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Background: N-Glycan branching modulates the diversity of protein functions. β1,4-N-acetylglucosaminyltransferase III (GnT-III or MGAT3) produces a unique GlcNAc branch, "bisecting GlcNAc", in N-glycans, and is involved in Alzheimer's disease and cancer. However, the 3D structure and catalytic mechanism of GnT-III are unclear. According to AlphaFold-based structure prediction, GnT-III likely contains two putative disordered segments, a long middle loop (Loop) and a C-terminal tail (Tail). We hypothesized that these segments play important roles in regulating the activity or intracellular behaviors of GnT-III., Methods: We expressed wild-type GnT-III (GnT-III-WT), GnT-III-Loop- and -Tail-deletion mutants in cells. Their in vitro catalytic activity and glycan biosynthesis in cells were examined using high-performance liquid chromatography, UDP-Glo glycosyltransferase assays, and glycomic analysis. Subcellular localization of WT and GnT-III mutants was investigated by immunostaining, and degradation rate and secretion were also examined., Results: The Loop-deletion mutant had higher in vitro and in cellulo activity than GnT-III-WT, indicating that Loop suppresses catalytic activity. In contrast, the Tail-deletion mutant showed weaker activity, increased ER localization, and faster degradation than GnT-III-WT, indicating that Tail is required for proper folding. In addition, deletion of Loop led to aberrant shedding of GnT-III, indicating that Loop contains the cleavage site or regulates GnT-III shedding., Conclusions: Loop and Tail of GnT-III play important roles in catalytic activity, folding and shedding., General Significance: Our results provide further understanding of the catalysis and shedding mechanisms of GnT-III and can help in the development of methods for modifying the levels of bisecting GlcNAc on glycoproteins and in cells., 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.)

Gold nanorods (GNR) produce heat upon irradiation with near-infrared light, enabling a tumor-targeted photothermal therapy. In this study, we prepared GNR coated with sulfated hyaluronic acid (sHA) with a binding affinity for CD44 via electrostatic interactions to deliver GNR to tumors efficiently and stably, and evaluated their usefulness for photothermal therapy. Cationic GNR modified with trimethylammonium groups electrostatically interacted with native HA or sHA with varying degrees of sulfation to form complexes. While GNR/HA was unstable in saline, GNR/sHA maintained the absorbance peak in the near-infrared region, particularly for GNR/sHA with higher degrees of sulfation. GNR/sHA exhibited an intense photothermal effect upon irradiation with near-infrared light. Furthermore, in vitro and in vivo studies revealed that GNR coated with sHA containing approximately 1.2 sulfated groups per HA unit could accumulate in CD44-positive tumors via an HA-specific pathway. These findings indicate the effectiveness of GNR/sHA as a tumor-targeted photothermal therapeutic agent., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The β1,6-GlcNAc branch in N-glycans, produced by a glycosyltransferase N-acetylglucosaminyltransferase V (GnT-V or MGAT5), is associated with cancer and autoimmune diseases., Scope: Here, we summarize the structure and activity regulation of GnT-V. We also describe the roles of the β1,6-GlcNAc branch on glycoproteins in cells and the phenotypes of Mgat5-deficient mice, focusing on cancer and the immune system., Major Conclusions: GnT-V has a unique structure for substrate recognition, and its activity and function are regulated by shedding. The glycans produced by GnT-V play pivotal roles in the differentiation of neural cells, cancer malignancy and immunotherapy, and the development of autoimmune diseases by regulating the functions and cell surface residency of glycoproteins., General Significance: Controlling the expression or activity of GnT-V could be a therapeutic option against cancer and autoimmune diseases. Future work should clarify how GnT-V selectively modifies the specific glycoproteins or N-glycosylation sites in vivo., 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.)

N-Glycan branching critically regulates glycoprotein functions and is involved in various diseases. Among the glycosyltransferases involved in N-glycan branching is the human N-acetylglucosaminyltransferase-IV (GnT-IV) family, which has four members: GnT-IVa, GnT-IVb, GnT-IVc, and GnT-IVd. GnT-IVa and GnT-IVb have glycosyltransferase activity that generates the type-2 diabetes-related β1,4-GlcNAc branch on the α1,3-Man arm of N-glycans, whereas GnT-IVc and GnT-IVd do not. Recently, this enzyme family was found to have a unique lectin domain in the C-terminal region, which is essential for enzyme activity toward glycoprotein substrates but not toward free N-glycans. Furthermore, interaction between the lectin domain of GnT-IV and N-glycan attached to GnT-IV enables self-regulation of GnT-IV activity, indicating that the lectin domain plays a unique and pivotal role in the regulation of GnT-IV activity. In this review, we summarize the GnT-IV family's biological functions, selectivity for glycoprotein substrates, and regulation of enzymatic activity, with a focus on its unique C-terminal lectin domain., 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 Ltd. All rights reserved.)

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the alimentary tract. The prognosis depends on the primary site, and small intestinal GISTs have a worse prognosis than gastric GISTs. Molecularly targeted drugs to inhibit tyrosine kinase activity of KIT were used for unresectable or recurrent GISTs. However, secondary resistance to the drugs is often acquired, and treatments based on other mechanisms are needed. Previously, we reported that cell adhesion molecule 1 (CADM1) was highly expressed in most of small intestinal GISTs but not in most of gastric GISTs. In the present study, we examined whether the antibody-drug conjugate (ADC) with anti-CADM1 antibody and monomethyl auristatin E (anti-CAD-ADC) shows anti-tumor effect on CADM1-expressing human GIST cells. The ADC adhibited in this study was previously used for CADM1-expressing human mesothelioma cells and showed anti-tumor effect for them in vitro. GIST-T1 cell line of gastric origin which scarcely expresses CADM1 and GIST-T1 cells transfected with CADM1 cDNA (GIST-T1-CAD cells) which highly expresses CADM1 and represents small intestinal GIST were used. In vitro, anti-CAD-ADC showed remarkable cytotoxic activity on GIST-T1-CAD cells, but control ADC did not. Both anti-CAD-ADC and control ADC did not show anti-tumor effect on original GIST-T1 cells. When GIST-T1-CAD cells were subcutaneously injected to the nude mice, intravenous administration of anti-CAD-ADC showed inhibitory effect for tumor enlargement. Tumor of GIST-T1 cells grew even after anti-CAD-ADC injection. When GIST-T1-CAD cells were injected into peritoneal cavity of the SCID mice, intraperitoneal administration of anti-CAD-ADC showed reduction of the peritoneal tumor. On the other hand, peritoneal tumor grew after control ADC administration. Tissue and organ damage due to administration of anti-CAD-ADC was not apparent by macroscopic and histological examinations in mice. These results indicate that anti-CAD-ADC could have apparent anti-tumor effect on CADM1-expressing human GIST cells both in in vitro and in vivo mouse models., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This case report presents CT-guided transperineal biopsy as an alternative method for diagnosis of prostate cancer in a patient with anorectal stenosis. A 69-year-old male had a history of anorectal surgeries. Conventional transrectal biopsy was unfeasible due to anorectal stenosis. The CT-guided transperineal biopsy was successfully performed using a cranio-caudal puncture technique, revealing adenocarcinoma. After the biopsy, the patient received appropriate hormone therapy and radiation therapy. This case report highlights the feasibility and safety of CT-guided transperineal biopsy for the patients with anorectal complications., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: The diagnostic criteria for respiratory sarcopenia have been recently reported. However, no studies have clarified the characteristics of skeletal muscle impairment of the limbs in subjects with respiratory sarcopenia. This study aimed to explore the factors, including skeletal muscle, associated with probable respiratory sarcopenia in elderly subjects., Methods: Subjects were classified into the probable respiratory sarcopenia group and nonrespiratory sarcopenia group. Probable respiratory sarcopenia was defined as the concurrent presence of respiratory muscle weakness (as less than the predicted value calculated from age, sex, and height) and low skeletal muscle mass (<7.0 kg/m 2 in males and 5.7 kg/m 2 in females). The following factors were measured: respiratory muscle strength, skeletal muscle mass index, muscle thickness and echo intensity of the rectus femoris, extracellular-to-intracellular