bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Insights into the Binding of Nanobodies Lam2 and Lam4 to the Red Fluorescent Protein mCherry
Authors: Wang Ziying , Li Long , Hu Rongting , Zhong Peiyu , Zhang Yiran , Cheng Shihao , Liu Rui , Ding Yu 
Published: April 2021

Abstract
Background

Red fluorescent proteins (RFPs) are widely used in molecular biology research, especially in deep tissues and animal models, because of their superior autofluorescence, light scattering, and phototoxicity to GFP. Although RFP can be easily monitored in vivo, improved manipulation of RFP is still desired. Using suitable nanobodies (Nbs) to bind to different epitopes of RFP is the most promising approach; thus, it is crucial to obtain structural information on how the different Nbs interact with RFP.
Results

We determined the crystal structures of the LaM2-mCherry and LaM4-mCherry complexes at 1.4 Å and 1.9 Å resolution. Our results showed that LaM2 binds to the side of the mCherry β-barrel, while Lam4 binds to the bottom of the β-barrel and does not interfere with the homo-oligomerization interface. The distinct binding sites of LaM2 and LaM4 were further verified by ITC, F-SEC and DLS assays. Our results also showed that LaM2 and LaM4 can bind simultaneously to mCherry, which is crucial for recruiting multiple operation elements to the RFP. The binding of LaM2 or LaM4 did not significantly change the chromophore environment of mCherry, which is important for fluorescence quantification assays, while several GFP Nbs significantly altered the fluorescence. Mutation of the residues of the LaM2 or LaM4 binding interface to mCherry significantly decreased the binding affinity of the Nb to mCherry.
Conclusions

Our results provided atomic resolution interaction information on the binding of Nbs LaM2 and LaM4 binding with mCherry, which is important for developing detection and manipulation methods for RFP-based biotechnology.
The Proportion, Species Distribution and Dynamic Trends of Bloodstream Infection Cases in a Tertiary Hospital in China, 2010-2019
Authors: Cui Jiewei , Li Meng , Wang Juan , Qiang Xiaofei , Liang Zhixin 
Published: April 2021

Abstract
Background: Recent epidemiological studies on bloodstream infection (BSI) that include the proportion, species distribution and dynamic changes are scarce in China. This study was performed to understand these epidemiological data of BSI over the past 10 years in China. Methods: Using real-time nosocomial infection surveillance system, this study was retrospectively performed in one of the largest hospitals in China. The time trend was tested using the Cochran-Armitage trend test in R Programming Language.Results: From 2010 to 2019, there were totally 9381 episodes of BSI cases out of 1,437,927 adult-hospitalized patients in the hospital, the total proportion of BSI cases was 6.50‰ (6.50 episodes per 1000 adult-hospitalized patients per year) and the proportion had significantly decreased (8.24‰ to 6.07‰, time trend P<0.001). Among the 9381 episodes of BSI, 93.1% were bacteremia and others were fungemia (6.9%). As the most common species, the composition ratios of coagulase-negative staphylococcus (25.6% to 32.5%), Escherichia coli (9.8% to 13.6%) and Klebsiella pneumonia (5.3% to 10.4%) had been dynamically increased (all time trends P<0.05) and the proportion of Pseudomonas aeruginosa had decreased (4.0% to 2.4%, time trend P=0.032). However, Staphylococcus aureus (3.3% to 3.1%) and Acinetobacter baumannii (4.4% to 4.2%) had not changed significantly (P>0.05). These common species were consistent with China Antimicrobial Surveillance Network reported in 2018 (2018 CHINET report), but their composition ratios were different. Additionally, among bacteremia, the proportion of multidrug-resistant bacteria gradually increased from 52.9% to 68.4% (time trend P<0.001). Conclusion: The proportion and species distribution of BSI were dynamically changing along certain trends. These trends deserved more attention from clinicians and researchers.
Self-Assembling Ferritin-Dendrimer Nanoparticles for Targeted Delivery of Nucleic Acids to Myeloid Leukemia Cells
Authors: Palombarini Federica , Masciarelli Silvia , Incocciati Alessio , Liccardo Francesca , Fabio Elisa Di , Iazzetti Antonia , Fabrizi Giancarlo , Fazi Francesco , Macone Alberto , Bonamore Alessandra , Boffi Alberto 
Published: April 2021

