Publications by authors named "Yu Kobayashi"

58 Publications

Severe immune checkpoint inhibitor-associated gastritis: A case series and literature review.

Endosc Int Open 2022 Jul 15;10(7):E982-E989. Epub 2022 Jul 15.

Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.

Recent advances in cancer treatment have involved the clinical application of immune checkpoint inhibitors (ICIs) for various type of cancers. The adverse events associated with ICIs are generally referred to as immune-related adverse events (irAEs). Gastrointestinal irAEs are a major disorder, but gastritis is not frequently observed. The aims of this study were to elucidate the clinical, endoscopic, and histological characteristics of irAE gastritis. Information on patients treated with ICIs were collected from a single institute over 3 years. IrAE gastritis was identified based on the clinical course and endoscopic and histopathological findings. Of the 359 patients treated with ICIs, four cases of irAE gastritis were identified in clinical records from the endoscopy unit. The endoscopic and histopathological findings were analyzed, and further immunohistochemical studies with immune subtype markers and programmed cell death ligand-1 (PD-L1) antibody were conducted. Among four patients with irAE gastritis, the remarkable endoscopic characteristics were network-pattern erosion, erythematous and edematous mucosa with thick purulent discharge, and fragile mucosa. Corresponding histological features were fibrinopurulent exudate, severe inflammatory cell infiltration, and epithalaxia, respectively. The PD-L1 expression rate was ≥ 1 % in the gastric tissue of all patients with gastritis. These patients were treated with prednisolone (PSL) and their symptoms improved within a few days to 2 weeks. IrAE gastritis were characterized by specific endoscopic findings. The appropriate endoscopic diagnosis may lead to effective treatment with PSL.
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http://dx.doi.org/10.1055/a-1839-4303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286772PMC
July 2022

Nasal breathing is superior to oral breathing in performing and undergoing transnasal endoscopy: a randomized trial.

Endoscopy 2022 Jul 14. Epub 2022 Jul 14.

Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.

Background And Study Aims: Transnasal endoscopy presents a technical difficulty when inserting the flexible endoscope, and it is unclear whether a particular breathing method is useful for transnasal endoscopy. Therefore, we conducted a prospective randomized controlled trial to compare endoscopic operability and patient tolerance between patients in the nasal breathing and oral breathing groups.

Patients And Methods: A total of 198 eligible patients were randomly assigned to undergo the transnasal endoscopy with nasal breathing and with oral breathing. Endoscopists and patients answered questionnaires on the endoscopic operability and patient tolerance using a 100-mm visual analog scale ranging from 0 (non-existent) to 100 (most difficult/ unbearable). The visibility of the upper-middle pharynx was recorded.

Results: Patient characteristics didn't differ significantly in both groups. Nasal breathing showed a higher rate of good visibility of the upper-middle pharynx than oral breathing (91.9% vs. 27.6%; p<0.05). Nasal breathing showed lower scores than oral breathing in overall technical difficulty (21.0±11.4 vs. 35.4±15.0; p<0.05). Regarding patient tolerance, nasal breathing showed lower scores than oral breathing in overall discomfort (22.1±18.8 vs. 30.5±20.9; p<0.05) and other symptoms, including nasal and throat pain, choking, suffocating, gagging, belching, and bloating (p<0.05). Pharyngeal bleeding rate was lower in the nasal breathing group than that in the oral breathing group (0% vs. 9.2%; p<0.05).

Conclusions: Nasal breathing is superior to oral breathing in performing and undergoing transnasal endoscopy. Nasal breathing led to good visibility of the upper-middle pharynx, improved endoscopic operability and patient tolerance, and showed safety by decreasing pharyngeal bleeding.
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http://dx.doi.org/10.1055/a-1900-6004DOI Listing
July 2022

Gastro-colic Fistula-associated Hypersplenism Causes Pancytopenia in a Patient with Crohn's Disease: A Case Report.

Intern Med 2022 May 21. Epub 2022 May 21.

Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan.

A 24-year-old woman was admitted to our hospital due to abdominal pain and a high fever. She was diagnosed with ileocolonic Crohn's disease (CD), complicated with a gastro-colic fistula and splenomegaly. After initial treatment with an infliximab-biosimilar, all blood cell line counts markedly decreased. Three-dimensional reconstructed computed tomography revealed splenic vein narrowing. Thus, her pancytopenia was deemed to have likely been caused by hypersplenism. Surgery was performed, and clinical remission was maintained without pancytopenia. This is the first report of a CD patient with pancytopenia caused by hypersplenism that was triggered by gastro-colic fistula-associated splenic vein obstruction.
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http://dx.doi.org/10.2169/internalmedicine.9590-22DOI Listing
May 2022

Recurrence rates and risk factors for seizure recurrence following antiseizure medication withdrawal in adolescent patients with genetic generalized epilepsy.

Epilepsia Open 2022 06 28;7(2):332-343. Epub 2022 Apr 28.

Department of Child Neurology, NHO Nishiniigata Chuo Hospital, Niigata, Japan.

Objective: This study aimed to identify the recurrence rate of genetic generalized epilepsy (GGE) and risk factors for recurrence after antiseizure medication (ASM) withdrawal in adolescent patients.

Methods: We retrospectively reviewed medical records of patients with GGE who were included in the registry at the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital from 2000 through 2020. The eligibility criteria were as follows: onset of epileptic seizures at <15 years of age, treatment with an ASM, and attempted treatment withdrawal at 10-19 years of age. The rates of seizure recurrence after drug withdrawal were evaluated. Moreover, several variables were evaluated as predictors of recurrence.

