Search

While silk fibroin (SF) obtained from silkworm cocoons is expected to become a next-generation natural polymer, a fabrication method for SF-based artificial nerve conduits (SFCs) has not yet been established. Here, we report a bioresorbable SFC, fabricated using a novel freeze–thaw process, which ensures biosafety by avoiding any harmful chemical additives. The SFC demonstrated favorable biocompatibility (high hydrophilicity and porosity with a water content of > 90%), structural stability (stiffness, toughness, and elasticity), and biodegradability, making it an ideal candidate for nerve regeneration. We evaluated the nerve-regenerative effects of the SFC in a rat sciatic-nerve-defect model, including its motor and sensory function recovery as well as histological regeneration. We found that SFC transplantation significantly promoted functional recovery and nerve regeneration compared to silicone tubes and was almost equally effective as autologous nerve transplantation. Histological analyses indicated that vascularization and M2 macrophage recruitment were pronounced inside the SFC. These results suggest that the unique properties of the SFC further enhanced the peripheral nerve regeneration mechanism. As no SFC has been applied in clinical practice, the SFC reported herein may be a promising candidate for repairing extensive peripheral nerve defects. [ABSTRACT FROM AUTHOR]

Background: The association of Mini-Mental State Examination (MMSE) with microstructure of individual regions across the entire brain remains unexplored. Purpose: To investigate the relationship between cognitive function and the microstructure of each brain region in the gray matter using diffusion kurtosis imaging (DKI) in older adults with mild cognitive impairment (MCI), which is the transitional stage before the onset of dementia. Material and Methods: DKI and MMSE were obtained for 34 older adults with MCI and 16 cognitively normal (CN) individuals aged 65–85 years. The DKI parameters were measured from 31 distinct regions of interest in the gray matter. A multiple regression analysis was used to examine the association between DKI parameters and MMSE scores; subsequently, interactions between the DKI parameters and the groups (MCI and CN) were examined. Results: The mean (±SD) MMSE score for the MCI group was 27.67 ± 1.90. Significant positive correlations were observed between MMSE score and mean kurtosis (MK) in the superior frontal, middle frontal, inferior frontal, precentral, postcentral, angular, middle temporal, and inferior occipital gyri, and superior parietal lobe for the MCI group. In addition, the interaction term of the MK in the middle frontal, precentral, postcentral, and angular gyri, and the groups was statistically significant. Conclusion: Older adults with MCI may exhibit histological damage in certain regions of the brain, such as the middle frontal and angular gyri, as observed in this study. The findings could provide insights into understanding the pathophysiology of cognitive decline in this population group. [ABSTRACT FROM AUTHOR]

Introduction: While patients who experience improved cognition following carotid endarterectomy (CEA) typically demonstrate restored brain perfusion after the procedure, it is worth noting that less than 50% of patients in whom postoperative cerebral blood flow (CBF) restoration is achieved actually show improved cognition after postoperatively. This suggests that factors beyond the mere restoration of CBF may play a role in postoperative cognitive improvement. Increased iron deposition in the cerebral cortex may cause neural damage, and quantitative susceptibility mapping (QSM) obtained using magnetic resonance imaging (MRI) quantifies magnetic susceptibility in the cerebral cortex, allowing for the assessment of iron deposition in vivo. The purpose of the present study was to determine whether preoperative cortical magnetic susceptibility as well as postoperative changes in CBF are associated with cognitive improvement after CEA. Methods: Brain MRI with a three-dimensional gradient echo sequence was preoperatively performed in 53 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%), and QSM with brain surface correction and vein removal was obtained. Cortical magnetic susceptibility was measured in the cerebral hemisphere ipsilateral to surgery on QSM. Preoperatively and at 2 months after the surgery, brain perfusion single-photon emission computed tomography and neuropsychological assessments were conducted. Using these collected data, we evaluated alterations in CBF within the affected hemisphere and assessed cognitive improvements following the operation. Results: A logistic regression analysis showed that a postoperative greater increase in CBF (95% confidence interval [CI], 1.06–1.90; p = 0.0186) and preoperative lower cortical magnetic susceptibility (95% CI, 0.03–0.74; p = 0.0201) were significantly associated with postoperatively improved cognition. Although sensitivity, specificity, and positive and negative predictive values with the cutoff value lying closest to the upper left corner of a receiver operating characteristic curve for the prediction of postoperatively improved cognition did not differ between postoperative changes in CBF and preoperative cortical magnetic susceptibility, the specificity and the positive predictive value were significantly greater for the combination of postoperative changes in CBF and preoperative cortical magnetic susceptibility (specificity, 95% CI, 93–100%; positive predictive value 95% CI, 68–100%) than for the former parameter alone (specificity, 95% CI, 63–88%; positive predictive value 95% CI, 20–64%). Conclusion: Preoperative cortical magnetic susceptibility as well as postoperative changes in CBF are associated with cognitive improvement after CEA. [ABSTRACT FROM AUTHOR]

Objectives: Patients with myeloproliferative neoplasms (MPNs) are at higher risk of developing secondary malignancies. In this study, we focused on patients with MPNs that complicated lymphoid neoplasms. To analyze the real-world status of lymphoid neoplasm treatment in patients with pre-existing MPNs in Japan, we conducted a multicenter retrospective study. Methods: Questionnaires were sent to collect the data on patients who were first diagnosed with either polycythemia vera, essential thrombocythemia or myelofibrosis and who later were complicated with lymphoid neoplasms defined as malignant lymphoma, multiple myeloma, or chronic lymphocytic leukemia/small cell lymphoma. Results: Twenty-four patients with MPNs complicated by lymphoid neoplasms were enrolled (polycythemia vera, n = 8; essential thrombocythemia, n = 14; and primary myelofibrosis, n = 2). Among these, diffuse large B-cell lymphoma (DLBCL) was the most frequently observed (n = 13, 54.1%). Twelve (92.3%) of the patients with DLBCL received conventional chemotherapy. Among these 12 patients, regarding cytoreductive therapy for MPNs, 8 patients stopped treatment, one continued treatment, and two received a reduced dose. Consequently, most patients were able to receive conventional chemotherapy for DLBCL with a slightly higher dose of granulocyte colony-stimulating factor support than usual without worse outcomes. All 3 patients with multiple myeloma received a standard dose of chemotherapy. Conclusion: Our data indicate that if aggressive lymphoid neoplasms develop during the course of treatment in patients with MPNs, it is acceptable to prioritize chemotherapy for lymphoma. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (ICC) is a challenging primary liver cancer with a poor prognosis, especially in unresectable cases. Traditional palliative irradiation is limited in reducing liver doses. This study aimed to evaluate the efficacy and toxicity of respiratory-gated proton beam therapy without fiducial markers for intrahepatic cholangiocarcinoma. Methods: Between October 2011 and February 2022, 24 patients (median [range] age, 71 [41–88] years) were evaluated at our institution. Twelve patients were pathologically diagnosed with ICC. All patients underwent respiratory-gated proton beam therapy at a dose of 48–83.6 (relative biological effectiveness) in 20–38 fractions with four-dimensional computed tomography planning. The median follow-up period was 18.5 (range, 2.0–74.0) months. The median tumor size was 41 (range, 10–134) mm. Twenty-one patients were classified as having Child–Pugh class A, and three patients were classified as having Child–Pugh class B. Local progression was defined as any growth of the irradiated tumor. Results: The median survival time was 28 months for all patients. The Kaplan–Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 51%, 26%, and 73%, respectively. Local tumor control rates were non-inferior to those reported in previous studies using fiducial markers. One patient had grade 4 pleural effusion; however, whether this was an adverse event due to the proton beam therapy was unclear. Conclusions: Respiratory-gated proton beam therapy without fiducial markers is an effective and less invasive treatment option for ICC, showing potential for improved local control and tolerable adverse effects. [ABSTRACT FROM AUTHOR]

