bluuebunny/crossref_metadata_2025 huggingface dataset:
Martinus Nijhoff, 1894-1953
Authors: Sanders Mathijs
Published: May 2021

Behalve als dichter geniet Martinus Nijhoff ook als vertaler een bijzondere reputatie. Niet toevallig is de meest prestigieuze Nederlandse vertaalprijs, ingesteld na de dood van de dichter in 1953, naar hem vernoemd. Ook is herhaaldelijk gewezen op de samenhang tussen Nijhoffs vertalingen en zijn oorspronkelijke werk. ‘Als iemand ooit pogen wil het wezen van Nijhoff’s dichterschap te analyseren, zullen de vertalingen onmisbaar blijken om hem de weg te wijzen,’ schreef Pierre H. Dubois in Het Vaderland van 5 maart 1955 naar aanleiding van het verschijnen van het derde deel van Nijhoffs Verzameld werk, waarin tekstbezorger Gerrit Kamphuis de vertalingen van Nijhoff bijeenbracht. In zijn ‘Verantwoording’ gaf Kamphuis een treffend beeld van Nijhoffs vertalingen: Vertalen was voor Nijhoff niet slechts iets bijkomstigs. Hij vatte dit soort werk zeer serieus op en streefde ernaar de originelen over te zetten in het Nederlands op een wijze, die minder duidelijk met het woord vertalen is aan te duiden dan te karakteriseren is als: een opnieuw in onze taal doen geboren worden. Door zich zo, gelijkelijk passief en actief, in anderer werk te verdiepen, kon hij tot groter ontplooiing van eigen mogelijkheden komen. Vertalen was voor Nijhoff dus niet het eenvoudigweg omzetten van een tekst in een andere taal. Een geslaagde vertaling was het resultaat van een creatieve transformatie. Of het nu The Tempest van William Shakespeare of een versje van François Villon betrof, telkens zette Nijhoff vorm en inhoud naar zijn hand. Dat leverde vertalingen op die zich voegden naar de voorstellingswereld die zich ook aftekent in zijn oorspronkelijke gedichten.
EFEKTIVITAS PEMBELAJARAN ONLINE VERSUS TATAP MUKA
Authors: Nurlatifah Nurlatifah , Ahman Eeng , Machmud Amir , Sobandi A
Published: May 2021

Penelitian ini dilatar belakangi oleh rendahnya hasil belajar siswa di Indonesia khususnya Kabupaten Cianjur. Hal ini ditunjukan dengan hasil Ujian Tengah Semester (UTS). Penelitian ini  bertujuan untuk menganalisis  efektivitas pembelajaran online dan tatap muka pada mata pelajaran ekonomi yang memiliki karakteristik yang sama (guru, waktu belajar dan penilaian akhir). Metode yang digunakan dalam penelitian ini adalah survei. Adapun teknik pengumpulan data menyebar kuesioner secara online melalui Google-Form. Populasi dalam penelitian ini siswa Madrasah Aliyah Swasta Bojongjati yang berjumlah 160 siswa dengan sample 110 siswa dengan teknik pengambilan sampel secara random sampling. Tingkat efektivitas diukur melalui satu indikator objektif yaitu nilai UTS dan tiga indikator subjektif (kahadiran, keaktifan dan kepuasan). Hasil penelitian ini menunjukan bahwa pembelajaran online kurang efektif daripada pembelajaran tatap muka (face to face).
From Students' Questions of Safety Education in a Chemistry Laboratory
Authors: Akitsu Takashiro
Published: May 2021

Chemists operate fairly scary chemicals with their bare hands, but drug injuries and addiction is very rare. This is because we are familiar with what is dangerous and what is not dangerous, and for that reason, the experimental curriculum is designed with the idea of gaining sufficient experience of failure in the undergraduate years in the chemistry classroom of the university. From the experience of safety education in the author's laboratory, this article will describe some points that are easy to overlook (metal powder), fire extinguishers, and the opinions are divided (cyanide). Beside general viewpoints of chemical aspects fire safety and chemistry experiments similar to that I have written for high-school and college students and teachers, this Editorial focused on “Question” that my (under) graduate students have practically.
Host Response to Biomaterials for Cartilage Tissue Engineering: Key to Remodeling
Authors: Wei Fu , Liu Shuyun , Chen Mingxue , Tian Guangzhao , Zha Kangkang , Yang Zhen , Jiang Shuangpeng , Li Muzhe , Sui Xiang , Chen Zhiwei , Guo Quanyi
Published: May 2021

Biomaterials play a core role in cartilage repair and regeneration. The success or failure of an implanted biomaterial is largely dependent on host response following implantation. Host response has been considered to be influenced by numerous factors, such as immune components of materials, cytokines and inflammatory agents induced by implants. Both synthetic and native materials involve immune components, which are also termed as immunogenicity. Generally, the innate and adaptive immune system will be activated and various cytokines and inflammatory agents will be consequently released after biomaterials implantation, and further triggers host response to biomaterials. This will guide the constructive remolding process of damaged tissue. Therefore, biomaterial immunogenicity should be given more attention. Further understanding the specific biological mechanisms of host response to biomaterials and the effects of the host-biomaterial interaction may be beneficial to promote cartilage repair and regeneration. In this review, we summarized the characteristics of the host response to implants and the immunomodulatory properties of varied biomaterial. We hope this review will provide scientists with inspiration in cartilage regeneration by controlling immune components of biomaterials and modulating the immune system.
The Interaction Analysis of SNP Variants and DNA Methylation Identifies Novel Methylated Pathogenesis Genes in Congenital Heart Diseases
Authors: Wang Jing , Ma Xiaoqin , Zhang Qi , Chen Yinghui , Wu Dan , Zhao Pengjun , Yu Yu
Published: May 2021

