Search

ABSTRACT: The aim of this study was to evaluate the effect of hoof trimming on overall limb movements by comparing the changes in 8 limb joint angles 1 wk before and 1 wk after hoof trimming. Seventeen Holstein-Friesian dairy cows that were able to move freely and had no history of hoof diseases were included in the study. The cows were walked on rubber mats with a high friction coefficient (HFM) and a low friction coefficient (LFM) due to the spraying of sodium polyacrylate. Each cow had 15 reflective markers applied to its right side. A high-speed camera was set to 200 frames per second (fps) on the image analysis software, and the images of the cows were captured while cows walked on the test mat. The tests were conducted 1 wk before and 1 wk after hoof trimming, and the cows were trimmed by the functional hoof trimming method. With image analysis software, video clips of walking cows were confirmed visually and tracked during 1 gait cycle by each reflective marker attached to the hoof of the forelimb and hindlimb, after which the stance phase and swing phase were identified. The durations of the stance phase and swing phase of the forelimb and hindlimb, respectively, and the maximum, minimum, and range of motion (ROM) values of the 8 joint angles (shoulder joint, elbow joint, carpus joint, forelimb fetlock joint, hip joint, stifle joint, hock joint, and hindlimb fetlock joint) during 1 gait cycle were included in the analysis. The maximum and minimum angles of the hip and stifle joints were narrower after hoof trimming than before, although the ROM did not change and was clearer for HFM than for LFM. It was thought that the flexion of the proximal hindlimb would progress smoothly during walking after trimming.

Properties of the nuclear equation of state (EoS) can be probed by measuring the dynamical properties of nucleus-nucleus collisions. In this study, we present the directed flow (v1), elliptic flow (v2) and stopping (VarXZ) measured in fixed target Sn + Sn collisions at Image 1 with the SπRIT Time Projection Chamber. We perform Bayesian analyses in which EoS parameters are varied simultaneously within the Improved Quantum Molecular Dynamics-Skyrme (ImQMD-Sky) transport code to obtain a multivariate correlated constraint. The varied parameters include symmetry energy, S0, and slope of the symmetry energy, L, at saturation density, isoscalar effective mass, ms⁎/mN, isovector effective mass, mv⁎/mN and the in-medium cross-section enhancement factor η. We find that the flow and VarXZ observables are sensitive to the splitting of proton and neutron effective masses and the in-medium cross-section. Comparisons of ImQMD-Sky predictions to the SπRIT data suggest a narrow range of preferred values for ms⁎/mN, mv⁎/mN and η.

Detailed γ-ray spectroscopy of the exotic neon isotope 28Ne has been performed for the first time using the one-neutron removal reaction from 29Ne on a liquid hydrogen target at 240 MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for 28Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder p-wave strength providing evidence of the breakdown of the N=20 and N=28 shell gaps. Only a weak, possible f-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large p-wave and small f-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain.

Unbound states in C17 were investigated via one-neutron removal from a C18 beam at an energy of 245 MeV/nucleon on a carbon target. The energy spectrum of C17, above the single-neutron decay threshold, was reconstructed using invariant mass spectroscopy from the measured momenta of the C16 fragment and neutron, and was found to exhibit resonances at Er=0.52(2), 0.77(2), 1.36(1), 1.91(1), 2.22(3) and 3.20(1) MeV. The resonance at Er=0.77(2) MeV [Ex=1.51(3) MeV] was provisionally assigned as the second 5/2+ state. The two resonances at Er=1.91(1) and 3.20(1) MeV [Ex=2.65(2) and 3.94(2) MeV] were identified, through comparison of the energies, cross sections and momentum distributions with shell-model and eikonal reaction calculations, as p-shell hole states with spin-parities 1/21− and 3/21−, respectively. A detailed comparison was made with the results obtained using a range of shell-model interactions. The YSOX shell-model Hamiltonian, the cross-shell part of which is based on the monopole-based universal interaction, was found to provide a very good description of the present results and those for the neighbouring odd-A carbon isotopes – in particular for the negative parity cross-shell states.

The rapidity distributions of hydrogen isotopes emitted from central collisions of neutron-rich 132Sn+124Sn and neutron-deficient 108Sn+112Sn systems at 270 MeV/nucleon were investigated at RIKEN-RIBF. The data are compared with antisymmetrized molecular dynamics (AMD) calculations and the rapidity distributions can be reproduced after adjusting the in-medium nucleon-nucleon cross sections. The double ratios between the two reaction systems taken for the relative yields of deuteron to proton (d/p) and triton to proton (t/p) are further examined in the midrapidity domain, where the adjustments in the AMD calculations do not affect much on them. The d/p and t/p double ratios at midrapidity agree well with the ratio of the system neutron numbers and its squared value, respectively, and the rapidity dependence of these double ratios is consistent with a picture of partial mixing of colliding nuclei. By comparing with the AMD model which shows a strong symmetry energy dependence of the t/p double ratio, the experimental result in the midrapidity domain favors the calculation with a symmetry-energy slope parameter around L=46 MeV rather than L=108 MeV.

