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Background: Chemotherapy-induced nausea and vomiting (CINV) are common side effects, classified according to timing and severity. Conventional agents such as dexamethasone are effective but have various side effects. For moderately emetogenic chemotherapy, dexamethasone-sparing antiemetic therapies have been developed to minimize these side effects. This systematic review evaluated the efficacy and safety of dexamethasone-sparing antiemetic therapy for highly emetogenic chemotherapy (HEC). Methods: We performed a thorough literature search for studies related to dexamethasone-sparing antiemetic therapy with neurokinin-1 antagonists (NK1RA) for HEC using the PubMed, Cochrane Library, and Ichushi-Web databases. A qualitative analysis of the combined data was performed and risk differences with confidence intervals were calculated. Results: Two reviewers independently assessed the 425 records and 12 full-text articles were evaluated for eligibility. Two studies were included in the qualitative and meta-analyses. These studies included anthracycline-cyclophosphamide (AC) regimens and cisplatin-based regimens, with palonosetron as the serotonin receptor antagonist. In the two studies, no difference was found in the prevention of vomiting (delayed complete response). However, non-inferiority was not demonstrated in the subgroup that received cisplatin-containing regimens. Delayed complete control showed different results for nausea prevention; however, there was no significant difference in the meta-analysis. Only one report has shown non-inferiority for delayed total control. Although the strength of evidence for individual outcomes varied, there was no difference in the duration of dexamethasone administration. Conclusions: This systematic review and meta-analysis revealed that dexamethasone-sparing antiemetic therapy with NK1RA and palonosetron can be used to prevent CINV in HEC, limited to AC combination therapy. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced nausea and vomiting (CINV) commonly affects patient quality of life and the overall effectiveness of chemotherapy. This study aimed to evaluate whether adding neurokinin-1 receptor antagonists (NK1RAs) to 5-hydroxytryptamine-3 receptor antagonists (5-HT3RAs) and corticosteroids provides clinically meaningful benefits in preventing CINV in patients receiving moderately emetogenic chemotherapy (MEC). Methods: We conducted a systematic review of PubMed, Cochrane Library, and Ichushi-Web to identify clinical studies evaluating NK1RAs combined with 5-HT3RAs and dexamethasone for managing CINV in MEC. The endpoints were complete response (CR), complete control (CC), total control (TC), adverse events, and costs. The data were analyzed using a random effects model. Results: From 142 articles identified, 15 randomized controlled trials (RCTs), involving 4,405 patients, were included in the meta-analysis. Approximately 60% of the patients received carboplatin (CBDCA)-based chemotherapy. The meta-analysis showed that triplet antiemetic prophylaxis with NK1RA was significantly more effective for achieving CR than doublet prophylaxis in each phase. Regarding CC, the triplet antiemetic prophylaxis was significantly more effective than the doublet in the overall (risk difference [RD]: 0.11, 95% confidence interval [CI]: 0.06–0.17) and delayed (RD: 0.08, 95% CI: 0.02–0.13) phases. For TC, no significant differences were observed in any phase. Adding NK1RA did not cause adverse events. Conclusions: Adding NK1RA to CBDCA-based chemotherapy has shown clinical benefits. However, the clinical benefits of NK1RA-containing regimens for overall MEC have not yet been established and require RCTs that exclusively evaluate MEC regimens other than CBDCA-based chemotherapy. [ABSTRACT FROM AUTHOR]

The role of torso computed tomography (CT) in evaluating body composition has been unexplored. This study assessed the potential of low-dose torso CT from positron emission tomography (PET)/CT for analyzing body composition and its relation to muscle strength. We retrospectively recruited 384 healthy Korean adults (231 men, 153 women) who underwent torso 18F-FDG PET/CT, bioelectrical impedance analysis (BIA), and muscle strength tests (handgrip strength [HGS] and knee extension strength [KES]). CT images were segmented into three compartments: torso volumetric, abdominal volumetric, and abdominal areal. Muscle amounts from each compartment were indexed to height (m2). BIA and HGS served as reference standards, with correlation coefficients (r) calculated. Torso muscle volumetric index (TorsoMVI) had the strongest correlations with BIA-derived values (r = 0.80 for men; r = 0.73 for women), surpassing those from the abdominal compartments. TorsoMVI was also correlated significantly with HGS (r = 0.39, p < 0.01) and differentiated between normal and possible sarcopenia in men (n = 225, 5960 ± 785 cm3/m2 vs. n = 6, 5210 ± 487 cm3/m2, p = 0.02). In women, KES correlated more strongly with muscle parameters than HGS. Despite gender-specific variations, torso CT-derived parameters show promise for evaluating body composition and sarcopenia. [ABSTRACT FROM AUTHOR]

Fucosterols have been widely studied for their antioxidant, anticancer, and anti-inflammatory properties. However, they have not yet been studied in the field of dentistry. This study aimed to determine whether pretreatment of dentin with fucosterol before resin restoration enhances bond stability in resin-dentin hybrid layers. After applying 0.1, 0.5, and 1.0 wt% fucosterol to demineralized dentin, microtensile bond strength (MTBS) and nanoleakage tests were performed before and after collagenase aging, and the surface was observed using scanning electron microscope (SEM). The fucosterol-treated group showed better bond strength and less nanoleakage both before and after collagenase aging, and the corresponding structures were confirmed using SEM. MMP zymography confirmed that the activity of MMPs was relatively low along the concentration gradient of fucosterol, and the FTIR analysis confirmed the production of collagen crosslinks. In addition, fucosterol exhibits cytotoxicity against Streptococcus mutans, the main cause of dental decay. The results of this study suggest that fucosterol pretreatment improves bond strength and reduces nanoleakage at the resin-dentin interface, possibly through a mechanism involving collagen cross-link formation via the inhibition of endogenous and exogenous MMP activity. This study demonstrates the potential of fucosterol as an MMP inhibitor in dentin, which contributes to long-term resin-dentin bond stability and can be used as a restorative material. [ABSTRACT FROM AUTHOR]

Background: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. Methods: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case–control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. Results: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49–0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32–0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. Conclusions: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings. [ABSTRACT FROM AUTHOR]

Background: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens. Methods: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020. Results: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated. Conclusions: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers. [ABSTRACT FROM AUTHOR]

Background: Thymic cysts are a rare benign disease that needs to be distinguished from low-risk thymoma. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a non-invasive imaging technique used in the differential diagnosis of thymic epithelial tumours, but its usefulness for thymic cysts remains unclear. Our study evaluated the utility of visual findings and quantitative parameters of [18F]FDG PET/CT for differentiating between thymic cysts and low-risk thymomas. Methods: Patients who underwent preoperative [18F]FDG PET/CT followed by thymectomy for a thymic mass were retrospectively analyzed. The visual [18F]FDG PET/CT findings evaluated were PET visual grade, PET central metabolic defect, and CT shape. The quantitative [18F]FDG PET/CT parameters evaluated were PET maximum standardized uptake value (SUVmax), CT diameter (cm), and CT attenuation in Hounsfield units (HU). Findings and parameters for differentiating thymic cysts from low-risk thymomas were assessed using Pearson's chi-square test, the Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. Results: Seventy patients (18 thymic cysts and 52 low-risk thymomas) were finally included. Visual findings of PET visual grade (P < 0.001) and PET central metabolic defect (P < 0.001) showed significant differences between thymic cysts and low-risk thymomas, but CT shape did not. Among the quantitative parameters, PET SUVmax (P < 0.001), CT diameter (P < 0.001), and CT HU (P = 0.004) showed significant differences. In ROC analysis, PET SUVmax demonstrated the highest area under the curve (AUC) of 0.996 (P < 0.001), with a cut-off of equal to or less than 2.1 having a sensitivity of 100.0% and specificity of 94.2%. The AUC of PET SUVmax was significantly larger than that of CT diameter (P = 0.009) and CT HU (P = 0.004). Conclusions: Among the [18F]FDG PET/CT parameters examined, low FDG uptake (SUVmax ≤ 2.1, equal to or less than the mediastinum) is a strong diagnostic marker for a thymic cyst. PET visual grade and central metabolic defect are easily accessible findings. [ABSTRACT FROM AUTHOR]

Somatostatin analogues have recently been used as therapeutic targets for metastatic or surgically unresectable gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), and associated somatostatin receptor (SSTR) expression has been well demonstrated in most GEP NETs, with the exception of rectal NETs. SSTR2 immunohistochemical expressions were evaluated in 350 surgically or endoscopically resected rectal NETs and compared to clinicopathologic factors. SSTR2 expression was observed in 234 (66.9%) rectal NET cases and associated tumors with smaller size (p = 0.001), low pT classification (p = 0.030), low AJCC tumor stage (p = 0.012), and absence of chromogranin expression (p = 0.009). Patients with rectal NET and SSTR2 expression had significantly better overall survival than those without SSTR2 expression both by univariable (p = 0.006) and multivariable (p = 0.014) analyses. In summary, approximately two-thirds of rectal NETs expressed SSTR2. SSTR2 expression was significantly associated with favorable behavior and good overall survival in patients with rectal NETs. Furthermore, SSTR2 expression can be used as prognostic factors. When metastatic disease occurs, SSTR2 expression can be used a possible target for somatostatin analogues. [ABSTRACT FROM AUTHOR]