Congenital heart defect (CHD) is a rare and complicated disease with a high mortality rate. Its etiology remains unclear and includes many aspects. DNA methylation has been indicated to be involved in heart development in the early stage of life, and aberrant methylation level was related to CHDs. This study provides the first evidence of the cross talk of SNP variants and DNA methylation in clarifying CHD underlying genomic cause. We gathered whole exome sequencing (WES) data for Group 1 consisting of patients with PA (n = 78), TOF (n = 20), TAPVC (n = 78), and PDA (n = 40), and 100 healthy children as control group. Rare non-synonymous mutations and novel genes were found and highlighted. Meanwhile, we carried out the second analysis of DNA methylation data from patients with PA (n = 3), TAPVC (n = 3), TOF (n = 3), and PDA (n = 2), and five healthy controls using 850 K array in Group 2. DNA methylation was linked to WES data, and we explored an obvious overlap of hyper/hypomethylated genes. Next, we identified some candidate genes by Fisher’s exact test and Burden analysis; then, those methylated genes were figured out by the criteria of the mutation located in the CpG islands of the genome, differential methylation sites (DMS), and DNA methylation quantitative trait loci (meQTLs) in the database, respectively. Also, the interaction of differentially methylated candidate genes with known CHD pathogenetic genes was depicted in a molecular network. Taken together, our findings show that nine novel genes (ANGPTL4, VEGFA, PAX3, MUC4, HLA-DRB1, TJP2, BCR, PKD1, and HK2) in methylation level are critical to CHD and reveal a new insight into the molecular pathogenesis of CHD.
Application of Metallic Nanoparticles and Their Hybrids as Innovative Sorbents for Separation and Pre-concentration of Trace Elements by Dispersive Micro-Solid Phase Extraction: A Minireview
Authors: Hagarová Ingrid , Nemček Lucia
Published: May 2021

It is indisputable that separation techniques have found their rightful place in current analytical chemistry, considering the growing complexity of analyzed samples and (ultra)trace concentration levels of many studied analytes. Among separation techniques, extraction is one of the most popular ones due to its efficiency, simplicity, low cost and short processing times. Nonetheless, research interests are directed toward the enhancement of performance of these procedures in terms of selectivity. Dispersive solid phase extraction (DSPE) represents a novel alternative to conventional solid phase extraction (SPE) which not only delivers environment-friendly extraction with less solvent consumption, but also significantly improves analytical figures of merit. A miniaturized modification of DSPE, known as dispersive micro-solid phase extraction (DMSPE), is one of the most recent trends and can be applied for the extraction of wide variety of analytes from various liquid matrices. While DSPE procedures generally use sorbents of different origin and sizes, in DMSPE predominantly nanostructured materials are required. The aim of this paper is to provide an overview of recently published original papers on DMSPE procedures in which metallic nanoparticles and hybrid materials containing metallic particles along with other (often carbon-based) constituent(s) at the nanometer level have been utilized for separation and pre-concentration of (ultra)trace elements in liquid samples. The studies included in this review emphasize the great analytical potential of procedures producing reliable results in the analysis of complex liquid matrices, where the detection of target analyte is often complicated by the presence of interfering substances.
Rational Design of Peptide-Based Inhibitors Disrupting Protein-Protein Interactions
Authors: Wang Xuefei , Ni Duan , Liu Yaqin , Lu Shaoyong
Published: May 2021

Protein-protein interactions (PPIs) are well-established as a class of promising drug targets for their implications in a wide range of biological processes. However, drug development toward PPIs is inevitably hampered by their flat and wide interfaces, which generally lack suitable pockets for ligand binding, rendering most PPI systems “undruggable.” Here, we summarized drug design strategies for developing peptide-based PPI inhibitors. Importantly, several quintessential examples toward well-established PPI targets such as Bcl-2 family members, p53-MDM2, as well as APC-Asef are presented to illustrate the detailed schemes for peptide-based PPI inhibitor development and optimizations. This review supplies a comprehensive overview of recent progresses in drug discovery targeting PPIs through peptides or peptidomimetics, and will shed light on future therapeutic agent development toward the historically “intractable” PPI systems.
Pulse Pressure, Cognition, and White Matter Lesions: A Mediation Analysis
Authors: Zang Jiabin , Shi Jian , Liang Jianwen , Zhang Xiaocong , Wei Wenbin , Yao Chun , Zhuang Xiaodong , Wu Guifu
Published: May 2021

This study aimed to investigate the effects of pulse pressure (PP) on cognition and the role of white matter lesions (WMLs) in mediating this association. We enrolled 3,009 participants from the SPRINT-MIND study. Of those, 755 participants underwent brain magnetic resonance imaging. Cognitive tests were summarized in five cognition domains, including global cognition, executive function, attention, memory, and language. Multiple linear regression models were employed to analyze PP in association with cognition, and mediation analysis was applied to determine the role of WMLs in the association between PP and cognition. We found that PP was negatively linearly associated with global cognition (β = −0.048, P = 0.008), executive function (β = −0.014, P = 0.040), attention (β = −0.013, P = 0.035), memory (β = −0.021, P = 0.045), and language (β = −0.020, P = 0.001), respectively. Furthermore, PP was not significantly associated with brain component volume changes, except for WMLs (β = 0.029, P = 0.044). Additionally, mediation analysis showed that increased WML volume contributed to 10.8% of global cognition, 9.5% of executive function, 10.6% of memory, and 7.2% of language decline associated with PP. Exposure to higher PP levels was associated with poor cognitive performance, and WMLs partially moderated the influence of PP on cognition.
The Associations Between Problematic Internet Use, Healthy Lifestyle Behaviors and Health Complaints in Adolescents
Authors: Klavina Aija , Veliks Viktors , Zusa-Rodke Anna , Porozovs Juris , Aniscenko Aleksandrs , Bebrisa-Fedotova Luize
Published: May 2021

This study aimed to explore relationship between problematic internet use (PIU), healthy lifestyle behaviors and subjective health complaints.

