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Particle dark matter could belong to a multiplet that includes an electrically charged state. WIMP dark matter (χ0) accompanied by a negatively charged excited state (χ−) with a small mass difference (e.g. < 20 MeV) can form a bound-state with a nucleus such as xenon. This bound-state formation is rare and the released energy is O(1−10) MeV depending on the nucleus, making large liquid scintillator detectors suitable for detection. We searched for bound-state formation events with xenon in two experimental phases of the KamLAND-Zen experiment, a xenon-doped liquid scintillator detector. No statistically significant events were observed. For a benchmark parameter set of WIMP mass mχ0=1 TeV and mass difference Δm=17 MeV, we set the most stringent upper limits on the recombination cross section times velocity 〈σv〉 and the decay-width of χ− to 9.2×10−30 cm3/s and 8.7×10−14 GeV, respectively at 90% confidence level.

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

ApoA-I-containing lipoproteins exist in plasma in two main forms: one contains only apoA-I (LpA-I) while the other contains both apoA-I and apoA-II (LpA-I/A-II). We characterized structural and functional changes of these lipoproteins in six patients with cholesteryl ester transfer protein (CETP) deficiency. In these patients, the amount of LpA-I and LpA-I/A-II had increased significantly. Sixty-five percent of plasma apoA-I was associated with LpA-I/A-II, which indicated that LpA-I/A-II was predominant. The chemical composition of both LpA-I and LpA-I/A-II was characterized by increased ratios of neutral to polar lipid, compared with findings in normal subjects. Particle sizes of these lipoproteins shifted to larger diameter ranges, as compared to the size seen in normal subjects. Incubation of patients' LpA-I and LpA-I/A-II with CETP markedly corrected the chemical and physical abnormalities in these lipoproteins. Cholesterol-reducing capacities of these lipoproteins from macrophage foam cells were significantly lower than in normal controls. Cholesterol esterification rates in LpA-I, LpA-I/A-II, and plasma were significantly lower in patients than in normal controls. We propose that the structure and function of LpA-I and LpA-I/A-II are severely affected in the presence of CETP deficiency.

The pathophysiology of laryngopharyngeal reflux (LPR) and its impact on the vocal fold is not well understood, but may involve acid damage to vocal fold barrier functions. Two different components encompass vocal fold barrier function: the mucus barrier and tight junctions. Mucus retained on epithelial microprojections protects the inside of the vocal fold by neutralizing acidic damage. Tight junctions control permeability between cells. Here we developed an in vitro experimental system to evaluate acidic injury and repair of vocal fold barrier functions. We first established an in vitro model of rat vocal fold epithelium that could survive at least one week after barrier function maturation. The model enabled repeated evaluation of the course of vocal fold repair processes. Then, an injury experiment was conducted in which vocal fold cells were exposed to a 5-min treatment with acidic pepsin that injured tight junctions and cell surface microprojections. Both of them healed within one day of injury. Comparing vocal fold cells treated with acid alone with cells treated with acidic pepsin showed that acidic pepsin had a stronger effect on intercellular permeability than acid alone, whereas pepsin had little effect on microprojections. This result suggests that the proteolytic action of pepsin has a larger effect on protein-based tight junctions than on phospholipids in microprojections. This experimental system could contribute to a better understanding of vocal fold repair processes after chemical or physical injuries, as well as voice problems due to LPR pathogenesis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masanobu Mizuta, Ichiro Tateya reports financial support was provided by Japan Society for the Promotion of Science. 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 Elsevier Inc. All rights reserved.)

