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Background: As a surrogate of malnutrition, degree of weight loss and recovery from head and neck cancer (HNC) treatment is understudied. The influence of modifiable factors that affect weight, including speech/language pathology (SLP) and nutrition counseling, is also poorly defined. We characterize weight loss trends, baseline weight recovery (BWR), and the impact of interdisciplinary care on oncologic outcomes., Methods: Retrospective cohort study assessing 266 newly diagnosed patients with HNC who completed curative-intent radiation (definitive or adjuvant) between January 2016 to January 2022. Relevant treatment factors were analyzed using multivariable Cox regression models., Results: Altogether, 266 patients completed full-course radiation therapy (RT), encompassing definitive chemoRT (53.0%), surgery with chemoRT (18.4%), surgery with RT (17.7%), and RT alone (10.9%). Patient weight reached a nadir at median 3.0 months (IQR 3.0-11.3) after radiation, with a median weight loss of 12.6% (IQR 7.9-18.7). Notably, only 47.4% exhibited BWR. For those who recovered, median time to BWR was 10.5 months (IQR 3.0-24.0). On multivariable analysis, BWR by 6 months was significantly associated with overall survival (HR 0.28 [95% CI 0.10-0.76], p = 0.013), as was SLP consultation (HR 0.40 [95% CI 0.17-0.92], p = 0.031) and nutrition consultation (HR 0.34 [95% CI 0.13-0.89], p = 0.028)., Conclusion: A high proportion of patients with HNC fail to recover baseline weight after treatment; those that do can take longer than expected to return. Failure to recover baseline weight is associated with a notable decrease in survival. Similarly, SLP and nutrition consultation are independent, modifiable determinants correlated with outcomes, supporting the emphasis on multidisciplinary management. Measures to promote BWR may reduce mortality., (© 2024 Wiley Periodicals LLC.)

Background and Aims: Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system., Approach and Results: A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references., Conclusions: ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Purpose: This study assessed the impact of hepatic fibrosis on the diagnostic performance of the controlled attenuation parameter (CAP) in quantifying hepatic steatosis in patients with chronic hepatitis B (CHB)., Methods: CHB patients who underwent liver stiffness measurement (LSM) and CAP assessment using transient elastography before liver resection between 2019 and 2022 were retrospectively evaluated. Clinical data included body mass index (BMI) and laboratory parameters. The histologically determined hepatic fat fraction (HFF) and fibrosis stages were reviewed by pathologists blinded to clinical and radiologic data. The Pearson correlation coefficient between CAP and HFF was calculated. The diagnostic performance of CAP for significant hepatic steatosis (HFF ≥10%) was assessed using areas under the receiver operating curve (AUCs), stratified by fibrosis stages (F0-1 vs. F2-4). Factors significantly associated with CAP were determined by univariable and multivariable linear regression analyses., Results: Among 399 CHB patients (median age 59 years; 306 men), 16.3% showed significant steatosis. HFF ranged from 0% to 60%. Of these patients, 9.8%, 19.8%, 29.3%, and 41.1% had fibrosis stages F0-1, F2, F3, and F4, respectively. CAP positively correlated with HFF (r=0.445, P<0.001). The AUC of CAP for diagnosing significant steatosis was 0.786 (95% confidence interval [CI], 0.726 to 0.845) overall, and significantly lower in F2-4 (0.772; 95% CI, 0.708 to 0.836) than in F0-1 (0.924; 95% CI, 0.835 to 1.000) (P=0.006). Multivariable analysis showed that BMI (P<0.001) and HFF (P<0.001) significantly affected CAP, whereas LSM and fibrosis stages did not., Conclusion: CAP evaluations of significant hepatic steatosis are less reliable in CHB patients with significant or more advanced (F2-4) than with no or mild (F0-1) fibrosis.

Background & Aims: The clinicopathologic and imaging features of hepatocellular adenomas (HCAs) in Asian population remain unclear. We aimed to analyse clinicopathologic and imaging features of HCAs in Korea and propose an imaging-based method to differentiate β-catenin mutated HCA (βHCA) from other subtypes., Methods: This retrospective multicenter study included pathologically confirmed HCAs from three tertiary institutions in Korea between 2010 and 2023. HCA subtypes were determined according to the current World Health Organization classification using immunohistochemical staining. Two abdominal radiologists reviewed computed tomography and magnetic resonance imaging scans. The clinical characteristics and imaging features of HCA subtypes were compared. A scoring system for βHCA was developed and validated using development (January 2010-April 2021) and validation (May 2021-March 2023) cohorts., Results: 121 patients (47 men; mean age, 39.0 years ±13.5) with 138 HCAs were included. HCAs displayed characteristic clinicopathologic features, including a high proportion of male (38.8%) and obese patients (35.5%), with the inflammatory subtype being the most common (38.4%) and a low percentage of patients using oral contraceptive (5.0%). Each HCA subtype demonstrated distinct clinical and imaging features. The scoring system incorporating tumour heterogeneity and iso to high hepatobiliary phase signal intensity on MRI for differentiating βHCA exhibited high performance in both the development (AUC 0.92, 95% CI: 0.87-0.97) and the validation cohort (AUC 0.91, 95% CI: 0.77-1.00)., Conclusions: This comprehensive analysis of clinicopathologic and imaging features of HCAs in Korea contributes to the characterisation of HCAs across different geographical regions. The imaging-based scoring system effectively differentiates βHCA., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: This study aimed to assess the prognostic value of the National Comprehensive Cancer Network (NCCN) criteria for resection following neoadjuvant therapy for patients with localized pancreatic ductal adenocarcinoma (PDAC)., Methods: This retrospective single-center study assessed 193 consecutive patients with localized PDAC (104 males and 89 females; mean age, 61.1 ± 9.4 years) who underwent neoadjuvant therapy followed by surgery between January 2010 and March 2021. Combined resectability and carbohydrate antigen (CA) 19-9 evaluation before and after neoadjuvant therapy was used to determine whether patients were eligible for resection according to the NCCN criteria. Post-surgical overall survival (OS), recurrence free survival (RFS), and pathologic results were evaluated and compared between patients considered eligible according to the NCCN criteria and those considered ineligible. Preoperative factors associated with better OS and RFS also were investigated., Results: Of the 193 patients, 168 (87.0 %) were eligible for resection according to the NCCN criteria. The patients eligible according to the NCCN criteria showed marginally longer OS than those considered ineligible (p = 0.056). After adjustment of variables, meeting the NCCN criteria for resection was an independent predictor of better OS (hazard ratio, 0.57; 95 % confidence interval, 0.34-0.96; p = 0.034). The two groups had similar RFS. Lower T-staging (T2 or less) and less lympho-vascular invasion and peri-neural invasion were noted in the patients who met the NCCN criteria (p ≤ 0.045)., Conclusions: The patients eligible for resection according to the NCCN criteria showed a trend toward longer OS and better pathologic results than the patients considered ineligible., Competing Interests: Disclosure: There are no conflicts of interest., (© 2024. Society of Surgical Oncology.)

Background: Contrast-enhanced T1-weighted magnetic resonance cholangiography (CE-T1-MRC) after gadoxetate disodium administration can be used for preoperative evaluation of the bile ducts in live liver donors. This study aimed to determine whether CE-T1-MRC with 3-hour delayed imaging improves bile duct visualization both qualitatively and quantitatively compared with 20-minute delayed imaging in potential living liver donors., Methods: We retrospectively identified 33 potential living liver donors (mean age, 30.1 years; 18 men and 15 women) who underwent preoperative CE-T1-MRC with both 20-minute delayed and 3-hour delayed imaging in a single session. The radiologist scored biliary visualization for right and left hepatic ducts (RHD and LHD), their secondary confluences and segmental bile ducts, common hepatic duct (CHD), and cystic duct (CD), and measured relative contrast ratio (rC) and relative signal intensity (rS) for RHD, LHD, and CHD. The data were analyzed using Wilcoxon's signed-rank test and paired t-test., Results: In qualitative analysis, duct visualization scores for RHD and LHD, their secondary confluences and segmental bile ducts, CHD, and CD were significantly higher on CE-T1-MRC with 3-hour delayed imaging than with 20-minute delayed imaging (all, P ≤ .046). In quantitative analysis, both rC and rS of RHD, LHD, and CHD were significantly higher on CE-T1-MRC with 3-hour delayed imaging than with 20-minute delayed imaging (all, P < .001)., Conclusions: CE-T1-MRC with 3-hour delay imaging improves bile duct visualization both qualitatively and quantitatively in potential living liver donors., Competing Interests: Declaration of competing interest Sunyoung Lee reports honoraria from Bracco and Bayer. The remaining authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