Results: In total, 77 patients with GGE (21, 13, and 43 patients with juvenile myoclonic epilepsy [JME], juvenile absence epilepsy [JAE], and epilepsy with generalized tonic-clonic seizures alone [EGTCSA], respectively) were included in this study. Recurrence was detected in 68% of patients with GGE (86%, 31%, and 70% of patients with JME, JAE, and EGTCSA, respectively). Recurrence rates for patients who developed epilepsy at ≥13 years of age, those who started dose reduction at ≥16 years of age, those who exhibited a seizure-free period of <36 months before withdrawal, and those who chose to discontinue treatment at their own discretion were significantly higher than those for their counterparts. Multivariate analysis revealed that initiation of dose reduction at ≥16 years of age was associated with increased recurrence risk. Meanwhile, a diagnosis of JAE was associated with decreased recurrence risk. All patients with JAE were treated with valproic acid.

Significance: Antiseizure medication withdrawal at ≥16 years of age and a diagnosis other than JAE may be independent risk factors for seizure recurrence after drug withdrawal in adolescent patients.
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http://dx.doi.org/10.1002/epi4.12603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159251PMC
June 2022

Correlation Among Body Composition Parameters and Long-Term Outcomes in Crohn's Disease After Anti-TNF Therapy.

Front Nutr 2022 1;9:765209. Epub 2022 Apr 1.

Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.

Background: The impact of the body composition on the pathophysiology and clinical course of Crohn's disease (CD) has not been fully elucidated.

Aims: To reveal the correlations among body composition and long-term outcomes in CD after anti-TNF therapy.

Methods: patients who received anti-TNF therapy as their first biologic treatment were enrolled. The skeletal muscle index (SMI), visceral and subcutaneous fat area (VFA, SFA), and the ratio of the VFA to SFA (mesenteric fat index; MFI) at the 3 lumbar level were measured using computed tomography (CT) imaging before the induction. The correlation among the body composition and outcomes were retrospectively analyzed.

Results: The 5-year cumulative secondary failure- and resection-free rates in patients with a low SMI (39.1% and 64.8%) were significantly lower than those with a high SMI (67.5% and 92.7%; = 0.0071 and 0.0022, respectively). The 5-year cumulative secondary failure-free rate in the patients with low VF (45.0%) was significantly lower than that in those with high VF (77.6%; = 0.016), and the 5-year cumulative resection-free rate in patients with a high MFI (68.9%) was significantly lower than that in those with a low MFI (83.0%; = 0.031). Additionally, patients with low age and BMI had significantly lower cumulative secondary failure- and resection-free rates than those with high age and BMI (low age: 37.4% and 71.2%; high age: 70.7% and 88.9%; = 0.0083 and 0.027, respectively) (low BMI: 27.2% and 64.8%; high BMI: 68.3% and 87.9%; = 0.014 and 0.030, respectively), respectively. In the multivariate analyses, a low SMI was the only independent risk factor for secondary failure (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.04-4.44), while low age (HR 4.06, 95% CI 1.07-15.4), a low SMI (HR 4.19, 95% CI 1.01-17.3) and high MFI were risk factors for bowel resection (HR 4.31, 95% CI 1.36-13.7).

Conclusion: The skeletal muscle mass and ratio of visceral to subcutaneous fat were suggested to reflect the long-term clinical outcome and may be helpful as prognostic markers after anti-TNF therapy in CD.
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http://dx.doi.org/10.3389/fnut.2022.765209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010511PMC
April 2022

Endoscopic recanalization for the complete closure of long-gap esophageal atresia after reconstruction surgery.

BMC Gastroenterol 2022 Mar 22;22(1):132. Epub 2022 Mar 22.

Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido, 078-8510, Japan.

Background: Reconstruction surgery-associated stricture frequently occurs in patients with long-gap esophageal atresia (LGEA). While several endoscopic dilatation methods have been applied and would be desirable, endoscopic recanalization is very difficult in cases with complete esophageal closure. Surgical treatment has been performed for a severe stricture, which causes extensive damage to the infant. No reports have described successful endoscopic recanalization for complete closure due to scarring after surgery for LGEA. We herein report the case of successful endoscopic recanalization by single endoscopist in an LGEA patient with complete closure after reconstruction surgery.

Case Presentation: A seven-month-old boy with LGEA who received reconstruction surgery and gastrostomy immediately after birth presented to our unit due to vomiting and malnutrition. Contrast radiography and peroral endoscopy detected complete closure of the esophagus at the anastomotic site. After confirming the length of stricture as several millimeters, we punctured the center of the lumen with a 25-G puncture needle under fluoroscopy. An endoscope was then inserted via the gastrostomy and the puncture hole was detected at the center of the lumen. After passing the guidewire, endoscopic balloon dilation was performed three times, and the hole was sufficiently dilatated. Oral ingestion was feasible, and his nutritional condition was improved.

Conclusions: To our knowledge, this is the first report to propose a less invasive endoscopic approach to recanalize a site of complete esophageal closure in a LGEA patient after reconstruction surgery by single endoscopist. Our endoscopic procedure using an ultrathin endoscope and puncture needle may be a therapeutic option for the treatment of patients with complete esophageal closure in a LGEA patient after reconstruction surgery.
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http://dx.doi.org/10.1186/s12876-022-02207-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8939221PMC
March 2022

Carbazochrome sodium sulfonate is not effective for prevention of post-gastric endoscopic submucosal dissection bleeding: A retrospective study.

Surg Endosc 2022 Mar 7. Epub 2022 Mar 7.

Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido, 078-8510, Japan.

Background: Carbazochrome sodium sulfonate (CSS) is conventionally administered to prevent post-endoscopic submucosal dissection (ESD) bleeding in many institutions, but research on its preventive efficacy is lacking. Therefore, we investigated the risk of post-ESD bleeding and the preventive efficacy of CSS administration.

Methods: We retrospectively reviewed 304 lesions in 259 patients with gastric neoplasms who underwent ESD at Asahikawa Medical University Hospital from 2014 to 2021. In the CSS group, CSS 100 mg/day was intravenously infused with maintenance fluid replacement on postoperative days 0-2. The risk factors of post-ESD bleeding, including CSS administration, were investigated.