Objectives: Coronary flow reserve (CFR) is a strong predictor of cardiovascular events and prognosis in patients with coronary artery disease. This study aimed to evaluate preoperative factors associated with the unsuccessful restoration of CFR after coronary artery bypass grafting (CABG)., Methods: Included in this study were the 65 patients who presented with functionally significant left anterior descending artery (LAD) lesions confirmed by both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), and who underwent successful CABG at our hospital within the study period. After CABG, graft patency was confirmed by coronary computed tomography angiography, and CFR in the LAD artery was measured by echocardiography. We defined postoperative CFR <2.5 as impaired CFR, and CFR ≥2.5 as preserved CFR., Results: Of the 65 patients, 14 patients (22%) showed impaired CFR, while 51 patients had preserved CFR. Patients with impaired CFR had significantly higher HbA1c (6.7% vs. 6.0%, P < 0.01), greater use of insulin (43% vs. 4%, P < 0.01), longer lesion length (33 mm vs. 25 mm, P = 0.044), and lower iFR (0.69 vs 0.81, P = 0.01) than those with preserved CFR, although both groups had comparable FFR (0.65 vs 0.64, P = 0.46). In receiver operating characteristic curve analysis, iFR had a significantly larger area under the curve than FFR in terms of the prediction of impaired CFR (0.74 vs 0.42, P = 0.01)., Conclusions: Poorly-controlled preoperative diabetes, greater reliance on insulin, longer lesion length and lower iFR were associated with postoperative impaired CFR, suggesting the involvement of microvascular dysfunction., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Schistosomiasis, caused by trematodes of genus Schistosoma, is among the most seriously neglected tropical diseases. Although rapid surveillance of risk areas for Schistosoma transmission is vital to control schistosomiasis, the habitat and infection status of this parasite are difficult to assess. Environmental DNA (eDNA) analysis, involving the detection of extra-organismal DNA in water samples, facilitates cost-efficient and sensitive biomonitoring of aquatic environments and is a promising tool to identify Schistosoma habitat and infection risk areas. However, in tropical wetlands, highly turbid water causes filter clogging, thereby decreasing the filtration volume and increasing the risk of false negatives. Therefore, in this study, we aimed to conduct laboratory experiments and field surveys in Lake Victoria, Mbita, to determine the appropriate filter pore size for S. mansoni eDNA collection in terms of particle size and filtration volume. In the laboratory experiment, aquarium water was sequentially filtered using different pore size filters. Targeting >3 µm size fraction was found to be sufficient to capture S. mansoni eDNA particles, regardless of their life cycle stage (egg, miracidia, and cercaria). In the field surveys, GF/D (2.7 µm nominal pore size) filter yielded 2.5-times the filtration volume obtained with a smaller pore size filter and pre-filtration methods under the same time constraints. Moreover, a site-occupancy model was applied to the field detection results to estimate S. mansoni eDNA occurrence and detection probabilities and assess the number of water samples and PCR replicates necessary for efficient eDNA detection. Overall, this study reveals an effective method for S. mansoni eDNA detection in turbid water, facilitating the rapid and sensitive monitoring of its distribution and cost-effective identification of schistosomiasis transmission risk areas., Competing Interests: Declaration of competing interest Toshifumi Minamoto is an inventor of the patent for the use of benzalkonium chloride for eDNA preservaion., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: Acute graft-versus-host disease (GVHD) grading systems that use only clinical symptoms at treatment initiation such as the Minnesota risk identify standard and high-risk categories but lack a low-risk category suitable to minimize immunosuppressive strategies. We developed a new grading system that includes a low-risk stratum based on clinical symptoms alone and determined whether the incorporation of biomarkers would improve the model's prognostic accuracy. We randomly divided 1863 patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) who were treated for GVHD into training and validation cohorts. Patients in the training cohort were divided into 14 groups based on similarity of clinical symptoms and similar nonrelapse mortality (NRM); we used a classification and regression tree (CART) algorithm to create three Manhattan risk groups that produced a significantly higher area under the receiver operating characteristic curve (AUC) for 6-month NRM than the Minnesota risk classification (0.69 vs 0.64, P = .009) in the validation cohort. We integrated serum GVHD biomarker scores with Manhattan risk using patients with available serum samples and again used a CART algorithm to establish 3 MAGIC composite scores that significantly improved prediction of NRM compared to Manhattan risk (AUC, 0.76 vs 0.70, P = .010). Each increase in MAGIC composite score also corresponded to a significant decrease in day 28 treatment response (80% vs 63% vs 30%, P < .001). We conclude that the MAGIC composite score more accurately predicts response to therapy and long-term outcomes than systems based on clinical symptoms alone and may help guide clinical decisions and trial design., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Methylmercury (MeHg) is widely distributed in nature and is known to cause neurotoxic effects. This study aimed to examine the anti-MeHg activity of oleanolic acid-3-glucoside (OA3Glu), a synthetic oleanane-type saponin derivative, by evaluating its effects on motor function, pathology, and electrophysiological properties in a mouse model of MeHg poisoning. Mice were orally administered 2 or 4 mg·kg -1 ·d -1 MeHg with or without 100 µg·kg -1 ·d -1 OA3Glu 5x/week for four weeks. Motor function was evaluated using beam-walking and dynamic weight-bearing (DWB) tests. High-dose MeHg exposure significantly increased the frequency of stepping off the hind leg while crossing the beam in the beam-walking test, and increased weight on forelegs when moving freely in the DWB test. OA3Glu treatment alleviated motor abnormality caused by high-dose MeHg exposure in both motor function tests. Additionally, OA3Glu treatment reduced the number of contracted Purkinje cells frequently observed in the cerebellum of MeHg-treated groups, although cerebrum histology was similar in all experimental groups. The synaptic potential amplitude in the cerebellum decreased as MeHg exposure increased, which was restored by OA3Glu treatment. Even in the cerebrum, where the effects of MeHg were not observed, the amplitude of the field potential was suppressed with increasing MeHg exposure but was restored with OA3Glu treatment. Taken together, the study findings suggest that OA3Glu improves neurotransmission and movement disorders associated with MeHg exposure via protection of Purkinje cells in the cerebellum while ameliorating pre/post-synaptic deficits in the cerebral cortex in which no changes were observed at the tissue level, potentially providing a treatment to mitigate MeHg toxicity., Competing Interests: Declaration of Competing Interest The authors 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 Elsevier B.V. All rights reserved.)

Background: In microvascular breast reconstruction, the internal mammary vein (IMV) has emerged as the most common recipient vein. The open-Y technique can increase the vessel diameter via the bifurcation site. This study aimed to investigate the open-Y technique for IMV., Methods: The characteristics and details of the operative procedure in patients who had undergone unilateral breast reconstruction with and without the open-Y approach for the free abdominal flap were compared. Differences in IMV anastomosis site (the bifurcation of the main duct or that of the perforator branch) were also compared in patients with the open-Y technique. The open-Y technique was performed on the IMV side., Results: The open-Y and conventional groups included 127 and 62 patients, respectively. The main duct diameter of IMV was significantly smaller (median 2.5 vs. 3.0 mm, P < 0.001), and the rate of right-sided anastomosis (47.2 vs. 82.3%, P < 0.001) was significantly lower in the open-Y group. When comparing the main duct and perforator groups, the branch diameter (1.8 vs. 1.0 mm, P < 0.001) and the diameter after the open-Y technique (5.0 vs. 3.9 mm, P < 0.001) were significantly higher, and the angle of bifurcation (45° vs. 60°, P = 0.007) was significantly lower in the main duct group., Conclusions: Given a small venous diameter, the open-Y technique is superior, especially for left-sided breast reconstruction. Owing to the lower angle of bifurcation and large diameter, the open-Y technique at the main duct bifurcation of IMV causes less turbulence in the blood flow., Take Home Message: The open-Y technique is especially effective for left-sided breast reconstruction. Considering the lower angle of bifurcation and large diameter, the open-Y technique at the main duct bifurcation of the internal mammary vein causes less turbulence in the blood flow., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest One of the authors declares financial competing interests from Olympus Terumo Biomaterials and AUSPICIOUS.

