bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next‐generation sequencing of tissue and circulating tumor DNA: Resistance mechanisms to EGFR targeted therapy in a cohort of patients with advanced non‐small cell lung cancer
Authors: Zhang Yujun , Xiong Liwen , Xie Fangfang , Zheng Xiaoxuan , Li Ying , Zhu Lei , Sun Jiayuan 
Published: June 2021

AbstractBackgroundEpidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) has been considered as an effective treatment in epidermal growth factor receptor‐mutant (EGFR‐mutant) advanced non‐small cell lung cancer (NSCLC). However, most patients develop acquired resistance eventually. Here, we compared and analyzed the genetic alterations between tissue assay and circulating tumor DNA (ctDNA) and further explored the resistance mechanisms after EGFR‐TKI treatment.Methods and MaterialsAmplification refractory mutation system‐polymerase chain reaction (ARMS‐PCR), Cobas® ARMS‐PCR and next‐generation sequencing (NGS) were performed on tissue samples after pathological diagnosis. Digital droplet PCR (ddPCR) and NGS were performed on plasma samples. The association between genetic alterations and clinical outcomes was analyzed retrospectively.ResultsThirty‐seven patients were included. The success rate of re‐biopsy was 91.89% (34/37). The total detection rate of EGFR T790M was 62.16% (23/37) and the consistency between tissue and ctDNA was 78.26% (18/23). Thirty‐four patients were analyzed retrospectively. For tissue re‐biopsy, 24 patients harbored concomitant mutations. Moreover, tissue re‐biopsy at resistance showed 21 patients (21/34, 61.76%) had the concomitant somatic mutation. The three most frequent concomitant mutations were TP53 (18/34, 52.94%), MET (4/34, 11.76%), and PIK3CA (4/34, 11.76%). Meanwhile, 21 patients (21/34, 61.76%) with EGFR T790M mutation. Progression‐free survival (PFS) and overall survival (OS) were better in patients with T790M mutation (p = 0.010 and p = 0.017) or third‐generation EGFR‐TKI treatment (p < 0.0001 and p = 0.073). Interestingly, concomitant genetic alterations were significantly associated with a worse prognosis for patients with EGFR T790M mutation receiving third‐generation EGFR‐TKIs (p = 0.037).ConclusionsMulti‐platforms are feasible and highly consistent for re‐biopsy after EGFR‐TKI resistance. Concomitant genetic alterations may be associated with a poor prognosis for patients with EGFR T790M mutation after third‐generation EGFR‐TKIs.
Impact of bromodomain‐containing protein 4 (BRD4) and intestine‐specific homeobox (ISX) expression on the prognosis of patients with hepatocellular carcinoma' for better clarity
Authors: Chuang Kai‐Ting , Wang Shen‐Nien , Hsu Shih‐Hsien , Wang Li‐Ting 
Published: June 2021

AbstractEpigenetic regulation is important for cancer tumor metastasis and progression, including lung and liver cancer. However, the mechanism of epigenetic regulation in liver cancer leaves much to be discussed. According to a previous study, p300/CBP‐associated factor (PCAF) mediated epithelial–mesenchymal transition (EMT) and promotes cancer metastasis by recruiting intestine‐specific homeobox (ISX) and bromodomain‐containing protein 4 (BRD4) in lung cancer. To figure out whether the three genes are also expressed in patients with hepatocellular carcinoma (HCC) or not, and their correlation with patients’ outcome, BRD4, PCAF, and ISX messenger RNA (mRNA) expression levels in 377 patients with HCC were investigated using quantitative polymerase chain reaction and confocal fluorescence imaging. The correlation of the gene expression (PCAF, ISX, and BRD4) in liver cancer is also being investigated. Here, we show that the mRNA expression of PCAF, BRD4, and ISX in 377 paired specimens from patients with HCC, and the adjacent normal tissues exhibited a tumor‐specific expression pattern, highly correlated with disease pathogenesis, patient survival time, progression stage, and poor prognosis. The results show that ISX and BRD4 can potentially be a target for improving the survival rate.
The origin of the A/G single nucleotide polymorphism of starch synthase IIa in rice and its relation to gelatinization temperature
Authors: Song Jiling , Hu Yaqi , Deng Guofu , Dai Gaoxing , Bao Jinsong 
Published: June 2021

