bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Nanobody-horseradish Peroxidase Fusion Protein-based Competitive ELISA&nbsp;for Rapid Detection of Antibodies Against Porcine Circovirus Type 2
Authors: MU Yang , Jia Cunyu , Zheng Xu , Zhu Haipeng , Zhang Xin , Xu Haoran , Liu Baoyuan , Zhao Qin , Zhou En-Min 
Published: October 2020

Abstract
Background: The widespread popularity of porcine circovirus type 2(PCV2) has seriously affected the healthy development of the pig industry and caused huge economic losses worldwide. A rapid and reliable method is required for epidemiological investigation and evaluating the effect of immunization. However, the current methods for PCV2 antibody detection are time-consuming or very expensive and rarely meet the requirements for clinical application. we have constructed the platform for expressing the nanobody(Nb)‑horseradish peroxidase(HRP) fusion protein as an ultrasensitive probe to detect antibodies against the Newcastle disease virus(NDV), previously. In the present work, an Nb-HRP fusion protein-based competitive ELISA(cELISA) for rapid and simple detection antibodies against PCV2 was developed using this platform to detect anti-PCV2 antibodies in clinical porcine serum.Results: Using phage display technology, 19 anti-PCV2-Cap protein nanobodies were screened from a PCV2-Cap protein immunized Bactrian camel. With the platform, the PCV2-Nb15‑HRP fusion protein was then produced and used as a sensitive reagent for developing a cELISA to detect anti‑PCV2 antibodies. The cut‑off value of the cELISA was 20.72%, 360 porcine serum samples were tested by both newly developed cELISA and commercial kits. The sensitivity and specificity were 99.68% and 95.92%, respectively. The coincidence rate of the two methods was 99.17%. When detecting 620 clinical porcine serum samples, a good consistent (kappa value=0.954) was found between the result of the cELISA and that of commercial kits.Conclusions: In brief, the newly developed cELISA based PCV2-Nb15‑HRP fusion protein is a rapid, low-cost, reliable and useful nanobody-based tool for the serological evaluation of current PCV2 vaccines efficacy and indirect diagnosis of PCV2 infection.
The Clonogenic Assay: Robustness of Plating-Efficiency-Based Analysis is Strongly Compromised by Cellular Cooperation
Authors: Brix Nikko , Samaga Daniel , Hennel Roman , Gehr Katharina , Zitzelsberger Horst , Lauber Kirsten 
Published: October 2020

Abstract
Background:The clonogenic assay is a versatile and frequently used tool to quantify reproductive cell survival in vitro. Current state-of-the-art analysis relies on plating efficiency-based calculations which assume a linear correlation between the number of cells seeded and the number of colonies counted. The present study was designed to test the validity of this assumption and to evaluate the robustness of clonogenic survival results obtained.Methods:A panel of 50 established cancer cell lines was used for comprehensive evaluation of the clonogenic assay procedure and data analysis. We assessed the performance of plating efficiency-based calculations and examined the influence of critical experimental parameters, such as cell density seeded, assay volume, incubation time, as well as the cell line-intrinsic factor of cellular cooperation by auto‑/paracrine stimulation. Our findings were integrated into a novel mathematical approach for the analysis of clonogenic survival data.Results:For various cell lines, clonogenic growth behavior failed to be adequately described by a constant plating efficiency, since the density of cells seeded severely influenced the extent and the dynamics of clonogenic growth. This strongly impaired the robustness of survival calculations obtained by the current state-of-the-art method using plating efficiency-based normalization. A novel mathematical approach utilizing power regression and interpolation of matched colony numbers at different irradiation doses applied to the same dataset substantially reduced the impact of cell density on survival results. Cellular cooperation was observed to be responsible for the non-linear clonogenic growth behavior of a relevant number of cell lines and the impairment of survival calculations. With 28/50 cell lines of different tumor entities showing moderate to high degrees of cellular cooperation, this phenomenon was found to be unexpectedly common.Conclusions:Our study reveals that plating efficiency-based analysis of clonogenic survival data is profoundly compromised by cellular cooperation resulting in strongly underestimated assay-intrinsic errors in a relevant proportion of established cancer cell lines. This severely questions the use of plating efficiency-based calculations in studies aiming to achieve more than semiquantitative results. The novel approach presented here accounts for the phenomenon of cellular cooperation and allows the extraction of clonogenic survival results with clearly improved robustness.
Vemurafenib Sensitizes Melanoma Cells to Temozolomide by Downregulating MGMT Expression.
Authors: Ren Bingjie , Li Qiang , Zhao Jing , Guo Xia , Hu Yingxi , Wu Mengyao , Li Dapeng , Li Daoming , Tao Min , Liang Rongrui 
Published: October 2020

