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Mesenteric phlebosclerosis is a rare form of intestinal ischemia characterized by thickening of the right-sided colon and calcification of the mesenteric vein. We describe the case of a 58-year-old woman admitted to our hospital because of abdominal pain and distension. An abdominal computed tomography study revealed remarkable dilatation and fluid collection of the small intestine compatible with intestinal obstruction, which was considered to be the result of stenosis of the ascending colon. The thickened wall of the cecum and ascending colon was associated with calcification of the colonic wall and mesenteric veins. Colonoscopy showed dark purple discoloration of the edematous mucosa from the splenic flexure through the hepatic flexure, at which point the colonoscope could not be advanced further because of stenosis of the ascending colon. Over 10 years previously, the patient had taken an herbal medicine containing gardenia fruit, which can cause mesenteric phlebosclerosis. An extensive colonic resection was performed after intestinal decompression. This case highlights extensive mesenteric phlebosclerosis causing intestinal obstruction from the cecum through the proximal portion of the sigmoid colon, which was treated with extensive colonic resection.

A 69-year-old man presented with bloody pleural fluid effusion with elevated human chorionic gonadotropin (hCG) levels obtained by thoracentesis. The patient’s condition rapidly declined, and he died. An autopsy revealed primary lung choriocarcinoma. The early diagnosis of choriocarcinoma based on β-hCG levels in pleural fluid may be possible.

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., 「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.

Some patients with coronavirus disease 2019 (COVID-19) experienced sudden death because of sudden symptom deterioration. Thus, an alarm system that could detect early signs of COVID-19 exacerbation beforehand, to prevent serious illness or death of patients while receiving outpatient treatment at home or in hotels is necessary. Here, we tested whether estimated oxygen variations (EOV), a relative physiological scale that represents users' blood oxygen saturation level during sleep measured by Fitbit, predicted COVID-19 symptom exacerbation. Study period was from August to November 2020. We enrolled 23 COVID-19 patients diagnosed by SARS-CoV-2 polymerase chain reaction-positive (mean age ± standard deviation, 50.9±20 years; 70% female), let each patient wore the Fitbit for 30 days; COVID-19 symptoms were exacerbated in 6 (26%). High EOV signal (a patient's oxygen level exhibits significant dip and recovery within the index period) had 80% sensitivity before symptom exacerbations, whereas resting heart rate signal only had 50% sensitivity. Coincidental obstructive sleep apnea syndrome confirmed by polysomnography was detected in a patient by consistently high EOV signals. This pilot study successfully detected early COVID-19 symptoms exacerbation by measuring EOV and may help to identify early signs of COVID-19 exacerbation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The investigational device used in this study, Fitbit Charge 3, was provided by Fitbit Japan. Summary of high EOV signals and eventsThe clinical course of COVID-19

Organic thin-film transistors (OTFTs) are promising building blocks for low cost, low-environmental load, and lightweight electronic devices. Carbon-based conductors can be potentially used as TFT electrodes. However, a concern is that the carbon electrode is unsuitable for carrier injection into organic semiconductors due to the difficulty in precise work function control. Herein, we have demonstrated that molecular dopants in carbon networks can improve carrier injection with a reasonably low contact resistance of 510 Ω·cm, which constitutes a key step in the realization of noble-metal-free electronic devices.

The objective of this study was to describe a novel amplitude-integrated electroencephalography (aEEG) pattern in infants with hypoxic–ischemic encephalopathy (HIE) and to assess the clinical significance. The aEEG traces of infants with HIE who were treated with therapeutic hypothermia (TH) from 2012 to 2017 were analyzed. A pseudo-sawtooth (PST) pattern was defined as a periodic increase of the upper and/or lower margin of the trace on aEEG without showing seizure activities on conventional EEG (CEEG). Of the 46 infants, 6 (13%) had the PST pattern. The PST pattern appeared following a flat trace or a continuous low-voltage pattern and was followed by a burst-suppression pattern. On CEEG, the PST pattern consists of alternating cycles of low-voltage irregular activities and almost flat tracing. The PST pattern was associated with neuroimaging abnormalities and with various degrees of neurodevelopmental outcomes. Positive predictive values of the PST or worse pattern for adverse outcomes were high at 12 h after birth. A novel aEEG background pattern in infants with HIE was reported. The PST pattern likely indicates a suppressed background pattern and may be linked to unfavorable outcomes. Further multicenter validation study is needed to clarify its clinical significance.

