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Background and Aims: The incidence of gastric and duodenal neuroendocrine tumors (GNET and DNET, respectively) is increasing, however associated factors of these diseases are not well known. Here, we investigated the factors associated with GNET and DNET., Methods: Patients with GNET and DNET presenting at eight tertiary referral centers between 2001 and 2020 were included and compared with healthy controls who underwent upper endoscopic screening. Clinical factors and laboratory data were analyzed to determine associated factors of GNET and DNET., Results: Overall, 396 patients with GNET and 193 patients with DNET were included and compared with 1725 healthy controls. Multivariate analysis showed that age (odds ratio [OR] 0.98), diabetes (OR 1.72), hypertension (OR 1.97), low serum high-density lipoprotein cholesterol (HDL-C) levels (OR 2.54), and past/present H. pylori infection (OR 1.46) were significantly associated with GNET. In contrast, DNET was significantly associated with diabetes (OR 1.80), hypertension (OR 1.68), low serum HDL-C levels (OR 2.29), and past/present H. pylori infection (OR 5.42). In the sex-based subgroup analysis in GNET, current smoking was strongly associated in women (OR 9.85), but not in men., Conclusions: This study identified several common metabolic factors associated with GNET and DNET. Additionally, some factors had sex-specific associations., Competing Interests: Conflict of interest The authors have no conflict of interest regarding this article., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Purpose: Flow-preservation bypass is a treatment option for complex intracranial aneurysms (IAs) that cannot be managed with microsurgical clipping or endovascular treatment. Various bypass methods are available, including interposition grafts such as the radial artery or saphenous vein. Size discrepancy, invasiveness, and procedure complexity must be considered when using interposition grafts. We describe our experience of treating complex IAs using a superficial temporal artery (STA) interposition bypass., Methods: We retrospectively reviewed the medical records and operative videos of all patients who were treated for complex IAs at our center from January 2009 to December 2021 using cerebral revascularization. Clinical, radiological, and surgical findings of the cases that underwent STA interposition bypass were investigated., Results: Seventy-six bypass procedures were performed of which seven (9.2%) complex IAs were managed using STA interposition bypass. Of these 5 cases were of anterior cerebral artery, 1 of middle cerebral artery, and 1 of posterior inferior cerebellar artery aneurysm. There were no postoperative ischemic complications. Revision surgery for postoperative pseudomeningocele was performed in one case. The long-term bypass patency rate was 85.7% (6 out of 7) and good long-term aneurysm control was achieved in all cases, with a mean follow-up of 64 months., Conclusions: When treating complex IAs, creative revascularization strategies are needed in selective cases for favorable outcomes. STA interposition graft bypass which can reduce the size discrepancy between the donor and recipient may be a less invasive, flexible, and practical option for treating complex IAs., (Copyright © 2023. Published by Elsevier B.V.)

Background: In treating anterior choroidal artery (AChA) aneurysms, preserving the AChA main trunk is of course necessary to prevent postoperative ischemic complications. However, in practice, complete occlusions are often limited by small branches., Objective: We aimed to demonstrate that even in cases where complete occlusion of the AChA aneurysm is complex due to small branches, complete occlusion can be safely achieved using indocyanine green video-angiography and intraoperative neurophysiological monitoring (IONM)., Methods: We performed a retrospective review of all unruptured AChA aneurysms surgically treated at our institution from 2012 to 2021. All available surgical videos were reviewed to find AChA aneurysms clipped with small branches; clinical and radiological data were collected for these cases., Results: Among 391 cases of unruptured AChA aneurysms treated surgically, 25 AChA aneurysms were clipped with small branches. AChA-related ischemic complications occurred in 2 cases (8%) without retrograde indocyanine green filling to the branches. These 2 cases had changes in IONM. There were no ischemic complications in the remaining cases with retrograde indocyanine green filling to the branches and no change in IONM. During an average follow-up of 47 months (12-111 months), a small residual neck was observed in 3 cases (12%) and recurrence or progression of the aneurysm was observed in only 1 case (4%)., Conclusions: The surgical treatment of AChA aneurysms carries the risk of devastating ischemic complications. Even in cases where complete clip ligation seems impossible due to small branches associated with AChA aneurysms, complete occlusion can be safely achieved using indocyanine green video-angiography and IONM., (Copyright © 2023. Published by Elsevier Inc.)

Objective: The mass effect associated with large or giant intracranial aneurysms is difficult for traditional endovascular treatment. This study investigated whether flow diverters can relieve the aneurysmal mass effect caused by aneurysmal compression symptoms., Methods: Fifty-five patients with unruptured large and giant intracranial aneurysms treated by a flow diverter at our institution from January 2014 to February 2022 were retrospectively evaluated., Results: In this study, 53 patients were included. Initially, 27 patients (51.9%), including 10 with compressive optic neuropathy, 12 with third nerve palsy, 2 with facial hyperesthesia, and 11 with sixth nerve palsy, were symptomatic. The symptom duration was shorter in the improved group (n = 2.2 ± 4.0 vs. n = 3.1 ± 3.9, P = 0.49). Thrombus formation following the flow diversion procedure was typically observed on magnetic resonance imaging (MRI) performed immediately and was not significantly associated with symptomatic improvement (OR = 0.395; 95% CI (0.058-2.698), P = 0.343). However, symptomatic improvement was seen in most patients when the aneurysm size decreased on MRI. A reduction in the aneurysm size on the MRI at the 3-month follow-up was correlated with symptomatic improvement in the multivariate analysis (OR = 0.08, 95% CI (0.013-0.485), P < 0.05)., Conclusions: A flow diverter might help alleviate compression symptoms caused by large or giant intracranial aneurysms. Shrinkage of the aneurysm within 3 months postoperatively and a shorter duration of symptoms contribute to the favorable outcomes of mass effect. Ultimately, prompt treatment is crucial for improving symptomatic intracranial artery aneurysms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Dural arteriovenous fistulas at the craniocervical junction (CCJ DAVFs) are a rare vascular disease. Endovascular treatment (EVT) and microsurgery are the primary treatment modalities for CCJ DAVFs. However, incomplete treatment or complications may occur after treatment because of the anatomical complexity., Objective: We analyzed the neurosurgical treatment experiences of CCJ DAVFs to recommend suitable classification and treatment options., Methods: CCJ DAVFs were anatomically classified into three types according to the feeding arteries and their relationships with the anterior spinal (ASAs) and lateral spinal arteries (LSAs). Type 1 was fed by the radiculomeningeal artery from the vertebral artery and was not associated with the ASA or LSA. Type 2 was fed by the radiculomeningeal artery, and the radicular artery supplied the LSA near the fistula point. Type 3 had the characteristics of type 1 or type 2 CCJ DAVFs, except the ASA also contributed to the fistula., Results: There were 5, 7, and 4 cases of type 1, type 2, and type 3 CCJ DAVFs, respectively. EVT was attempted in 12 patients, of whom only 1 (type 1) was completely cured without complications. Nine cases had residual lesions after EVT, and two had spinal cord infarction due to occlusion of the LSA. Fourteen patients underwent microsurgical treatment. In all 14 cases, CCJ DAVFs were completely obliterated after microsurgery., Conclusion: In cases of type 1 CCJ DAVF, both microsurgical treatment and EVT may be considered. However, for type 2 and 3 CCJ DAVFs, microsurgery may be a superior treatment modality., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Many neurosurgeons routinely perform