The objective of the study is to investigate the safety, feasibility, and degradation profile of a novel Mg alloy-based bioresorbable coronary scaffold (JFK-PRODUCT BRS) with thin struts (110 μm). Polymer- or Mg alloy-based BRSs have not replaced nondegradable metal stents because of the higher prevalence of scaffold thrombosis and restenosis in clinical practice; these poor clinical outcomes were due to inadequate scaffold designs, including thick struts (more than 150 μm) and their inappropriate degradation processes. Fourteen healthy pigs received 17 JFK-PRODUCT BRSs in the coronary arteries and were sacrificed at 1, 6, 12, 18, and 26 months after implantation. Angiography, optical coherence tomography, microfocus X-ray computed tomography (µCT), scanning electron microscopy with energy-dispersive X-ray spectrometry (SEM–EDX), and histopathological evaluation were performed. The JFK-PRODUCT had a median percent late recoil of 11.28% at 1 month. The µCT observation confirmed that scaffold discontinuity reached 64.8% at 12 months with increased scaffold inner area thereafter, suggesting artery positive remodeling. The inflammation was mild, peaked at 18 months, and decreased thereafter. The SEM–EDX analysis demonstrated gradual degradation of the scaffold with formation of inorganic deposits, presumed to be calcium phosphates. It also revealed the disappearance of calcium phosphates at 26 months, achieving almost complete replacement of the scaffold by biocomponents. The current study demonstrated the safety and feasibility of JFK-PRODUCT with a lower acute recoil rate despite its thin struts. The scaffolds were almost completely disappeared at 26 months after implantation. [ABSTRACT FROM AUTHOR]

Bone fractures represent a common health problem, particularly in an increasingly aging population. Bioresorbable magnesium (Mg) alloy‐based implants offer promising alternatives to traditional metallic implants for the treatment of bone fractures because they eliminate the need for implant removal after healing. The Mg‐Y‐rare‐earth (RE)‐Zr alloy WE43, designed for orthopedic implants, has received European Conformity mark approval. However, currently, WE43 is not clinically used in certain countries possibly because of concerns related to RE metals. In this study, we investigated the use of a RE‐free alloy, namely, Mg‐Zn‐Zr alloy (ZK30), as an implant for bone fractures. Hydrofluoric acid (HF) treatment was performed to improve the corrosion resistance of ZK30. HF‐treated ZK30 (HF‐ZK30) exhibited lower corrosion rate and higher biocompatibility than those of WE43 in in vitro experiments. After implanting a rod of HF‐ZK30 into the fractured femoral bones of mice, HF‐ZK30 held the bones and healed the fracture without deformation. Treatment results of HF‐ZK30 were comparable to those of WE43, indicating the potential of HF‐ZK30 as a bioresorbable and safe implant for bone repair. [ABSTRACT FROM AUTHOR]

Background: Constipation causes substantial morbidity worldwide. Methods: This survey assessed constipation-related factors in Japan using the Japanese version of the Irritable Bowel Syndrome Quality of Life (IBS-QOL-J) instrument. We also examined the relationship among laxative type, Bristol Stool Form Scale (BSFS) scores, and treatment cost. Finally, we examined differences in satisfaction scores according to laxative type, treatment type, treatment cost, and BSFS score. Results: IBS-QOL-J was higher among those taking salt and/or irritation laxatives. Those paying >JPY 5000 (USD 50.00) had the lowest IBS-QOL-J. IBS-QOL-J was significantly lower among those with a BSFS score of 1 or 2 (severe constipation). Conclusions: This study's findings suggest that a variety of factors, including treatment type and cost, are associated with defecation satisfaction. Those who had hard stools, used multiple laxatives, or spent more on treatment were less satisfied. Future strategies should target therapies that do not require multiple laxatives with lower treatment costs. Adequate defecation with a small number of appropriate laxatives at minimal cost appears to improve defecation satisfaction. It is desirable to identify appropriate laxatives and improve dietary habits and exercise routines. It is also necessary to stop blindly increasing laxative usage and properly diagnose constipation disorders such as anatomical abnormalities other than functional constipation. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the dose reduction using gonad shielding (GS) during pelvic imaging. Three types of pelvic images (radiography, magnetic resonance and computed tomography) were fused to elucidate the three-dimensional relationship between the position of ovaries and GS. To estimate the dose received by the ovaries, the off-axis dose at any given depth was measured under two different imaging conditions using thermoluminescence dosemeters and a polymethyl methacrylate phantom. The mean ovarian depth was 8.4 cm. The mean estimated ovarian dose without an additional filter was 0.36 mGy without GS and 0.14 mGy with GS. The mean estimated ovarian dose with an additional filter was 0.24 mGy without GS and 0.10 mGy with GS. The efficacy of ovarian dose reduction should be evaluated based on the achieved ovarian dose, considering the ovarian depth and use of additional filtration, rather than the ovarian protection rate of GS. [ABSTRACT FROM AUTHOR]