water ratio, hand grip strength, 5 sit-to-stand, knee extension strength, bone mineral density, age, sex, body mass index, degree of frailty, presence or absence of medical history, presence or absence of habitual exercise, period of time since the start of exercise, and number of hours of exercise at a time. The association subjects with probable respiratory sarcopenia were analyzed using hierarchical logistic regression analysis., Results: Twenty-six with probable respiratory sarcopenia and 54 with nonrespiratory sarcopenia were included. Hierarchical logistic regression analysis revealed that echo intensity was a significant predictor of probable respiratory sarcopenia. The odds ratio for echo intensity was 2.54 (95% confidence interval: 1.04-6.23)., Conclusions: Our results suggest that a decrease in muscle quality in the lower extremity is associated with probable respiratory sarcopenia., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Purpose: We aimed to investigate the relationship between quantitative evaluation by compositional MRI, including T1ρ, and histological and macroscopic assessments, to verify the validity of compositional MRI, and examine the relationship between compositional MRI evaluation reconstructed in three dimensions (3D) and histological and visual assessments., Method: Twenty-seven patients with knee osteoarthritis underwent T1ρ and T2 magnetic resonance imaging (MRI). Histological and gross tissue evaluations were performed on the excised bone sections of total knee arthroplasty. Semi-quantitative histological evaluation of tissue changes were assessed by measuring the optical density of digitally captured safranin O-stained and Collagen type II antibody-stained paraffin sections. Macroscopic cartilage severity was determined on a 5-grade scale (G0-G5). T1ρ and T2 values (3D and 2D), and their correlation with each of these parameters were investigated., Results: 3D T1 ρ is negatively correlated with histological evaluations and positively correlated with visual assessments. Only 3D T1ρ values correlated with histological quantitative evaluation (Safranin-O staining; r = -0.53, P = 0.014, Collagen type II antibody staining; r = -0.60, P = 0.019). 2D T1ρ and 3D, 2D T2 values did not correlate with histological evaluation results. Macroscopic cartilage severity grade correlated with all T1ρ and T2 values (3D T1ρ; r = 0.61, P < 0.001, 2D T1ρ; r = 0.52, P < 0.001, 3D T2; r = 0.33, P = 0.045, 2D T2; r = 0.41, P = 0.01)., Conclusions: 3D T1ρ mapping reflects the changes in the molecular structure of the cartilage matrix that occur in arthropathic changes and may be an effective tool for detecting cartilage degeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC., Methods: We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab. Radiological tumor burden was represented by baseline tumor size (BTS) and baseline tumor number (BTN). Optimal cut-off value of BTS was determined as 50 mm using the Youden index (small BTS: n = 194, large BTS: n = 114). Overall (OS), cancer-specific (CSS), progression-free survival (PFS), and objective response rate (ORR) were compared. Non-linear associations between BTS and OS and CSS were evaluated using restricted cubic splines., Results: Patients with large BTS were less likely to have undergone the surgical resection of the primary tumor (P = 0.01), and more likely to have liver metastasis (P < 0.001) and more metastatic lesions (P < 0.001). On multivariable analyses controlling for the effects of confounders (resection of primary tumor, metastatic site, number of metastases and lactate dehydrogenase level), large BTS and high BTN were independently associated with worse OS (HR 1.52; P = 0.015, and HR 1.69; P = 0.018, respectively) and CSS (HR 1.59; P = 0.01, and HR 1.66; P = 0.031, respectively), but not PFS. Restricted cubic splines revealed BTS was correlated with OS and CSS in linear relationships. Additionally, large BTS was significantly predictive of lower ORR and complete response rate on univariable analyses (P = 0.041 and P = 0.032, respectively), but its association disappeared on multivariable analyses., Conclusion: Radiological tumor burden has independent prognostic value with a linear relationship in pembrolizumab-treated patients with mUC and might help drive the earlier introduction of second-line pembrolizumab and/or switching to subsequent therapies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bacterial co-infection has been reported to contribute to a poor prognosis in patients with COVID-19. However, iliopsoas abscess (IPA) has not been previously reported as a comorbidity during the course of COVID-19. We report two cases of IPA in patients with COVID-19 pneumonia. Both patients required prolonged immunosuppressive therapy for COVID-19 pneumonia and developed bacteremia due to Serratia marcescens in one and Staphylococcus aureus in the other. Although immunosuppressive therapy is commonly used for COVID-19 pneumonia with hypoxemia, the comorbidity of IPA may have been underestimated in these cases., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

A 70-year-old man with supraglottic carcinoma underwent computed tomography (CT) for staging purposes. A tumor measuring approximately 7 × 10 cm was found incidentally in the left perirenal space. The tumor showed homogeneous high signal intensity on chemical shift subtraction magnetic resonance imaging (CSS-MRI) suggesting the presence of minimal amounts of fat. Five months later, the tumor had grown to approximately 10 × 12 cm with indistinct margins. CSS-MRI showed high signal intensity in the tumor periphery only. The tumor was resected and the pathological diagnosis was angiosarcoma. Angiosarcomas are malignant endothelial vascular neoplasms that are highly invasive to their surroundings. Here we report a case of primary perirenal angiosarcoma that was difficult to differentiate from a dedifferentiated liposarcoma. On CSS-MRI, high signal intensity within a tumor may be a characteristic feature of primary perirenal angiosarcoma., (© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Macrophage infiltration is a characteristic feature of atherosclerotic plaque progression. Since liposomes containing 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) are efficiently phagocytosed by macrophages, we deduced that radiolabeled liposomes containing DSPG could potentially be used for nuclear imaging of vulnerable atherosclerotic plaques. Indium-111 ( 111 In)-labeled liposomes containing different ratios of DSPG were developed with a high labeling efficiency. 111 In-labeled liposomes with higher DSPG content showed higher uptake by macrophage-like RAW264 cells. A biodistribution study demonstrated rapid blood clearance and selective accumulation in the liver and spleen, especially in normal mice injected with 111 In-labeled liposomes with higher DSPG content. Accumulation in atherosclerotic plaques was evaluated using 111 In-labeled DSPG liposomes, which had the highest DSPG content among the studied liposomes. 111 In-labeled DSPG liposomes accumulated in the plaques and the radioactive regions were mostly consistent with the distribution of macrophages. The target-to-non-target ratio of 111 In-labeled DSPG liposomes was higher than that of 111 In-labeled control liposomes without DSPG. These results suggest that 111 In-labeled liposomes containing DSPG are useful for nuclear medical diagnosis of atherosclerotic plaques., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

In this paper, we address the swing-down control of the Acrobot, a two-link planar robot operating in a vertical plane with only the second joint being actuated. The control objective is to rapidly stabilize the Acrobot around the downward equilibrium point, with both links in the downward position, from almost all initial states. Under the conditions of no friction and measurability of only the angle and angular velocity of the actuated joint, we present a sinusoidal-derivative (SD) controller. This controller consists of a linear feedback of the sinusoidal function of the angle of the actuated joint and a linear feedback of its angular velocity. We prove that the control objective is achieved if the sinusoidal gain is greater than a negative constant and the derivative gain is positive. We establish crucial relationships between the relative stability of the Acrobot under the SD controller and its physical parameters, presenting analytically all optimal control gains. These gains minimize the real parts of the dominant poles of the linearized model of the resulting closed-loop system around the downward equilibrium point. We demonstrate that the resulting dominant closed-loop poles can be double complex conjugate poles, or a quadruple real pole, or a triple real pole, depending on the Acrobot's physical parameters. Simulation studies indicate that the proposed SD controller outperforms the derivative (D) controller in rapidly stabilizing the Acrobot at the downward equilibrium point., 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 ISA. Published by Elsevier Ltd. All rights reserved.)