postoperative intensive care unit (ICU) management after clipping of unruptured intracranial aneurysms (UIAs). However, whether routine postoperative ICU care is necessary remains a clinical question. Therefore, we investigated which factors acted as risk factors that actually required ICU care after microsurgical clipping of unruptured aneurysms., Methods: We included a total of 532 patients who underwent clipping surgery for UIA between January 2020 and December 2020. The patients were divided into two groups: those who really required ICU care (41 patients, 7.7%) and those who did not (491 patients, 92.3%). A backward stepwise logistic regression model was used to identify factors that were independently associated with ICU care requirement., Results: The mean hospital stay duration and the operation time were significantly longer in the ICU requirement group than in the no ICU requirement group (9.9 ± 10.7 vs. 6.3 ± 3.7 days, p = 0.041), (259.9 ± 128.4 vs. 210.5 ± 46.1 min, p = 0.019). The transfusion rate was significantly higher (p = 0.024) in the ICU requirement group. Multivariable logistic regression analysis identified male sex (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.15-4.76; p = 0.0195), operation time (OR, 1.01; 95% CI, 1.00-1.01; p = 0.0022), and transfusion (OR, 2.35; 95% CI, 1.00-5.51; p = 0.0500) as independent risk factors for requiring ICU care after clipping., Conclusions: Postoperative ICU management may not be mandatory after clipping surgery for UIAs. Our results suggest that postoperative ICU management may be more required in the male sex, patients with longer operation times, and those who received a transfusion., Competing Interests: Declarations The authors declare no competing interests regarding this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Cerebral myxomatous aneurysms (CMA) are intracranial aneurysms caused by cardiac myxoma. The exact mechanism underlying their development has not yet been elucidated. And an optimal treatment method has not yet been established because of rarity of the disease. In addition, most existing reports have had a short follow-up period or lack of follow-up imaging test results. The aim of this study was to provide better insights into the course and treatment options of CMAs., Methods: We describe 4 CMA patients treated in our hospital and literature search was performed using PubMed and Embase databases. Keywords used were as follows: "cerebral myxomatous aneurysm", "myxomatous aneurysm", "cardiac myxoma", and "intracranial aneurysm". Only publications in English and related to this disorder with adequate follow-up periods and aneurysmal wall biopsy results were included. Clinical, radiological, pathological, and treatment characteristics were analyzed., Results: A total of 149 CMA cases were managed conservatively that included 9 enlargements, 6 regressions, and 134 stable aneurysms, which were identified for a total of 453.33 aneurysm years (1.91% per aneurysm year, 1.27% per aneurysm year, and 28.76% per aneurysm year, respectively). Poor outcome rate was high in cases with hemorrhage (either parenchymal or subarachnoidal hemorrhage) due to rupture of the CMA (46.67%, 7 out of 15). Thirteen cases had aneurysm biopsy results of which 11 showed tumor invasion on the aneurysm wall., Conclusions: Even though the natural course of unruptured, benign-looking CMAs appears to be favorable, the presence or absence of viable tumor cells in the aneurysm may promote an unfavorable disease course. In the case of large, symptomatic, and enlarging CMAs, surgical, endovascular, or combined treatment should be considered as the mortality and morbidity due to rupture might be high., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Black and Latinx Americans are disproportionately at greater risk for having Alzheimer's disease and related dementias (ADRD) than White Americans. Such differences in risk for ADRD are arguably explained through health disparities, social inequities, and historical policies. Structural racism and discrimination (SRD), defined as "macro-level conditions that limit opportunities, resources, and well-being of less privileged groups," have been linked with common comorbidities of ADRD, including hypertension, obesity, diabetes, depression. Given the historical impact of SRD-including discriminatory housing policies resulting in racial residential segregation that has been shown to limit access to education, employment, and healthcare-Black and Latinx populations with ADRD are directly or indirectly negatively affected by SRD in terms of access, quality and cost for healthcare. Emerging studies have brought to light the value of structural-level hospital and public health collaboration on care coordination for improving healthcare quality and access, and thus could serve as a macro-level mechanism for addressing disparities for minoritized racial and ethnic populations with ADRD. This paper presents a conceptual framework delineating how care coordination can successfully be achieved through health information technology (HIT) systems and ultimately address SRD. To address health inequities, it is therefore critical that policy initiatives invest in HIT capacities and infrastructures to promote care coordination, identify patient needs and preferences, and promote engagement of patients with ADRD and their caregivers., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Internal carotid artery (ICA) injury during transsphenoidal surgery is a rare but serious complication. We analyzed a series of ICA injuries that occurred during a transsphenoidal approach to suggest an optimal management strategy., Methods: Between January 2015 and May 2020, we enrolled 10 cases of ICA injury at our institution., Results: Among the 10 patients enrolled, 5 had pituitary adenoma, 2 had craniopharyngioma, and 1 each had skull base chondrosarcoma, tuberculum sellae meningioma, and nasopharyngeal cancer; 4 were revision surgery cases. The cavernous segment of the ICA was the most commonly injured area. The most common reason for ICA injury was a drill injury at the sellar floor opening. A direct repair was performed using a clip in only 1 patient. In the others, bleeding control of the injured ICA was achieved by packing multiple cotton pads. After angiography, 6 patients underwent immediate endovascular sacrifice of the injured ICA. In 3 patients who showed poor collateral flow from the anterior communicating and posterior communicating arteries, revascularization surgery was performed before endovascular trapping. After 6 postoperative months, 6 patients showed favorable functional outcomes, and 4 patients showed poor functional outcomes., Conclusions: Prompt control of bleeding, endovascular management of injured ICA, and consideration of revascularization surgery based on collateral flow may prevent catastrophic neurological sequelae., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Monogonont rotifers are common species in aquatic environments and make model species for ecotoxicology studies. Whole genomes of several species of the genus Brachionus have been assembled, but no information on the freshwater rotifer Brachionus rubens has been reported. In this study, the whole-genome sequence of B. rubens was successfully assembled using NextDenovo. The total length of the genome was 132.7 Mb (N50 = 2.51 Mb), including 122 contigs. The GC contents accounted for 29.96% of the genome. Aquatic organisms are always exposed to various external stresses, and a comprehensive genomic analysis is needed to better understand the adverse effects on organisms. This paper focuses on the ecotoxicological aspect and conducted genome analysis of representative gene families involved in detoxification mechanisms against environmental stressors. Specifically, we identified cytochrome P450 genes (CYPs) of phase I, glutathione S-transferase genes (GSTs) of phase II, and ATP-binding cassette transporter genes (ABCs) of phase III in the genome of B. rubens. Gene duplications were found in CYP, GST, and ABC genes, as is the case for other Brachionus rotifers. Our results suggest that these detoxification-related gene families have evolved in a species-specific and/or lineage-specific manner. This paper improves our understanding of how the freshwater Brachionus rotifers respond to environmental stressors in a molecular ecotoxicology context., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Particulate matter (PM 2.5 ) generated in large cities creates new problems in marine ecosystems and may