bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and characterisation of NKp44‐based chimeric antigen receptors that confer T cells with NK cell‐like specificity
Authors: Kasahara Yasushi , Shin Chansu , Kubo Nobuhiro , Mihara Keichiro , Iwabuchi Haruko , Takachi Takayuki , Imamura Masaru , Saitoh Akihiko , Imai Chihaya 
Published: July 2020

AbstractObjectivesOne of the reasons as to why chimeric antigen receptors (CAR)‐T cell therapy for malignancies other than CD19‐ or BCMA‐positive tumors has yet to produce remarkable progress is the paucity of targetable antigens. NKp44 is only expressed by activated natural killer cells and detects a variety of transformed cells, while it reportedly does not react with normal tissues. The aim of this study is to develop CAR‐T cell that can target multiple types of tumor cells.MethodsWe created a series of novel CAR constructs in first‐generation (1G) and second‐generation (2G) CAR format with the extracellular immunoglobulin‐like domain of NKp44 (NKp44‐CAR).ResultsTransduction of the best 1G construct into human primary T cells led to specific cytotoxic effects and cytokine secretion upon encountering multiple types of neoplastic cells including AML, T‐ALL and childhood solid tumors. Replacement of the extracellular hinge domain of NKp44 with that of CD8α resulted in diminished CAR function. The 1G NKp44‐CAR‐T cells exhibited significantly better tumor control in long‐term co‐culture assays compared with activated NK cells, as well as with NK cells transduced with identical NKp44‐CAR. T cells transduced with the best 2G‐CAR construct with 4‐1BB co‐stimulatory domain proliferated at significantly higher levels upon single antigen exposure and showed significantly better tumor control compared with the 1G‐CAR and 2G‐CAR with CD28 co‐stimulatory domain.ConclusionsNKp44‐based CAR endows T cells with NK cell‐like anti‐tumor specificity. The CAR gene created in this study will be useful for the development of novel gene‐modified T‐cell immunotherapy.
Novel pathogenic mutations identified in the first Chinese pedigree of complete C6 deficiency
Authors: Li Philip H , Wong William WY , Leung Evelyn NY , Lau Chak‐sing , Au Elaine 
Published: July 2020

AbstractObjectivesComplete C6 deficiency (C6Q0) is a rare primary immunodeficiency leading to increased susceptibility to recurrent Neisseria infections. Patients with C6Q0 have mostly been reported in individuals of African ancestry previously, but never in Chinese. We identify the first Chinese patients with C6Q0 through family screening of an index case presenting with recurrent Neisseria meningitis with septicaemia and performed extensive clinical, serological and genetic investigations.MethodsTwo variants in C6 were identified by next‐generation sequencing and confirmed by Sanger sequencing in an index case of C6Q0. Immunological investigations, complement haemolytic assays (CH50/AH50), C6 gene sequencing and quantification of serum C6 levels were performed for all available members of his nonconsanguineous family.ResultsThree C6Q0 patients were identified with near‐absent C6 levels, absent CH50/AH50 activity and compound heterozygous for two nonsense mutations in the C6 gene: NM_000065.4:c.1786C>T (p.Arg596Ter) and NM_000065.4:c.1816C>T (p.Arg606Ter). Neither mutations have been reported to be pathogenic previously. Two other family members who were heterozygous for either p.Arg596Ter or and p.Arg606Ter had intermediate C6 levels but preserved CH50/AH50 activity. These two loss‐of‐function mutations showed a strong genotype–phenotype correlation in C6 levels.ConclusionsWe report on two compound heterozygous mutations in C6, p.Arg596Ter and p.Arg606Ter inherited in three patients of the first recorded Chinese pedigree of C6Q0. Neither mutations had been reported to be pathogenic previously. We demonstrate that heterozygous family members with subtotal C6 levels had preserved complement haemolytic function and demonstrate a threshold effect of C6 protein level.
Observation of 1D−1S forbidden optical emission of atomic oxygen in atmospheric‐pressure N2/O2 plasma jet
Authors: Sasaki Koichi , Nishiyama Shusuke , Shirai Naoki 
Published: July 2020