This report describes the one‐pot direct N‐acylation of indazole with carboxylic acids using our previously developed 4‐(N,N‐dimethylamino)pyridine N‐oxide (DMAPO)/di‐tert‐butyl dicarbonate (Boc2O) system. This simple system provides N1‐acyl indazoles in high yield with high N1 selectivities and does not require the use of activated derivatives of carboxylic acids or high temperatures. This new method exhibits a wide substrate scope (>40 examples). In addition, a new synthesis of N1‐functionalized alkyl indazoles utilizing N1‐acyl indazoles as starting materials was achieved. This stepwise protocol is useful for the selective synthesis of structurally diverse N1‐functionalized alkyl indazoles, which are difficult to synthesize by other methods such as the Mitsunobu reaction and classical SN2 alkylation of indazole. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to determine the excess risk of antithrombotic‐related bleeding due to cerebral small vessel disease (SVD) burden. Methods: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events. Results: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient‐years of follow‐up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1–3). Incidence rate of major bleeding was 0.39 (per 100 patinet‐years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26–13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99–43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08–2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13–10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02–6.35) significantly increased in SVD score 4 compared to score 0. Interpretation: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774–787 [ABSTRACT FROM AUTHOR]

We investigated the mass dependency of the high-wavenumber turbulence, which occurs at scales smaller than the ion effective Larmor radius, in a partially magnetized plasma column. In this system, two different types of fluctuations were observed: one exhibiting a coherent discrete spectrum, while the other displaying a broadband continuous spectrum. The phase velocities of both types showed a similar mass dependency, approximately matching the ion sound velocity or electron diamagnetic drift velocity. Additionally, we found that the discrete spectrum has a peak interval frequency comparable to the ion cyclotron frequency, which is consistent with ion cyclotron ranges of fluctuations, including ion Bernstein waves. [ABSTRACT FROM AUTHOR]

Background: Centrally located lung tumours present a challenge because of their tendency to exhibit symptoms such as airway obstruction, atelectasis, and bleeding. Surgical resection of these tumours often requires sacrificing the lungs, making definitive radiotherapy the preferred alternative to avoid pneumonectomy. However, the proximity of these tumours to mediastinal organs at risk increases the potential for severe adverse events. To mitigate this risk, we propose a dual-method approach: deep inspiration breath-hold (DIBH) radiotherapy combined with adaptive radiotherapy. The aim of this single-centre, single-arm phase II study is to investigate the efficacy and safety of DIBH daily online adaptive radiotherapy. Methods: Patients diagnosed with centrally located lung tumours according to the International Association for the Study of Lung Cancer recommendations, are enrolled and subjected to DIBH daily online adaptive radiotherapy. The primary endpoint is the one-year cumulative incidence of grade 3 or more severe adverse events, as classified by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Discussion: Delivering definitive radiotherapy for centrally located lung tumours presents a dilemma between ensuring optimal dose coverage for the planning target volume and the associated increased risk of adverse events. DIBH provides measurable dosimetric benefits by increasing the normal lung volume and distancing the tumour from critical mediastinal organs at risk, leading to reduced toxicity. DIBH adaptive radiotherapy has been proposed as an adjunct treatment option for abdominal and pelvic cancers. If the application of DIBH adaptive radiotherapy to centrally located lung tumours proves successful, this approach could shape future phase III trials and offer novel perspectives in lung tumour radiotherapy. Trial registration. Registered at the Japan Registry of Clinical Trials (jRCT; https://jrct.niph.go.jp/); registration number: jRCT1052230085 (https://jrct.niph.go.jp/en-latest-detail/jRCT1052230085). [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy for the hemodialysis (HD) patient is a challenging situation because it requires special considerations including dose modifications and timing of drug administration in relation with HD sessions. Polaltuzumab vedotin (PV), an antibody–drug conjugate in which monomethyl auristatin E (MMAE) is linked to an anti-CD79b monoclonal antibody, is an extremely promising therapeutic for treating diffuse large B cell lymphoma (DLBCL), but the pharmacokinetics are unknown in HD patients. Methods: We carried out pharmacokinetic studies of PV when administered at 1.2 mg/kg to a DLBCL patient on HD, and compared the results with that of non-HD patients. PV was administered in conjunction with bendamustine and rituximab. Results: Serum concentration–time curves of both antibodyconjugated and unconjugated MMAE in the presented HD patient were similar compared to that of non-HD patients. We also demonstrate that elimination of both antibody-conjugated and unconjugated MMAE through HD is limited. PV administration at 1.2 mg/kg to an HD patient was also clinically feasible, and no signs of peripheral neuropathy were observed. Conclusions: PV therapy may be a relatively safe treatment method for DLBCL patients on HD. [ABSTRACT FROM AUTHOR]

Genetic testing is key in modern healthcare, particularly for monogenic disorders such as familial hypercholesterolemia. This Tohoku Medical Megabank Project study explored the impact of first-degree relatives' dyslipidemia history on individual responses to familial hypercholesterolemia genomic results. Involving 214 participants and using Japan's 3.5KJPN genome reference panel, the study assessed preferences and intentions regarding familial hypercholesterolemia genetic testing results. The data revealed a significant inclination among participants with a family history of dyslipidemia to share their genetic test results, with more than 80% of participants intending to share positive results with their partners and children and 98.1% acknowledging the usefulness of positive results for personal health management. The study underscores the importance of family health history in genetic-testing perceptions, highlighting the need for family-centered approaches in genetic counseling and healthcare. Notable study limitations include the regional scope and reliance on questionnaire data. The study results emphasize the association between family health history and genetic-testing attitudes and decisions. [ABSTRACT FROM AUTHOR]