adversely affect its inhabitants. However, the mechanisms underlying the same remain unclear; hence, we investigated the effects of PM 2.5 on life history traits (e.g., mortality, development, and fecundity), cellular reactive oxygen species (ROS) levels, antioxidant enzyme (e.g., glutathione peroxidase [GPx], superoxide dismutase [SOD], and catalase [CAT]) activities, and the transcript levels of detoxification-related genes (cytochrome P450s [CYPs]) and antioxidant (glutathione S-transferases [GSTs]) in the copepod Tigriopus japonicus. Among the life history traits, developmental time was the only trait to significantly deviate (P < 0.05) in response to PM 2.5 (compared to that in the controls). Significant changes in ROS levels and antioxidant enzymatic activities (P < 0.05) in response to PM 2.5 , suggested that PM 2.5 can induce oxidative stress, leading to adverse effects on the T. japonicus life history. In addition, PM 2.5 induced a differential regulation of various CYP and GST genes, particularly CYP307E1, GST-kappa, and GST-sigma were significantly upregulated (P < 0.05), suggesting that these genes likely play crucial roles in detoxification mechanisms and could be useful as reliable biomarkers for PM 2.5 toxicity. Overall, the results of this study provide new insights into the potential toxicity of PM 2.5 ., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: This study aimed to reveal the clinical significance of the platelet reactivity unit (PRU) and the efficacy of adjunctive cilostazol and its association with thromboembolic and microembolic events after coil embolization for unruptured intracranial aneurysms (UIAs)., Methods: We retrospectively analyzed the data of 427 patients with UIAs who underwent endovascular treatment between July 2011 and June 2014. When clopidogrel resistance was confirmed via PRU assay after dual antiplatelet medication (aspirin plus clopidogrel) administration for 5 days, triple antiplatelet therapy with cilostazol was administered (Group I, 274 patients). The other group was placed on standard dual antiplatelet therapy (Group II, 153 patients). All patients underwent magnetic resonance diffusion-weighted imaging within 2 days after endovascular coiling., Results: No significant associations with the occurrence of thromboembolic and microembolic events were found between the groups. The occurrence of thromboembolic and microembolic events showed no statistical difference between groups I and II (p = 0.725 for thromboembolic events and p = 0.109 for microembolic events). Also, the PRU value and the occurrence of microembolic events, using a PRU cutoff value of 240, showed no statistical difference (p = 0.114 in group I and 0.064 in group II). There was significant increase in microembolic events after the use of a stent-assisted endovascular procedure. As the PRU value increased, there was a trend toward an increase in the mean number of microembolic lesions without statistical significance., Conclusion: Even though there is a presumed anti-thromboembolic effect for clopidogrel resistance in other literature, the clinical efficacy of adjustment of additional cilostazol for endovascular coiling of unruptured aneurysms may be limited due to the unspecified cutoff value of the PRU assay for evaluating the resistance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Cardiac myxoma is a very rare disease for which resection is the gold standard treatment. Many neurological manifestations are associated with this disease, including embolic infarctions, arterial aneurysms, and brain metastatic myxomas, but few large-scale studies have addressed this. The aim of this study was to retrospectively analyze the incidence, type, and prognosis of these neurological disorders., Methods: We enrolled 317 patients who underwent a cardiac myxoma resection between 2004 and 2019 at our institution. A retrospective review of medical records and radiological imaging was performed for each patient, and clinical factors were compared and analyzed with regard to clinical outcomes and the incidence of adverse events., Results: Patients with a neurological disorder before surgery were found to be more likely to develop new postoperative neurological complications (P = 0.003). Patients with a neurological disorder arising at any time before or after surgery had poorer outcomes (P < 0.001)., Conclusions: The clinical management of cardiac myxoma must take account of neurological sequelae independently of the surgical intervention to remove the lesion. Patients with cardiac myxoma and any neurological disorder should undergo both neurosurgical follow-up and cardiac surgical follow-up, even if myxoma removal surgery has been performed. We recommend active neuroimaging during long-term follow-up as essential in these cases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

G protein-coupled receptors (GPCRs) are considered to have originated from early evolution of eukaryotic species, therefore, the genome-wide identification of GPCR genes can provide insight into the adaptive strategy and evolutionary tendency in an animal taxon. Here, we identified a total 216 full-length GPCR genes in the marine water flea Diaphanosoma celebensis genome, which were classified into five distinct classes (A, B, C, F, and other). Phylogenetic comparison of GPCRs in D. celebensis to those in humans (Homo sapiens), fruitfly (Drosophila melanogaster), and freshwater water flea (Daphnia magna) reveals a high level of orthological relationship of amine, neuropeptide, and opsin receptor repertoire, while purinergic and chemokine receptors were highly differentiated in humans. Our findings suggest sporadic evolutionary processes within the GPCR gene families identified in D. celebensis. In this study, these results may provide a better understanding on the evolution of GPCRs, and expand our knowledge of the cladoceran GPCR gene repertories which in part, mediate cell physiological mechanisms in response to various environmental stimuli., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Microplastics are ubiquitous environmental pollutants and a great threat to the aquatic environment. Due to their small size (ranging from 1 µm to 5 mm), microplastics be easily ingested by a wide range of organisms and can serve as a vector for various contaminants. In this study, additive or possible synergistic effects of microplastics and zinc were demonstrated through sex-specific alterations in behavior, redox status, and modulation of detoxification-related genes in Daphnia magna, with males being more sensitive than females with stronger modulations of antioxidant responses, particularly on glutathione S-transferases expressions. Furthermore, we demonstrated microplastics may act as vectors for metals (Zn 2+ ) in the aquatic environment in D. magna, with reduced bio-concentration of the total Zn concentration, inducing greater toxicity. Our findings demonstrated synergistic toxicity of the heavy metal Zn and microplastics and could contribute to greater understanding of sex-specific effects of microplastics in aquatic organisms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Brachionus spp. rotifers have been proposed as model organisms for ecotoxicological studies. We analyzed the whole-genome sequence of B. paranguensis through NextDenovo, resulting in a total length of 106.2 Mb and 71 contigs. The N50 and the GC content were 4.13 Mb and 28%, respectively. A total of 18,501 genes were predicted within the genome of B. paranguensis. Prominent detoxification-related gene families of phase I and II detoxifications have been investigated. In parallel with other Brachionus rotifers, high gene expansion was observed in CYP clan 3 and GST sigma class in B. paranguensis. Moreover, species-specific expansion of sulfotransferase (SULTs) and gain of UDP-glucuronosyltransferases (UGTs) through horizontal gene transfer has been specifically found within B. plicatilis complex. This whole-genome analysis of B. paranguensis provides a basis for molecular ecotoxicological studies and provides useful information for comparative studies of the evolution of detoxification mechanisms in Brachionus spp., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Constant evolution of omics-technologies has provided access to identification of various important gene families. Recently, genome assemblies on widely used ecotoxicological model species, including rotifers and copepods have been completed and representative detoxification-related gene families have been discovered for biomarker