Results: The overall rate of post-ESD bleeding was 4.6% (14/304). The univariate analysis showed that atrial fibrillation (Af), warfarin intake, heparin replacement, and tumor location in the lower third were significant risk factors for increasing the likelihood of postoperative bleeding. In the multivariate analysis, Af (odds ratio [OR] 3.83, 95% CI 1.02-14.30; p < 0.05), heparin replacement (OR 4.60, 95% CI 1.02-20.70; p < 0.05), and tumor location in the lower third of the stomach (OR 6.67, 95% CI 1.43-31.00; p < 0.05) were independent factors for post-ESD bleeding. Post-ESD bleeding was observed in 5.2% (9/174) of the CSS group and 3.8% (5/130) of the non-CSS group, with no significant difference between the two groups (p = 0.783). Additionally, CSS was not shown to have preventive effects in groups with higher-risk factors, such as Af diagnosis, warfarin use, heparin replacement, and tumor location in the lower third of the stomach.

Conclusion: CSS administration was not effective for the prevention of the post-ESD bleeding in the overall patient population as well as in higher-risk patients. This suggests that the administration of CSS for post-ESD bleeding prevention may need to be reconsidered.
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http://dx.doi.org/10.1007/s00464-022-09171-4DOI Listing
March 2022

Prognostic factors to predict the survival in patients with advanced gastric cancer who receive later-line nivolumab monotherapy-The Asahikawa Gastric Cancer Cohort Study (AGCC).

Cancer Med 2022 01 29;11(2):406-416. Epub 2021 Nov 29.

Division of Metabolism and Biosystemic Science, Gastroenterology and Hematology/Oncology Department of Medicine, Asahikawa Medical University, Asahikawa Hokkaido, Japan.

Background: Chemotherapy for advanced gastric cancer is recommended in the guidelines; however, later-line treatment remains controversial. Since immune checkpoint inhibitors have been used for the treatment of various malignancies, trials have been performed for gastric cancer. A phase 3 trial indicated the survival benefit of nivolumab monotherapy for gastric cancer patients treated with prior chemotherapy regimens.

Patients And Methods: A regional cohort study was undertaken to determine the real-world data of nivolumab treatment for patients with advanced or recurrent gastric cancer. The patients were enrolled for 2 years from October 2017 to October 2019 and were prospectively followed for 1 year to examine the overall survival (OS). The patient characteristics were analyzed in a multivariate analysis and a nomogram to predict the probability of survival was generated.

Results: In total, 70 patients who received nivolumab as ≥third-line chemotherapy were included in the Asahikawa Gastric Cancer Cohort. The median OS was 7.5 (95% CI, 4.8-10.2) months and the response rate was 18.6%. Diffuse type classification, bone metastasis, high neutrophil/lymphocyte ratio, and high CRP were associated with poor OS/prognosis in the multivariate analysis. A nomogram was developed based on these clinical parameters and the concordance index was 0.80 (95% CI, 0.68-0.91). The responders were aged and were frequently diagnosed with intestinal type gastric cancer, including patients with a HER2-positive status (27.3%) or microsatellite instability-high (27.3%) status.

Conclusions: The regional cohort study of nivolumab monotherapy for gastric cancer patients revealed prognostic factors and a nomogram was developed that could predict the probability of survival.
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http://dx.doi.org/10.1002/cam4.4461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729046PMC
January 2022

Deep learning-based diagnosis of temporal lobe epilepsy associated with hippocampal sclerosis: An MRI study.

Epilepsy Res 2021 Dec 21;178:106815. Epub 2021 Nov 21.

Department of Neurosurgery, Brain Research Institute, Niigata University, Japan.

Purpose: The currently available indicators-sensitivity and specificity of expert radiological evaluation of MRIs-to identify mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) are deficient, as they cannot be easily assessed. We developed and investigated the use of a novel convolutional neural network trained on preoperative MRIs to aid diagnosis of these conditions.

Subjects And Methods: We enrolled 141 individuals: 85 with clinically diagnosed mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis International League Against Epilepsy (HS ILAE) type 1 who had undergone anterior temporal lobe hippocampectomy were assigned to the MTLE-HS group, and 56 epilepsy clinic outpatients diagnosed as nonepileptic were assigned to the normal group. We fine-tuned a modified CNN (mCNN) to classify the fully connected layers of ImageNet-pretrained VGG16 network models into the MTLE-HS and control groups. MTLE-HS was diagnosed using MRI both by the fine-tuned mCNN and epilepsy specialists. Their performances were compared.

Results: The fine-tuned mCNN achieved excellent diagnostic performance, including 91.1% [85%, 96%] mean sensitivity and 83.5% [75%, 91%] mean specificity. The area under the resulting receiver operating characteristic curve was 0.94 [0.90, 0.98] (DeLong's method). Expert interpretation of the same image data achieved a mean sensitivity of 73.1% [65%, 82%] and specificity of 66.3% [50%, 82%]. These confidence intervals were located entirely under the receiver operating characteristic curve of the fine-tuned mCNN.

Conclusions: Deep learning-based diagnosis of MTLE-HS from preoperative MR images using our fine-tuned mCNN achieved a performance superior to the visual interpretation by epilepsy specialists. Our model could serve as a useful preoperative diagnostic tool for ascertaining hippocampal atrophy in patients with MTLE.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106815DOI Listing
December 2021

Usefulness of endoscopic band ligation with gel immersion endoscopy for colonic diverticular bleeding and hemorrhoidal bleeding.

Endoscopy 2022 Jul 9;54(7):E384-E385. Epub 2021 Aug 9.

Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan.

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http://dx.doi.org/10.1055/a-1550-1913DOI Listing
July 2022

Fecal calprotectin is a useful biomarker for predicting the clinical outcome of granulocyte and monocyte adsorptive apheresis in ulcerative colitis patients: a prospective observation study.

BMC Gastroenterol 2021 Aug 6;21(1):316. Epub 2021 Aug 6.

Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan.