Although cognitive decline after carotid endarterectomy (CEA) is mainly related to postoperative cerebral hyperperfusion, approximately 30% of patients with cognitive decline do not have postoperative cerebral hyperperfusion. In patients with acute ischemic events, the development of cognitive decline after such events is associated with the presence of chronic cerebral white matter hyperintensities (WMHs). The present prospective observational study aimed to determine whether preoperative WMHs and postoperative new ischemic lesions (PNILs) are associated with cognitive decline after CEA in patients without cerebral hyperperfusion after CEA. Brain magnetic resonance imaging (MRI) was performed preoperatively, and WMHs were graded according to the Fazekas scale in patients undergoing CEA for severe stenosis of the ipsilateral internal carotid. Diffusion-weighted MRI was performed before and after CEA to determine the development of PNILs. Neuropsychological testing was performed preoperatively and at 2 months postoperatively to determine the development of postoperative cognitive decline (PCD). In 142 patients without postoperative cerebral hyperperfusion, logistic regression analysis revealed that preoperative Fazekas scale of periventricular WMHs (PVWMHs) (95% confidence interval [CI]: 1.78–28.10; P = 0.0055) and PNILs in the eloquent areas (95% CI: 7.42–571.89; P = 0.0002) were significantly associated with PCD. The specificity and positive-predictive value for the prediction of PCD were significantly greater for the combination of preoperative Fazekas scale 2 or 3 of PVWMHs and PNILs in the eloquent areas than for each individually. Preoperative PVWMHs, PNILs in the eloquent areas, and the combination of both were associated with PCD in patients without cerebral hyperperfusion after CEA. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial therapy is necessary to eradicate Helicobacter pylori infection. The emergence of antimicrobial‐resistant bacteria poses a threat to continued treatment with antimicrobial agents. For those who prescribe antimicrobial therapy, it is necessary to constantly monitor the emergence of antimicrobial‐resistant bacteria. Method: H. pylori clinical isolates were collected in Japan from August 2018 to December 2020 for antimicrobial susceptibility testing. The agar dilution method was used for the determination of the minimum inhibitory concentration (MIC) of clarithromycin (CLR), amoxicillin (AMX), metronidazole (MNZ), and sitafloxacin (STX). Results: MICs for 938 H. pylori isolates were examined. The primary resistance rates of H. pylori clinical isolates for CLR, AMX, MNZ, and STX in Japan were 35.5%, 2.7%, 4.2%, and 27.6%, respectively. The primary resistance rates for CLR, AMX, and MNZ were significantly higher than those of the 2002–2005 isolates. The resistance rate for CLR was significantly higher in females (males: 30.7%, females: 41.5%, p < 0.001) and higher in the ≤29 years age group (54.8%) than in the other age groups, although there were no significant differences (p = 0.104). The MNZ resistance rate was significantly higher in the ≤29 years age group than in the other age groups (p = 0.004). The resistance rate for STX increased with age, but a significant difference was only seen between the 30–49 years age group and the ≥70 years age group (p < 0.001), and the resistance rate was significantly higher in strains isolated in the Kyushu region than in the other regions (p < 0.001). Conclusions: The primary resistance rates for CLR, AMX, and MNZ of H. pylori clinical isolates in Japan were higher than those of the 2002–2005 isolates. Continuous surveillance is needed to monitor the trends in antimicrobial‐resistant H. pylori. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have been employed to develop numerous risk prediction models using polygenic risk scores (PRSs) for multifactorial diseases. However, healthcare providers lack confidence in their understanding of PRS risk stratification for multifactorial diseases, which underscores the need to assess the readiness of PRSs for clinical use. To address this issue, we surveyed the perceptions of healthcare providers as stakeholders in the clinical implementation of genetic-based risk prediction for multifactorial diseases. We conducted a web-based study on the need for risk prediction based on genetic information and the appropriate timing of testing for 12 multifactorial diseases. Responses were obtained from 506 stakeholders. Positive perceptions of genetic risk testing were found for adult-onset chronic diseases. As per participant opinion, testing for adult-onset diseases should be performed after the age of 20 years, whereas testing for psychiatric and allergic disorders that manifest during childhood should be performed from birth to 19 years of age. The stakeholders recognized the need for genetic risk testing for diseases that develop in adulthood, believing that the appropriate testing time is after maturity. This study contributes to the discussion on the clinical implementation of the PRS for genetic risk prediction of multifactorial diseases. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to demonstrate the potential clinical applicability of an organ‐contour‐driven auto‐matching algorithm in image‐guided radiotherapy. Methods: This study included eleven consecutive patients with cervical cancer who underwent radiotherapy in 23 or 25 fractions. Daily and reference magnetic resonance images were converted into mesh models. A weight‐based algorithm was implemented to optimize the distance between the mesh model vertices and surface of the reference model during the positioning process. Within the cost function, weight parameters were employed to prioritize specific organs for positioning. In this study, three scenarios with different weight parameters were prepared. The optimal translation and rotation values for the cervix and uterus were determined based on the calculated translations alone or in combination with rotations, with a rotation limit of ±3°. Subsequently, the coverage probabilities of the following two planning target volumes (PTV), an isotropic 5 mm and anisotropic margins derived from a previous study, were evaluated. Results: The percentage of translations exceeding 10 mm varied from 9% to 18% depending on the scenario. For small PTV sizes, more than 80% of all fractions had a coverage of 80% or higher. In contrast, for large PTV sizes, more than 90% of all fractions had a coverage of 95% or higher. The difference between the median coverage with translational positioning alone and that with both translational and rotational positioning was 1% or less. Conclusion: This algorithm facilitates quantitative positioning by utilizing a cost function that prioritizes organs for positioning. Consequently, consistent displacement values were algorithmically generated. This study also revealed that the impact of rotational corrections, limited to ±3°, on PTV coverage was minimal. [ABSTRACT FROM AUTHOR]

Flow diverters (FDs) are utilized for a wide range of aneurysms, but show safety issues such as adverse interactions with static magnetic fields (displacement force and torque) and radiofrequency-induced heating during magnetic resonance imaging (MRI). The present study aimed to assess these adverse interactions in a 7-tesla (7T) static magnetic field and radiofrequency-induced heating during a 7T MRI for two types of FD. Displacement force and magnetically induced torque were assessed using the deflection angle method and low friction surface method, respectively. To assess heating, each FD was set in a phantom filled with gelled-saline mixed with polyacrylic acid and underwent a 7T MRI using a three-dimensional fast spin echo method. Displacement force and magnetically induced torque in the 7T static magnetic field were undetectable, and radiofrequency-induced heating during 7T MRI remained ≤ 0.6 °C for both types of FD, suggesting that magnetic field interactions and heating on FDs during a 7T MRI are acceptable from a safety perspective. [ABSTRACT FROM AUTHOR]

The mutual interaction of drift wave-type modes and zonal flows causes the formation of higher-order nonlinear structures. This study focuses on the spatio-temporal behavior of these higher-order structures in a linear magnetized plasma. The structures include a solitary vortex, a long-lived circumnavigating motion localized both radially and azimuthally, and a short-lived packet of finer-scale fluctuations excited at the position of the solitary vortex. Observing the time evolution of the two-dimensional cross-sectional structures revealed that the packet of finer-scale fluctuations is trapped in the solitary vortex. The trapping times found are consistent with the theoretical evaluation. [ABSTRACT FROM AUTHOR]

Spectral transition between continuous and discrete spectra has been observed in high-wavenumber turbulence excitation experiments. The transition appeared in neutral gas scanning, which shows that continuous spectra dominate at low gas pressures and discrete spectra dominate at high gas pressures. Both spectra have well smaller spatial scale than the ion effective Larmor radius. The discrete spectra have 6–11 peaks and maximum peak values at 4th or 5th peak. Correlation length analysis reveals that the continuous component is turbulent and the discrete component is coherent. The bicoherence analysis shows that the turbulent spectra have finite nonlinear coupling, whereas the discrete spectra have no corresponding coupling. [ABSTRACT FROM AUTHOR]