AbstractWe observed green optical emission from an atmospheric‐pressure N2/O2 plasma jet. The green optical emission was composed of a line emission at λ = 557.71 ± 0.03 nm and a broadband component at 530 ≤ λ ≤ 560 nm. The line emission was assigned to the 1D−1S forbidden transition of atomic oxygen, whereas the broadband emission was due to the formation of O(1S)N2 excimer. We measured the absolute densities of O(1S) and O(1S)N2 using a spectrograph with the absolute sensitivity calibration, and we discussed the kinetics in the green plasma jet on the basis of the absolute O(1S) and O(1S)N2 densities. According to the rate coefficients and the transition probabilities reported in literature, the present experimental results are explained if the densities of and O(3P) are 9 × 1013 and 3 × 1013cm−3, respectively.
Hybrid genetic and shuffled frog‐leaping algorithm for neural network structure optimization and learning model to predict free spectrum in cognitive radio
Authors: Supraja P. , Babu S. , Gayathri V.M. , Divya G. 
Published: July 2020

SummaryCognitive radio, which is called an intelligent radio, will dynamically access the available spectrum. This mechanism will bring revolt in wireless communication, which lightens the spectrum utilization problem. Machine learning plays a vital role in every technology. Here, in cognitive radio, it helps train the model to predict the free spectrum. The cognitive clients utilize range‐detecting procedures to detect the groups previously transmitting on them to stay away from impact with the authorized clients that prompts deferral and moderates more vitality. To decrease postponement and vitality utilization and to foresee the future use of channels, range expectation procedures are utilized. Spectrum prediction is used to anticipate the future channel status in light of gathered chronicled information; here, to take care of the issue, the neural system‐based spectrum prediction utilizes a backpropagation training model that has been proposed. To enhance the structure of the neural system and to decrease the forceful weight auxiliary pattern, genetic algorithm (GA) along with the hybrid combination of shuffled frog‐leaping algorithm (SFLA) is proposed. Here, GA has been utilized to abstain from catching nearby ideal solutions. The selection, crossover, and mutation functions were performed to build the haphazardness, which stretches out the populace unite to the set that contains the global ideal solution. SFLA has been proposed for structure improvement; the paired structure has been recommended to demonstrate the memes with the motivation behind building up a subaccumulation with lesser measurements than that of the original group where recognizing affectability and precision would be versatile with that of the primary status. Simulation results show the GA‐SFLA‐based hybrid algorithm that is used has increased the results of getting the best weights by improving the system; additionally, the proposed conspire results show high forecast accuracy.
Interface Effect of Ru‐MoS2 Nanoflowers on Lignin Substrate for Enhanced Hydrogen Evolution Activity
Authors: Xu Yeqing , Jiang Xingxing , Shao Gonglei , Xiang Haiyan , Si Sisi , Li Xing , Hu Travis Shihao , Hong Guo , Dong Shengyi , Li Huimin , Feng Yexin , Liu Song 
Published: July 2020

The catalytic performance of Molybdenum disulfide (MoS2) has been still far from that of Pt‐based catalysts for inadequate active sites and sluggish electron transfer kinetics. Through engineering the interface between MoS2‐based materials and supported substrates, hybrid Ru‐doped MoS2 on carbonized lignin (CL) is designed and prepared as efficient catalyst for hydrogen evolution reaction (HER). The CL substrate not only facilitates the growth of MoS2 nanoflowers, but also promotes the electron transfer. Ru doping increases active sites greatly for HER. The hybrid catalyst achieves a low onset overpotential of 25 mV and a low Tafel slope of 46 mV dec−1. The favorable HER activity ascribes to the interfacial interaction between MoS2 and CL. Density functional theory calculations further confirm the improved HER performance with doped Ru atoms. This study presents a prototype application to design electrocatalysts with enhanced carrier mobility and high‐density active sites based on interface effect.
Clinical and genetic characteristics of patients with Doose syndrome
Authors: Hinokuma Nodoka , Nakashima Mitsuko , Asai Hideyuki , Nakamura Kazuyuki , Akaboshi Shinjiro , Fukuoka Masataka , Togawa Masami , Oana Shingo , Ohno Koyo , Kasai Mariko , Ogawa Chikako , Yamamoto Kazuna , Okumiya Kiyohito , Chong Pin Fee , Kira Ryutaro , Uchino Shumpei , Fukuyama Tetsuhiro , Shinagawa Tomoe , Miyata Yohane , Abe Yuichi , Hojo Akira , Kobayashi Kozue , Maegaki Yoshihiro , Ishikawa Nobutsune , Ikeda Hiroko , Amamoto Masano , Mizuguchi Takeshi , Iwama Kazuhiro , Itai Toshiyuki , Miyatake Satoko , Saitsu Hirotomo , Matsumoto Naomichi , Kato Mitsuhiro 
Published: July 2020