Background: Safinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice., Methods: This multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment., Results: In total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change -7.0 [p = 0.012], -2.4 [p = 0.007] and - 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild., Conclusion: Safinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns., Study Registration: University Hospital Medical Information Network in Japan; study ID: UMIN000044341., Competing Interests: Declaration of competing interest N.N., S.S. and W.S. report honoraria and consultation fees from Eisai Co., Ltd. during the conduct of the study. T.H., K.N., R.N., A.Y., Y.S. and H.S. report honoraria from Eisai Co., Ltd. during the conduct of the study. S.-I.U., T.O. and Y.F. have no competing interests to declare. T.K. and T.I. are employees of Eisai Co. Ltd. N.H. reports honoraria, consultation fees and grants from Eisai Co., Ltd. during the conduct of the study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The measurement of antigen-specific serum IgE is common in clinical assessments of type I allergies. However, the interaction between antigens and IgE won't invariably trigger mast cell activation. We previously developed the IgE crosslinking-induced luciferase expression (EXiLE) method using the RS-ATL8 mast cell line; however, the method may not be sensitive enough in some cases., Methods: In this study, we introduced an NF-AT-regulated luciferase reporter gene into the RBL-2H3 rat mast cell line and expressed a chimeric high-affinity IgE receptor (FcεRI) α chain gene, comprising an extracellular domain from humans and transmembrane/intracellular domains from rats., Results: We generated multiple clones expressing the chimeric receptor. Based on their responsiveness and proliferation, we selected the HuRa-40 clone. This cell line exhibited significantly elevated human α chain expression compared to RS-ATL8 cells, demonstrating a 10-fold enhancement of antigen-specific reactivity. Reproducibility across different batches and operators was excellent. Moreover, we observed a detectable response inhibition by an anti-allergy drugs (omalizumab and cyclosporin A)., Conclusions: HuRa-40 cells-which carry the human-rat chimeric IgE receptor-comprise a valuable reporter cell line for the EXiLE method. Their versatility extends to various applications and facilitates high-throughput screening of anti-allergy drugs., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Medial unicompartmental knee osteoarthritis is a common condition that is frequently associated with significant pain and dysfunction. Medial opening wedge high tibial osteotomy (MOWHTO) offers a unique opportunity to preserve the knee joint and potentially alter the course of the degenerative process. Recent advances in this field of surgery have enabled surgeons to perform a MOWHTO in a safe, reliable and reproducible manner. This state-of-the-art review highlights the most important advances in the field of MOWHTO. Key concepts related to patient selection, pre-operative planning, surgical accuracy and patient outcome are considered. The importance of an individualized approach is emphasized and its influence on the future direction of the procedure is discussed., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

T-cell large granular lymphocytic leukemia (T-LGLL) is a clonal proliferation of cytotoxic T lymphocytes that can result in severe neutropenia, anemia, and bone marrow failure. Strong evidence from patients and mouse models demonstrate the critical role of interleukin-15 (IL-15) in T-LGLL pathogenesis. BNZ-1 is a pegylated peptide that selectively inhibits the binding of IL-15 and other γc cytokines to their cellular receptor complex, which has demonstrated efficacy in ex vivo T-LGLL cells and transgenic mice in preclinical studies. We conducted a phase 1/2 trial of BNZ-1 in patients with T-LGLL who had hematocytopenias (anemia or neutropenia) and required therapy. Clinical responses were assessed using hematologic parameters (improvement in hematocytopenias) based on response criteria from the Eastern Cooperative Oncology Group 5998 T-LGLL trial. BNZ-1 demonstrated clinical partial responses in 20% of patients with T-LGLL with minimal toxicity and the maximum tolerated dose was not reached. Furthermore, T-LGL leukemic cells showed significantly increased apoptosis in response to BNZ-1 treatment as early as day 2, including in clinical nonresponders, with changes that remained statistically different from baseline throughout treatment (P < .005). We report first-in-human proof that T-LGL leukemic cells are dependent on IL-15 and that intervention with IL-15 inhibition with BNZ-1 in patients with T-LGLL shows therapeutic effects, which carries important implications for the understanding of the pathogenesis of this disease. This trial was registered at www.clinicaltrials.gov as #NCT03239392.

Background: The ideal umbilical position is midway between the two iliac crests. Some patients complained that the umbilicus position shifted from the midline after the breast reconstruction with a free muscle-sparing transverse rectus abdominis musculocutaneous (MS-TRAM) flap. We considered that the fascia of the external oblique muscle could be applied to the rectus abdominis fascia defect. This study aimed to introduce this "fascia turnover procedure" and compare the umbilical position in this procedure with that in primary fascial closure for the MS-TRAM flap of breast reconstruction., Methods: A total of 152 patients were enrolled (80 patients with fascia turnover (+) vs. 72 patients (-)). The patients' demographics were compared. Horizontal distances (right side: a; left side: b) were measured bilaterally from the lateral abdominal wall to the center of the umbilicus. Frontal abdominal photographs were taken preoperatively (a 1 , b 1 ) and postoperatively (a 2 , b 2 ). The rate of umbilical migration (= | (a 1 - b 1 ) / (a 1 + b 1 ) - (a 2 - b 2 ) / (a 2 + b 2 ) | × 100%) was calculated. Because the aponeurosis of the external oblique muscle is confirmed in front of the lateral side of the anterior rectus sheath, this procedure could be performed in cases with a medial defect., Results: No significant differences in the patients' demographics, including abdominal bulging rates and abdominal wall defect widths were observed between the two groups. The rate of umbilical migration showed a significant difference (median 1.78% vs. 3.70%, P < 0.001)., Conclusions: This procedure could decrease the rate of umbilical migration., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Medial meniscal posterior root tears disrupt the "hoop" function of the meniscus and may lead to knee osteoarthritis. Although root repair could be a key to osteoarthritis prevention, this surgery does not necessarily guarantee an optimal result even when combined with meniscal centralization and high tibial osteotomy. To address this issue, we made five modifications to the original combined approach, namely two anchors to fix the root, instead of one; bridging centralization instead of single centralization; release of the meniscotibial capsule vs no release; release of valgus stress before knot tying vs no release; and prohibiting postoperative cross-legged sitting and sitting on heels. The advantages of this approach over the original approach are numerous and comprise ease of performing concurrent open wedge high tibial osteotomy, shorter fixation distance, better anatomical reattachment of the meniscal root, increased bone-meniscus contact and contact pressure, and larger contact area between the capsule and tibial rim. The disadvantages of the approach are that knot-tying is cumbersome, pie-crusting of the medial collateral ligament is necessary in patients not undergoing open wedge high tibial osteotomy, and tears >3 mm from the attachment are a contraindication. We describe the steps in this modified approach in detail., (© 2023 The Authors.)