A thiosulfate-oxidizing bacterium, Thiomicrospira sp. strain V2501, was isolated from groundwater collected in a terrestrial deep subsurface environment. This strain was capable of chemolithoautotrophic growth on CO 2 and thiosulfate. Here, we report the 2,240,851 bp complete genome sequence of strain V2501.

We report the pulsed laser deposition (PLD) of nanocrystalline/amorphous homo-composite BaTiO 3 (BTO) films exhibiting an unprecedented combination of a colossal dielectric constant ( ε r ) and extremely low dielectric loss (tan δ ). By varying the substrate deposition temperature ( T d ) over a wide range (300-800 °C), we identified T d = 550 °C as the optimal temperature for growing BTO films with an ε r as high as ~3060 and a tan δ as low as 0.04 (at 20 kHz). High-resolution transmission electron microscopy revealed that the PLD-BTO films consist of BTO nanocrystals (~20-30 nm size) embedded within an otherwise amorphous BTO matrix. The impressive dielectric behavior is attributed to the combination of highly crystallized small BTO nanograins, which amplify interfacial polarization, and the surrounding amorphous matrix, which effectively isolates the nanograins from charge carrier transport. Our findings could facilitate the development of next-generation integrated dielectric devices.

Although coil embolization is commonly perceived as a minimally invasive procedure, the associated radiation exposure cannot be disregarded. To date, no specific study has investigated radiation exposure during coil embolization. This study aimed to investigate the potential of lowering the pulse rate to decrease radiation exposure during coil embolization while maintaining patient safety. Radiation data and clinical features of 70 patients who underwent coil embolization between 2015 and 2020 were retrospectively analyzed. Since July 2017, the pulse rate was regulated from 7.5 to 4 frames per second (f/s). Statistical analyses were performed to examine the correlation between pulse rate and radiation exposure. Out of the 70 procedures, 30 were performed at the standard pulse rate (7.5 f/s), and 40 were performed at the lower pulse rate (4 f/s). In the lower-pulse-rate group, the absorbed dose to the patient (AK) was 2580.7 (±217) mGy, whereas in the standard-pulse-rate group, it was 4760 (±411.1). Both the dose-area product (DAP) and AK were substantially reduced in the low pulse rate group (p = 0.000002). There was a significant correlation between DAP and AK and pulse rate (p = 0.004, p = 0.0017, respectively). Moreover, there was no significant correlation between pulse rate and perioperative complications. Our findings suggest that using a lower pulse rate (4 f/s) can effectively reduce radiation exposure during coil embolization for cerebral aneurysms while ensuring patient safety.

Agents that target PD-1 and PD-L1 have been developed in the treatment of bladder cancer (BC). However, the diversity of immune cell infiltration in non-muscle-invasive BC (NMIBC) and the dynamics of the microenvironment as it progresses to muscle-invasive/metastatic disease remains unknown. To assess tumor immune activity, hierarchical clustering was applied to 159 BC samples based on cellular positivity for the defined immune cellular markers (CD3/CD4/CD8/FOXP3/CD20/PD-1/PD-L1/LAG3/TIGIT), divided into two clusters. There was a "hot cluster" (25%) consisting of patients with a high expression of these markers and a "cold cluster" (75%) comprising those without. The expression of CD39, CD44, CD68, CD163, IDO1, and Ki67 was significantly higher in tumors in the hot cluster. Immunologically, high-grade T1 tumors were significantly hotter, whereas tumors that had progressed to muscle invasion turned cold. However, a certain number of high-grade NMIBC patients were in the cold cluster, and these patients had a significantly higher risk of disease progression. Using an externally available TCGA dataset, RB1 and TP53 alterations were more frequently observed in TCGA hot cluster; rather FGFR3, KDM6A, and KMT2A alterations were common in TCGA cold/intermediate cluster. Analyses of recurrent tumors after BCG therapy revealed that tumor immune activity was widely maintained before and after treatment, and high FGFR3 expression was detected after recurrence in tumors initially classified into the cold cluster. Collectively, we revealed the dynamics of the tumor microenvironment in BC as a whole and identified candidate molecules as therapeutic targets for recurrent NMIBC, e.g., after BCG therapy., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background and study aims We previously demonstrated the efficacy of an additional-30-seconds (Add-30s) observation with linked color imaging (LCI) or narrow band imaging (NBI) of the cecum and ascending colon (right-sided colon) after white light imaging (WLI) observation for improving adenoma detection rate (ADR) by 3% to 10%. We herein compared Add-30s LCI with Add-30s NBI in a large number of cases. Patients and methods We retrospectively collected 1023 and 1011 cases with Add-30s LCI and NBI observation for right-sided colon in 11 affiliated institutions from 2018 to 2022 and propensity score matching was performed. Add-30s observation was as follows. First observation: WLI observation of the right-sided colon as first observation. Second observation: Reobservation of