Methods: Participants (396 adolescents, aged 11–18 years) from 34 general education schools across Latvia completed online survey. The PIU was assessed by the Problematic and Risky Internet Use Screening Scale (PRIUSS) collecting data on social impairment, emotional impairment, and risky/impulsive internet use. The subjective health complaints assessed were somatic and psychological symptoms. Healthy lifestyle behaviors assessed were daily physical activities, time spent in using information technologies (IT), eating habits, and duration of sleep.

Results: This study found that 31.00% (n = 124) of the participants scored at risk for PIU. Correlates associated with PIU were subjective health complaints, low physical activity, lack of meals together with family and disturbed sleeping regimes on weekends (P < 0.001). Stepwise multiple regression analyses showed that 34% of the variance in the PRIUSS scores was explained by psychological health complaints (irritability, depression, and nervousness), screen time use on weekends, physical activity, drinking sweetened soft drinks and unhealthy eating habits.

Conclusion: PIU behaviors among adolescents in Latvia are associated with psychological symptoms and unhealthy lifestyle. Further effective measures and interventions are needed to prevent development of psychosomatic health problems.
Erectile Dysfunction Is Associated With Excessive Growth Hormone Levels in Male Patients With Acromegaly
Authors: Chen Zhengyuan , Shao Xiaoqing , He Min , Shen Ming , Gong Wei , Wang Meng , Zhang Yichao , Liu Wenjuan , Ma Zengyi , Ye Zhao , Lu Yongning , Yang Nianqin , Chen Shanwen , Hu Lydia , Li Yiming , Wang Yongfei , Zhao Yao , Zhang Zhaoyun
Published: May 2021

Objective

To determine the risk factors for erectile dysfunction (ED) in male patients with acromegaly and to prospectively investigate the short-term changes of erectile function after surgery or medical treatment.

Methods

Sixty-three male patients were subjected to nocturnal penile tumescence and rigidity (NPTR) test for the evaluation of erectile function. The measurement of serum nitric oxide (NO) was also performed. Twenty-seven patients were re-evaluated by NPTR after surgery or long-term somatostatin analogues (SSA) treatment.

Results

Twenty-two patients (34.9%) had ED. Patients with ED showed higher random GH (17.89 [10.97-44.19] μg/L vs 11.63 [4.31-28.80] μg/L, p = 0.020) and GH nadir (GHn) (10.80 [6.69-38.30] μg/L vs 8.76 [3.62-18.19] μg/L, p = 0.044) during oral glucose tolerance test (OGTT). The NO levels of ED patients were lower than non-ED patients (9.15 [5.58-22.48] μmol/L vs 16.50 [12.33-31.78] μmol/L, p = 0.012). After treatment, patients who present improvement in erectile function showed lower post-GHn (0.07 [0.03-0.12] ng/ml vs 1.32 [0.09-3.60] ng/ml, p = 0.048) and post-IGF-1 index (1.03 ± 0.38 vs 1.66 ± 0.95, p = 0.049). The multivariate analysis indicated post-GHn was still associated with the improvement of erectile function after correction of other covariates (OR: 0.059, 95% CI: 0.003-1.043, p = 0.053).

Conclusions

Excessive GH is related to ED in male patients with acromegaly. GH normalization after treatment is beneficial for short-term erectile function recovery.
Risk Analysis of Wheat Yield Losses at the County Level in Mainland China
Authors: Li Xuan , Fang Shibo , Zhu Yongchao , Wu Dong
Published: May 2021

There have been few pieces of research focused on quantifying wheat yield loss risk based on high-resolution long-term historical data. What is more, the existence of the area scale effect reduces the certainty and spatial comparability of results. In this study, long-term wheat yield and planting area data at the county level from 1981 to 2010 were used. The spatial distribution of wheat yield loss risks was analyzed in the mainland of the People’s Republic of China (China for short). An improved comprehensive risk index of yield loss risk was established by integrating the reduction rate, coefficient of variation, and the probability of occurrence for different yield reduction rates after removing the effect of area scale. 874 main wheat-growing counties in the mainland of China were divided into lowest, lower, moderate, higher, and highest risk areas based on it. The high-risk areas are located in Yellow-Huai-Hai Plain, including Shandong, Henan, northern Anhui, and parts of Jiangsu Province.
Impact of Grazing Intensity on Soil Properties in Teltele Rangeland, Ethiopia
Authors: Fenetahun Yeneayehu , Yuan You , Xinwen Xu , Fentahun Tihunie , Nzabarinda Vincent , Yong-dong Wang
Published: May 2021