genes. However, despite ubiquitous presence of stress-response proteins, limited information on full genome-wide report on heat shock proteins (Hsps) is available. Various studies have demonstrated multiple cellular functions of Hsps in living organisms as an important biomarker in response to abiotic and biotic stressors, however, full genome-wide identification of Hsps, particularly in aquatic invertebrates, has not been reported. This is the first study to report the entire Hsps and basal gene expression levels in three regional-specific copepods: Tigriopus japonicus and kingsejongensis, Paracyclopina nana, and Eurytemora affnis, and how each Hsp family gene is regulated at a basal level., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Effective therapies are lacking for recurrent, metastatic adenoid cystic carcinoma (R/M ACC) and preclinical models suggest retinoic acid agonists inhibit ACC growth. This phase II trial evaluated all-trans retinoic acid (ATRA) as a novel therapy for ACC., Methods: Patients with R/M ACC (any site) with clinical and/or radiographic progression ≤12 months prior to study entry were eligible. Cohort 1 (CH1) received ATRA 45 mg/m 2 split oral daily dosing on days 1-14 of a 28-day cycle; Cohort 2 (CH2) received the same dosing continuously. Primary endpoint was best overall response rate (CR + PR) (RECIST v1.1). Secondary endpoints: safety and progression-free survival (PFS). Exploratory analyses: ATRA impact on MYB expression and genomic predictors of response., Results: Eighteen patients enrolled. There were no responses, but 61% (11/18) had stable disease (SD) and 28% (5/18) progression as best response; 11% (2/18) unevaluable. Median duration of stability: 3.7 months (95%CI, 1.9-3.9). One patient (CH1) remains on drug with SD approaching 1 year. Half of those who received prior VEGFR therapy achieved SD (4/8). At median follow up of 7.9 months, median PFS was 3.2 months (95%CI, 1.8-3.9). N = 1 required dose adjustment; N = 1 came off drug for toxicity. There were no grade 3-4 adverse events. NOTCH1 and PI3K pathway alterations were most frequent. Low MYB protein expression was associated with longer duration of stability on ATRA (P < 0.01)., Conclusion(s): While the trial did not meet its prespecified response endpoint, ATRA alone or in combination may be a low toxicity treatment for disease growth stabilization in R/M ACC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Brachionus spp. rotifers, which are widely distributed in aquatic environments, have been proposed as model organisms for ecotoxicological studies. Although the genomes of several rotifers belonging to the genus Brachionus have been assembled, the genome for the freshwater rotifer Brachionus angularis remains unknown. In this study, we analyzed the whole-genome sequence of B. angularis, which revealed a total length of 56.5 Mb and 21 contigs. The N50 and the GC content were 5.42 Mb and 23.66%, respectively. A total of 13,952 genes were predicted. Of them, we identified the main detoxification-related gene families, including those for cytochrome P450, glutathione S-transferase (GST), and the ATP-binding cassette transporter. In comparison with other Brachionus rotifers, massive species-specific expansion in GST sigma genes was found in B. angularis. This whole-genome analysis of B. angularis provides a basis for molecular ecotoxicological studies and provides useful biological tools for comparative studies of the evolution of detoxification mechanisms in Brachionus spp., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this study, we sequenced and assembled the genome of a European estuarine calanoid copepod using Oxford Nanopore PromethION and Illumina HiSeq 2500 platforms. The length of the assembled genome was 776.1 Mb with N50 = 474.9 kb (BUSCO 85.9%), and the genome consisted of 2473 contigs. A total of 18,014 genes were annotated and orthologous gene clusters were analyzed in comparison to other copepods. In addition, genome-wide identification of cytochrome P450s, glutathione S-transferases, and ATP-binding cassette transporters in E. affinis was performed to determine gene repertoire of these detoxification-related gene families. Results revealed the presence of species-specific gene inventories, indicating that these gene families have evolved through species-specific gene loss/expansion processes, possibly due to adaptation to different environmental stressors. Our study provides a new inventory of the European estuarine calanoid copepod E. affinis genome with emphasis on phase I, II, and III detoxification systems., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Down-regulation of serum and glucocorticoid-regulated kinase1 (SGK1) expression has been reported in the postmortem prefrontal cortex (PFC) of subjects with post-traumatic stress disorder. Furthermore, experimental treatments that reduce SGK1 function in the medial prefrontal cortex (mPFC) cause depressive-like behaviors and synaptic dysfunction. Therefore, we examined the effect of SGK1 down-regulation in the mPFC on resistance to stress-induced cognitive impairment. Rats with viral-mediated knockdown of SGK1 in the mPFC were subjected to either a brief 20-min restraint plus 20 intermittent tail shocks or a prolonged 60-min restraint plus 60 intermittent tail shocks, after which their performance in an object recognition task was assessed. Recognition memory remained intact in control rats following the brief stress, but was impaired in rats with SGK1 knockdown in the mPFC. Prolonged stress impaired recognition memory in both control rats and rats with SGK1 knockdown. Our findings indicate that altered mPFC SGK1 signaling is a potential mechanism for resistance to stress-induced cognitive impairment., Competing Interests: Conflict of Interest The authors have no biomedical financial interests or conflicts of interests to declare., (Copyright © 2021. Published by Elsevier B.V.)

To assemble the genome of the marine water flea Diaphanosoma celebensis, a sentinel model for marine environmental monitoring, we constructed a high-quality genome using PromethION and HiSeq 2500 platforms. The total length of the assembled genome was 100.08 Mb, with N50 = 2.56 Mb (benchmarking universal single-copy orthologs, 96.9%) and consisted of 179 scaffolds. A total of 15,427 genes were annotated, and orthologous gene clusters in D. celebensis were analyzed and compared with those of the cladocerans Daphnia magna and Daphnia pulex. In addition, phase I, II, and III detoxification gene families of cytochrome P450s, glutathione S-transferases, and ATP-binding cassette were fully identified and revealed lineage-specific gene loss and/or expansion, suggesting that the evolution of detoxification gene families likely modulates fitness and susceptibility in response to environmental stressors. The study improves our understanding of the detoxification-related gene system and should contribute to future studies of molecular ecotoxicology in cladoceran species and their responses to emerging pollutants., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Inflammation is a significant clinical problem that can arise from full-thickness wounds or burn injuries or microbial disease. Although topical wound healing substances could promote rapid wound healing by preventing or reducing the consequences of inflammation, there still remains a need for the development of novel substances that can effectively reduce infection and inflammation in initial wound healing phase. In this study, collagen was combined with asiaticoside (AS) and ε-poly-l-lysine (εPLL). This complex was then applied to in vitro models of infection and inflammation. Collagen-AS coatings inhibited the initial inflammatory response to LPS through a sustained release of AS, and a bilayer coating-εPLL showed a notable antimicrobial effect using microbial infection test. In this study, we determined whether asiaticoside and εPLL have anti-inflammatory and antibacterial effects through different mechanisms. Collectively, the collagen-AS/εPLL complex indicated great therapeutic potentials for accelerate wound healing and the complex may be considered as a artificial scaffold substitute product to full-thickness wound healing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Objective: Microsurgical clipping, along with endovascular treatment, has evolved in the treatment of unruptured intracranial aneurysms (UIA), and these developments have resulted in a reduction of the complication rate. We discuss the need for a central venous catheter (CVC) insertion