Background: Granulocyte and monocyte adsorptive apheresis (GMA) is widely used as a remission induction therapy for active ulcerative colitis (UC) patients. However, there are no available biomarkers for predicting the clinical outcome of GMA. We investigated the utility of Fecal calprotectin (FC) as a biomarker for predicting the clinical outcome during GMA therapy in active UC patients.

Methods: In this multicenter prospective observation study, all patients received 10 sessions of GMA, twice a week, for 5 consecutive weeks. FC was measured at entry, one week, two weeks, and at the end of GMA. Colonoscopy was performed at entry and after GMA. The clinical activity was assessed based on the partial Mayo score when FC was measured. Clinical remission (CR) was defined as a partial Mayo score of ≤ 2 and endoscopic remission (ER) was defined as Mayo endoscopic subscore of either 0 or 1. We analyzed the relationships between the clinical outcome (CR and ER) and the change in FC concentration.

Result: Twenty-six patients were included in this study. The overall CR and ER rates were 50.0% and 19.2%, respectively. After GMA, the median FC concentration in patients with ER was significantly lower than that in patients without ER (469 mg/kg vs. 3107 mg/kg, p = 0.03). When the cut-off value of FC concentration was set at 1150 mg/kg for assessing ER after GMA, the sensitivity and specificity were 0.8 and 0.81, respectively. The FC concentration had significantly decreased by one week. An ROC analysis demonstrated that the reduction rate of FC (ΔFC) at 1 week was the most accurate predictor of CR at the end of GMA (AUC = 0.852, P = 0.002). When the cut-off value of ΔFC was set at ≤ 40% at 1 week for predicting CR at the end of GMA, the sensitivity and specificity were 76.9% and 84.6%, respectively.

Conclusion: We evaluated the utility of FC as a biomarker for assessing ER after GMA and predicting CR in the early phase during GMA in patients with active UC. Our findings will benefit patients with active UC by allowing them to avoid unnecessary invasive procedures and will help establish new strategies for GMA.
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http://dx.doi.org/10.1186/s12876-021-01889-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348877PMC
August 2021

Room-Temperature Chiral Light-Emitting Diode Based on Strained Monolayer Semiconductors.

Adv Mater 2021 Sep 24;33(36):e2100601. Epub 2021 Jul 24.

Department of Applied Physics, Nagoya University, Nagoya, 464-8603, Japan.

Room-temperature chiral light sources whose optical helicity can be electrically switched are one of the most important devices for future optical quantum information processing. The emerging valley degree of freedom in monolayer semiconductors allows generation of chiral luminescence via valley polarization. However, relevant valley-polarized light-emitting diodes (LEDs) have only been achieved at low temperatures (typically below 80 K). Here, a room-temperature chiral LED with strained transition metal dichalcogenide monolayers is realized. Spatially resolved polarization spectroscopy reveals that strain effects are crucial to yielding robust valley-polarized electroluminescence. The broken threefold rotational symmetry of strained monolayers induce inequivalent valley drifts at the K/K' valleys, resulting in different amounts of spin recombination driven by electric fields. Based on this scenario, ideally strained conditions are designed for LEDs on flexible substrates, in which the helicity of room-temperature valley-polarized electroluminescence is electrically tuned. The results provide a new pathway for practical chiral light sources based on monolayer semiconductors.
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http://dx.doi.org/10.1002/adma.202100601DOI Listing
September 2021

Long-term Observation of Gastric Adenocarcinoma of Fundic Gland Mucosa Type before and after Eradication: a Case Report.

J Gastric Cancer 2021 Mar 29;21(1):103-109. Epub 2021 Mar 29.

Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.

Gastric adenocarcinoma of the fundic gland mucosa type (GA-FGM) was proposed as a new variant of gastric adenocarcinoma of the fundic gland type (GA-FG). However, at present, the influence of and the speed of progression and degree of malignancy in GA-FGM remain unclear. Herein, we report the first case of intramucosal GA-FGM that was endoscopically observed before and after eradication over 15 years. The lesion showed the same tumor size with no submucosal invasion and a low MIB-1 labeling index 15 years after its detection using endoscopy. The endoscopic morphology changed from 0-IIa before eradication to 0-IIa+IIc and then 0-I after eradication. These findings suggest that the unaltered tumor size reflects low-grade malignancy and slow growth, and that the endoscopic morphology is influenced by eradication.
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http://dx.doi.org/10.5230/jgc.2021.21.e11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020006PMC
March 2021

The Optimal Dose of Tacrolimus in Combination Therapy with an Anti-TNFα Antibody in a Mouse Colitis Model.

Biol Pharm Bull 2021 ;44(4):564-570

Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University.

An attempt to use combination therapy with anti-tumor necrosis factor α (TNFα) antibodies and tacrolimus (TAC) has been tried to induce remission in ulcerative colitis (UC). However, the optimal dose of TAC in combination therapy with anti-TNFα antibodies (TAC + anti-TNFα therapy) remains unclear. We examined the efficacy of various doses of TAC + anti-TNFα therapy in a mouse colitis model. Dextran sulfate sodium induced colitis model mice were divided into an anti-TNFα antibody monotherapy group and the groups that received various doses of TAC + anti-TNFα therapy. The nuclear factor expression of activated T-cells, cytoplasmic 1 (NFATc1) in the nuclei and the mRNA expression of inflammatory cytokines were assessed by immunohistochemistry and RT-PCR, respectively. The serum anti-TNFα antibody concentration was measured with an enzyme-linked immunosorbent assay. The colon length and histological severity were significantly improved in the groups that received any dose of TAC + anti-TNFα therapy. The nuclear expression of NFATc1 was inversely proportional to the administered doses of TAC. The expression levels of inflammatory cytokines tended to decrease in proportion to the dose of TAC. The serum concentration of anti-TNFα antibodies in the high-dose TAC + anti-TNFα therapy was significantly higher than those in the other groups. Low-dose TAC exerted its immunosuppressive effect on T-cells, and additionally, high-dose TAC maintained the serum anti-TNFα antibody concentration. When administered in combination with anti-TNFα antibodies, the dose of TAC should be adjusted according to the disease severity.
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http://dx.doi.org/10.1248/bpb.b20-00916DOI Listing
November 2021

Clinicopathological characteristics of Epstein-Barr virus and microsatellite instability subtypes of early gastric neoplasms classified by the Japanese and the World Health Organization criteria.