Grazing intensity (GI) is a major determining factor that controls the functioning of rangelands and the overall nutrient cycle. The Teltele rangeland is used for communal grazing area by the local pastorals; however, to date, there is no documented study data about the impact of GI. The objective of this study was to evaluate the impacts of grazing intensity on selected soil properties in the Teltele rangeland, Ethiopia. Soil samples were collected from different GI sites using different elevation gradient and soil depth from both open grazing and bush-encroached grazing land sand-assessed soil properties. Grazing intensity, elevation, and soil depth significantly (p < 0.05) affected both soils’ physical and chemical properties but rangeland types had no significant effect. The correlation analysis of soil characteristics with the principal component analysis axes showed significant variation. The highly weighted and correlated properties under principal component 1 (PC1) were electrical conductivity, organic carbon, total nitrogen, available phosphorus, and potassium, and under principal component 2, sand and bulk density with equal loaded value (r = −0.998), clay and silt, with silt (0.962) a more loaded one. Soil pH (0.743) demonstrated a significant (p < 0.05) positive correlation with sodium (−0.960) at PC1 (r = 0.610). Based on our results, we recommend further model-based studies on spatial–temporal change of soil properties due to impact of grazing intensity, combined with GIS and remote sensing data to be developed for sustainable rangeland management.
CLGBO: An Algorithm for Constructing Highly Robust Coding Sets for DNA Storage
Authors: Zheng Yanfen , Wu Jieqiong , Wang Bin
Published: May 2021

In the era of big data, new storage media are urgently needed because the storage capacity for global data cannot meet the exponential growth of information. Deoxyribonucleic acid (DNA) storage, where primer and address sequences play a crucial role, is one of the most promising storage media because of its high density, large capacity and durability. In this study, we describe an enhanced gradient-based optimizer that includes the Cauchy and Levy mutation strategy (CLGBO) to construct DNA coding sets, which are used as primer and address libraries. Our experimental results show that the lower bounds of DNA storage coding sets obtained using the CLGBO algorithm are increased by 4.3–13.5% compared with previous work. The non-adjacent subsequence constraint was introduced to reduce the error rate in the storage process. This helps to resolve the problem that arises when consecutive repetitive subsequences in the sequence cause errors in DNA storage. We made use of the CLGBO algorithm and the non-adjacent subsequence constraint to construct larger and more highly robust coding sets.
Epigenetic Regulation of Genomic Stability by Vitamin C
Authors: Brabson John P. , Leesang Tiffany , Mohammad Sofia , Cimmino Luisa
Published: May 2021

DNA methylation plays an important role in the maintenance of genomic stability. Ten-eleven translocation proteins (TETs) are a family of iron (Fe2+) and α-KG -dependent dioxygenases that regulate DNA methylation levels by oxidizing 5-methylcystosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). These oxidized methylcytosines promote passive demethylation upon DNA replication, or active DNA demethylation, by triggering base excision repair and replacement of 5fC and 5caC with an unmethylated cytosine. Several studies over the last decade have shown that loss of TET function leads to DNA hypermethylation and increased genomic instability. Vitamin C, a cofactor of TET enzymes, increases 5hmC formation and promotes DNA demethylation, suggesting that this essential vitamin, in addition to its antioxidant properties, can also directly influence genomic stability. This review will highlight the functional role of DNA methylation, TET activity and vitamin C, in the crosstalk between DNA methylation and DNA repair.
Metabolic Reprogramming of GMP Grade Cord Tissue Derived Mesenchymal Stem Cells Enhances Their Suppressive Potential in GVHD
Authors: Mendt Mayela , Daher May , Basar Rafet , Shanley Mayra , Kumar Bijender , Wei Inng Francesca Lim , Acharya Sunil , Shaim Hila , Fowlkes Natalie , Tran Jamie P. , Gokdemir Elif , Uprety Nadima , Nunez-Cortes Ana K. , Ensley Emily , Mai Thao , Kerbauy Lucila N. , Melo-Garcia Luciana , Lin Paul , Shen Yifei , Mohanty Vakul , Lu JunJun , Li Sufang , Nandivada Vandana , Wang Jing , Banerjee Pinaki , Reyes-Silva Francia , Liu Enli , Ang Sonny , Gilbert April , Li Ye , Wan Xinhai , Gu Jun , Zhao Ming , Baran Natalia , Muniz-Feliciano Luis , Wilson Jeffrey , Kaur Indreshpal , Gagea Mihai , Konopleva Marina , Marin David , Tang Guilin , Chen Ken , Champlin Richard , Rezvani Katayoun , Shpall Elizabeth J.
Published: May 2021

Acute graft-vs.-host (GVHD) disease remains a common complication of allogeneic stem cell transplantation with very poor outcomes once the disease becomes steroid refractory. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for the treatment of GVHD, but so far this strategy has had equivocal clinical efficacy. Therapies using MSCs require optimization taking advantage of the plasticity of these cells in response to different microenvironments. In this study, we aimed to optimize cord blood tissue derived MSCs (CBti MSCs) by priming them using a regimen of inflammatory cytokines. This approach led to their metabolic reprogramming with enhancement of their glycolytic capacity. Metabolically reprogrammed CBti MSCs displayed a boosted immunosuppressive potential, with superior immunomodulatory and homing properties, even after cryopreservation and thawing. Mechanistically, primed CBti MSCs significantly interfered with glycolytic switching and mTOR signaling in T cells, suppressing T cell proliferation and ensuing polarizing toward T regulatory cells. Based on these data, we generated a Good Manufacturing Process (GMP) Laboratory protocol for the production and cryopreservation of primed CBti MSCs for clinical use. Following thawing, these cryopreserved GMP-compliant primed CBti MSCs significantly improved outcomes in a xenogenic mouse model of GVHD. Our data support the concept that metabolic profiling of MSCs can be used as a surrogate for their suppressive potential in conjunction with conventional functional methods to support their therapeutic use in GVHD or other autoimmune disorders.
HLA-B*13 :01 Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients
Authors: Satapornpong Patompong , Pratoomwun Jirawat , Rerknimitr Pawinee , Klaewsongkram Jettanong , Nakkam Nontaya , Rungrotmongkol Thanyada , Konyoung Parinya , Saksit Niwat , Mahakkanukrauh Ajanee , Amornpinyo Warayuwadee , Khunarkornsiri Usanee , Tempark Therdpong , Wantavornprasert Kittipong , Jinda Pimonpan , Koomdee Napatrupron , Jantararoungtong Thawinee , Rerkpattanapipat Ticha , Wang Chuang-Wei , Naisbitt Dean , Tassaneeyakul Wichittra , Ariyachaipanich Manasalak , Roonghiranwat Thapana , Pirmohamed Munir , Chung Wen-Hung , Sukasem Chonlaphat
Published: May 2021