right-sided colon by Add-30s LCI or NBI. The comparison of the mean numbers of adenoma+sessile serrated lesions (SSLs) and adenomas per patient (MASP and MUTYH-associated polyposis) were analyzed in the Add-30s LCI/NBI groups. The increase in right-sided ADR was also analyzed in the groups. Results Among 748 matched cases in the Add-30s LCI/NBI groups, the MASP and MAP were 0.18/0.19 ( P = 0.54) and 0.14/0.15 ( P = 0.70). Among experts, they were 0.17/0.22 ( P = 0.16) and 0.15/0.21 ( P = 0.08). Among non-experts, they were 0.13/0.12 ( P = 0.71) and 0.12/0.07 ( P = 0.04). The right-sided ADRs of the first+second observations in the LCI and NBI groups were 32.2% and 28.9% ( P = 0.16) and the increase of ADRs were 7.5% and 7.2% ( P = 0.84). Conclusions In right-sided colon, the detection of adenoma/SSL did not differ between Add-30s LCI and NBI. Both of them significantly increased ADR., Competing Interests: Conflict of Interest Yoshida N and Dohi O have received a research grant from Fujifilm. Yoshida N have received payment for lectures from Fujifilm. The other author declares no conflict of interest for this article., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Amyloidosis is a group of diseases in which proteins become amyloid, an insoluble fibrillar aggregate, resulting in organ dysfunction. Amyloid deposition has been reported in various animal species. To diagnose and understand the pathogenesis of amyloidosis, it is important to identify the amyloid precursor protein involved in each disease. Although 42 amyloid precursor proteins have been reported in humans, little is known about amyloidosis in animals, except for a few well-described amyloid proteins, including amyloid A (AA), amyloid light chain (AL), amyloid β (Aβ), and islet amyloid polypeptide-derived amyloid. Recently, several types of novel amyloidosis have been identified in animals using immunohistochemistry and mass spectrometry-based proteomic analysis. Certain species are predisposed to specific types of amyloidosis, suggesting a genetic background for its pathogenesis. Age-related amyloidosis has also emerged due to the increased longevity of captive animals. In addition, experimental studies have shown that some amyloids may be transmissible. Accurate diagnosis and understanding of animal amyloidosis are necessary for appropriate therapeutic intervention and comparative pathological studies. This review provides an updated classification of animal amyloidosis, including associated protein misfolding disorders of the central nervous system, and the current understanding of their pathogenesis. Pathologic features are presented together with state-of-the-art diagnostic methods that can be applied for routine diagnosis and identification of novel amyloid proteins in animals., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: In patients with diabetic macular edema (DME) from YOSEMITE/RHINE, dual angiopoietin-2/vascular endothelial growth factor-A (VEGF-A) inhibition with faricimab resulted in visual/anatomic improvements with extended dosing. The SWAN trial (jRCTs031230213) will assess the efficacy, durability, and safety of faricimab during the treatment maintenance phase in patients with DME using a treat-and-extend (T&E)-based regimen adapted to clinical practice and the characteristics of patients achieving extended dosing intervals., Methods: SWAN is a 2-year, open-label, single-arm, interventional, multicenter trial enrolling adults with center-involving DME. All patients will receive three initial faricimab 6.0 mg doses every 4 weeks (Q4W). From week 12 onwards, in patients without active DME, dosing intervals will be extended in 8-week increments up to Q24W. In contrast, patients with active DME (central subfield thickness [CST] >325 μm and intraretinal fluid [IRF] or subretinal fluid [SRF] resulting in vision loss/disease aggravation) will receive a dose within a day and the dosing interval will be shortened by 4 weeks to a minimum of Q8W relative to the previous dosing interval. Recruitment commenced in August 2023 across a planned 16 sites in Japan., Results: The primary endpoint is change in best-corrected visual acuity (BCVA) from baseline at 1 year (averaged over weeks 52, 56, and 60). Key secondary endpoints include: change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire scores over time; proportion of patients with BCVA (decimal visual acuity) ≥0.5, ≥0.7, ≥1.0, or ≤0.1; proportion of patients with absence of DME, and IRF and/or SRF over time. Safety endpoints include incidence/severity of ocular/nonocular adverse events., Conclusions: The SWAN trial is expected to provide evidence to support individualized faricimab dosing regimens, with the potential to reduce the burden of frequent treatments on patients, caregivers, and healthcare systems., Competing Interests: Takao Hirano: Speaker Fees: Bayer, Canon, Chugai Pharmaceutical Co., Ltd., Kowa, Novartis Pharma KK, Santen Pharmaceutical Co., Senju, ZEISS Toshinori Murata: Speaker Fees: Bayer, Novartis, Santen, Zeiss Meditec: Consultant: Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Hoya, Kowa, Wakamoto Shintaro Nakao: Consultant: Alcon, Boehringer Ingelheim, Novartis, Riverfield; Speaker Fees: Bayer, Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Hoya, Kowa, Machida, Mitsubishi Tanabe, Novartis, Novo Nordisk, Otsuka, Santen, Senju, Wakamoto