J Pathol Clin Res 2021 Jul 22;7(4):397-409. Epub 2021 Mar 22.

Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.

Gastric cancer is a heterogenous disease with different phenotypes, genotypes, and clinical outcomes, including sensitivity to treatments and prognoses. Recent medical advances have enabled the classification of this heterogenous disease into several groups and the consequent analysis of their clinicopathological characteristics. Gastric cancer associated with Epstein-Barr virus (EBV) and microsatellite-unstable tumors are considered to be the two major subtypes as they are clearly defined by well-established methodologies, such as in situ hybridization and polymerase chain reaction-based analyses, respectively. However, discrepancies in the histological diagnosis of gastric neoplasms remain problematic, and international harmonization should be performed to improve our understanding of gastric carcinogenesis. We re-evaluated Japanese cases of early gastric cancer according to the current World Health Organization (WHO) criteria and classified them into genomic subtypes based on microsatellite instability (MSI) and EBV positivity to determine the initial genetic events in gastric carcinogenesis. A total of 113 Japanese early gastric cancers (including low- and high-grade dysplasias) treated with endoscopic resection over 5 years were archived in our hospital. A histological re-evaluation according to the WHO criteria revealed 54 adenocarcinomas, which were divided into 6 EBV-positive (11.1%), 7 MSI-high (MSI-H, 13.0%), and 41 microsatellite stable cases (75.9%). MSI-H adenocarcinoma was confirmed by an immunohistochemistry assay of mismatch repair proteins. Programmed death-ligand 1 immunostaining with two antibodies (E1L3N and SP263) was positive in tumor cells of one MSI-H adenocarcinoma case (1/7, 14.3%). The proportion of stained cells was higher with clone SP263 than with E1L3N. Histologically, EBV-positive carcinomas were poorly differentiated (83.8%), and MSI-H cancers were frequent in well to moderately differentiated adenocarcinoma (85.7%), indicating that the EBV-positive subtype presented with high-grade morphology even when an early lesion. Our study indicates that the WHO criteria are useful for subdividing Japanese early gastric cancers, and this subdivision may be useful for comparative analysis of precursor lesions and early carcinoma.
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http://dx.doi.org/10.1002/cjp2.209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185367PMC
July 2021

Cardiac Metastasis Caused Fatal Ventricular Arrhythmia in a Patient with a Rectal Neuroendocrine Tumor.

Intern Med 2021 1;60(3):373-378. Epub 2021 Feb 1.

Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan.

A 60-year-old man had received octreotide for a metastatic neuroendocrine tumor (NET) in the rectum. Computed tomography and ultrasonography revealed a cardiac tumor, diffuse thickness of the ventricular wall and pericardial effusion, which was diagnosed as cardiac metastasis. The metastatic lesions continued to grow despite the alteration of chemotherapy, and the patient complained of repeated syncope and was admitted to our hospital at 11 months after the diagnosis of cardiac metastasis. An electrocardiogram during syncope showed sustained ventricular tachycardia, which was considered to be caused by the cardiac metastasis. We herein report a case of NET with cardiac metastasis which caused lethal arrhythmia along with a review of the pertinent literature.
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http://dx.doi.org/10.2169/internalmedicine.5208-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925266PMC
April 2021

Clinical manifestations and epilepsy treatment in Japanese patients with pathogenic CDKL5 variants.

Brain Dev 2021 Apr 9;43(4):505-514. Epub 2021 Jan 9.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Objective: Patients with pathogenic cyclin-dependent kinase-like-5 gene (CDKL5) variants are designated CDKL5 deficiency disorder (CDD). This study aimed to delineate the clinical characteristics of Japanese patients with CDD and elucidate possible appropriate treatments.

Methods: We recruited patients with pathogenic or likely pathogenic CDKL5 variants from a cohort of approximately 1,100 Japanese patients with developmental and epileptic encephalopathies, who underwent genetic analysis. We retrospectively reviewed clinical, electroencephalogram, neuroimaging, and genetic information.

Results: We identified 29 patients (21 females, eight males). All patients showed severe developmental delay, especially in males. Involuntary movements were observed in 15 patients. No antiepileptic drugs (AEDs) achieved seizure freedom by monotherapy. AEDs achieving ≥ 50% reduction in seizure frequency were sodium valproate in two patients, vigabatrin in one, and lamotrigine in one. Seizure aggravation was observed during the use of lamotrigine, potassium bromide, and levetiracetam. Adrenocorticotrophic hormone (ACTH) was the most effective treatment. The ketogenic diet (KD), corpus callosotomy and vagus nerve stimulation did not improve seizure frequency in most patients, but KD was remarkably effective in one. The degree of brain atrophy on magnetic resonance imaging (MRI) reflected disease severity. Compared with females, males had lower levels of attained motor development and more severe cerebral atrophy on MRI.

Conclusion: Our patients showed more severe global developmental delay than those in previous studies and had intractable epilepsy, likely because previous studies had lower numbers of males. Further studies are needed to investigate appropriate therapy for CDD, such as AED polytherapy or combination treatment involving ACTH, KD, and AEDs.
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http://dx.doi.org/10.1016/j.braindev.2020.12.006DOI Listing
April 2021

Polymicrogyria with calcification in Pallister-Killian syndrome detected by microarray analysis.

Brain Dev 2021 Mar 21;43(3):448-453. Epub 2020 Nov 21.

Department of Child Neurology, NHO Nishiniigata Chuo Hospital, 1-14-1 Masago, Nishi-ku, Niigata 950-2085, Japan. Electronic address:

Background: Pallister-Killian syndrome (PKS) is a rare disorder caused by the mosaic tetrasomy of chromosome 12p, and is characterized by facial dysmorphism, developmental delay, hypotonia and seizures.