Objective: In elderly populations, the enlargement of the perivascular space is related to small vessel disease and the glymphatic system. Enlarged perivascular spaces (EPVS) in the basal ganglia (EPVS-BG) and EPVS in the centrum semiovale (EPVS-CSO) are associated with different pathophysiological processes. However, the prevalence of EPVS and the factors associated with EPVS location in healthy middle-aged individuals are still unclear. We aimed to determine the prevalence of EPVS and the factors associated with EPVS location among healthy individuals in their 40 s METHODS: This study included 5000 consecutive healthy individuals who underwent screening for brain diseases in Japan from August to December 2018. Of them, the data of individuals in their 40 s were extracted and analyzed. The associations of age, sex, body mass index, smoking and drinking history, and medical history with EPVS location were investigated. Similar analyses were performed for the other age groups. A literature review on the factors associated with EPVS location was also performed., Results: A total of 1720 individuals in their 40 s were finally included. The prevalence of EPVS-BG and EPVS-CSO was 7.7% and 9.2%, respectively. Age (years), smoking history, and hypertension were associated with EPVS-BG; none of the studied factors were found to be associated with EPVS-CSO. In the elderly, the factors previously reported to be associated with EPVS-BG included atherosclerosis change, while the factors associated with EPVS-CSO were cerebral amyloid angiopathy-related formation., Conclusion: Both EPVS-BG and EPVS-CSO occurred among healthy individuals in their 40 s, but they did so rarely, and less prevalently than in older age groups. EPVS-BG and EPVS-CSO may represent early imaging signs of the atherosclerotic and cerebral amyloid angiopathy processes, respectively., Data Availability: The anonymized data for this study will be shared upon any qualified investigator's request to the corresponding author. Primary data from this study will be made available upon reasonable request in accordance with the review board of the research institute., Competing Interests: Declaration of Competing Interest Dr. Kitamura receives personal fees from Medical Network Systems, MNES Inc., related to this work. Mr. Tomoaki Hamano, as the CEO of SmartScan, Inc., receives officers' remuneration from SmartScan, Inc., and holds more than 5% of SmartScan shares. All the other authors report that they have no conflict of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The messenger RNA vaccine against SARS-CoV-2 is effective at preventing COVID-19-associated hospitalization, and the Centers for Disease Control and Prevention has recommended vaccination for all eligible individuals. We demonstrate a case involving a patient who developed a life-threatening acute asthma exacerbation after receiving their third dose of the BNT16b2 vaccine. Because eosinophilia was observed after the second inoculation, it was considered likely that the patient had been sensitized to the BNT16b2 vaccine. Theoretically, the SARS-CoV-2 vaccine could trigger the exacerbation of asthma. It should be recognized that repeated SARS-CoV-2 vaccination may be a risk factor for the acute exacerbation of asthma., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Cluster of differentiation 81 (CD81) is a tetraspanin membrane protein consisting of 4 transmembrane domains and 2 outer membrane loops. CD81 inhibition is a potential treatment for rheumatoid arthritis (RA). Here, we investigated the therapeutic effects of the cytoplasmic RNA vector expressing anti-CD81 antibodies (the anti-CD81 vector) on the ankle joint synovium in collagen-induced arthritis (CIA) rats., Methods: Body weight, paw volume, and clinical scores were measured on days 0, 7, and 10 and daily thereafter. On day 28, the ankle joints of the rats were removed and stained with haematoxylin, eosin, and Safranin O. Arthritic changes such as inflammatory cell infiltration, synovial proliferation, articular cartilage destruction, and bone erosion were evaluated by histological scoring., Results: Symptom onset was delayed in the right lower limbs of the rats administered the cytoplasmic RNA vector (CIA + anti-CD81) compared with that in the control group (CIA + control). The CIA + anti-CD81 rats were heavier than the CIA + control rats. The paw volume and clinical scores were significantly lower in the CIA + anti-CD81 than in the CIA + control. The histological scores indicated significantly milder manifestations of RA in the CIA + anti-CD81 than in the CIA + control., Conclusions: Administration of the cytoplasmic RNA vector expressing anti-CD81 antibodies suppressed arthritis and joint destruction in CIA rats. Our findings suggest that the cytoplasmic RNA vector can be used to treat RA., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Recently, switch maintenance with avelumab has been approved for the treatment of advanced or metastatic urothelial carcinoma (UC), with no progression after four to six cycles of first-line platinum-based chemotherapy. However, the optimal number of cycles of platinum-based chemotherapy has not been determined., Objective: To analyze the clinical characteristics of patients with advanced UC who were treated with platinum-based chemotherapy and investigate the association between the number of cycles of the treatment and the patients' overall survival., Methods: A total of 124 patients with advanced UC who were treated with first-line platinum-based chemotherapy at Osaka City University Hospital between April 2009 and January 2020 were retrospectively reviewed., Results: Of the 124 patients, clinical information regarding overall survival was available for 115 patients. The median age was 72 years (range, 43-95 years). Only 59 patients (51.3 %) were treated with gemcitabine and cisplatin, and 52 patients (45.2 %) were treated with gemcitabine and carboplatin. The median number of cycles was three (1-8), and the percentage of patients who discontinued chemotherapy due to progressive disease was 80.3%, 64.0%, and 86.4% in those receiving one to three, four, and five or more cycles, respectively. Moreover, no difference in overall survival was observed between patients who received four cycles and those who received five or more cycles at both univariate and multivariate levels., Conclusions: The present study shows that five or more cycles of first-line platinum-based chemotherapy did not prolong overall survival compared with four cycles, suggesting that four cycles of chemotherapy might be sufficient, considering the new treatment strategy involving switch maintenance with avelumab., Competing Interests: Conflict of interest The authors have no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: We developed a laboratory test-based regression model for early detection of hepatocellular carcinoma (HCC) associated with HCV in its surveillance., Methods: This matched case-control study was conducted by enrolling 452 patients with chronic hepatitis and/or cirrhosis, including 129 patients complicated with HCC. One-to-one propensity score matching was performed by referring to sex, age, and fibrosis-4 index, which resulted in 102 patients each in HCC and non-HCC groups. Logistic regression models (LRM) for distinguishing the two groups were explored from variable combinations of laboratory tests. The model was validated by our new scheme of applying it retroactively to trimonthly previous datasets., Results: Models with a practical level of diagnostic accuracy (C-statistic) were α-fetoprotein (AFP) alone (0.810), LRM3 comprising AFP, AST, and ALT (0.850), and LRM4 comprising AFP, AFP/(AST × ALT), and AST (0.862). After retroactive application of each model, LRM4 