The current need for the upgradation of biohydrogen generation and contaminant removal in two-chambered microbial electrolysis cells (MECs) compels the design of alternatives i.e. bioelectrochemical systems (BESs) to conventional reactors. In this study, a novel three-chambered design of MEC (BES-1) was developed with a common anodic chamber and a two-cathodic chambers at both ends of the anodic chamber, separated by a membrane (MEC-MEC). To facilitate electricity recovery, a microbial fuel cell (MFC) was integrated with an MEC in BES-2. Cathodic hydrogen recovery of 8.89 and 4.81 mL/L.day, and organic matter removal of 82% and 76% were obtained in BES-1 and BES-2, respectively, demonstrating their capabilities for bioremediation. Electrochemical analyses also revealed that cathodic reduction reactions improved with the effective utilization of protons during integration. Our design regulates H 2 /O 2 -associated electrochemical reactions and is beneficial for maintaining pH equilibrium. From cost and energy perspectives, the integrated BES provides a platform for two different reactions simultaneously and is capable of boosting overall hydrogen recovery and organic matter removal. Moreover, the compactness and competitiveness of such an integrated BES increase its scope for real-world applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Circulating tumor DNA assays have robust potential as molecular surveillance tools. They may also exacerbate patient distress without improving outcomes. We investigate patient acceptability of a validated ctHPVDNA assay (NavDx) during cancer surveillance for HPV(+) oropharyngeal cancer (OPC)., Methods: Consented HPV(+) OPC participants completed the NCCN Distress Thermometer, the Hospital Anxiety Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) scale both (1) before NavDx blood draw, and (2) after results were provided. Patients then completed a series of focused questions related to their perceptions of the assay., Results: Overall, 55 patients completed the study, with 98.2 % showing no recurrence. For the NCCN Distress Thermometer, median patient distress decreased (2.0 (IQR 1-5) vs. 1.0 (IQR 0-3)) (p < 0.001) in association with NavDx. Using scores ≥ 4 as a cutoff point to define clinically elevated distress, scores also improved (36.4 % vs. 18.2 %, p = 0.031). For HADS, anxiety significantly improved (5.0 (IQR 2.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.037), but not depression (3.0 (IQR 1.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.870). FACT-G scores showed no substantial differences. On survey questionnaires, 95.5 % of patients believed the test to be helpful, and 100 % felt "somewhat" or "extremely" confident in the assay as a monitoring tool. While 59.1 % felt that it reduced anxiety, 88.4 % concordantly felt that it did not introduce anxiety., Conclusion: ctHPVDNA as a molecular surveillance tool reduced distress levels in HPV(+) OPC patients, with notably high patient confidence in the approach. Further investigation is warranted to judiciously incorporate this emerging modality in surveillance guidelines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Zumsteg’s spouse does legal work for Johnson & Johnson, Merck, Allergan, and Boehringer Ingelheim through her law firm]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mitosis and meiosis have two mechanisms for regulating the accuracy of chromosome segregation: error correction and the spindle assembly checkpoint (SAC). We have investigated the function of several checkpoint proteins in meiosis I of Drosophila oocytes. Evidence of a SAC response by several of these proteins is found upon depolymerization of microtubules by colchicine. However, unattached kinetochores or errors in biorientation of homologous chromosomes does not induce a SAC response. Furthermore, the metaphase I arrest does not depend on SAC genes, suggesting the APC is inhibited even if the SAC is silenced. Two SAC proteins, ROD of the ROD-ZW10-Zwilch (RZZ) complex and MPS1, are also required for the biorientation of homologous chromosomes during meiosis I, suggesting an error correction function. Both proteins aid in preventing or correcting erroneous attachments and depend on SPC105R for localization to the kinetochore. We have defined a region of SPC105R, amino acids 123-473, that is required for ROD localization and biorientation of homologous chromosomes at meiosis I. Surprisingly, ROD removal, or "streaming", is independent of the dynein adaptor Spindly and is not linked to the stabilization of end-on attachments. Instead, meiotic RZZ streaming appears to depend on cell cycle stage and may be regulated independently of kinetochore attachment or biorientation status. We also show that dynein adaptor Spindly is also required for biorientation at meiosis I, and surprisingly, the direction of RZZ streaming.

Objectives: The purpose of this study was to compare the different versions of the National Comprehensive Cancer Network (NCCN) guidelines for defining resectability of pancreatic ductal adenocarcinoma (PDAC) in predicting margin-negative (R0) resection, and to assess inter-reader agreement., Methods: This retrospective study included 283 patients (mean age, 65.1 years ± 9.4 [SD]; 155 men) who underwent upfront pancreatectomy for PDAC between 2017 and 2019. Two radiologists independently determined the resectability on preoperative CT according to the 2017, 2019, and 2020 NCCN guidelines. The sensitivity and specificity for R0 resection were analyzed using a multivariable logistic regression analysis with generalized estimating equations. Inter-reader agreement was assessed using kappa statistics., Results: R0 resection was accomplished in 239 patients (84.5%). The sensitivity and specificity averaged across two readers were, respectively, 76.6% and 29.5% for the 2020 guidelines, 74.1% and 32.9% for the 2019 guidelines, and 72.6% and 34.1% for the 2017 guidelines. Compared with the 2020 guidelines, both 2019 and 2017 guidelines showed significantly lower sensitivity for R0 resection (p ≤ .009). Specificity was significantly higher with the 2017 guidelines (p = .043) than with the 2020 guidelines. Inter-reader agreements for determining the resectability of PDCA were strong (k ≥ 0.83) with all guidelines, being highest with the 2020 guidelines (k = 0.91)., Conclusion: The 2020 NCCN guidelines showed significantly higher sensitivity for prediction of R0 resection than the 2017 and 2019 guidelines., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The possible genetic variants associated with blepharospasm (BSP) and facial dystonia have been investigated. Although genetic variants associated with BSP have been extensively studied, the contribution of single-nucleotide polymorphisms towards this condition remains poorly understood. In addition, the etiology of BSP remains to be fully elucidated. Therefore, the present study aimed to assess the role of polymorphisms in the torsin 1A (TOR1A), dopamine receptor D (DRD)2 and DRD5 genes in South Korean patients with BSP. Furthermore, the role of genetic variants of these three aforementioned genes was investigated. A prospective case-control study was established, where 56 patients with BSP and 115 healthy controls were recruited at the Department of Ophthalmology of CHA Bundang Medical Center (Seongnam, South Korea) using single nucleotide polymorphisms analysis by real-time PCR. The TOR1A rs1182CC/ DRD5 rs6283TC genotype combination was found to be associated with decreased BSP risk [adjusted odds ratio (AOR), 0.288; P=0.013]. DRD5 rs6283 was observed to be associated with the periocular type of BSP in the co-dominant (for the TC genotype; AOR, 0.370; P=0.029) and dominant models (AOR, 0.406; P=0.029). The recessive model of TOR1A rs1801968 (AOR, 0.245; P=0.030), and the recessive (AOR, 0.245; P=0.029) and over-dominant models (AOR, 2.437; P=0.019) of DRD2 rs1800497 were found to be associated with superior responses to botulinum neurotoxin A (BoNT) treatment. By contrast, dominant (AOR, 0.205; P=0.034) and additive (AOR, 0.227; P=0.030) models of DRD5 rs6283 were associated with poor responses to BoNT treatment. To conclude, these results suggested that DRD2 rs1800497 can confer genetic susceptibility to BSP responses to BoNT treatment, whereas the TOR1A rs1182CC/ DRD5 rs6283TC genotype combination appeared to contribute to the association with BoNT efficacy in BSP., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Jang et al.)

