bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life
Authors: Zhang Baoshan , Gollapudi Deepika , Gorman Jason , O’Dell Sijy , Damron Leland F. , McKee Krisha , Asokan Mangaiarkarasi , Yang Eun Sung , Pegu Amarendra , Lin Bob C. , Chao Cara W. , Chen Xuejun , Gama Lucio , Ivleva Vera B. , Law William H. , Liu Cuiping , Louder Mark K. , Schmidt Stephen D. , Shen Chen-Hsiang , Shi Wei , Stein Judith A. , Seaman Michael S. , McDermott Adrian B. , Carlton Kevin , Mascola John R. , Kwong Peter D. , Lei Q. Paula , Doria-Rose Nicole A. 
Published: April 2022

Abstract
The broadly neutralizing antibody (bNAb) CAP256-VRC26.25 has exceptional potency against HIV-1 and has been considered for clinical use. During the characterization and production of this bNAb, we observed several unusual features. First, the antibody appeared to adhere to pipette tips, requiring tips to be changed during serial dilution to accurately measure potency. Second, during production scale-up, proteolytic cleavage was discovered to target an extended heavy chain loop, which was attributed to a protease in spent medium from two-week culture. To enable large scale production, we altered the site of cleavage via a single amino acid change, K100mA. The resultant antibody retained potency and breadth while avoiding protease cleavage. To further improve the antibody, we added the half-life extending mutation LS, which improved the in vivo persistence in animal models, but did not impact neutralization activity; we observed the same preservation of neutralization for bNAbs VRC01, N6, and PGDM1400 with LS. The final engineered construct, CAP256V2LS, retained the extraordinary neutralization potency of the parent antibody, had a favorable pharmacokinetic profile in animal models, and was negative in in vitro assessment of autoreactivity. CAP256V2LS has the requisite potency, developability and suitability for scale-up, allowing its advancement as a clinical candidate.
Therapeutic effects of bumetanide on neurological dysfunction in a mouse model of Angelman syndrome
Authors: Egawa Kiyoshi , Watanabe Miho , Shiraishi Hideaki , Sato Daisuke , Takahashi Yukitoshi , Fukuda Atsuo 
Published: April 2022

Abstract
Angelman syndrome is a neurodevelopmental disorder caused by loss of function of the maternally expressed UBE3A gene. Treatments for the main manifestations, including cognitive dysfunction or epilepsy, are still under development. Recently, the Cl- importer Na+-K+-Cl- cotransporter 1 (NKCC1) has gained attention as a therapeutic target in many neurological disorders. Dysregulation of neuronal intracellular Cl- concentration ([Cl-]i) is generally regarded as one of the mechanisms underlying neuronal dysfunction caused by the activation of brain NKCC1. Here, we analyzed the regulation of [Cl-]i and the effects of bumetanide, an NKCC1 inhibitor, in Angelman syndrome models (Ube3am-/p+ mice). We observed increased NKCC1 expression in the hippocampus of Ube3am-/p+ mice. The average [Cl-]i of CA1 pyramidal neurons was not significantly different, but demonstrated greater variance in Ube3am-/p+ mice. Tonic GABAA receptor-mediated Cl- conductance was reduced, which may have contributed to maintaining the normal average [Cl-]i. Bumetanide administration restores cognitive dysfunction in Ube3am-/p+ mice. Seizure susceptibility was also reduced regardless of the genotype. These results suggest that aberrantly activated NKCC1 has a pathophysiological impact, leading to cognitive dysfunction in Ube3am-/p+ mice, although the average [Cl-]i is not altered. The blockage of NKCC1 may be a potential therapeutic strategy for patients with Angelman syndrome.
Typical artificial forest soil bacterial community response to the soil environment of Grain for Green area in the Loess Plateau, China
Authors: Liu Xiaohua , Wei Tianxing 
Published: April 2022