as an anesthetic preparation for microsurgical clipping., Methods: Between January 2019 and September 2019, 722 patients with UIA were treated at our institution. We excluded patients with a history of endovascular treatment or bypass surgery, recurrent aneurysms after coil embolization, brain tumors, or subarachnoid hemorrhages. A total of 272 patients were enrolled. Eighty-four patients underwent CVC insertion, and 188 patients underwent clipping surgery without CVC insertion. Outcome-related factors were compared between the 2 groups. We performed propensity score matching of the 2 groups to increase comparability., Results: There were no significant differences in outcome, sex, aneurysm location, aneurysm multiplicity, aneurysm size, or comorbid disease between the 2 groups. The mean age at the time of surgery was higher in the non-CVC insertion group than in the CVC insertion group. There were no meaningful differences in primary outcomes, including premature rupture and intraoperative motor evoked potential/somatosensory evoked potential change, and secondary outcomes, including estimated blood loss, duration of intensive care unit stay, duration of hospitalization, and Glasgow Outcome Scale score at discharge., Conclusions: CVC insertion for clipping surgery for UIA is not mandatory. Considering the possible complications associated with CVCs, we cautiously suggest aneurysm surgery with CVC insertion in patients with serious medical comorbidities, aneurysm sizes >10 mm, and difficult proximal parent artery control., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To determine the effects of tributyltin (TBT) upon multiple exposures of diet and microplastic in rotifer, in vivo life parameters were measured. In 10 μg/L TBT-exposed rotifer, the 1 and 0.5 x diet groups resulted in reproduction reduction. However, 10 x diet treatment showed no significant changes in the total fecundity, despite a decrease in daily reproduction. Besides, differences in the lifespan were observed in response to different diet regimens. TBT and/or MP-exposed parental rotifer (F0) showed a significant delay in the pre-reproductive day under 0.5 x diet regimen. In all dietary regimens, exposure to TBT and MP induced an increase in reactive oxygen species, but antioxidant activities were perturbed. To further verify the carryover effect of TBT toxicity, progeny rotifer (F1) obtained from 24 h TBT and/or MP-exposed F0 was used. Interestingly, the faster hatching rate was observed only in F1 obtained from 1 x diet regimen-exposed F0. However, in the 0.5 x diet, the total fecundity was reduced and the pattern of the daily reproduction was collapsed. Thus, the toxicity of TBT can be alleviated by MP and nutrition status, but TBT-induced toxicity and its carryover effect are inevitable., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The impact of COVID-19 on patients with cancer is emerging, but data are urgently needed for head and neck cancer (HNC) patients or survivors who are inherently high-risk for severe illness and mortality with SARS-CoV-2 infection., Methods: This multi-institution, academic cohort study collected comprehensive data on clinical risk factors, COVID-19 symptoms and viral testing patterns, information about hospitalization rates, and predictors of survival among HNC patients with active disease or in remission. The primary endpoint was 30-day all-cause mortality from the date of confirmed COVID-19. We performed multivariate analysis to understand the prognostic value of clinical and laboratory parameters on outcomes., Results: Thirty-two patients with COVID-19 and HNC were included. Median age was 70 (range: 38-91) with 38% aged 75+, and 34% resided in long-term care facilities (LTCF). Thirteen (41%) had active cancer, with 6 (19%) on cancer therapy within 4 weeks of COVID-19 diagnosis. New or worsening cough and fatigue were the most commonly reported presenting symptoms. More than 30% required >1 SARS-CoV-2 test before confirming a positive result. Twenty (63%) required hospitalization. At data cutoff, 7 (22%) had died (1 on active cancer treatment), with a 30-day all-cause mortality of 18.9% (95%CI: 11.4-33.6) among all patients, and 71.5% (95%CI: 38.2-92.3) among those requiring intensive care unit (ICU) admission. ICU admission and residing in a LTCF predicted worse outcomes (p < 0.01), while age, gender, and recent treatment did not., Conclusions: We observed high 30-day all-cause mortality among HNC patients with COVID-19, but most were not on active cancer therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To examine the impact of treatment sequences of Immune checkpoint inhibitor (ICI) and cetuximab on clinical outcomes in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: Clinicopathologic data were retrospectively collected on patients with R/M HNSCC who received ICI treatment. Association between treatment sequence and clinical outcomes were assessed., Results: A total of 113 patients with R/M HNSCC were analyzed. Patients who had cetuximab prior to ICI had worse overall (HR, 1.83) and progression-free survival (HR, 1.76) compare to those without prior cetuximab. Among patients who had subsequent therapy after ICI, cetuximab-based therapy was associated with a trend toward higher response rate and longer survival than non-cetuximab regimen., Conclusion: Our single institution analysis showed that treatment sequence of cetuximab and ICI in R/M HNSCC may affect clinical outcomes. Cetuximab prior to ICI was associated with worse outcomes while the efficacy of cetuximab may be enhanced after ICI therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Heat shock proteins (Hsp) are class of conserved and ubiquitous stress proteins present in all living organisms from primitive to higher level. Various studies have demonstrated multiple cellular functions of Hsp in living organisms as an important biomarker in response to abiotic and biotic stressors including temperature, salinity, pH, hypoxia, environmental pollutants, and pathogens. However, full understanding on the mechanism and pathway involved in the induction of Hsp still remains challenging, especially in aquatic invertebrates. In this study, the entire Hsp family and subfamily members in the marine rotifers Brachionus spp., one of the cosmopolitan ecotoxicological model organisms, have been genome-widely identified. In Brachionus spp. Hsp family was comprised of Hsp10, small hsp (sHsp), Hsp40, Hsp60, Hsp70/105, and Hsp90, with highest number of genes found within Hsp40 DnaJ homolog subfamily C members. Also, the differences in the orientation of the conserved motifs within Hsp family may have induced differences in transcriptional gene modulation in response to thermal stress in Brachionus koreanus. Overall, Hsp family-specific domains were highly conserved in all three Brachionus spp., relative to Homo sapiens and across other animal taxa and these findings will be helpful for future ecotoxicological studies focusing on Hsps., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Copepods in the genus Tigriopus are widely distributed in the intertidal zone worldwide. To assess differences in fatty acid (FA) metabolism among congeneric species in this genus inhabiting polar and temperate environments, we analyzed and compared FA profiles of the Antarctic copepod Tigriopus kingsejongensis and the temperate copepod T. japonicus. Higher amounts of total FAs were found in the Antarctic copepod T. kingsejongensis than the temperate copepod T. japonicus under administration of the identical amount of Tetraselmis suecica. To determine the genomic basis for this, we identified fatty acid metabolism-related genes in an improved genome of T. kingsejongensis. The total length of the assembled genome was approximately 338 Mb with N50 = 1.473 Mb, 938 scaffolds, and a complete Benchmarking Universal Single-Copy Orthologs value of 95.8%. A total of 25,470 genes were annotated using newly established pipeline. We identified eight elongation of very long-chain fatty acid protein (Elovl) genes and nine fatty acid desaturase (Fad) genes in the genome of T. kingsejongensis. In addition, fatty acid profiling suggested that the duplicated Δ5/6 desaturase gene in T. kingsejongensis is likely to play an essential role in synthesis of different FAs in T. kingsejongensis to those in T. japonicus. However, further experimental research is required to validate our in silico findings. This study provides a better understanding of fatty acid metabolism in the Antarctic copepod T. kingsejongensis., Competing