Introduction: Given the recent additions of immune checkpoint inhibitors (ICIs) to various cancer treatments, adverse effects, especially involving the eyes, have been on the rise. Here, we report an acute exacerbation of cancer-associated retinopathy (CAR) triggered by durvalumab treatment of small-cell lung cancer (SCLC)., Case Presentation: An 81-year-old Asian male complained of a scotoma in the left eye after durvalumab administration, to treat SCLC. Humphrey visual field examination revealed a C-shaped temporal scotoma. Spectralis domain optical coherence tomography revealed outer retinal layer atrophy and progressive loss of the ellipsoid zone in the atrophic peripapillary area. Fundus autofluorescence (AF) images evidenced a large C-shaped hypo-AF with enhanced AF at the margin of the atrophic area, thus at the position of the scotoma. We prescribed subtenon triamcinolone injections under suspicion of CAR exacerbation, supported by positive Western blotting results for Rab6 and aldolase, and immunohistochemical staining of photoreceptor cells. The disrupted ellipsoid zone evident on OCT partially recovered, and a visual field test showed that the scotoma had improved., Conclusion: ICI-triggered exacerbation of CAR should be considered in SCLC patients before ICI treatment commences; an optimal treatment should preserve functional vision., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: To measure inter-reader agreement and identify associated factors in interpreting complete response (CR) on magnetic resonance imaging (MRI) following chemoradiotherapy (CRT) for rectal cancer., Materials and Methods: This retrospective study involved 10 readers from seven hospitals with experience of 80-10210 cases, and 149 patients who underwent surgery after CRT for rectal cancer. Using MRI-based tumor regression grading (mrTRG) and methods employed in daily practice, the readers independently assessed mrTRG, CR on T2-weighted images (T2WI) denoted as mrCR T2W , and CR on all images including diffusion-weighted images (DWI) denoted as mrCR overall . The readers described their interpretation patterns and how they utilized DWI. Inter-reader agreement was measured using multi-rater kappa, and associated factors were analyzed using multivariable regression. Correlation between sensitivity and specificity of each reader was analyzed using Spearman coefficient., Results: The mrCR T2W and mrCR overall rates varied widely among the readers, ranging 18.8%-40.3% and 18.1%-34.9%, respectively. Nine readers used DWI as a supplement sequence, which modified interpretations on T2WI in 2.7% of cases (36/1341 [149 patients × 9 readers]) and mostly (33/36) changed mrCR T2W to non-mrCR overall . The kappa values for mrTRG, mrCR T2W , and mrCR overall were 0.56 (95% confidence interval: 0.49, 0.62), 0.55 (0.52, 0.57), and 0.54 (0.51, 0.57), respectively. No use of rectal gel, larger initial tumor size, and higher initial cT stage exhibited significant association with a higher inter-reader agreement for assessing mrCR overall ( P ≤ 0.042). Strong negative correlations were observed between the sensitivity and specificity of individual readers (coefficient, -0.718 to -0.963; P ≤ 0.019)., Conclusion: Inter-reader agreement was moderate for assessing CR on post-CRT MRI. Readers' varying standards on MRI interpretation (i.e., threshold effect), along with the use of rectal gel, initial tumor size, and initial cT stage, were significant factors associated with inter-reader agreement., Competing Interests: Joon Seok Lim and Seong Ho Park, who hold respective positions on the Editorial Board Member and Editor-in-Chief of the Korean Journal of Radiology, were not involved in the editorial evaluation or decision to publish this article. The remaining author has declared no conflicts of interest., (Copyright © 2024 The Korean Society of Radiology.)

With advancements in research and the necessity of improving the performance of bioelectrochemical system (BES), coupling anaerobic digestion (AD) with BES is crucial for energy gain from wastewater and bioremediation. Hybridization of BES-AD concept opens new avenues for pollutant degradation, carbon capture and nutrient-resource recovery from wastewater. The strength of merging BES-AD lies in synergy, and this approach was employed to differentiate fads from strategies with the potential for full-scale implementation and making it an energy-positive system. The integration of BES and AD system increases the overall performance and complexity of combined system and the cost of operation. From a technical standpoint, the primary determinants of BES-AD feasibility for field applications are the scalability and economic viability. High potential market for such integrated system attract industrial partners for more industrial trials and investment before commercialization. However, BES-AD with high energy efficacy and negative economics demands performance boost., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The generation of spectrally pure microwave signals is a critical functionality in fundamental and applied sciences, including metrology and communications. Optical frequency combs enable the powerful technique of optical frequency division (OFD) to produce microwave oscillations of the highest quality 1,2 . Current implementations of OFD require multiple lasers, with space- and energy-consuming optical stabilization and electronic feedback components, resulting in device footprints incompatible with integration into a compact and robust photonic platform 3-5 . Here we demonstrate all-optical OFD on a photonic chip by synchronizing two distinct dynamical states of Kerr microresonators pumped by a single continuous-wave laser. The inherent stability of the terahertz beat frequency between the signal and idler fields of an optical parametric oscillator is transferred to a microwave frequency of a Kerr soliton comb, and synchronization is achieved via a coupling waveguide without the need for electronic locking. OFD factors of N = 34 and 468 are achieved for 227 GHz and 16 GHz soliton combs, respectively. In particular, OFD enables a 46 dB phase-noise reduction for the 16 GHz soliton comb, resulting in the lowest microwave noise observed in an integrated photonics platform. Our work represents a simple, effective approach for performing OFD and provides a pathway towards chip-scale devices that can generate microwave frequencies comparable to the purest tones produced in metrological laboratories., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: The present study examined the microbiome abundance and composition of drug-naive or drug-free patients with obsessive-compulsive disorder (OCD) compared with healthy controls. In addition, in the OCD group, the microbiome composition was compared between early-onset and late-onset OCD., Methods: Serum samples were collected from 89 patients with OCD and 107 age- and sex-matched healthy controls. Bacterial DNA was isolated from bacteria-derived extracellular vesicles in serum and then amplified and quantified using primers specific to the V3-V4 hypervariable region of the 16S ribosomal RNA gene. The 16S ribosomal DNA gene amplicon sequencing was performed., Results: The pooled estimate showed that α-diversity was significantly reduced in patients with OCD compared with that in healthy controls (P Shannon  = 0.00015). In addition, a statistically significant difference was observed in β-diversity between patients with OCD and healthy controls at the order (P = 0.012), family (P = 0.003), genus (P < 0.001), and species (P = 0.005) levels. In the microbiome composition, Pseudomonas, Caulobacteraceae (f), Streptococcus, Novosphingobium, and Enhydrobacter at the genus level were significantly less prevalent in patients with OCD than in controls. In addition, among patients with OCD, the microbial composition in the early-onset versus late-onset types was significantly different with respect to the genera Corynebacterium and Pelomonas., Conclusion: The present study showed an aberrant microbiome in patients with OCD, suggesting a role of the microbiota-brain interaction in the pathophysiology of OCD. Further longitudinal studies with larger sample sizes adjusting for various confounders are warranted., (© 2023 The Authors. Psychiatry and Clinical Neurosciences © 2023 Japanese Society of Psychiatry and Neurology.)

The centromere is an epigenetic mark that is a loading site for the kinetochore during meiosis and mitosis. This mark is characterized by the H3 variant CENP-A, known as CID in Drosophila. In Drosophila, CENP-C is critical for maintaining CID at the centromeres and directly recruits outer kinetochore proteins after nuclear envelope break down. These two functions, however, happen at different times in the cell cycle. Furthermore, in Drosophila and many other metazoan oocytes, centromere maintenance and kinetochore assembly are separated by an extended prophase. We have investigated the dynamics of function of CENP-C during the extended meiotic prophase of Drosophila oocytes and found that maintaining high levels of CENP-C for metaphase I requires expression during prophase. In contrast, CID is relatively stable and does not need to be expressed during prophase to remain at high levels in metaphase I of meiosis. Expression of CID during prophase can even be deleterious, causing ectopic localization to non-centromeric chromatin, abnormal meiosis and sterility. CENP-C prophase loading is required for multiple meiotic functions. In early meiotic prophase, CENP-C loading is required for sister centromere cohesion and centromere clustering. In late meiotic prophase, CENP-C loading is required to recruit kinetochore proteins. CENP-C is one of the few proteins identified in which expression during prophase is required for meiotic chromosome segregation. An implication of these results is that the failure to maintain recruitment of CENP-C during the extended prophase in oocytes would result in chromosome segregation errors in oocytes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fellmeth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study investigated the value of Doppler ultrasonography in predicting clinical outcomes after antirejection treatment for patients with acute cellular rejection (ACR) following liver transplantation (LT)., Methods: This retrospective study included 84 patients who were pathologically diagnosed with ACR and received antirejection treatment within 90 days following LT. Two radiologists searched for abnormal Doppler parameters at ACR diagnosis and within 7 days after antirejection treatment initiation, including portal blood velocity (PBV) <20 cm/s, hepatic artery resistive index <0.5, and a monophasic hepatic vein flow pattern. Interval PBV changes were also evaluated. The frequencies of abnormal Doppler parameters and PBV changes were compared by treatment outcome., Results: The frequency of abnormal PBV in the early post-treatment phase (PBVearly post-treatment) was significantly higher among poor responders (50.0% [10/20]) than among good responders (7.8% [5/64]) (P<0.001). The sensitivity, specificity, and accuracy of abnormal PBVearly post-treatment as a predictor of poor response to antirejection treatment were 50.0% (10/20), 92.2% (59/64), and 82.1% (69/84), respectively. A decrease (>10%) from the PBV at event (PBVevent) to PBVearly post-treatment was significantly more common among poor responders (50.0% [10/20]) than among good responders (20.3% [13/64]) (P=0.019). The sensitivity, specificity, and accuracy of this PBV decrease in predicting poor treatment response were 50.0% (10/20), 79.7% (51/64), and 72.6% (61/84), respectively., Conclusion: Abnormal PBVearly post-treatment and a decrease between PBVevent and PBVearly post-treatment were significantly associated with poor treatment response in patients with ACR after LT. Consequently, Doppler ultrasonography may be useful for predicting clinical outcomes in these patients.