Results: We report a patient with PKS showing unique polymicrogyria with calcification. He had delayed development and dysmorphic facial features including frontal bossing, hypertelorism, and high arched palate at 6 months of age. Neuroimaging revealed unilateral polymicrogyria with spot calcifications, which predominantly affected the right perisylvian region. Chromosome G-banding showed the karyotype 46,XY, however, array-based comparative genomic hybridization analysis showed mosaic duplication of chromosome 12p, in which CCND2, which encodes cyclin D2 and is a downstream mediator of PI3K-AKT pathway, is located. Supernumerary chromosome of 12p was detected in 58% of buccal mucosa cells by the interphase fluorescence in situ hybridization analysis using chromosome 12 centromere-specific D12Z3 probe. The diagnosis of PKS was made based on distinctive clinical features of our patient and the results of cytogenetic analyses.

Conclusion: This report is, to our knowledge, the first case of a patient with PKS who clearly demonstrates polymicrogyria colocalized with calcifications, as shown by CT scans and MRI, and suggests that a patient with PKS could show structural brain anomalies with calcification. We assume that somatic mosaicism of tetrasomy could cause asymmetrical polymicrogyria in our patient, and speculate that increased dosages of CCND2 at chromosome 12p might be involved in the abnormal neuronal migration in PKS.
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http://dx.doi.org/10.1016/j.braindev.2020.11.003DOI Listing
March 2021

De novo variants in CELF2 that disrupt the nuclear localization signal cause developmental and epileptic encephalopathy.

Hum Mutat 2021 01 10;42(1):66-76. Epub 2020 Nov 10.

Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.

We report heterozygous CELF2 (NM_006561.3) variants in five unrelated individuals: Individuals 1-4 exhibited developmental and epileptic encephalopathy (DEE) and Individual 5 had intellectual disability and autistic features. CELF2 encodes a nucleocytoplasmic shuttling RNA-binding protein that has multiple roles in RNA processing and is involved in the embryonic development of the central nervous system and heart. Whole-exome sequencing identified the following CELF2 variants: two missense variants [c.1558C>T:p.(Pro520Ser) in unrelated Individuals 1 and 2, and c.1516C>G:p.(Arg506Gly) in Individual 3], one frameshift variant in Individual 4 that removed the last amino acid of CELF2 c.1562dup:p.(Tyr521Ter), possibly resulting in escape from nonsense-mediated mRNA decay (NMD), and one canonical splice site variant, c.272-1G>C in Individual 5, also probably leading to NMD. The identified variants in Individuals 1, 2, 4, and 5 were de novo, while the variant in Individual 3 was inherited from her mosaic mother. Notably, all identified variants, except for c.272-1G>C, were clustered within 20 amino acid residues of the C-terminus, which might be a nuclear localization signal. We demonstrated the extranuclear mislocalization of mutant CELF2 protein in cells transfected with mutant CELF2 complementary DNA plasmids. Our findings indicate that CELF2 variants that disrupt its nuclear localization are associated with DEE.
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http://dx.doi.org/10.1002/humu.24130DOI Listing
January 2021

Endoscopic finding of a lace pattern in a case of Epstein-Barr virus-associated early gastric carcinoma.

Gastrointest Endosc 2021 Mar 15;93(3):768-769. Epub 2020 Oct 15.

Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan.

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http://dx.doi.org/10.1016/j.gie.2020.10.008DOI Listing
March 2021

Genetic alteration of colorectal adenoma-carcinoma sequence among gastric adenocarcinoma and dysplastic lesions in a patient with attenuated familial adenomatous polyposis.

Mol Genet Genomic Med 2020 09 16;8(9):e1348. Epub 2020 Jun 16.

Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.

Background: Familial adenomatous polyposis (FAP) is characterized by colorectal polyposis and adenocarcinoma that is frequently accompanied by extracolonic neoplasm. The risk of gastric carcinoma is increasing in Western FAP patients as well as Asian patients.

Methods: We report the case of an FAP patient with fundic gland polyposis who developed gastric adenocarcinoma and metachronous pyloric gland adenomas. These tumors were endoscopically resected, and immunohistochemistry with gastric mucin (i.e., MUC6, MUC5AC) showed that the tumors belonged to the gastric subtype. Somatic mutation profiles were determined by target amplicon sequencing using a next-generation sequencer.

Results: Germline APC variant c.5782delC was found by direct sequencing and somatic KRAS mutations in these tumors were identified by next-generation sequencing. Different KRAS mutation alleles (KRAS p.Gly12Ala, p.Gly12Arg, and p.Gly12Asp) indicated these dysplastic lesions developed from a distinct origin in fundic gland polyposis. Sequential mutations of the APC and KRAS were judged-based on a database search-to be characteristic of the adenoma-carcinoma sequence in colorectal carcinogenesis.

Conclusion: The colonic adenoma-carcinoma sequence among gastric adenocarcinoma and dysplastic lesions was indicated in FAP-associated gastric carcinogenesis.
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http://dx.doi.org/10.1002/mgg3.1348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507424PMC
September 2020

Serrated adenomas with a BRAF mutation in a young patient with familial adenomatous polyposis.

Int J Colorectal Dis 2020 Oct 5;35(10):1967-1972. Epub 2020 Jun 5.

Division of Gastroenterology and Hematology/Oncology Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan.

Introduction: Familial adenomatous polyposis (FAP) is typically characterized by more than hundred adenomatous polyps in the colorectum, caused by germline APC mutation. A small proportion of the polyps progress to colorectal adenocarcinoma via adenoma-carcinoma sequence. Serrated lesions and polyps, characterized by a serrated architecture of the epithelium, are noted for two types of genetic pathways in colorectal carcinogenesis. BRAF and KRAS mutations are observed in the serrated pathway.

