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Reproducing instructed movements is crucial for practice in motor learning. In this study, we compared the short-term reproduction of active pelvis movements with visual feedback and passive movement with the therapist's hands in an upright stance. Sixteen healthy males (M age = 34.1; SD = 10.2 years) participated in this study. In one condition, healthy males maintained an upright stance while a physical therapist moved the participant's pelvis (passive movement instruction), and in a second condition, the participant actively moved their pelvis with visual feedback of the target and the online trajectory of the center of pressure (active movement instruction). Reproduction errors (displacement of the center of pressure in the medial–lateral axis) 10 s after the passive movement instruction were significantly greater than after the active movement instruction (p < 0.001), but this difference disappeared 30 s after the instruction (p = 0.118). Error of movement reproduction in the anterior–posterior axis after the passive movement instruction was significantly greater than after the active movement instruction, no matter how long the retention interval was between the instruction and reproduction phases (p = 0.025). Taken together, active pelvis movements with visual feedback, rather than passive movement with the therapist's hand, is better to be used for instructing pelvis movements. [ABSTRACT FROM AUTHOR]

Following the discovery of podocyte phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A, various potential target antigens for membranous nephropathy (MN) have been reported one after another. MN target antigens have now been identified in a significant proportion of patients, and a new classification framework classifies patients with MN based on the detected antigen and associated disease phenotype. A serology-based approach that does not require a histological diagnosis for patients suspected of having MN has also been proposed. However, there have been cases in which dual positivity for MN antigens and/or corresponding antibodies has been shown. Importantly, some of them showed a transition of the affected patient's immune responses to MN antigens, suggesting that serological diagnosis changes depending on the timing of the analysis. In this review, we provide detailed information on these cases and present an overview of our recent understanding of their putative mechanisms involved in these cases. Greater awareness is required to adequately recognize and develop appropriate therapeutic strategies for this condition. [ABSTRACT FROM AUTHOR]

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions. [ABSTRACT FROM AUTHOR]

AbstractThis study examined whether tactile gating induced by the descending motor command to one finger spreads out to the other fingers to which the command is not delivered and whether this gating is dependent on the target finger to which the command is delivered. The change in perceptual threshold to the digital nerve stimulation of one finger induced by tonic contraction of the first dorsal interosseous or abductor digiti minimi muscle was examined. The perceptual threshold to the digital nerve stimulation of the thumb or little finger was increased by tonic contraction of the abductor digiti minimi muscle. This finding indicates that the descending motor command to the prime mover of the little finger abduction induces tactile gating not only in the finger to which the command is delivered but also in the other finger to which the command is not delivered. Tonic contraction of the first dorsal interosseous muscle did not change the perceptual threshold to the digital nerve stimulation in any finger. This finding means that tactile gating occurs particularly when the descending motor command is delivered to the dependent finger. Spreading out of tactile gating of one finger, to which the descending motor command is not delivered, is likely mediated by surround inhibition. [ABSTRACT FROM AUTHOR]

We report the histological changes over time for a patient with infection-related glomerulonephritis (IRGN) that developed in a transplanted kidney. A 47-year-old man had undergone renal transplantation 3 years ago for end-stage kidney disease (ESKD). After several episodes of acute rejection, the patient was in a stable CKD condition. The abrupt development of severe microscopic hematuria and renal dysfunction was observed approximately 2 weeks after the onset of a phlegmon in his right leg. An allograft biopsy showed prominent glomerular endocapillary proliferation on light microscopy, granular C3 deposition on immunofluorescent microscopy, and subepithelial electron-dense deposits on electron microscopy, suggesting IRGN accompanied by moderate interstitial fibrosis and tubular atrophy (IFTA). Positive glomerular staining for nephritis-associated plasmin receptor (NAPlr) and plasmin activity, which are biomarkers of bacterial IRGN, supported the diagnosis. Although the infection was completely cured with antibiotic therapy, renal dysfunction persisted. A re-biopsy of the allograft 2 months later revealed resolution of the glomerular endocapillary proliferation and negative staining for NAPlr/plasmin activity, with worsening IFTA. We showed, for the first time, the chronological changes in infiltrating cells and histological markers of IRGN in transplanted kidneys. Glomerular changes, including NAPlr/plasmin activity staining, almost disappeared after the cessation of infection, while interstitial changes continuously progressed, contributing to ESKD progression. [ABSTRACT FROM AUTHOR]

In this study, we investigated the role of serum/glucocorticoid-regulated kinase 1 (SGK1) in varicella-zoster virus (VZV) replication. VZV DNA replication and plaque formation were inhibited by SGK1 knockout and treatment with an SGK1 inhibitor. Furthermore, SGK1 inhibition suppressed the increase in cyclin B1 expression induced by VZV infection. These results suggest that VZV infection induces SGK1 activation, which is required for efficient viral proliferation through the expression of cyclin B1. This is the first study to report that SGK1 is involved in the VZV life cycle. [ABSTRACT FROM AUTHOR]

• Activated factor VIII (FVIIIa) functions as a cofactor for FIXa in the tenase complex. • Emicizumab is a humanized bispecific monoclonal antibody acts as a FVIIIa-mimetic. • We examined the binding affinity among emicizumab, FIXa and FX by FRET. • Emicizumab orientates FIXa and FX in close proximity on phospholipid membranes. [ABSTRACT FROM AUTHOR]

Bacteria have two routes for the L-methionine biosynthesis. In one route called the direct sulfuration pathway, acetylated L-homoserine is directly converted into L-homocysteine. The reaction using H2S as the second substrate is catalyzed by a pyridoxal 5'-phosphate-dependent enzyme, O-acetylhomoserine sulfhydrylase (OAHS). In the present study, we determined the enzymatic functions and the structures of OAHS from Lactobacillus plantarum (LpOAHS). The LpOAHS enzyme exhibited the highest catalytic activity under the weak acidic pH condition. In addition, crystallographic analysis revealed that the enzyme takes two distinct structures, open and closed forms. In the closed form, two acidic residues are sterically clustered. The proximity may cause the electrostatic repulsion, inhibiting the formation of the closed form under the neutral to the basic pH conditions. We concluded that the pH-dependent regulation mechanism using the two acidic residues contributes to the acidophilic feature of the enzyme. [ABSTRACT FROM AUTHOR]

Being a professional teacher involves developing professional agency. Among the important standards of professional agency is the ability to justify classroom practices in light of conceptual knowledge and transformative reflection and clarify personal commitments and intentions in decision-making processes. This study explored how 12 student teachers participating in a teacher education programme in Norway revealed their sense of professional agency while sharing their thoughts about their commitments, intentions, and experiences regarding teaching and mentor support when practising teaching in schools. The study used semi-structured interviews. The student teachers revealed a strong sense of professional agency and a strong intention to develop this agency. However, the practice context did not seem to support them in exploiting their capacity to develop professional agency. Consequently, studies and discussions on how the practice context helps student teachers in their professional learning are required. [ABSTRACT FROM AUTHOR]

Hemophagocytic syndrome/macrophage activation syndrome (HPS/MAS) is a serious clinical condition that frequently leads to multiple organ failure, including acute kidney injury (AKI). Although the pathogenesis of AKI is not yet fully understood, it is believed to result from uncontrolled activation of the immune system involving macrophages and cytotoxic lymphocytes. Renal histology in HPS/MAS often presents with characteristic foamy glomerular lesions (glomerular lipidosis) with massive macrophage infiltration, known as histiocytic glomerulopathy. In this review, we introduce the recently proposed concept of renal-limited HPS/MAS as a novel etiology of histiocytic glomerular lipidosis. Patients with renal-limited HPS/MAS often develop AKI but do not fulfill the diagnostic criteria for HPS/MAS because their systemic manifestations are less severe. Therefore, the diagnosis largely depends on characteristic histological findings, that is, diffuse and global glomerular accumulation of foamy macrophages and cytotoxic lymphocytes accompanied by the interaction of these cells as well as the exclusion of various differential diseases. Although there are no established therapeutic regimens, these patients receive various types of therapies, including high-dose glucocorticoids, immunosuppressants, or anti-interleukin-1 drug, and generally achieve favorable outcomes. We summarized the concept, diagnostic challenges, and recent topics of this disease entity and discussed treatment options based on our own experiences. [ABSTRACT FROM AUTHOR]