In vanadium redox flow batteries (VRFBs), simultaneously achieving high proton conductivity, low vanadium-ion permeability, and outstanding chemical stability using electrolyte membranes is a significant challenge. In this study, we report the fabrication of a tri-directional poly(2,5-benzimidazole) (T-ABPBI) membrane using a direct casting method. The direct-cast T-ABPBI (D-T-ABPBI) membrane was fabricated by modifying the microstructure of the membrane while retaining the chemical structure of ABPBI, having outstanding chemical stability. The D-T-ABPBI membrane exhibited lower crystallinity and an expanded free volume compared to the general solvent-cast T-ABPBI (S-T-ABPBI) membrane, resulting in enhanced hydrophilic absorption capabilities. Compared to the S-T-ABPBI membrane, the enhanced hydrophilic absorption capability of the D-T-ABPBI membrane resulted in a decrease in the specific resistance (the area-specific resistance of S-T-ABPBI and D-T-ABPBI membrane is 1.75 and 0.98 Ωcm 2 , respectively). Additionally, the D-T-ABPBI membrane showed lower vanadium permeability (3.40 × 10 -7 cm 2 min -1 ) compared to that of Nafion 115 (5.20 × 10 -7 cm 2 min -1 ) due to the Donnan exclusion effect. Owing to the synergistic effects of these properties, the VRFB assembled with D-T-ABPBI membrane had higher or equivalent coulomb efficiencies (>97%) and energy efficiencies (70-91%) than Nafion 115 at various current densities (200-40 mA cm -2 ). Furthermore, the D-T-ABPBI membrane exhibited stable performance for over 300 cycles at 100 mA cm -2 , suggesting its outstanding chemical stability against the highly oxidizing VO 2 + ions during practical VRFB operation. These results indicate that the newly fabricated D-T-ABPBI membranes are promising candidates for VRFB application.

Background: The comparative impact of histologic variants and grade has not been well described., Methods: Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival., Results: On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73)., Conclusion: Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems., (© 2023 Wiley Periodicals LLC.)

The pulverization of lithium metal electrodes during cycling recently has been suppressed through various techniques, but the issue of irreversible consumption of the electrolyte remains a critical challenge, hindering the progress of energy-dense lithium metal batteries. Here, we design a single-ion-conductor-based composite layer on the lithium metal electrode, which significantly reduces the liquid electrolyte loss via adjusting the solvation environment of moving Li + in the layer. A Li||Ni 0.5 Mn 0.3 Co 0.2 O 2 pouch cell with a thin lithium metal (N/P of 2.15), high loading cathode (21.5 mg cm -2 ), and carbonate electrolyte achieves 400 cycles at the electrolyte to capacity ratio of 2.15 g Ah -1 (2.44 g Ah -1 including mass of composite layer) or 100 cycles at 1.28 g Ah -1 (1.57 g Ah -1 including mass of composite layer) under a stack pressure of 280 kPa (0.2 C charge with a constant voltage charge at 4.3 V to 0.05 C and 1.0 C discharge within a voltage window of 4.3 V to 3.0 V). The rational design of the single-ion-conductor-based composite layer demonstrated in this work provides a way forward for constructing energy-dense rechargeable lithium metal batteries with minimal electrolyte content., (© 2023. The Author(s).)

Purpose: This study compared the controlled attenuation parameter (CAP) to attenuation imaging (ATI) in the diagnosis of steatosis and transient elastography (TE) to two-dimensional shear wave elastography (2D-SWE) for the diagnosis of fibrosis in a prospectively constructed nonalcoholic fatty liver disease (NAFLD) patient cohort., Methods: Participants who underwent TE with CAP were included from a previously constructed NAFLD cohort with multiparametric ultrasound data. The degree of hepatic steatosis and stage of liver fibrosis were assessed. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUROC) for the grades of steatosis (S1-3) and fibrosis (F0-F4)., Results: There were 105 participants. The distribution of hepatic steatosis grades (S0-S3) and liver fibrosis stages (F0-F4) was as follows: S0, n=34; S1, n=41; S2, n=22; S3, n=8; F0, n=63; F1, n=25; F2, n=5; F3, n=7; and F4, n=5. No significant difference was found between CAP and ATI in detecting ≥S1 (AUROC: 0.93 vs. 0.93, P=0.956) or ≥S2 (0.94 vs. 0.94, P=0.769). However, the AUROC of ATI in detecting ≥S3 was significantly higher than that of CAP (0.94 vs. 0.87, P=0.047). Regarding the detection of liver fibrosis, no significant difference was found between TE and 2D-SWE. The AUROCs of TE and 2D-SWE were as follows: ≥F1, 0.94 vs. 0.89 (P=0.107); ≥F2, 0.89 vs. 0.90 (P=0.644); ≥F3, 0.91 vs. 0.90 (P=0.703); and ≥F4, 0.88 vs. 0.92 (P=0.209)., Conclusion: 2D-SWE and TE showed comparable diagnostic performance in assessing liver fibrosis, and ATI provided significantly better performance in detecting ≥S3 steatosis than CAP.

Background: Extramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer. Recent advances in magnetic resonance imaging (MRI) allow for the detection of EMVI before surgery. This study aimed to analyze the correlations between MRI-detected EMVI (MR-EMVI) and pathologic parameters in patients with rectal cancer., Materials and Methods: This study retrospectively analyzed 721 patients who underwent radical resection for locally advanced rectal cancer between 2018 and 2019 at the Asan Medical center. All patients underwent an MRI before surgery. The lesions of patients who received neoadjuvant chemoradiation therapy (CRT) were evaluated by MRI before and after the neoadjuvant CRT., Results: Of the 721 patients, 118 (16.4%) showed a positive MR-EMVI, which significantly correlated with advanced pathologic T-category and N-category, extranodal extension, poor differentiation, lymphatic invasion, venous invasion, and perineural invasion. In addition, MR-EMVI was an independent factor for predicting the pathologic nodal status (OR 3.476, 95% CI, 2.186-5.527, P < .001). Patients with a positive MR-EMVI had a sensitivity of 28.0% and specificity of 91.9% for predicting regional lymph node metastasis, whereas the MR-N category had a sensitivity of 88.7% and specificity of 30.6%. Patients whose MR-EMVI changed from positive to negative after neoadjuvant CRT had no significant differences in pathologic parameters except for lymphatic invasion with patients who were negative before and after neoadjuvant CRT., Conclusion: MR-EMVI correlated with aggressive pathologic features, which indicated a poor prognosis. MR-EMVI may be a complementary imaging biomarker for predicting nodal status and evaluating tumor response to neoadjuvant CRT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To investigate the effects of deep learning-based imaging reconstruction (DLR) on the image quality of MRI of rectal cancer after chemoradiotherapy (CRT), and its accuracy in diagnosing pathological complete responses (pCR)., Methods: We included 39 patients (men: women, 21:18; mean age ± standard deviation, 59.1 ± 9.7 years) with mid-to-lower rectal cancer who underwent a long-course of CRT and high-resolution rectal MRIs between January 2020 and April 2021. Axial T2WI was reconstructed using the conventional method (MRI conv ) and DLR with two different noise reduction factors (MRI DLR30 and MRI DLR50 ). The signal-to-noise ratio (SNR) of the tumor was measured. Two experienced radiologists independently made a blind assessment of the complete response on MRI. The sensitivity and specificity for pCR were analyzed using a multivariable logistic regression analysis with generalized estimating equations., Results: Thirty-four patients did not have a pCR whereas five (12.8%) had pCR. Compared with the SNR of MRI conv (mean ± SD, 7.94 ± 1.92), MRI DLR30 and MRI DLR50 showed higher SNR (9.44 ± 2.31 and 11.83 ± 3.07, respectively) (p < 0.001). Compared to MRI conv , MRI DLR30 and MRI DLR50 showed significantly higher specificity values (p < 0.036) while the sensitivity values were not significantly different (p > 0.301). The sensitivity and specificity for pCR were 48.9% and 80.8% for MRI conv ; 48.9% and 88.2% for MRI DLR30 ; and 38.8% and 86.7% for MRI DLR50 , respectively., Conclusion: DLR produced MR images with higher resolution and SNR. The specificity of MRI for identification of pCR was significantly higher with DLR than with conventional MRI., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We have previously shown that monoamine oxidase A (MAO A) mediates prostate cancer growth and metastasis. Further, MAO A/Pten double knockout (DKO) mice were generated and demonstrated that the deletion of MAO A delayed prostate tumor development in the Pten knockout mouse model of prostate adenocarcinoma. Here, we investigated its effect on immune cells in the tumor microenvironment in MAO A/Pten DKO mouse model. Our results shows that Paraffin embedded prostate tissues from MAO A/Pten DKO mice had elevated markers of immune stimulation (CD8 + cytotoxic T cells, granzyme B, and IFNγ) and decreased expression of markers of immune suppression (FoxP3, CD11b, HIF-1-alpha, and arginase 1) compared to parental Pten knockouts (MAO A wildtype). CD11b + myeloid derived suppressor cells (MDSC) were the primary immunosuppressive cell types in these tumors. The data suggest that deletion of MAO A reduces immune suppression in prostate tumors to enhance antitumor immunity in prostate cancer. Thus, MAO A inhibitor may alleviate immune suppression, increase the antitumor immune response and be used for cancer immunotherapy., Competing Interests: Declarations of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JCS is an inventor on the related U. S. patents concerning MAO inhibitor-based compounds for cancer treatment. All other authors have no competing interests to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Microinjection of cocaine- and amphetamine-regulated transcript (CART) peptide 55-102 into the nucleus accumbens (NAcc) core significantly attenuates psychostimulant-induced locomotor activity. However, the molecular mechanism remains poorly understood. We examined the phosphorylation levels of Akt, glycogen synthase kinase 3β (GSK3β), and glutamate receptor 1 (GluA1) in NAcc core tissues obtained 60 min after microinjection of CART peptide 55-102 into this site, followed by systemic injection of amphetamine (AMPH). Phosphorylation levels of Akt at Thr308 and GSK3β at Ser9 were decreased, while those of GluA1 at Ser845 were increased, by AMPH treatment. These effects returned to basal levels following treatment with CART peptide 55-102. Furthermore, the negative regulatory effects of the CART peptide on AMPH-induced changes in phosphorylation levels and locomotor activity were all abolished by pretreatment with the S9 peptide, an artificially synthesized indirect GSK3β activator. These results suggest that the CART peptide 55-102 in the NAcc core plays a negative regulatory role in AMPH-induced locomotor activity by normalizing the changes in phosphorylation levels of Akt-GSK3β, and subsequently GluA1 modified by AMPH at this site. The present findings are the first to reveal GSK3β as a key regulator of the inhibitory role of the CART peptide in psychomotor stimulant-induced locomotor activity.