HLA-B*13:01 allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR). We investigated the association of HLA alleles and cytochrome P450 (CYP) alleles with dapsone-induced SCAR in Thai non-leprosy patients. A prospective cohort study, 16 Thai patients of dapsone-induced SCARs (5 SJS-TEN and 11 DRESS) and 9 Taiwanese patients of dapsone-induced SCARs (2 SJS-TEN and 7 DRESS), 40 dapsone-tolerant controls, and 470 general Thai population were enrolled. HLA class I and II alleles were genotyped using polymerase chain reaction-sequence specific oligonucleotides (PCR-SSOs). CYP2C9, CYP2C19, and CYP3A4 genotypes were determined by the TaqMan real-time PCR assay. We performed computational analyses of dapsone and DDS-NHOH interacting with HLA-B*13:01 and HLA-B*13:02 alleles by the molecular docking approach. Among all the HLA alleles, only HLA-B*13:01 allele was found to be significantly associated with dapsone-induced SCARs (OR = 39.00, 95% CI = 7.67–198.21, p = 5.3447 × 10−7), SJS-TEN (OR = 36.00, 95% CI = 3.19–405.89, p = 2.1657 × 10−3), and DRESS (OR = 40.50, 95% CI = 6.38–257.03, p = 1.0784 × 10−5) as compared to dapsone-tolerant controls. Also, HLA-B*13:01 allele was strongly associated with dapsone-induced SCARs in Asians (OR = 36.00, 95% CI = 8.67–149.52, p = 2.8068 × 10−7) and Taiwanese (OR = 31.50, 95% CI = 4.80–206.56, p = 2.5519 × 10−3). Furthermore, dapsone and DDS-NHOH fit within the extra-deep sub pocket of the antigen-binding site of the HLA-B*13:01 allele and change the antigen-recognition site. However, there was no significant association between genetic polymorphism of cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) and dapsone-induced SCARs (SJS-TEN and DRESS). The results of this study support the specific genotyping of the HLA-B*13:01 allele to avoid dapsone-induced SCARs including SJS-TEN and DRESS before initiating dapsone therapy in the Asian population.
Targeted Inhibition of FTO Demethylase Protects Mice Against LPS-Induced Septic Shock by Suppressing NLRP3 Inflammasome
Authors: Luo Jiahui , Wang Faxi , Sun Fei , Yue Tiantian , Zhou Qing , Yang Chunliang , Rong Shanjie , Yang Ping , Xiong Fei , Yu Qilin , Zhang Shu , Wang Cong-Yi , Li Jinxiu
Published: May 2021

Sepsis refers to the systemic inflammatory response syndrome caused by infection. It is a major clinical problem and cause of death for patients in intensive care units worldwide. The Fat mass and obesity-related protein (FTO) is the primary N6-methyladenosine demethylase. However, the role of FTO in the pathogenesis of inflammatory diseases remains unclear. We herein show that nanoparticle-mediated Fto-siRNA delivery or FTO inhibitor entacapone administration dramatically inhibited macrophage activation, reduced the tissue damage and improved survival in a mouse model of LPS-induced endotoxic shock. Importantly, ablation of FTO could inhibit NLRP3 inflammasome through FoxO1/NF-κB signaling in macrophages. In conclusion, FTO is involved in inflammatory response of LPS-induced septic shock and inhibition of FTO is promising for the treatment of septic shock.
Immunologic Profiling of the Atlantic Salmon Gill by Single Nuclei Transcriptomics
Authors: West Alexander C. , Mizoro Yasutaka , Wood Shona H. , Ince Louise M. , Iversen Marianne , Jørgensen Even H. , Nome Torfinn , Sandve Simen Rød , Martin Samuel A. M. , Loudon Andrew S. I. , Hazlerigg David G.
Published: May 2021