Background In May 2022, mpox cases were reported in nonendemic countries, including the United States. We examined mpox infections in the Veterans Health Administration (VHA). Methods Mpox diagnostic and whole genome sequencing (WGS) results, demographics, risk factors, hospitalizations, exposures, deaths, and pharmacy and immunization data were obtained from VHA data sources (23 May 2022–31 May 2023). Results Of 1144 Veterans tested, 251 (21.9%) were presumptive positive for nonvariola orthopoxvirus (NVO) or confirmed positive for NVO and Monkeypox virus (MPXV). Incidence rate was 7.5 per 100 000 Veterans in care, with the highest rate observed in Veterans aged 25–34 years (13.83 cases per 100 000). Higher odds of NVO or NVO/MPXV positivity was associated with male sex; non-Hispanic Black race/ethnicity; syphilis or human immunodeficiency virus (HIV) positivity; or genital/rectal sample site, whereas older age and vaccination with JYNNEOS or vaccinia (smallpox) had lower odds. Among 209 with confirmatory testing, 90.4% reported intimate contact and/or an epidemiological link, 84.5% were men who have sex with men (MSM), 24.2% received tecovirimat, and 8.1% were hospitalized with 1 death. Eighty-six sequenced samples had evaluable WGS results. All were clade IIb, representing 10 different lineages from 20 states and the District of Columbia. Conclusions Mpox affected younger, MSM, non-Hispanic Black, and HIV/syphilis-positive men among US Veterans. Viral diversity was noted across geographic regions. At-risk Veterans would benefit from vaccination and risk reduction strategies for mpox and other sexually transmitted infections. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions Studies have shown that children develop a higher body weight during summer months. This has been demonstrated repeatedly using the body mass index (BMI), but the effect of season on other weight‐related anthropometric measurements is still unclear.Measurements of height, weight, waist circumference (WC), triceps, and subscapular skinfolds (TSF and SSF), collected from September till May in a cross‐sectional sample of 4–16‐year‐old children and adolescents (n = 4525) from the Bergen Growth Study 1 (BGS1). Differences in z‐score by season were tested with linear models adjusted for age group and separately for sex. Overall differences were tested with a one‐way between‐group analysis of variance.The girls had higher BMIz (+0.12, p = .03) and WCz (+0.18, p = .002) in fall compared with spring. TSFz (−0.19, p < .001) and SSFz (−0.18, p < .001) were lower in winter in girls, and in boys both in fall (TSFz −0.10, p = .046; SSFz – 0.16, p < .001), and winter (TSFz −0.15, p = .004; SSFz −0.14, p = .003), when compared with spring.Seasonal variation was detected for all anthropometric measures, but differences in the direction of the effect between measures of global (BMI), central (WC) or subcutaneous (SF) adiposity suggest a more complex mechanism that needs further exploration. [ABSTRACT FROM AUTHOR]

This paper has proposed an efficient analysis method to calculate interface stress intensity factors (SIFs) based on a proportional stress field of a reference problem whose exact solution is available. In the previous proportional methods, the same crack length and the same element size were applied to both reference and unknown problems so that the same FEM error can be produced. Therefore, when analyzing many unknown problems, the conventional method needs to analyze many reference problems at the same time. Since this approach is time-consuming, this paper considers how to calculate many crack lengths efficiently by using only one single reference solution modeling. For this purpose, several general relations of SIFs are derived for the unknown and the reference problems when both crack length and element size are different. To analyze many unknown problems accurately by using a single reference solution modeling, how to choose the most suitable element dimension of the reference model is clarified. The proposed method is especially useful for crack propagation analysis. [ABSTRACT FROM AUTHOR]

We aimed to evaluate patient-reported outcomes (PROs) of stereotactic radiosurgery (SRS) for TN in terms of treatment efficacy and toxicity. We retrospectively analyzed patients who underwent Gamma Knife SRS for idiopathic or classic TN between January 2013 and February 2022. Questionnaires regarding pain relief, treatment toxicity, and post-SRS treatment were sent between late 2022 and early 2023, and the responses received were analyzed. The Faces Pain Scale (FPS, 0: best, 5: worst) was used for quantitative evaluation. Responses were received from 51 patients (76%). The mean pre-SRS FPS score was 4.1 (standard deviation (SD) 1.1). Forty-three patients (83%) reported initial pain relief and the best post-SRS FPS score was 1.1 (SD 1.5) (P < 0.001). At a median follow-up of 50 months, the FPS score was still 1.1 (SD 1.6) (P < 0.001). Analysis of factors contributing to durable pain relief showed neurovascular compression to be associated with FPS score improvement (Odds ratio 5.7, 95% CI 1.1–29.7, P = 0.038). Facial dysesthesia had a mean pre-SRS FPS score of 1.7 (SD 2.0) and a mean score of 1.4 (SD 1.7) at the last follow-up (P = 0.32). Eight patients (15%) received post-SRS interventions and 21 (40%) no longer required pharmacotherapy without post-SRS intervention. Forty-four patients (85%) reported being satisfied with SRS. We analyzed PROs of SRS for TN using the FPS and showed SRS to be a safe and effective treatment modality achieving long lasting pain relief. [ABSTRACT FROM AUTHOR]

Aims: Amikacin requires therapeutic drug monitoring for optimum efficacy; however, the optimal model‐informed precision dosing strategy for the area under the concentration–time curve (AUC) of amikacin is uncertain. This simulation study aimed to determine the efficient blood sampling points using the Bayesian forecasting approach for early achievement of the target AUC range for amikacin in critically ill patients. Methods: We generated a virtual population of 3000 individuals using 2 validated population pharmacokinetic models identified using a systematic literature search. AUC for each blood sampling point was evaluated using the probability of achieving a ratio of estimated/reference AUC at steady state in the 0.8–1.2 range. Results: On day 1, the 1‐point samplings for population pharmacokinetic models showed a priori probabilities of 26.3 and 45.6%, which increased to 47.3 and 94.4% at 23 and 15 h, respectively. Using 2‐point sampling at the peak (3 and 4 h) and trough (24 h) on day 1, these probabilities further increased to 72.3 and 99.5%, respectively. These probabilities were comparable on days 2 and 3, regardless of 3 and 6 sampling points or estimated glomerular filtration rate. These results indicated the higher predictive accuracy of 2‐point sampling than 1‐point sampling on day 1 for amikacin AUC estimation. Moreover, 2‐point sampling was a more reasonable approach than rich sampling. Conclusions: This study contributes to the development of an efficient model‐informed precision dosing strategy for early targeting of amikacin AUC in critically ill patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Bulbourethral glands are a major accessory sex gland in the boar. Their rate of growth is similar to general body growth at 6 weeks of age, but subsequently, bulbourethral glands grow faster than the general body. This study evaluated the expression of two genes that would increase androgen signaling despite the relatively low androgen concentrations during this interval. Neither gene exhibited increased expression to provide an androgen-mediated stimulus for growth. Hence, the normally occurring reduction in endogenous estrogen synthesis, which would alleviate G protein-coupled estrogen receptor 1 (GPER)-mediated inhibition of growth, may be the cause for the initial stimulus of growth during this late juvenile interval. The porcine bulbourethral glands produce a gel-type secretion. Although the role of these contributions to reproductive success remains murky, the bulbourethral glands are major accessory sex glands in this species. Isometric growth in the early neonatal interval is followed by allometric growth in the late juvenile interval (6 to 11 weeks of age), while circulating endogenous steroids are low. The rate of allometric growth increases during the peripuberal interval (16 to 20 weeks of age) when systemic testosterone is relatively high. Gene expression for androgen receptor (AR) and for the steroid 5 alpha-reductase 2 (SRD5A2) enzyme that synthesizes the more potent androgen dihydrotestosterone from its precursor was evaluated by qPCR analyses of bulbourethral gland tissue. Tissues were collected from control boars (2 weeks to 40 weeks of age) and from littermates of these boars treated with letrozole to suppress endogenous estrogen synthesis. Gene expression for these two key proteins in androgen signaling was quite low during the initial allometric growth in the late juvenile and prepuberal intervals, suggesting that this initial growth was not primarily stimulated by androgens. These observations are consistent with a more direct estrogen-mediated inhibition of growth via GPER previously proposed, with the sensitivity extending into the late juvenile interval when estrogens as well as androgens are normally relatively low. [ABSTRACT FROM AUTHOR]