Background: Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE has shown efficacy in patients with metastatic neuroendocrine tumours (NETs). Personalised dosimetry is crucial to optimise treatment outcomes and minimise adverse events. In this study, we investigated the correlation between the tumour-absorbed dose (TAD) estimated from [177Lu]Lu-DOTA-TATE SPECT/CT and the therapeutic response. Method: A retrospective analysis was conducted on patients with advanced well-differentiated NETs grades 1–3 who underwent PRRT and exhibited greater uptake than liver on pre-therapeutic [68Ga]Ga-DOTA-TOC PET/CT. Target lesions were selected based on the RECIST 1.1 and PERCIST 1.0 criteria using [177Lu]Lu-DOTA-TATE SPECT/CT and pre-therapeutic contrast-enhanced CT scans. For anatomical image analysis, the sum of the longest diameter (SLD) of the target lesions was measured using the RECIST 1.1 criteria for patient-based analysis and the longest diameter (LD) of the target lesion using the RECIST-L criteria for lesion-based analysis. Standardised uptake values (SUVs) were measured on SPECT/CT images, and TADs were calculated based on the SUVs. Dosimetry was performed using a single SPECT/CT imaging time point at day 4–5 post-therapy. Statistical analyses were conducted to investigate correlations and determine the target lesion responses. Results: Twenty patients with primary tumour sites and hepatic metastases were included. Fifty-five target lesions, predominantly located in the pancreas and liver, were analysed. The cumulative TAD (lesion-based analysis: r = 0.299–0.301, p = 0.025–0.027), but not the cycle 1 SUV (lesion-based analysis: r = 0.198–0.206, p = 0.131–0.147) or cycle 1 TAD (lesion-based analysis: r = 0.209–0.217, p = 0.112–0.126), exhibited a significant correlation with the change in LD of the target lesion. Binary logistic regression analysis identified the significance of the cumulative TAD in predicting disease control according to the RECIST-L criteria (odds ratio = 1.031–1.051, p = 0.024–0.026). Conclusions: The cumulative TAD estimated from [177Lu]Lu-DOTA-TATE SPECT/CT revealed a significant correlation with change in LD, which was significantly higher for the cumulative TAD than for the cycle 1 SUV or TAD. A higher cumulative TAD was associated with disease control in the target lesion. However, considering the limitations inherent to a confined sample size, careful interpretation of these findings is required. Estimation of the cumulative TAD of [177Lu]Lu-DOTA-TATE therapy could guide the platform towards personalised therapy. [ABSTRACT FROM AUTHOR]

Background: The increased expression of the nicotinic acetylcholine receptor (nAChR) in muscle denervation is thought to be associated with electrophysiological acetylcholine supersensitivity after nerve injury. Hence, we investigated the utility of the 18F-ASEM alpha7-nAChR targeting radiotracer as a new diagnostic method by visualizing skeletal muscle denervation in mouse models of sciatic nerve injury. Methods: Ten-week-old C57BL/6 male mice were utilized. The mice were anesthetized, and the left sciatic nerve was resected after splitting the gluteal muscle. One week (n = 11) and three weeks (n = 6) after the denervation, 18F-ASEM positron emission tomography/magnetic resonance imaging (PET/MRI) was acquired. Maximum standardized uptake values (SUVmax) of the tibialis anterior muscle were measured for the denervated side and the control side. Autoradiographic evaluation was performed to measure the mean counts of the denervated and control tibialis anterior muscles at one week. In addition, immunohistochemistry was used to identify alpha7-nAChR-positive areas in denervated and control tibialis anterior muscles at one week (n = 6). Furthermore, a blocking study was conducted with methyllycaconitine (MLA, n = 5). Results: 18F-ASEM PET/MRI showed significantly increased 18F-ASEM uptake in the denervated tibialis anterior muscle relative to the control side one week and three weeks post-denervation. SUVmax of the denervated muscles at one week and three weeks showed significantly higher uptake than the control (P = 0.0033 and 0.0277, respectively). The relative uptake by autoradiography for the denervated muscle was significantly higher than in the control, and immunohistochemistry revealed significantly greater alpha7-nAChR expression in the denervated muscle (P = 0.0277). In addition, the blocking study showed no significant 18F-ASEM uptake in the denervated side when compared to the control (P = 0.0796). Conclusions: Our results suggest that nAChR imaging with 18F-ASEM has potential as a noninvasive diagnostic method for peripheral nervous system disorders. [ABSTRACT FROM AUTHOR]

Background: Lutetium (Lu)-177 peptide receptor radionuclide therapy (PRRT) is one of the standard treatments for somatostatin receptor-positive well-differentiated neuroendocrine tumors (NETs). However, limited Asian representation in the pivotal NETTER-1 trial and a lack of real-world data for Lu-177 PRRT from Asian regions exist. Objective: This retrospective study aimed to evaluate the efficacy and safety of Lu-177 PRRT in Korean patients with advanced NETs. Patients and Methods: This study analyzed 64 patients treated with Lu-177 DOTATATE PRRT at the Asan Medical Center, Seoul, Korea, between November 2019 and December 2022. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), and safety profile. Results: The median age of patients was 55 years. Prior to PRRT, patients received a median of two lines (range 0–6) of systemic therapy. Fifty (78%) patients received the planned four cycles of Lu-177 DOTATATE PRRT. The median PFS was 21.7 months (95% confidence interval 16.7–not available) and the ORR was 20%. With a median follow-up of 15.7 months (range 1.0–39.3), the median OS was not reached and the 1-year OS rate was 88%. The median PFS was better in patients with grade 1–2 NETs than in those with grade 3 NET (not reached vs. 14.2 months; hazard ratio 3.15; p = 0.0058). Hematological toxicities were the common adverse events, including grade ≥ 3 anemia (7.8%), neutropenia (10.9%), and thrombocytopenia (9.4%). Conclusions: In Korean patients with advanced NETs, Lu-177 DOTATATE PRRT showed efficacy and safety outcomes, consistent with those in the NETTER-1 trial and previous Western real-world studies. [ABSTRACT FROM AUTHOR]

Transition metal hydroxides (TM(OH)2) have drawn significant attention for their potential applications in the environmental and energy field. In this study, we investigated the phase transition of cobalt hydroxide (Co(OH)2) under electron beam irradiation using in situ high-resolution transmission electron microscopy. Both the α- and β-Co(OH)2 phases underwent a phase transition to a spinel Co3O4 phase, forming nanograins with a porous morphology. However, the α-Co(OH)2 showed a faster phase transition and dramatic volume shrinkage during the phase transition. Our results provide a detailed explanation of the mechanism behind the deterioration of the layered structure and the emergence of defects during the phase transition. [ABSTRACT FROM AUTHOR]

Animal models have been utilized to understand the pathogenesis of Zellweger spectrum disorders (ZSDs); however, the link between clinical manifestations and molecular pathways has not yet been clearly established. We generated peroxin 5 homozygous mutant zebrafish (pex5−/−) to gain insight into the molecular pathogenesis of peroxisome dysfunction. pex5−/− display hallmarks of ZSD in humans and die within one month after birth. Fasting rapidly depletes lipids and glycogen in pex5−/− livers and expedites their mortality. Mechanistically, deregulated mitochondria and mechanistic target of rapamycin (mTOR) signaling act together to induce metabolic alterations that deplete hepatic nutrients and accumulate damaged mitochondria. Accordingly, chemical interventions blocking either the mitochondrial function or mTOR complex 1 (mTORC1) or a combination of both improve the metabolic imbalance shown in the fasted pex5−/− livers and extend the survival of animals. In addition, the suppression of oxidative stress by N-acetyl L-cysteine (NAC) treatment rescued the apoptotic cell death and early mortality observed in pex5−/−. Furthermore, an autophagy activator effectively ameliorated the early mortality of fasted pex5−/−. These results suggest that fasting may be detrimental to patients with peroxisome dysfunction, and that modulating the mitochondria, mTORC1, autophagy activities, or oxidative stress may provide a therapeutic option to alleviate the symptoms of peroxisomal diseases associated with metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Primary mediastinal germ cell tumor (MGCT) is an uncommon tumor. Although it has histology similar to that of gonadal germ cell tumor (GCT), the prognosis for MGCT is generally worse than that for gonadal GCT. We performed visual assessment and quantitative analysis of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) for MGCTs. A total of 35 MGCT patients (age = 33.1 ± 16.8 years, F:M = 16:19) who underwent preoperative PET/CT were retrospectively reviewed. The pathologic diagnosis of MGCTs identified 24 mature teratomas, 4 seminomas, 5 yolk sac tumors, and 2 mixed germ cell tumors. Visual assessment was performed by categorizing the uptake intensity, distribution, and contour of primary MGCTs. Quantitative parameters including the maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter were compared between benign and malignant MGCTs. On visual assessment, the uptake intensity was the only significant parameter for differentiating between benign and malignant MGCTs (p = 0.040). In quantitative analysis, the SUVmax (p < 0.001), TBR (p < 0.001), MTV (p = 0.033), and TLG (p < 0.001) showed significantly higher values for malignant MGCTs compared with benign MGCTs. In receiver operating characteristic (ROC) curve analysis of these quantitative parameters, the SUVmax had the highest area under the curve (AUC) (AUC = 0.947, p < 0.001). Furthermore, the SUVmax could differentiate between seminomas and nonseminomatous germ cell tumors (p = 0.042) and reflect serum alpha fetoprotein (AFP) levels (p = 0.012). The visual uptake intensity and SUVmax on [18F]FDG PET/CT showed discriminative ability for benign and malignant MGCTs. Moreover, the SUVmax may associate with AFP levels. [ABSTRACT FROM AUTHOR]