BACKGROUND Some patients with COVID-19 experienced sudden death due to rapid symptom deterioration. Thus, it is important to predict COVID-19 symptom exacerbation at an early stage prior to increasing severity in patients. Patients with COVID-19 could experience a unique “silent hypoxia” at an early stage of the infection when they are apparently asymptomatic, but with rather low SpO2 (oxygen saturation) levels. In order to continuously monitor SpO2 in daily life, a high-performance wearable device, such as the Apple Watch or Fitbit, has become commercially available to monitor several biometric data including steps, resting heart rate (RHR), physical activity, sleep quality, and estimated oxygen variation (EOV). OBJECTIVE This study aimed to test whether EOV measured by the wearable device Fitbit can predict COVID-19 symptom exacerbation. METHODS We recruited patients with COVID-19 from August to November 2020. Patients were asked to wear the Fitbit for 30 days, and biometric data including EOV and RHR were extracted. EOV is a relative physiological measure that reflects users’ SpO2 levels during sleep. We defined a high EOV signal as a patient’s oxygen level exhibiting a significant dip and recovery within the index period, and a high RHR signal as daily RHR exceeding 5 beats per day compared with the minimum RHR of each patient in the study period. We defined successful prediction as the appearance of those signals within 2 days before the onset of the primary outcome. The primary outcome was the composite of deaths of all causes, use of extracorporeal membrane oxygenation, use of mechanical ventilation, oxygenation, and exacerbation of COVID-19 symptoms, irrespective of readmission. We also assessed each outcome individually as secondary outcomes. We made weekly phone calls to discharged patients to check on their symptoms. RESULTS We enrolled 23 patients with COVID-19 diagnosed by a positive SARS-CoV-2 polymerase chain reaction test. The patients had a mean age of 50.9 (SD 20) years, and 70% (n=16) were female. Each patient wore the Fitbit for 30 days. COVID-19 symptom exacerbation occurred in 6 (26%) patients. We were successful in predicting exacerbation using EOV signals in 4 out of 5 cases (sensitivity=80%, specificity=90%), whereas the sensitivity and specificity of high RHR signals were 50% and 80%, respectively, both lower than those of high EOV signals. Coincidental obstructive sleep apnea syndrome confirmed by polysomnography was detected in 1 patient via consistently high EOV signals. CONCLUSIONS This pilot study successfully detected early COVID-19 symptom exacerbation by measuring EOV, which may help to identify the early signs of COVID-19 exacerbation. CLINICALTRIAL University Hospital Medical Information Network Clinical Trials Registry UMIN000041421; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047290

To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5p35 (rs60200309-A at DOCK2) that was significantly associated with severe COVID-19 in younger (-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.

In this paper we compare the combinatorial Ricci curvature on cell complexes and the LLY-Ricci curvature defined on graphs. A cell complex is correspondence to a graph such that the vertexes are cells and the edges are vectors on the cell complex. We compare this two Ricci curvature by the cooupling and Kantrovich duality., Comment: 22 pages, 9 figures

An addressable packing parameter approach was developed for reversibly tuning the self-assembly of oligo(aniline)-based supra-amphiphiles., We present a newly developed approach to non-covalently address the packing parameter of an electroactive amphiphile. The pH-responsive reversible switching of a tetra(aniline)-based cationic amphiphile, TANI-pentyl trimethylammonium bromide (TANI-PTAB), between self-assembled vesicles and nanowires by acid/base chemistry in aqueous solution is used to exemplify this approach. Trifluoroacetic acid (TFA) was selected as a prototypical acid to form emeraldine salt (ES) state (TANI(TFA)2-PTAB) vesicles for this new class of small-molecule supramolecular amphiphiles. UV-vis-NIR spectroscopy, transmission electron microscopy (TEM), tapping-mode atomic force microscopy (AFM), and fluorescence spectroscopy were used to investigate the reversible structural transformation from vesicles to nanowires. We show that utilising different protonic acid-dopants for TANI-PTAB can regulate the packing parameter, and thus the final self-assembled structures, in a predictable fashion. We envisage potential application of this concept as smart and switchable delivery systems.