Masahiko Shimura: Consultant: Bayer, Boehringer Ingelheim, Chugai, HOYA, Nikki HD, Roche, Wakamoto; Lecture Fees: Bayer, Chugai, Kowa, Novartis, Otsuka, Senju Miho Nozaki: Speaker Fees: Bayer, Canon, Chugai Pharmaceutical Co., Ltd., Kowa, Nikon, Novartis Pharma KK, Santen, Senju, Sumitomo Pharma Co., Ltd., Topcon Medical, Wakamoto Kiyoshi Suzuma: Speaker Fees: AMO, Alcon, Bayer, Chugai Pharmaceutical Co., Ltd., HOYA, Kowa, Novartis, Senju Consultant: Senju, Chugai Pharmaceutical Co., Ltd., Boehringer Ingelheim Taiji Nagaoka: Consultant: Boehringer Ingelheim, Novartis, TES Holdings; Speaker Fees: Bayer, Chugai Pharmaceutical Co., Ltd., Hoya, Kowa, Mitsubishi Tanabe, Novartis, Santen, Senju, Wakamoto; Research Fees: Daicel, Kowa, LTT, Santen Masahiko Sugimoto: Research Fees: Alcon Japan, Bayer, Chugai Pharmaceutical Co., Ltd., Novartis; Speaker Fees: Alcon Japan, Bayer, Kowa, Novartis, Senju, Wakamoto Yoshihiro Takamura: Lecture Fees: Chugai Pharmaceutical Co., Ltd. Tomoaki Murakami: Speaker Fees: Bayer, Canon, Chugai Pharmaceutical Co., Ltd., Johnson & Johnson, Kowa, Novartis Pharma KK, Santen; Consultant: Boehringer Ingelheim Keisuke Iwasaki: Employee: Chugai Pharmaceutical Co., Ltd. Jun Tsujimura: Employee: Chugai Pharmaceutical Co., Ltd. Shigeo Yoshida: Consultant: Chugai Pharmaceutical Co., Ltd., Novartis; Speaker Fees: Bayer, Chugai Pharmaceutical Co., Ltd., Novartis, Senju; Research Fees: Kowa, Otsuka, Senju We confirm that the author competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Hirano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This randomized controlled trial compared the outcomes of recombinant human fibroblast growth factor (rhFGF)-2 plus carbonate apatite (CO 3 Ap) granules with rhFGF-2 alone in the treatment of intrabony periodontal defects., Materials and Methods: Patients with Stage III Grade B/C periodontitis who had completed initial periodontal therapy and had intrabony defects with a depth of ≥ 3 mm were included. Defects were treated solely with rhFGF-2 (control) or rhFGF-2 plus CO 3 Ap (test). Periodontal parameters and a patient-reported outcome measure (PROM) were assessed at baseline, at 6, 9 and 12 months postoperatively. The primary outcome was the change in clinical attachment level (CAL) from baseline to 12 months postoperatively. Using the Friedman test with Dunn's post-test, intragroup data were compared over time, and Mann-Whitney U test was used to assess intergroup data at each time point., Results: Forty-eight sites in 38 patients were subjected to analysis. At 12 months postoperatively, CAL in both groups showed a significant improvement from baseline (p < 0.001). CAL gain was 3.4 ± 1.3 mm in the test group and 3.2 ± 1.2 mm in the control group, with no significant intergroup difference (p = 0.567). Radiographic bone fill in the test group (67.2%) was significantly greater than in the control group (32.4%) (p < 0.001). PROM scores showed no difference between groups., Conclusions: At 12 months, the outcomes including CAL gain and PROM showed no significant differences between groups, although the combination treatment enhanced radiographic bone fill., Clinical Relevance: The use of rhFGF-2 (with/without CO 3 Ap) could lead to significant improvement in clinical parameters in the treatment of intrabony periodontal defects. The benefit of adding CO 3 Ap to rhFGF-2 therapy needs further evaluation., Clinical Trial Registration Number: The University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) : UMIN000040783., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Wnt/β-catenin signaling is essential for adrenocortical development. Zinc and ring finger 3 (ZNRF3), an E3 ubiquitin ligase that attenuates Wnt/β-catenin signaling, is negatively regulated by R-spondin via an extracellular domain that is partially encoded by exon 2 of ZNRF3. We recently identified ZNRF3 exon 2 deletions in three individuals with congenital adrenal hypoplasia. ZNRF3 exon 2 deletion impairs R-spondin binding, thereby attenuating β-catenin expression and eventually leading to the development of congenital adrenal hypoplasia. To elucidate the influence of ZNRF3/Znrf3 exon 2 deletion on adrenocortical development, we generated homozygous Znrf3 exon 2 deletion (Znrf3Δ2/Δ2) mice. Whereas the adrenal glands of Znrf3Δ2/Δ2 mice did not show gross morphological changes at birth, moderate hyperplasia of the zona fasciculata (ZF), dispersed medulla arrangement, and a radially spreading zone with macrophage infiltration between the ZF and medulla were observed at 6 weeks of age. 20α-hydroxysteroid dehydrogenase, a marker of the adrenal X-zone, was hardly detected by immunostaining, and gene expression was significantly downregulated. The number of activated β-catenin-positive cells decreased in the zona glomerulosa, consistent with the results of in situ hybridization for Axin2, a Wnt/β-catenin target gene. Plasma ACTH and serum corticosterone levels in Znrf3Δ2/Δ2 mice did not differ significantly from those in wild-type mice. These results show a species-specific difference in the effects of ZNRF3/Znrf3 exon 2 deletions in humans and mice; Znrf3Δ2/Δ2 mice do not develop congenital adrenal hypoplasia but instead exhibit moderate ZF hyperplasia, dispersed medulla arrangement, X-zone dysplasia, and macrophage infiltration occurred in the inner cortex.