Abstract
Purpose: This study aims to analyze the differences of soil bacterial community structure under different vegetation restoration types, and to determine feasible strategies for revegetation of grain for green area in the Loess Plateau. Methods: High-throughput sequencing technology was used to analyze the alpha diversity of soil bacteria, community structure characteristics and the correlation between soil environmental factors and bacterial communities in different vegetation restoration types. Results: The findings reveal that soil microbial C and N in different soil layers shows a decreasing trend with an increase in soil layers. Across all samples, the dominant groups are Proteobacteria, Acidobacteria, Chloroflexi, Gemmatimonadetes, Nitrospirae, Bacteroidetes, GAL15, and Firmicutes. Soil nutrient supply, such as TOC, TN, AN, AP, and AK, had crucial roles in shaping the composition and diversity of the bacterial communities. Conclusions: Based on the results, our data provides a starting point for establishing soil bacterial databases in the Loess Plateau, as well as for the plants associated with the vegetation restoration.
The identification of two newly discovered fluorescent proteins in human glioblastoma
Authors: lyu xiao , Wei Yutian 
Published: April 2022

Abstract
Glioblastoma (GBM) is a common malignancy featured by an extremely strong proliferation with enriched genetic information. Due to the rapid proliferation and the unstable genome-induced evolutionary potential, unique proteins may be expressed in GBM cells under the certain influence of the microenvironment. We therefore speculated that fluorescent proteins exist in GBM cells. During the immunofluorescence staining assay, we accidently discovered autofluorescence in primary GBM cells without fluorescent labeling, which were further validated as 2 newly discovered fluorescent proteins excited by 467 nm and 378 nm wavelength, respectively, namely human fluorescent protein Ⅰ and Ⅱ (HFP1, HFP2). Fluorescence colocalization and fluorescence resonance energy transfer (FRET) results showed the tight interaction of HFP1 and HFP2, and their synergistic effect. Our results for the first time identified 2 newly discovered fluorescent proteins in GBM cells, and clarified their chemical properties.
Unique inverse association between allergic rhinitis and periodontitis: a nationwide population-based study
Authors: Kim Dae-Yeob , Lee Jae-Kwan , Pang Eun-Kyoung , Choi Seong-Ho , Lee Jong-Bin 
Published: April 2022

Abstract
The increase in fine dust levels in the atmosphere has been associated with a growth in the incidence of environmental diseases, including allergic rhinitis (AR). Nasal obstruction caused by AR can impact the conditions in the oral cavity. The aim of this study was to determine the association between AR and periodontitis in the Republic of Korea. This study was based on data from the Seventh Korea National Health and Nutrition Examination Survey (KNHANES VII-1, 2016), which was conducted by the Korea Centers for Disease Control and Prevention. The study included 3,525 adults older than 19 years. Sociodemographic information and medical variables including history of treatment of periodontitis (HTP) and diagnosis of diseases such as AR were extracted from the data. HTP and AR were reported for 22.81 ± 0.84% (weighted mean ± standard error) and 15.32 ± 0.63% of the studied population, respectively. A diagnosis of AR was reported for 11.07 ± 1.28% of those with HTP and for 17.55 ± 1.84% of those without HTP. From these, it was inferred that the prevalence of HTP was 1.536-fold higher in the non-AR group than in their counterparts with AR. Multiple logistic analysis revealed that AR patients had relatively lower risk of periodontal disease, especially among those aged ≤ 64 years.
Prevalence and Patterns of Mutations in RAS/RAF/MEK/ERK/MAPK Signaling Pathway in Colorectal Cancer in North Africa
Authors: Jafari Meryem , Laraqui Abdelilah , Baba Walid , Benmokhtar Soukaina , Zaitouni Sara EL , Ali Abdelmounaim Ait , Bounaim Ahmed , Moujahid Mountassir , Tanz Rachid , Mahfoud Tarik , Sbitti Yassir , Annaz Hicham El , Abi Rachid , Tagajdid Mohamed Rida , Kochri Safae El , Lahlou Idriss Amine , Hsaini Houda El , Belayachi Lamiae , Benjouad Abdelaziz , Ichou Mohammed , En-Nya Amina , Ennibi Khalid 
Published: April 2022