Purpose: We compared the feasibility of quantitative analysis methods using bone SPECT/CT with those using planar bone scans to assess active sacroiliitis. Methods: We retrospectively reviewed whole-body bone scans and pelvic bone SPECT/CTs of 8 patients who had clinically confirmed sacroiliitis and enrolled 24 patients without sacroiliitis as references. The volume of interest of each sacroiliac joint, including both the ilium and sacrum, was drawn. Active arthritis zone (AAZ) was defined as the zone of voxels with higher SUV than sacral mean SUV within the VOI of SI joint. Then, the following SPECT/CT quantitative parameters, SUVmax (maximum SUV), SUV50% (mean SUV in highest 50% of SUV), and SUV-AAZ, and the ratio of those values to sacral mean SUV (SUVmax/S, SUV50%/S, SUV-AAZ/S) were calculated. For the planar bone scan, the mean count ratio of SI joint/sacrum (SI/S) was conventionally measured. Results: Most of the SPECT/CT parameters of the sacroiliitis group were significantly higher than the normal group, whereas SI/S of the planar bone scan was not significantly different between the two groups. In receiver operating characteristic curve analysis, SUV-AAZ/S showed the highest AUC of 0.992, followed by SUV50%/S and SUVmax/S. All ratio parameters of the SPECT/CT showed higher AUC values than the SUV parameters of SI joint or SI/S of the planar scan. Conclusions: The quantitative analyses of bone SPECT/CT showed better performance in assessing active sacroiliitis than the planar bone scan. SPECT/CT parameters using the ratio of the SI joint to sacrum showed more favorable results than SUV parameters such as SUVmax, SUV50%, and SUV-AAZ. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the prognostic value of basal and interim [68Ga]Ga-DOTA-TOC PET/CT in patients with locally advanced or metastatic neuroendocrine tumour (NET) who received peptide receptor radionuclide therapy (PRRT).Patients with NET who received PRRT with [177Lu]Lu-DOTA-TATE at our institution were retrospectively reviewed. Among them, patients who underwent both basal and interim (after two cycles of PRRT) [68Ga]Ga-DOTA-TOC PET/CT were included. Alongside clinicopathologic parameters, PET parameters of maximum standardised uptake value (SUVmax), tumour-to-liver ratio (TLR), whole tumour volume (WTV) and total receptor expression (TRE: WTV multiplied by mean standardised uptake value) were obtained from basal and interim [68Ga]Ga-DOTA-TOC PET/CT, and their proportional changes (∆) were assessed for associations with progression-free survival (PFS) using Kaplan–Meier analysis, log-rank tests, and a Cox proportional-hazards regression model.Twenty-four patients were finally included (10 men and 14 women, median age of 56.5 years, age range 32–74 years). Among them, 16 patients (66.7%) experienced disease progression. In univariate analysis, high ∆WTV (≥ −10%, hazard ratio [HR] = 3.053 [1.003–9.289], p = 0.049) and high ∆TRE (≥ −21%, HR = 3.567 [1.144–11.122], p = 0.028) were significantly associated with shorter PFS. In multivariate analyses adjusted for WHO grade, high ∆WTV (HR = 3.345 [1.055–10.601], p = 0.043) and high ∆TRE (HR = 3.894 [1.194–12.695], p = 0.024) were significant predictors of shorter PFS.The study demonstrates that basal and interim [68Ga]Ga-DOTA-TOC PET/CT scans, through proportional changes in WTV and TRE, effectively predict PFS in neuroendocrine tumour patients receiving PRRT.QuestionPeptide receptor radionuclide therapy is utilised for patients with somatostatin receptor-positive well-differentiated neuroendocrine tumours; however, prognostic predictors are not well established.FindingsProgression-free survival was significantly associated with the proportional change in whole tumour volume and total receptor expression between basal and interim [68Ga]Ga-DOTA-TOC PET/CT.Clinical relevanceInterim [68Ga]Ga-DOTA-TOC PET/CT can serve as a valuable imaging method to predict prognosis of peptide receptor radionuclide therapy.Methods: This study evaluated the prognostic value of basal and interim [68Ga]Ga-DOTA-TOC PET/CT in patients with locally advanced or metastatic neuroendocrine tumour (NET) who received peptide receptor radionuclide therapy (PRRT).Patients with NET who received PRRT with [177Lu]Lu-DOTA-TATE at our institution were retrospectively reviewed. Among them, patients who underwent both basal and interim (after two cycles of PRRT) [68Ga]Ga-DOTA-TOC PET/CT were included. Alongside clinicopathologic parameters, PET parameters of maximum standardised uptake value (SUVmax), tumour-to-liver ratio (TLR), whole tumour volume (WTV) and total receptor expression (TRE: WTV multiplied by mean standardised uptake value) were obtained from basal and interim [68Ga]Ga-DOTA-TOC PET/CT, and their proportional changes (∆) were assessed for associations with progression-free survival (PFS) using Kaplan–Meier analysis, log-rank tests, and a Cox proportional-hazards regression model.Twenty-four patients were finally included (10 men and 14 women, median age of 56.5 years, age range 32–74 years). Among them, 16 patients (66.7%) experienced disease progression. In univariate analysis, high ∆WTV (≥ −10%, hazard ratio [HR] = 3.053 [1.003–9.289], p = 0.049) and high ∆TRE (≥ −21%, HR = 3.567 [1.144–11.122], p = 0.028) were significantly associated with shorter PFS. In multivariate analyses adjusted for WHO grade, high ∆WTV (HR = 3.345 [1.055–10.601], p = 0.043) and high ∆TRE (HR = 3.894 [1.194–12.695], p = 0.024) were significant predictors of shorter PFS.The study demonstrates that basal and interim [68Ga]Ga-DOTA-TOC PET/CT scans, through proportional changes in WTV and TRE, effectively predict PFS in neuroendocrine tumour patients receiving PRRT.QuestionPeptide receptor radionuclide therapy is utilised for patients with somatostatin receptor-positive well-differentiated neuroendocrine tumours; however, prognostic predictors are not well established.FindingsProgression-free survival was significantly associated with the proportional change in whole tumour volume and total receptor expression between basal and interim [68Ga]Ga-DOTA-TOC PET/CT.Clinical relevanceInterim [68Ga]Ga-DOTA-TOC PET/CT can serve as a valuable imaging method to predict prognosis of peptide receptor radionuclide therapy.Results: This study evaluated the prognostic value of basal and interim [68Ga]Ga-DOTA-TOC PET/CT in patients with locally advanced or metastatic neuroendocrine tumour (NET) who received peptide receptor radionuclide therapy (PRRT).Patients with NET who received PRRT with [177Lu]Lu-DOTA-TATE at our institution were retrospectively reviewed. Among them, patients who underwent both basal and interim (after two cycles of PRRT) [68Ga]Ga-DOTA-TOC PET/CT were included. Alongside clinicopathologic parameters, PET parameters of maximum standardised uptake value (SUVmax), tumour-to-liver ratio (TLR), whole tumour volume (WTV) and total receptor expression (TRE: WTV multiplied by mean standardised uptake value) were obtained from basal and interim [68Ga]Ga-DOTA-TOC PET/CT, and their proportional changes (∆) were assessed for associations with progression-free survival (PFS) using Kaplan–Meier analysis, log-rank tests, and a Cox proportional-hazards regression model.Twenty-four patients were finally included (10 men and 14 women, median age of 56.5 years, age range 32–74 years). Among them, 16 patients (66.7%) experienced disease progression. In univariate analysis, high ∆WTV (≥ −10%, hazard ratio [HR] = 3.053 [1.003–9.289], p = 0.049) and high ∆TRE (≥ −21%, HR = 3.567 [1.144–11.122], p = 0.028) were significantly associated with shorter PFS. In multivariate analyses adjusted for WHO grade, high ∆WTV (HR = 3.345 [1.055–10.601], p = 0.043) and high ∆TRE (HR = 3.894 [1.194–12.695], p = 0.024) were significant predictors of shorter PFS.The study demonstrates that basal and interim [68Ga]Ga-DOTA-TOC PET/CT scans, through proportional changes in WTV and TRE, effectively predict PFS in neuroendocrine tumour patients receiving PRRT.QuestionPeptide receptor radionuclide therapy is utilised for patients with somatostatin receptor-positive well-differentiated neuroendocrine tumours; however, prognostic predictors are not well established.FindingsProgression-free survival was significantly associated with the proportional change in whole tumour volume and total receptor expression between basal and interim [68Ga]Ga-DOTA-TOC PET/CT.Clinical relevanceInterim [68Ga]Ga-DOTA-TOC PET/CT can serve as a valuable imaging method to predict prognosis of peptide receptor radionuclide therapy.Conclusion: This study evaluated the prognostic value of basal and interim [68Ga]Ga-DOTA-TOC PET/CT in patients with locally advanced or metastatic neuroendocrine tumour (NET) who received peptide receptor radionuclide therapy (PRRT).Patients with NET who received PRRT with [177Lu]Lu-DOTA-TATE at our institution were retrospectively reviewed. Among them, patients who underwent both basal and interim (after two cycles of PRRT) [68Ga]Ga-DOTA-TOC PET/CT were included. Alongside clinicopathologic parameters, PET parameters of maximum standardised uptake value (SUVmax), tumour-to-liver ratio (TLR), whole tumour volume (WTV) and total receptor expression (TRE: WTV multiplied by mean standardised uptake value) were obtained from basal and interim [68Ga]Ga-DOTA-TOC PET/CT, and their proportional changes (∆) were assessed for associations with progression-free survival (PFS) using Kaplan–Meier analysis, log-rank tests, and a Cox proportional-hazards regression model.Twenty-four patients were finally included (10 men and 14 women, median age of 56.5 years, age range 32–74 years). Among them, 16 patients (66.7%) experienced disease progression. In univariate analysis, high ∆WTV (≥ −10%, hazard ratio [HR] = 3.053 [1.003–9.289], p = 0.049) and high ∆TRE (≥ −21%, HR = 3.567 [1.144–11.122], p = 0.028) were significantly associated with shorter PFS. In multivariate analyses adjusted for WHO grade, high ∆WTV (HR = 3.345 [1.055–10.601], p = 0.043) and high ∆TRE (HR = 3.894 [1.194–12.695], p = 0.024) were significant predictors of shorter PFS.The study demonstrates that basal and interim [68Ga]Ga-DOTA-TOC PET/CT scans, through proportional changes in WTV and TRE, effectively predict PFS in neuroendocrine tumour patients receiving PRRT.QuestionPeptide receptor radionuclide therapy is utilised for patients with somatostatin receptor-positive well-differentiated neuroendocrine tumours; however, prognostic predictors are not well established.FindingsProgression-free survival was significantly associated with the proportional change in whole tumour volume and total receptor expression between basal and interim [68Ga]Ga-DOTA-TOC PET/CT.Clinical relevanceInterim [68Ga]Ga-DOTA-TOC PET/CT can serve as a valuable imaging method to predict prognosis of peptide receptor radionuclide therapy.Key Points: This study evaluated the prognostic value of basal and interim [68Ga]Ga-DOTA-TOC PET/CT in patients with locally advanced or metastatic neuroendocrine tumour (NET) who received peptide receptor radionuclide therapy (PRRT).Patients with NET who received PRRT with [177Lu]Lu-DOTA-TATE at our institution were retrospectively reviewed. Among them, patients who underwent both basal and interim (after two cycles of PRRT) [68Ga]Ga-DOTA-TOC PET/CT were included. Alongside clinicopathologic parameters, PET parameters of maximum standardised uptake value (SUVmax), tumour-to-liver ratio (TLR), whole tumour volume (WTV) and total receptor expression (TRE: WTV multiplied by mean standardised uptake value) were obtained from basal and interim [68Ga]Ga-DOTA-TOC PET/CT, and their proportional changes (∆) were assessed for associations with progression-free survival (PFS) using Kaplan–Meier analysis, log-rank tests, and a Cox proportional-hazards regression model.Twenty-four patients were finally included (10 men and 14 women, median age of 56.5 years, age range 32–74 years). Among them, 16 patients (66.7%) experienced disease progression. In univariate analysis, high ∆WTV (≥ −10%, hazard ratio [HR] = 3.053 [1.003–9.289], p = 0.049) and high ∆TRE (≥ −21%, HR = 3.567 [1.144–11.122], p = 0.028) were significantly associated with shorter PFS. In multivariate analyses adjusted for WHO grade, high ∆WTV (HR = 3.345 [1.055–10.601], p = 0.043) and high ∆TRE (HR = 3.894 [1.194–12.695], p = 0.024) were significant predictors of shorter PFS.The study demonstrates that basal and interim [68Ga]Ga-DOTA-TOC PET/CT scans, through proportional changes in WTV and TRE, effectively predict PFS in neuroendocrine tumour patients receiving PRRT.QuestionPeptide receptor radionuclide therapy is utilised for patients with somatostatin receptor-positive well-differentiated neuroendocrine tumours; however, prognostic predictors are not well established.FindingsProgression-free survival was significantly associated with the proportional change in whole tumour volume and total receptor expression between basal and interim [68Ga]Ga-DOTA-TOC PET/CT.Clinical relevanceInterim [68Ga]Ga-DOTA-TOC PET/CT can serve as a valuable imaging method to predict prognosis of peptide receptor radionuclide therapy.Graphical Abstract: This study evaluated the prognostic value of basal and interim [68Ga]Ga-DOTA-TOC PET/CT in patients with locally advanced or metastatic neuroendocrine tumour (NET) who received peptide receptor radionuclide therapy (PRRT).Patients with NET who received PRRT with [177Lu]Lu-DOTA-TATE at our institution were retrospectively reviewed. Among them, patients who underwent both basal and interim (after two cycles of PRRT) [68Ga]Ga-DOTA-TOC PET/CT were included. Alongside clinicopathologic parameters, PET parameters of maximum standardised uptake value (SUVmax), tumour-to-liver ratio (TLR), whole tumour volume (WTV) and total receptor expression (TRE: WTV multiplied by mean standardised uptake value) were obtained from basal and interim [68Ga]Ga-DOTA-TOC PET/CT, and their proportional changes (∆) were assessed for associations with progression-free survival (PFS) using Kaplan–Meier analysis, log-rank tests, and a Cox proportional-hazards regression model.Twenty-four patients were finally included (10 men and 14 women, median age of 56.5 years, age range 32–74 years). Among them, 16 patients (66.7%) experienced disease progression. In univariate analysis, high ∆WTV (≥ −10%, hazard ratio [HR] = 3.053 [1.003–9.289], p = 0.049) and high ∆TRE (≥ −21%, HR = 3.567 [1.144–11.122], p = 0.028) were significantly associated with shorter PFS. In multivariate analyses adjusted for WHO grade, high ∆WTV (HR = 3.345 [1.055–10.601], p = 0.043) and high ∆TRE (HR = 3.894 [1.194–12.695], p = 0.024) were significant predictors of shorter PFS.The study demonstrates that basal and interim [68Ga]Ga-DOTA-TOC PET/CT scans, through proportional changes in WTV and TRE, effectively predict PFS in neuroendocrine tumour patients receiving PRRT.QuestionPeptide receptor radionuclide therapy is utilised for patients with somatostatin receptor-positive well-differentiated neuroendocrine tumours; however, prognostic predictors are not well established.FindingsProgression-free survival was significantly associated with the proportional change in whole tumour volume and total receptor expression between basal and interim [68Ga]Ga-DOTA-TOC PET/CT.Clinical relevanceInterim [68Ga]Ga-DOTA-TOC PET/CT can serve as a valuable imaging method to predict prognosis of peptide receptor radionuclide therapy. [ABSTRACT FROM AUTHOR]