AbstractObjectiveTo elucidate the genetic background and genotype‐phenotype correlations for epilepsy with myoclonic‐atonic seizures, also known as myoclonic‐astatic epilepsy (MAE) or Doose syndrome.MethodsWe collected clinical information and blood samples from 29 patients with MAE. We performed whole‐exome sequencing for all except one MAE case in whom custom capture sequencing identified a variant.ResultsWe newly identified four variants: SLC6A1 and HNRNPU missense variants and microdeletions at 2q24.2 involving SCN1A and Xp22.31 involving STS. Febrile seizures preceded epileptic or afebrile seizures in four patients, of which two patients had gene variants. Myoclonic‐atonic seizures occurred at onset in four patients, of which two had variants, and during the course of disease in three patients. Variants were more commonly identified in patients with a developmental delay or intellectual disability (DD/ID), but genetic status was not associated with the severity of DD/ID. Attention‐deficit/hyperactivity disorder and autistic spectrum disorder were less frequently observed in patients with variants than in those with unknown etiology.SignificanceMAE patients had genetic heterogeneity, and HNRNPU and STS emerged as possible candidate causative genes. Febrile seizures prior to epileptic seizures and myoclonic‐atonic seizure at onset indicate a genetic predisposition to MAE. Comorbid conditions were not related to genetic predisposition to MAE.
Prelacrimal approach vs conventional surgery for inverted papilloma in the maxillary sinus
Authors: Nakayama Tsuguhisa , Tsunemi Yasuhiro , Kuboki Akihito , Asaka Daiya , Okushi Tetsushi , Tsukidate Toshiharu , Otori Nobuyoshi , Kojima Hiromi , Haruna Shin‐ichi 
Published: July 2020

AbstractBackgroundThe prelacrimal approach, termed endoscopic modified medial maxillectomy (EMMM), has recently been applied for treatment of inverted papilloma (IP) in the maxillary sinus. EMMM provides wider access to the maxillary sinus while preserving the inferior turbinate and nasolacrimal duct.MethodsWe reviewed patients with IP in the maxillary sinus to compare the surgical results obtained by conventional surgery (ie, endoscopic maxillary sinus antrostomy or in combination with the Caldwell‐Luc approach) with those obtained by EMMM.ResultsAll patients had a T3 on the Krouse staging system, and the average follow‐up time was 46.0 months. Of the 18 patients in the conventional group, recurrence was seen in 3 patients (16.6%). No recurrence was seen in the 27 patients who showed preservation of the inferior turbinate and nasolacrimal duct, and no complications occurred in the EMMM group.ConclusionsEMMM is an effective surgical approach that reduces recurrence with fewer complications.
Drugging “undruggable” genes for cancer treatment: Are we making progress?
Authors: Duffy Michael J. , Crown John 
Published: July 2020

AbstractRAS, TP53 (p53) and MYC are among the most frequently altered driver genes in cancer. Thus, RAS is the most frequently mutated oncogene, MYC the most frequently amplified gene and TP53 the most frequently mutated tumor suppressor gene and overall the most frequently mutated gene in cancer. Theoretically, therefore, these genes are highly attractive targets for cancer treatment. However, as the protein products of each of these genes lack an accessible hydrophobic pocket into which low molecular weight compounds might bind with high affinity, they have proved difficult to target and have traditionally been referred to as “undruggable.” Despite this branding, several low molecular weight compounds targeting each of these proteins have recently been reported to have anticancer activity in preclinical models. Indeed, several drugs inhibiting mutant KRAS, MYC overexpression or reactivating mutant p53 have undergone or are currently undergoing clinical trials. For targeting mutant KRAS and reactivating mutant p53, trials have progressed to a Phase III stage, that is, the mutant‐p53 reactivating drug, APR‐246 is currently being investigated in patients with myelodysplastic syndrome (MDS) and the RAS inhibitor, rigosertib is also undergoing evaluation in patients with MDS. Although there appears to be no directly acting MYC inhibitor currently being tested in a clinical trial, an anti‐MYC compound, known as OmoMYC has been extensively validated in multiple preclinical models and is being developed for clinical evaluation. Based on current evidence, the traditional perception of RAS, p53 and MYC as being “undruggable” would appear to be coming to an end.
Vulvar intraepithelial neoplasia: Incidence and long‐term risk of vulvar squamous cell carcinoma
Authors: Thuijs Nikki B. , van Beurden Marc , Bruggink Annette H. , Steenbergen Renske D. M. , Berkhof Johannes , Bleeker Maaike C. G. 
Published: July 2020