Background Some patients with COVID-19 experienced sudden death due to rapid symptom deterioration. Thus, it is important to predict COVID-19 symptom exacerbation at an early stage prior to increasing severity in patients. Patients with COVID-19 could experience a unique “silent hypoxia” at an early stage of the infection when they are apparently asymptomatic, but with rather low SpO2 (oxygen saturation) levels. In order to continuously monitor SpO2 in daily life, a high-performance wearable device, such as the Apple Watch or Fitbit, has become commercially available to monitor several biometric data including steps, resting heart rate (RHR), physical activity, sleep quality, and estimated oxygen variation (EOV). Objective This study aimed to test whether EOV measured by the wearable device Fitbit can predict COVID-19 symptom exacerbation. Methods We recruited patients with COVID-19 from August to November 2020. Patients were asked to wear the Fitbit for 30 days, and biometric data including EOV and RHR were extracted. EOV is a relative physiological measure that reflects users’ SpO2 levels during sleep. We defined a high EOV signal as a patient’s oxygen level exhibiting a significant dip and recovery within the index period, and a high RHR signal as daily RHR exceeding 5 beats per day compared with the minimum RHR of each patient in the study period. We defined successful prediction as the appearance of those signals within 2 days before the onset of the primary outcome. The primary outcome was the composite of deaths of all causes, use of extracorporeal membrane oxygenation, use of mechanical ventilation, oxygenation, and exacerbation of COVID-19 symptoms, irrespective of readmission. We also assessed each outcome individually as secondary outcomes. We made weekly phone calls to discharged patients to check on their symptoms. Results We enrolled 23 patients with COVID-19 diagnosed by a positive SARS-CoV-2 polymerase chain reaction test. The patients had a mean age of 50.9 (SD 20) years, and 70% (n=16) were female. Each patient wore the Fitbit for 30 days. COVID-19 symptom exacerbation occurred in 6 (26%) patients. We were successful in predicting exacerbation using EOV signals in 4 out of 5 cases (sensitivity=80%, specificity=90%), whereas the sensitivity and specificity of high RHR signals were 50% and 80%, respectively, both lower than those of high EOV signals. Coincidental obstructive sleep apnea syndrome confirmed by polysomnography was detected in 1 patient via consistently high EOV signals. Conclusions This pilot study successfully detected early COVID-19 symptom exacerbation by measuring EOV, which may help to identify the early signs of COVID-19 exacerbation. Trial Registration University Hospital Medical Information Network Clinical Trials Registry UMIN000041421; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047290

Gastric metastasis from ovarian cancer is exceptionally rare and generally occurs in advanced stages. A 71-year-old woman presented with a solitary gastric submucosal mass 8 years after the diagnosis of a stage IA ovarian serous adenocarcinoma. Endoscopy showed a tumor covered with normal gastric mucosa. Initially, a gastrointestinal stromal tumor was suspected, but biopsy revealed a histology of invasive micropapillary carcinoma, similar to the histological findings of the previously resected ovarian tumor. Clinicians should consider that in patients with a submucosal tumor and a history of ovarian cancer, gastric lesions may be secondary metastases from ovarian cancer.

The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients.Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients.Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P0.001), and incidence of acute subdural hematoma (OR, 1.89; P0.001) were associated with in-hospital mortality in elderly patients with TBI.Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

Increasing reports have showed several kinds of dermatological manifestation in Coronavirus disease 2019 (COVID-19). Some of them may occur as a direct implication of coronavirus infection. Within those, acral skin changes, recently called COVID toes, have a potential to provide a diagnostic value. We herein described a 49-year old Japanese man with COVID toes. The skin lesions appeared simultaneously with fever. The rash was similar for cold-induced erythema multiforme of the patients with familial Chilblain; hereditary type I interferonopathy. Histopathological staining indicated up-regulated expression of MxA, effected by local enhancement of type I interferon. These speculated that the specificity of COVID toes may depend on interferon up-regulated by specific mechanisms.

Purpose Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy. Methods A total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20 years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB)). Results The DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration. Conclusion LTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range.