AbstractBackground and objectivesThe domestication of cultivated rice (Oryza sativa L.) has long been studied, and many agronomically relevant genes have undergone artificial selection. Among them, the selection history of the starch synthase IIa (SSIIa) has not been fully discovered. The SSIIa is a genetic factor that controls the gelatinization temperature (GT) of rice starch, an important parameter for rice cooking quality.FindingsThe A/GC haplotype in SSIIa only presented in the japonica subspecies. GT was found to be strongly associated with SNPs in SSIIa, that is, G/GC haplotype rice had high or intermediate GT, while G/TT or A/GC haplotype rice had low GT. The nucleotide diversity (π) in japonica was much lower than that of indica and wild rice, indicating that a population bottleneck was experienced during japonica rice domestication. A possible positive selection on the A SNP of SSIIa in temperate japonica rice favoring low GT starch synthesis was proposed.ConclusionsThe evolution of SSIIa in the japonica rice was possibly under positive selection favoring low GT rice, which requires low energy input for cooking. The A SNP of SSIIa is only present in the japonica rice, which might be derived from a recent mutation. There are two ways, A/GC and G/TT, to make japonica rice with low GT, explaining why all the temperate japonica rice cultivars have low GT.Significance and noveltyFindings of this study provide an understanding of why all the temperate japonica rice have low GT starch, because there are two ways to make it GT low.
Anal tuberculosis presenting as refractory perianal abscess
Authors: Sasahara Kotaro , Kitahama Keiichiro , Aiko Satoshi , Namkoong Ho 
Published: June 2021

AbstractAlthough most cases occur in immunocompromised individuals, anal tuberculosis can occur in the absence of HIV infection. Anal tuberculosis should be considered in the differential diagnosis of chronic or recurrent anal fistulas.
Pore‐forming process in dehydration of metakaolin‐based geopolymer
Authors: Yang Yaru , Le Thi‐Chau‐Duyen , Kudo Isamu , Do Thi‐Mai‐Dung , Niihara Koichi , Suematsu Hisayuki , Thorogood Gordon 
Published: June 2021

AbstractThe geopolymer catalyst supports utilized in the nuclear waste containers for the Fukushima Daiichi Nuclear Power Station will be required to have high porosity and durability. This work presents the synthesis of a potassium and metakaolin‐based geopolymer and its performance upon dehydration. During water content measurements of the samples, it was seen that in the demolded samples, the water content quickly decreased to less than 30% within 7 days, while the samples that had the cap removed from the container retained more than 50% of the water after 28 days. The pore size distribution of the samples that were post‐cured at different temperatures up to 28 days did not vary greatly with respect to the average pore size. We can infer that structurally stable pores were formed in the first 4 days and were not affected by the post‐curing rate, which may be related to rheological properties and the drainage path of water or hydrogen gas during post‐curing.
Production of surfactin by Bacillus subtilis LAMI005 and evaluation of its potential as tensoactive and emulsifier
Authors: de França Ítalo Waldimiro Lima , de Oliveira Darlane Wellen Freitas , Giro Maria Estela Aparecida , Melo Vânia Maria Maciel , Gonçalves Luciana Rocha Barros 
Published: June 2021

AbstractIn this study, the kinetic of lipopeptide biosurfactant production by Bacillus subtilis LAMI005 and its tensoactive and emulsifier properties were evaluated. The influence of the concentrations of nitrogen ((NH4)2SO4) and carbon source (glucose and fructose) on biosurfactant production, using a mineral medium, were evaluated. A production of about 930 mg · L−1 of surfactin was observed for mineral medium supplied with total reducing sugars (16.55 g · L−1) and (NH4)2SO4 (1 g · L−1) as carbon and nitrogen sources, respectively. The crude biosurfactant exhibited its potential as tensoactive, presenting the capability to reach surface tension of about 28 mN ⋅ m−1 for water and exhibiting low CMC (~14–20 mg · L−1). The analysis of emulsifying activity showed a greater stability of emulsion formed in motor oil (3.5 U), soybean oil (2.0 U), and biodiesel (1.5 U). The emulsion formulated on motor oil remained stable for more than 200 h, which was explained by its average drop diameter (~0–10 μm). The surface‐active properties of surfactin did not seem to be affected by different NaCl concentrations, which may promote its applicability in high salt environments, such as oil spills in marine areas.
Syndiospecific Polymerization of Styrene Catalyzed by Half‐titanocenes Containing Monodentate Anionic Nitrogen Ligands
Authors: Pan Dan‐Dan , Fan Ke‐Xin , Zhang Shu , Wu Yi‐Xian 
Published: June 2021