Patellar subluxation and recurrent dislocation are commonly treated with medial patellofemoral ligament reconstruction, and patients with predisposing factors for these problems often require additional bony realignment procedures. However, these procedures mainly address problems in the axial plane, and patients with medial-compartmental knee osteoarthritis may require further realignment in the coronal plane. In this Technical Note article, we introduce our technique for derotational hybrid closed-wedge high tibial osteotomy. Using this technique, simultaneous 3-dimensional realignment in the axial, coronal, and sagittal planes can be achieved in patients with medial compartmental knee osteoarthritis and patellar subluxation caused by a tibial torsional deformity. The indications for the technique and the preoperative planning assessments involving a static torsional deformity analysis on computed tomography images and a dynamic gait analysis by our walking-on-paper method are presented. This is followed by a detailed description of the surgical procedure, together with consideration of the pearls and pitfalls of the procedure. A video of the surgery performed in a representative case with medial knee osteoarthritis and patellar subluxation in the right knee owing to an outward tibial torsion deformity is also provided., (© 2023 The Authors.)

Background: Heparin prophylaxis for venous thromboembolism can be used in microsurgery. If vein anastomosis is performed before the artery, heparin irrigation into the artery can be performed locally without systematic effect. This study aimed to introduce this "intraflap perfusion procedure" in autologous breast reconstruction., Methods: Among the 220 patients with unilateral breast cancer who had received the free abdominal flap, we retrospectively compared those that had undergone the intraflap perfusion procedure (n = 108) and those who did not (n = 112). A 10 mL injection of heparinized physiological saline solution (100 units/mL) was administered into the deep inferior epigastric artery. Intraflap perfusion was performed before, during, and after vein anastomosis, without the vessel clip of the vein. Artery anastomosis was performed without the use of a vein clamp. Further, vein anastomosis was performed tightly to prevent leakage from the vein anastomosis site during artery anastomosis., Results: The rates of superficial inferior epigastric vein (SIEV) superdrainage (18.5% vs. 42.0%, P < 0.001), and intraoperative flap congestion (0.9% vs. 8.0%, P = 0.01) were significantly lower in patients undergoing this procedure. There were no significant differences regarding other factors (age, BMI, laterality, comorbidities, and other operative details)., Conclusions: Intraflap perfusion prevented long-term stasis at the venous anastomosis site and capillary level. It could reduce flap congestion. SIEV superdrainage was performed to manage flap congestion, particularly in patients who did not undergo this procedure. Consequently, it can be inferred that this procedure reduces the rate of superdrainage., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Study Objective: The combined use of the ProSeal laryngeal mask airway and a bronchial blocker may reduce postoperative hoarseness and sore throat. We aimed to test the feasibility and efficacy of this combination technique in thoracoscopic surgery., Design: A single-center, patient-assessor blinded, randomized controlled trial., Setting: Nagoya City University Hospital (between November 2020 and April 2022)., Patients: A total of 100 adult patients undergoing lobectomy or segmentectomy by video- or robotic-assisted thoracoscopic surgery., Interventions: Patients were randomly assigned to either group using a combination of the ProSeal laryngeal mask airway and a bronchial blocker (pLMA+BB group) or a double-lumen endobronchial tube (DLT group)., Measurements: The primary outcome was the hoarseness incidence on 1-3 postoperative days. Secondary outcomes included sore throat, intraoperative complications (hypoxemia, hypercapnia, surgical interruption, malposition of devices, unintended lung expansion, and ventilatory difficulty), lung collapse, device placement-related outcomes, and coughing during emergence., Main Results: A total of 100 patients underwent randomization (51 to the pLMA+BB group and 49 to the DLT group). After drop outs, a total of 49 patients in each group were analyzed per-protocol. The incidences of hoarseness in the pLMA+BB and DLT groups were 42.9% and 53.1% (difference, -10.2%; 95% confidence interval, -30.1% to 10.3%; p = 0.419), 18.4% vs. 32.7%, and 20.4% vs. 24.5% on postoperative day 1, 2, and 3, respectively. The incidences of sore throat in the pLMA+BB and DLT groups were 16.3% vs. 34.7% (difference, -18.4%; 95% confidence interval, -35.9% to -0.9%; p = 0.063) on postoperative day 1. In the pLMA+BB group, more intraoperative complications and less coughing during emergence were observed compared to the DLT group. Lung collapse and placement-related outcomes were comparable between the groups., Conclusions: The combination of ProSeal laryngeal mask airway and bronchial blocker did not significantly reduce hoarseness compared to the double-lumen endobronchial tube., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Allogeneic hematopoietic stem cell transplantation (alloHCT) is potentially curative for relapsed/refractory (r/r) B-cell non-Hodgkin's lymphoma (B-cell NHL). However, relapse remains a major cause of treatment failure, especially in patients with either positron emission tomography (PET)-positive and/or chemoresistant disease prior to alloHCT. 90 Y-ibritumomab tiuxetan (Zevalin) is a radiolabeled anti-CD20 antibody which is a safe and effective therapy in multiple histologic subtypes of B-cell NHL and has also been incorporated in both autologous HCT (autoHCT) and alloHCT conditioning regimens., Objectives: The purpose of this study was to evaluate the efficacy and confirm the safety of the radiolabeled anti-CD20 antibody ibritumomab tiuxetan (Zevalin) combined with the reduced intensity conditioning (RIC) regimen of fludarabine and melphalan (Flu/Mel) in patients with high-risk B-cell NHL., Study Design: We conducted a phase II trial (NCT00577278) of Zevalin with Flu/Mel in patients with high-risk B-cell NHL. We enrolled 41 patients from October 2007 to April 2014, all of whom had either a fully matched sibling or 8/8 or 7/8 matched unrelated donor (MUD). Patients received 111 In-Zevalin (5.0 mCi) on day -21 pre-HCT, followed by 90 Y-Zevalin (0.4 mCi/kg) on day -14. Fludarabine (25 mg/m 2 daily) was given from days -9 to -5 and melphalan (140 mg/m 2 ) was administered on day -4. All patients received rituximab 250 mg/m2 on day +8 and an additional dose on either day +1 or -21 depending on the baseline rituximab level. Patients with a low rituximab level were given rituximab on days -21 and -15. All patients received tacrolimus/sirolimus (T/S) with or without methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis starting on day -3, and stem cells were infused on day 0., Results: The 2-year overall survival (OS) and progression-free survival (PFS) for all patients were 63% and 61%, respectively. The incidence of relapse at 2 years was 20%. Nonrelapse mortality (NRM) at day +100 and 1 year were 5% and 12%, respectively. The overall cumulative incidence of grade II-IV and III-IV acute GVHD (aGVHD) were 44% and 15%, respectively. Extensive chronic GVHD (cGVHD) occurred in 44% of patients. On univariate analysis, histology (diffuse large B cell lymphoma (DLBCL) vs. others) was negatively predictive for OS (P = .0013) and PFS (P = .0004), while histology (DLBCL vs. others, P = .0128) predicted for relapse. PET positivity pre-HCT did not correlate with any of the efficacy endpoints., Conclusion: Addition of Zevalin to Flu/Mel is safe and effective in high-risk NHL and met the prespecific endpoint. Results were suboptimal in patients with DLBCL., Competing Interests: Disclosure Declarations of interest: MM reports consultancies with Novartis, SeaGen, Janssen, EUSA, CTI, participation in speakers’ bureaus with SeaGen and Morphosys, and research funding from BMS, BeiGene, and Morphosys. AFH reports consultancies with BMS, Genentech, Merck, SeaGen, AstraZeneca, Karyopharm, ADC Therapeutics, Takeda, Tubulis, Regeneron, Genmab, Pfizer, Caribou, Adicet Bio, Abbvie, Allogene, and research funding from Genentech, Merck, Seagen, KiTE Pharma, Gilead Sciences, AstraZeneca, ADC Therapeutics., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI) to improve the sensitivity and enhance diagnostic performance. GBCAs are mostly eliminated from the body through the kidney after administration; however small amounts of gadolinium are retained in the brain and other tissues. Although there is increasing concern about the adverse health effects of gadolinium, the cellular effects of GBCAs remains poorly understood. Here, we elucidated the potential cytotoxicity of the GBCAs Omniscan and Gadovist in 12 different cell lines, especially 3T3-L1 adipocyte cell line. Omniscan and Gadovist treatments significantly increased intracellular gadolinium levels in 3T3-L1 cells in a time- and dose-dependent manner. Additionally, Omniscan and Gadovist treatments downregulated the expression of adipocyte differentiation markers, including peroxisome proliferator-activated receptor γ (PPARG), adiponectin (ADIPOQ), and fatty acid-binding protein (FABP4), in 3T3-L1 cells, especially during early differentiation (day 0-2). Moreover, histological analysis using Oil red O staining showed that gadolinium chloride (GdCl 3 ) treatment suppressed lipid droplet accumulation and the expression of adipocyte differentiation markers. Overall, the results showed that Omniscan and Gadovist treatment suppressed adipocyte differentiation in 3T3-L1 cells, contributing to the understanding of the potential toxic effects of GBCA exposure., Competing Interests: Declaration of Competing Interest The authors 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 © 2023 Elsevier B.V. All rights reserved.)