Licensed mRNA COVID-19 vaccines require booster doses to sustain SARS-CoV-2-specific responses, creating the need for novel, broadly immunogenic vaccines. We aimed to compare the immunogenicity, safety, and tolerability of ARCT-154—a self-amplifying mRNA vaccine against SARS-CoV-2 D614G variant—with the BNT162b2 (Comirnaty; Pfizer–BioNTech) mRNA vaccine when administered as a fourth-dose booster. This double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial, conducted at 11 outpatient clinical sites in Japan, enrolled healthy adults aged at least 18 years who had previously been immunised with two doses of an mRNA COVID-19 vaccine (BNT162b2 or mRNA-1273 [Spikevax; Moderna]) followed by a third dose of BNT162b2 at least 3 months before enrolment. Participants were randomly assigned, in a 1:1 ratio using an Interactive Response Technology system with a block size of four, and with stratification by age (18–64 years or ≥65 years) and by interval since last COVID-19 vaccination (<5 months or ≥5 months), to receive either ARCT-154 or BNT162b2 as a fourth-dose booster via deltoid intramuscular injection. Participants and investigators assessing outcomes were masked to group assignment. The primary objective, measured in per-protocol set 1 (consisting of participants with no evidence of previous SARS-CoV-2 infection who received their intended injection according to protocol), was to show that the immune response 28 days after the ARCT-154 vaccine was non-inferior to that of the BNT162b2 vaccine, measured in terms of both pseudovirus neutralising antibody geometric mean titre (GMT) ratios and seroresponse rates against the wild-type Wuhan-Hu-1 strain of SARS-CoV-2. Non-inferiority was declared when the lower limit of the 95% CI of the ARCT-154 to BNT162b2 GMT ratio exceeded 0·67, and when the lower limit for the difference in seroresponse rates exceeded −10%. Key secondary endpoints included the immune response against the omicron BA.4/5 subvariant, which was assessed for non-inferiority and superiority in per-protocol set 1. Safety was assessed in the full analysis set. This study was registered on the Japan Registry for Clinical Trials, jRCT 2071220080, and is ongoing. Between Dec 13, 2022, and Feb 25, 2023, we enrolled and randomly assigned 828 participants to receive ARCT-154 (n=420) or BNT162b2 (n=408) vaccines as a fourth-dose booster. In per-protocol set 1, the GMTs of surrogate neutralising antibodies induced against the Wuhan-Hu-1 SARS-CoV-2 strain in the ARCT-154 group (5641 [95% CI 4321–7363]) were non-inferior to those in the BNT162b2 group (3934 [2993–5169]) when measured at 28 days after boosting, with a GMT ratio of 1·43 (95% CI 1·26–1·63). Seroresponse rates were 65·2% (95% CI 60·2–69·9) in the ARCT-154 group versus 51·6% (46·4–56·8) in the BNT162b2 group, a difference of 13·6% (95% CI 6·8–20·5). GMTs against the omicron BA.4/5 variant on day 29 were 2551 (1687–3859) in the ARCT-154 group and 1958 (1281–2993) in the BNT162b2 group—a GMT ratio of 1·30 (1·07–1·58)—with seroresponse rates of 69·9% (65·0–74·4) and 58·0% (52·8–63·1). Both boosters were equally well tolerated. No treatment-related deaths were reported, nor were there severe or serious adverse events considered to be causally associated related to study vaccination. One serious adverse event, a foot deformity reported in a participant in the BNT162b2 group, was observed but determined not to have a causal relationship to the study vaccination. One severe adverse event, a case of abnormal hepatic function in the ARCT-154 group, was considered to be related to study vaccine. Adverse events of special interest for detection of myocarditis and pericarditis included chest pain (one case in the ARCT-154 group and three cases in the BNT162b2 group) and shortness of breath (two cases in the BNT162b2 group), all of which were considered to have a reasonable possibility of being related to vaccination. Local reactions were reported by 398 (95%) of 420 participants receiving the ARCT-154 vaccine and 395 (97%) of 408 participants receiving the BNT162b2 vaccine, and solicited systemic adverse events by 276 (66%) of those receiving the ARCT-154 vaccine and 255 (63%) of those receiving the BNT162b2 vaccine. Adverse events were mainly mild in severity, occurring and resolving within 3–4 days after vaccination. In adults who had previously received three doses of an mRNA COVID-19 vaccine, immune responses 28 days after an ARCT-154 booster dose were non-inferior to those observed after a BNT162b2 booster dose for the Wuhan-Hu-1 strain of SARS-CoV-2 and superior for the Omicron BA.4/5 variant. Increased immune responses at 28 days might provide increased likelihood of protection against these strains during this period and could also result in longer duration of protection. Further studies will assess the immunogenicity induced against more recent SARS-CoV-2 variants. Japanese Ministry of Health, Labour, and Welfare. For the Japanese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

We investigated changes in youths' intentions to quit school after following a group-based cognitive behaviour therapy (CBT) based intervention for depressed adolescents in upper secondary school: the Adolescent Coping with Depression Course (ACDC). Data were collected from 228 youths, 133 of whom received the 14-week ACDC intervention and 95 who received usual care (UC). Structural equation models showed that symptoms of depression at post-test positively predicted intention to quit school at six-month follow-up after the intervention ended (β =.291, p <.001). Furthermore, ACDC, which showed a decrease in depressive symptoms post-test, had an indirect effect on adolescents' intention to quit school at six-month follow-up (indirect β = −0.117 p =.018). Hence, targeting depression and implementing effective preventive programmes may prevent dropout from upper secondary school. Such interventions should thus be investigated in future studies. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Sturge–Weber syndrome (SWS) is a neurocutaneous syndrome characterized by angiomas. This report presents airway management using submental intubation in sagittal split ramus osteotomy under general anesthesia and aimed to explore better anesthetic management for avoiding the rupture of angiomas in a patient with SWS. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES After staged reconstruction for hypoplastic left heart syndrome, the neoaortic root tends to dilate, and the incidence of significant neoaortic valve insufficiency increases with time. This study aimed to evaluate the mid-term outcomes of the neoaortic root geometries and valve function after chimney reconstruction in the Norwood procedure. METHODS Between 2013 and 2021, 20 consecutive patients who underwent chimney reconstruction during the Norwood procedure for hypoplastic left heart syndrome and its variants in our institution were enrolled. The actual diameters of the following points were measured, and Z-scores were calculated based on the normal aortic root geometries using the long axis view of echocardiography at the pre-Norwood stage and the lateral view of angiography at pre-Glenn, pre-Fontan, post-Fontan and follow-up (age 5–6 years) stages: neoaortic valve annulus; sinus of Valsalva; sinotubular junction; and ascending aorta just proximal to the anastomosis to the aortic arch. The degree of neoaortic valve regurgitation was evaluated by echocardiography at each stage. RESULTS The median follow-up period was 3.9 years. Neoaortic roots after chimney reconstruction were spared from progressive dilation over time. With growth, the conical configuration of the neoaortic roots was preserved without geometrical distortion. The Z-scores of the annulus, sinus of Valsalva, sinotubular junction and ascending aorta ranged roughly from 4 to 6, 4 to 6, 2 to 4 and 0 to 2, respectively. All neoaortic valves at each stage had mild or no regurgitation. CONCLUSIONS Chimney reconstruction prevented neoaortic root dilation and avoided significant neoaortic valve regurgitation in the mid-term. These neoaortic dimensions with smooth flow profiles in the neoaorta after chimney reconstruction may have contributed to the current results. Further studies are needed to clarify the long-term outcomes. [ABSTRACT FROM AUTHOR]