showed the highest distinction of the two groups at -12M, -6M, -3M with C-statistics of 0.654, 0.786, 0.834, respectively. LRM4 was accurate even after limiting cases to early-stage HCC., Conclusions: LRM4 was proved useful in prompting clinicians to perform timely image study in the surveillance. The retroactive validation scheme is applicable to assess diagnostic models of other neoplastic diseases., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The application of gold nanorods (GNRs) in photothermal therapy is a promising avenue for cancer treatment. The aim of this study was to develop a GNR-based targeted photothermal therapy for melanoma., Methods: We utilized the electrostatic interaction between cationic GNRs and an anionic polymer chondroitin sulfate A (CSA), which has an affinity for binding to melanoma cells, to construct an anionic binary GNR-CSA complex (GNR-CS) at an optimal theoretical charge ratio of the trimethylammonium groups of GNR: carboxyl and sulfate groups of CSA = 1:2.5. The cytotoxicity to normal cells and erythrocyte agglutination activity of GNR-CS were evaluated. After the cellular uptake of GNR-CS by melanoma cells (B16-F10) was investigated, the photothermal performance of GNR-CS against B16-F10 cells was evaluated in vitro., Results: The particle size and zeta potential of GNR-CS were approximately 35 nm and -20 mV, respectively. GNR-CS showed little cytotoxicity to normal cells and low erythrocyte agglutination activity, indicating good biocompatibility. Compared with negatively-charged GNR, GNR-CS was highly taken up by B16-F10 cells even if it was negatively charged. Cellular uptake was significantly suppressed upon treatment with excess CSA, suggesting the involvement of a CSA-specific uptake pathway. Furthermore, irradiation of the GNR-CS solution with near-infrared (NIR) light increased its temperature in light-intensity and GNR-concentration dependent manners. GNR-CS exhibited significant and GNR-dose dependent cytotoxicity in melanoma cells in combination with NIR light irradiation., Conclusion: GNRs coated with CSA have the potential as a medicine in targeted photothermal therapy for melanoma., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The EGFR-A763&#95;Y764insFQEA is a unique mutation among EGFR exon 20 insertion mutations in that it is associated with sensitivity to conventional EGFR-tyrosine kinase inhibitors. This mutation, which was not initially covered by conventional reverse transcription polymerase chain reaction (RT-PCR) genotyping method, has only been detected in clinical practice when a next-generation sequencing (NGS)-based cancer panel is implemented. We present the case of a female patient with recurrent lung adenocarcinoma from a lung tumor resected 10 years earlier. Sequential single-gene investigations and the OncomineTM Comprehensive Assay (ver.3) analysis of the recurrent tumor did not reveal any targetable driver mutations. However, the second NGS analysis with the OncoGuideTM NCC oncopanel found the EGFR-A763&#95;Y764insFQEA mutation after tumor progression with carcinomatous lymphangiomatosis and multiple brain metastases. Osimertinib treatment improved her condition immediately. The identical EGFR-A763&#95;Y764insFQEA mutation was detected in the tumor resected 10 years earlier. Based on this common mutation the patient was diagnosed with late recurrence of lung cancer harboring the EGFR-A763&#95;Y764insFQEA mutation. The OncoGuideTM NCC oncopanel covered whole exons of the EGFR gene and was able to detect this mutation. In the present clinical practice, the EGFR-A763&#95;Y764insFQEA mutation is the only treatable mutation among EGFR Ex.20 insertion mutations. We need to understand the gene mutation profile identified by each panel and consider reexamining them for this mutation., (Copyright © 2021. Published by Elsevier Inc.)

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound, which was then radiolabeled with fluorine-18 via a facile S N Ar reaction to form 2-[ 18 F]fluoropyridine scaffold. Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [ 18 F] 14 (also named as [ 18 F]MAGL-1902). This work may serve as a roadmap for clinical translation and further design of potent 18 F-labeled MAGL PET tracers., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Background & Aims: Chronic liver diseases, including hepatocellular carcinoma (HCC), lead to an imbalance in energy metabolism. The non-protein respiratory quotient (npRQ), which estimates energy malnutrition, can be evaluated using an indirect calorimeter; however, npRQ measurement is limited in routine work. This study aimed to investigate the relationship between the albumin-bilirubin (ALBI) score and npRQ in patients with HCC., Methods: We conducted a retrospective cohort study in 109 patients with HCC who underwent indirect calorimetry and then compared the npRQ with various clinical parameters, including liver function and tumor factors., Results: The median npRQ was 0.82. A significant negative correlation was found between the npRQ and the ALBI score (r = -0.35, p < 0.001). The median npRQ in modified ALBI (mALBI) grades 1, 2a, 2b, and 3 were 0.84, 0.86, 0.81, and 0.79, respectively (grade 2a vs. 2b, p = 0.002). Factors associated with npRQ <0.85, which is reported to be the best cutoff value for energy malnutrition, were analyzed. On multivariate analysis, the ALBI score (cutoff value, -2.18) was the only significant independent factor (odds ratio, 7.65; p < 0.001). The proportion of HCC patients with npRQ <0.85 significantly increased among patients with an ALBI score ≥-2.18 (45/51, 88.2%) compared with those with an ALBI score <-2.18 (29/58, 50%) (p < 0.001)., Conclusions: The ALBI score might be a useful predictor for energy malnutrition in patients with HCC. In addition, most HCC patients with mALBI grade 2b or 3 can be considered to have energy malnutrition., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

There has been no report on the prevalence of Campylobacter spp. in farm animals in Mongolia. To uncover the prevalence of Campylobacter spp. in chickens in Mongolia and their antimicrobial resistance, in this study, we isolated and characterized Campylobacter spp. from chickens in Mongolia. We collected 71 cloacal swabs of chickens from 5 farms including 4 layer farms and one broiler farm near Ulaanbaatar city and isolated 25 Campylobacter jejuni and 6 Campylobacter coli isolates. All isolates were resistant to tetracycline, and 3 C. coli isolates were resistant to erythromycin. The C. coli isolates possessed either the erm(B) gene or nucleotide substitution at nt 2,075 of 23S rDNA, both of which are known to be associated with erythromycin resistance. Sixteen of the 31 C. jejuni/C. coli isolates (51.6%) were resistant to nalidixic acid and fluoroquinolones. All the fluoroquinolone-resistant isolates possessed amino acid substitution from threonine to isoleucine at codon 86 (nucleotide substitution: ACA to ATA). Multilocus sequence typing and phylogenetic analyses showed a variation in C. jejuni/C. coli in chickens in Mongolia. In addition, some of the C. jejuni isolates seemed to be phylogenetically close to isolates in Asian and Oceanian countries. This is the first report on the characterization of antimicrobial resistance of Campylobacter spp. in farm animals in Mongolia and is valuable for implementation of measures for a prudent use of antimicrobials in farm animals., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the clinical significance of the effect of age on disease control in men who received high-dose intensity-modulated radiation therapy (IMRT) for nonmetastatic prostate cancer (NMPCa)., Methods: NMPCa patients with favorable intermediate to very high-risk features (National Comprehensive Cancer