Objective This study used quantitative analysis to determine whether increased variability in fetal heart rate (FHR) is related to the risk of developing periventricular leukomalacia (PVL). Methods We analyzed 124 FHR traces of neonates delivered preterm at 27–33 weeks’ gestation to 105 mothers. FHR traces 1–3 h before delivery were translated into power-spectrum curves using a fast Fourier transformation. The total power (the area under the curve of 1–10 cycles per minute), segmental power of every cycle per minute, peak power, and frequency edges were calculated, and their relationship with the subsequent development of PVL was examined. Results Total power was significantly higher in the PVL group (n = 9, median 1813, range 1064–2426) compared to the non-PVL group (n = 114, median 1383, range 381–3324, p = 0.029). Infants in the PVL group had greater segmental power in segments with 1–2, 2–3, and 9–10 cycles per minute, than those in the non-PVL group. Total power of ⩾1550 was significantly correlated with the subsequent development of PVL and premature rupture of membranes. Furthermore, the frequency of pregnancy-induced hypertension was significantly reduced in the fetuses with a total power of ⩾1550. Conclusion Our study suggests that a fetus with increased FHR variability is at risk of developing PVL. This study provides additional evidence supporting the contribution of antenatal factors to the subsequent development of PVL.

Pre-fishing season (June and July) Pacific saury Cololabis saira occur offshore, east of Japan, before migrating west to nearshore waters where they are exploited by Japanese fishers in the autumn (September–November). To forecast the location of these fishing grounds we develop a migration model using oceanographic (temperature and current velocity) and fisheries (pre-fishing Pacific saury distribution obtained from stock assessment surveys) data, and migration characteristics determined from fishery data analysis. We speculate that Pacific saury migrate seasonally, first north, staying within a certain temperature zone from May to July, then west, remaining within a preferred but gradually increasing temperature zone. We tune our model using hindcast calculation to reproduce actual fishing grounds around Japan. In July 2018 we forecast the locations of early Pacific saury fishing grounds from August to September. Our forecast fishing grounds were subsequently validated by actual positions of the fishing grounds. Our model successfully forecast the locations of early fishing grounds along the Kuril Islands archipelago, and forecast particles that reached an offshore region roughly predicted offshore fishing grounds. This model also identified Pacific saury migration route trajectories in detail, and that these two fishing grounds in 2018 were formed from geographically separated pre-fishing season shoals via different migration routes. We believe that applying our model will improve the efficiency of the Pacific saury fishery and fleet operation through savings in vessel fuel and time spent searching for shoals.

The value of diffusion-weighted imaging (DWI) in children with acute central nervous system (CNS) symptoms has not been fully established. We aimed to elucidate whether DWI gives additional information in children with acute CNS disorder. The subjects were eight children with acute CNS symptoms, whose cranial DWI showed signal abnormality. Two patients were suffered from cerebral infarction, and one had systemic lupus erythematosus with CNS involvement, four had acute encephalopathy, and one had relapsing encephalopathy. We retrospectively compared (1) the size of signal abnormality, (2) latency until appearance of signal abnormality, and (3) ability to differentiate old lesions between DWI and fluid-attenuation inversion recovery (FLAIR). In addition, we analyzed cerebral blood flow (CBF) changes in lesions detected by DWI, using single-photon emission computed topography (SPECT). In seven of eight patients, the size of signal abnormality was larger in DWI compared to FLAIR. In four of five patients with magnetic resonance imaging obtained during the very acute phase of CNS symptoms, the latency until appearance of signal abnormality was shorter on DWI compared to FLAIR. Combination of DWI and FLAIR successfully differentiated new lesions from old ones in all three subjects with a history of old lesions. DWI revealed signal abnormality not during the very acute phase but on 5th day of CNS symptoms in a patient with encephalopathy. In seven patients with SPECT available, lesions detected by DWI showed decreased CBF in four patients, increased CBF in two, normal CBF in one. DWI may provide useful additional information in children with acute CNS symptoms. Signal abnormalities on DWI may represent ischemic lesions or inflammatory lesions with increased or normal CBF on SPECT.

The older of two siblings began to have spasms and partial seizures at 1 month of age. Head magnetic resonance imaging showed an abnormal area in the left temporo-parieto-occipital region. Interictal electroencephalogram (EEG) showed a suppression-burst pattern. Adrenocorticotropic hormone stopped the spasms, but the seizures continued. Clonazepam, carbamazepine, zonisamide, and clobazam were ineffective. She underwent focal resection at age 8 months. Postoperatively, the seizures disappeared. Histopathologically, the lesion appeared to be focal cortical dysplasia type IIa. The younger sibling had spasms from birth. Head magnetic resonance imaging showed left hemi-megalencephaly. Interictal EEG showed a suppression-burst pattern. Phenobarbital, valproic acid, and zonisamide were ineffective. He underwent hemispherotomy at age 2 months and became seizure free. The histopathological features were consistent with those of hemi-megalencephaly. The siblings' EEG and clinical courses had some similarities. These siblings' conditions may have the same genetic background.