Main observation and conclusionStyrene polymerization catalyzed by the half‐titanocenes CpTiCl2[1,3‐R2(CH2N)2C=N] (6b: R= 2,6‐Me2C6H3, T4: R = 2,4,6‐Me3C6H2; T5: R = 2,6‐iPr2C6H3) was carried out in the presence of methylaluminoxane (MAO). Compared to the styrene conversion (31%) and syndiospecific index (45%) using reported 6b as precatalyst, T5 bearing ligand with isopropyl substitutes on the N‐aryl‐rings exhibits much higher styrene conversion (61%) and syndiospecific index (99%), indicating that the catalytic behavior could be improved obviously by the introduction of electronic donating and steric bulky substituents. One N atom in imidazolin‐2‐iminato ligand was replaced by O atom, affording half‐titanocenes CpTiCl2[3‐C6H5(CH2N)(CH2O)C=N (T1) and CpTiCl2[2,6‐Me2(C6H3O)(NiPr2)C=N] (T2). Compared to 6b, both higher styrene conversion and syndiospecific index are afforded by using half‐titanocene T1 containing 2‐imino‐3‐phenyloxazolidine ligand. All the results illustrate that both the chemical structure and the nature of substituents of the ligand have obvious influence on the styrene conversion and syndiospecific index in the polymerization of styrene. All the resulting syndiotactic polystyrenes (sPSs) are highly syndiospecific (rrr > 99%). Correspondingly, the sPS prepared using T5/MAO catalytic system exhibits high melting point and narrow molecular weight distribution. The results might show new light on designing more efficient half‐titanocenes for styrene polymerization with both high styrene conversion and high syndiospecific selectivity.
First symptoms and health care pathways in hospitalized patients with acute heart failure: ICPS2 survey. A report from the Heart Failure Working Group (GICC) of the French Society of Cardiology
Authors: Beauvais Florence , Tartière Lamia , Pezel Théo , Motet Chloé , Aumont Marie‐Claude , Baudry Guillaume , Eicher Jean‐Christophe , Galinier Michel , Gellen Barnabas , Guihaire Julien , Legallois Damien , Lequeux Benoit , Mika Delphine , Mouquet Frederic , Salvat Muriel , Taieb Charles , Zorès Florian , Berthelot Emmanuelle , Damy Thibaud 
Published: June 2021

AbstractBackgroundAcute heart failure (AHF) is a common serious condition that contributes to about 5% of all emergency hospital admissions in Europe.HypothesisTo assess the type and chronology of the first AHF symptoms before hospitalization and to examine the French healthcare system pathways before, during and after hospitalization.Material and MethodsA retrospective observational study including patients hospitalized for AHFResults793 patients were included, 59.0% were men, 45.6% identified heart failure (HF) as the main cause of hospitalization; 36.0% were unaware of their HF. Mean age was 72.9 ± 14.5 years. The symptoms occurring the most before hospitalization were dyspnea (64.7%) and lower limb edema (27.7%). Prior to hospitalization, 47% had already experienced symptoms for 15 days; 32% of them for 2 months. Referral to hospital was made by the emergency medical assistance service (SAMU, 41.6%), a general practitioner (GP, 22.3%), a cardiologist (19.5%), or the patient (16.6%). The modality of referral depended more on symptom acuteness than on type of symptoms. A sudden onset of AHF symptoms led to making an emergency call or to spontaneously attending an emergency room (ER), whereas cardiologists were consulted when symptoms had already been present for over 15 days. Cardiologists referred more patients to cardiology departments and fewer patients to the ER than general practitioners or the SAMU.ConclusionThis study described the French healthcare system pathways before, during and after hospitalization AHF. AHF clinic network should be developed to provide adequate care for all HF patients and create awareness regarding AHF symptoms.
Structural Basis of Selective Human Indoleamine‐2,3‐dioxygenase 1 (hIDO1) Inhibition
Authors: Kassab Shaymaa Emam , Mowafy Samar 
Published: June 2021

AbstracthIDO1 is a heme−dioxygenase overexpressed in the tumor microenvironment and is implicated in the survival of cancer cells. Metabolism of tryptophan to N‐formyl−kynurenine by hIDO1 leads to immune suppression to result in cancer cell immune escape. In this article, we discuss the discovery of selective hIDO1 inhibitors for therapeutic intervention that have been promoted to clinical trials and for which crystallographic structural information is available for the respective inhibitor−enzyme complex. The structural insights are based on the complex crystal structures and the relative biological data profiles. The structural basis of selective hIDO1 inhibition, as discussed herein, opens new avenues to the discovery of novel inhibitors with improved activity profiles, selectivity, and distinct structure frameworks.
Polycomb Paralog Chromodomain Inhibitors Active against Both CBX6 and CBX8**
Authors: Milosevich Natalia , Wilson Chelsea R. , Brown Tyler M. , Alpsoy Aktan , Wang Sijie , Connelly Katelyn E. , Sinclair Kirsten A. D. , Ponio Felino R. , Hof Rebecca , Dykhuizen Emily C. , Hof Fraser 
Published: June 2021