Network risk classification) treated with IMRT at our institution between September 2000 and May 2011 were analyzed retrospectively. Treatment consisted of high-dose IMRT (74-78 Gy/37-39 fractions) combined with 6 months of neoadjuvant hormonal therapy. Multivariable analysis using Fine and Gray's regression model was performed to evaluate whether age at initiation of IMRT was associated with biochemical failure (BF) and castration-resistant prostate cancer (CRPC) progression., Results: A total of 367 patients were analyzed. The median follow-up period was 8.8 years after IMRT. The 5- and 10-year BF rates were 22.1 and 31.7%, and those of CRPC rates were 4.5 and 12.6%, respectively. Multivariable analysis revealed that a younger age (cut-off: 70 years old) at the initiation of IMRT was significantly correlated with both a higher BF rate (hazard ratio: 1.691, P= 0.0064) and higher CRPC rate (hazard ratio: 2.579, P = 0.0079)., Conclusions: Younger men with NMPCa had increased risks of BF and CRPC after high-dose IMRT, and may benefit from more intensive treatments. Our findings should be further tested in prospective studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The Clinical Practice Guidelines for Osteonecrosis of the Femoral Head (ONFH) 2019 Edition, written by the working group for ONFH guidelines of the Japanese Investigation Committee (JIC) for ONFH under the auspices of the Japanese Ministry of Health, Labour, and Welfare and endorsed by the Japanese Orthopaedic Association, were published in Japanese in October 2019. The objective of this guideline is to provide a support tool for decision-making between doctors and patients., Methods: Procedures for developing this guideline were based on the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014, which proposed an appropriate method for preparing clinical guidelines in Japan., Results: This clinical practice guideline consists of 7 chapters: epidemiology; pathology; diagnosis; conservative therapy; surgical treatment: bone transplantation/cell therapy; surgical treatment: osteotomy; and surgical treatment: hip replacement. Twelve background questions and 13 clinical questions were determined to define the basic features of the disease and to be addressed when deciding treatment in daily practice, respectively., Conclusions: The clinical practice guidelines for the ONFH 2019 edition will be useful for physicians, investigators, and medical staff in clinical practice, as well as for patients, during the decision-making process when defining how to treat ONFH., Competing Interests: Declaration of competing interest Conflicts of interest were confirmed by self-reporting of all co-authors and the members of the working group for ONFH guidelines. No company was directly involved in the guideline recommendations., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Hemolysis is a common problem in the handling of serum specimens. The hemolysis index (HI) provides a warning of hemolysis in auto-analyzers. However, HI has not been standardized, and each laboratory's original method is applied. Especially, the wavelength used for HI measurement is different in each laboratory. Thus, we investigated the warning ability of HI at various wavelengths., Methods: We selected 4 wavelength types, and each HI was measured and calculated (410 nm/HI-1, 451 nm/HI-2, 545 nm/HI-3, and 571 nm/HI-4). To compare the 4 HI types, we investigated the influence of 3 interference components using artificially hemolyzed specimens (AHSs). We also investigated both the relationship between HI and hemoglobin concentration (Hb) and that between HI and 31 biochemical test values in AHSs., Results: In the interference assessment, only HI-4 showed no influence on the 3 interference components. The correlation between Hb and HI-4 was very strong (r S  = 0.9987). A 1-unit increase in HI-4 corresponded to a 14.8-mg/dL increase in Hb., Conclusion: We found the best wavelength for HI to be at or near 571 nm., (Copyright © 2020. Published by Elsevier B.V.)

Background: Serum LacdiNAc-glycosylated prostate-specific antigen (LDN-PSA) and LDN-PSA density together with PSA and PSA density (PSAD) were measured as a diagnostic tool for prostate cancer (PCa)., Patients and Methods: We included 150 patients with PCa without hormonal therapy and 41 patients without PCa obtained from the Kyoto University Hospital between 2012 and 2017. LDN-PSA levels were measured through a WFA-anti-PSA antibody sandwich immunoassay using a highly sensitive surface plasmon field-enhanced fluorescence spectroscopy (SPFS) system. Diagnostic performance of serum LDN-PSA and LDN-PSAD was evaluated by measuring the area under the receiver-operating characteristic curve (AUC)., Results: The AUCs of LDN-PSA, LDN-PSAD, and PSAD levels (0.780, 0.848, and 0.835, respectively) detected in patients with PCa were significantly higher (P = .0001, P < .0001, and P < .0001, respectively) than that of PSA (0.590). Moreover, among 143 patients with PCa who received radical prostatectomy (RP), the AUCs of LDN-PSA, LDN-PSAD, and PSAD levels (0.750, 0.812, and 0.769, respectively) detected in patients with a pathologic Gleason grade group ≥ 2 were significantly higher (P = .0170, P = .0028, and P = .0003, respectively) than that of PSA (0.578). In the group comprising 35 patients who received RP with a Gleason grade group 1-graded biopsy, the LDN-PSA, LDN-PSAD, and PSAD levels were significantly different (P = .0097, P = .0024, and P = .0312, respectively). However, PSA alone could not discriminate cases with adverse features (P = .454)., Conclusions: LDN-PSAD is a potential marker for detecting PCa and selecting candidates for RP., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Cranioplasty is a common procedure in neurosurgery. However, cosmetic and neuroprotective reconstructions are necessary after cranioplasty. Treatment of patients with a meningioma with bone infiltration requires removal of the tumor-infiltrated bone and subsequent cranioplasty. We report an efficient technique for cosmetic and neuroprotective reconstructions using a custom-made ultra-high-molecular-weight polyethylene cranial plate (SKULPIO, Kyocera Medical, Kyoto, Japan) in a single-step surgery involving tumor removal and skull reconstruction., Methods: We present 2 illustrative cases of a 49-year-old female with a right frontal convexity meningioma and 69-year-old male with a bilateral parasagittal atypical meningioma, both involving extensive skull invasion. We preoperatively planned craniotomy size to facilitate the removal of the tumor-infiltrated skull bone using the patients' 3-dimensional cranial models followed by the construction of a custom-made cranial plate. After tumor removal, we drilled out the outer table and the diploe of the cranial edge until the custom-made bone plate accurately fit the bone defect. Finally, the cranial plate was fixed using titanium plates and screws., Results: Postoperative magnetic resonance imaging for each case revealed total meningioma removal and an aesthetically reconstructed skull. Using this technique, precise adjustment of the cranial edge to the plate contributes to a gapless and aesthetic reconstruction. Furthermore, the intact inner table of the skull firmly supports the custom-made bone plate., Conclusions: This technique involving the placement of a custom-made cranial plate during a single-step surgery was found to be efficient for cosmetic and neuroprotective reconstructions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Carboplatin and paclitaxel (CP) had shown moderate efficacy in treating castration-resistant prostate cancer (CRPC) before standard first-line docetaxel chemotherapy became available. Currently, for patients with homology-directed repair gene