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare but severe cutaneous adverse drug reactions. Certain human leukocyte antigen (HLA) types have been associated with SJS/TEN onset, e.g., HLA-B ∗ 58:01 with allopurinol-induced SJS/TEN, but HLA typing is time-consuming and expensive; thus, it is not commonly used in clinical situations. In the previous work, we demonstrated that the single-nucleotide polymorphisms (SNP) rs9263726 was in absolute linkage disequilibrium with HLA-B ∗ 58:01 in the Japanese population, and can be used as a surrogate marker for the HLA. Here, we developed a new genotyping method for the surrogate SNP using the single-stranded tag hybridization chromatographic printed-array strip (STH-PAS) technique and performed an analytical validation. The results of genotyping rs9263726 using STH-PAS correlated well with those obtained using the TaqMan SNP Genotyping Assay for 15 HLA-B ∗ 58:01-positive and 13 HLA-B ∗ 58:01-negative patients (analytical sensitivity and specificity were both 100%). Additionally, at least 1.11 ng of genomic DNA was sufficient to digitally and manually detect positive signals on the strip. Robustness studies showed that the annealing temperature (66 °C) was the most important condition related to reliable results. Collectively, we developed an STH-PAS method that can rapidly and easily detect rs9263726 for predicting SJS/TEN onset., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation. In experimental models, interleukin-22 promotes epithelial regeneration and induces innate antimicrobial molecules. We conducted a multicenter single-arm phase 2 study evaluating the safety and efficacy of a novel recombinant human interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD. The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. Out of 27 patients, 19 (70%; 80% confidence interval, 56%-79%) achieved a day-28 treatment response, meeting the prespecified primary endpoint. Responders exhibited a distinct fecal microbiota composition characterized by expansion of commensal anaerobes, which correlated with increased overall microbial α-diversity, suggesting improvement of GVHD-associated dysbiosis. This work demonstrates a potential approach for combining immunosuppression with tissue-supportive strategies to enhance recovery of damaged mucosa and promote microbial health in patients with gastrointestinal GVHD. This trial was registered at www.clinicaltrials.gov as NCT02406651., (© 2023 by The American Society of Hematology.)