Objective: To propose standardized MRI-proton density fat fraction (PDFF) cutoff values for diagnosing hepatic steatosis, evaluated using contemporary PDFF measuring methods in a large population of healthy adults, using histologic fat fraction (HFF) as the reference standard., Materials and Methods: A retrospective search of electronic medical records between 2015 and 2018 identified 1063 adult donor candidates for liver transplantation who had undergone liver MRI and liver biopsy within a 7-day interval. Patients with a history of liver disease or significant alcohol consumption were excluded. Chemical shift imaging-based MRI (CS-MRI) PDFF and high-speed T2-corrected multi-echo MR spectroscopy (HISTO-MRS) PDFF data were obtained. By temporal splitting, the total population was divided into development and validation sets. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of the MRI-PDFF method. Two cutoff values with sensitivity > 90% and specificity > 90% were selected to rule-out and rule-in, respectively, hepatic steatosis with reference to HFF ≥ 5% in the development set. The diagnostic performance was assessed using the validation set., Results: Of 921 final participants (624 male; mean age ± standard deviation, 31.5 ± 9.0 years), the development and validation sets comprised 497 and 424 patients, respectively. In the development set, the areas under the ROC curve for diagnosing hepatic steatosis were 0.920 for CS-MRI-PDFF and 0.915 for HISTO-MRS-PDFF. For ruling-out hepatic steatosis, the CS-MRI-PDFF cutoff was 2.3% (sensitivity, 92.4%; specificity, 63.0%) and the HISTO-MRI-PDFF cutoff was 2.6% (sensitivity, 88.8%; specificity, 70.1%). For ruling-in hepatic steatosis, the CS-MRI-PDFF cutoff was 3.5% (sensitivity, 73.5%; specificity, 88.6%) and the HISTO-MRI-PDFF cutoff was 4.0% (sensitivity, 74.7%; specificity, 90.6%)., Conclusion: In a large population of healthy adults, our study suggests diagnostic thresholds for ruling-out and ruling-in hepatic steatosis defined as HFF ≥ 5% by contemporary PDFF measurement methods., Competing Interests: So Yeon Kim and Seung Soo Lee who is on the editorial board of the Korean Journal of Radiology was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2022 The Korean Society of Radiology.)

Background Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for use in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Case reports have suggested an association between T-DM1 and portal hypertension. Purpose To evaluate the association of T-DM1 therapy with spleen volume changes and portal hypertension on CT scans and clinical findings compared with lapatinib and capecitabine therapy. Materials and Methods Patients with HER2-positive breast cancer who were administered at least two cycles of T-DM1 or lapatinib and capecitabine (controls) in a tertiary institution from 2001 to 2020 and who underwent CT before initial treatment and at least once during treatment were retrospectively enrolled. Spleen volume changes and the signs of portal hypertension (gastroesophageal varix [GEV], spontaneous portosystemic shunt [SPSS], and ascites) were evaluated at contrast-enhanced CT. Patients were followed until treatment ended or for 2 years after the start of treatment. Spleen volume changes were measured with a deep learning algorithm and evaluated by using a linear mixed model. The incidences of splenomegaly and portal hypertension were compared between the T-DM1 and control groups by using a χ 2 test or Fisher exact test. Results The T-DM1 group included 111 patients (mean age, 54 years ± 11 [SD]; 111 women) and the control group included 122 patients (mean age, 50 years ± 9; 121 women). Spleen volume progressively increased with T-DM1 therapy but was constant in the control group (104% ± 5 vs -1% ± 6 at the 33rd treatment cycle, respectively; P < .001). Incidences of splenomegaly (46% [51 of 111] vs 3% [four of 122] of patients; P < .001), GEV (11% [12 of 111] vs 1% [one of 122] of patients; P < .001), and SPSS (27% [30 of 111] vs 1% [one of 122] of patients; P < .001) were higher in the T-DM1 group than in the control group. Conclusion Trastuzumab emtansine therapy was associated with noncirrhotic portal hypertension at CT, with higher incidences of splenomegaly, gastroesophageal varix, and spontaneous portosystemic shunt than those with lapatinib and capecitabine therapy. © RSNA, 2022 Online supplemental material is available for this article.

Background Multiparametric US examination may have potential in the comprehensive evaluation of nonalcoholic fatty liver disease (NAFLD), but multicenter studies are lacking. Purpose To evaluate the diagnostic performance of multiparametric US with the attenuation coefficient (AC) from attenuation imaging (ATI) and liver stiffness (LS) and dispersion slope (DS) from two-dimensional (2D) shear-wave elastography (SWE) in a multicenter study of patients with NAFLD. Materials and Methods This prospective study enrolled consecutive participants between December 2019 and June 2021 with suspected nonalcoholic steatohepatitis (NASH) who were scheduled to undergo liver biopsy in five tertiary hospitals. Before the procedure, all participants underwent US with ATI and 2D SWE according to the study protocol. Multivariable linear regression analyses were performed to determine the significant determinant factors for AC, LS, and DS. Diagnostic performance was decided based on the areas under the receiver operating characteristic curve (AUCs). Results A total of 132 participants (median age, 38 years; IQR, 27-54 years; 69 women) were evaluated. Among the participant characteristics, including pathologic findings, demographic characteristics, body mass index, and serum markers, hepatic steatosis for AC ( P < .001), lobular inflammatory activity for DS ( P = .007), and both fibrosis ( P = .01) and lobular inflammatory activity ( P = .04) for LS were significant determinant factors. At histopathologic examination, 53 of the 132 participants (40.2%) had NASH. The risk score system obtained using unweighted sum of scores from AC and DS showed the best diagnostic performance in the detection of NASH (AUC = 0.94; 95% CI: 0.89, 0.98; P < .05 for all), as compared with serum markers or other US parameters alone (AUC ≤ 0.88). Conclusion US attenuation imaging and two-dimensional shear-wave elastography were useful for assessing hepatic steatosis, lobular inflammation, and fibrosis. The risk score system obtained using the attenuation coefficient and dispersion slope showed the best diagnostic performance fo r nonalcoholic steatohepatitis. cris.nih.go.kr no. KCT0004326 © RSNA, 2022 Online supplemental material is available for this article .