This study aimed to assess the effectiveness of a new patient-setup procedure using surface-guided imaging during the coronavirus disease 2019 (COVID-19) pandemic for left-sided whole-breast irradiation with deep inspiration breath-hold. Two setup procedures were compared regarding patient positioning accuracy for the first 22 patients. The first was a traditional setup (T-setup) procedure that used a surface-guided system after patient setup with traditional skin marks and lasers. The second procedure involved a new setup (N-setup) that used only a surface-guided system. The positioning accuracy of the remaining 23 patients was assessed using a setup that combined marker reduction and the N-setup procedure. No significant difference was observed in positioning accuracy between the two setups. The positioning accuracy of the marker-reduction setup was within 3 mm in all directions. The N-setup procedure may be a useful strategy for preventing infection during or after the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

This nationwide, multicenter, open-label, single-arm study evaluated the efficacy and safety of the oral proteasome inhibitor (PI), ixazomib plus lenalidomide (LEN) and dexamethasone (DEX) (IRd) following injectable PI-based therapy for relapsed/refractory multiple myeloma (RRMM). Of 45 patients enrolled, 36 patients received IRd after achieving at least a minor response to 3 cycles of bortezomib or carfilzomib plus LEN + DEX (VRd, n=6; KRd, n=30). At median follow-up of 20.8 months, the 12-month event-free survival rate (primary endpoint) was 49% (90% CI: 35.9−62.0), counting 11 events of progressive disease/death, 8 dropouts and 4 missing response data. The 12-month progression-free survival (PFS) rate by Kaplan-Meier analysis (dropouts as censoring) was 74% (95% CI: 56−86). Median PFS and time to next treatment (95% CI) were 29.0 (21.3−NE) and 32.3 (14.9−35.4) months, respectively; median OS was not evaluable. The overall response rate was 73%, and 42% of patients had a very good partial response or better. Frequent (≥10% incidence) grade ≥3 treatment emergent adverse events were decreased neutrophil and platelet counts (n=7 [16%] each). Two deaths occurred (one during KRd treatment and one during IRd treatment), both due to pneumonia. IRd following injectable PI-based therapy was tolerable and efficacious in RRMM patients. Trial registration number: NCT03416374; Date of registration: January 31, 2018 [ABSTRACT FROM AUTHOR]

This report describes a general method for the one‐pot direct N‐acylation of N‐heterocycles using our previously developed 4‐(N,N‐dimethylamino)pyridine N‐oxide (DMAPO)/di‐tert‐butyl dicarbonate (Boc2O) system. This system enables one‐pot N‐acylation reactions to provide bulky N‐acyl heterocycles starting from a wide variety of less nucleophilic N‐heterocycles and sterically hindered α‐fully substituted carboxylic acids in high yields. Moreover, this one‐pot method does not involve pre‐activation of substrates. The protocol has been successfully extended to one‐pot N‐acylation of 7‐azaindoles. [ABSTRACT FROM AUTHOR]

The purpose of this study was to retrospectively assess target localization accuracy across different soft-tissue matching protocols using cone-beam computed tomography (CBCT) in a large sample of patients with pancreatic cancer and to estimate the optimal margin size for each protocol. Fifty-four consecutive patients with pancreatic cancer who underwent 15-fraction volumetric modulated arc therapy under the end-exhalation breath-hold condition were enrolled. Two soft-tissue matching protocols were used according to the resectability classification, including gross tumor volume (GTV) matching for potentially resectable tumors and planning target volume (PTV) matching for borderline resectable or unresectable tumors. The tolerance of the target localization error in both matching protocols was set to 5 mm in any direction. The optimal margin size for each soft-tissue matching protocol was calculated from the systematic and random errors of the inter- and intrafraction positional variations using the van Herk formula. The inter- and intrafraction positional variations of PTV matching were smaller than those of GTV matching. The percentage of target localization errors exceeding 5 mm in the first CBCT scan of each fraction in the superior–inferior direction was 12.6 and 4.8% for GTV and PTV matching, respectively. The optimal margin sizes for GTV and PTV matching were 3.7 and 2.7, 5.4 and 4.1 and 3.9 and 3.0 mm in the anterior–posterior, superior–inferior and left–right directions, respectively. Target localization accuracy in PTV matching was higher than that in GTV matching. By setting the tolerance of the target localization error, treatment can be successful within the planned margin size. [ABSTRACT FROM AUTHOR]

Background: Whether past disaster experiences affect the association between changes in social isolation and depressive symptoms is largely unknown. This study examined the association between changes in social isolation and depressive symptoms among survivors who experienced earthquake damage in the aftermath of the Great East Japan Earthquake (GEJE). Methods: We analyzed longitudinal data from 10,314 participants who responded to self-report questionnaires on the Lubben Social Network Scale-6 (LSNS-6) and the Center for Epidemiological Studies-Depressive Scale (CES-D) in both the baseline survey (FY2013 to FY2015) and follow-up survey (FY2017 to FY2019) after the GEJE. According to changes in the presence of social isolation (< 12 of LSNS-6) at two time points, participants were categorized into four groups: “not socially isolated,” “improved socially isolated,” “newly socially isolated,” and “continuously socially isolated.” At the follow-up survey, a CES-D score of ≥ 16 indicates the presence of depressive symptoms. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using the logistic regression analysis to examine the influence of the change in social isolation over four years on depressive symptoms. Results: Participants who were newly socially isolated had a significantly higher prevalence of depressive symptoms than those who were not socially isolated (AOR = 1.89, 95% CI = 1.61 − 2.23). In addition, AORs were highest for those who were continuously socially isolated and had experienced house damage (AOR = 2.17, 95% CI = 1.73 − 2.72) and those who were newly socially isolated and had not experienced the death of family members due to the GEJE (AOR = 1.88, 95%CI = 1.60 − 2.22). Conclusion: Our longitudinal findings suggest that being newly or continuously socially isolated is associated with a risk of depressive symptoms, not only among those who had experienced house damage or the death of a family member, but also those who had not, in the disaster-affected area. Our study underlines the clinical importance of social isolation after a large-scale natural disaster and draws attention to the need for appropriate prevention measures. [ABSTRACT FROM AUTHOR]

Decreased swallowing function increases the risk of choking and aspiration pneumonia. Videofluoroscopy and computed tomography allow for detailed observation of the swallowing movements but have radiation risks. Therefore, we developed a method using surface electromyography (sEMG) to noninvasively assess swallowing function without radiation exposure. A 44-channel flexible sEMG sensor was used to measure the sEMG signals of the hyoid muscles during swallowing in 14 healthy young adult and 14 elderly subjects. Muscle synergy analysis was performed to extract the muscle synergies from the sEMG signals, and the three synergies were extracted from the hyoid muscle activities during the swallowing experiments. The experimental results showed that the three synergies represent the oral, early pharyngeal, and late pharyngeal swallowing phases and that swallowing strength is tuned by the strength of the muscle activities, whereas swallowing volume is controlled by adjusting muscle activation timing. In addition, the timing of the swallowing reflex is slower in elderly individuals. The results confirm that the proposed approach successfully quantifies swallowing function from sEMG signals, mapping the signals to the swallowing phases. [ABSTRACT FROM AUTHOR]