Targeting novel inhibitory ligands beyond anti-PD-1 and PD-L1 and CTLA-4 therapies is essential for the next decade of the immunotherapy era. Agents for the B7 family molecules B7-H3, B7-H4, and B7-H5 are emerging in clinical trial phases; therefore, further accumulation of evidence from both clinical and basic aspects is vital. Here, we applied a 7-color multiplexed imaging technique to analyze the profile of B7 family B7-H3/B7-H4/B7-H5 expression, in addition to PD-L1, and the spatial characteristics of immune cell infiltrates in urothelial carcinoma (UC). The results revealed that B7-H3 and B7-H4 were mainly expressed on tumor cells and B7-H5 on immune cells in UC, and most of the B7-H3/B7-H4/B7-H5-positive cells were mutually exclusive with PD-L1-positive cells. Also, the expression of B7-H4 was elevated in patients with advanced pathologic stages, and high B7-H4 expression was a significant factor affecting overall mortality following surgery in UC. Furthermore, spatial analysis revealed that the distance from the B7-H4 + cells to the nearest CD8 + cells was markedly far compared with other B7 family-positive tumor cells. Interestingly, the distance from B7-H4 + cells to the nearest CD8 + cells was significantly farther in patients dying from cancer after surgery or immune checkpoint inhibitors compared with cancer survivors; thus, high B7-H4 expression in tumor cells may inhibit CD8 infiltration into the tumor space and that B7-H4-positive cells form a specific spatial niche. In summary, we performed a comprehensive evaluation of B7 family member expression and found that the spatial distribution of B7-H4 suggests the potentially useful role of combination blockade with both B7-H4 and the current anti-PD-1/PD-L1 axis in the treatment of UC., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the effect of hoof trimming on overall limb movements by comparing the changes in 8 limb joint angles 1 wk before and 1 wk after hoof trimming. Seventeen Holstein-Friesian dairy cows that were able to move freely and had no history of hoof diseases were included in the study. The cows were walked on rubber mats with a high friction coefficient (HFM) and a low friction coefficient (LFM) due to the spraying of sodium polyacrylate. Each cow had 15 reflective markers applied to its right side. A high-speed camera was set to 200 frames per second (fps) on the image analysis software, and the images of the cows were captured while cows walked on the test mat. The tests were conducted 1 wk before and 1 wk after hoof trimming, and the cows were trimmed by the functional hoof trimming method. With image analysis software, video clips of walking cows were confirmed visually and tracked during 1 gait cycle by each reflective marker attached to the hoof of the forelimb and hindlimb, after which the stance phase and swing phase were identified. The durations of the stance phase and swing phase of the forelimb and hindlimb, respectively, and the maximum, minimum, and range of motion (ROM) values of the 8 joint angles (shoulder joint, elbow joint, carpus joint, forelimb fetlock joint, hip joint, stifle joint, hock joint, and hindlimb fetlock joint) during 1 gait cycle were included in the analysis. The maximum and minimum angles of the hip and stifle joints were narrower after hoof trimming than before, although the ROM did not change and was clearer for HFM than for LFM. It was thought that the flexion of the proximal hindlimb would progress smoothly during walking after trimming., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Purpose: This study aimed to compare the fixed and flexible protocols for progestin-primed ovarian stimulation (PPOS) in poor ovarian responders., Methods: This retrospective study included 95 poor ovarian responders classified using the Patient-Oriented Strategies Encompassing Individualized Oocyte Number group 4 criteria. Treatment involved assisted reproductive medicine using fixed and flexible PPOS protocols at Shiga University of Medical Science between July 2019 and August 2023. PPOS cycles were assigned to the fixed and flexible groups at the discretion of attending physicians. The results of assisted reproductive medicine were compared between groups., Results: The fixed and flexible groups included 68 and 27 patients, respectively. The flexible group obtained more retrieved oocytes and two pro-nuclei than the fixed group, without an early luteinizing hormone surge. Multiple linear regression analysis demonstrated that differences in protocols and anti-müllerian hormone (AMH) levels were related to the number of retrieved oocytes. The differences in protocols were more strongly correlated with the number of oocytes than with the AMH levels., Conclusion: Among poor ovarian responders, the flexible PPOS protocol provided more retrieved oocytes than the fixed PPOS protocol, possibly because the total dosage of progestins was lower in the flexible group and progestins were not administered at the time when ovarian stimulation was initiated., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study aimed to propose reference values for day-to-day home blood pressure (BP) variability that