Case Report: We report a young FAP patient with rectal serrated adenomas that were removed by colonoscopic procedures. The histological features with villiform projections and slit-like serration indicated traditional serrated adenoma. A genetic examination with next-generation sequencing showed a somatic BRAF mutation in the serrated adenoma and APC mutations in the tubular adenomas. His germline mutation was found at APC p.Q1928fs*.

Conclusion: Serrated adenomas with dual genetic alterations in a FAP patient may be associated with colorectal carcinogenesis and should be considered a target lesion for treatment. The present study demonstrated the malignant potential of serrated adenoma in a FAP patient.
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http://dx.doi.org/10.1007/s00384-020-03657-0DOI Listing
October 2020

One-dimensional van der Waals heterostructures.

Science 2020 01;367(6477):537-542

Department of Mechanical Engineering, The University of Tokyo, Tokyo 113-8656, Japan.

We present the experimental synthesis of one-dimensional (1D) van der Waals heterostructures, a class of materials where different atomic layers are coaxially stacked. We demonstrate the growth of single-crystal layers of hexagonal boron nitride (BN) and molybdenum disulfide (MoS) crystals on single-walled carbon nanotubes (SWCNTs). For the latter, larger-diameter nanotubes that overcome strain effect were more readily synthesized. We also report a 5-nanometer-diameter heterostructure consisting of an inner SWCNT, a middle three-layer BN nanotube, and an outer MoS nanotube. Electron diffraction verifies that all shells in the heterostructures are single crystals. This work suggests that all of the materials in the current 2D library could be rolled into their 1D counterparts and a plethora of function-designable 1D heterostructures could be realized.
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http://dx.doi.org/10.1126/science.aaz2570DOI Listing
January 2020

Lymph Node Metastasis From Gastroesophageal Cancer Successfully Treated by Nivolumab: A Case Report of a Young Patient.

Front Oncol 2019 16;9:1375. Epub 2019 Dec 16.

Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.

Immuno-oncology is a novel target of cancer therapy. Nivolumab is a monoclonal anti-programed death-1 antibody recently used to treat patients with chemotherapy-resistant gastric and gastroesophageal cancer. Although the disease control rate is reported to be very high, few cases demonstrate a complete response. A 25-year-old man diagnosed with gastroesophageal cancer was treated with chemotherapy followed by surgical resection. Pathological diagnosis was poorly differentiated adenocarcinoma with distant lymph node metastasis. Residual lymph node metastasis was treated with nivolumab monotherapy, resulting in complete disappearance. No recurrence has been observed for 2 years since discontinuation of nivolumab. This rare case was additionally subjected to pathological and genetic analysis, suggesting that a high tumor mutation burden (10.7 mutations/Mb) might be associated with sensitivity to nivolumab. We reported a case of advanced gastroesophageal junction cancer with distal lymph node metastasis that was successfully treated with chemotherapy, surgical resection, and nivolumab therapy. An aggressive search for biomarkers implying benefit effects of nivolumab should be performed.
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http://dx.doi.org/10.3389/fonc.2019.01375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927466PMC
December 2019

High-Resolution Electrochemical Mapping of the Hydrogen Evolution Reaction on Transition-Metal Dichalcogenide Nanosheets.

Angew Chem Int Ed Engl 2020 Feb 24;59(9):3601-3608. Epub 2020 Jan 24.

Graduate School of Environmental Studies, Tohoku University, 6-6-11-604, Aramaki Aoba, Aoba-ku, Sendai, 980-8579, Japan.

High-resolution scanning electrochemical cell microscopy (SECCM) is used to image and quantitatively analyze the hydrogen evolution reaction (HER) catalytically active sites of 1H-MoS nanosheets, MoS , and WS heteronanosheets. Using a 20 nm radius nanopipette and hopping mode scanning, the resolution of SECCM was beyond the optical microscopy limit and visualized a small triangular MoS nanosheet with a side length of ca. 130 nm. The electrochemical cell provides local cyclic voltammograms with a nanoscale spatial resolution for visualizing HER active sites as electrochemical images. The HER activity difference of edge, terrace, and heterojunction of MoS and WS were revealed. The SECCM imaging directly visualized the relationship of HER activity and number of MoS nanosheet layers and unveiled the heterogeneous aging state of MoS nanosheets. SECCM can be used for improving local HER activities by producing sulfur vacancies using electrochemical reaction at the selected region.
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http://dx.doi.org/10.1002/anie.201912863DOI Listing
February 2020

Gastric submucosa-invasive carcinoma associated with Epstein-Barr virus and endoscopic submucosal dissection: A case report.

World J Gastrointest Oncol 2019 Oct;11(10):925-932

Division of Gastroenterology and Hematology/Oncology Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.

Background: Epstein-Barr virus (EBV)-associated carcinoma is a gastric cancer subtype with a morphology characterized by gastric carcinoma with lymphoid stroma (GCLS). Clinicopathological studies have indicated a better prognosis for GCLS than for common gastric carcinomas. Some previous cases of early gastric cancer associated with EBV had been diagnosed by endoscopic resection.

Case Summary: We present two GCLS cases subjected to endoscopic submucosal dissection (ESD) for a definitive diagnosis. A protruded gastric lesion was identified by routine endoscopic examination, but forceps biopsy showed no atypical cells before ESD. The resected specimen showed a poorly differentiated adenocarcinoma with lymphoid cells involving the mucosa and submucosa. The final diagnosis was submucosa-invasive poorly differentiated gastric adenocarcinoma. Accordingly, additional gastrectomy was recommended to obtain a complete cure. One patient underwent additional distal gastrectomy with lymph node dissection, but the other was refused because of cardiovascular complications. Both patients remained in remission for more than half a year. EBV positivity was determined by EBV-encoded RNA hybridization. We also conducted a literature review of cases of early gastric cancer associated with EBV that had been diagnosed by ESD.

