferior iliac spine (AIIS) on both sides in axial CT images. Next, we performed a simulation study using the CT images, in which the virtual fixation rod was bent according to the shape of the patients' abdomen in the supine position. The shortest rod-to-CFA distance when the virtual rod was positioned directly above the AIIS in the CT image was measured. The correlation between body mass index (BMI) and the rod-to-CFA distance was measured.Results: The average shortest rod-to-CFA distance was 18.4 ± 11.1 mm, and the simulated rod compressed the CFA in three of the 47 cases (6.4%). A statistically significant positive correlation between BMI and the rod-to-CFA distance was found (r = 0.47, p = 0.001).Conclusions: The course of the CFA should be confirmed before ASIF surgery, and if there is danger of compression of the CFA such as in patients with low BMI, the rod-to-AIIS distance should be adjusted to the optimal distance. However, considering the disadvantages, such as decreased stability of the fixation, when adjusting the rod-to-AIIS distance, and skin irritation and abrasion by the rod, ASIF is not recommended in cases in which the rod is close to the CFA. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is reported to produce anti-HLA antibodies. We report a case of chronic active antibody-mediated rejection caused by pre-existing donor-specific antibody (DSA) in a patient with SLE without a history of sensitization. The case was a 29-year-old man with end-stage renal disease due to lupus nephritis. Cross-match with the mother was negative, but low titer anti-DQ DSA was detected, although he had no prior history of sensitization. After desensitization with rituximab and mycophenolate mofetil, a living donor kidney transplant was undergone, and his early postoperative period was uneventful. However, his renal function started to decline at 2 years post-transplant. Although there was no rejection on the biopsy at 2.5 years post-transplant, his renal function continued to decline after that. At 7 years, he had failed his graft due to chronic active antibody-mediated rejection. Retrospective analysis of human leukocyte antigen antibody tests revealed that anti-DQ DSA had disappeared at 1 year post-transplant, but high titer DSA was detected again with complement-binding capacity at 2 years and after that. Careful monitoring might be warranted in an SLE patient with pre-existing DSA, even though the titer was low and without any prior histories of sensitization events. [ABSTRACT FROM AUTHOR]

To investigate if the pretreatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-based radiomics machine learning predicts the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients. Seventy-eight breast cancer patients who underwent DCE-MRI before NAC and confirmed as pCR or non-pCR were enrolled. Early enhancement mapping images of pretreatment DCE-MRI were created using subtraction formula as follows: Early enhancement mapping = (Signal 1 min – Signal pre)/Signal pre. Images of the whole tumors were manually segmented and radiomics features extracted. Five prediction models were built using five scenarios that included clinical information, subjective radiological findings, first order texture features, second order texture features, and their combinations. In texture analysis workflow, the corresponding variables were identified by mutual information for feature selection and random forest was used for model prediction. In five models, the area under the receiver operating characteristic curves (AUC) to predict the pCR and several metrics for model evaluation were analyzed. The best diagnostic performance based on F-score was achieved when both first and second order texture features with clinical information and subjective radiological findings were used (AUC = 0.77). The second best diagnostic performance was achieved with an AUC of 0.76 for first order texture features followed by an AUC of 0.76 for first and second order texture features. Pretreatment DCE-MRI can improve the prediction of pCR in breast cancer patients when all texture features with clinical information and subjective radiological findings are input to build the prediction model. [ABSTRACT FROM AUTHOR]

Wild boar meat containing radioactive cesium (Cs) of approximately 1,000 Bq/kg (134Cs+137Cs) was processed into bacon, sausage, and ham. To understand the concentration and quantity change of radioactive Cs, the processing factor (Pf) and food processing retention factor (Fr) were calculated. The radioactive Cs quantity in the meat did not reduce during smoking. The dehydration-related meat mass reduction during smoking without decrease of radioactive Cs led to Cs condensation in the bacon compared with the raw rib meat before processing, resulting in a Pf of 1.18. Soaking in liquid, such as pickling in liquid and desalting or boiling in water, effectively removed radioactive Cs by leakage into water. Therefore, the Fr value of the boiled ham produced from a loin meat block through three liquid-soaking processes was 0.27. The Pf value of the boiled ham was 0.30 due to meat block mass reduction after boiling as a result of dehydration, along with protein thermal denaturation-related muscle tissue shrinkage. The steamed ham Fr value was 0.53, because the removal of radioactive Cs was less efficient by steaming than by boiling. The Pf value of the steamed ham was 0.54, almost the same as the Fr value, because the mass decrease rate was the same as the radioactive Cs decrease rate by steaming. The Fr and the Pf values of the boiled sausage, whose processing did not include soaking in the pickling liquid, were 0.64 and 0.62, respectively. Steaming the sausage meat did not remove radioactive Cs during the dehydration-related mass reduction, leading to Fr and Pf values of 1.01 and 1.17, respectively. This study found that processing into boiled ham was the most effective measure for reducing radioactive Cs quantity and concentration in raw meat. Processing into bacon and steamed sausage showed no Cs quantity reduction, with the moisture loss resulting in Cs condensation compared with the raw material. sausage, and ham were made from boar meat contaminated with radioactive Cs. into bacon and steamed sausage increased the Cs concentration in meat. in pickling liquid or water and boiling in water effectively removed Cs. into boiled ham reduced the amount of Cs to 27% in raw meat. was less effective than boiling for Cs reduction in meat. [ABSTRACT FROM AUTHOR]