Background: It is important to have precise image guidance throughout proton therapy in order to take advantage of the therapy's physical selectivity. Purpose: We evaluated the effectiveness of computed tomography (CT)‐image guidance in proton therapy for patients with hepatocellular carcinoma (HCC) by assessing daily proton dose distributions. The importance of daily CT image‐guided registration and daily proton dose monitoring for tumors and organs at risk (OARs) was investigated. Methods: A retrospective analysis was conducted using 570 sets of daily CT (dCT) images throughout whole treatment fractions for 38 HCC patients who underwent passive scattering proton therapy with either a 66 cobalt gray equivalent (GyE)/10 fractions (n = 19) or 76 GyE/20 fractions (n = 19) protocol. The actual daily delivered dose distributions were estimated by forward calculation using the dCT sets, their corresponding treatment plans, and the recorded daily couch correction information. We then evaluated the daily changes of the dose indices D99%, V30GyE, and Dmax for the tumor volumes, non‐tumorous liver, and other OARs, that is, stomach, esophagus, duodenum, colon, respectively. Contours were created for all dCT sets. We validated the efficacy of the dCT‐based tumor registrations (hereafter, "tumor registration") by comparing them with the bone registration and diaphragm registration as a simulation of the treatment based on the positioning using the conventional kV X‐ray imaging. The dose distributions and the indices of three registrations were obtained by simulation using the same dCT sets. Results: In the 66 GyE/10 fractions, the daily D99% value in both the tumor and diaphragm registrations agreed with the planned value with 3%–6% (SD), and the V30GyE value for the liver agreed within ±3%; the indices in the bone registration showed greater deterioration. Nevertheless, tumor‐dose deterioration occurred in all registration methods for two cases due to daily changes of body shape and respiratory condition. In the 76 GyE/20 fractions, in particular for such a treatment that the dose constraints for the OARs have to be cared in the original planning, the daily D99% in the tumor registration was superior to that in the other registration (p < 0.001), indicating the effectiveness of the tumor registration. The dose constraints, set in the plan as the maximum dose for OARs (i.e., duodenum, stomach, colon, and esophagus) were maintained for 16 patients including seven treated with re‐planning. For three patients, the daily Dmax increased gradually or changed randomly, resulting in an inter‐fractional averaged Dmax higher than the constraints. The dose distribution would have been improved if re‐planning had been conducted. The results of these retrospective analyses indicate the importance of daily dose monitoring followed by adaptive re‐planning when needed. Conclusions: The tumor registration in proton treatment for HCC was effective to maintain the daily dose to the tumor and the dose constraints of OARs, particularly in the treatment where the maintenance for the dose constraints needs to be considered throughout the treatment. Nevertheless daily proton dose monitoring with daily CT imaging is important for more reliable and safer treatment. [ABSTRACT FROM AUTHOR]

Knowledge of genetics is essential for understanding the results of genetic testing and its implications. Recent advances in genomic research have allowed us to predict the risk of onset of common diseases based on individual genomic information. It is anticipated that more people will receive such estimates of risks based on their genomic data. However, currently, there is no measure for genetic knowledge that includes post-genome sequencing advancements in Japan. In this study, we translated the genomic knowledge measure in the International Genetics Literacy and Attitudes Survey (iGLAS-GK) into Japanese and validated it in a general Japanese adult population (n = 463). The mean score was 8.41 (SD 2.56, range 3–17). The skewness and kurtosis were 0.534 and 0.088, respectively, and the distribution showed a slightly positive skewness. Exploratory factor analysis proposed a six-factor model. Results for 16 of the 20 items of the Japanese version of the iGLAS-GK were comparable to those from previous studies in other populations. These results indicate that the Japanese version is reliable and can be used to measure the genomic knowledge of adults in the general population, and this version of the knowledge measure maintains the multidimensional structure for assessing genomic knowledge. [ABSTRACT FROM AUTHOR]

A procedure to calculate normalized electron temperature and electron density fluctuations using dual wavelength emission intensity tomography in a linear magnetized plasma is proposed. Expression of emission intensity is modeled as \(\epsilon_{k} \propto T_{\text{e}}^{\alpha_{k}}n_{\text{e}}^{2}\) where \(\epsilon_{k}\) is emission intensity, Te is electron temperature, ne is electron density, k = 1 for ArI, and k = 2 for ArII. Using the model, normalized Te and ne fluctuations can be expressed as linear function of both the normalized emission intensity fluctuations. To calculate αk, we perform least squares method between real \(\epsilon_{k}\) measured with a tomography system and artificial \(\epsilon_{k}\) reconstructed using Te and ne measured with a Langmuir probe located downstream of the tomography system. The results show that α1 = 2.2 and α2 = 2.6, and normalized Te and ne fluctuations are preliminarily evaluated from emission intensity tomography data. [ABSTRACT FROM AUTHOR]

In contrast to the considerable progress in the development of methodologies for amide bond formation in amines, the development of direct N‐acylation of less nucleophilic N‐heterocycles and amides with carboxylic acids is still challenging. In this report, we describe the direct N‐acylation of less nucleophilic heterocycles and amides with carboxylic acids promoted by the 4‐(N,N‐dimethylamino)pyridine N‐oxide (DMAPO)/di‐tert‐butyl dicarbonate (Boc2O) system. The new one‐pot method, which does not involve pre‐activation of substrates, enables the direct N‐acylation of a wide variety of nitrogen nucleophiles such as indole, carbazole, pyrrole, pyrazole, lactam, oxazolidinone, and anilide with carboxylic acids in high yield. The new method also exhibits excellent functional group tolerance and broad substrate scope. As the present method is practical, operationally simple, and scalable, it should find wide applications in both academic and industrial laboratories. [ABSTRACT FROM AUTHOR]

Xanthine oxidoreductase (XOR) and its products contribute to the development of chronic inflammation and oxidative stress. Excessive XOR activity is believed to promote inflammatory responses and atherosclerotic plaque formation, which are major cardiovascular risk factors. The mechanisms of XOR activity in the development and progression of cardiovascular disease (CVD), coupled with the complexity of the relationship between XOR activity and the biological effects of uric acid; reactive oxygen species; and nitric oxide, which are the major products of XOR activity, have long been debated, but have not yet been clearly elucidated. Recently, a system for measuring highly sensitive XOR activity in human plasma was established, and there has been progress in the research on the mechanisms of XOR activity. In addition, there are accumulating findings about the relationship between XOR activity and CVD. In this narrative review, we summarize existing knowledge regarding plasma XOR activity and its relationship with CVD and discuss future perspectives. [ABSTRACT FROM AUTHOR]