Focusing on a VGa–VN complex vacancy defect in GaN, the adiabatic potential for conformational changes of the VGa–VN is investigated using the density functional theory. There are two types of configurations due to the symmetry of the crystal, it is confirmed that there is almost no difference in their stability or electronic state. Using these configurations as the initial and final states, the defect reaction is analyzed when VGa–VN moves using the climbing‐image nudged elastic band method. The reaction barrier for the migration of VGa (VN) is found to be 2.2 (3.3) eV. It is concluded that these reactions occur frequently as GaN is annealed since the atomic diffusion potential barrier is similar to that in other semiconductors. These results suggest that VGa–VN in GaN moves through the crystal as a pair of vacancies by alternately repeating the VGa and the VN migration. These results provide important knowledge for elucidating the microscopic mechanism of the experimentally observed VGa–VN aggregation reaction. [ABSTRACT FROM AUTHOR]

Aberrant glycosylation in tumor cells is a hallmark during carcinogenesis. KRAS gene mutations are the most well-known oncogenic abnormalities but their association with glycan alterations in pancreatic ductal adenocarcinoma (PDAC) is largely unknown. We employed patient-derived 3D organoids to culture pure live PDAC cells, excluding contamination by fibroblasts and immune cells, to gasp the comprehensive cancer cell surface glycan expression profile using lectin microarray and transcriptomic analyses. Surgical specimens from 24 PDAC patients were digested and embedded into a 3D culture system. Surface-bound glycans of 3D organoids were analyzed by high-density, 96-lectin microarrays. KRAS mutation status and expression of various glycosyltransferases were analyzed by RNA-seq. We successfully established 16 3D organoids: 14 PDAC, 1 intraductal papillary mucinous neoplasm (IPMN), and 1 normal pancreatic duct. KRAS was mutated in 13 (7 G12V, 5 G12D, 1 Q61L) and wild in 3 organoids (1 normal duct, 1 IPMN, 1 PDAC). Lectin reactivity of AAL (Aleuria aurantia) and AOL (Aspergillus oryzae) with binding activity to α1-3 fucose was higher in organoids with KRAS mutants than those with KRAS wild-type. FUT6 (α1-3fucosyltransferase 6) and FUT3 (α1-3/4 fucosyltransferase 3) expression was also higher in KRAS mutants than wild-type. Meanwhile, mannose-binding lectin (rRSL [Ralstonia solanacearum] and rBC2LA [Burkholderia cenocepacia]) signals were higher while those of galactose-binding lectins (rGal3C and rCGL2) were lower in the KRAS mutants. We demonstrated here that PDAC 3D-cultured organoids with KRAS mutations were dominantly covered in increased fucosylated glycans, pointing towards novel treatment targets and/or tumor markers. [ABSTRACT FROM AUTHOR]

Background: Ethnoveterinary medicinal plants have been used by the people of Dugda District in the primary health care system to treat various livestock ailments for generations, particularly, in underserved rural areas. However, these ethnoveterinary practices and medicinal plants are dwindling without proper documentation, due to undergoing socio-cultural and environmental changes. Hence, this study aimed at inventory and analysis of ethnoveterinary medicinal plants and the associated indigenous and local knowledge used in the treatment of livestock health problems in Dugda District. Methods: Data were collected from 378 local inhabitants through semi-structured interviews, 18 focus group discussions with 6 to 8 participants in each couple with participant field observations. Informant consensus factor (ICF), fidelity-level (FL) and relative importance value (RI) were used to evaluate the agreement of informants on ethnoveterinary practices, healing potential of medicinal plants and the most multipurpose species. Using standard taxonomic procedures, voucher specimens were collected, identified and deposited at the National Herbarium of Addis Ababa University. Results: In total, 64 medicinal plants of ethnoveterinary uses, belonging to 33 families were reported to treat 37 livestock health problems. Anthrax, inappetence and diarrhoea were said to be the most prevalent veterinary health problems treated by traditional medicinal plants. Family Fabaceae was the most widely reported (7 spp.), followed by Apocynaceae, Cucurbitaceae and Solanaceae (5 spp. each). Herbs were the dominant life forms (21spp.), followed by shrubs (20 spp.). The most commonly sought plant parts were leaves (55.25%), followed by roots (23.44%). The principal method of preparation was pounding remedial parts (46.85%) and mixing with cold water. The main route of administration was via oral application (72.67%), drenching diseased livestock. Withania somnifera and Kedrostis foetidissima were the most cited medicinal plants with 53 and 43 use reports (URs), respectively. ICF showed that respiratory diseases scored the highest value (0.94), while most of the reported medicinal plants were gastrointestinal agents. RI value analysis revealed that Croton macrostachyus had highest diversity of uses, followed by K. foetidissima and W. somnifera. Ethnoveterinary uses of some medicinal plants such as Phytolacca dodecandra, Calpurnia aurea, Cyphostemma cyphopetalum and Verbascum sinaiticum as prophylaxis against rabies were a new input for ethnoveterinary database. Conclusion: The study revealed that the people of the Dugda District are endowed with rich ethnoveterinary knowledge and medicinal plants. However, ethnoveterinary knowledge associated with medicinal plant species significantly differ (P < 0.05) between general and key informants, young and matured age groups and informants' educational level. This infers the impact of mode of ethnoveterinary knowledge transfer, literacy, modern education and globalization on ethnoveterinary uses of medicinal plant species. And also most of the medicinal plants are found in wild habitats with nearly no conservation attention. Therefore, it is imperative to implement participatory conservation actions for medicinal plants in collaboration with traditional institutions (Gada system). The disparity of ethnoveterinary knowledge could be also minimized through awareness creation among local communities about the knowledge and its revitalization. Furthermore, medicinal plants, which are widely utilized and multipurpose, should be screened for their phytochemicals, pharmacological and toxicological activities to confirm ethnoveterinary uses and for future development of veterinary pharmaceuticals. [ABSTRACT FROM AUTHOR]

The semantics of Japanese yorimo-comparatives remained somewhat mysterious until Beck et al. (2004) proposed a contextdependent analysis that accounted for the peculiar behavior of clausal yorimo-comparatives. Despite its contribution, however, many arguments have been made against the idea of the contextdependent comparisons of yorimo-comparatives. Kennedy (2007a) and Sudo (2015) argue that yorimo-comparatives can still be captured within the framework of traditional compositional comparison. This study focuses on phrasal yorimo-comparatives and argues that context-dependent analysis remains a viable option. Phrasal yorimo-comparatives in Japanese and bi-comparatives in Mandarin Chinese are largely considered equivalents of phrasal more than-comparatives. However, I will first point out that phrasal yorimo/bi-comparatives behave more like compared to/im Vergleich zu "in comparison to"-constructions rather than more than-comparatives. I will argue that indirect strategy, another context-dependent analysis developed by Hohaus (2015), captures the behaviors of phrasal yorimo/bi-comparatives. Her framework of indirect strategy was originally proposed to explain the semantics of compared to/im Vergleich zu "in comparison to"- constructions; it also captures the behaviors of phrasal yorimo/bi-comparatives. This study further proposes that variations in judgments that arise in phrasal yorimo/bi-comparatives are explained by Interpretive Economy proposed by Kennedy (2007b). Such rule-governed mechanism enriches the framework of indirect strategy and makes it more plausible. [ABSTRACT FROM AUTHOR]