Abstract
BackgroundThe alkylating agent temozolomide (TMZ) is widely used to treat melanoma in clinical practice. However, cells expressing the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) are highly resistant to this drug. Vemurafenib (vMF), a targeted BRAF kinase inhibitor, is applied to treat BRAF-V600 mutant metastatic melanoma. Studies have suggested that blocking this pathway prevents MGMT from affecting TMZ sensitization. However, reports of the use of the combination of vMF and TMZ in the treatment of melanoma are lacking.MethodsCell viability was detected by MTT assay, cell apoptosis was assayed by flow cytometry, and the mRNA level of the MGMT gene was measured by RT-qPCR. Western blotting, immunofluorescence staining were utilized to determine the expression of the protein. The pcDNA3.1-MGMT vector was transiently transfected to generate MGMT-overexpressing cells for experiments. A nude mouse malignant melanoma xenograft model was established for in vivo drug experiments.ResultsvMF increased TMZ-induced cytotoxicity by increasing DNA damage. vMF inhibited the MAPK/ERK signaling pathway and the mRNA and protein expression of the MGMT gene. vMF did not inhibit MGMT protein expression in A375-MGMT OE cells, and the vMF-induced sensitization effect was attenuated. Moreover, TMZ exposure activated ERK activity in malignant melanoma. The expression of MGMT and p-ERK1/2 was positively correlated in melanoma tissues.ConclusionvMF sensitized melanoma to TMZ by inhibiting the MAPK/ERK-MGMT pathway, and the combination of vMF and TMZ is expected to improve the clinical treatment effect on malignant melanoma.
Neuropsychiatric Symptoms and Mortality Among Patients With Mild Cognitive Impairment and Dementia Due to Alzheimer’s Disease
Authors: Huang Mei-Feng , Lee Wei-Ju , Yeh Yi-Chun , Lin Yung-Shuan , Lin Hsiu-Fen , Wang Shuu-Jiun , Yang Yi-Hsin , Chen Cheng-Sheng , Fuh Jong-Ling 
Published: October 2020

Abstract
BackgroundNeuropsychiatric symptoms (NPS) could increase mortality risk in people with dementia due to Alzheimer’s disease (AD). However, whether NPS affects mortality risk in people with mild cognitive impairment (MCI) and whether any specific syndrome of NPS influences this risk are still unclear.MethodsIn total, 984 participants with dementia due to AD, 338 with MCI, and 365 controls were enrolled. Over a mean of 5-year follow-up, cause of death data were obtained from the Ministry of Health and Welfare in Taiwan. NPS were assessed using Neuropsychiatric Inventory Questionnaire (NPI-Q), and psychosis, mood, and frontal domain scores were determined. Survival analyses were conducted to determine the hazard ratio (HR) of death.ResultsIn controlled analyses, HR of death for AD was 2.19 (95% confidence interval [CI] = 1.29–3.71) compared with the control group, whereas no statistical significance was noted for the MCI group. A high NPI-Q score (above the median score) increased mortality risk for both the MCI and AD groups, with HRs of 2.32 (95% CI = 1.07–5.03) and 2.60 (95% CI = 1.51–4.47), respectively. Among NPI-Q domain scores, only high mood domain, but not psychosis or frontal domain, scores increased death risk for both the MCI (HR = 2.89, 95% CI = 1.00–8.51) and AD (HR = 2.59, 95% CI = 1.47–4.55) groups.ConclusionsMortality risk is high for patients with AD. Not only for AD, patients with MCI presenting with NPS, particularly mood symptoms, have high death risk.
An electronic neuromorphic system for real-time detection of High Frequency Oscillations (HFOs) in intracranial EEG
Authors: Sharifhazileh Mohammadali , Burelo Karla , Sarnthein Johannes , Indiveri Giacomo 
Published: October 2020