Abstract
Background
Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk.
Methods
Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia.
Results
Seventeen studies were identified through electronic searches with five studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9–51% in Morocco, 23.1–68.2% in Tunisia, 31.4–50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈ 50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%).
Conclusion
KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.
Biomarkers of nanomaterials hazard from multi-layer data
Authors: Fortino Vittorio , Kinaret Pia , Fratello Michele , Serra Angela , Saarimäki Laura , Gallud Audrey , Gupta Govind , Vales Gerard , Correia Manuel , Rasool Omid , Ytterberg A. Jimmy , Monopoli Marco , Skoog Tiina , Ritchie Peter , Moya Sergio , Vázquez-Campos Socorro , Handy Richard , Grafström Roland , Tran Lang , Zubarev Roman , Lahesmaa Riitta , Dawson Kenneth , Löschner Katrin , Larsen Erik , Krombach Fritz , Norppa Hannu , Kere Juha , Savolainen Kai , Alenius Harri , Fadeel Bengt , Greco Dario 
Published: April 2022

Abstract
There is an urgent need to apply effective, data-driven approaches to reliably predict engineered nanomaterial (ENM) toxicity. Here we introduce a predictive computational framework based on the molecular and phenotypic effects of a large panel of ENMs across multiple in vitro and in vivo models. Our methodology allows for the grouping of ENMs based on multi-omics approaches combined with robust toxicity tests. Importantly, we identified novel mRNA-based toxicity markers and extensively replicated them in multiple independent datasets. We found that models based on combinations of omics-derived features and material intrinsic properties displayed significantly improved predictive accuracy as compared to physicochemical properties alone.
Assessment of Vulnerability in three agro-climatic zones of Chhattisgarh with reference to climate change
Authors: Avi AVINASH YADU , Sir G. K. Das 
Published: April 2022

Abstract
The present study was conducted at the Department of Agrometeorology, IGKV Raipur (C.G.) from 2019 to 2021, to assess the zone-level vulnerability in three agro-climatic zones of Chhattisgarh with respect to climate change. The data on various components were collected from the Census directorate of Chhattisgarh (2001 and 2011), Department of Agrometeorology, Raipur and the report of Directorate of economics & statistics Raipur, C.G. for the period of 2000 to 2018 and divided into three different study periods i.e. 2000–2005, 2006–2010 and 2011–2018. We have used Hiremath & Shiyani and Iyenger & Sudershan's methodology to contract the vulnerability index. The outcome of the study indicates that the agricultural sector played a major role and contributed significantly to quantifying the vulnerability followed by climatic and demographic indicators during all three study periods. Results of the composite vulnerability index indicate that Bastar Plateau agro-climatic zone (BP ACZ) was categorized as a more vulnerable zone followed by the Northern Hills agro-climatic zone (NH ACZ) and Chhattisgarh Plain agro-climatic zone (CGP ACZ) in decreasing order of vulnerability in all the study periods. Zone-wise classification of degree of vulnerability, Chhattisgarh Plain agro-climatic zone (CGP ACZ) and the Northern Hills agro-climatic zone (NH ACZ) was categorized as highly vulnerable category, while Bastar Plateau agro-climatic zone (BP ACZ) fell under the Very highly vulnerable category, during all the three study period. We have not found the less vulnerable, moderately vulnerable and vulnerable categories of the zone during all the three study periods.
Site-Selective, Stereocontrolled Glycosylation Catalyzed by Bis-Thioureas
Authors: Jacobsen Eric , Li Qiuhan , Levi Samuel , Wagen Corin , Wendlandt Alison 
Published: April 2022