Herein, a novel approach for preparing ionic, helically π-stacked polymer assemblies with high dissymmetry factors is presented. We synthesized cationic chiral poly(para-biphenylene) [PPP1] and poly(para-terphenylene) [PPP2] derivatives by introducing alkyl substituents containing both asymmetric centers and quaternary ammonium cations into the side chains of the polymers. We discovered that these polymers have an intrachain helical structure bearing one-handed twisted main chains in solution; however, there was only a slight preference for one twisted conformation over its opposite. Subsequently, by adding an anionic π-conjugated molecule to the cationic polymers, we prepared polymer assemblies bearing an interchain helically π-stacked structure between the polymers and the molecules. Additionally, we clarified that the anionic molecule functioned as the binding species that closed the cationic π-conjugated polymers through both electrostatic and π–π interactions. Although the polymer assembly of PPP1 wa...

Chikako Ogawa *, Jun Natsume , Hiroyuki Yamamoto , Naoko Ishihara , Atsushi Tashiro , Hiroyuki Kidokoro , Tamiko Negoro , Mari Yoshida , Kazuyoshi Watanabe a Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan Department of Pediatrics, Social Insurance Chukyo Hospital, Nagoya, Japan Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan

Fibroblast growth factor receptor 1 (FGFR1) amplification has been identified in 10-20% of patients with squamous non-small-cell lung cancer. Preclinical models showed promising activity of specific FGFR inhibitors, but early clinical trials showed that only a small fraction of patients with FGFR1-amplified lung cancer responded to FGFR inhibitors. These unsatisfactory results were partly explained by heterogeneous amplicons around the 8p11 genomic region, leading to false-positive amplification results. Furthermore, discrepancies in the gene amplification and protein expression of FGFR1 were also reported. In this study, we identified the roles of alternative receptor tyrosine kinases (RTKs) in FGFR1-amplified lung cancer. These alternative RTKs dominantly activate phosphoinositide 3-kinase-AKT signaling and also mitigate sustained inhibition of mitogen-activated protein kinase signaling by FGFR inhibitors. The rebound activation of extracellular signal-regulated kinase phosphorylation was associated with sensitivity to the drugs. Combinatorial inhibition of alternative RTKs and FGFR1 was required to suppress both AKT and extracellular signal-regulated kinase phosphorylation and to induce key pro-apoptotic proteins BIM and p53 upregulated modulator of apoptosis (PUMA). Furthermore, even in FGFR inhibitor-sensitive NCI-H1581 lung cancer cells, MET-expressing clones were already detectable at a very low frequency before resistance induction. Selection of these pre-existing subclones resulted in FGFR inhibitor resistance because of the activation of AKT and extracellular signal-regulated kinase by MET signaling that was mediated by GRB2 associated binding protein 1 (GAB1). These results suggest that incomplete suppression of key survival signals led to intrinsic and acquired resistance to FGFR inhibitors. Our results may help explain the low clinical response rates to FGFR inhibitors in FGFR1-amplified lung cancer.

In this paper we present the Ricci curvature on cell-complexes and show the Gauss-Bonnnet type theorem on graphs and 2-complex that decomposes closed surface. The defferential forms on a cell complex is defined as linear maps on chain complex, and Laplacian operates this defferential forms. Then we construct the Bochner-Weitzenb\"ock formula and define the Ricci curvature. This curvature is determined by the combinatorial calculation. We show also the properties of combinatorial vector fields on a cell complex

Objective To clarify the semiology of febrile seizures (FS) and to determine the frequency of FS with symptoms suggestive of focal onset. Methods FS symptoms in children were reported within 24 h of seizure onset by the parents using a structured questionnaire consisting principally of closed-ended questions. We focused on events at seizure commencement, including changes in behavior and facial expression, and ocular and oral symptoms. We also investigated the autonomic and motor symptoms developing during seizures. The presence or absence of focal and limbic features was determined for each patient. The associations of certain focal and limbic features with patient characteristics were assessed. Results Information was obtained on FS in 106 children. Various events were recorded at seizure commencement. Behavioral changes were observed in 35 children, changes in facial expression in 53, ocular symptoms in 78, and oral symptoms in 90. In terms of events during seizures, autonomic symptoms were recognized in 78, and convulsive motor symptoms were recognized in 68 children. Focal features were evident in 81 children; 38 children had two or more such features. Limbic features were observed in 44 children, 9 of whom had two or more such features. There was no significant relationship between any patient characteristic and the numbers of focal or limbic features. Significance The semiology of FS varied widely among children, and symptoms suggestive of focal onset were frequent. FS of focal onset may be more common than is generally thought.