Background: Open wedge high tibial osteotomy (OWHTO) brings new complications such as screw breakages with or without correction loss and time-dependent increased posterior tibial slopes (PTS) due to the opening gap. For preventive purposes, we changed our OWHTO procedure from anteromedial plating without filling the gap (non-grafted group, n = 40, 2009-2012) to medial plating with bone-substitute insertion (grafted group, n = 45, 2012-2015). The objectives of this study were to evaluate the complication patterns and the effects of the modifications., Methods: Patients undergoing OWHTO with TomoFix plates were included in this retrospective study. Demographics, clinical outcomes (flexion range and Japanese Orthopaedic Association score) and radiological outcomes (femorotibial angle) were assessed in both groups pre-operatively and 2-years postoperatively. The plate installation angle [PIA] and screw insertion depth [SID] were measured on computed tomographic slices at 6 months. PIA/SID was defined as the angle between the tibial anteroposterior axis and plate-width axis/the distance between the proximal screw tip and the proximal tibiofibular joint. The non-grafted group was further divided into complication and non-complication subgroups. Screw breakages were assessed during plate removal (1.5-2.5 years postoperatively)., Results: There were no differences in baseline characteristics or radiological/clinical outcomes between the non-grafted and grafted groups. There were 0 and 11 complications in the grafted and non-grafted groups, respectively. Complications included 7 screw breakages, 4 correction losses, and 5 time-dependent increased PTS with some overlaps. PIA and SID were significantly lower (p < 0.001) and higher (p < 0.001), respectively, in the grafted group and significantly lower (p = 0.018) and higher (p = 0.040), respectively, in the non-complication subgroup within the non-grafted group. The cutoff value of PIA for complications was calculated at 48.0°., Conclusions: Medial plating OWHTO (PIA<48°) using bone-substitute with deeper screw insertion reinforces the opening gap for better angular stability compared with anteromedial plating without bone-substitute., Competing Interests: Declaration of competing interest Dr. Ryuichi Nakamura has a consultancy with Olympus Terumo Biomaterials. All other authors have no conflicts of interest relevant to this article to declare., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Chronic exposure to methylmercury (MeHg) is positively associated with obesity and metabolic syndromes. However, the effect of MeHg on adipogenesis has not been thoroughly investigated. This study investigated the effects of continuous exposure to 0.5 µM MeHg on adipocyte differentiation in 3T3-L1 cells. Oil Red O staining and triglycerides (TG) assays demonstrated that MeHg enhanced the TG content in 3T3-L1 cells. MeHg enhanced the mRNA and protein expression of adipocyte differentiation markers including peroxisome proliferator-activated receptor γ, adiponectin, and fatty acid-binding protein, and their expression levels were prominent during the late stages (days 6-8) after the induction of differentiation. In addition, 0.5 µM MeHg promoted the expression of autophagy-related genes, including light chain 3 B-II and p62, after induction of differentiation. Treatment of 3T3-L1 cells with chloroquine (CQ), an autophagy inhibitor, during the early stages (days 0-2) after induction of differentiation inhibited cellular lipid accumulation in the presence of 0.5 µM MeHg. However, treatment with CQ during the late stages (days 6-8) had little effect on the MeHg-induced increase in TG content and the expression of adipocyte differentiation markers. Although the underlying mechanisms in the late stages remain to be completely elucidated, but the present data suggest that autophagy and other mechanisms play critical roles in adipogenesis during MeHg-induced differentiation. Collectively, our results suggest that continuous exposure to MeHg induces TG accumulation and expression of genes related to adipogenesis, especially during the late stages of 3T3-L1 differentiation, which may contribute to an improved understanding of MeHg-induced adipogenesis., Competing Interests: Declaration of Competing Interest The authors 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 © 2023 Elsevier B.V. All rights reserved.)

In conventional closed-wedge high tibial osteotomy (CWHTO) with preservation of the medial hinge, flexion contracture cannot be improved because of the two-dimensional correction. Conversely, in hybrid CWHTO, for which the name is derived from a hybrid of the lateral closing and medial opening, the medial cortex is intentionally disrupted. The medial hinge disruption enables three-dimensional correction, which helps eliminate flexion contracture by decreasing posterior tibial slope (PTS). The fine adjustment of the anterior closing distance and thigh-compression technique further facilitates PTS control. In this study, we describe the use of the Reduction-Insertion-Compression Handle (RICH), which maximizes the benefits of hybrid CWHTO. This device permits accurate osteotomy reduction, easy screw insertion, and assists with providing sufficient compressive force at the osteotomy site, as well as the elimination of the flexion contracture. This Technical Note presents the details of using the RICH and the associated advantages and disadvantages in hybrid CWHTO for medial compartmental knee arthritis., (© 2022 The Authors.)