Conclusion: Submucosa-invasive GCLS could be dissected using ESD, and EBV positivity should be subsequently assessed to determine whether or not any additional curative surgery is required. Further prospective investigations on the prevalence of lymph node metastasis in EBV-associated carcinoma should be performed to expand the indications for endoscopic resection.
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http://dx.doi.org/10.4251/wjgo.v11.i10.925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815925PMC
October 2019

Tunable Chemical Coupling in Two-Dimensional van der Waals Electrostatic Heterostructures.

ACS Nano 2019 Oct 7;13(10):11214-11223. Epub 2019 Oct 7.

World Premier International Center for Materials Nanoarchitectonics (WPI-MANA) , National Institute for Materials Science(NIMS) , 1-1 Namiki , Tsukuba , Ibaraki 305-0044 , Japan.

Heterostructures of two-dimensional (2D) atomic crystals provide fascinating molecular-scale design elements for emergent physical phenomena and functional materials, as integrating distinct monolayers into vertical heterostructures can afford coupling between disparate properties. However, the available examples have been limited to either van der Waals (vdW) or electrostatic (ES) heterostructures that are solely composed of noncharged and charged monolayers, respectively. Here, we propose a "vdW-ES heterostructure" chemical design in which charge-neutral and charged monolayer-building blocks with highly disparate chemical and physical properties are conjugated vertically through asymmetrically charged interfaces. We demonstrate vdW-ES heteroassembly of semiconducting MoS and dielectric CaNbO (CNO) monolayers using an amphipathic molecular starch, resulting in the emergence of trion luminescence observed at the lowest energy among MoS-related materials, probably due to interfacial confinement effects given by vdW-ES dual interactions. In addition, interface engineering leads to tailored exciton of the vdW/ES heterostructures owing to the pronounced dielectric proximity effects, bringing an intriguing interlayer chemistry to modify 2D materials. Furthermore, the current approach was successfully extended to create a graphene/CNO heterostructure, which verifies the versatility of the preparative method.
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http://dx.doi.org/10.1021/acsnano.9b04256DOI Listing
October 2019

Exciton Polarization and Renormalization Effect for Optical Modulation in Monolayer Semiconductors.

ACS Nano 2019 Aug 13;13(8):9218-9226. Epub 2019 Aug 13.

Department of Applied Physics , Nagoya University , Nagoya 464-8603 , Japan.

The ideal quantum confinement structure of monolayer semiconductors offers prominent optical modulation capabilities that are mediated by enhanced many-body interactions. Herein, we establish an electrolyte-gating method for tuning the luminescence properties that are in transition metal dichalcogenide (TMDC) monolayers. We fabricate electric double-layer capacitors on TMDC/graphite heterostructures to investigate electric-field- and carrier-density-dependent photoluminescence. The exciton peak energy initially shows a slight quadratic red shift of ∼1 meV without carrier accumulations, which is caused by the quantum-confined Stark effect. In contrast, the exciton resonance exhibits a larger red shift up to 10 meV with the accumulated carrier density above 10 cm. These results indicate that the optical transitions can be largely modulated by the carrier density control in S- and Se-based TMDCs, as triggered by the doping-induced band gap renormalization effect. To further inspire this modulation capability, we also apply our method to electrolyte-based TMDC light-emitting devices. Biasing solely in electrolyte-induced p-i-n junctions yields pronounced red shifts up to 40 meV for exciton and trion electroluminescence. Consequently, our approach reveals that the doping effects in the high-carrier-density regimes are potentially significant for efficient optical modulation in monolayer semiconductors.
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http://dx.doi.org/10.1021/acsnano.9b03563DOI Listing
August 2019

Comprehensive analysis of coding variants highlights genetic complexity in developmental and epileptic encephalopathy.

Nat Commun 2019 06 7;10(1):2506. Epub 2019 Jun 7.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.

Although there are many known Mendelian genes linked to epileptic or developmental and epileptic encephalopathy (EE/DEE), its genetic architecture is not fully explained. Here, we address this incompleteness by analyzing exomes of 743 EE/DEE cases and 2366 controls. We observe that damaging ultra-rare variants (dURVs) unique to an individual are significantly overrepresented in EE/DEE, both in known EE/DEE genes and the other non-EE/DEE genes. Importantly, enrichment of dURVs in non-EE/DEE genes is significant, even in the subset of cases with diagnostic dURVs (P = 0.000215), suggesting oligogenic contribution of non-EE/DEE gene dURVs. Gene-based analysis identifies exome-wide significant (P = 2.04 × 10) enrichment of damaging de novo mutations in NF1, a gene primarily linked to neurofibromatosis, in infantile spasm. Together with accumulating evidence for roles of oligogenic or modifier variants in severe neurodevelopmental disorders, our results highlight genetic complexity in EE/DEE, and indicate that EE/DEE is not an aggregate of simple Mendelian disorders.
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http://dx.doi.org/10.1038/s41467-019-10482-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555845PMC
June 2019

Restoring the intrinsic optical properties of CVD-grown MoS monolayers and their heterostructures.

Nanoscale 2019 Jul;11(27):12798-12803

Department of Physics, Tokyo Metropolitan University, Hachioji, 192-0397, Japan.

This study investigated the intrinsic optical properties of MoS2 monolayers and MoS2/WS2 van der Waals (vdW) heterostructures, grown using chemical vapor deposition. To understand the effect of the growth substrate, samples grown on a SiO2/Si surface were transferred and suspended onto a porous substrate. This transfer resulted in a blue shift of the excitonic photoluminescence (PL) peak generated by MoS2 monolayers, together with an intensity increase. The blue shift and the intensity increase are attributed to the release of lattice strain and the elimination of substrate-induced non-radiative relaxation, respectively. This suspension technique also allowed the observation of PL resulting from interlayer excitons in the MoS2/WS2 vdW heterostructures. These results indicate that the suppression of lattice strain and non-radiative relaxation is essential for the formation of interlayer excitons, which in turn is crucial for understanding the intrinsic physical properties of vdW heterostructures.
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http://dx.doi.org/10.1039/c9nr01481kDOI Listing
July 2019
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