Plasma 4β‐hydroxycholesterol (OHC) has drawn attention as an endogenous substrate indicating CYP3A activity. Plasma 4β‐OHC is produced by hydroxylation by CYP3A4 and CYP3A5 and by cholesterol autoxidation. Plasma 4α‐OHC is produced by cholesterol autoxidation and not affected by CYP3A activity. This study aimed to evaluate the usefulness of plasma 4β‐OHC concentration minus plasma 4α‐OHC concentration (4β‐OHC–4α‐OHC) compared with plasma 4β‐OHC concentration and 4β‐OHC/total cholesterol (TC) ratio in cross‐sectional evaluation of CYP3A activity. Four hundred sixteen general adults were divided into 191 CYP3A5*1 carriers and 225 non‐carriers. Twenty‐six patients with chronic kidney disease (CKD) with CYP3A5*1 allele were divided into 14 with CKD stage 3 and 12 with stage 4–5D. Area under the receiver operating characteristic curve (AUC) for the three indices were evaluated for predicting presence or absence of CYP3A5*1 allele in general adults, and for predicting CKD stage 3 or stage 4–5D in patients with CKD. There was no significant difference between AUC of 4β‐OHC–4α‐OHC and AUC of plasma 4β‐OHC concentration in general adults and in patients with CKD. AUC of 4β‐OHC–4α‐OHC was significantly smaller than that of 4β‐OHC/TC ratio in general adults (p = 0.025), but the two indices did not differ in patients with CKD. In conclusion, in the present cross‐sectional evaluation of CYP3A activity in general adults and in patients with CKD with CYP3A5*1 allele, the usefulness of 4β‐OHC–4α‐OHC was not different from plasma 4β‐OHC concentration or 4β‐OHC/TC ratio. However, because of the limitations in study design and subject selection of this research, these findings require verification in further studies. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the clinical impact of pathogenic organism (PO) positivity early after transplantation, we evaluated the impact of perioperative airway POs on outcomes after living-donor lobar lung transplantation (LDLLT), where the graft airway is supposed to be sterile from a healthy donor. Method: A retrospective review of 67 adult LDLLT procedures involving 132 living donors was performed. Presence of POs in the recipients' airways was evaluated preoperatively and postoperatively in intensive-care units. Results: POs were detected preoperatively in 13 (19.4%) recipients. No POs were isolated from the donor airways at transplantation. POs were detected in 39 (58.2%) recipients postoperatively; most were different from the POs isolated preoperatively. Postoperative PO isolation was not associated with short-term outcomes other than prolonged postoperative ventilation. The 5-year overall survival was significantly better in the PO-negative group than in the PO-positive group (89.1% vs. 63.7%, P = 0.014). In the multivariate analysis, advanced age (hazard ratio [HR]: 1.041 per 1-year increase, P = 0.033) and posttransplant PO positivity in the airway (HR: 3.684, P = 0.019) significantly affected the survival. Conclusions: The airways of the living-donor grafts were microbiologically sterile. PO positivity in the airway early after transplantation negatively impacted long-term outcomes. [ABSTRACT FROM AUTHOR]

Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator that triggers various inflammatory conditions, including eosinophil activation and recruitment. This study aimed to evaluate the expressions of PAF-metabolism-associated genes, namely genes coding the enzymes involved in PAF synthesis (LPCAT1, LPCAT2, LPCAT3, and LPCAT4), PAF degradation (PAFAH1B2, PAFAH1B3, and PAFAH2), and the gene for the PAF receptor (PTAFR) in subtypes of CRSwNP classified by clinical- or hierarchal-analysis-based classifications. Transcriptomic analysis using bulk RNA barcoding and sequencing (BRB-seq) was performed with CRSwNP, including eosinophilic CRS (ECRS) (n = 9), nonECRS (n = 8), ECRS with aspirin-exacerbated respiratory disease (Asp) (n = 3), and controls with a normal uncinate process mucosa (n = 6). PTAFR was only upregulated in ECRS and nonECRS. In the hierarchical cluster analysis with clusters 1 and 2 reflecting patients with low-to-moderate and high levels of type 2 inflammation, respectively, cluster 1 exhibited a significant downregulation of LPCAT2 and an upregulation of PTAFR expression, while cluster 2 showed an upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. Understanding this strong PAF-associated pathophysiology in the severe type 2 inflammation group could provide valuable insights into the treatment and management of CRSwNP. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to identify the relationship between locomotive syndrome (LS) status, physical performance and limb and trunk skeletal muscle mass before and after surgery in adult spinal surgery (ASD) patients. Methods: A retrospective observational investigation of 63 consecutive patients with ASD who underwent spinal surgery was conducted. The total skeletal muscle mass of the arms and legs was considered a measure of the total appendicular skeletal muscle mass measured with whole-body dual-energy X-ray absorptiometry. All data pertaining to the physical performance tests and LS were collected preoperatively with follow-up one year postoperatively. Results: Gait speed, the one-leg standing test and the stand-up test were significantly improved one year after surgery compared to preoperative measurements. The lower extremity skeletal muscle mass predominantly influences physical function improvement including gait stride, one-leg standing and the stand-up test after ASD surgery. Conclusions: This study is the first to show that assessing lower extremity muscles prior to ASD surgery is useful in predicting postoperative recovery. [ABSTRACT FROM AUTHOR]

We present the manifestly covariant canonical operator formalism of a Weyl invariant (or equivalently, a locally scale invariant) gravity whose classical action consists of the well-known conformal gravity and Weyl invariant scalar-tensor gravity, on the basis of the Becchi-Rouet-Stora-Tyupin (BRST) formalism. It is shown that there exists a Poincaré-like IOSp(8|8) global symmetry as in Einstein’s general relativity, which should be contrasted to the case of only the Weyl invariant scalar-tensor gravity where we have a more extended Poincaré-like IOSp(10|10) global symmetry. This reduction of the global symmetry is attributed to the presence of the Stückelberg symmetry. [ABSTRACT FROM AUTHOR]

This paper discusses the concept of weak head in Chomsky's (2015. Problems of projection: Extensions. In Elisa Di Domenico, Cornelia Hamann & Simona Matteini (eds.), Structures, strategies and beyond: Studies in honour of Adriana Belletti, 3–16. Amsterdam: John Benjamins) sense from a typological perspective. This paper first establishes a novel generalization that large-scale pied-piping is available in a language only if the language has indeterminate pronouns in Kuroda's (1965. Generative grammatical studies in the Japanese language. Cambridge, MA: Massachusetts Institute of Technology dissertation) sense and the clause to be pied-piped is head-final. To deduce this generalization, this paper first offers a labeling theoretic account of large-scale pied-piping. It then proposes that weak heads are (i) heads that have unvalued features and (ii) morpho-phonologically weak. It is shown that the generalization is deduced from this conception of weak heads, given Inaba's (2011. The morphosyntax of constituent ordering patterns. The Hiroshima University Studies, Graduate School of Letters 71. 43–72) generalization that head-final complementizers are generally affixal. This paper further argues that the proposed conception of weak heads also allows us to deduce Agree from Minimal Search, which is a third factor principle according to Chomsky (2013. Problems of projection. Lingua 130. 33–49), hence minimizes UG. [ABSTRACT FROM AUTHOR]

Objectives: Myocardial extracellular volume (ECV) on computed tomography (CT), an alternative to cardiac magnetic resonance (CMR), has significant practical clinical advantages. However, the consistency between ECVs quantified via CT and CMR in cardiac amyloidosis (CA) has not been investigated sufficiently. Therefore, the current study investigated the application of CT-ECV in CA with CMR-ECV as the reference standard. Methods: We retrospectively evaluated 31 patients with CA who underwent cardiac CT and CMR. Pearson correlation analysis was performed to investigate correlations between CT-ECV and CMR-ECV at each segment. Further, correlations between ECV and clinical parameters were assessed. Results: There were no significant differences in the mean global ECVs between CT scan and CMR (51.3% ± 10.2% vs 50.0% ± 10.5%). CT-ECV was correlated with CMR-ECV at the septal (r = 0.88), lateral (r = 0.80), inferior (r = 0.79), anterior (r = 0.77) segments, and global (r = 0.87). In both CT and CMR, the ECV had a weak to strong correlation with high-sensitivity cardiac troponin T level, a moderate correlation with global longitudinal strain, and an inverse correlation with left ventricular ejection fraction. Further, the septal ECV and global ECV had a slightly higher correlation with the clinical parameters. Conclusions: Cardiac CT can quantify myocardial ECV and yield results comparable to CMR in patients with CA. Moreover, a significant correlation between CT-ECV and clinical parameters was observed. Thus, CT-ECV can be an imaging biomarker and alternative to CMR-ECV. Clinical relevance statement: Cardiac CT can quantify myocardial ECV and yield results comparable to CMR in patients with CA, and CT-ECV can be used clinically as an imaging biomarker and alternative to CMR-ECV. Key Points: • A significant correlation was found between CT myocardial extracellular volume and cardiac MR myocardial extracellular volume in patients with cardiac amyloidosis. • In CT and cardiac MR, the myocardial extracellular volume correlated well with high-sensitivity cardiac troponin T level, global longitudinal strain, and left ventricular ejection fraction. • CT myocardial extracellular volume can be an imaging biomarker and alternative to cardiac MR myocardial extracellular volume. [ABSTRACT FROM AUTHOR]