AbstractMethyllysine reader proteins bind to methylated lysine residues and alter gene transcription by changing either the compaction state of chromatin or by the recruitment of other multiprotein complexes. The polycomb paralog family of methyllysine readers bind to trimethylated lysine on the tail of histone 3 (H3) via a highly conserved aromatic cage located in their chromodomains. Each of the polycomb paralogs are implicated in several disease states. CBX6 and CBX8 are members of the polycomb paralog family with two structurally similar chromodomains. By exploring the structure‐activity relationships of a previously reported CBX6 inhibitor we have discovered more potent and cell permeable analogs. Our current report includes potent, dual‐selective inhibitors of CBX6 and CBX8. We have shown that the −2 position in our scaffold is an important residue for selectivity amongst the polycomb paralogs. Preliminary cell‐based studies show that the new inhibitors impact cell proliferation in a rhabdoid tumor cell line.
Forty‐eight‐year‐old female MUTYH carrier presenting with five concurrent primary cancers
Authors: Arroyave Aaron , Nodit Laurentia , Clegg Devin , Russ Andrew 
Published: June 2021

AbstractBackgroundMUTYH‐associated polyposis is a rare disorder resulting from mutations involved in DNA mismatch repair. This results in an increased susceptibility to colonic adenomatosis and other cancers. Studies have examined the resulting frequency of extracolonic manifestations; however, these typically occur alone, concurrently, or temporally separate from an already diagnosed colorectal cancer in individuals with a biallelic mutation.CaseReported here is a case of five distinct primary neoplasms presenting simultaneously in a patient monoallelic for an MYH mutation. These neoplasms included squamous cell carcinoma of the vulva, rectal adenocarcinoma, synchronous anal adenocarcinoma, papillary thyroid carcinoma, and ovarian serous psammocarcinoma. Throughout her course, she underwent multiple surgical procedures, neoadjuvant chemoradiation, with further adjuvant therapy, and treatment ongoing. Due to her unique presentation, she underwent genetic testing that demonstrated she was monoallelic for an MYH mutation.ConclusionThe patient had a positive response to her treatment and surgical procedures with ongoing adjuvant therapy. She will continue to undergo further genetic testing, and testing for her children is being considered. This case demonstrates a unique presentation associated with a monoallelic MYH mutation that is not described in the current literature and warrants further investigation.
Cytodiagnosis of chondroid syringoma—Series of three cases
Authors: Agarwal Ruchi , Kulhria Amrita , Singh Kulwant , Agarwal Deepti 
Published: June 2021

AbstractChondroid syringoma is a rare, benign, appendegeal neoplasm. It was initially termed as mixed tumor as it comprises both epithelial cells and chondromyxoid stroma. It usually presents as a slow growing, solitary, painless, subcutaneous, or intracutaneous mass, frequently in the head and neck region. Cytological features usually include the presence of both components, similar to histology but aspiration of only one component or atypical features can pose challenges in diagnosis. According to literature, only a few single case reports describing the cytological features of chondroid syringoma has been published. We report three cases of chondroid syringoma and its differential diagnosis on cytology.
Effects of notoginsenoside R1 on attenuating depressive behavior induced by chronic stress in rats through induction of PI3K/AKT/NF‐κB pathway
Authors: Zhan Qiongqiong , Wu Yanfeng , Liu Lin 
Published: June 2021