Non-destructive stress measurement by ultrasonic testing is based on calculating the acoustoelastic modulus obtained from the relationship between material stress and sound wave velocity. A critically refracted longitudinal (LCR) wave, which is a bulk longitudinal wave penetrating below and parallel to the surface below an effective depth, is most suitable for ultrasonic stress measurement tests because it exhibits a relatively large change in travel time in response to a change in stress. In particular, the residual stress distribution through the thickness of the subject can be calculated if transducers of different frequencies are applied because of the characteristic of propagation to different depths of penetration depending on the frequency. The main purpose of this study was to visualize the internal or residual stress distribution through the thickness of rails using LCR waves. To this end, LCR probes with different center frequencies were designed and manufactured, and the residual stress values ​​of an unused railroad rail and two used railroad rails operated under different conditions were calculated. This was done using the ultrasonic signals received from each probe, of which the distributions were mapped. Through these mapping results, different residual stress values could be calculated according to the depth. The differences in residual stress generation and distribution according to the conditions surrounding the contact between train wheels and rails, and their characteristics, were visualized and analyzed. As a result, it could be concluded that the non-destructive evaluation technique using LCR waves could detect differences in the residual stress of a rail, and thus can be used to measure the residual stress of the rail accurately. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). Methods: One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. Results: The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 − 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 − 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p < 0.001), whereas MTV and TLG were not. SUVmax was a significant predictor for overall survival in conjunction with clinical stage and resection margin. Conclusion: SUVmax showed excellent diagnostic performance for prediction of TC and significant prognostic value in terms of recurrence and survival. Key Points: • Maximum standardised uptake value (SUVmax) shows excellent performance in the differentiation of thymic carcinoma from low- and high-risk thymoma. • SUVmax is an independent prognostic factor for freedom-from-recurrence in the multivariable Cox proportional hazard model and a significant predictor for overall survival. • 2-[18F]FDG PET/CT can provide a useful diagnostic and prognostic imaging biomarker in conjunction with histologic classification and stage and help choose appropriate management for thymic epithelial tumours. [ABSTRACT FROM AUTHOR]

Permeation properties of hydrogen gas (H2) into nitrile butadiene rubber (NBR), ethylene propylene diene monomer (EPDM), and fluoroelastomer (FKM) which are the strong candidates for sealing material in H2 energy infrastructures, was quantified using a thermal desorption analysis gas chromatography (TDA GC) and a self-developed diffusion-analysis program. The samples were charged with H2 in a high-pressure chamber for 24 h then decompressed into atmosphere, and the mass of H2 released from the sample was measured as a function of elapsed time after decompression. The developed program calculated the total charging amount C0 and diffusivity D, which were then used to calculate the H2 solubility S and permeability P for variation of pressure. The samples were polymerized with and without carbon black (CB) filler in cylindrical shapes with different diameters. There was no appreciable pressure up to 12 MPa or diameter dependence investigated in this study on D, S and P. NBR and EPDM showed dual hydrogen diffusion with fast and slow diffusion behaviors caused by CB, whereas FKM showed a single diffusion behavior. The determined D are Dfast, NBR = (1.55 ± 0.28) × 10–10 m2/s, Dslow, NBR = (3.1 ± 0.5) × 10–11 m2/s, Dfast, EPDM = (3.65 ± 0.66) × 10–10 m2/s, Dslow, EPDM = (3.3 ± 0.5) × 10–11 m2/s, DFKM = (7.7 ± 0.8) × 10–11 m2/s. It appeared that the filler contributes to increase S and decrease D. The uncertainty analysis against the evaluated data was carried out, too, in order that the method could be applicable as a standard test for the permeation properties of various polymer membranes. [ABSTRACT FROM AUTHOR]

Purpose: To determine the prognostic and predictive value of early metabolic response assessed by a change in standardized uptake value (SUV) on interim 18F-FDG PET in patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy. Methods: PubMed and Embase were searched up until 10 September, 2020, for studies evaluating a change in SUV on interim 18F-FDG PET for predicting a pathologic response, progression-free survival (PFS), or overall survival (OS) in patients with esophageal cancer. The sensitivity and specificity for predicting a pathologic response were pooled using bivariate and hierarchical summary receiver operating characteristic (HSROC) models. Meta-analytic pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were derived using a random-effects model. Results: A total of 11 studies (695 patients) were included in the meta-analysis. For nine studies assessing predictive accuracy, the pooled sensitivity and specificity of an early metabolic response for predicting a pathologic response were 0.80 (95% CI 0.61–0.91) and 0.54 (95% CI 0.45–0.63), respectively. The area under the HSROC curve was 0.64 (95% CI 0.60–0.68). Across the nine studies assessing prognostic value, an early metabolic response determined by interim PET showed pooled HRs for predicting PFS and OS of 0.44 (95% CI, 0.30–0.63) and 0.42 (95% CI, 0.31–0.56), respectively. Conclusion: Change in SUV on interim 18F-FDG PET had significant prognostic value and moderate predictive value for a pathologic response in esophageal cancer treated with neoadjuvant chemoradiotherapy. Interim 18F-FDG PET may help prognostic stratification and guide treatment planning in oncologic practice. [ABSTRACT FROM AUTHOR]