Interests: Declaration of competing interest The authors have no conflict of interest in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The selfing fish Kryptolebias hermaphroditus has unique reproductive system for self-fertilization, making genetically homozygous offsprings. Here, we report on high density genetic map-based genome assembly for the K. hermaphroditus Panama line (PanRS). The numbers of scaffolds were 5212 and the genome was 683,992,224 bp (N50 = 27.45 Mb). The length of anchored scaffold onto 24 linkage groups was 652,231,070 bp (95.3% of genome) with 0.01% of the gap and 39.33% of GC content and complete Benchmarking Universal Single-Copy Orthologs value was 96.6%. The numbers of annotated genes were 36,756 (average gene length 1368 bp) with the GC content of 54.1%. To examine the difference between the two sister species in the genus Kryptolebias, we compared the genomes of K. hermaphroditus PanRS and Kryptolebias marmoratus PAN line on the composition of transposable elements. To demonstrate applications of genome library, phase I and II detoxification related gene families have been analyzed, and compared the syntenies containing loci of CYP and GST genes on linkage groups. This K. hermaphroditus genome information will be helpful for a better understanding on genome-wide mechanistic view of detoxification and antioxidant-related genes over evolution in the view of fish environmental ecotoxicology., Competing Interests: Declaration of competing interest There is no conflict of interest on this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Various xenobiotics are constantly being released and accumulated into the aquatic environments and consequently, the aquatic organisms are continuously being exposed to exogenous stressors. Among various xenobiotic detoxifying enzymes, Glutathione S-transferase (GST) is one of the major xenobiotic detoxifying enzyme which is widely distributed among living organisms and thus, understanding of the nature of GSTs is crucial. Previous studies have shown GST activity in response to various xenobiotics yet, full identification of GSTs in marine invertebrates is still limited. This review covers information on the importance of GSTs as a biomarker for emerging chemicals and their response to wide ranges of environmental pollutants as well as in-depth phylogenetic analysis of marine invertebrates, including recently identified GSTs belonging to rotifers (Brachionus spp.) and copepods (Tigriopus japonicus and Paracyclopina nana), with unique class-specific features of GSTs, as well as a new suggestion of GST evolutionary pathway., Competing Interests: Declaration of competing interest The authors have no conflict of interest in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Global warming is a big concern for all organisms and many efforts have been made to reveal the potential effects of temperature elevation on aquatic organisms. However, limited studies on molecular mechanistic approaches on physiological effects due to temperature changes are available. Here, we investigated the effects of temperature changes on life parameters (e.g., population growth [total number of rotifers], and lifespan), oxidative stress levels and antioxidant activities (e.g., glutathione S-transferase [GST], catalase [CAT], superoxide dismutase [SOD]) with expression levels in the monogonont marine rotifer Brachionus plicatilis. The changes in temperatures led to significant reduction (P < 0.05) in lifespan, possibly due to significant decrease (P < 0.05) in antioxidant activities, reducing the potential to cope with significant elevation in the temperature-induced oxidative stress in B. plicatilis. To further assess the actual induction and clearance of reactive oxygen species (ROS), N-acetyl-L-cysteine was used to examine whether the temperature-induced oxidative stress could be successfully scavenged. Furthermore, expression patterns of the antioxidant-related genes (GSTs, SODs, and CATs) were down- or upregulated (P < 0.05) in response to different temperatures in B. plicatilis. Overall, these findings indicate that ROS-mediated oxidative stress led to cellular damage and antioxidant defense system, resulting in deleterious effects on life parameters in rotifer., 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 © 2020. Published by Elsevier Ltd.)

The Java medaka (Oryzias javanicus) is distributed in tropical brackish water and is considered as an ecotoxicological experimental organism for assessing diverse pollutions and global climate change effects in the ocean. In this study, we sequenced and assembled the genome of O. javanicus using the Oxford Nanopore technique and anchored the scaffolds to the 24 genetic linkage map of a sister species Oryzias melastigma. The assembled genome consisted of 773 scaffolds including 24 LG-based scaffolds, and the estimated genome length was 846.3 Mb (N50 = 19.3 Mb), containing 24,498 genes. As detoxification processes are crucial in aquatic organisms, antioxidant-related genes including glutathione S-transferases, superoxide dismutase, catalase, and glutathione peroxidase were identified in this study. In the genome of O. javanicus, a total of 21 GSTs, 4 SODs, 1 CAT, and 7 GPxs were identified and showed high similarities between sister species O. melastigma and Oryzias latipes. In addition, despite having 8 classes of cytosolic GSTs family, medaka showed no presence of GST pi and sigma classes, which are predominantly found in carp and salmon, but not in neoteleostei. This study adds another set to genome-library of Oryzias spp. and is a useful resource for better understanding of the molecular ecotoxicology., 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 © 2020. Published by Elsevier Ltd.)

Background: Alzheimer's disease and related dementias (ADRD) is a growing public health challenge. Prior research suggests that non-Hispanic whites (whites), non-Hispanic African Americans (African Americans), and Hispanics have differing risks for ADRD., Objective: To examine the existence of serious psychological distress (SPD) among whites, African Americans, and Hispanics; to calculate the predicted probability of ADRD in whites, African Americans, and Hispanics, and to decompose the differences among ADRD populations, quantifying the burden of higher SPD among African Americans and Hispanics, compared to whites., Data and Method: The authors use nationally representative data from the Medical Expenditure Panel Survey (2007-2015) to estimate the association between ADRD and race, ethnicity, and SPD. Using Blinder-Oaxaca decomposition analysis, the authors estimate to what extent higher SPD among Hispanics and African Americans was associated with higher ADRD rates compared to whites., Results: After controlling for individuals' demographic and socioeconomic characteristics and co-existing medical conditions, the presence of SPD was still significantly associated with a higher likelihood of having ADRD. The model predicted significantly higher likelihood of having ADRD among African Americans (7.1%) and Hispanics (5.7%) compared to whites (4.5%). Higher rates of having SPD among African Americans explained 15% of white-black difference and 40% of the white-Hispanic difference in ADRD rates, respectively., Discussion and Conclusion: Our findings suggest a significant relationship between SPD and ADRD and that the burden of SPD was greater among African Americans and Hispanics with ADRD. Efficient screening using self-reported SPD, compared to simply using diagnoses codes of mental illness, may be more helpful to reduce racial and ethnic disparities in ADRD., (Published by Elsevier Inc.)

We investigated differences in the feeding habits of the starspotted smooth-hound, Mustelus manazo, in Tokyo Bay between the mid-1990s (low stock size) and the late 2000s (high stock size). The frequency of M. manazo with empty stomachs increased from 5.9% in the mid-1990s to 16.1% in the late 2000s. A decrease in the relative weight of the stomach contents was evident from the mid-1990s to the late 2000s, especially in the small size classes, along with changes in the species composition in the stomach contents. Although crustaceans were the main constituents of the stomach contents, the proportion of crabs increased while those of shrimps and hermit crabs decreased. Changes in the feeding habits of M. manazo may be associated with shifts in the benthic community structure in Tokyo Bay., 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 © 2020 Elsevier Ltd. All rights reserved.)