Anadromous salmonids begin life adapted to the freshwater environments of their natal streams before a developmental transition, known as smoltification, transforms them into marine-adapted fish. In the wild, smoltification is a photoperiod-regulated process, involving radical remodeling of gill function to cope with the profound osmotic and immunological challenges of seawater (SW) migration. While prior work has highlighted the role of specialized “mitochondrion-rich” cells (MRCs) and accessory cells (ACs) in delivering this phenotype, recent RNA profiling experiments suggest that remodeling is far more extensive than previously appreciated. Here, we use single-nuclei RNAseq to characterize the extent of cytological changes in the gill of Atlantic salmon during smoltification and SW transfer. We identify 20 distinct cell clusters, including known, but also novel gill cell types. These data allow us to isolate cluster-specific, smoltification-associated changes in gene expression and to describe how the cellular make-up of the gill changes through smoltification. As expected, we noted an increase in the proportion of seawater mitochondrion-rich cells, however, we also identify previously unknown reduction of several immune-related cell types. Overall, our results provide fresh detail of the cellular complexity in the gill and suggest that smoltification triggers unexpected immune reprogramming.
Antibodies Elicited by the Shigella sonnei GMMA Vaccine in Adults Trigger Complement-Mediated Serum Bactericidal Activity: Results From a Phase 1 Dose Escalation Trial Followed by a Booster Extension
Authors: Micoli Francesca , Rossi Omar , Conti Valentino , Launay Odile , Sciré Antonella Silvia , Aruta Maria Grazia , Nakakana Usman Nasir , Marchetti Elisa , Rappuoli Rino , Saul Allan , Martin Laura B. , Necchi Francesca , Podda Audino
Published: May 2021

Shigella is the second most deadly diarrheal disease among children under five years of age, after rotavirus, with high morbidity and mortality in developing countries. Currently, no vaccine is widely available, and the increasing levels of multidrug resistance make Shigella a high priority for vaccine development. The single-component candidate vaccine against Shigella sonnei (1790GAHB), developed using the GMMA technology, contains the O antigen (OAg) portion of lipopolysaccharide (LPS) as active moiety. The vaccine was well tolerated and immunogenic in early-phase clinical trials. In a phase 1 placebo-controlled dose escalation trial in France (NCT02017899), three doses of five different vaccine formulations (0.06/1, 0.3/5, 1.5/25, 3/50, 6/100 µg of OAg/protein) were administered to healthy adults. In the phase 1 extension trial (NCT03089879), conducted 2–3 years following the parent study, primed individuals who had undetectable antibody levels before the primary series received a 1790GAHB booster dose (1.5/25 µg OAg/protein). Controls were unprimed participants immunized with one 1790GAHB dose. The current analysis assessed the functionality of sera collected from both studies using a high-throughput luminescence-based serum bactericidal activity (SBA) assay optimized for testing human sera. Antibodies with complement-mediated bactericidal activity were detected in vaccinees but not in placebo recipients. SBA titers increased with OAg dose, with a persistent response up to six months after the primary vaccination with at least 1.5/25 µg of OAg/protein. The booster dose induced a strong increase of SBA titers in most primed participants. Correlation between SBA titers and anti-S. sonnei LPS serum immunoglobulin G levels was observed. Results suggest that GMMA is a promising OAg delivery system for the generation of functional antibody responses and persistent immunological memory.
MoO2 Nanospheres Synthesized by Microwave-Assisted Solvothermal Method for the Detection of H2S in Wide Concentration Range at Low Temperature
Authors: An Fei , Mu Shanjun , Zhang Shucai , Xu Wei , Li Na , Wang Haozhi , Wang Shiqiang , Zhao Chenyang , Feng Junjie , Wang Lin , Sun Bing
Published: May 2021

It is crucial to develop highly energy-efficient and selective sensors for wide concentration range of H2S, a common toxic gas that widely exists in petrochemical industries. In this work, MoO2 nanospheres were rapidly synthesized by microwave-assisted solvothermal method, and were subsequently fabricated into H2S gas sensor. The MoO2 nanospheres-based sensor exhibited excellent response toward H2S with good linearity in a wide concentration range (10–240 ppm). Besides, this sensor presented low working temperature, good repeatability, and selectivity against CH4, H2, and CO. The outstanding sensing performance results from the reaction between H2S and abundant chemisorbed oxygen introduced by oxygen vacancies of MoO2. This result indicates that MoO2 nanosphere synthesized by microwave-assisted solvothermal method is a promising sensing material for H2S detection.
Biodiversity and Geographic Distribution of Rhizobia Nodulating With Vigna minima
Authors: Liu Guohua , Liu Xiaoling , Liu Wei , Gao Kangning , Chen Xiaoli , Wang En-Tao , Zhao Zhenjun , Du Wenxiao , Li Yan
Published: May 2021

Vigna minimais a climbing annual plant widely distributed in barren wilderness, grass land, and shrub bush of China and other countries such as Japan. However, the rhizobia nodulating with this plant has never been systematically studied. In order to reveal the biodiversity of nodulating rhizobia symbiosis withV. minima, a total of 874 rhizobium isolates were obtained from root nodules of the plant spread in 11 sampling sites of Shandong Peninsula, China, and they were designated as 41 haplotypes in the genusBradyrhizobiumbased uponrecAsequence analyses. By multilocus sequence analysis (MLSA) of five housekeeping genes (dnaK,glnII,gyrB,recA, andrpoB), the 41 strains representing differentrecAhaplotypes were classified into nine defined species and nine novel genospecies.Bradyrhizobium elkanii,Bradyrhizobium ferriligni, andBradyrhizobium pachyrhiziwere the predominant and universally distributed groups. The phylogeny of symbiotic genes ofnodCandnifHshowed similar topology and phylogenetic relationships, in which all the representative strains were classified into two clades grouped with strains nodulating withVignaspp., demonstrating thatVignaspp. shared common nodulating groups in the natural environment. All the representative strains formed nodules withV. minimain a nodulation test performed in green house conditions. The correlation betweenV. minimanodulating rhizobia and soil characteristics analyzed by CANOCO indicates that available nitrogen, total nitrogen, and organic carbon in the soil samples were the main factors affecting the distribution of rhizobia isolated in this study. This study systematically uncovered the biodiversity and distribution characteristics ofV. minimanodulating rhizobia for the first time, which provided novel information for the formation of the corresponding rhizobium community.
LpxT-Dependent Phosphorylation of Lipid A in Escherichia coli Increases Resistance to Deoxycholate and Enhances Gut Colonization
Authors: Tian Xudong , Manat Guillaume , Gasiorowski Elise , Auger Rodolphe , Hicham Samia , Mengin-Lecreulx Dominique , Boneca Ivo Gomperts , Touzé Thierry
Published: May 2021