Objective The aim of this study was to clarify the characteristics of paroxysmal nonepileptic events (PNEs) suspected as being epileptic seizures by families of children with epilepsy. Methods The video-EEG (vEEG) recordings of habitual paroxysmal events in children with epilepsy at Nagoya University Hospital between October 2006 and January 2016 were reviewed. Based on the doctor's suspicion before the vEEG, the PNEs were divided into two groups that included PNEs suspected as epileptic seizures and PNEs suspected as PNEs. PNEs in the former group were classified based on the suspected seizure type. Results Of 886 habitual paroxysmal events, vEEG confirmed that 83 events (68 children) were PNEs. The median age of the 68 children was 3.2 years. Concurrent epilepsies included focal epilepsies (n=33), infantile spasms (n=16), and other types (n=19). The most common types of PNEs were sleep myoclonus (n=11), followed by stereotypies (n=9), awake myoclonus (n=8), paroxysmal ocular deviations (PODs, n=8), and tonic posturing (n=8). Even after direct observation or video viewing, the doctors suspected epileptic seizures in all three of the PODs and two of the tonic posturing children. Before the vEEG, however, the accurate visual information led to the speculation that the four psychogenic and two sleep myoclonus events were all PNEs. Myoclonus, stereotypies, and head drops were often misdiagnosed as epileptic spasms, while PODs and tonic posturing were often misdiagnosed as focal seizures with motor components. Additionally, staring and motion arrest during a drowsy state were often misdiagnosed as focal dyscognitive seizures. Seven of eight patients with PODs had epileptic spasms that were concurrent with epileptic seizures. A diffuse cerebral lesion or reduced visual acuity was seen in seven patients with PODs. Conclusion We re-emphasize that vEEG is essential for accurate diagnosis and provides evidence for listing POD in the differential diagnosis of oculomotor paroxysmal events.

Background and objectives: Conventional electroencephalogram (cEEG) is a reliable predictor of outcome in term infants with hypoxic ischemic encephalopathy (HIE). Early therapeutic hypothermia initiated within 6 h after birth is a beneficial treatment in these infants. However, a classification system with reduced cEEG recording time to determine early intervention has not been reported. The aim of this study is to propose a new classification of depression on cEEG with reduced recording time in infants with HIE and to examine the correlation between the classification and short-term outcome. Patients and methods: We retrospectively investigated 20 term infants with HIE in whom cEEG was performed within 12 h after birth, and deaths or outcomes at 18 months of age were assessed. We determined grades 0–3 EEG depression in each 10-min epoch based on the most common EEG patterns of each 20 s epoch defined by our criteria. Results: Eighteen infants could be assessed by depression grade. The Spearman’s rank correlation coefficient Rs between the maximum depression grade in 10-min epochs and three-grade outcomes was 0.68 ( P = 0.002), and that between the minimum one and outcomes was 0.66 ( P = 0.003). The area under the receiver operating characteristic curve of the maximum and minimum depression grades for predicting abnormal outcome were 0.885 and 0.869, respectively. Conclusions: We demonstrated a new cEEG depression classification with a recording time of at least 10 min in term infants with HIE and a good correlation with short-term outcome.

Recently, amplitude-integrated EEG (aEEG) has been increasingly used and proved useful in neonatal intensive care units (NICU) for the management of neonatal seizures. It does not replace, but is supplementary to standard EEG. This article reviews some of findings obtained with standard EEGs, and tries to interpret them with recent findings in the field of basic science. Seizures mainly occur in active-REM sleep in neonates. This is in sharp contrast to those in older children and adults, in whom epileptic seizures occur mainly in NREM sleep. This may be explained by neurotransmitter effects on sleep mechanisms of the neonatal brain that are different from those of older individuals. When all clinical seizures have no electrical correlates, they are non-epileptic, but when the correlation between clinical seizures and frequent electrical discharges are inconsistent, they should rather be considered epileptic, reflecting progression of status epilepticus causing electro-clinical dissociation. Electro-clinical dissociation is not a characteristic of neonatal seizures per se, but a feature of prolonged status epilepticus in adults as well as children. It occurs when prolonged status epilepticus itself causes a progressively severe encephalopathy, or when status occurs in the presence of a severe underlying encephalopathy. In neonates without pre-existing brain damage, frequent seizures per se may cause mild depression characterized by the loss of high voltage slow patterns, an important constituent of slow wave sleep reflecting cortico-cortical connectivity. Mild depression only in the acute stage is not associated with neurological sequelae, but previously damaged brain may be more vulnerable than normal brain.