Purpose: We investigated the cytologic findings of primary acquired nasolacrimal duct obstruction (PANDO) based on the thin-prep cytology method using sheath-guided dacryoendoscopy., Methods: A retrospective review was conducted of 66 cases from 50 patients who were diagnosed with PANDO. Slit-lamp examination, the lacrimal irrigation test, and dacryocystography were performed for the evaluation of PANDO. The dacryocystography (DCG) findings were classified into primary and secondary change. Each patient was treated with transcanalicular dacryoplasty using catheter sheath-guided dacryoendoscopy (RUIDO Fiberscope, Fiber Tech Co., Ltd., Tokyo, Japan) and obtained cytologic specimens. The liquid-based thin-prep cytology method was used for the analysis of histopathology., Results: The cellular detection rate was as follows: epithelial cells with 56 cases (84.8%), 33 cases (50.0%) with inflammatory cells, 1 case (1.5%) with mucin, and bacterial colonies with 2 cases (3.0%). In the dacryoendoscopic findings, all cases of a presence of pus were related to the detection of the columnar epithelium (p = 0.026), while there was no statical significance according to the presence of an epithelial cell. In the DCG findings, the PANDOs with the secondary change showed a higher detection rate than those with the primary change (p = 0.005), and columnar epithelial cells were observed (p = 0.011). The detection rate of inflammatory cells was 50.0% (33/66) and all inflammatory cells were lymphocytes but it was not correlated with clinical findings. One case of mucin (1.5%) and 2 cases of bacterial colonies (3.0%) were presented using liquid-based thin-prep cytology analysis. The overall success rate of transcanalicular dacryoplasty and silicone intubation was 86.4%., Conclusion: Liquid based thin prep cytology can be used to analyze histopathological changes of lacrimal passage in PANDO without invasive biopsy. These cytologic findings of lacrimal passage provide a better understanding of the pathogenesis of lacrimal passage in patients with PANDO., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Accurate assessment of pancreatic ductal adenocarcinoma (PDAC) resectability after neoadjuvant therapy (NAT) is crucial. Recently, the NCCN introduced criteria for resection of PDAC following NAT., Methods: We analyzed 127 patients who underwent NAT and pancreatectomy for PDAC between January 2010 and March 2020. CT-determined resectability according to the NCCN guideline and CA 19-9 level was evaluated before and after NAT. Diagnostic performance of the NCCN criteria for margin-negative (R0) resection was investigated and compared with CT alone., Results: R0 resection was achieved in 104 (81.9%) patients. After NAT, there were 30 (23.6%) resectable, 90 (70.9%) borderline resectable, and seven (5.5%) locally advanced tumors. Significantly decreased or stable CA 19-9 levels were noted in 114 (89.8%) patients. The sensitivity and specificity of the NCCN criteria were 87.5% (91/104) and 21.7% (5/23), respectively, which were significantly different from CT including only resectable PDAC (26.9% [28/104] and 91.3% [21/23]; P < .001), but less prominently different from CT including resectable and borderline resectable PDAC (95.2% [99/104]; P = .022 and 8.7% [2/23]; P = .375)., Conclusions: The NCCN criteria for resection following NAT showed high sensitivity and low specificity for predicting R0 resection. It had supplementary benefit over CT alone, mainly in preventing underestimation of R0 resection., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objectives: This study was designed to investigate the frequency of computed tomography features indicating progression of portal hypertension and their clinical relevance in patients who experienced acute cellular rejection after liver transplantation., Materials and Methods: This retrospective study included 141 patients with pathologically diagnosed acute cellular rejection following liver transplant. Patients were divided into early and late rejection groups according to the time of diagnosis. Two radiologists analyzed the interval changes in spleen size and variceal engorgement on computed tomography images obtained at the times of surgery and biopsy. Aggravation of splenomegaly and variceal engorgement were considered computed tomography features associated with the progression of portal hypertension. Clinical outcomes, including responses to treatment and graft survival, were compared between patients with and without these features., Results: The frequency of progression of portal hypertension was 31.9% and did not differ significantly in patients who experienced early (30.8% [28/91]) and late (34.0% [17/50]) rejection (P = .694). In the late rejection group, computed tomography features indicating progression of portal hypertension were significantly associated with poor response to treatment (P = .033). Graft survival in both the early and late rejection groups did not differ significantly in patients with and without progression of portal hypertension., Conclusions: Computed tomography features suggesting the progression of portal hypertension were encountered in about one-third of patients who experienced acute cellular rejection after liver transplant. Progression of portal hypertension was significantly related to poor response to treatment in the late rejection group.

Purpose: We aimed to determine a new strategy for Liver Imaging Reporting and Data System category M (LR-M) criteria to improve the diagnosis of HCC ≤ 3.0 cm on magnetic resonance imaging (MRI)., Methods: A total of 463 pathologically confirmed hepatic observations ≤ 3.0 cm (375 HCCs, 32 other malignancies, 56 benignities) in 384 patients at risk of HCC who underwent gadoxetate-enhanced MRI were retrospectively analyzed. Two radiologists evaluated the presence of major, ancillary, and LR-M features according to LI-RADS v2018. Of the ten LR-M features, those significantly associated with non-HCC malignancy were identified using multivariable logistic regression analysis, and new LR-M criteria for improving the diagnosis of HCC were investigated. Generalized estimating equations were used to compare sensitivity and specificity of LR-5 for diagnosing HCC using the new LR-M criteria with values calculated using the original LR-M criteria. p < 0.05 was considered to indicate a significant difference., Results: Of ten LR-M features, rim arterial-phase hyperenhancement, delayed central enhancement, targetoid restriction, and targetoid transitional-phase/hepatobiliary-phase appearance were independently significantly associated with non-HCC malignancy (adjusted odds ratio ≥ 6.2; p ≤ 0.02). Using the new LR-M criteria (two or more of these significant features), the sensitivity of LR-5 for diagnosing HCC was higher than that with the original LR-M criteria (69% [95% confidence interval 64-73%] vs. 65% [61-70%], p = 0.002), whereas the specificity was similar (90% [82-95%] vs. 92% [83-96%], p = 0.28)., Conclusion: The new LR-M criteria (two or more significant features) can improve the sensitivity of LR-5 for diagnosing HCC ≤ 3.0 cm, without compromising specificity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To determine the diagnostic value of [ 68  Ga]Ga-DOTA-labeled-somatostatin analogue ([ 68  Ga]Ga-DOTA-SSA) PET/MRI for detecting liver metastasis in patients with neuroendocrine tumor (NET) and to compare it with [ 68  Ga]Ga-DOTA-SSA PET/CT., Methods: A search of MEDLINE, EMBASE, and Cochrane was performed to identify original articles reporting the detection rate of [ 68  Ga]Ga-DOTA-SSA PET/MRI for liver metastasis in comparison with PET/CT. The pooled detection rates for liver metastasis on PET/MRI and PET/CT were calculated and compared using a restricted maximum likelihood estimation of random-effects model. The pooled added value of PET/MRI in comparison with PET/CT was calculated. Sensitivity analysis and subgroup analysis were performed to explore causes of study heterogeneity., Results: In the six included studies (638 liver metastases), the pooled detection rates for liver metastasis on [ 68  Ga]Ga-DOTA-SSA PET/MRI and PET/CT were 93.5% (95% confidence interval [CI], 85.1-97.3%; I 2  = 84.8%) and 76.8% (95% CI, 64.8-85.6%; I 2  = 87.8%), respectively. PET/MRI had a significantly higher detection rate than PET/CT (p = 0.02), with 15.3% (95% CI, 8.0-27.4%) added value over PET/CT. After sensitivity analysis, the recalculated detection rates for liver metastasis were 94.8% (95% CI, 90.8-97.2%; I 2  = 42.1%) for PET/MRI and 80.0% (95% CI, 65.3-89.5%; I 2  = 90.0%) for PET/CT. The study location and the use of predefined imaging criteria for liver metastasis were associated with PET/MRI study heterogeneity., Conclusion: [ 68  Ga]Ga-DOTA-SSA PET/MRI had good overall performance for detecting liver metastasis in patients with NET. Because of the small number of eligible studies, further studies are needed to validate the clinical usefulness of [ 68  Ga]Ga-DOTA-SSA PET/MRI., Key Points: • [ 68  Ga]Ga-DOTA-SSA PET/MRI had a higher pooled detection rate for liver metastasis than PET/CT (93.5% vs. 76.8%). • The added value of [ 68  Ga]Ga-DOTA-SSA PET/MRI for detecting liver metastasis in comparison with PET/CT was 15.3%. •Study location and the predefined imaging criteria for liver metastasis were significant factors causing PET/MRI study heterogeneity., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment option for patients with refractory hematological malignancies. However, its efficacy in glioblastoma remains unclear. Here, we performed a systematic review to summarize the safety and efficacy of CAR T-cell therapy in glioblastoma., Methods: The PubMed, EMBASE, and Cochrane databases were searched to identify articles published before June 30, 2021 describing the use of CAR T-cell therapy in glioblastoma. Information on the toxicity of CAR T-cell therapy was summarized. The pooled objective response rate (ORR) and overall survival (OS) of patients who underwent CAR T-cell therapy were estimated using a random-effects model with an inverse-variance weighting model and quantile estimation method, respectively., Results: Of 397 articles identified, eight studies including 63 patients with recurrent glioblastoma treated with various CAR T-cell regimens were included in the analysis. Six (9.5%) patients developed cytokine release syndrome (grade ≤2), and 16 (25.4%) experienced non-critical neurological events. The pooled ORR was 5.1% (95% confidence interval [CI], 0.0-10.4; I 2 = 0.05%), and the pooled median OS was 8.1 months (95% CI, 6.7-9.5; I 2 = 0.00%)., Conclusion: Although CAR T -cell therapy is a relatively safe therapeutic option in patients with glioblastoma, it shows marginal efficacy, suggesting that further research is necessary for its translation into clinical practice for the treatment of recurrent glioblastoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jang, Pyo, Suh, Park, Chae and Kim.)