Background: While type 2 diabetes (T2D) is a major risk for ischemic stroke, the associated vessel wall characteristics remain essentially unknown. This study aimed to clarify intracranial vascular changes on three-dimensional vessel wall imaging (3D-VWI) using fast spin echo by employing 7Tesla (7T) magnetic resonance imaging (MRI) in T2D patients without advanced atherosclerosis as compared to healthy controls. Methods: In 48 T2D patients and 35 healthy controls, the prevalence of cerebral small vessel diseases and intracranial plaques were evaluated by 3D-VWI with 7T MRI. Results: The prevalence rate of lacunar infarction was significantly higher in T2D than in controls (n = 8 in T2D vs. n = 0 in control, p = 0.011). The mean number of intracranial plaques in both anterior and posterior circulation of each subject was significantly larger in T2D than in controls (2.23 in T2D vs. 0.94 in control, p < 0.01). In T2D patients, gender was associated with the presence of intracranial plaques. Conclusion: This is the first study to demonstrate the high prevalence of intracranial plaque in T2D patients with neither confirmed atherosclerotic disease nor symptoms by performing intracranial 3D-VWI employing 7TMRI. Investigation of intracranial VWI with 7T MRI is expected to provide novel insights allowing early intensive risk management for prevention of ischemic stroke in T2D patients. [ABSTRACT FROM AUTHOR]

A 46-year-old man, receiving continuous steroid therapy for refractory ulcerative colitis with an insufficient response to anti-tumor necrosis factor-α therapy, presented with left buttock pain. He was diagnosed with steroidal left femoral head necrosis, and total proctocolectomy with permanent ileostomy was performed. At 6 months postoperatively, the patient developed general fatigue, abdominal pain, and severe ileostomy diarrhea. Computed tomography revealed continuous intestinal edema from the descending duodenal leg to the upper jejunum. Gastrointestinal endoscopy revealed deep ulcers, coarse mucosa, and duodenal erosion. Based on clinical progress, findings, and pathology, the patient was diagnosed with ulcerative colitis-related postoperative enteritis. Although 5-aminosalicylic acid treatment was initiated, his symptoms persisted, bloody diarrhea from colostomy was observed. Subsequently, granulocyte and monocyte apheresis treatment was added. Symptoms and endoscopic findings improved with granulocyte and monocyte apheresis. Azathioprine was introduced as maintenance therapy, and no sign of recurrence was observed. Although ulcerative colitis-related postoperative enteritis has no definitive treatment, granulocyte and monocyte apheresis may be considered for initial treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgery has shown that early-stage esophageal cancer is accompanied by extensive lymph node metastasis. Therefore, elective nodal irradiation is indispensable for chemoradiotherapy instead of surgery for the radical cure of esophageal cancer. In contrast, attention must be paid to adverse effects when applying radiation to a wide area. Adverse events are generally more intense with high-dose irradiation. Therefore, determining the appropriate dose for prophylactic irradiation to the elective nodal area is important. However, the appropriate dose has not been fixed. In this study, the therapeutic effects and adverse events of a group of 36 Gy elective nodal irradiation doses were similar to those of 40 Gy or higher. This study's results indicate that preventing lymph node metastasis at lower doses is possible, thus suppressing adverse events. We evaluated elective nodal irradiation (ENI) doses during radical chemoradiotherapy (CRT) for esophageal cancer (EC). A total of 79 patients (65 men and 14 women) aged 52–80 years with T1-3, N0-3, and M0 (including M1ly) who underwent CRT for EC during November 2012–September 2019 were eligible for this retrospective analysis. Patients were divided into two groups: the high-dose group (HG), including 38 patients who received ≥40 Gy as ENI; and the low-dose group (LG), including 41 patients who received <40 Gy. The median doses were 40.0 and 36.0 Gy in HG and LG, respectively. During the follow-up (median: 36.7 months), no lymph node recurrence was observed in the ENI field in all patients. Lymph node recurrence near the ENI field was observed in six patients. No significant differences were observed between the two groups in median overall survival, progression-free survival, and local control. Grade 3–4 acute and late adverse events were observed in five patients of HG and six patients of LG, respectively. No ulceration or stricture was observed in the ENI field on endoscopy examined with 58 Gy irradiation. In conclusion, an ENI dose of 36 Gy could be considered to control the elective nodes of EC. [ABSTRACT FROM AUTHOR]

Introduction: Xanthine oxidoreductase (XOR) has been identified as a critical source of reactive oxygen species in various pathophysiological conditions, including hypertension, endothelial dysfunction, and atherosclerosis. This study investigated the association between XOR and renal function in a general Japanese population. Methods: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a community-based cohort study in Iwate prefecture. Chronic kidney disease (CKD) was estimated using the estimated glomerular filtration rate of cystatin C (eGFRcys). Individuals with a history of hyperuricemia or severe renal dysfunction (eGFRcys <15 mL/min/1.73 m2 or undergoing dialysis) were excluded from the study. We performed a multinominal multivariate logistic analysis adjusted for age, blood pressure, uric acid, glycated hemoglobin A1c, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to associate XOR activity and renal function. Results: The present study included 4,248 participants (male/female: 1,373/2,875, age: 62.9 ± 11.7 years). When participants were divided according to XOR quartiles, blood pressure, body mass index, uric acid, low-density lipoprotein cholesterol, and glycated hemoglobin A1c were highest in the highest XOR quartile (all p < 0.001). The XOR activity was significantly higher in the subgroup with CKD stage G3 and G4 (G1 vs. G2 vs. G3-G4: 44.8 ± 40.5 vs. 52.0 ± 42.9 vs. 54.1 ± 43.9 pmol/h/mL, p = 0.02). The higher XOR activity was significantly associated with an increase of CKD stage: the odd ratios (95% confidence intervals) per 1 pmol/h/mL increase in XOR activity with CKD stage G1 as a reference were 1.37 (1.13–1.73) in G2 and 1.51 (1.30–1.84) in G3-G4. Conclusion: The present study concluded that high XOR activity was associated with the severity of CKD in a general Japanese population, suggesting that upregulated XOR activity may be involved in advanced renal dysfunction. [ABSTRACT FROM AUTHOR]