Mutations in GABRG2, which encodes the γ2 subunit of GABAA receptors, can cause both genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. Most GABRG2 truncating mutations associated with Dravet syndrome result in premature termination codons (PTCs) and are stably translated into mutant proteins with potential dominant-negative effects. This study involved search for mutations in candidate genes for Dravet syndrome, namely SCN1A, 2A, 1B, 2B, GABRA1, B2, and G2. A heterozygous nonsense mutation (c.118C>T, p.Q40X) in GABRG2 was identified in dizygotic twin girls with Dravet syndrome and their apparently healthy father. Electrophysiological studies with the reconstituted GABAA receptors in HEK cells showed reduced GABA-induced currents when mutated γ2 DNA was cotransfected with wild-type α1 and β2 subunits. In this case, immunohistochemistry using antibodies to the α1 and γ2 subunits of GABAA receptor showed granular staining in the soma. In addition, microinjection of mutated γ2 subunit cDNA into HEK cells severely inhibited intracellular trafficking of GABAA receptor subunits α1 and β2, and retention of these proteins in the endoplasmic reticulum. The mutated γ2 subunit-expressing neurons also showed impaired axonal transport of the α1 and β2 subunits. Our findings suggested that different phenotypes of epilepsy, e.g., GEFS+ and Dravet syndrome (which share similar abnormalities in causative genes) are likely due to impaired axonal transport associated with the dominant-negative effects of GABRG2.

Kohka Public Hospital(KPH)focuses primarily on the treatment of acute diseases. However, as the only general hospital in the medical district and established under the National Health Insurance, KPH has a mandate in comprehensive medical care. With the aim of becoming a hospital that can cope with the anticipated super-aging society, a meeting was started to raise staff awareness of home care medicine. Senior managers were placed in each team along with staff with no involvement on the issue. Initially, a SWOT analysis was conducted to understand the current status. Views raised in the meetings will be summarized, and consequent measures will be announced both internally and externally as part of the Strengths Dissemination Project. Interest in home care medicine at acute medical care hospitals is undeniably low, but the reality is that many do not know how to get involved due to the lack of exposure. It is unquestionable that the need for home care medicine and regional cooperation will rise in our nation. We must direct the attention of health care providers there and start discussions.

The KSTAR (Korea Superconducting Tokamak Advanced Researc pursued to develop key technologies for superconducting tokamak operation and to contribute to a few research items for ITER relevant issue...

IFMIF-EVEDA progresses in Japan as one of the EU-Japan Broader Approach Activities. The research is performed to decide whether or not IFMIF is constructed after some uncertainties included in the ...

The aim of this study is to clarify the differences of EEG activities according to the presence or absence of disorganized patterns using amplitude spectral analysis. We compared EEGs of 17 preterm infants with disorganized patterns with those of 34 matched controls. Amplitude was defined as a square root of EEG power analyzed by fast Fourier transform algorithm, and was calculated in the 9 frequency bands. Six EEG segments of 10 s were collected from the part of EEG with continuous high voltage slow waves in the absence of artifacts. The results were separately evaluated according to the post-conceptional age at EEG recordings. In patients with disorganized patterns, reduced amplitude of delta waves in the central areas and increased amplitude of beta waves in the occipital areas were observed at 29-30 weeks of post-conceptional age. The results were almost similar at 31-32 weeks of post-conceptional age. Amplitude in theta or alpha frequency bands was not different between those with and without disorganized patterns either at 29-30 or 31-32 weeks of post-conceptional age. Amplitude spectral analyses will contribute to objective evaluation of disorganized patterns.