Abstract
The identification of general and efficient methods for the construction of oligosaccharides stands as one of the great challenges for the field of synthetic chemistry. Selective glycosylation of unprotected sugars and other polyhydroxylated nucleophiles is a particularly significant goal, requiring not only control over the stereochemistry of the forming bond but also differentiation between similarly reactive nucleophilic sites in stereochemically complex contexts. Chemists have generally relied on multi-step protecting-group strategies to achieve site control in glycosylations, but practical inefficiencies arise directly from the application of such approaches. We describe here a new strategy for small-molecule-catalyst-controlled, highly stereo- and site-selective glycosylations of unprotected or minimally protected mono- and disaccharides using precisely designed bis-thiourea small-molecule catalysts. Stereo- and site-selective galactosylations and mannosylations of a wide assortment of polyfunctional nucleophiles is thereby achieved. Kinetic and computational studies provide evidence that site selectivity arises from stabilizing C–H/π interactions between the catalyst and the nucleophile, analogous to those documented in sugar-binding proteins. This work demonstrates that highly selective glycosylation reactions can be achieved through control of stabilizing noncovalent interactions, a potentially general strategy for selective functionalization of carbohydrates.
Comparison of the short-term effects of Quadrant channel fenestration decompression and Delta large channel endoscopy in the treatment of elderly patients with lumbar spinal stenosis
Authors: Zhang Jianing , Liang Dingjie , Xu Mengmeng , Yan Kun , Zhang Dapeng , Qian Weiqing 
Published: April 2022

Abstract
Objective
To compare the clinical efficacy of Quadrant channel fenestration decompression and Delta large channel endoscopic spinal decompression in the treatment of elderly patients with lumbar spinal stenosis.
Methods
A total of 40 patients suffering from lumbar spinal stenosis whose age were over 75 years old were selected for the present study, which was admitted to the Department of Orthopedics from June 2019 to August 2021. The observation group received Delta large channel endoscopy treatment, the control group received Quadrant channel fenestration decompression. Count of general information, course of disease, operation time, intraoperative blood loss, visual analogue scale (VAS) preoperatively, 3 days postoperatively, 3 months postoperatively, and 6 months postoperatively and Oswestry dysfunction score (ODI) of the two groups of patients were recorded and compared.
Results
The duration of the disease course between the two groups was roughly the same, and the difference was not statistically significant (P > 0.05).The two groups of patients had high waist and leg pain and dysfunction index before operation, and the difference in VAS score and ODI index was not statistically significant (P > 0.05).The operation time and intraoperative blood loss of the observation group were less than those of the control group, and the difference was statistically significant (P < 0.05).There were no statistically significant difference in VAS scores and in ODI index at 3 and 6 months between the two groups of patients after surgery (P > 0.05), the difference at 3 days after surgery was statistically significant (P < 0.05).
Conclusion
Both the two surgical methods have a good clinical outcome in the treatment of lumbar spinal stenosis. However, the Delta large channel endoscopy technology has more clearer vision, less trauma, lower incidence of early postoperative low back and faster recovery time than that of Quadrant channel fenestration decompression.
Construction of risk prediction models for chronic kidney disease complicated with renal hypertension based on machine learning algorithms
Authors: Zhu Qin , Du Zhiyin , Liu Ting 
Published: April 2022

Abstract
Background: Chronic kidney disease (CKD) is a causal relationship with hypertension. Renal hypertension, the main complication of CKD, is a traditional risk factor for cardiovascular events. Objective: This retrospective study aimed to establish a risk prediction model for CKD with renal hypertension (RH) using machine learning algorithms.Methods: Using the electronic medical record database of seven large hospitals in Chongqing, 1572 patients with CKD were selected. Based on the presence of RH, they were divided into RH (n = 400) and non-RH (n = 1172) groups. Data from 70% of patients were randomly allocated to the training set to construct the prediction model. The remaining 30% was used as the test set for internal verification. Single-factor logistic regression and correlation analysis were used to screen input indicators. Prediction models were constructed using these machine learning algorithms: support vector machine, random forest, XGBoost, LightGBM, GBDT, and CatBoost. The optimal parameters of these algorithms were determined using the grid search algorithm. The predictive values of the models constructed for predicting CKD with RH were compared.Results: Urinary protein, urinary occult blood, creatinine, cystatin C, age, creatine kinase-MB, and β2 microglobulin were predictors of CKD with RH. The XGBoost model performed best with a sensitivity of 0.820, a specificity of 0.945, an F1 score of 0.840, and an area under the relative operating characteristic curve of 0.935.Conclusion: The clinical prediction model constructed by the XGBoost algorithm had the potential to predict CKD with RH.
Lived Experiences of Medical Sciences Students about their Exams:A Qualitative Study
Authors: Karimi Shahnaz , Fereidouni Zhila , Kouhpayeh Seyed Amin , Shirazi Zahra Hadian 
Published: April 2022