Background: Indocyanine green (ICG) video angiography has been widely used in cerebrovascular surgery. ICG injection is generally safe, with a low incidence of complications. ICG-related anaphylactic reactions during neurosurgery have been rarely reported. We report the cases of 2 patients who had experienced anaphylactic shock in response to intravenous ICG injection (DID Indocyanine Green [Dongindang, Inc., Gyeonggi-do, Republic of Korea]) during intracranial aneurysm (IA) surgery., Case Description: The first patient, a 69-year-old woman with an unruptured IA, had been undergoing clipping surgery under general anesthesia. Immediately after ICG injection, her blood pressure suddenly decreased from 140/80 mm Hg to 50/30 mm Hg and she developed a skin rash on her abdomen and all extremities. Chest compression was initiated, and her vital signs gradually recovered to their pre-ICG levels within 10 minutes. The second patient was a 58-year-old woman with an unruptured IA who had been undergoing clipping surgery. After ICG injection, her blood pressure had decreased from 130/80 mm Hg to 60/40 mm Hg, and a rash-like skin lesion was observed on her abdomen. After intravenous injection of norepinephrine and dexamethasone, her blood pressure recovered to its pre-ICG level within 30 minutes and remained stable thereafter. The postoperative ICG skin provocation test findings were positive for both patients; however, only 1 patient showed markedly increased serum tryptase levels., Conclusion: Despite the rarity of ICG-related anaphylaxis, clinicians should be aware of this unexpected, but potentially life-threatening, drug reaction in patients undergoing cerebrovascular surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Vasospasm (VSP)-related ischemic complications have been associated with poor outcomes in patients with subarachnoid hemorrhage due to ruptured blood blister-like aneurysms (BBAs) in the communicating segment of the internal carotid artery (ICA). The purpose of the present study was to investigate the incidence of, and factors related to, VSP-related cerebral infarction (VSP-CI) in patients with surgically treated BBAs in the communicating segment of the ICA., Methods: The medical records of 25 consecutive patients with surgically treated BBAs in the communicating segment of the ICA were reviewed. The preoperative angiographic findings, surgical methods, and patient outcomes, including VSP-CI, were evaluated., Results: Of the 25 patients, 10 had undergone extracranial-intracranial (EC-IC) bypass with trapping and 15 had undergone clipping surgery. VSP-CI occurred in the ipsilateral hemisphere to the aneurysm in 4 patients with EC-IC bypass with trapping and in 6 patients who had undergone received clipping. Positive balloon test occlusion findings did not affect the occurrence of VSP-CI in the EC-IC bypass and trapping group. The occurrence of VSP-CI was significantly greater in the patients with a dominant anterior cerebral artery ipsilateral to the aneurysm on the preoperative angiogram (P = 0.023), with a hazard ratio of 14.14 (95% confidence interval, 1.57-127.68)., Conclusions: The results of preoperative balloon test occlusion were less reliable for predicting postoperative ischemic complications of EC-IC bypass with trapping in patients with ruptured BBAs in the communicating segment of the ICA. However, anterior cerebral artery dominance ipsilateral to the ruptured aneurysm could be predictive for postoperative VSP-CI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The association of primary brain tumors with coexisting unruptured intracranial aneurysms (UIAs) has been debated, and treatment strategies have not yet been established. We evaluated the flow association between brain tumors and coexisting UIAs and the outcomes of patients with brain tumor who did not receive treatment of coexisting UIAs., Methods: The medical records of patients with coexisting UIAs and brain tumors who had undergone surgical tumor resection were retrospectively analyzed to evaluate the incidence of UIAs according to tumor type, association of arterial feeder vessels and coexisting UIAs, and the occurrence of subarachnoid hemorrhage during the follow-up period for patients who had not receive treatment for the UIAs., Results: Of the 55 patients, 21 (38.9%) had undergone treatment of UIAs and 33 (61.1%) had received regular follow-up examinations without UIA treatment. Two patients (6.1%) developed subarachnoid hemorrhage. Of the 33 patients with astrocytic or oligodendroglial tumors who had not undergone treatment of UIAs, 2 had experienced an interval increase. Flow-related UIAs were found to be significantly more common in patients with astrocytic or oligodendroglial tumors than in those with tumors of other histological types (P = 0.01)., Conclusions: The incidence of UIAs among patients with primary brain tumors appears to be greater than that in the general population. An interval increase in aneurysm size and aneurysmal rupture was observed in 2 patients with astrocytic or oligodendroglial tumors. We would recommend perioperative treatment of flow-related UIAs in patients with astrocytic or oligodendroglial tumors and noninvasive evaluations such as magnetic resonance angiography if coexisting UIAs remain untreated., (Copyright © 2019. Published by Elsevier Inc.)

Extensive skin loss caused by burns or diabetic ulcers may lead to major disability or even death. Therefore, cell-based therapies that enhance skin regeneration are clinically needed. Previous approaches have been applied the injections of cell suspensions and the implantation of biodegradable three-dimensional scaffolds seeded cells. However, these treatments have limits due to poor localization of the injected cells and insufficient delivery of oxygen and nutrients to cells. Recently, cell sheet-based tissue engineering has been developed to transplant cell sheets, which are cell-dense tissues without scaffolds. Because cell density is one of the important factors for improving the therapeutic effect of cell transplantation, transplanting layered cell sheet constructs can promote the recovery of tissue function and tissue regeneration compared with a single cell sheet. Thus, this study designed ROS-induced cell sheet stacking method with newly fabricated hematoporphyrin-incorporated polyketone film (Hp-PK film) to enhance cell sheet delivery efficiency and application in wound healing. We have demonstrated the therapeutic effect of a multi-layered mesenchymal stem cell sheets onto a full-thickness wound defect in nude mice. Consequentially, three-layered cell sheets transplanted and stacked by ROS-induced method promoted angiogenesis and skin regeneration at the wound site. Thus, our strategy based on Hp-PK film, which allows for easy stacking and transplantation of cell sheets, could be applied to enhance tissue regeneration. STATEMENT OF SIGNIFICANCE: We herein report exogenous ROS-induced cell sheet stacking method with newly fabricated hematoporphyrin-incorporated polyketone film (Hp-PK film) to enhance cell sheet transplantation efficiency and application in wound healing. Although there are several ways to stack-up cell sheets, all of these methods have limitations in transplanting the cell sheet directly to the target site. The method is simple and takes a relatively short time compared to previously reported methods for stacking and transplanting cell sheets. Thus, our study will provide a scientific impact because the method of applying exogenous ROS generated from Hp-PK film on cell detachment can transplant the cell sheet through a process of putting a cell sheet-cultured film on the lesion, irradiating with light, and then removing only the film., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Although many studies showed the predictive factors of stent thrombosis (ST) occurrence, there are few data about clinical outcomes and recurrent ST after percutaneous coronary intervention (PCI) for ST. Furthermore, it is uncertain which factors can cause adverse clinical events including recurrent ST., Methods: This study examined the clinical outcomes after treatment for definite ST. Among 18,739 patients between June 2003 and December 2016 who underwent PCI using a drug-eluting stent (DES) or bare-metal stent (BMS), 243 consecutive patients who suffered definite ST were enrolled in this study. The overall incidence of ST was 1.3% (DES 1.4% and BMS 0.8%). The study endpoint was 1-year cardiac death or recurrent definite ST after the initial ST., Results: Study endpoint occurred in 57 patients (23.5%) during the 1-year follow-up after the initial ST. In multivariate analysis, the factors predicting 1-year endpoint were early ST [adjusted hazard ratio (HR): 2.23, 95% confidence interval (CI): 1.26-4.08, p=0.006], BMS ST (HR: 2.42, 95% CI: 1.27-4.81, p=0.045), serum level of glucose (HR: 1.03, 95% CI: 1.01-1.05, p=0.048), and ST-segment elevation myocardial infarction (STEMI) at the initial ST (HR: 3.73, 95% CI: 1.82-7.65, p<0.001)., Conclusions: Recurrent ST or cardiac death during the first year after the initial ST event occurred in ∼25% of patients treated for definite ST. BMS ST, serum level of glucose, STEMI, and early ST at the initial ST were associated with adverse cardiac events., (Copyright © 2019. Published by Elsevier Ltd.)