The cell surface of Gram-negative bacteria usually exhibits a net negative charge mostly conferred by lipopolysaccharides (LPS). This property sensitizes bacterial cells to cationic antimicrobial peptides, such as polymyxin B, by favoring their binding to the cell surface. Gram-negative bacteria can modify their surface to counteract these compounds such as the decoration of their LPS by positively charged groups. For example, in Escherichia coli and Salmonella, EptA and ArnT add amine-containing groups to the lipid A moiety. In contrast, LpxT enhances the net negative charge by catalyzing the synthesis of tri-phosphorylated lipid A, whose function is yet unknown. Here, we report that E. coli has the intrinsic ability to resist polymyxin B upon the simultaneous activation of the two component regulatory systems PhoPQ and PmrAB by intricate environmental cues. Among many LPS modifications, only EptA- and ArnT-dependent decorations were required for polymyxin B resistance. Conversely, the acquisition of polymyxin B resistance compromised the innate resistance of E. coli to deoxycholate, a major component of bile. The inhibition of LpxT by PmrR, under PmrAB-inducing conditions, specifically accounted for the acquired susceptibility to deoxycholate. We also report that the kinetics of intestinal colonization by the E. coli lpxT mutant was impaired as compared to wild-type in a mouse model of infection and that lpxT was upregulated at the temperature of the host. Together, these findings highlight an important function of LpxT and suggest that a tight equilibrium between EptA- and LpxT-dependent decorations, which occur at the same position of lipid A, is critical for the life style of E. coli.
Cancer Susceptibility Candidate 9 (CASC9) Promotes Colorectal Cancer Carcinogenesis via mTOR-Dependent Autophagy and Epithelial–Mesenchymal Transition Pathways
Authors: Islam Khan Md Zahirul , Law Helen Ka Wai
Published: May 2021

Background

Colorectal cancer (CRC) is the third most common cancer worldwide. Many recent studies have demonstrated that different long non-coding RNAs (lncRNAs) are involved in the initiation, advancement, and metastasis of many cancers including CRC. Cancer susceptibility candidate 9 (CASC9) is an lncRNA that has been reported in many cancers, but its role in CRC is poorly understood. In this study, we aimed to examine the expression of CASC9 in CRC cell lines and to determine the mechanism of action of CASC9 in CRC carcinogenesis.

Methods

The expression of CASC9 in CRC tissues was compared with normal samples from publicly available datasets in The Cancer Genome Atlas (TCGA) and The Encyclopedia of RNA Interactomes (ENCORI). CASC9 expression was further verified in four CRC cell lines (DLD1, HT-29, SW480, and HCT-116) and normal colorectal cell line (CCD-112CoN) by real-time quantitative polymerase chain reaction (RT-qPCR). After gene silencing in HCT-116 and SW480, Cell Counting Kit-8 assay, clonogenic assay, and wound healing assay were performed to evaluate cell proliferation, viability, and migration index of cells. Western blotting was used to explore the key pathways involved.

Results

CASC9 was significantly upregulated as analyzed from both public datasets TCGA and ENCORI where its overexpression was associated with poor survival of CRC patients. Similarly, CASC9 was significantly overexpressed in the CRC cell lines compared with normal cells studied. The silencing of CASC9 in HCT-116 and SW480 attenuated cell proliferation and migration significantly. Furthermore, pathways investigations showed that silencing of CASC9 significantly induced autophagy, promoted AMP-activated protein kinase (AMPK) phosphorylation, inhibited mTOR and AKT signaling pathways, and altered epithelial–mesenchymal transition (EMT) marker protein expression.

Conclusion

We demonstrated that silencing of CASC9 contributes to the reduced CRC cell proliferation and migration by regulating autophagy and AKT/mTOR/EMT signaling. Therefore, CASC9 plays an important role in carcinogenesis, and its expression may act as a prognostic biomarker and a potential therapeutic target of CRC management.
Case Report: Barely Able to Speak, Can’t Stop Echoing: Echolalic Dynamic Aphasia in Progressive Supranuclear Palsy
Authors: Berthier Marcelo L. , Hoet Florencia , Beltrán-Corbellini Álvaro , Santana-Moreno Daniel , Edelkraut Lisa , Dávila Guadalupe
Published: May 2021