Novel derivatives of polythiophenes and their phenylene copolymers were synthesized by introducing chiral alkoxy carbonyl substituents into their side chains. Most of these polymers showed enantiotropic main-chain liquid crystallinity at high temperatures and across a wide range of elevated temperatures. They exhibited fluorescence that ranged in color from blue to orange in chloroform solutions and from blue to red in films. The bisignate Cotton effect was observed in the π–π* transition region of the circular dichroism (CD) spectra of the polymers consisting of three aromatic rings in the repeating unit, which was attributed to the formation of a polymer assembly with an interchain helically π-stacked structure. The dependence of UV–vis absorption and CD spectra on the concentration and temperature of the solution indicated that the polymer assembly exists, even in dilute concentration at room temperature, but it dissociated into single polymers at high temperatures. Additionally, the polymer films exhi...

In IFMIF/EVEDA, tasks for lithium target system consist of 5 validation tasks (LF1-5) and a design task (LF6), and are shared by Japan and Europe. Japan is covering LF1, LF2, LF4, LF5 and LF6, and JAEA as an Implementing Agency is organizing these tasks. Japanese universities contribute these tasks. The purpose of LF1 task is to construct and operate EVEDA Li test loop (ELTL) with diagnostics and purification systems for the validation of Li target facility. ELTL will be constructed at the end of February in 2011 and the operation will be started at the summer in 2011. LF2 and LF4 are basic research for the diagnostics and purification system, respectively. And LF2 and LF4 have also contributed the construction of the ELTL (LF1). LF5 is focusing on the remote handling for the replacement of the target assembly. Major deliverable of LF6 is finally engineering design report, which is assembled with all validation tasks, and this activity will be gradually enhanced to the end of IFMIF/EVEDA.

The Engineering Validation and Engineering Design Activities (EVEDA) of the International Fusion Materials Irradiation Facility (IFMIF) are in progress under the Broader Approach (BA) Agreement. As a part of this engineering design, we carried out thermo-structural analysis of the back plate in the IFMIF target. In this analysis, the target assembly of the integrated back plate option was modeled with the nuclear heating to simulate the IFMIF normal operation. The thermal boundary conditions of a mechanical joint between the target assembly and the beam duct were employed as the calculation parameters. The calculated results showed the effects of these parameters on thermal stress and deformation were not large. The maximum von Mises stresses occurred at the back plate center and these values, 204–218 MPa were lower than half of the yield strength of F82H (455 MPa). The maximum displacement was about 0.3 mm which occurred at the back plate center also.

IFMIF is an accelerator-based intense neutron source for testing candidate materials for fusion reactors. The Engineering Validation and Engineering Design Activities (EVEDA) of IFMIF are in progress under the Broader Approach Agreement. In the EVEDA Li test loop, two types of target assemblies, “an integrated type target assembly without a back plate”, made of SUS316L, and “a target assembly with replaceable bayonet back plate”, made of F82H steel, will be evaluated. For these target assemblies, thermal stresses were evaluated using the ABAQUS code. As the permitted stress, the values of yield strengths at 300 °C were used. In the case of the integrated target assembly, the maximum thermal stress was below the allowed stress (164 MPa). However, in the case of the target assembly with the bayonet back plate, thermal insulation around the back plate should be necessary to reduce the thermal stress below the allowed value (455 MPa).

Objective To investigate the accuracy of conventional electroencephalograms (cEEGs) and amplitude-integrated EEGs (aEEGs) in the evaluation of brain maturation in normal pre-term infants. In addition, extrauterine acceleration of brain maturation was investigated. Methods A total of 129 EEGs recorded between 27 and 37 weeks of postconceptional age (PCA) from 37 clinically stable pre-term infants were analysed. One expert investigator blindly estimated PCA using cEEG and total cerebral function monitoring (CFM) score on aEEG. The estimated PCA (ePCA) on aEEG was calculated from a regression equation. Results The linear regression analysis showed a significant correlation between chronological PCA (cPCA) and ePCA on cEEG and between cPCA and total CFM score on aEEG. The estimation gap was smaller on cEEG, which was between −2 and +2 weeks in 96.9%. No significant correlation was observed between postnatal age and the estimation gap on cEEG or aEEG. Conclusions Estimated brain maturation was well correlated with cPCA on cEEG and aEEG. However, the evaluation of brain maturation was much more accurate on cEEG than aEEG. Extrauterine acceleration of brain maturation was not observed on either cEEG or aEEG. Significance cEEG and aEEG will be valuable tools for evaluation of brain maturation in pre-term infants.