High-spatial resolution observation of high-wavenumber broadband turbulence is achieved by controlling the magnetic field to be relatively low and measuring with a azimuthally arranged multi-channel Langmuir array in a basic laboratory plasma. The observed turbulence consists of narrowband low-frequency fluctuations and broadband high-frequency turbulent fluctuations. The low-frequency fluctuations have a frequency of about 0.7 times the ion cyclotron frequency and a spatial scale of 1/10 of the ion inertial scale. In comparison, high-frequency fluctuations have a higher frequency than the ion cyclotron frequency and spatial scales of 1/10–1/40 of the ion inertial scale. Two-dimensional correlation analysis evaluates the spatial and temporal correlation lengths and reveals that the high-wavenumber broadband fluctuations have turbulent characteristics. The measurements give us further understanding of small scale turbulence in space and fusion plasmas. [ABSTRACT FROM AUTHOR]

Background: 17O‐labeled water (PSO17) is a contrast agent developed to measure brain water dynamics and cerebral blood flow. Purpose: To evaluate the safety and feasibility of PSO17. Study Type: Prospective study. Subjects: A total of 12 male healthy volunteers (23.1 ± 1.9 years) were assigned to three groups of four subjects: placebo (normal saline), PSO17 10%, and PSO17 20%. Field Strength/Sequence: Dynamic 3D fluid attenuated inversion recovery (FLAIR, fast spin echo with variable refocusing flip angle) scans of the brain were performed with 3‐T MRI. Assessment: Contrast agents were injected 5 minutes after the start of a 10‐minute scan. Any symptoms, vital signs, and blood and urine tests were evaluated at five timepoints from preinjection to 4 days after. Blood samples for pharmacokinetic analysis, including half‐life (T1/2), maximum fraction (Cmax), time‐to‐maximum fraction (Tmax), and area under the curve (AUC), were collected at 13 timepoints from preinjection to 168 hours after. Regions of interest were set in the cerebral cortex (CC), basal ganglia/thalamus (BG/TM), and white matter (WM), and 17O concentrations were calculated from signal changes and evaluated using Cmax. Statistical Tests: All items were compared among the three groups using Tukey–Kramer's honestly significant difference test. Statistical significance was defined as P < 0.5. Results: No safety issues were noted with the intravenous administration of PSO17. The T1/2 was approximately 160 hours, and the AUCs were 1.77 ± 0.10 and 3.75 ± 0.36 in the PSO17 10% and 20% groups, respectively. 17O fractions calculated from MRI signals were higher in the PSO17 20% group than in the 10% and placebo groups. Significant differences were noted between all pairs of groups in the CC and BG/TM, and between PSO17 20% and both placebo and 10% groups in the WM. Data Conclusion: PSO17 might be considered safe as a contrast medium. Dynamic 3D‐FLAIR might detect dose‐dependent signal changes and estimate 17O. Evidence Level: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

The etiology of POEMS syndrome and its associated polyneuropathy have not been fully elucidated. The clinical picture of POEMS-associated polyneuropathy and nutritional polyneuropathy due to vitamin B6 (VB6) deficiency are strikingly similar, both being typically sensorimotor, symmetrical, stocking and glove distribution, and more severe in the lower extremities. We report two consecutive POEMS patients with VB6 deficiency who showed unusual rapid and drastic recovery of polyneuropathies within 6–8 weeks after oral VB6 supplementation. Case 1 was supplemented with VB6 from time of autologous stem cell transplantation. Polyneuropathy began to improve within one week, and he became walker-free and could walk unaided with a cane within 6 weeks. Case 2 was supplemented with VB6 from time of stem cell harvest, and he became cane-free and his gait almost normalized within two months. Nerve conduction studies were also confirmatory of neurologic recovery in both cases. Objective physical improvement of POEMS-associated polyneuropathy has been reported to typically require approximately a year after autologous stem cell transplantation, and together with our observations of VB6 deficiency and supplementations leading to accelerated recoveries of polyneuropathy, VB6 deficiency most probably contributes to POEMS-associated polyneuropathy. VB6 acts as a coenzyme in approximately 150 biochemical reactions. VB6 has been reported to inhibit the hypoxia-inducible factor/vascular endothelial growth factor (VEGF) pathway, and VEGF levels are known to corollate with disease activity of POEMS syndrome. Therefore, VB6 deficiency may contribute not only to POEMS-associated polyneuropathy, but also to the etiology of POEMS syndrome itself. [ABSTRACT FROM AUTHOR]

Simple Summary: We investigated the long-term outcomes of patients with hepatocellular carcinoma (HCC) who underwent image-guided respiratory-gated proton therapy (IGPT) without fiducial markers with 4D-CT planning. IGPT achieved good local control, increased overall survival, and caused less severe toxicity. Our results suggest that less invasive IGPT for HCC is safe and effective without causing severe complications. We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan–Meier method. Toxicity was graded per CTCAE v5.0. Patients (n = 105; median age 73 years, range 38–90 years) with 128 lesions were treated. The median radiation dose was 66 gray relative biological effectiveness (GyRBE) (range, 52.8–82.5 GyRBE) delivered in 2.0 to 6.6 GyRBE fractions, depending on lesion volume, the involved liver, and the patient's condition. The median follow-up of surviving patients was 63 months (range, 1–126 months), and the 5-year LTC and OS rates were 93.2% and 40.4%, respectively. Univariate and multivariate analyses identified tumors near the gastrointestinal tract as an independent risk factor for local recurrence and revealed that hepatic reserve, tumor stage, performance status, operability, sex, and portal vein thrombosis were independent risk factors for OS. Acute and late treatment-related grade 3 toxicities were experienced by eight patients (7.6%). Adverse events ≥ grade 4 were not evident. Marker-less respiratory-gated PT for HCC is a safe and effective treatment without severe complications. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to investigate the influence of the trunk position during the single-leg landing on the knee angle and muscle activity. Forty healthy university students (20 men and 20 women) performed right single-leg landings from a 40 cm-high platform with the trunk in neutral, flexion, extension, and right and left lateral flexion. Knee flexion and valgus angles were determined by two-dimensional video analysis, and rectus femoris (RF) and biceps femoris (BF) muscle activities were assessed. The knee flexion angle was significantly higher in the trunk-flexion position than in the other trunk positions. The knee valgus angle was significantly lower in the trunk-neutral and trunk-flexion positions than in the trunk-extension, trunk-right-lateral-flexion, and trunk-left-lateral flexion positions. Muscle activity of the RF was significantly lower in the trunk-flexion position than in the trunk-extension position and that of the BF was significantly higher in the trunk-flexion position than in the trunk-neutral, trunk-extension, and trunk-right-lateral-flexion positions. Single (right)-leg landing with the trunk in flexion may confer a low risk of anterior cruciate ligament injury compared to that with the trunk in extension or right lateral flexion. [ABSTRACT FROM AUTHOR]