align with the established hypertension threshold of home BP for the risk of two different outcomes: cardiovascular mortality and cognitive decline., Methods: This prospective study was conducted in Ohasama town, Japan, with 1212 participants assessed for cardiovascular mortality risk (age: 64.7 years, 33.6% men). Additionally, 678 participants (age: 62.7 years, 31.1% men) were assessed for cognitive decline risk (Mini-Mental Scale Examination score <24). The within-individual coefficient of variation (CV) of home morning SBP (HSBP) was used as the index of day-to-day BP variability (%). Adjusted Cox regression models were used to estimate the HSBP-CV values, which provided the 10-year outcome risk at an HSBP of 135 mmHg., Results: A total of 114 cardiovascular deaths and 85 events of cognitive decline (mean follow-up:13.9 and 9.6 years, respectively) were identified. HSBP and HSBP-CV were associated with increased risks for both outcomes, with adjusted hazard ratios per 1-standard deviation increase of at least 1.25 for cardiovascular mortality and at least 1.30 for cognitive decline, respectively. The adjusted 10-year risks for cardiovascular mortality and cognitive decline were 1.67 and 8.83%, respectively, for an HSBP of 135 mmHg. These risk values were observed when the HSBP-CV was 8.44% and 8.53%, respectively., Conclusion: The HSBP-CV values indicating the 10-year risk of cardiovascular mortality or cognitive decline at an HSBP of 135 mmHg were consistent, at approximately 8.5%. This reference value will be useful for risk stratification in clinical practice., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To evaluate the renal prognosis of dipeptidyl peptidase-4 inhibitor (DPP-4i) users and non-users using real-world Asian data., Methods: Using databases from DeSC Healthcare, Inc., patients aged 30 years or older who used antidiabetic drugs from 2014 to 2021 were identified. Propensity score matching analyses were used to compare renal prognosis between DPP-4i users and non-users. The primary outcomes were estimated glomerular filtration rate (eGFR) decline and end-stage kidney disease (ESKD) development in the eGFR of 45 mL/min/1.73m 2 or higher and eGFR of less than 45 mL/min/1.73m 2 groups, respectively., Results: In total, 65 375 and 9866 patients were identified in the eGFR of 45 mL/min/1.73m 2 or higher and eGFR of less than 45 mL/min/1.73m 2 groups, respectively. In the eGFR of 45 mL/min/1.73m 2 or higher group, propensity score matching created 16 002 pairs. A significant difference was observed in the primary outcome of eGFR decline between DPP-4i users and non-users at 2 years (-2.31 vs. -2.56 mL/min/1.73m 2 : difference, 0.25 mL/min/1.73m 2 ; 95% confidence interval [CI], 0.06-0.44) and 3 years (-2.75 vs. -3.41 mL/min/1.73m 2 : difference, 0.66 mL/min/1.73m 2 ; 95% CI, 0.39-0.93). In the eGFR less than 45 mL/min/1.73m 2 group, propensity score matching created 2086 pairs. After a mean of 2.2 years of observation, ESKD development was 1.15% and 2.30% in users and non-users, respectively, and Kaplan-Meier analysis revealed a significant difference (log rank P = .005)., Conclusions: This retrospective real-world study revealed that patients using DPP-4is had a better renal prognosis than those not using DPP-4is., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: Ulcerative colitis-associated neoplasia (UCAN) is characterised by multifocal tumourigenesis. A wide range of metachronous lesions have been reported to occur after endoscopic treatment of UCAN, which suggests the development of sporadic tumours in lesions treated as UCAN. Therefore, we aimed to evaluate differences of immunohistochemistry (IHC) in features and clinicopathological characteristics of intramucosal lesions in patients with ulcerative colitis (UC)., Methods and Results: We examined 35 intramucosal lesions resected for carcinoma or dysplasia by total colectomy from patients with UC and 71 sporadic adenomas (SAs) endoscopically resected from patients without UC. UC lesions were divided into the conventional UCAN group, defined as p53 mutant pattern and normal expression of β-catenin, and the non-conventional UCAN group, defined as the rest. Ki-67 distribution, α-methylacyl-CoA racemase (AMACR) expression and mucin phenotypes were compared using IHC, and clinicopathological characteristics were investigated. Conventional and non-conventional UCAN lesions were located in the left colon and rectum. Relative to the SA lesions, UCAN lesions occurred in much younger patients and exhibited more frequent basal distribution of Ki-67 in tumour crypts. Conventional UCAN lesions tended to be non-polyploid and exhibited a higher frequency of normal AMACR expression than SA lesions. UC lesions were heterogeneous-only two of the eight patients with multiple lesions had lesions (both non-conventional UCAN lesions) exhibiting concordant IHC staining features., Conclusions: The basal pattern of Ki-67 distribution, normal expression of AMACR and a non-intestinal mucin phenotype were determined as characteristic features suggestive of UCAN. Non-polypoid growth was another a key feature of UCAN., (© 2024 John Wiley & Sons Ltd.)