AbstractThe risk of vulvar squamous cell carcinoma (VSCC) in patients with high‐grade vulvar intraepithelial neoplasia (VIN) is considered lower in high‐grade squamous intraepithelial lesion (HSIL) compared to differentiated VIN (dVIN), but studies are limited. Our study investigated both the incidence of high‐grade VIN and the cumulative incidence of VSCC in patients with HSIL and dVIN separately. A database of women diagnosed with high‐grade VIN between 1991 and 2011 was constructed with data from the Dutch Pathology Registry (PALGA). The European standardized incidence rate (ESR) and VSCC risk were calculated, stratified for HSIL and dVIN. The effects of type of VIN (HSIL vs dVIN), age and lichen sclerosis (LS) were estimated by Cox regression. In total, 1148 patients were diagnosed with high‐grade VIN between 1991 and 2011. Between 1991‐1995 and 2006‐2011, the ESR of HSIL increased from 2.39 (per 100 000 woman‐years) to 3.26 and the ESR of dVIN increased from 0.02 to 0.08. The 10‐year cumulative VSCC risk was 10.3%; 9.7% for HSIL and 50.0% for dVIN (log rank P < .001). Type of VIN, age and presence of LS were independent risk factors for progression to VSCC, with hazard ratios of 3.0 (95% confidence interval [CI] 1.3‐7.1), 2.3 (95% CI 1.5‐3.4) and 3.1 (95% CI 1.8‐5.3), respectively. The incidence of high‐grade VIN is rising. Because of the high cancer risk in patients with dVIN, better identification and timely recognition are urgently needed.
Survival impact of adjuvant chemotherapy in patients with stage IIA colon cancer: Analysis of the National Cancer Database
Authors: Achilli Pietro , Crippa Jacopo , Grass Fabian , Mathis Kellie L. , D'Angelo Anne‐Lise D. , Abd El Aziz Mohamed A. , Day Courtney N. , Harmsen William S. , Larson David W. 
Published: July 2020

AbstractUtility of adjuvant chemotherapy for stage II cancer remains a matter of debate. Clinical guidelines suggest adjuvant chemotherapy for stage II tumors with high‐risk features, in particular T4 tumors. However, limited consensus exists regarding the importance of other high‐risk features (lymphovascular or perineural invasion, microsatellite instability). Our study aimed to investigate the impact of adjuvant chemotherapy for stage IIA (T3N0) colon cancer patients. Patients who underwent colectomy for stage IIA colon adenocarcinoma (2010‐2015) were identified in the National Cancer Database (NCDB) and divided in two groups based on receipt of adjuvant chemotherapy vs observation. Inverse probability of treatment weighting (IPTW)‐adjusted Kaplan‐Meier and Cox proportional hazards regression analyses were performed to compare overall survival between the two groups. Subgroup analysis of patients with specific high‐risk features LVI, PNI and MSI was performed. Among 46 688 surgical patients with stage IIA colon adenocarcinoma 5937 (12.7%) received adjuvant chemotherapy, while 40 751 (87.3%) were observed. Five‐year IPTW‐adjusted survival was higher in the adjuvant chemotherapy group (79.7% [95% CI 79.1, 80.2]) compared to the observation group (70.3% [95% CI 69.7, 70.9]). Patients with high‐risk pathological features showed an estimated 5‐year survival benefit of 11.3% (78.2% [95% CI 77.4, 79.1] vs 66.9% [95% CI 65.9, 67.8]) when treated with adjuvant chemotherapy. This NCDB analysis revealed a survival benefit for patients with stage IIA colon adenocarcinoma and high‐risk features that were treated with adjuvant chemotherapy.
Testicular seminoma with a progressing pulmonary nodule and mediastinal lymphadenopathy without retroperitoneal metastasis
Authors: Sano Yuta , Fujiwara Motohiro , Yuasa Takeshi , Komai Yoshinobu , Yamamoto Tatsuya , Kohno Atsushi , Nakao Masayuki , Inamura Kentaro , Yonese Junji 
Published: July 2020