Abstract
The analysis of biomedical signals for clinical studies and therapeutic applications can benefit from compact and portable devices that can process these signals locally, in real-time, without the need for off-line processing. An example is the recording of intracranial EEG(iEEG) during epilepsy surgery with the detection of High Frequency Oscillations (HFOs, 80-500 Hz), which are a biomarker for the epileptogenic zone. Conventional approaches of HFO detection involve the offline analysis of prerecorded data, often on bulky computers. However, clinical applications during surgery or in long-term intracranial recordings demand a self-sufficient embedded device that is battery-powered to avoid interfering with other electronic equipment in the operation room. Mixed-signal and analog-digital neuromorphic circuits offer the possibility of building compact, embedded, and low-power neural network processing systems that can analyze data on-line and produce results with short latency in real-time. These characteristics are well suited for clinical applications that involve the processing of biomedical signals at (or very close to) the sensor level. In this work, we present a neuromorphic system that combines for the first time a neural recording headstage with a signal-to-spike conversion circuit and a multi-core spiking neural network (SNN) architecture on the same die for recording, processing, and detecting clinically relevant HFOs in iEEG from epilepsy patients. The device was fabricated using a standard 0.18μm CMOS technology node and has a total area of 99 mm2. We demonstrate its application to HFO detection in the iEEG recorded from 9 patients with temporal lobe epilepsy who subsequently underwent epilepsy surgery. The total average power consumption of the chip during the detection task was 614.3 μW. We show how the neuromorphic system can reliably detect HFOs: the system predicts postsurgical seizure outcome with state-of-the-art accuracy, specificity, and sensitivity (78%, 100%, and 33% respectively). This is the first feasibility study towards identifying relevant features in intracranial human data in real-time, on-chip, using event-based processors and spiking neural networks. By providing “neuromorphic intelligence” to neural recording circuits the approach proposed will pave the way for the development of systems that can detect HFO areas directly in the operation room and improve the seizure outcome of epilepsy surgery.
Squamous cell carcinoma antigens (SCCAs) are sensitive biomarkers for atopic dermatitis in children and adolescents: a cross-sectional study
Authors: Hirayama Junya , Fujisawa Takao , Nagao Mizuho , Kuwabara Yu , Kainuma Keigo , Azuma Yoshinori , Ono Junya , Ohta Shoichiro , Hirayama Masahiro , Izuhara Kenji 
Published: October 2020

Abstract
Background We recently reported that squamous cell carcinoma antigen 2 (SCCA2) is a reliable biomarker for atopic dermatitis (AD) in children. To further clarify its utility, we investigated for possible effects of comorbid allergies and AD treatment on serum SCCA levels in children and adolescents.Methods Volunteers aged less than 18 years were recruited through our website. Their allergic status was elucidated using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. We also recruited pediatric patients who needed to be hospitalized because of severe AD. The serum levels of SCCA1 and SCCA2 were measured by ELISAs. In the severe AD patients, the levels of thymus and activation-regulated chemokine (TARC), SCCA1 and SCCA2 were measured before and after hospitalization. The severity of AD was assessed using the severity scoring of atopic dermatitis (SCORAD) index.Results A total of 576 participants (547 volunteers and 29 patients) were enrolled in the study. The levels of SCCA1 and SCCA2 were significantly higher in volunteers with mild AD and patients with severe AD than in healthy volunteers without allergic diseases. In contrast, the levels were not elevated in those who had mild bronchial asthma or mild allergic rhinitis without AD. TARC, SCCA1 and SCCA2 were decreased in patients with severe AD, reflecting clinical improvement in response to treatment. Linear regression analysis for predicting a decrease in the SCORAD index showed R2 values of 0.16, 0.38 and 0.48 for TARC, SCCA1 and SCCA2, respectively..Conclusions SCCAs, especially SCCA2, are sensitive biomarkers for detecting AD in children and adolescents, even in the mild stage, and for assessing the severity and response to treatment of severe AD.
Mitochondria-Related Core Genes and TF-miRNA-hub mrDEGs Network in Breast Cancer
Authors: Yan Li-rong , Wang Ang , Lv Zhi , Yuan Yuan , Xu Qian 
Published: October 2020