Abstract
Background: Evaluation of medical students is of particular importance. Written examinations have a major role in assessing medical students’ academic abilities and achievements. This research aimed to determine medical students’ experiences about their examinations. Methods: This study was conducted using qualitative research method with phenomenological approach. In doing so, individual in-depth interviews were conducted with 23 students. The observation method was also used during written examinations. The data were analyzed using the interpretive phenomenological method. Results: Based on the findings, three main themes were extracted, which could indicate the students’ views of their exam experiences. These themes included blessing in disguise, stressful difficulties, and emotional fluctuations. Conclusions: The students considered the exams to be blessing in disguise. Although they tended to escape from the exams, they considered it to be necessary as a “learning tool” and “a tool for achieving job position”. On the other hand, because of the psychological stress and score orientation, they regarded it as a stressful difficulty. The test also gave them a range of positive to negative emotional fluctuations. These results revealed important implications that could be applied at educational policymaking levels.
SNG-YOLOX: Non-obvious remote sensing target detection based on enhanced YOLOX
Authors: Mei Yuan , Wu Kaijun , Xu Zehao , Shan Hongquan , Wang Mengsi 
Published: April 2022

Abstract
In the problem of remote sensing target detection, due to the large differences in size and shape of the target, uneven distribution of the target, and strong background interference in remote sensing images, it is difficult to identify and loca te the detection algorithm. To solve this problem, this paper starts from YOLOX. Firstly, self-calibration convolution is used to replace the deep convolution module in CSPLayer in YOLOX to enhance the context-aware ability of the model and expand the receptive field of the model. Then, in order to solve the interference of local information caused by too much consideration of the surrounding context information in the self-calibration convolution, the normalized attention module is introduced at the end of the self-calibration convolution to enhance the attention to local and non-obvious information. Finally, considering the defects of IOU in boundary box regression, GIOU loss is introduced to replace the boundary box regression. Experiments on RSOD remote sensing dat a set show that the improved algorithm improves the detection performance of 7.87 % mAP compared with YOLOX on this data set, and improves 22.03 % AP on non-obvious overpass images. In addition, compared with the current advanced detection algorithm, the improved algorithm has advanced detection performance.
Ultra-thin Optically Transparent Broadband Microwave Metamaterial Absorber Based on Indium Tin oxide
Authors: Xiong Yao , Chen Fu , Cheng Yongzhi , Luo Hui 
Published: April 2022

Abstract
A broadband metamaterial absorber (MMA) with optical transmittance property was designed to address the electromagnetic (EM) pollution in gigahertz (GHz). The proposed MMA with high optical transmittance polymethyl methacrylate (PMMA) between a periodic arrayed indium tin oxide (ITO) film and a low-resistivity ITO reflective layer. Over 90% microwave absorbance can be achieved in the frequency range of 6-17.8 GHz and three distinct absorption peaks can be found in the reflection spectrum. The results also show wide-angular stability, good polarization insensitiveness, and optical transmittance properties. The microwave attenuation mechanisms of the proposed MMA were investigated using surface current distribution and power loss density. The excellent microwave absorption and optical transmittance properties indicate that the designed MMA has strong potential for developing optical transmittance microwave absorption windows and devices.