Populations occurring at the limit of a species' altitudinal distribution undergo strong environmental filtering. Rapid climate change intensifies this process, impacting ecological responses of populations. Understanding the effects of climate change, especially in the early stages of plant development, has become essential to predict vulnerability to extinction. However, few studies have explored initial establishment strategies of plant populations at the limit of their distribution in the face of global warming. We tested the effects of increasing temperatures on germination performance and on initial seedling establishment on two populations of Euterpe edulis, a palm tree widely distributed in the Atlantic Forest between 0 and 1400 m altitude. The tests were conducted in a laboratory, where the seeds were exposed to three conditions for 90 days: control at 25°C, and two treatments at higher temperatures (35 and 40°C). Germination percentage was not affected by population, seed size class or treatments. Average time for germination only increased in the Montane Forest population in the most extreme treatment, while in the sea level Restinga population, time for germination was affected by a small temperature increase. Mortality percentage in the Restinga population was similar in the post‐germination phase and in the temperature treatments. We concluded that E. edulis populations located at their lower altitudinal limit are closer to the species thermal limit, thus being more vulnerable to temperature increase than populations at the upper limit of the species' altitudinal distribution. [ABSTRACT FROM AUTHOR]

Objective: Although lung cancer screening trials have showed the efficacy of computed tomography to decrease mortality compared with chest radiography, the two are widely taken as different kinds of clinical practices. Artificial intelligence can improve outcomes by detecting lung tumors in chest radiographs. Currently, artificial intelligence is used as an aid for physicians to interpret radiograms, but with the future evolution of artificial intelligence, it may become a modality that replaces physicians. Therefore, in this study, we investigated the current situation of lung cancer diagnosis by artificial intelligence. Methods: In total, we recruited 174 consecutive patients with malignant pulmonary tumors who underwent surgery after chest radiography that was checked by artificial intelligence before surgery. Artificial intelligence diagnoses were performed using the medical image analysis software EIRL X-ray Lung Nodule version 1.12, (LPIXEL Inc., Tokyo, Japan). Results: The artificial intelligence determined pulmonary tumors in 90 cases (51.7% for all patients and 57.7% excluding 18 patients with adenocarcinoma in situ). There was no significant difference in the detection rate by the artificial intelligence among histological types. All eighteen cases of adenocarcinoma in situ were not detected by either the artificial intelligence or the physicians. In a univariate analysis, the artificial intelligence could detect cases with larger histopathological tumor size (p < 0.0001), larger histopathological invasion size (p < 0.0001), and higher maximum standardized uptake values of positron emission tomography-computed tomography (p < 0.0001). In a multivariate analysis, detection by AI was significantly higher in cases with a large histopathological invasive size (p = 0.006). In 156 cases excluding adenocarcinoma in situ, we examined the rate of artificial intelligence detection based on the tumor site. Tumors in the lower lung field area were less frequently detected (p = 0.019) and tumors in the middle lung field area were more frequently detected (p = 0.014) compared with tumors in the upper lung field area. Conclusions: Our study showed that using artificial intelligence, the diagnosis of tumor-associated findings and the diagnosis of areas that overlap with anatomical structures is not satisfactory. While the current standing of artificial intelligence diagnostics is to assist physicians in making diagnoses, there is the possibility that artificial intelligence can substitute for humans in the future. However, artificial intelligence should be used in the future as an enhancement, to aid physicians in the role of a radiologist in the workflow. [ABSTRACT FROM AUTHOR]

Renal biopsy is the gold standard for making the final diagnosis and for predicting the progression of renal disease, but monitoring disease status by performing biopsies repeatedly is impossible because it is an invasive procedure. Urine tests are non-invasive and may reflect the general condition of the whole kidney better than renal biopsy results. We therefore investigated the diagnostic value of extensive urinary sediment analysis by immunofluorescence staining for markers expressed on kidney-derived cells (cytokeratin: marker for tubular epithelial cells, synaptopodin: marker for podocytes, claudin1: marker for parietal epithelial cells, CD68: marker for macrophages (MΦ), neutrophil elastase: marker for neutrophils). We further examined the expression levels of the mRNAs for these markers by real-time reverse transcription polymerase chain reaction. We also examined the levels of mRNAs associated with the M1 (iNOS, IL-6) and M2 (CD163, CD204, CD206, IL-10) MΦ phenotypes. Evaluated markers were compared with clinical and histological findings for the assessment of renal diseases. Claudin1- and CD68-positive cell counts in urinary sediments were higher in patients with glomerular crescents (especially cellular crescents) than in patients without crescents. The relative levels of mRNA for CD68 and the M2 MΦ markers (CD163, CD204, CD206, and IL-10) in urinary sediments were also higher in patients with glomerular crescents. These data suggest that immunofluorescence staining for claudin1 and CD68 in urinary sediments and the relative levels of mRNA for CD68 and M2 MΦ markers in urinary sediments are useful for evaluating the state of glomerular diseases. [ABSTRACT FROM AUTHOR]

Amniotic fluid embolism (AFE) and placental abruption (PA) are typical obstetric diseases associated with disseminated intravascular coagulation (DIC). AFE is more likely to be complicated with enhanced fibrinolysis than PA. AFE may have an additional mechanism activating fibrinolytic cascade. We aimed to compare the coagulation/fibrinolysis factors among AFE, PA, and peripartum controls. We assessed AFE cases registered in the Japanese AFE Registry, and PA cases complicated with DIC (severe PA) and peripartum controls recruited at our hospital. The following factors in plasma were compared: prothrombin fragment 1 + 2 (PF1 + 2), plasmin α2-plasmin inhibitor complex (PIC), tissue factor (TF), tissue plasminogen activator (tPA), annexin A2 (AnnA2), total thrombin activatable fibrinolysis inhibitor (TAFI) including its activated form (TAFIa), and plasminogen activator inhibitor-type 1 (PAI-1). PF1 + 2 and PIC were markedly increased in both AFE (n = 27) and severe PA (n = 12) compared to controls (n = 23), without significant difference between those disease groups; however, PIC in AFE showed a tendency to elevate relative to PF1 + 2, compared with severe PA. AFE had significantly increased tPA and decreased total TAFI levels compared with severe PA and controls, which might be associated with further plasmin production in AFE and underlie its specific fibrinolytic activation pathway. [ABSTRACT FROM AUTHOR]

The study aimed to compare the performance of photon-counting detector computed tomography (PCD CT) with high-resolution (HR)-plaque kernel with that of the energy-integrating detector CT (EID CT) in terms of the visualization of the lumen size and the in-stent stenotic portion at different coronary vessel angles. The lumen sizes in PCD CT and EID CT images were 2.13 and 1.80 mm at 0°, 2.20 and 1.77 mm at 45°, and 2.27 mm and 1.67 mm at 90°, respectively. The lumen sizes in PCD CT with HR-plaque kernel were wider than those in EID CT. The mean degree of the in-stent stenotic portion at 50% was 69.7% for PCD CT and 90.4% for EID CT. PCD CT images with HR-plaque kernel enable improved visualization of lumen size and accurate measurements of the in-stent stenotic portion compared to conventional EID CT images regardless of the stent direction. [ABSTRACT FROM AUTHOR]