Abstract
BackgroundMitochondria-nuclear cross talk and mitochondrial retrograde regulation are involved in the genesis and development of breast cancer (BC). Therefore, mitochondria can be regarded as a promising target for BC therapeutic strategies. In the present study, we aimed to construct regulating network and seek the potential biomarkers of BC diagnosis, prognosis and also the molecular therapeutic targets from the perspective of mitochondrial dysfunction. MethodsThe microarray data of mitochondria-related encoding genes of BC were downloaded from GEO including GSE128610 and GSE72319. GSE128610 was treated as test set and validation sets consisted of GSE72319 and TCGA, which were used for identifying mitochondria-related differential expressed genes (mrDEGs). We performed enrichment analysis, PPI network, hub mrDEGs, and overall survival analysis and constructed transcription factor (TF)-miRNA-hub mrDEGs network. ResultsA total of 23 up-regulated and 71 down-regulated mrDEGs were identified and validated. Enrichment analyses indicated that mrDEGs were associated with several cancer-related biological processes, Moreover, 9 hub mrDEGs were identified and validated in tissues. Finally, 5 hub coregulated mrDEGs, 21 miRNA and 117 TF were used to construct TF-miRNA-hub mrDEGs network. MAZ, HDGF and SP2 could regulate 3 hub mrDEGs. hsa-mir-21-5p, hsa-mir-1-3p, hsa-mir-218-5p, hsa-mir-26a-5p, and hsa-mir-335-5p regulated 2 hub mrDEGs. Overall survival analysis suggested that the up-regulated FN1 and down-regulated DDR2 conferred to poor BC prognosis. ConclusionTF-miRNA-hub mrDEGs has instruction significance for the etiology exploration of BC. The identified hub mrDEGs, such as FN1 and DDR2, were likely to regulate mitochondrial function and might be novel biomarkers of BC diagnosis and prognosis as well as the therapeutic targets.
Metabotropic Glutamate Receptor 5 Regulates Synaptic Plasticity in a Chronic Migraine Rat Model Through the PKC/NR2B&nbsp;Signal
Authors: Niu Yingying , Zeng Xiaoxu , Zhao Lilin , Zhou Yang , Qin Guangcheng , Zhang Dunke , Fu Qingqing , Zhou Jiying , Chen Li-Xue 
Published: October 2020

Abstract
Background: The mechanism of chronic migraine(CM) is complex, central sensitization is considered as one of the pathological mechanism. Synaptic plasticity is the basis of the central sensitization. Metabotropic glutamate receptor 5 (mGluR5) plays a vital role in the synaptic plasticity of the central nervous system. However, whether mGluR5 can promote the central sensitization by regulating synaptic plasticity in CM is unknown. Methods: Male Wistar rats were used to establish a CM rat model, and the expression of mGluR5 mRNA and protein were detected by qRT-PCR and western blotting. The allodynia was assessed by mechanical and thermal thresholds, and central sensitization was assessed by expression of the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) at Serine 133（pCREB-S133）and c-Fos. The synaptic-associated protein postsynaptic density protein 95 (PSD), synaptophysin (Syp), and synaptophysin-1(Syt-1) and synaptic ultrastructure were detected to explore synaptic plasticity. Results: We found that the expression of mGluR5 was upregulated in CM rats. Downregulated the mGluR5 with MPEP alleviated the allodynia and central sensitization. Moreover, mGluR5 regulated the synaptic plasticity by PKC/NR2B signal. Conclusions: These results indicate that mGluR5 contributed to central sensitization by regulating synaptic plasticity in CM through the PKC/NR2B signal, which suggests that mGluR5 may be a potential therapeutic candidate for CM.
Ursolic acid loaded-mesoporous hydroxylapatite/ chitosan therapeutic scaffolds promote the bone regeneration
Authors: Yu Xijiao , Wang Yuxuan , Liu Xiao-Liang , Yu Degang , Zhang Shanyong 
Published: October 2020

Abstract
Background: Mesoporous hydroxylapatite (MHAP) could play an important role in bone regeneration, and UA (Ursolic acid) also promote the osteogenic differentiation. Accordingly, we developed the UA loaded MHAP scaffolds to cure bone defects. In vitro, we synthesize biomaterial scaffolds. By SEM, XRD, EDS and FTIR, we test the performance of the hybrid scaffolds. By drug release, ALP staining, Alizarin red staining, and Western blotting, we test the osteo-inductive properties of scaffold materials. In vivo, We verify bone regeneration through a rat skull defect model.Results: The MHAP is a rod-shaped structure with a length of 100~300nm and a diameter of 40~60nm. The critical structure gives the micro scaffold a property of control release due to the pore sizes of 1.6~4.3 nm in hydroxyapatite and the hydrogen bonding between the scaffolds and UA drugs. The released UA drugs could notably promote the expression of osteogenic-related genes (COL1, ALP, OPG) and osteogenic-related proteins (BMP-2, RUNX2 and COL1). Both the images of μCT and the results of double fluorochrome labelling demonstrated that therapeutic scaffolds promoted the bone regeneration. We obtained the similar results through immunohistochemistry. Conclusions: The MHAP-CS-UA scaffolds have good osteo-inductivity and bone regeneration. And they will be the novel and promising candidates to cure the bone disease.
“EosFit-Pinc: A simple GUI for host-inclusion elastic thermobarometry” by Angel et al. (2017)—Discussion
Authors: Zhong Xin , Dabrowski Marcin , Powell Roger , Jamtveit Bjørn 
Published: October 2020