Purpose: To compare changes in liver enzyme levels on postoperative day 1 between patients with and without silicone disc (SD) use during liver retraction in laparoscopic gastrectomy for gastric cancer and laparoscopic gastric mobilization for esophageal cancer., Methods: This prospective randomized controlled phase II trial was conducted between June 30, 2020, and November 30, 2022, to investigate the benefits of using an SD with a Nathanson liver retractor (NLR) compared with those using an NLR in laparoscopic gastrectomy and gastric mobilization. The primary endpoint was the change in transaminase level on postoperative day 1., Results: A total of 86 patients received randomized assignments and were included in the analysis, with 44 assigned to the SD (-) group and 42 to the SD (+) group. On postoperative day 1, the SD (+) group showed a significantly lower increase in the aspartate aminotransferase levels than the SD (-) group (SD [+], 94.4% vs. SD [-], 179.8%; p = 0.012). Similarly, the SD (+) group showed a significantly lower increase in alanine aminotransferase levels than the SD (-) group (SD [+], 71.6% vs. SD [-], 201.5%; p = 0.014)., Conclusion: In laparoscopic gastrectomy, the use of an SD combined with an NLR appears to mitigate postoperative liver dysfunction., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

This study aimed to evaluate the associations of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels at <24 weeks of gestation with hypertensive disorders of pregnancy (HDP) and compare the strengths of the associations of HDP with FPG and HbA1c levels. Totally, 1,178 participants were included in this prospective cohort study. HDP, FPG, HbA1c, and potential confounding factors were included in multiple logistic regression models. The number of HDP cases was 136 (11.5%). When FPG and HbA1c were included in the model separately, quartile 4 (Q4) of FPG (87-125 mg/dL) and HbA1c (5.2-6.3% [33-45 mmol/mol]) levels had higher odds of HDP than quartile 1. The odds ratios (ORs) were 1.334 (95% confidence interval [CI]: 1.002-1.775) for Q4 of FPG and 1.405 (95% CI: 1.051-1.878) for Q4 of HbA1c. When the participants were divided into two categories based on the cut-off value with the maximum Youden Index of FPG or HbA1c, the ORs for high FPG (≥84 mg/dL) or high HbA1c (≥5.2% [33 mmol/mol]) were 1.223 (95% CI: 1.000-1.496) and 1.392 (95% CI: 1.122-1.728), respectively. When both FPG and HbA1c were included in the model simultaneously, the statistical significance of Q4 of FPG disappeared, whereas that of HbA1c remained. In two-category models, the same results were obtained. High FPG and HbA1c levels at <24 weeks of gestation were risk factors for HDP in pregnant Japanese women. In addition, high HbA1c levels were more strongly associated with HDP than high FPG levels.