AbstractChronic unpredictable mild stress (CUMS) can cause a series of depressive symptoms in depression patients. Recently, notoginsenoside R1 (NGR1) has been reported to play crucial roles in the anti‐inflammatory, antioxidant, and anti‐apoptotic. However, the role and mechanisms of NGR1 in improving symptoms of depressive behavior remain unknown. Evaluating and identifying its value and exploring the mechanisms of NGR1 on CUMS‐induced depressive behavior were the aims of this study. Here, rats were separated into five different groups and treated with or without different concentrations of the NGR1. Then, the body weight, sucrose preference rate, immobility time, crossing number, rearing number, and grooming number were determined to evaluate the effect of NGR1 on improving the depressive behavior of CUMS rats. Subsequently, the morphology of hippocampal neurons and protein expression of brain‐derived neurotrophic factor in each group were examined by hematoxylin and eosin staining and western blot to show the neuroprotective effects of NGR1. Furthermore, the mRNA and protein expression of TNF‐α, IL‐6, and IL‐1β were also detected by quantitative polymerase chain reaction (qPCR) and enzyme‐linked immunosorbent assay to verify the anti‐inflammatory effects of NGR1 on CUMS rats. In addition, the cell apoptosis‐related proteins were examined to reveal that NGR1 can inhibit cell apoptosis in CUMS rats. Moreover, it was confirmed that NGR1 attenuated the symptoms of depressive behavior by mediated PI3K/Akt/NF‐κB pathway. Together, this study shows that NGR1 improves depressive behavior induced by chronic stress in rats through activation of PI3K/AKT/NF‐κB pathway.
Fathering behavior, attachment, and engagement in childcare predict testosterone and cortisol
Authors: Ahnert Lieselotte , Deichmann Felix , Bauer Markus , Supper Barbara , Piskernik Bernhard 
Published: June 2021

AbstractThe present study examined testosterone (T) and cortisol (Cort) in fathers engaged with caregiving. We collected saliva samples in the mornings and evenings of two consecutive days in 150 fathers of 1‐ to 5‐year‐old children. Fathers completed questionnaires on socioeconomic status, family structure and life, sleep characteristics and body mass index (BMI), and reported on their engagement in childcare. Fathers used smartphone‐based experience sampling throughout 1 week to sample ongoing activities with their children, including times of supervision, joint play, rough‐and‐tumble play, and cuddling episodes. External observers rated father–child attachment during a home visit.We began by testing for widely characterized covariates of T and excluded seasonal variations and known predictors associated with lowered T, such as older fathers and those with multiple and young children, lower BMI, shorter sleep duration, and sexual activity before sampling. Most interestingly, however, fathers’ engagement in childcare and attachment to the child appeared more pronounced the greater the diurnal decline in T. Cuddling predicted a similar negative association, whereas joint play and rough‐and‐tumble play (RTP) showed enhancing effects on declining T. Interestingly, all fathering behaviors (except RTP) were positively related to lower Cort. In contrast, supervision was ineffective on both Cort and T.
Enzyme electrode for glucose oxidation using low‐solubility 4‐aminodiphenylamine derivatives as electron mediator
Authors: Masakari Yosuke , Totsuka Naoya , Shinohara Yasutomo , Yoshida Shotaro , Abe Hiroya , Ito Kotaro , Nishizawa Matsuhiko 
Published: June 2021

AbstractA novel enzyme electrode system for glucose oxidation was constructed by co‐immobilization of glucose dehydrogenase (GDH) and N,N’‐diphenyl‐p‐phenylenediamine (DPPD) on carbon electrodes. This enzyme electrode system was applied to porous carbon fabric to produce a glucose oxidation current of 7 mA/cm2, while the electrode catalytic activity was maintained at approximately 100% for more than 4 h, indicating that DPPD molecules were stably retained on the electrodes during the continuous redox cycling. Further, a stable mediation was also observed for other 4‐aminodiphenylamine derivatives similar to DPPD. The difference was found in the adsorptivity between the reduced and oxidized forms of DPPD on the carbon electrode, suggesting that a portion of oxidized DPPD can access the active center of GDH without desorbing to solution. This electrode system with 4‐aminodiphenylamine derivatives can be used in sensors for glucose monitoring and to anodes of separator‐free glucose fuel cells.
Investigation of pile‐induced filtering of seismic ground motion considering embedment effect
Authors: Varghese Ramon , Boominathan Adimoolam , Banerjee Subhadeep 
Published: June 2021

AbstractThe Foundation Input Motion (FIM) arising out of kinematic soil‐pile interaction forms an integral part of the seismic analysis of pile‐supported structures. Several studies in the recent past have recognized the importance of the filtering effect produced by pile foundations. This paper presents a comprehensive investigation of the influence of raft embedment on the Foundation Input Motion from piled rafts. A hybrid numerical methodology based on the finite element‐boundary element method is employed to rigorously model rectangular piled rafts in varying soil conditions. Analysis of transfer functions in the frequency domain suggests that the translational response is suppressed by increasing embedment of the raft. An increase in rocking response is also synchronous with this decrease in translational motion. A transient response analysis carried out using eight different earthquake time histories showed that the spectral acceleration curve is altered by the embedment effect. A set of simplified expressions are proposed to incorporate the embedment effects in the spectral acceleration ratio curve of a pile group. These proposed expressions have the potential to enable a quick estimation of the effect of embedment in the seismic design of pile‐supported structures.