Abstract
In this comment, we show mathematically that the equations of Angel et al. (2017) and Guiraud and Powell (2006) are equivalent. The tiny difference is due to different definitions of strain.
Identifikasi Chemophobia dan faktor yang mempengaruhi Persepsi pada Mahasiswa
Authors: Herlina Nina , Pratiwi Resi , Mulyanti Sri 
Published: October 2020

<p>“<em>Chemophobia</em>” atau kecemasan kimia diyakini menjadi salah satu penyebab sedikitnya minat siswa terhadap jurusan kimia. Siswa juga kurang optimal dalam memahami pelajaran kimia. Siswa memandang kimia sebagai sesuatu yang negatif yang disebabkan oleh persepsi dan informasi yang mengenai kimia. Jenis penelitian ini adalah penelitian deskriptif dengan menggunakan pendekatan kualitatif. Penelitian ini bertujuan untuk mengidentifikasi eksistensi <em>Chemophobia</em> di kalangan mahasiswa serta faktor-faktor yang mempengaruhi pembentukan persepsi tersebut. Identifikasi dilakukan terhadap 60 mahasiswa jurusan sains dari beberapa universitas di Jawa dan Aceh menggunakan kuisioner <em>googleform</em>. Analisis dilakukan dengan tiga tahapan; penerimaan stimulus, pengelolaan stimulus, dan pembentukan persepsi. Berdasarkan hasil identifikasi didapatkan 55% responden tidak mengalami <em>chemophobia</em> sedangkan 45% responden mengalami chemophobia. Hal ini menunjukkan bahwa 45% responden memiliki ketakutan terhadap bahan kimia. Analisi pembentukan persepsi menunjukkan sebanyak 87% respoden mengaatakan bahan kimia berdampak positif. Hasil analiss faktor pembentukan persepsi dapat disimpulkan bahwa faktor internal memiliki pengaruh lebih besar dibandingkan dengan faktor eksternal dalam pembentukan persepsi tentang kimia jumlah yang mengalami <em>Chemophobia</em> sedikit.</p>
Analysis of Chinese Herbal Formulae Recommended for COVID-19 in Different Schemes in China: A Data Mining Approach
Authors: Yin LiWei , Gao YaCen , Li ZiPing , Wang MengYu , Chen KaiXin 
Published: October 2020

Background:
Novel coronavirus pneumonia (NCP), or coronavirus disease 2019
(COVID-19), is a worldwide health threat that has affected millions of people globally. Traditional
Chinese medicine (TCM) has been introduced for the treatment of COVID-19. However, efficacy
differs among herbal medicines, and the ideal prescription pattern for TCM herbal formulae for
COVID-19 treatment needs to be explored. Therefore, the data mining method has been used in
this study to analyze the TCM prescription pattern for COVID-19.

Objective:
The aim of this study was to analyze the TCM prescription pattern in Regional Schemes
in China for COVID-19 in order to provide a new reference for the use of TCM in COVID-19 treatment.

Methods:
By searching the TCM treatment protocols of COVID-19 in 23 Regional Schemes, TCM
syndromes and herbal medicines were analyzed by data mining. The Ancient and Modern Medical
Case Cloud Platform (V2.1 personal Edition) was used to perform frequency statistics, correlation
analysis, and cluster analysis. A total of 82 TCM syndromes and 171 Chinese herbal medicines
were found. The course of the disease can be divided into the early stage, middle stage, severe
stage, and recovery stage.

Results:
In the early stage, the focus is primarily on resolving dampness, dispelling cold, and diffusing
the lungs. In the middle stage, the treatment priority is clearing heat and resolving toxins,
promoting lung function, and relieving asthma. In the severe stage, the focus is on tonifying Qi, restoring
Yang, and relieving the depletion of Yin and Yang. In the recovery stage, the main treatment
is to invigorate the spleen and regulate Qi, tonify Qi, nourish Yin, and clear residual disease. There
are certain differences between the Regional Schemes and the Nation Schemes, but the core prescription
pattern of the former is consistent with the latter. The effectiveness of these 171 Chinese
herbs include but are not limited to inhibiting COVID-19, strengthening immune system function,
preventing heart failure, acting as antioxidants, oxidative stress inhibitory effects, maintaining organ
function, and improving leukocyte survival.

Conclusion:
This study may help to improve understanding of TCM herbal prescription pattern,
practices, reveal the efficacy of combinations of Chinese herbs, and provide new ideas for TCM
treatment for COVID-19.