defects as well as for unselected patients, platinum chemotherapy is administered after all standard treatments have been ineffective. Here, we retrospectively studied the efficacy and safety of CP administered as the first-, second-, and third-line chemotherapy in patients with CRPC., Patients and Methods: A retrospective chart review was performed for 58 patients with CRPC who received CP between 2001 and 2018 in a single institution. Twenty-seven patients received CP as the first-line chemotherapy, 21 as the second-line after docetaxel, and 10 as the third-line after docetaxel and cabazitaxel. Prostate-specific antigen (PSA) responses (> 50% decline of PSA from baseline), progression-free survival, overall survival, and adverse events were examined., Results: PSA responses at any time were 55.6%, 19.0%, and 10.0%; PSA responses at 12 weeks were 48.1%, 14.3%, and 10.0%; the median progression-free survival was 3, 1, and 1 month; and the median overall survival was 19, 11, and 6 months, respectively, for the first-, second-, and third-line settings. The only patient who achieved exceptional and durable PSA response in the third-line setting had a deleterious germline BRCA2 mutation (5645C>A). The adverse event profile was favorable., Conclusion: CP shows moderate efficacy against CRPC in the first-line setting, but shows little effect in the third-line setting. CP after docetaxel and cabazitaxel may be recommended in selected patients with CRPC with homology-directed repair gene defects., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Non-muscle-invasive bladder cancer (NMIBC) can be treated using transurethral resection (TUR), but high incidence of intravesical recurrence remains a clinical challenge. Single immediate postoperative instillation of chemotherapy (IPIOC) is controversial for NMIBC patients with intermediate recurrence risk. The aim of the present study was to report the efficacy and toxicity of IPIOC, particularly in intermediate-risk NMIBC patients, in the real-world setting., Patients and Methods: We retrospectively analyzed 363 consecutive patients with primary NMIBC who underwent radical TUR at Kyoto University Hospital between 2007 and 2016., Results: In low-risk patients, recurrence-free survival (RFS) was significantly better for IPIOC than non-IPIOC (2-year RFS: 89.3% vs. 59.4%; P = .001). In intermediate-risk patients, IPIOC was associated with significantly longer RFS compared with non-IPIOC (2-year RFS: 85.5% vs. 58.2%; P = .011). IPIOC and bacillus Calmette-Guérin (BCG) were independent predictors for post-TUR recurrence (non-IPIOC vs. IPIOC: hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.14-4.88; P = .02; non-BCG vs. BCG: HR, 2.22; P = .045, 95% CI, 1.02-5.30). In the high-risk group, only BCG was an independent prognostic factor of recurrence in a multivariate Cox proportional hazards model (HR, 2.55; P = .006, 95% CI, 1.32-4.87). There were no significant differences between the BCG-only group and the IPIOC with BCG group in Grade 3 or more local (16 patients [21%] vs. 21 patients [24%]; P = .61) or systemic (3 patients [4%] vs. 6 patients [7%]; P = .40) toxicity rates., Conclusion: Our study showed the efficacy of IPIOC for the prevention of intravesical recurrence in primary intermediate-risk NMIBC patients regardless of BCG therapy., (Copyright © 2019. Published by Elsevier Inc.)

Background: Joint-preserving procedures should be considered as much as possible for hip disorders in pediatric and young patients. However, in patients with extensive osteonecrosis (ON) of the femoral head combined with severe collapse and advanced secondary osteoarthritis (OA), the optimal procedure has not been elucidated. This retrospective study aimed to investigate the postoperative outcomes of 11 patients who underwent transtrochanteric rotational osteotomy (TRO) alone or with a combination treatment for various hip disorders in young patients and to evaluate the usefulness of TRO., Methods: Eleven patients (11 hips) with a mean age at operation of 22 years were included. The mean follow-up duration was 9.4 years. Preoperative diagnosis was secondary OA in 6 patients (pigmented villonodular synovitis, 2; after rotational acetabular osteotomy, 1; pyogenic arthritis, 1; femoroacetabular impingement, 1; acetabular dysplasia, 1) and ON in 5 patients (slipped capital femoral epiphysis, 4; femoral neck fracture, 1). Combination treatment was performed in 2 patients with distraction arthroplasty and in 6 patients with intra-articular procedures (mosaicplasty, 1; drilling, 1; microfracture, 4; cam resection, 1). Clinical evaluation was performed by using the Merle d'Aubigne and Postel score (MDPS). Joint congruency and progression of osteoarthritic change in all cases, and progression of collapse in the ON patients were evaluated radiographically., Results: The mean MDPS improved from 10.3 to 14.2 in the OA patients and from 9.4 to 14.8 in the ON patients. The OA grade was maintained or improved in 10 hips (91%). Progressive collapse was prevented in all ON patients, and good remodeling was demonstrated., Conclusion: Even in the highly degenerative cases, TRO enabled repair and prevention of the progression of OA. This procedure might be a useful salvage operation for treating secondary OA and ON of the hip even if the clinical condition is advanced, especially in young patients., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

The recently discovered circular RNAs (circRNAs) are mostly formed by back-splicing where the downstream 5' splice site splices to the upstream 3' splice site by conventional pre-mRNA splicing. These circRNAs regulate gene expression by acting as sponges for micro-RNAs or RNA-binding proteins. Here we show that the NR5A1 (previously called Ad4BP or SF-1) gene which is exclusively expressed in the adrenal cortex and steroidogenic tissue can form atypical circRNAs by unconventional splicing. Two stem loops with inositol-requiring protein-1α (IRE1α) cleavage sites are connected by an IRE1α cleavage site to form a circRNA (circIRE RNA). From total RNA of normal human adrenal cortex, we detected a circIRE RNA with connected ends by IRE1α cleavage sites in exon 6 and exon 1 (circIRE NR5A1 ex6-1 RNA). circIRE NR5A1 ex6-1 RNA was not detected in the adrenocortical cancer cell line, H295R. When IRE1α was expressed in H295R cells a different circIRE NR5A1 RNA connecting IRE1-cleavage sites in exon 7 and exon 1 was detected (circIRE NR5A1 ex7-1 RNA). The expression of this circIRE RNA was inhibited by the IRE1 inhibitor 1, STF-083010, implicating that it was formed via the ER stress pathway, where IRE1α is a major factor. This is the first report of this type of circular RNA connected by IRE1-cleavage sites found to be expressed in mammalian cells in a tissue-specific manner. To our surprise, the concomitant expression of NR5A1 was increased by IRE1α implicating that NR5A1 was not subjected to IRE1-dependent decay of mRNA (RIDD) but rather activating a transcriptional regulatory network to cope with ER stress in steroidogenic tissue reminiscent to XBP1 in other tissue. We believe this is the first report of such tissue-specific transcriptional cascade responding to ER stress as well as the novel finding of circular RNAs connected by IRE1α cleavage sites expressed in mammalian tissue., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: This study sought to compare the procedural outcomes of percutaneous coronary intervention for chronic total occlusion between the periods before and after introduction of 3-dimensional (3D) wiring., Background: Previously, we reported a 3D wiring method by which the operator can construct real-time mental 3D images from 2 perpendicular angles of X-ray system monitor during percutaneous coronary