Therapeutic combinations to alter immunosuppressive, solid tumor microenvironments (TME), such as in breast cancer, are essential to improve responses to immune checkpoint inhibitors (ICI). Entinostat, an oral histone deacetylase inhibitor, has been shown to improve responses to ICIs in various tumor models with immunosuppressive TMEs. The precise and comprehensive alterations to the TME induced by entinostat remain unknown. Here, we employed single-cell RNA sequencing on HER2-overexpressing breast tumors from mice treated with entinostat and ICIs to fully characterize changes across multiple cell types within the TME. This analysis demonstrates that treatment with entinostat induced a shift from a protumor to an antitumor TME signature, characterized predominantly by changes in myeloid cells. We confirmed myeloid-derived suppressor cells (MDSC) within entinostat-treated tumors associated with a less suppressive granulocytic (G)-MDSC phenotype and exhibited altered suppressive signaling that involved the NFκB and STAT3 pathways. In addition to MDSCs, tumor-associated macrophages were epigenetically reprogrammed from a protumor M2-like phenotype toward an antitumor M1-like phenotype, which may be contributing to a more sensitized TME. Overall, our in-depth analysis suggests that entinostat-induced changes on multiple myeloid cell types reduce immunosuppression and increase antitumor responses, which, in turn, improve sensitivity to ICIs. Sensitization of the TME by entinostat could ultimately broaden the population of patients with breast cancer who could benefit from ICIs., (©2022 American Association for Cancer Research.)

Objectives: To determine the diagnostic performance of the liver surface nodularity (LSN) score for assessment of hepatic fibrosis., Methods: Major databases were searched to identify studies reporting the diagnostic performance of the LSN score published from January 2011 to April 2021. The pooled sensitivity and specificity of the LSN score in the diagnosis of significant fibrosis (F2-4), advanced fibrosis (F3-4), and liver cirrhosis (F4) were calculated using a bivariate random-effects model, and the summary areas under the hierarchical summary receiver operating characteristics curve (AUC) for each were calculated. Subgroup analysis was performed to explore the causes of study heterogeneity., Results: Of 168 screened studies, six were included in the analysis. The pooled sensitivity, specificity, and AUC of the LSN score were 68% (95% confidence interval [CI], 45-84%), 89% (95% CI, 83-93%), and 0.90 (95% CI, 0.87-0.92), respectively, for the diagnosis of significant fibrosis; 88% (95% CI, 60-97%), 78% (95% CI, 57-90%), and 0.89 (95% CI, 0.86-0.91), respectively, for the diagnosis of advanced fibrosis; and 83% (95% CI, 71-91%), 80% (95% CI, 72-85%), and 0.87 (95% CI, 0.83-0.89), respectively, for the diagnosis of liver cirrhosis. Cutoff values of the LSN score affected study heterogeneity in the diagnosis of advanced fibrosis (p = 0.03) and liver cirrhosis (p = 0.01). Imaging modality (p = 0.01) and reference standard (p = 0.01) affected study heterogeneity in the diagnosis of liver cirrhosis., Conclusions: The LSN score showed good diagnostic performance in assessing the hepatic fibrosis stage. Additional investigations are needed to improve and standardize the LSN score. Key Points • The liver surface nodularity (LSN) score showed overall good diagnostic performance in assessing hepatic fibrosis. • The pooled sensitivity of the LSN score was highest in the diagnosis of advanced fibrosis (88%; 95% confidence interval [CI], 60-97%), and the pooled specificity was highest in the diagnosis of significant fibrosis (89%; 95% CI, 83-93%). • The diagnostic performance of the LSN score differed according to the cutoff value, imaging modality, and reference standard., (© 2021. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: Since its introduction in 2011, the CT/MRI diagnostic Liver Imaging Reporting and Data System (LI-RADS) has been updated in 2014, 2017, and 2018. We evaluated the impact of CT/MRI diagnostic LI-RADS on liver MRI research methodology for the diagnosis of hepatocellular carcinoma (HCC)., Materials and Methods: The MEDLINE, EMBASE, and Cochrane databases were searched for original articles reporting the diagnostic performance of liver MRI for HCC between 2011 and 2019. The MRI techniques, image analysis methods, and diagnostic criteria for HCC used in each study were investigated. The studies were classified into three groups according to the year of publication (2011-2013, 2014-2016, and 2017-2019). We compared the percentage of studies adopting MRI techniques recommended by LI-RADS, image analysis methods in accordance with the lexicon defined in LI-RADS, and diagnostic criteria endorsed by LI-RADS. We compared the pooled sensitivity and specificity between studies that used the LI-RADS and those that did not., Results: This systematic review included 179 studies. The percentages of studies using imaging techniques recommended by LI-RADS were 77.8% for 2011-2013, 85.7% for 2014-2016, and 84.2% for 2017-2019, with no significant difference ( p = 0.951). After the introduction of LI-RADS, the percentages of studies following the LI-RADS lexicon were 0.0%, 18.4%, and 56.6% in the respective periods ( p < 0.001), while the percentages of studies using the LI-RADS diagnostic imaging criteria were 0.0%, 22.9%, and 60.7%, respectively ( p < 0.001). Studies that did not use the LI-RADS and those that used the LI-RADS version 2018 showed no significant difference in sensitivity and specificity (86.3% vs. 77.7%, p = 0.102 and 91.4% vs. 89.9%, p = 0.770, respectively), with some difference in heterogeneity (I² = 94.3% vs. 86.7% in sensitivity and I² = 86.6% vs. 53.2% in specificity)., Conclusion: LI-RADS imparted significant changes in the image analysis methods and diagnostic criteria used in liver MRI research for the diagnosis of HCC., Competing Interests: So Yeon Kim and Seung Soo Lee who is on the editorial board of the Korean Journal of Radiology was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2022 The Korean Society of Radiology.)

Kerr soliton combs operate in the anomalous group-velocity dispersion regime through the excitation of dissipative solitons. The generated bandwidth is largely dependent on the cavity dispersion, with higher-order dispersion contributing to dispersive-wave (DW) generation that allows for power enhancement of the comb lines at the wings of the spectrum. However, the spectral position of the DW is highly sensitive to the overall cavity dispersion, and the inevitable dimension variations that occur during the fabrication process result in deviations in the DW emission wavelength. Here, we demonstrate active tuning of the DW wavelength, enabling post-fabrication spectral shaping of the soliton spectrum. We control the DW position by introducing a wavelength-controllable avoided mode crossing through actively tuning the resonances of a silicon nitride coupled microresonator via integrated heaters. We demonstrate DW tuning over 113 nm with a spectral power that can exceed the peak soliton spectral power. In addition, our modeling reveals buildup and enhancement of the DW in the auxiliary resonator, indicating that the mode hybridization arising from the strong coupling between the two resonators is critical for DW formation.

Microbial electrolysis cells (MECs) have attracted significant interest as sustainable green hydrogen production devices because they utilize the environmentally friendly biocatalytic oxidation of organic wastes and electrochemical proton reduction with the support of relatively lower external power compared to that used by water electrolysis. However, the commercialization of MEC technology has stagnated owing to several critical technological challenges. Recently, many attempts have been made to utilize nanomaterials in MECs owing to the unique physicochemical properties of nanomaterials originating from their extremely small size (at least <100 nm in one dimension). The extraordinary properties of nanomaterials have provided great clues to overcome the technological hurdles in MECs. Nanomaterials are believed to play a crucial role in the commercialization of MECs. Thus, understanding the technological challenges of MECs, the characteristics of nanomaterials, and the employment of nanomaterials in MECs could be helpful in realizing commercial MEC technologies. Herein, the critical challenges that need to be addressed for MECs are highlighted, and then previous studies that used nanomaterials to overcome the technological difficulties of MECs are reviewed.