Influenza virus and coronavirus, belonging to enveloped RNA viruses, are major causes of human respiratory diseases. The aim of this study was to investigate the broad spectrum antiviral activity of a naturally existing sulfated polysaccharide, lambda-carrageenan (λ-CGN), purified from marine red algae. Cell culture-based assays revealed that the macromolecule efficiently inhibited both influenza A and B viruses with EC50 values ranging from 0.3 to 1.4 μg/ml, as well as currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an EC50 value of 0.9 ± 1.1 μg/ml. No toxicity to the host cells was observed at concentrations up to 300 μg/ml. Plaque titration and western blot analysis verified that λ-CGN reduced expression of viral proteins in cell lysates and suppressed progeny virus production in culture supernatants in a dose-dependent manner. This polyanionic compound exerts antiviral activity by targeting viral attachment to cell surface receptors and preventing virus entry. Moreover, its intranasal administration to mice during influenza A viral challenge not only alleviated infection-mediated reductions in body weight but also protected 60% of mice from virus-induced mortality. Thus, λ-CGN could be a promising antiviral agent for preventing infection with several respiratory viruses. [ABSTRACT FROM AUTHOR]

Patients with cancer should appropriately receive antiemetic therapies against chemotherapy-induced nausea and vomiting (CINV). Antiemetic guidelines play an important role in managing CINV. Accordingly, the first Japanese antiemetic guideline published in 2010 by the Japan Society of Clinical Oncology (JSCO) has considerably aided Japanese medical staff in providing antiemetic therapies across chemotherapy clinics. With the yearly advancements in antiemetic therapies, the Japanese antiemetic guidelines require revisions according to published evidence regarding antiemetic management worldwide. A revised version of the first antiemetic guideline that considered several upcoming evidences had been published online in 2014 (version 1.2), in which several updated descriptions were included. The 2015 JSCO clinical practice guideline for antiemesis (version 2.0) (in Japanese) has addressed clinical antiemetic concerns and includes four major revisions regarding (1) changes in emetogenic risk categorization for anti-cancer agents, (2) olanzapine usage as an antiemetic drug, (3) the steroid-sparing method, and (4) adverse drug reactions of antiemetic agents. We herein present an English update summary for the 2015 JSCO clinical practice guideline for antiemesis (version 2.0). [ABSTRACT FROM AUTHOR]

Objectives: We performed a systematic review and meta-analysis on the prognostic values of 18F-FDG PET/CT in patients with newly diagnosed multiple myeloma (MM). Methods: PubMed and Embase were searched until July 10, 2019, for studies that reported the prognostic significance of 18F-FDG PET in patients with newly diagnosed MM, with overall (OS) and progression-free survival (PFS) included as outcomes. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were meta-analytically pooled using a random-effects model. Results: Fifteen studies (1670 patients) were included for qualitative synthesis. Among multiple PET parameters, the presence of extramedullary disease (EMD), more than three focal lesions (FLs), and high FDG uptake were widely evaluated and significantly associated with shorter OS and PFS in most of the included studies. Among 11 studies included in quantitative synthesis, the overall HRs of EMD, more than three FLs, and high FDG uptake on PFS were 2.12 (95% CI, 1.52–2.96), 2.38 (95% CI, 1.84–3.07), and 2.02 (95% CI, 1.51–2.68), respectively. The pooled HRs of those three parameters on OS were 2.37 (95% CI, 1.77–3.16), 3.29 (95% CI, 2.38–4.56), and 2.28 (95% CI, 1.67–3.13). No statistical differences were found across parameters for either PFS (p = 0.6822) or OS (p = 0.2147). Conclusions: Pretreatment 18F-FDG PET/CT is a significant predictor for disease progression and survival in patients with MM. It may be a useful prognostic biomarker capable of accurate risk stratification and application in clinical decision-making for newly diagnosed MM. Key Points: • There remain unmet clinical needs for reliable prognostic biomarkers in patients with newly diagnosed multiple myeloma. • This meta-analysis shows that the presence of extramedullary disease, more than three focal lesions, and high FDG uptake from baseline18F-FDG PET are significant prognostic factors. • These imaging biomarkers might help the accurate stratification of patient prognosis which is required for choosing an appropriate therapeutic strategy in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to construct a database of the effective doses (ED) from F-18 fluorodeoxyglucose (FDG) torso positron emission tomography/computed tomography (PET/CT) in Korea to provide data that supports the reduction of the CT dose of PET/CT and optimization of PET/CT protocols in Korea. Methods: We investigated data of ED and CT parameters of FDG PET/CT. The data were analyzed by body weight groups. Results: A total of 31 hospitals participated in the survey (99 adults). The mean total EDs (± SD) were 8.77 ± 2.76, 10.93 ± 3.14, and 12.57 ± 3.79 mSv for the 55-, 70-, and 85-kg groups, respectively. The FDG EDs were 4.80 ± 0.98, 6.05 ± 1.15, and 6.89 ± 1.52 mSv, and the CT EDs were 4.00 ± 2.12, 4.88 ± 2.51, and 5.68 ± 2.89 mSv, respectively. Of the enrolled hospitals, 54.5% used ultra-low-dose CT protocols, and their CT ED was significantly lower than low-dose CT group in all groups (2.9 ± 1.0, 3.2 ± 1.1, and 3.3 ± 1.0 mSv vs. 6.6 ± 1.6, 7.2 ± 2.1, and 7.9 ± 2.2 mSv, all p < 0.001, respectively). In the ultra-low-dose CT group, the CT ED with the iterative reconstruction was significantly lower than that of CT without iterative reconstruction in the 55-kg group (2.4 ± 0.9 vs. 3.3 ± 0.9, p = 0.04). Conclusions: These results and current recommendations can be helpful for optimizing PET/CT diagnostic reference level (DRL) and reducing unnecessary PET/CT radiation exposure. [ABSTRACT FROM AUTHOR]

Background: Lanreotide is a long-acting somatostatin analogue with proven antitumour effects against well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumours (GEP-NETs). However, there are no globally established prognostic factors associated with the efficacy of lanreotide as a treatment for GEP-NETs. We investigated the prognostic value of [68Ga]Ga-DOTA-TOC positron emission tomography (PET)/computed tomography (CT) somatostatin receptor imaging for patients with WD GEP-NETs treated with lanreotide. Methods: In this retrospective study, we included 31 patients with unresectable or metastatic WD GEP-NETs who received lanreotide and underwent [68Ga]Ga-DOTA-TOC PET/CT before receiving lanreotide. We captured the following clinicopathological variables: Eastern Cooperative Oncology Group (ECOG) performance status, primary tumour site, NET World Health Organization grade, existence of carcinoid symptoms, previous surgery, previous chemotherapy, and hepatic tumour volume assessed by CT or magnetic resonance imaging (MRI). We also assessed the following [68Ga]Ga-DOTA-TOC PET/CT variables: Krenning score, tumour-to-liver ratio (TLR), maximum standardized uptake value (SUVmax), whole tumour volume (WTV), and total receptor expression (TRE, WTV multiplied by SUVmean). The associations between these markers and progression-free survival (PFS) with lanreotide were analysed. Results: The mean age was 55.1 ± 15.5 years (range 16.0–81.0). The most common primary tumour site was the pancreas, followed by the stomach, and rectum. The median PFS interval with lanreotide was 14.4 months (range 1.3–34.9), with identified disease progression in 20 patients (64.5%). Among the [68Ga]Ga-DOTA-TOC PET/CT variables, TLR (< 8.1 vs. ≥ 8.1; p = 0.013), SUVmax (< 42.9 vs. ≥ 42.9; p = 0.037), and WTV (≥ 58.9 cm3 vs. < 58.9 cm3; p = 0.030) were significantly associated with PFS in the univariate analyses, but only TLR (hazard ratio 3.182 [95% CI 1.189–8.514], p = 0.021) remained an independent factor for PFS in the multivariate analysis. Conclusions: Low TLR, determined via [68Ga]Ga-DOTA-TOC PET/CT, can be a factor of worse prognosis in patients with advanced WD GEP-NETs treated with lanreotide. [ABSTRACT FROM AUTHOR]

Background: Recent progress in amyloid positron emission tomography (PET) has enabled the targeted imaging of cardiac amyloidosis with accuracy. We performed a systematic review and meta-analysis on the diagnostic performance of cardiac amyloidosis using amyloid PET.Methods: A systematic search was performed using key words: cardiac amyloidosis, amyloid, and PET. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio (DOR). Furthermore, the semiquantitative parameters of PET were evaluated to diagnose cardiac amyloidosis and discern its type [systemic light chain amyloidosis (AL) vs transthyretin amyloidosis (ATTR)] using the pooled standardized mean difference (SMD).Results: In total, six eligible studies with a total of 98 subjects were included in this meta-analysis. The pooled sensitivity was 0.95, the specificity was 0.98, positive LR was 10.130, negative LR was 0.1, and DOR was 148.83. The semiquantitative parameters of amyloid PET showed significantly higher values for cardiac amyloidosis patients than those for controls (pooled SMD = 1.42; P < .001), and in AL than ATTR (pooled SMD = 0.96; P < .001).Conclusion: Amyloid PET imaging can be a useful method for diagnosing cardiac amyloidosis. The semiquantitative parameters of amyloid PET can help diagnose cardiac amyloidosis and discern its type. [ABSTRACT FROM AUTHOR]