intervention for chronic total occlusion., Methods: A total of 137 chronic total occlusion lesions that could not be passed by tapered soft wires in our hospital between 2012 and 2017 were retrospectively enrolled in the study., Results: Overall success rate was significantly higher in the 3D wiring group (n = 69) than the non-3D wiring group (n = 68) (98% vs. 90%, respectively; p = 0.027). In the primary antegrade cases, the first antegrade approach time was significantly shorter in the 3D wiring group than the non-3D wiring group (42 ± 29 vs. 30 ± 16 min, respectively; p = 0.01). In cases where the antegrade approach was continued throughout the procedure, the success rate was significantly higher in the 3D wiring group than the non-3D wiring group (100% vs. 89.2%, respectively; p = 0.033). Vessel perforation by the antegrade wire tended to be lower in the 3D wiring group than the non-3D wiring group (1% vs. 11%, respectively; p = 0.055)., Conclusions: 3D wiring enables accurate guidewire control, which improves the success rate of antegrade wiring and reduces the antegrade procedure time, resulting in improvement of the overall success rate., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Proteins coating Plasmodium merozoite surface and secreted from its apical organelles are considered as promising vaccine candidates for blood-stage malaria. The rhoptry neck protein 12 of Plasmodium falciparum (PfRON12) was recently reported as a protein specifically expressed in schizonts and localized to the rhoptry neck of merozoites. Here, we assessed its potential as a vaccine candidate. We expressed a recombinant PfRON12 protein by a wheat germ cell-free system to obtain anti-PfRON12 antibody. Immunoblot analysis of schizont lysates detected a single band at approximately 40 kDa under reducing conditions, consistent with the predicted molecular weight. Additionally, anti-PfRON12 antibody recognized a single band around 80 kDa under non-reducing conditions, suggesting native PfRON12 forms a disulfide-bond-mediated multimer. Immunofluorescence assay and immunoelectron microscopy revealed that PfRON12 localized to the rhoptry neck of merozoites in schizonts and to the surface of free merozoites. The biological activity of anti-PfRON12 antibody was tested by in vitro growth inhibition assay (GIA), and the rabbit antibodies significantly inhibited merozoite invasion of erythrocytes. We then investigated whether PfRON12 is immunogenic in P. falciparum-infected individuals. The sera from P. falciparum infected individuals in Thailand and Mali reacted with the recombinant PfRON12. Furthermore, human anti-PfRON12 antibodies affinity-purified from Malian serum samples inhibited merozoite invasion of erythrocytes in vitro. Moreover, pfron12 is highly conserved with only 4 non-synonymous mutations in the coding sequence from approximately 200 isolates deposited in PlasmoDB. These results suggest that PfRON12 might be a potential blood-stage vaccine candidate antigen against P. falciparum., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ventricular septal rupture with ventricular free wall dissection is an extremely rare complication after inferior myocardial infarction, and the optimal surgical strategy remains unclear because of the limited number of survival cases. Electrocardiography-synchronized contrast computed tomography was performed before surgery to identify the dissected area and to set up a surgical strategy. We report on modified double patch repair with ventricular wall dissection exclusion, which might be effective for preventing residual shunt and maintaining cardiac function., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The early detection of Shiga toxin-producing Escherichia coli (STEC) is important for early diagnosis and preventing the spread of STEC. Although the confirmatory test for STEC should be based on the detection of Shiga toxin using molecular analysis, isolation permits additional characterization of STEC using a variety of methods, including O:H serotyping. The conventional slide agglutination O-antigen serogrouping used in many clinical laboratories is laborious and time-consuming. Surface plasmon resonance (SPR)-based immunosensors are commonly used to investigate a large variety of bio-interactions such as antibody/antigen, peptide/antibody, DNA/DNA, and antibody/bacteria interactions. SPR imaging (SPRi) is characterized by multiplexing capabilities for rapidly screening (approximately 100 to several hundred sensorgrams in parallel) molecules. SPRi-based O-antigen serogrouping method for STEC was recently developed by detecting the interactions between O-antigen-specific antibodies and bacterial cells themselves. The aim of this study was to evaluate its performance for E. coli serogrouping using clinical STEC isolates by comparing the results of slide agglutination tests. We tested a total of 188 isolates, including O26, O45, O91, O103, O111, O115, O121, O128, O145, O157, and O159. The overall sensitivity of SPRi-based O-antigen serogrouping was 98.9%. Only two O157 isolates were misidentified as nontypeable and O121. The detection limits of all serotypes were distributed between 1.1 × 10 6 and 17.6 × 10 6  CFU/ml. Pulsed-field gel electrophoresis (PFGE) revealed the heterogeneity of the examined isolates. In conclusion, SPRi is a useful method for the O-antigen serogrouping of STEC isolates, but the further evaluation of non-O157 minor serogroups is needed., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Preconcentration is an effective way to improve analytical sensitivity. Many types of methods are used for enrichment of ionic solute analytes. However, current methods are batchwise and include procedures such as trapping and elution. In this manuscript, we propose in-line electrodialytic enrichment of ionic solutes. The method can enrich ionic solutes within seconds by quantitative transfer of analytes from the sample solution to the acceptor solution under an electric field. Because of quantitative ion transfer, the enrichment factor (the ratio of the concentration in the sample and to that in the obtained acceptor solution) only depends on the flow rate ratio of the sample solution to the acceptor solution. The ratios of the concentrations and flow rates are equal for ratios up to 70, 20, and 70 for the tested ionic solutes of inorganic cations, inorganic anions, and heavy metal ions, respectively. The sensitivity of ionic solute determinations is also improved based on the enrichment factor. The method can also simultaneously achieve matrix isolation and enrichment. The method was successively applied to determine the concentrations of trace amounts of chloroacetic acids in tap water. The regulated concentration levels cannot be determined by conventional high-performance liquid chromatography with ultraviolet detection (HPLC-UV) without enrichment. However, enrichment with the present method is effective for determination of tap water quality by improving the limits of detection of HPLC-UV. The standard addition test with real tap water samples shows good recoveries (94.9-109.6%)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: External beam radiation therapy (EBRT) with short-term androgen deprivation therapy is the standard of care for intermediate-risk prostate cancer patients. However, no study to date has evaluated the hormonal kinetics or sexual and hormonal function recovery after cessation of short-term luteinizing hormone (LH)-releasing hormone (LHRH) antagonist treatment., Patients and Methods: Ten intermediate-risk prostate cancer patients (mean age, 69.9 years) were included. All patients received 4 months of LHRH antagonist (degarelix) treatment followed by EBRT. The testosterone, luteinizing hormone (LH), follicle-stimulating