Purpose: Weight loss and deterioration in body composition are observed in patients with gastric cancer (GC) following gastrectomy. This study aimed to investigate the impact of residual stomach volume (RSV) on the nutritional status and body composition of patients with GC treated with distal gastrectomy., Materials and Methods: In total, 227 patients who underwent minimally invasive distal gastrectomy with Billroth 1 anastomosis for stage I GC between February 2015 and May 2018 were enrolled. Clinicodemographic and laboratory data were collected from the GC registry. The RSV, abdominal muscle area, and subcutaneous/visceral fat areas were measured using computed tomography data., Results: A larger RSV was associated with a lower decrease in the nutritional risk index (P=0.004) and hemoglobin level (P=0.003) during the first 3 months after surgery, and better recovery at 12 months. A larger RSV demonstrated an advantage in the preservation of abdominal muscle area (P=0.02) and visceral fat (P=0.04) after surgery, as well as less reduction in weight (P=0.02) and body mass index (P=0.03)., Conclusions: Larger RSV was associated with improved nutritional status and better preservation of muscle and fat after distal gastrectomy., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2022. Korean Gastric Cancer Association.)

Objective: As stereotactic body radiation therapy (SBRT) becomes widely available for early-stage non-small cell lung cancer (NSCLC), there may be concerns in the surgical community that SBRT is being offered for patients with operable tumors, even though surgery is standard of care. We evaluated the trends in SBRT and surgery over time for patients with NSCLC., Materials and Methods: The National Cancer Database was queried for patients with node-negative NSCLC ≤5 cm from 2004 to 2016. The relationships between definitive local treatment modalities and year were analyzed using a multinomial regression model while controlling for other covariates., Results: Among the 202,367 patients who met the inclusion criteria, there was a steady decrease in mean tumor size in all treatment modalities, from 2.44 cm (SD=1.08) to 2.25 cm (SD=1.00) over the study period. In the multinomial model, the probability of receiving lobectomy demonstrated a slight decline from 58% (2004) to 53% (2016). The use of SBRT increased from 1% to 20%, while patients receiving no therapy declined from 27% to 16%. The likelihood of SBRT increased with year of diagnosis (P<0.0001) and decreasing tumor size (P<0.0001), compared with lobectomy. Age, race, income, facility, and Charlson-Deyo score were also associated with treatment modality., Conclusions: The mean tumor size of early-stage NSCLC decreased over the study period for all treatment modalities. SBRT use has increased, mostly among older patients with smaller tumors and Charlson-Deyo scores ≥3. The increase in SBRT contributed to the significant decline in patients who had no therapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To investigate the diagnostic performance of attenuation imaging (ATI) for the assessment of low-grade hepatic steatosis using liver biopsy as the reference standard., Methods: The study included 57 potential donor candidates for living liver transplantation who underwent ATI, transient elastography (TE), and liver biopsy for evaluation of hepatic steatosis between February 2020 and April 2020. The attenuation coefficient (AC) from ATI and the controlled attenuation parameter (CAP) from TE were measured for each participant in a random and blind manner. The histologic hepatic fat fraction (HFF) was graded (S0, < 5%; S1, 5-33%; S2, 33-66%; S3, > 66%). The accuracy of ATI for diagnosing hepatic steatosis was compared with that of CAP using ROC analysis. Correlations between AC and HFF were evaluated, and factors affecting AC were determined by linear regression analysis., Results: The median HFF was 3% (range: 0-35%), with 31 (54.4%), 24 (42.0%), and 2 (3.5%) participants being graded as S0, S1, and S2, respectively. The AUCs for the ROCs of AC and CAP for the detection of hepatic steatosis were 0.808 (95% CI: 0.682-0.900) and 0.829 (95% CI: 0.706-0.916), respectively, with the difference not being statistically significant (p = 0.762). AC showed 61.5% of sensitivity and 90.3% of specificity. AC was positively correlated with HFF (p < 0.001). HFF was the only factor significantly affecting AC., Conclusions: ATI showed moderate sensitivity and high specificity in the diagnosis and quantification of hepatic steatosis in low-grade steatosis without fibrosis. Only HFF significantly affected AC., Key Points: • Attenuation imaging showed moderate sensitivity and high specificity performance in the diagnosis and quantification of hepatic steatosis in low-grade steatosis without fibrosis. • The diagnostic performance of the attenuation coefficient by attenuation imaging did not significantly differ from that of the controlled attenuation parameter by transient elastography in quantifying low-grade steatosis. • The histopathologically determined hepatic fat fraction was the only factor significantly affecting the attenuation coefficient., (© 2021. European Society of Radiology.)

During wastewater treatment, microbial electrochemical technologies (METs) are a promising means for in situ energy harvesting and resource recovery. The primary constraint for such systems is scaling them up from the laboratory to practical applications. Currently, most research (∼90%) has been limited to benchtop models because of bioelectrochemical, economic, and engineering design limitations. Field trials, i.e., 1.5 m 3 bioelectric toilet, 1000 L microbial electrolysis cell and industrial applications of METs have been conducted, and their results serve as positive indicators of their readiness for practical applications. Multiple startup companies have invested in the pilot-scale demonstrations of METs for industrial effluent treatment. Recently, advances in membrane/electrode modification, understanding of microbe-electrode interaction, and feasibility of electrochemical redox reactions have provided new directions for realizing the practical application. This study reviews the scaling-up challenges, success stories for onsite use, and readiness level of METs for commercialization that is inexpensive and sustainable., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The accurate detection and quantification of hepatic steatosis using a noninvasive method are important for the management of nonalcoholic fatty liver disease. We performed a systematic review and meta-analysis of the accuracy of the ultrasound-measured attenuation coefficient (AC) in the evaluation of hepatic steatosis., Methods: The PubMed, Embase, and Cochrane databases were searched for prospective studies reporting the diagnostic accuracy of AC for assessing hepatic steatosis. The meta-analytic pooled sensitivity and specificity of AC for any grade of steatosis (S≥1) and advanced steatosis (S≥2) were estimated using a bivariate random-effects model. Meta-regression analysis was conducted to investigate the causes of heterogeneity among studies., Results: Thirteen studies including 1,509 patients were identified. The pooled sensitivity and specificity of AC for S≥1 were 76% (95% confidence interval [CI], 73% to 80%; I2=43%) and 84% (95% CI, 77% to 89%; I2=74%), respectively, while for S≥2 they were 87% (95% CI, 83% to 91%; I2=0%) and 79% (95% CI, 75% to 83%; I2=59%), respectively. Study heterogeneity was associated with body mass index (BMI) and the prevalence of steatosis or significant fibrosis., Conclusion: AC can be clinically useful for assessing hepatic steatosis, with good overall diagnostic performance. The data reported in the published literature differed according to BMI and the prevalence of steatosis or significant fibrosis, and careful interpretation with consideration of these factors might be needed.

Microresonator-based platforms with ${\chi ^{(2)}}$ nonlinearities have the potential to perform frequency conversion at high efficiencies and ultralow powers with small footprints. The standard doctrine for achieving high conversion efficiency in cavity-based devices requires "perfect matching," that is, zero phase mismatch while all relevant frequencies are precisely at a cavity resonance, which is difficult to achieve in integrated platforms due to fabrication errors and limited tunabilities. In this Letter, we show that the violation of perfect matching does not necessitate a reduction in conversion efficiency. On the contrary, in many cases, mismatches should be intentionally introduced to improve the efficiency or tunability of conversion. We identify the universal conditions for maximizing the efficiency of cavity-based frequency conversion and show a straightforward approach to fully compensate for parasitic processes such as thermorefractive and photorefractive effects that, typically, can limit the conversion efficiency. We also show the design criteria that make these high-efficiency states stable against nonlinearity-induced instabilities.

Synchronization is a ubiquitous phenomenon in nature that manifests as the spectral or temporal locking of coupled nonlinear oscillators. In the field of photonics, synchronization has been implemented in various laser and oscillator systems, enabling applications including coherent beam combining and high-precision pump-probe measurements. Recent experiments have also shown time-domain synchronization of Kerr frequency combs via coupling of two separate oscillators operating in the dissipative soliton [i.e., anomalous group velocity dispersion (GVD)] regime. Here, we demonstrate all-optical synchronization of Kerr combs in the nonsolitonic, normal GVD regime in which phase-locked combs with high pump-to-comb conversion efficiencies and relatively flat spectral profiles are generated. Our results reveal the universality of Kerr comb synchronization and extend its scope beyond the soliton regime, opening a promising path toward coherently combined normal GVD Kerr combs with spectrally flat profiles and high comb-line powers in an efficient microresonator platform.