Objectives: Fluorodeoxyglucose (FDG) PET/CT is effective for predicting recurrence of hepatocellular carcinoma after liver transplantation. This study aimed to design composite criteria for predicting post-transplantation recurrence using clinical and FDG PET/CT factors.Methods: We retrospectively enrolled 239 patients who underwent living donor transplantation in two independent centers between 2005 and 2013. On PET, maximum tumor-to-background ratio (TBRmax) was measured. Significant predictors for recurrence were selected by logistic regression and survival analyses. With varying cutoff values for the selected factors, composite criteria were designed to maximize the predictive performance for recurrence, and tenfold cross-validation was performed. Predictive values were compared between the composite criteria and the conventional recipient selection criteria.Results: Tumor size, number, alpha-fetoprotein, and TBRmax were selected as significant predictors in both logistic regression and multivariate survival analyses. In combination of these factors, the highest diagnostic performance was sensitivity of 75.7% and specificity of 88.5% with cutoff values of tumor size < 6.0 cm, tumor number < 8, alpha-fetoprotein < 465 ng/mL, and TBRmax < 2.8. The composite criteria exhibited the highest performance for predicting recurrence and recurrence-free survival among the tested criteria including conventional ones.Conclusions: The composite criteria adding FDG PET findings to clinical factors are effective in selecting appropriate liver cancer patients who are candidates for liver transplantation.Key Points: • In patients with HCC, tumor uptake on FDG PET/CT, tumor size, number, and serum AFP level are recognized individual predictors for tumor recurrence after LT. • A composite criterion set, combining tumor size, number, serum AFP level, and maximum tumor-to-background ratio (TBR max ), predicts post-LT recurrence most effectively when compared with conventional criteria sets in selecting candidates for living donor LT. [ABSTRACT FROM AUTHOR]

Objective: To examine the morphologic similarities and differences in mandibular condyle and glenoid fossa between the deviated and non-deviated sides in patients with facial asymmetry using statistical analysis. Methods: One hundred eighty-four patients (95 men, 89 women; mean age, 22.30 ± 3.87 years) with facial asymmetry were examined with cone-beam computed tomography (CBCT). Shape analysis was performed to compare the shapes and sizes of the condyle and fossa between the deviated and non-deviated sides in the frontal and lateral aspects. Ordinary Procrustes analysis (OPA) was used to determine shape variations of the fossa and condyle. Results: Shape variations derived from ordinary sum of squares (OSS) suggested that, in the frontal aspect, there was a difference between the two sides in both the fossa and condyle (P < 0.05). In the lateral aspect, there was no difference in fossa shape between the two sides (P > 0.05); however, the shape of condyle was different between the non-deviated and deviated sides (P < 0.05). Size comparison in OPA matching and centroid size (CS) in the frontal aspect demonstrated that the non-deviated side was larger than the deviated side. In the lateral aspect, fossa showed no difference in CS between the two sides (P > 0.05); however, the non-deviated side was larger than the deviated side for condyle (P < 0.05). Conclusions: Morphometric differences in condyle and fossa between the deviated and non-deviated sides were observed. Structures of the non-deviated side were relatively larger than those of the deviated side, except for fossa in the lateral aspect. [ABSTRACT FROM AUTHOR]

Glass fiber reinforced plastics (GFRP) have been widely used for wind turbine blades because of the relative ease of manufacturing them into complex shapes, and their excellent fatigue and corrosion resistance. Acoustic emission (AE) testing has become a primary method for monitoring fiber reinforced plastic structures. However, commercial PZT based AE sensors for general usage may not be useful for GFRP wind-turbine blades because of the acoustic mismatching between GFRP and AE sensors. The objective of this study is to develop high sensitive AE sensors for use on GFRP. To accomplish it, PZT based 1–3 composite and PMN–PT single crystal AE sensors were fabricated and their performances were compared with PZT AE sensor. As results, the PZT based 1-3 composite and PMN–PT AE sensors showed better performance than the PZT AE sensor. PZT based 1-3 composite and PMN–PT AE sensors will be promising alternatives to PZT AE sensors for GFRP materials. [ABSTRACT FROM AUTHOR]

Objectives: To synthesize two different sizes of bioactive glass-coated mesoporous silica nanoparticles (BGN@MSNs) and to investigate their effects on dentinal tubule occlusion and remineralization. Materials and methods: Two different sizes of mesoporous silica nanoparticles (MSNs) were synthesized using the Stöber method (368A, 1840A) and coated with bioactive glass nanoparticles (BGNs) using a modified quick alkali-mediated sol-gel method (368B, 1840B). Sensitive tooth disc models were prepared and divided into six groups and the following treatments were applied: group 1—no treatment, group 2—bioglass, group 3—368A, group 4—368B, group 5—1840A, and group 6—1840B. Then, five discs were selected from each group and soaked in 6 wt% citric acid to test acid resistance. Dentinal tubule occlusion and occlusion ratio were observed using field-emission scanning electron microscopy. In vitro mineralization tests using simulated body fluid solution were performed to evaluate the remineralization effect of the treatment. Results: All samples effectively occluded the dentinal tubule and formed a membrane-like layer. After acid treatment, 1840B (group 6) exhibited the highest rate of dentinal tubule occlusion. Remineralization was observed in 368B and 1840B, and 1840B exhibited the fastest remineralization. Conclusions: Dentinal tubule remineralization induced by the BGN@MSN biocomposite can be used to stabilize long-term prognosis in dentin hypersensitivity. The 1840B induced the most efficient remineralization, and its smaller size and larger surface area were effective for remineralization. Clinical relevance: The BGN@MSN biocomposite with its smaller size and larger surface area was more effective for remineralization and dentinal tubule sealing. [ABSTRACT FROM AUTHOR]

Objective: For symptomatic metastasis of the long bones, intramedullary nailing has been the most accepted fixation method. Intramedullary nailing has effective control of pain, perioperative bleeding, and local tumor progression by augmentation with bone cement around the nail. Here, we report the preliminary results of a new surgical implant that allows for simultaneous injection of bone cement while inserting a percutaneous, flexible intramedullary nail.Materials and Methods: We performed palliative surgeries for long-bone metastasis using a multi-hole injection nail (MIN) with multiple side holes in the distal one third. When the nail tip entered the metastatic cancer lesion, the bone cement injection was started, and continued until the nail was completely seated. Ten patients with advanced cancer underwent palliative surgery using the new implant with simultaneous bone cement injection for humeral (n = 4), femoral (n = 4), and tibial (n = 2) metastases.Results: The mean operative time was 42 min (range, 36-52 min). The mean length of the injection nail was 23.0 cm (range, 18.0-33.0 cm), and the mean volume of cement was 28.0 ml (range, 14.0-40.0 ml). Marked pain palliation (p < 0.001) and functional recovery (p = 0.01) were verified. The mean Musculoskeletal Tumor Society (MSTS) functional score improved significantly from 12.5 at 6 weeks preoperatively, to 24.9 postoperatively. No acute postoperative complications, including cement embolism, occurred.Conclusion: This minimally invasive surgical method with MIN could be useful for stabilization of long-bone metastases in patients with advanced cancer. [ABSTRACT FROM AUTHOR]

Backgrounds: TOR and autophagy are essential pathways to mediate anabolic and catabolic reactions, respectively, in response to various nutritional stimuli. Vertebrate development requires such reactions to achieve the common goal of generating an independent organism from a single fertilized egg.Methods: Using the zebrafish as an animal model, we characterized the role of Wdr24, a component of the GATOR2 complex that reportedly activates TORC1.Results: Sequence analysis and subcellular localization of zebrafish Wdr24 suggested functional resemblance to its mammalian counterpart. We found that wdr24 expression commences during early embryogenesis, implicating its requirement. Accordingly, wdr24 knockdown induced defective embryogenesis accompanied by massive cell death. The developmental defects induced by wdr24 knockdown were attributable, at least in part, to dysregulated autophagy, which could be partially restored by wdr24 overexpression.Conclusion: These findings suggest that a conserved role of Wdr24 may be a critical part of the cellular metabolism in different species. [ABSTRACT FROM AUTHOR]

Objectives: To synthesize a silver-doped bioactive glass/mesoporous silica nanoparticle (Ag-BGN@MSN), as well as to investigate its effects on dentinal tubule occlusion, microtensile bond strength (MTBS), and antibacterial activity.Materials and methods: Ag-BGN@MSN was synthesized using a modified "quick alkali-mediated sol-gel" method. Demineralized tooth disc models were made and divided into four groups; the following treatments were then applied: group 1—no treatment, group 2—bioglass, group 3—MSN, group 4—Ag-BGN@MSN. Next, four discs were selected from each group and soaked into 6 wt% citric acid to test acid-resistant stability. Dentinal tubule occlusion, as well as the occlusion ratio, was observed using field-emission scanning electron microscopy. The MTBS was also measured to evaluate the desensitizing effect of the treatments. Cytotoxicity was examined using the MTT assay. Antibacterial activity was detected against Lactobacillus casei, and ion dissolution was evaluated using inductively coupled plasma optical emission spectrometry.Results: Ag-BGN@MSN effectively occluded the dentinal tubule and formed a membrane-like layer. After the acid challenge, Ag-BGN@MSN had the highest rate of dentinal tubule occlusion. There were no significant differences in MTBS among the four groups (P > 0.05). All concentrations of Ag-BGN@MSN used had a relative cell viability above 72%.Conclusions: Ag-BGN@MSN was successfully fabricated using a modified sol-gel method. The Ag-BGN@MSN biocomposite effectively occluded dentinal with acid-resistant stability, did not decrease bond strength in self-etch adhesive system, had low cytotoxicity, and antibacterial effect.Clininal relevance: Dentinal tubule sealing induced by Ag-BGN@MSN biocomposite with antibacterial effect is likely to increase long-term stability in DH. [ABSTRACT FROM AUTHOR]