hormone, and prostate-specific antigen levels were measured and Expanded Prostate Cancer Index Composite questionnaires were completed before LHRH antagonist therapy at baseline; 1, 2, 3, and 4 months after the first injection of LHRH antagonist treatment; and every 2 months thereafter until 18 months., Results: The testosterone levels were at the castration level at 1 month after the first LHRH antagonist injection. The median interval to recover a normal testosterone level (> 7.2 nmol/L) was 7 months after the last LHRH antagonist administration. The LH and follicle-stimulating hormone levels decreased but had increased more than twice above baseline at 15 months after the last LHRH antagonist injection. The sexual function and hormonal bother subdomain scores and sexual and hormonal domain scores decreased once after LHRH antagonist treatment but had significantly recovered thereafter (P < .05)., Conclusion: In most patients, the testosterone level had normalized within 9 months after the last LHRH administration. Sexual and hormonal function recovered after short-term LHRH antagonist administration for neoadjuvant therapy before EBRT., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: `The growth hormone secretagogue receptor 1a (GHS-R1a) is the orphan G-protein-coupled receptor, and its endogenous ligand is ghrelin. GHS-R1a contributes to regulation of glucose homeostasis, memory and learning, food addiction, and neuroprotection. Several PET tracers for GHS-R1a have been developed, but none have been reported to be clinically applicable to GHS-R1a imaging. In this study, we developed three new PET tracers for GHS-R1a: 18 F-labeled 6-(4-chlorophenyl)-3-((1-(2-fluoroethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-one (1), 11 C-labeled 6-(4-chlorophenyl)-3-((1-(2-methoxyethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-one (2), and 11 C-labeled (S)-(4-(1H-indole-6-carbonyl)-3-methylpiperazin-1-yl)(4'-methoxy-[1,1'-biphenyl]-4-yl)methanone (3)., Methods: [ 18 F]1 was synthesized by the 18 F-fluoroethylation; [ 11 C]2 or [ 11 C]3 was synthesized by the 11 C-methylation. Biodistribution studies and PET studies were conducted in mice., Results: We successfully radiosynthesized [ 18 F]1, [ 11 C]2, and [ 11 C]3 with appropriate radioactivity for the animal study. In the ex vivo biodistribution study, 60min following injection, the radioactivity level of [ 18 F]1 was relatively high in the small intestine, that of [ 11 C]2 was high in the liver, and that of [ 11 C]3 was high in the pancreas. The radioactivity levels of the three PET tracers were relatively low in the brain. Under pretreatment with YIL781 (a selective and high affinity antagonist for GHS-R1a), the pancreas radioactivity level at 30min following [ 11 C]3 injection was significantly reduced to 55% of control, but the radioactivity in the brain was not changed. In the PET study under control conditions, high radioactivity levels in the liver and pancreas were observed following [ 11 C]3 injection. With YIL781 pretreatment, the accumulated radioactivity in the pancreas 15-60min after [ 11 C]3 injection was significantly decreased to 78% of control., Conclusion: [ 11 C]3 exhibited relatively high uptake and in vivo specific binding to GHS-R1a in the mouse pancreas. [ 11 C]3 may be a useful PET tracers for in vivo imaging of GHS-R1a in the pancreas., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: A positron emission tomography (PET) probe with ultra-high specific radioactivity (SA) enables measuring high receptor specific binding in brain regions by avoiding mass effect of the PET probe itself. It has been reported that PET probe with ultra-high SA can detect small change caused by endogenous or exogenous ligand. Recently, Kealey et al. developed [ 11 C]BU99008, a more potent PET probe for I 2 -imidazoline receptors (I 2 Rs) imaging, with a conventional SA (mean 76GBq/μmol) showed higher specific binding in the brain. Here, to detect small change of specific binding for I 2 Rs caused by endogenous or exogenous ligand in an extremely small region, such as hypothalamus in the brain, we synthesized and evaluated [ 11 C]BU99008 with ultra-high SA as a useful PET probe for small-animal PET imaging of I 2 Rs., Methods: [ 11 C]BU99008 was prepared by [ 11 C]methylation of N-desmethyl precursor with [ 11 C]methyl iodide. Biodistribution, metabolite analysis, and brain PET studies were conducted in rats., Results: [ 11 C]BU99008 with ultra-high SA in the range of 5400-16,600GBq/μmol were successfully synthesized (n=7), and had appropriate radioactivity for in vivo study. In the biodistribution study, the mean radioactivity levels in all investigated tissues except for the kidney did not show significant difference between [ 11 C]BU99008 with ultra-high SA and that with conventional SA. In the metabolite analysis, the percentage of unchanged [ 11 C]BU99008 at 30min after the injection of probes with ultra-high and conventional SA was similar in rat brain and plasma. In the PET study of rats' brain, radioactivity level (AUC 30-60 min ) in the hypothalamus of rats injected with [ 11 C]BU99008 with ultra-high SA (64 [SUV ∙ min]) was significantly higher than that observed for that with conventional SA (50 [SUV ∙ min]). The specific binding of [ 11 C]BU99008 with ultra-high SA (86% of total binding) for I 2 R was higher than that of conventional SA (76% of total binding)., Conclusion: A PET study using [ 11 C]BU99008 with ultra-high SA would thus contribute to the detection of small changes in or small regions with I 2 R expression and hence may be useful in elucidating new functions of I 2 R., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: [(18)F]FEDAC ([(18)F]1) has potent binding affinity and selectivity for translocator protein (18kDa, TSPO), and has been used to noninvasively visualize neuroinflammation, lung inflammation, acute liver damage, nonalcoholic fatty liver disease, and liver fibrosis. We had previously synthesized [(18)F]1 in two steps: (i) preparation of [(18)F]fluoroethyl bromide and (ii) coupling of [(18)F]fluoroethyl bromide with the appropriate precursor (2) for labeling. In this study, to clinically utilize [(18)F]1 as a PET radiopharmaceutical and to transfer the production technique of [(18)F]1 to other PET centers, we simplified its preparation by using a direct, one-step, tosyloxy-for-fluorine substitution. We also performed an acute toxicity study as a major non-clinical safety test, and determined radiometabolites using human liver microsomes., Methods: [(18)F]1 was prepared via direct (18)F-fluorination by heating the corresponding tosylated derivative (3) with [(18)F]fluoride as its Kryptofix 222 complex in dimethyl sulfoxide at 110°C for 15min, following by HPLC purification. Non-clinical safety tests were performed for the extended single-dose toxicity study in rats, and for the in vitro metabolite analysis with human liver microsomal incubation., Results: High quality batches of [(18)F]1, compatible with clinical applications, were obtained. At the end of irradiation, the decay-corrected radiochemical yield of [(18)F]1 using 1 and 5mg of precursor based on [(18)F]fluoride was 18.5±7.9% (n=10) and 52.0±5.8% (n=3), respectively. A single-dose of [(18)F]1 did not show toxicological effects for 14 days after the injection in male and female rats. In human liver microsomal incubations, [(18)F]1 was easily metabolized to [(18)F]desbenzyl-FEDAC ([(18)F]10) by CYPs (4.2% of parent compound left 60min after incubation)., Conclusion: We successfully synthesized clinical grade batches of [(18)F]1 and verified the absence of innocuity of this radiotracer. [(18)F]1 will be used to first-in-human studies in our facility., (Copyright © 2016 Elsevier Inc. All rights reserved.)