Purpose: Minimal misregistration of fused PET and MRI images can be achieved with simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI). However, the acquisition of multiple MRI sequences during a single PET emission scan may impair fusion precision of each sequence. This study evaluated the diagnostic utility of time-synchronized PET/MRI using an MR active trigger and a Bayesian penalized likelihood reconstruction algorithm (BPL) to assess the locoregional extension of endometrial cancer., Methods: Fifty-five patients with endometrial cancer who underwent pelvic 2-deoxy-2-[ 18 F]fluoro-D-glucose PET/MRI were retrospectively evaluated. The PET emission time for the BPL reconstruction was determined by the MR active trigger of each MR sequence. The concordance rates of image interpretation with pathological T-staging, diagnostic performance for deep myometrial invasion (MI), and diagnostic confidence levels were evaluated by two readers and compared between time-synchronized, overlapping (conventional and simultaneous, but not time-synchronized), and sequential (not simultaneous) PET/MRI and MRI with diffusion-weighted imaging. Misregistration of the PET/MRI-fused images was determined by evaluating the differences in bladder dimensions., Results: The T classification by time-synchronized PET/MRI was the most concordant with the pathological T classification for the two readers. Time-synchronized PET/MRI had a significantly higher diagnostic performance for deep MI and higher confidence level scores than overlapping PET/MRI for the novice reader (p = 0.033 and p = 0.038, respectively). The differences in bladder dimension on sequential PET/MRI were significantly larger than those on overlapping and time-synchronized PET/MRI (p <0.001)., Conclusion: Time-synchronized PET/MRI is superior to conventional PET/MRI for assessing the locoregional extension of endometrial cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Munenobu Nogami reports off-line reconstruction tool (Duetto) was provided by GE HealthCare. Takako Kurimoto is an employee of GE HealthCare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Centiloid (CL) scales play an important role in semiquantitative analyses of amyloid-β (Aβ) PET. CLs are derived from the standardized uptake value ratio (SUVR), which needs Aβ positron emission tomography (PET) normalization processing. There are two methods to collect the T1-weighted imaging (T1WI) for normalization: (i) anatomical standardization using simultaneously acquired T1WI (PET/MRI), usually adapted to PET images from PET/MRI scanners, and (ii) T1WI from a separate examination (PET + MRI), usually adapted to PET images from PET/CT scanners. This study aimed to elucidate the correlations and differences in CLs between when using the above two T1WI collection methods., Methods: Among patients who underwent Aβ PET/MRI (using 11 C-Pittuberg compound B ( 11 C-PiB) or 18 F-flutemetamol ( 18 F-FMM)) at our institution from 2015 to 2023, we selected 49 patients who also underwent other additional MRI examinations, including T1WI for anatomic standardization within 3 years. Thirty-one of them underwent 11 C-PiB PET/MRI, and 18 participants underwent 18 F-FMM PET/MRI. Twenty-five of them, additional MRI acquisition parameters were identical to simultaneous MRI during PET, and 24 participants were different. After normalization using PET/MRI or PET + MRI method each, SUVR was measured using the Global Alzheimer's Association Initiative Network cerebral cortical and striatum Volume of Interest templates (VOI) and whole cerebellum VOI. Subsequently, CLs were calculated using the previously established equations for each Aβ PET tracer., Results: Between PET/MRI and PET + MRI methods, CLs correlated linearly in 11 C-PiB PET (y = 1.00x - 0.11, R 2  = 0.999), 18 F-FMM PET (y = 0.97x - 0.12, 0.997), identical additional MRI acquisition (y = 1.00x + 0.33, 0.999), different acquisition (y = 0.98x - 0.43, 0.997), and entire study group (y = 1.00x - 0.24, 0.999). Wilcoxon signed-rank test revealed no significant differences: 11 C-PiB (p = 0.49), 18 F-FMM (0.08), and whole PET (0.46). However, significant differences were identified in identical acquisition (p = 0.04) and different acquisition (p = 0.02). Bland-Altman analysis documented only a small bias between PET/MRI and PET + MRI in 11 C-PiB PET, 18 F-FMM PET, identical additional MRI acquisition, different acquisition, and whole PET (- 0.05, 0.67, - 0.30, 0.78, and 0.21, respectively)., Conclusions: Anatomical standardizations using PET/MRI and using PET + MRI can lead to almost equivalent CL. The CL values obtained using PET/MRI or PET + MRI normalization methods are consistent and comparable in clinical studies., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Intracellular delivery of biomolecules is a prerequisite for genetic techniques such as recombinant engineering and genome editing. Realizing the full potential of this technology requires the development of safe and effective methods for delivering protein tools into cells. In this study, we demonstrated the spontaneous internalization of exogenous proteins into intact cells and root tissue of whole plants of Arabidopsis thaliana. We termed this internalization phenomenon as protein Delivery Independent of Vehicles or Equipment (DIVE), which efficiently delivered genome engineering proteins including Cre recombinase and zinc-finger nucleases (ZFN) into plant cells. Using protein DIVE, we achieved less toxic protein delivery than electroporation with up to 94% efficiency in Arabidopsis cell culture and 19% genome modification in Arabidopsis plants that was maintained in regenerated tissue. This work illustrates the potential of protein DIVE for a wide range of applications, including genome engineering in plants., (© 2024. The Author(s).)

Social networking services (SNSs) are useful tools; however, problematic use leads to mental health problems. This study aimed to examine whether SNS addiction is associated with occupational dysfunction while considering the effects of depression. This cross-sectional study included 268 undergraduates who responded to the questionnaire on the frequency and time of SNS use, the Center for Epidemiologic Studies Depression Scale (CES-D), SNS-X scale, and the Classification and Assessment of Occupational Dysfunction (CAOD). Hierarchical multiple regression analysis showed effect of the SNS-X score for Instagram was significant (β = 0.174, p = .001) adjusted by the CES-D total score. However, the effect of frequency and time of SNS use were not significant. This suggests that SNS addiction, and not SNS use, is a factor associated with occupational dysfunction that should be emphasized and depression., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM., Methods: We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023., Results: During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8-40.7%) and 70.0% (95% CI, 55.5-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates., Conclusion: Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.