Zinc oxide (ZnO) thin films were grown on silicon (100) substrate using radio frequency (RF) sputtering under various processing parameters including deposition time and annealing temperature. A series of characterization techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM) and scanning acoustic microscopy (SAM) have been used to analyze the crystallinity and crystal orientation, structural morphology, surface roughness, and acoustic properties of these films. In particular, quantitative analysis of elastic wave propagation in ZnO thin films by scanning acoustic microscopy has been performed for the first time in the present work. It has been shown that the propagation properties of acoustic waves on the surface of ZnO thin films strongly depend on film thickness, crystallinity, and surface roughness. The dispersion properties of surface acoustic waves (SAWs) are observed as a function of ZnO film thickness. The velocities of SAWs range from 5328.3 m/s to 4245.7 m/s with increasing film thickness from 32.5 nm to 2.04 μm, while smoother surface contributes to faster propagation of SAWs. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the usefulness of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) parameters provided by simultaneous F-fluorodeoxyglucose (FDG) PET/MRI for the prediction of treatment failure in surgically resected head and neck cancer. We hypothesized that PET parameters corrected by tumor cellularity (combined PET/MRI parameters) could predict the prognosis. On regional PET, maximum standardized uptake value (SUVmax) was measured as metabolic parameters. In addition, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were checked as metabolo-volumetric parameters. Mean apparent diffusion coefficient (ADCmean) of tumor was evaluated as the MRI parameter on the ADC map. Ratios between metabolic/metabolo-volumetric parameters and ADC were calculated as combined PET/MRI parameters. PET, MRI, and combined PET/MRI parameters were compared with clinicopathologic parameters in terms of treatment failure. Results: Seventy-two patients (mean age = 55.9 ± 14.6 year, M: F = 45: 27) who underwent simultaneous F-FDG PET/MRI before head and neck cancer surgery were retrospectively enrolled. Twenty-two patients (30.6%) showed tumor treatment failure after head and neck cancer surgery (mean treatment failure = 13.0 ± 7.0 months). In the univariate analysis, MTV ( P = 0.044) and ratios between metabolo-volumetric parameters and ADC (MTV/ADCmean, P = 0.022; TLG/ADCmean, P = 0.044) demonstrated significance among F-FDG PET/MRI parameters. Lymphatic invasion ( P = 0.044) and perineural invasion ( P = 0.046) revealed significance among clinicopathologic parameters. In the multivariate analysis, MTV ( P = 0.026), MTV/ADCmean ( P = 0.011), and TLG/ADCmean ( P = 0.002) with lymphatic invasion ( P = 0.026, 0.026, and 0.044, respectively) showed significance. Conclusions: Combined PET/MRI parameters (PET metabolo-volumetric parameters corrected by tumor cellularity) could be effective predictors of tumor treatment failure after head and neck cancer surgery in addition to MTV and clinicopathologic parameter. [ABSTRACT FROM AUTHOR]

Purpose: Triple-negative breast cancer has a poor prognosis. We evaluated several metabolic and volumetric parameters from preoperative F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the prognosis of triple-negative breast cancer and compared them with current clinicopathologic parameters. Methods: A total of 228 patients with triple-negative breast cancer (mean age 47.0 ± 10.8 years, all women) who had undergone preoperative PET/CT were included. The PET/CT metabolic parameters evaluated included maximum, peak, and mean standardized uptake values (SUVmax, SUVpeak, and SUVmean, respectively). The volumetric parameters evaluated included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Metabolic and volumetric parameters were evaluated separately for tumor (T) and lymph nodes (N). The prognostic value of these parameters was compared with that of clinicopathologic parameters. Results: All lymph node metabolic and volumetric parameters showed significant differences between patients with and without recurrence. However, tumor metabolic and volumetric parameters showed no significant differences. In a univariate survival analysis, all lymph node metabolic and volumetric parameters (SUVmax-N, SUVpeak-N, SUVmean-N, MTV-N, and TLG-N; all P < 0.001), T stage ( P = 0.010), N stage ( P < 0.001), and TNM stage ( P < 0.001) were significant parameters. In a multivariate survival analysis, SUVmax-N ( P = 0.005), MTV ( P = 0.008), and TLG ( P = 0.006) with TNM stage (all P < 0.001) were significant parameters. Conclusions: Lymph node metabolic and volumetric parameters were significant predictors of recurrence in patients with triple-negative breast cancer after surgery. Lymph node metabolic and volumetric parameters were useful parameters for evaluating prognosis in patients with triple-negative breast cancer by F-FDG PET/CT, rather than tumor parameters. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the potential clinical application of fractal analysis of midpalatal suture fusion for prediction of pubertal growth spurts. Methods: Cone-beam computed tomography (CBCT) scans and hand-wrist radiographs were obtained for 165 subjects (81 males, 84 females; mean age 15.5 ± 7.6 years). From the CBCT image of the midpalatal suture, the region of interest was obtained according to a previously described protocol. The fractal dimension (FD) of the midpalatal suture was calculated. Spearman's correlation coefficients were estimated to investigate the associations among age, skeletal maturation index (SMI), and FD of the midpalatal suture. Receiver-operating characteristic curves were used to determine the cutoff values for identification of pubertal growth spurts. Results: Significant correlations were observed among age, SMI, and FD of the midpalatal suture ( P < 0.05). The optimal cutoff value of the FD for evaluation of a pubertal growth spurt was 0.9484 in males and 1.1205 in females. Fractal analysis of the midpalatal suture on CBCT images might be a clinically meaningful, objective, and quantitative method for evaluating pubertal growth spurts. Conclusions: The present results suggest that fractal analysis of the midpalatal suture could be useful for decision-making on treatments involving growth modification in growing children with a skeletal discrepancy. [ABSTRACT FROM AUTHOR]

Background: This study constructed a partial-least-square path-modeling (PLS-PM) model and found the pathway by which the postsurgical vertical dimension (VD) affects the extent of the final mandibular setback on the B point at the posttreatment stage for the skeletal class III surgery-first approach (SFA). Methods: This study re-analyzed the data from the retrospective study by Lee et al. on 40 patients with skeletal class III bimaxillary SFA. Variables were obtained from cone beam computed tomography (CBCT)-generated cephalograms. Authors investigated all variables at each time point to build a PLS-PM model to verify the effect of the VD on the final setback of the mandible. Results: From PLS-PM, an increase in VD was found to decrease the absolute value of the final setback amount of the mandible, which reflects the postsurgical physiological responses to both surgery and orthodontic treatment, which, in turn, can be interpreted as an increase in postoperative mandibular changes. Conclusions: To resolve the issue of collinear cephalometric data, the present study adopted PLS-PM to assess the orthodontic treatment. From PLS-PM, it was able to summarize the effect of increased postsurgery occlusal vertical dimension on the increased changeability of the B point position at the posttreatment stage. [ABSTRACT FROM AUTHOR]

Purpose: Until now, there was no single standardized regional segmentation method of planar lung perfusion scan. We compared planar scan based two segmentation methods, which are frequently used in the Society of Nuclear Medicine, with reference to the lung perfusion single photon emission computed tomography (SPECT)/computed tomography (CT) derived values in lung cancer patients. Methods: Fifty-five lung cancer patients (male:female, 37:18; age, 67.8 ± 10.7 years) were evaluated. The patients underwent planar scan and SPECT/CT after injection of technetium-99 m macroaggregated albumin (Tc-99 m-MAA). The % uptake and predicted postoperative percentage forced expiratory volume in 1 s (ppoFEV1%) derived from both posterior oblique (PO) and anterior posterior (AP) methods were compared with SPECT/CT derived parameters. Concordance analysis, paired comparison, reproducibility analysis and spearman correlation analysis were conducted. Results: The % uptake derived from PO method showed higher concordance with SPECT/CT derived % uptake in every lobe compared to AP method. Both methods showed significantly different lobar distribution of % uptake compared to SPECT/CT. For the target region, ppoFEV1% measured from PO method showed higher concordance with SPECT/CT, but lower reproducibility compared to AP method. Preliminary data revealed that every method significantly correlated with actual postoperative FEV1%, with SPECT/CT showing the best correlation. Conclusion: The PO method derived values showed better concordance with SPECT/CT compared to the AP method. Both PO and AP methods showed significantly different lobar distribution compared to SPECT/CT. In clinical practice such difference according to different methods and lobes should be considered for more accurate postoperative lung function prediction. [ABSTRACT FROM AUTHOR]

Purpose: F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in I- or I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated. Methods: Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study. Clinical information-including histopathology, and serum markers-and several PET parameters-including SUVmax of the primary lesion (Psuv), target-to-background ratio (TBR), metabolic tumor volume (MTV), and coefficient of variation (CV)-were analyzed. The prognostic effect of PET parameters was evaluated in terms of progression-free survival (PFS). Results: Total 20 patients (4.5 ± 3.5 years) were divided as two groups by disease progression. Six patients (30.0 %) experienced disease progression and one patient (5.0 %) died during follow-up period. There were not statistically significant in age, stage, MYCN status, primary tumor size, serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), and ferritin level between two groups with progression or no progression. However, Psuv ( p = 0.017), TBR ( p = 0.09), MTV ( p = 0.02), and CV ( p = 0.036) showed significant differences between two groups. In univariate analysis, PFS was significantly associated with Psuv ( p = 0.021) and TBR ( p = 0.023). Conclusions: FDG-PET parameters were significantly related with progression of neuroblastoma. FDG-PET/CT may have the potential as a valuable modality for evaluating prognosis in the patients with MIBG-avid pediatric neuroblastoma. [ABSTRACT FROM AUTHOR]

Cumulative evidence suggests the importance of organelle homeostasis in regulating metabolic functions in response to various cellular stresses. Particularly, the dynamism and health of the mitochondria-peroxisome network through fission and fusion are essential for cellular function; dysfunctional dynamism underlies the pathogenesis of several degenerative diseases including Parkinson's disease. Here, we investigated the role of Fis1 in cartilage homeostasis and its relevance to osteoarthritis (OA). We found that Fis1 is significantly suppressed in human OA chondrocytes compared to that in normal chondrocytes. Fis1 depletion through siRNA induced peroxisomal dysfunction. Moreover, Fis1 suppression altered miRNA profiles, especially those implicated in lysosomal regulation. Lysosomal destruction using LAMP-1-specific targeted nanorods or lysosomal dysfunction through chloroquine treatment resulted in enhanced chondrocyte apoptosis and/or suppression of autophagy. Accordingly, lysosomal activity and autophagy were severely decreased in OA chondrocytes despite abundant LAMP-1-positive organelles. Moreover, Fis1 morpholino-injected zebrafish embryos displayed lysosome accumulation, mitochondrial dysfunction, and peroxisome reduction. Collectively, these data suggest interconnected links among Fis1-modulated miRNA, lysosomes, and autophagy, which contributes to chondrocyte survival/apoptosis. This study represents the first functional study of Fis1 with its pathological relevance to OA. Our data suggest a new target for controlling cartilage-degenerative diseases, such as OA. Key message: [ABSTRACT FROM AUTHOR]