IntroductionTesticular germ cell cancer has a relatively good prognosis even if visceral and/or lymph node metastases are present thanks to chemotherapy. Yet chemotherapy can lead to various adverse events. Therefore, it is crucial to distinguish whether a suspected metastatic disease is metastasis or not.Case presentationA 33‐year‐old male visited our hospital to receive subsequent therapy for suspected recurrent seminoma with a progressing pulmonary nodule and mediastinal lymphadenopathy after orchiectomy. The pathological diagnosis of needle aspiration and resected specimen of the several lesions was consistent with epithelioid cell granuloma without caseous necrosis. Based on these findings, the lung and mediastinal lymph node lesions were diagnosed as sarcoidosis.ConclusionIn cases where the simultaneous occurrence of other benign or malignant diseases is suspected, pathological confirmation is necessary for appropriate decision‐making.
Possible abscopal effect after discontinuation of nivolumab in metastatic renal cell carcinoma
Authors: Nakajima Nobuyuki , Kano Tatsuo , Oda Kazuya , Uchida Takato , Otaki Tatsuya , Nagao Kentaro , Shimizu Yuki , Kawakami Masayoshi , Kim Hakushi , Nitta Masahiro , Hasegawa Masanori , Kawamura Yoshiaki , Miyajima Akira 
Published: July 2020

IntroductionRenal cell carcinoma has been considered radioresistant. Recently, several studies have reported the efficacy of combination therapy using radiotherapy and immune checkpoint inhibitors.Case presentationIn 1999, a 56‐year‐old woman underwent left nephrectomy (clear cell carcinoma, pT1bN0M0). Seventeen years postoperatively, recurrence in the left lung hilum was observed. Despite administration of three molecular target drugs, all treatments were terminated due to adverse events. Nivolumab was initiated in December 2016. In August 2017, subcutaneous and lung metastases were observed. Moreover in January 2018, right renal metastasis was noted. After 22 cycles of nivolumab treatment, metastasis in the iliac bone was observed, and the patient was subjected to conventional palliative external beam radiation therapy. Five months after radiotherapy, there was significant reduction in multiple metastases. Here, we reported the case presenting with possible abscopal effect.ConclusionRadiotherapy combined with immune checkpoint inhibitors may induce systemic effects against metastatic renal carcinoma.
Optical coherence tomography angiography for mapping cerebral microvasculature based on normalized differentiation analysis
Authors: Zhu Jiang , Liu Jianting , Zhu Lianqing , Wang Chongyang , Fan Fan , Yang Qiang , Zhang Fan 
Published: July 2020

AbstractOptical coherence tomography angiography (OCTA) is a label‐free, noninvasive biomedical imaging modality for mapping microvascular networks and quantifying blood flow velocities in vivo. Simple computation and fast processing are critical for the OCTA in some applications. Herein, we report on a normalized differentiation method for mapping cerebral microvasculature with the advantages of simple analysis and high image quality, benefitting from computation of differentiation and characteristics of normalization. Normalized differentiation values are validated to have a nearly linear relationship with flow velocities in a range using a flow phantom. The measurements in a rat cerebral cortex show that the OCTA based on the normalized differentiation analysis can generate microvascular images with high quality and monitor spatiotemporal dynamics of blood flow with simple computation and fast processing before and after localized ischemia induced by arterial occlusion.
Poly(butyl methacrylate)‐grafted alginate/Fe3O4 nanocomposite: Synthesis and its application for removal of dyes
Authors: Alzahrani Eman , Abo‐Dief Hala M. , Algethami Faouzia 
Published: July 2020

AbstractThis study involved the utilization of a free radical‐graft copolymerization reaction for the development of a novel adsorbent, namely, poly(butyl methacrylate)‐grafted alginate/Fe3O4 nanocomposite (PBMA‐gft‐Alg/Fe3O4). Transmission electron microscopy, scanning electron microscopy, energy‐dispersive X‐ray analysis, X‐ray diffraction patterns analysis, and Fourier transform infrared spectroscopy (FT‐IR) were carried out for the characterization of Fe3O4 NPs and PBMA‐gft‐Alg/Fe3O4 nanocomposites. The capability of nanocomposites and nanoparticles to adsorb dyes such as MG and MB, resulting in their removal from aqueous media, was evaluated under different conditions such as pH, temperature, contact time, and dose of adsorbent. Optimum parameters for adsorption of dyes were found to be pH of 10, 50°C, contact time of 180 min, and 0.2 g of adsorbent. Efficiency of the PBMA‐gft‐Alg/Fe3O4 nanocomposite was found to be significantly greater than that of Fe3O4 NPs for eliminating the desired dye. Langmuir, Freundlich, Sips, and Temkin models were used for testing the experimental data. Freundlich model was the one that best described the adsorption.