Environmental stimuli modulate plant metabolite accumulation, facilitating adaptation to stressful conditions. In this study, the effects of blue and red light, photoperiod, CO 2 concentration, and air temperature on the chlorogenic acid (CGA) and rutin contents of lettuce (Lactuca sativa L.) were evaluated. Under continuous blue light and a high CO 2 concentration (1000 ppm), the CGA level increased. The increased expression of phenylalanine ammonia-lyase (PAL) and activity of its product were correlated with high expression of cinnamate 4-hydroxylase (C4H) and coumarate 3-hydroxylase (C3H). Furthermore, changes in PAL activity altered the CGA content in lettuce exposed to the three environmental factors, blue light, continuous lighting and high CO 2 concentration. In addition, the expression levels of genes related to flavonoid biosynthesis increased in accordance with the promotion of CGA accumulation by the environmental factors. Under continuous blue light, 400 ppm CO 2 promoted rutin accumulation to a greater degree compared to 1000 ppm CO 2 , by downregulating DFR expression. Low air temperature induced CGA accumulation in lettuce grown under continuous blue light and 1000 ppm CO 2. Therefore, light quality, photoperiod, CO 2 concentration, and air temperature exert synergistic effects on the CGA and rutin contents of lettuce by modulating activity in the corresponding biosynthesis pathways. [Display omitted] • Multi environmental factors modulate key genes expressions for CGA synthesis. • Continuous blue lighting and high CO 2 level increase PAL activity. • Low CO 2 level under continuous blue lighting increases rutin content. • Low air temperature has a synergic effect with other factors on CGA accumulation. [ABSTRACT FROM AUTHOR]

• Inhibition of caspases in neural lineage causes hydrocephalus and growth retardation in mice. • The flow of cerebrospinal fluid was disturbed without apparent obstruction by caspase inhibition. • Necroptosis was not responsible for the defects caused by the caspase inhibitor. • Protein amounts in CSF was abnormally increased in the hydrocephalic mice. • Activity of caspases in brain development is necessary for establishment of proper CSF dynamics. A large number of cells undergo apoptosis via caspase activation during and after neural tube closure (NTC) in mammals. Apoptosis is executed by either intrinsic or extrinsic apoptotic pathways, and inhibition of each pathway causes developmental defects around NTC stages, which hampers the physiological roles of apoptosis and caspases after NTC. We generated transgenic mice in which a broad spectrum of caspases could be suppressed in a spatiotemporal manner by pan-caspase inhibitor protein p35 originating from baculovirus. Mice with nervous system-specific expression of p35 (Nestin-Cre (NCre);p35V mice) exhibited postnatal lethality within 1 month after birth. They were born at the expected Mendelian ratio, but demonstrated severe postnatal growth retardation and hydrocephalus. The flow of cerebrospinal fluid (CSF) between the third and fourth ventricles was disturbed, whereas neither stenosis nor abnormality in ciliary morphology was observed in the pathway of CSF flow. Hydrocephalus and growth retardation of NCre;p35V mice were not rescued by the deletion of RIPK3 , an essential factor for necroptosis which occurs in the absence of caspase-8 activation during development. The CSF of NCre;p35V mice contained a larger amount of secreted proteins than that of the controls. These findings suggest that the establishment of proper CSF dynamics requires caspase activity during brain development after NTC. [ABSTRACT FROM AUTHOR]

To visualize whole cancerous region including hypoxic cancer without radiation exposure, we developed meglumine-gadopentetate-glucose solution for 7.0-T magnetic resonance imaging. The infusion solution consists of meglumine-gadopentetate and glucose solutions, and these solutions are mixed before the vein drip infusion. We used readily available solutions, and the concentrations of the meglumine-gadopentetate and glucose solutions were 37.14 and 5.0%, respectively. In the first and second experiments, vein infusions were conducted from a rabbit ear using meglumine-gadopentetate-saline and meglumine-gadopentetate-glucose solutions, and T1 weighted imaging was performed to visualize cancerous region. Using the meglumine-gadopentetate saline, it was not difficult to image cancer-growth regions with new blood vessels. Using the meglumine-gadopentetate-glucose solution, the signal intensity of whole cancerous region including hypoxic cancer substantially increased. The visualizing duration for the meglumine gadopentetate glucose was beyond 90 min, and the rabbit survived after the infusion. The signal intensity in the hypoxic cancer was increasing until 90 min using the meglumine-gadopentetate - glucose solution, since the meglumine-gadopentetate molecules were absorbed into almost the whole cancerous region along with glucose-molecule flows. [ABSTRACT FROM AUTHOR]