In this study, the enteric-coated delayed-release pellets of duloxetine hydrochloride (DLX) were formulated using a fluidized bed coater. Three separate layers, the drug layer, the barrier layer, and the enteric layer, were coated onto inert core pellets. Among the three formulations (F1-F3), the dissolution profiles of formulation F2 were most similar to those of the marketed product, with similarity and difference factors of 83.99 and 3.77, respectively. In addition, pharmacokinetic parameters of AUC, C, T, t, K, and MRT of DLX for the developed formulation (F2) did not differ significantly from those for the marketed product in beagle dogs, suggesting that they were bioequivalent. Our results demonstrated that the in vitro dissolution data resembled the in vivo performance of the drug. Therefore, this study has a positive scope for further scale up and development of the formulation for achievement of the generic product. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to establish multivariable regression models for the estimation of skeletal maturation status in Japanese boys and girls using the cone-beam computed tomography (CBCT)-based cervical vertebral maturation (CVM) assessment method and hand-wrist radiography. Materials and methods: The analyzed sample consisted of hand-wrist radiographs and CBCT images from 47 boys and 57 girls. To quantitatively evaluate the correlation between the skeletal maturation status and measurement ratios, a CBCT-based CVM assessment method was applied to the second, third, and fourth cervical vertebrae. Pearson's correlation coefficient analysis and multivariable regression analysis were used to determine the ratios for each of the cervical vertebrae ( p < 0.05). Results: Four characteristic parameters ((OH + PH)/W, (OH + AH)/W, D, AH/W), as independent variables, were used to build the multivariable regression models: for the Japanese boys, the skeletal maturation status according to the CBCT-based quantitative cervical vertebral maturation (QCVM) assessment was 5.90 + 99.11 × AH/W − 14.88 × (OH + AH)/W + 13.24 × D; for the Japanese girls, it was 41.39 + 59.52 × AH/W − 15.88 × (OH + PH)/W + 10.93 × D. Conclusions: The CBCT-generated CVM images proved very useful to the definition of the cervical vertebral body and the odontoid process. The newly developed CBCT-based QCVM assessment method showed a high correlation between the derived ratios from the second cervical vertebral body and odontoid process. Clinical relevance: There are high correlations between the skeletal maturation status and the ratios of the second cervical vertebra based on the remnant of dentocentral synchondrosis. [ABSTRACT FROM AUTHOR]

The emerging radionanomedicine has multifunctional and theranostic purposes. For these purposes, radionanomedicine should achieve the efficient and specific delivery of therapeutic agents by multifunctional characteristics, using low amounts of nanomaterials in vivo. Recent research on radiolabeled micelle-encapsulated nanomaterials has been made on the their efficacy and safety using a one-step surface modification method (Jeong's method). This one-step multifunctional approach to the nanoparticle can be the important challenge in producing effective nanoplatforms for cancer imaging and therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine the usefulness of MRI-assisted positron emission tomography (PET) parameters provided by simultaneous F-fluorocholine (FCH) PET/MRI for characterization of primary prostate cancer. Methods: Thirty patients with localized prostate cancer (mean age 69.4 ± 6.7 years) confirmed by biopsy were prospectively enrolled for simultaneous PET/MRI imaging. The patients underwent F-FCH PET/MRI 1 week before undergoing total prostatectomy. Multiple parameters of diffusion-weighted MRI [minimum and mean apparent diffusion coefficient (ADC and ADC)], metabolic PET [maximum and mean standardized uptake value (SUV and SUV)], and metabolic volumetric PET [metabolic tumor volume (MTV) and uptake volume product (UVP)] were compared with laboratory, pathologic, and immunohistochemical (IHC) features of the prostate cancer specimen. PET parameters were divided into two categories as follows: volume of interest (VOI) of prostate by SUV cutoff 2.5 (SUV, SUV, MTV, and UVP) and MRI-assisted VOI of prostate cancer (SUV, SUV, MTV, and UVP). Results: The rates of prostate cancer-positive cases identified by MRI alone, F-FCH PET alone, and F-FCH PET/MRI were 83.3, 80.0, and 93.3 %, respectively. Among the multiple PET/MRI parameters, MTV showed fair correlation with serum prostate-specific antigen (PSA; r = 0.442, p = 0.014) and highest correlation with tumor volume ( r = 0.953, p < 0.001). UVP showed highest correlation with serum PSA ( r = 0.531, p = 0.003), good correlation with tumor volume ( r = 0.908, p < 0.001), and it was significantly associated with Gleason score ( p = 0.041). High MTV and UVP values were significant for perineural invasion, lymphatic invasion, extracapsular extension, seminal vesicle invasion, and positive B-cell lymphoma 2 (Bcl-2) expression (all p < 0.05). Conclusion: Simultaneous F-FCH PET/MRI demonstrated a better diagnostic value for localized prostate cancer detection than each individual modality. MRI-assisted metabolic volumetric PET parameters (MTV and UVP) provided more accurate characterization of prostate cancer than conventional PET and MRI parameters. [ABSTRACT FROM AUTHOR]

Objective: The utility of serum thyroglobulin (Tg) level, 3 days after radioactive iodine (RAI) therapy, was assessed as a means of predicting successful ablation of thyroid remnant in patients with postoperative thyroid cancer. Methods: A total of 152 patients with thyroid cancer (mean age = 44.9 ± 13.7 year) undergoing RAI therapy after total thyroidectomy were included. Levels of TSH-stimulated Tg prior to ablation (stimTg) and serum Tg sampled immediately after RAI therapy (Day 3) were measured (immTg). ImmTg samples were collected during patient hospital visits for scheduled follow-up of radioiodine scans. Successful ablation was determined by the second time stimulated Tg levels (≤1 ng/ml) and negative radioiodine uptake at thyroid bed after 6.1 ± 1.1 months of RAI therapy. Univariate and multivariate analyses were done for immTg, stimTg, change in Tg levels (deltaTg: immTg − stimTg), immTg:stimTg ratio (ratioTg), and other potential clinical and pathologic markers of successful ablation. Results: Of selected laboratory variables, ratioTg was a significant predictor of successful ablation. StimTg, tumor diameter, metastatic lymph node (LN) numbers, lymphatic invasion were possible clinical markers of successful ablation by univariate analysis. By multivariate analysis, ratioTg (odds ratio = 7.851), stimTg (odds ratio = 16.819), metastatic LN numbers (odds ratio with stimTg = 6.732) proved significant results. Furthermore, combining high ratioTg and low stimTg provided added predictive value. Conclusions: High ratioTg (reflecting extensive release of Tg to the blood after RAI therapy) and low stimTg (reflecting small remnant thyroid tissue) constitute the indices of successful ablation after RAI therapy. Immediate Tg level could give an useful information on RAI ablation of postoperative thyroid remnant. [ABSTRACT FROM AUTHOR]

Objective: We aimed to improve Tc-99m DTPA glomerular filtration rate (GFR) scintigraphy (Gates' method) in a prospective study using Cr-51 EDTA GFR test as a gold standard. Methods: Fifty-seven Tc-99m DTPA GFR scintigrams in 45 subjects (male/female = 33:12, age = 45.9 ± 17.6 years, 14 healthy volunteers and 31 nephrectomised patients) were compared using Cr-51 EDTA GFR tests. Using the %renal uptake of Tc-99m DTPA and Cr-51 EDTA GFR, a revised equation for GFR was established through linear regression analysis. Results: The revised equation for improved GFR was GFR(mL/min) = ( %renal uptake × 11.7773) − 0.7354. Gates' original GFRs (70.1 ± 20.5 mL/min/1.73 m) were significantly lower than Cr-51 EDTA GFRs (97.0 ± 31.9 mL/min/1.73 m; P < 0.0001), but the improved GFRs (98.0 ± 26.3 mL/min/1.73 m) were not different from ( P = 0.7360) and had a significant correlation with ( r = 0.73, P < 0.0001) the Cr-51 EDTA GFRs. The revised GFR equation effectively demonstrated perioperative GFR changes in kidneys that were operated on and the contralateral kidneys at 3 and 6 months post-partial nephrectomy ( n = 25). Conclusions: GFR measurement using Tc-99m DTPA scintigraphy could be significantly improved by a revised equation derived from the comparison with Cr-51 EDTA GFR. Key Points: • Measurement of glomerular filtration rate is difficult following nephrectomy. • Measurements can be significantly improved by new renal sctintigraphic methods. • This helps physicians to measure kidney function of patients following nephrectomy. • Management of renal tumour patients should become more effective. [ABSTRACT FROM AUTHOR]

The main purpose of this work was to optimize the rheological properties of docetaxel (DCT)-loaded thermosensitive liquid suppositories for rectal administration. DCT-loaded liquid suppositories were prepared by a cold method and characterized in terms of physicochemical and viscoelastic properties. Major formulation parameters including poloxamer (P407) and Tween 80 were optimized to adjust the thermogelling and mucoadhesive properties for rectal administration. Notably, the gel strength and mucoadhesive force significantly increased with the increase in these variables. Furthermore, DCT incorporation did not alter the viscoelastic behavior, and the mean particle size of nanomicelles in it was approximately 16 nm with a distinct spherical shape. The formulation existed as liquid at room temperature and transformed into gel at physiological temperature through the reverse gelation phenomenon. Thus, DCT-loaded thermosensitive liquid suppositories [DCT/P407/P188/Tween 80 (0.25/11/15/10 %)] with optimal gel properties were easy to prepare and administer rectally, and might enable the gel to stay in the rectum without getting out from rectum. [ABSTRACT FROM AUTHOR]