Stem cells can differentiate into various body tissues and organs and thus are considered as promising tools for cell therapy and tissue engineering. Early passage stem cells have high differentiation ability compared to late passage stem cells. Thus, it is important to use early passage stem cells in cell therapy. Here, we investigated whether cell migration could be used to compare young and senescent cells. We used 'electrotaxis' where cells under electric treatment move towards the anode or cathode. Without an electric stimulus, stem cells moved randomly. However, under a direct electric current, the cells moved with directionality. Under stimulation with a direct electric current, early passage stem cells moved towards the anode; when the cells became senescent with increasing passages, the percentage of cells migrating to the anode decreased. These results suggest that the behavior of stem cells under the influence of a direct electric current is also related to their passage number. Therefore, electrotaxis migration analysis can be used to distinguish between young cell and senescent cells., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Subepithelial tumors (SETs) are difficult to diagnose accurately without invasive pathological confirmation. We created a noninvasive prediction model for diagnosing gastrointestinal stromal tumors (GISTs) using contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS)., Methods: We retrospectively reviewed 176 patients who underwent CEH-EUS from October 2011 to August 2017. Seventy patients with a diagnosis of GIST (n = 37) or leiomyoma (n = 33) were included. The long-to-short axis ratio (LSR) and enhancement patterns (vascularity, diffuse enhancement) on CEH-EUS were assessed. Logistic regression and classification and regression tree (CART) analyses were performed., Results: The mean age of all patients was 54.9 ± 13.68 years. The GIST group showed significantly higher rates of positive vascularity (81.1% vs. 15.2%, p < 0.001) and diffuse enhancement (51.4% vs. 15.2%, p = 0.001), and lower LSR (1.30 vs. 1.76, p < 0.001). In multivariate logistic regression, positive vascularity (odds ratio [OR] 27.765, 95% confidence interval [CI] 5.336-144.458) and low LSR (OR 18.940, 95% CI 3.623-99.007) were independent predictors of GIST. A noninvasive prediction model for GISTs was developed using the CART model, by allocating patients according to statistically significant variables., Conclusions: The LSR and vascularity of SETs on CEH-EUS can be used as parameters for a noninvasive prediction model of GISTs. This model may be helpful in the early identification and treatment of GISTs., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: Based on our clinical experience, posteroinferiorly projecting carotid-A1 junctional aneurysms are often difficult to treat microsurgically. Our objective was to classify peri-internal carotid artery (ICA) bifurcation aneurysms according to their location and analyze their characteristics., Methods: From January 2008 to October 2017, microsurgical or endovascular treatment of 6777 aneurysms were performed at our hospital. We identified 199 peri-ICA bifurcation aneurysms (2.94%) classified into true ICA bifurcation aneurysm, carotid-A1 junctional aneurysm, and carotid-M1 junctional aneurysm according to the anatomic location. Medical records including patient characteristics, aneurysm location, surgical method, any neurologic deficits, clinical outcomes, medical history, and radiologic findings were retrospectively reviewed. The anatomic position of the aneurysm was defined from the virtual surgical, anteroposterior, and lateral views, and the degree of agreement was calculated., Results: There were 103 true ICA bifurcation aneurysms, 92 carotid-A1 junctional aneurysms, and 4 carotid-M1 junctional aneurysms. Carotid-A1 junctional aneurysms tended to be smaller, elongated, and more often posteroinferiorly projecting than true ICA bifurcation aneurysms. Posteroinferiorly projecting carotid-A1 junctional aneurysms tended to require complex aneurysm surgery. The virtual surgical view had an almost perfect degree of agreement with the actual surgical view., Conclusions: The characteristics of carotid-A1 junctional aneurysms and true ICA bifurcation aneurysms differ. In particular, carotid-A1 junctional aneurysms tend to have a posteroinferior projection and that causes difficulty in surgical treatment. We recommend the virtual surgical view for preoperative planning. Furthermore, an adequate Sylvian fissure opening and a strategic approach using appropriate devices to inspect blind spots should be considered for a successful treatment outcome., (Copyright © 2019 Elsevier Inc. All rights reserved.)

To understand the lipid metabolism in invertebrate species, identification of the fatty acid (FA) synthesis gene families in invertebrate species is important, since some FA are unable to be synthesized in the organisms by themselves. In the study, to identify the elongation of very long chain fatty acid (Elovl) genes in the marine rotifer Brachionus koreanus, the genome-wide identification and phylogenetic analysis of Elovl genes have been conducted with the expression profile of Elovl genes on the alga Tetraslemis suecica-fed B. koreanus. A total 10 Elovl genes have been identified from the genome of B. koreanus, with conserved HXXHH motif. Synteny analysis showed that tandem duplication event has occurred (Elovl3/6a and b, Elovl9a and b, and Elovl9c and d) in the ancestor. Phylogenetic analysis have clearly revealed that Brachionus spp. has only 2/5 and 3/6 subfamilies, and two novel Elovl classes have been revealed, namely Elovl9 and 10. Transcriptional data showed that the 10 Elovl genes were differently expressed and their expression could be regulated by feeding the alga T. suecica. From fatty acid (FA) profile data of the alga Tetraslemis suecica-fed B. koreanus, we revealed that the marine rotifer B. koreanus may synthesize very long chain fatty acid (VLCFA; >22 carbons) by themselves, as VLCFA was hardly detected in the alga T. suecica. The study provides a better understanding of FA metabolism of the marine rotifer B. koreanus after feeding the T. suecica., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Aim: Adequate tissue acquisition is important in making treatment decisions for patients with upper gastrointestinal subepithelial tumors (SETs). This study aimed to compare the outcomes of endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) with those of the unroofing biopsy technique., Methods: This study was a single-center, prospective comparative study conducted at Severance Hospital, Yonsei University College of Medicine. A total of 39 patients with SETs ≥15 mm were enrolled between January 2016 and August 2017., Results: Of the 39 patients, 28 underwent biopsy with both techniques (4 underwent only unroofing and 7 underwent only EUS-FNB). Histological diagnosis was made with EUS-FNB in 64.3% and unroofing biopsy in 78.6% (p = 0.344), and immunohistochemical diagnosis was made with EUS-FNB in 46.4% and unroofing biopsy in 67.9% (p = 0.180). In the subgroup analysis (28 patients), there was no significant difference in diagnostic yield between the 2 methods The mean procedural time with EUS-FNB was shorter than that with unroofing biopsy (p < 0.001). The larger SET (≥ 20 mm) (p = 0.035) and satisfaction of procedure (p = 0.019) were positively associated with successful histological diagnosis by EUS-FNB., Conclusions: There was no significant difference in the histological diagnostic yield for SETs between the EUS-FNB and unroofing biopsy techniques (CinicalTrials.gov. identifier NCT02646241)., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)