The inheritance of racing performance in Thoroughbreds is of interest to breeders and geneticists. Therefore, the genetic parameters of racing performance have been investigated in various populations of Thoroughbreds. However, the predictability of the racing performance of a racehorse has not been assessed well. In this study, we built mixed‐effects models for Japanese Thoroughbreds and assessed their predictability of racing performance. We used the average velocity as an index of racing performance and treated each category of racecourse and distance as different traits. Model selection using the deviance information criterion showed that explanatory variables, such as race, age and jockey effects are important for racing performance. Using the selected models, the phenotypic values of horses born after 2009, adjusted using the entire dataset, were predicted with the breeding values estimated from a partial dataset until 2010. The correlation coefficients ranged from 0.000 to 0.235 (average of 0.084 ± 0.066) and were higher for longer distances. When predicting the graded race winners born after 2009 from the partial dataset until 2010, the area under the curve values ranged from 0.516 to 0.776 (average of 0.613 ± 0.073) and were also higher for longer distances. Although these results indicate the predictability of racing performance, further efforts, including exploring more suitable racing performance indices and refining statistical modelling, are required for improvement. [ABSTRACT FROM AUTHOR]

T7 phage libraries displaying random peptides are powerful tools for screening peptide sequences that bind to various target molecules. The T7 phage system has the advantage of less biased peptide distribution compared to the M13 phage system. However, the construction of T7 phage DNA is challenging due to its long 36 kb linear DNA. Furthermore, the diversity of the libraries depends strongly on the efficiency of commercially available packaging extracts. To address these issues, we examined the combination of seamless cloning with cell-free translation systems. Seamless cloning technologies have been widely used to construct short circular plasmid DNA, and several recent studies showed that cell-free translation can achieve more diverse phage packaging. In this study, we combined these techniques to construct four libraries (CX7C, CX9C, CX11C and CX13C) with different random regions lengths. The libraries thus obtained all showed diversity > 109 plaque forming units (pfu). Evaluating our libraries with an anti-FLAG monoclonal antibody yielded the correct epitope sequence. The results indicate that our libraries are useful for screening peptide epitopes against antibodies. These findings suggest that our system can efficiently construct T7 phage libraries with greater diversity than previous systems. [ABSTRACT FROM AUTHOR]

Objective: To assess the associations of omega-3 and omega-6 fatty acids consumption, and the ratio between the two, with self-reported doctor told Systemic Lupus Erythematosus (SLE) diagnosis. Further, to assess whether initiation of omega-3 supplements intake was related to time/year of SLE diagnosis. Methods: Data from 42,398 women in the Adventist Health Study-2 cohort were used for this cross-sectional study. Unconditional logistic regression modeling was used for all analyses with the following candidate covariates: age, race, education, smoking, and body mass index (BMI). Results: Compared to non-cases, participants with a diagnosis of SLE reported higher intakes of total omega-3 fatty acids and about the same intakes of omega-6 fatty acids. Overall, they had higher ratios of omega-3 to omega-6 fatty acids. When assessing odds ratios of SLE diagnosis by quartiles of omega-3 to omega-6 and DHA+EPA to omega-6, there was a positive significant trend (p trend = 0.005). Additionally, among those reporting intake of fish oil, 87% had initiated fish oil consumption around the time of SLE diagnosis. SLE was more likely to occur among Black women compared to White women, among ever smokers compared to never smokers, among overweight women compared to women with normal/underweight, and among women 50–59 years compared to those 30–49 year old. When a smaller 6 year follow-up study identified 64 incident SLE cases and assessed their omega-3 intake at baseline (6 years earlier and before the SLE diagnosis) their intake of omega-3 and fish oil was no different than among non-cases. Conclusion: We observed a significant positive association between the ratio of omega-3 to omega-6 fatty acids consumption and prevalence of SLE. Among those with prevalent SLE, their year of starting supplementation of omega-3 and fish oil was closely linked to year of SLE diagnosis. Further, baseline intake of omega-3 fatty acids was not increased among 64 incident SLE cases identified during 6 years of follow-up. Our surprising finding can best be explained by reverse causation. This could be an example of how public health information is assimilated and acted upon by a health conscious public. [ABSTRACT FROM AUTHOR]

Objective: To identify pulmonary/uterine thrombus formation in amniotic fluid embolism (AFE). Design: Retrospective, observational. Setting: Nationwide. Population: Eleven autopsy cases of AFE and control cases. Methods: We assessed pulmonary and uterine thrombus formation and thrombus area in AFE and pulmonary thromboembolism (PTE) as a control. The area of platelet glycoprotein IIb/IIIa, fibrin, neutrophil elastase, citrullinated histone H3 (a neutrophil extracellular trap marker) and mast cell chymase immunopositivity was measured in 90 pulmonary emboli, 15 uterine thrombi and 14 PTE. Main outcome measures: Pathological evidence of thrombus formation and its components in AFE. Results: Amniotic fluid embolism lung showed massive thrombus formation, with or without amniotic emboli in small pulmonary arteries and capillaries. The median pulmonary thrombus size in AFE (median, 0.012 mm2; P < 0.0001) was significantly smaller than that of uterine thrombus in AFE (0.61 mm2) or PTE (29 mm2). The median area of glycoprotein IIb/IIIa immunopositivity in pulmonary thrombi in AFE (39%; P < 0.01) was significantly larger than that of uterine thrombi in AFE (23%) and PTE (15%). The median area of fibrin (0%; P < 0.001) and citrullinated histone H3 (0%; P < 0.01) immunopositivity in pulmonary thrombi in AFE was significantly smaller than in uterine thrombi (fibrin: 26%; citrullinated histone H3: 1.1%) and PTE (fibrin: 42%; citrullinated histone H3: 0.4%). No mast cells were identified in pulmonary thrombi. Conclusions: Amniotic fluid may induce distinct thrombus formation in the uterus and lung. Pulmonary and uterine thrombi formation may contribute to cardiorespiratory collapse and/or consumptive coagulopathy in AFE. [ABSTRACT FROM AUTHOR]

Social networking services (SNSs) have become the primary means by which individuals express themselves. Consequently, the thoughts of individuals could be explored by analyzing primary topics on SNSs. In this study, we proposed and developed a novel system for visual analytics to address the following intriguing questions. When do topics change? Do they ever resurface? What do people typically discuss? Using document embedding and dimensionality reduction approaches, we abstracted dynamic topics as several points in a two-dimensional space. In addition, we provided other charts depicting words that appeared at certain moments and their time series dynamics over entire periods. In addition, we created a novel text visualization technique called semantic-preserving word bubbles to visualize words at a specific time. In addition, we demonstrated the efficacy of the proposed system utilizing Twitter data regarding early COVID-19 trends, Fukushima nuclear disaster trends, and user ratings of system usability. In general, we have presented this novel system to aid users in exploring and comprehending the transitions of contents uploaded on SNSs. [ABSTRACT FROM AUTHOR]

Aims: Indoxyl sulfate and parathyroid hormone (PTH), which accumulate in chronic kidney disease (CKD), have been reported to reduce cytochrome P450(CYP)3A activity. Homozygotes of the CYP3A5*3 allele have reduced CYP3A5 activity compared to carriers of at least one CYP3A5*1 allele. 4β‐Hydroxycholesterol (4β‐OHC) has been established as an endogenous substrate reflecting CYP3A activity. 4β‐OHC is produced through hydroxylation by CYP3A4 and CYP3A5 and by autoxidation of cholesterol, whereas 4α‐hydroxycholesterol (4α‐OHC) is produced solely by autoxidation of cholesterol. This study focused on CKD patients and evaluated the effects of plasma indoxyl sulfate and intact‐PTH concentrations on plasma 4β‐OHC concentration, 4β‐OHC/total cholesterol ratio and 4β‐OHC–4α‐OHC, with consideration of the influence of CYP3A5 polymorphism. Methods: Sixty‐three CKD patients were analysed and divided into CYP3A5 carrier group (n = 26) and non‐carrier group (n = 37). Results: Plasma indoxyl sulfate significantly correlated inversely with 4β‐OHC concentration and with 4β‐OHC–4α‐OHC in both the CYP3A5*1 carrier group (r = −0.42, P =.034; r = −0.39, P =.050, respectively) and the non‐carrier group (r = −0.45, P =.0054; r = −0.39, P =.019, respectively). However, multiple regression analysis did not identify plasma indoxyl sulfate concentration as a significant independent factor associated with any of the CYP3A activity indices. There was no significant correlation between plasma intact‐PTH concentration and any of the CYP3A activity indices. Conclusions: The present results suggest that plasma indoxyl sulfate and intact‐PTH concentrations do not have clinically significant effects on CYP3A activity in patients with CKD. [ABSTRACT FROM AUTHOR]