Background: Although proximal gastrectomy (PG) is a function-preserving surgical option, it remains unclear as to which reconstruction method can prevent reflux and maintain body composition., Methods: Patients who underwent PG at Keio University between April 2011 and November 2018 were analyzed. Changes in the subcutaneous and visceral adipose tissues were comparatively assessed before and after a year of surgery for three common reconstruction methods. We also compared the endoscopic findings of reflux esophagitis and the number of patients prescribed with proton-pump inhibitor after a year of surgery., Results: This study included 76 patients, of which 33 patients underwent esophagogastrostomy with a circular stapler (CS), 35 under double flap (DF) reconstruction, and 8 underwent double tract (DT) reconstruction. Comparing esophagogastrostomy (CS and DF) and DT showed that esophagogastrostomy could significantly preserve both subcutaneous and visceral adipose tissues (P < 0.001 and P = 0.04, respectively). However, the change in the subcutaneous and visceral adipose tissues was comparable between CS and DF. As for reflux esophagitis, DF showed the lowest incidence rate for esophagitis and the least number of patients who were prescribed a proton-pump inhibitor., Conclusion: DF is a relatively better reconstruction method for preserving fat mass and preventing reflux among the three common reconstruction methods., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome. CXCR5-PD-1hi peripheral T-helper (Tph) cells have an important pathogenic role in autoimmune diseases, but the role of Tph cells in cGVHD remains unknown. We show that in patients with cGVHD, expansion of Tph cells among blood CD4+ T cells was associated with cGVHD severity. These cells augmented memory B-cell differentiation and production of immunoglobulin G via interleukin 21 (IL-21). Tph cell expansion was also observed in a murine model of cGVHD. This Tph cell expansion in the blood is associated with the expansion of pathogenic tissue-resident T-helper (Trh) cells that form lymphoid aggregates surrounded by collagen in graft-versus-host disease (GVHD) target tissues. Adoptive transfer experiments showed that Trh cells from GVHD target tissues give rise to Tph cells in the blood, and conversely, Tph cells from the blood give rise to Trh cells in GVHD target tissues. Tph cells in the blood and Trh cells in GVHD target tissues had highly overlapping T-cell receptor α and β repertoires. Deficiency of IL-21R, B-cell lymphoma 6 (BCL6), or T-bet in donor T cells markedly reduced the proportions of Tph cells in the blood and Trh cells in GVHD target tissues and reduced T-B interaction in the lymphoid aggregates. These results indicate that clonally related pathogenic Tph cells and Trh cells traffic between the blood and cGVHD target tissues, and that IL-21R-BCL6 signaling and T-bet are required for the development and expansion of Tph and Trh cells in the pathogenesis of cGVHD., (© 2022 by The American Society of Hematology.)

The frequency of pathogenic/likely pathogenic (P/LP) germ line variants in patients with myelodysplastic syndrome (MDS) diagnosed at age 40 years or less is 15% to 20%. However, there are no comprehensive studies assessing the frequency of such variants across the age spectrum. We performed augmented whole-exome sequencing of peripheral blood samples from 404 patients with MDS and their related donors before allogeneic hematopoietic stem cell transplantation. Single-nucleotide and copy number variants in 233 genes were analyzed and interpreted. Germ line status was established by the presence of a variant in the patient and related donor or for those seen previously only as germ line alleles. We identified P/LP germ line variants in 28 of 404 patients with MDS (7%), present within all age deciles. Patients with P/LP variants were more likely to develop higher-grade MDS than those without (43% vs 25%; P = .04). There was no statistically significant difference in outcome parameters between patients with and without a germ line variant, but the analysis was underpowered. P/LP variants in bone marrow failure syndrome genes were found in 5 patients aged less than 40 years, whereas variants in DDX41 (n = 4), telomere biology disorder genes (n = 2), and general tumor predisposition genes (n = 17) were found in patients aged more than 40 years. If presumed germ line variants were included, the yield of P/LP variants would increase to 11%, and by adding suspicious variants of unknown significance, it would rise further to 12%. The high frequency of P/LP germ line variants in our study supports comprehensive germ line genetic testing for all patients with MDS regardless of their age at diagnosis., (© 2022 by The American Society of Hematology.)

Closed-wedge high tibial osteotomy (CWHTO) may be carried out to realign the knee in patients with knee osteoarthritis who do not meet the criteria for open-wedge high tibial osteotomy or total knee arthroplasty. The procedure involves both fibular and tibial osteotomy, and care is needed to prevent peroneal nerve and vessel injury during fibular osteotomy. Notably, use of a tourniquet may mask the development of hematomas or aneurysms until after surgery. We developed a 3-step ankle-angle-adjusting (triple-A) technique to relax the muscles, allowing easy retraction of the peroneal vessels. Crucially, the procedure does not require a tourniquet, thus allowing bleeding to be detected and stopped during surgery. The process involves adjusting the ankle angle by plantar-flexion and applying varus stress to highlight the tension difference between the lateral and posterior compartments; plantar-flexion of the great toe to loosen the flexor hallucis longus muscle, thus exposing the fibular posterior aspect; and valgus stress to loosen the peroneus longus muscle. The muscles can then be retracted sufficiently to allow distal and proximal osteotomies to be performed, and any bleeding can be detected and resolved before wound closure. This technique may improve the ease and safety of fibular osteotomy in patients undergoing CWHTO., (© 2022 The Authors.)