The diagnostic criteria for progressive supranuclear palsy (PSP) incorporate two speech-language disturbances (SLDs), non-fluent/agrammatic primary progressive aphasia and progressive apraxia of speech, but overlook the inclusion of other SLDs, including dynamic aphasia (DA). Thus, there is a need to reappraise the broad spectrum of SLDs in PSP to include other presenting phenotypes. Here we report findings from the study of two elderly patients with PSP presenting with DA and irrepressible echolalia. Both patients had markedly impoverished verbal production, but their performance in other tasks (repetition and naming) and auditory comprehension were preserved or only mildly impaired. Experimental tests of DA revealed impaired word and sentence generation in response to verbal and non-verbal stimuli. Additional language and cognitive testing revealed different types of echolalia (mitigated, automatic, and echoing approval) as well as impaired inhibitory control and social cognition (mentalizing). Both patients had negative neuropsychiatric alterations (i.e., apathy, aspontaneity, and indifference/emotional flatness). Brain magnetic resonance imaging in both patients showed atrophy of the midbrain tegmentum and superior medial frontal cortex suggestive of PSP, yet further evaluation of the neural correlates using multimodal neuroimaging and neuropathological data was not performed. However, based on the already known neural basis of DA and echolalia in PSP and stroke, we suggest that, in the present cases, neurodegeneration in the midbrain tegmentum, superior medial frontal lobe, and caudate nucleus was responsible for DA and that decreased activity in these regions may play a permissive role for eliciting verbal echoing via disinhibition of the perisylvian speech-language network.
Efficacy of Low-Dose Rituximab on Neuromyelitis Optica-Associated Optic Neuritis
Authors: Zhao Shuo , Zhou Huanfen , Xu Quangang , Dai Hong , Wei Shihui
Published: May 2021

Purpose: To prospectively investigate the efficacy and tolerance of low-dose rituximab (RTX) for the treatment of neuromyelitis optica-associated optic neuritis (NMO-ON).

Methods: Optic Neuritis patients with seropositive aquaporin 4-antibody (AQP4-Ab) were diagnosed with NMO-ON and recruited for treatment with low-dose RTX (100 mg * 4 infusions) and were then followed monthly for a minimum of 3 months. Reinfusion of 100 mg RTX was given when the CD19+ B lymphocyte frequency was elevated to above 1%. The serum AQP4-Ab level was tested by an enzyme-linked immunosorbent assay (ELISA).

Results: A total of 43 NMO-ON patients (1 male/42 female, 75 involved eyes) were included in this study. CD19+ B cell clearance in the peripheral blood was induced in 97.7% of patients after induction treatment. A significant decrease in serum AQP4-Ab concentration was observed after induction treatment (P = 0.0123). The maintenance time of B cell clearance was 5.2 ± 2.25 months. The relapse-free rate was 92.3% in patients followed-up for over 12 months, and patients with non-organ-specific autoimmune antibodies tended to relapse within 6 months. A total of 96.2% of patients had stable or improved vision, and a decrease in the average expanded disability status scale (EDSS) score was found. Structural alterations revealed by optic coherence tomography were observed in both ON and unaffected eyes. The rates of infusion-related reactions and long-term adverse events (AEs) were 18.6 and 23.1%, respectively. No severe AEs was observed.

Conclusions: Low-dose rituximab is efficient and well-tolerated in treating NMO-ON.
Motor Abnormalities in Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Are Associated With Regional Grey Matter Volumes
Authors: Albajara Sáenz Ariadna , Villemonteix Thomas , Van Schuerbeek Peter , Baijot Simon , Septier Mathilde , Defresne Pierre , Delvenne Véronique , Passeri Gianfranco , Raeymaekers Hubert , Victoor Laurent , Willaye Eric , Peigneux Philippe , Deconinck Nicolas , Massat Isabelle
Published: May 2021

Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are associated with motor impairments, with some children holding a comorbid diagnosis of Developmental Coordination Disorder (DCD). However, DCD is underdiagnosed in these populations and the volume abnormalities that contribute to explaining these motor impairments are poorly understood. In this study, motor abilities as measured by the Developmental Coordination Disorder Questionnaire (DCDQ) were compared between children with ADHD, children with ASD and typically developing (TD) children, aged 8–12 years old. Additionally, the association between the DCDQ scores (general coordination, fine motor/handwriting, control during movement, total) and regional volume abnormalities were explored in 6 regions of interest (pre-central gyrus, post-central gyrus, inferior parietal cortex, superior frontal gyrus, middle frontal gyrus, medial frontal gyrus), within each group and across all participants. Children with ASD and children with ADHD showed impaired motor abilities in all the DCDQ-derived scores compared to TD children. Additionally, most children with ASD or ADHD had an indication or suspicion of DCD. Within the ASD group, coordination abilities were associated with the volume of the right medial frontal gyrus, and within the ADHD group, the total DCDQ score was associated with the volume of the right superior frontal gyrus. This study underlines the importance of routinely checking motor abilities in populations with ASD or ADHD in clinical practise and contributes to the understanding of structural abnormalities subtending motor impairments in these disorders.
Dynamic Functional Connectivity Change-Point Detection With Random Matrix Theory Inference
Authors: Kim Jaehee , Jeong Woorim , Chung Chun Kee
Published: May 2021

To study the dynamic nature of brain activity, functional magnetic resonance imaging (fMRI) data is useful including some temporal dependencies between the corresponding neural activity estimates. Recent studies have shown that the functional connectivity (FC) varies according to time and location which should be incorporated into the model. Modeling this dynamic FC (DFC) requires time-varying measures of spatial region of interest (ROI) sets. To know about the DFC, change-point detection in FC is of particular interest. In this paper, we propose a method of detecting a change-point based on the maximum of eigenvalues via random matrix theory (RMT). From covariance matrices for FC of all ROI's, the temporal change-point of FC is decided by an RMT approach. Simulation results show that our proposed method can detect meaningful FC change-points. We also illustrate the effectiveness of our FC detection approach by applying our method to epilepsy data where change-points detected are explained by the changes in memory capacity. Our study shows the possibility of RMT based approach in DFC change-point problem and in studying the complex dynamic pattern of functional brain interactions.