We investigated the influence of Achilles tendon (AT) geometry on local-strain magnitude and distribution during loading, using finite element analysis. We calculated the following eight AT parameters for 18 healthy men: thickness and width of the most distal part, minimum cross-sectional area (mCSA), and most proximal part; length; and position of the mCSA. To investigate the effect of AT geometry on the magnitude and distribution of local strain, we created three-dimensional numerical models by changing the AT parameter values for every one standard deviation (SD) in the range of ±2 SD. A 4000 N lengthening force was applied to the proximal surface of all the models. The mean first principal strain (FPS) was determined every 3% of the length. The highest FPS in each model was mainly observed in the proximal regions; the 86–89% site (the most proximal site was set at 100%) had the highest number of models with the highest FPS (nine models). The highest FPS was observed in the model with a distal thickness of −2 SD, which was 27.1% higher than that of the standard model observed in the 2–5% site. Therefore, the AT geometry influences local-strain magnitude and distribution during loading. [ABSTRACT FROM AUTHOR]

While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (DLCO), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low DLCO, low minimum SpO2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately. Clinical Trial Registration: UMIN000009322. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by extensive and selective death of neurons and deterioration of synapses and circuits in the brain. The Aβ1–42 concentration is higher in an AD brain than in cognitively normal elderly individuals, and Aβ1–42 exhibits neurotoxicity. Brain-derived Aβ is transported into the cerebrospinal fluid (CSF), and CSF flow is driven in part by the beating of cilia and CSF secretion into ventricles. Ventricles are lined with ependyma whose apical surface is covered with motile cilia. Herein, we constructed an experimental system to measure the movement of ependymal cilia and examined the effects of Aβ1–42 to the beating of cilia and neurons. The circadian rhythm of the beating frequency of ependymal cilia was detected using brain wall explant-cultures containing ependymal cilia and neurons; the beating frequency was high at midday and low at midnight. Aβ1–42 decreased the peak frequency of ciliary beating at midday and slightly increased it at midnight. Aβ1–42 exhibited neurotoxicity to neurons on the non-ciliated side of the explant culture, while the neurotoxicity was less evident in neurons on the ciliated side. The neurotoxic effect of Aβ1–42 was diminished when 1 mPa of shear stress was generated using a flow chamber system that mimicked the flow by cilia. These results indicate that Aβ1–42 affects the circadian rhythm of ciliary beating, decreases the medium flow by the cilia-beating, and enhances the neurotoxic action of Aβ1–42 in the brain explant culture. [ABSTRACT FROM AUTHOR]

Purpose: Single-position surgery with patients in a lateral position, which involves inserting percutaneous pedicular screws (PPS) and lateral interbody fusion (LIF) to avoid changing the position, has been reported. The purpose of the present study was to evaluate the utility and appropriateness of single-position LIF-PPS using O-arm-based navigation in the innovative oblique position. Methods: This study involved a retrospective analysis of 92 consecutive patients with lumbar spondylolisthesis who underwent LIF-PPS using O-arm-based navigation. Thirty-five subjects demonstrated surgery with repositioning, as well as 24 in the lateral decubitus position, and 33 in the oblique during PPS, where the position was changed to the lateral decubitus position using bed rotation without resetting. We compared these three groups in terms of the surgery time, blood loss, and the accuracy of the screw placement. Results: The operative time was significantly shorter in the single-position surgery, both in the lateral and oblique positions, compared to surgery in a dual position. The blood loss was significantly increased in the lateral position compared to the dual and oblique positions. The screw trajectory angle on the downside was significantly smaller in the lateral position, and the accuracy of the screw placement on the downside was significantly lower in the lateral position compared to the dual and oblique positions. Conclusion: Single-position surgery could reduce the average surgery time by about 60 min. The present study indicated the oblique position during PPS insertion might make single-position surgery more useful to improve the accuracy of PPS on the downside, with less blood loss. [ABSTRACT FROM AUTHOR]

Background: Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC. Methods: Fresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdcscid1l2rgtm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate. Results: The PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P < 0.001). Finally, we demonstrated that the PDX tumour was sensitive to cisplatin and methotrexate; therefore, its clinical response to the agents was similar to that of the primary tumour. Conclusions: We successfully established a PDX model of NGC, to the best of our knowledge, for the first time. The established PDX retained the molecular and transcriptome characteristics of the primary tumour and can be used to predict drug effects. It may facilitate further research and the development of novel therapeutic agents for NGC. [ABSTRACT FROM AUTHOR]

In this study, we aimed to evaluate limited sampling strategies for achieving the therapeutic ranges of the area under the concentration‐time curve (AUC) of vancomycin on the first and second day (AUC0–24, AUC24–48, respectively) of therapy. A virtual population of 1000 individuals was created using a population pharmacokinetic (PopPK) model, which was validated and incorporated into our model‐informed precision dosing tool. The results were evaluated using six additional PopPK models selected based on a study design of prospective or retrospective data collection with sufficient concentrations. Bayesian forecasting was performed to evaluate the probability of achieving the therapeutic range of AUC, defined as a ratio of estimated/reference AUC within 0.8–1.2. The Bayesian posterior probability of achieving the AUC24–48 range increased from 51.3% (a priori probability) to 77.5% after using two‐point sampling at the trough and peak on the first day. Sampling on the first day also yielded a higher Bayesian posterior probability (86.1%) of achieving the AUC0–24 range compared to the a priori probability of 60.1%. The Bayesian posterior probability of achieving the AUC at steady‐state (AUCSS) range by sampling on the first or second day decreased with decreased kidney function. We demonstrated that second‐day trough and peak sampling provided accurate AUC24–48, and first‐day sampling may assist in rapidly achieving therapeutic AUC24–48, although the AUCSS should be re‐estimated in patients with reduced kidney function owing to its unreliable predictive performance. [ABSTRACT FROM AUTHOR]

Aluminum toxicity is the main factor limiting the elongation of plant roots in acidic soil. The tree species Eucalyptus camaldulensis is considerably more resistant to aluminum than herbaceous model plants and crops. Hydrolyzable tannins (HTs) accumulating in E. camaldulensis roots can bind and detoxify the aluminum taken up by the roots. However, in herbaceous model plants, HTs do not accumulate and the genes involved in the HT biosynthetic pathway are largely unknown. The aim of this study was to establish a method for reconstituting the HT biosynthetic pathway in the HT non-accumulating model plant Nicotiana benthamiana. Four E. camaldulensis enzymes were transiently expressed in N. benthamiana leaves via Agrobacterium tumefaciens-mediated transformation. These enzymes included dehydroquinate dehydratase/shikimate dehydrogenases (EcDQD/SDH2 and EcDQD/SDH3), which catalyze the synthesis of gallic acid, the first intermediate of the HT biosynthetic pathway that branches off from the shikimate pathway. The others were UDP-glycosyltransferases (UGT84A25 and UGT84A26), which catalyze the conversion of gallic acid to β-glucogallin, the second intermediate. The co-expression of the EcDQD/SDHs in transgenic N. benthamiana leaf regions promoted the synthesis of gallic acid. Moreover, the co-expression of the UGT84As in addition to the EcDQD/SDHs resulted in the biosynthesis of β-glucogallin, the universal metabolic precursor of HTs. Thus, we successfully reconstituted a portion of the HT biosynthetic pathway in HT non-accumulating N. benthamiana plants. This heterologous gene expression system will be useful for co-expressing candidate genes involved in downstream reactions in the HT biosynthetic pathway and for clarifying their in planta functions. [ABSTRACT FROM AUTHOR]