Objectives: Almost all preference-based measures (PBMs) have been developed in Western countries, with none having been formulated in Asian countries. In this study, we construct a new generic PBM based on concept elicitation using interview surveys in East and Southeast Asian countries and qualitative analysis., Methods: This cross-sectional study included 225 adults recruited from 9 East and Southeast Asian countries or regions (Indonesia, Japan, Korea, mainland China, Malaysia, the Philippines, Singapore, Taiwan, and Thailand). Trained interviewers conducted semistructured interviews with 25 participants from the general population of each country/region. Qualitative data were analyzed using a content analysis approach. The selection of items was determined based on interview surveys and team member discussions. The description of items was considered based on a detailed qualitative analysis of the interview survey., Results: A new region-specific PBM-the Asia PBM 7 dimensions instrument-was designed. It reflects East and Southeast Asian values and comprises 7 items: pain, mental health, energy, mobility, work/school, interpersonal interactions, and burden to others., Conclusions: The new region-specific instrument is one of the first PBMs developed in the context of non-Western countries. The Asia PBM 7 dimensions contains 7 items that address the core concepts of health-related quality of life that are deemed important based on East and Southeast Asian health concepts., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Medial meniscus posterior root tears (MMPRTs) can result in the development of osteoarthritis or osteonecrosis. Clinical experience suggests that symptoms such as dull pain or discomfort in the popliteal area or the calf area, which are sometimes misdiagnosed as sciatic nerve pain, may precede impending rupture. We found that bone marrow edema emanating from the meniscal root on magnetic resonance imaging (MRI) scans-spreading roots sign-may indicate the preliminary stage of an MMPRT. The purpose of this study was to evaluate the efficacy of the spreading roots sign as an MMPRT-predictor., Methods: In a retrospective study, we reviewed the chart data and MRI results of patients who had required surgery for an acute MMPRT. We grouped patients by whether or not they had reported the above-mentioned precursory symptoms prior to acute rupture (precursory symptom group/non-precursor group), and when possible, we examined MRI scans to identify with which events the appearance/disappearance of the spreading roots sign coincided. Sex, age, body mass index, bone mineral density, radiological parameters, and MRI parameters were compared between groups., Results: Data from 24 patients (precursory symptom group, n = 17 [70.8 %]; non-precursor group, n = 7 [29.2 %]) were included; data from 5 patients included MRI scans prior to acute rupture. There were no significant differences between precursory symptom and non-precursor groups, except for the ratio of the presence of the spreading roots sign (p = 0.005). The appearance of the spreading roots sign on MRI scans coincided with the onset of precursory symptoms, and its disappearance coincided with acute rupture and the appearance of other MRI signs typical of MMPRT (white meniscus/truncation/meniscal extrusion/giraffe neck signs)., Conclusions: Our findings suggest that the spreading roots sign can be used as a unique precursory sign for MMPRT., Competing Interests: Declaration of competing interest Dr. Ryuichi Nakamura has a consultancy with Olympus Terumo Biomaterials. All other authors have no conflicts of interest relevant to this article to declare., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: We previously reported that early alendronate administration accelerated bone formation and improved the quality of repaired cartilage in the donor site in rabbits. To investigate whether alendronate administration has effects in humans similar to those observed in rabbits., Methods: The study cohort included 35 patients over the age of 12-years old who underwent mosaicplasty without osteoporotic therapy from March 2011 to October 2012. The donor sites were medial or lateral in the patellofemoral joint. Placebo (P) or Bonalon containing 35 mg of alendronate (A) was administered orally every week for 8 weeks. The cohort comprised 15 male and 20 female, including 14 right and 21 left knees. The mean age at the time of surgery was 57.1 years. Bone formation was examined using computer tomography and lateral knee radiography, and cartilage formation was examined using magnetic resonance imaging (MRI), second-look assessment, and intraoperative acoustic evaluation. The clinical outcomes were assessed using the Japanese Orthopaedic Association knee score and visual analog scale (VAS). Bone and cartilage formation in the donor site and clinical outcomes were assessed at 3, 6, and 12 months after mosaicplasty., Results: The ratio of TRAP-5b in group A was significantly smaller than that in group P at 2 and 8 weeks after mosaicplasty. The extent of bone formation in the donor sites in group A was significantly greater than that in group P at 3 and 6 months after mosaicplasty. Cartilage formation did not differ significantly between the two groups as determined by MRI, macroscopic assessment, and intraoperative acoustic evaluation. Clinical outcomes did not differ significantly between the two groups, and no negative clinical outcomes were observed., Conclusion: Early alendronate administration accelerated bone formation but not cartilage formation in the mosaicplasty donor site in humans., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier B.V.)

SQSTM1/p62, hereinafter referred to as p62, is a stress-induced cellular protein that interacts with various signaling proteins as well as ubiquitinated proteins to regulate a variety of cellular functions and cell survival. Methylmercury (MeHg) exposure increases the levels of p62, the latter playing a protective role in MeHg-induced toxicity. However, the underlying mechanism by which p62 alleviates MeHg toxicity remains poorly understood. Herein, we report the interaction of p62 with neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), a HECT E3 ubiquitin ligase. The region of p62 where NEDD4 binds is located at the proline- and arginine (PR)-rich region (amino acids: 102-119), C-terminal extension of the Phox and Bem1 (PB1) domain. To evaluate the importance of the p62-NEDD4 complex, we examined the compensation of deletion mutant (GFP-Δ102-119 p62) for the lack of endogenous p62 in MEFs. GFP-p62/p62KO cells exhibited significantly higher cell viability than GFP-Δ102-119 p62/p62KO cells after treatment with MeHg. Our findings suggest novel mechanisms to alleviate MeHg toxicity through p62-NEDD4 complex formation., Competing Interests: Declaration of competing interest The authors 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 © 2022 Elsevier Inc. All rights reserved.)

DNAJC7 has recently been identified as an amyotrophic lateral sclerosis (ALS) gene via large-scale exome analysis, and its involvement in ALS is still unclear in various populations. This study aimed to determine the frequencies and characteristics of the DNAJC7 variants in a Japanese ALS cohort. A total of 807 unrelated Japanese patients with sporadic ALS were screened via exome analysis. In total, we detected six rare missense variants and one splice-site variant of the DNAJC7 gene, which are not reported in the Japanese public database. Furthermore, the missense variants are located around the TPR domain, which is important for the function of DNAJC7. The total frequency of the DNAJC7 variants in Japanese ALS patients was estimated at 0.87%. Collectively, these results suggest that variants of DNAJC7 are rare cause of Japanese patients with sporadic ALS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Biplanar open wedge high tibial osteotomy (OWHTO) has become common since the introduction of OWHTO-specific plates. However, the management of soft tissues, including skin, the pes anserinus, and the superficial medial collateral ligament (sMCL) release vary among surgeons. We introduce an OWHTO methodology that avoids pes incision and repair, uses bone substitute insertion into the opening gap and includes management of soft tissues to minimize complications. We adopted a reversed curved oblique incision to reduce the risk of saphenous nerve injury. We avoided pes incision, taking advantage of its posterior component force to allow it to function as a compressor of the ascending osteotomy site. The proximal component force of the pes provides compression between the bone substitute insertions and the proximal/distal cortices. This allows postoperative weight bearing to be distributed to the substitute, which may reduce the risk of implant failure. The sMCL is detached from the distal tibial attachment without cutting, enabling its return to its original position underneath the pes and to be repaired. This sMCL release with complete pes preservation may reduce the risk of deep infection or medial laxity during total knee arthroplasty conversion, and further reduce the risks of OWHTO., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier.)