Abstract
Background: In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells.Results: Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting the expected phenotypic effects and inducing morphological changes typical of the granulocyte differentiation process. Conclusion: The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells.
Effect of Synthesis Method on Antibacterial and Antibiofilm Activity Properties of BaFeO3-δ Perovskite Nanomaterials
Authors: khalaf eid , Abdel-Khalek E. K. , Askar Ahmed. A. , Motawea M. A. , Aboelnasr Mohamed A. , El-Bahnasawy H. H. 
Published: April 2021

Abstract
BaFeO3-δ perovskite nanomaterials have been synthesized by two different methods: co-precipitation (Cop) and sol-gel (Sol) methods. Rietveld analysis of the X-Ray diffraction (XRD) shows that the samples are crystallized in rhombohedral perovskite structure with space group R3c. Scanning electron microscope (SEM) of these samples showed the agglomerations of various particles. Dynamic light scattering (DLS) showed that the average particle size of BaFeO3-Cop sample is larger than that of BaFeO3-Sol sample. The amount of oxygen deficient (δ) and the valence states of Fe ions in these samples were determined from Mössbauer spectroscopy. X-ray photoelectron spectroscopy (XPS) shows the elemental compositions and surface electronic states of these samples. The thermal, optical and magnetic properties of these samples depend on the amount of oxygen deficient (δ) and the valence states of Fe ions. Furthermore, the antibacterial and antibiofilm activity of these samples was systematically investigated. The present results suggest that BaFeO3-δ superparamagnetic perovskite can be used as antibacterial and antibiofilm agent.
Somatic targeted mutation profiling of colorectal cancer precursor lesions
Authors: Santos Wellington dos , Reis Mariana Bisarro dos , Porto Jun , de Carvalho Ana Carolina , Matsushita Marcus , Oliveira Gabriela , Syrjänen Kari , Reis Rui Manuel , Guimaraes Denise 
Published: April 2021

Abstract
Most colorectal cancers (CRC) arise from precursor lesions. We aimed to characterize the mutation profile of CRC precursor lesions in a Brazilian population. In total, 90 FFPE lesions, including 67 adenomas, 7 sessile serrated lesions, and 16 hyperplastic polyps, were analyzed by next-generation sequencing. The genetic ancestry of the patients was estimated. Somatic driver mutations were identified in 66.7% of cases, including alterations in APC (32.2%), TP53 (20.0%), KRAS (18.9%), BRAF (13.3%) and EGFR (7.8%). Adenomas displayed a higher number of mutations, mainly in APC, compared to serrated polyps (73.1% vs. 47.8%, p = 0.039). Advanced adenomas had a higher frequency of mutation in KRAS and GNAS and a high overall mutation rate than early adenomas (92.9% vs. 59%, p = 0.002). Concerning the serrated pathway, a higher frequency of mutations, mainly in BRAF, was observed in sessile serrated lesions (85.7%) compared to hyperplastic polyps (31.3%, p = 0.027). A high degree of ancestry admixture was observed in the population, with a predominance of European followed by African components. The mutation profile of Brazilian colorectal precursor lesions exhibits a similar landscape to other populations. These results bestow the knowledge of CRC's biological history and may contribute to a molecular screening approach.
How Can Patient-Reported Outcomes of Periacetabular Osteotomy be Improved? A Short-Term Follow-up of 79 Hips.
Authors: Fan YiNuo , Li Weifeng , Wu Yunlong , Hong Guoju , Li Zhongfeng , Chen Lixin , Fang Hanjun , Zhou Chi , Chen Zhenqiu 
Published: April 2021

Abstract
Background

Bernese periacetabular osteotomy (PAO) is an effective treatment for patients with developmental dysplasia of the hip (DDH). PAO has been widely used in China, but few follow-up outcomes have been reported in the international community. Moreover, the risk factors affecting patient-reported outcomes have not been discussed in recent studies. In this study, patient-reported outcomes after PAO were reported, and risk factors affecting patient-reported outcomes were analyzed.
Methods

Patients who underwent PAO for DDH from January 2014 to January 2020 were selected as the study subjects, and 79 hips were included in the analysis after screening (71 patients, with an average follow-up time of 2.98 years). The Harris Hip Score (HHS) and International Hip Outcome Instrument-12 (iHOT-12) were used to assess hip function and patient quality of life. A HHS < 80 was defined as symptomatic hips, that is, an adverse outcome; otherwise, it indicated preserved hips. Multivariate logistic regression analysis was used to predict the risk factors influencing the patient-reported outcomes, and receiver operating characteristic (ROC) curve analysis was performed on the risk factors to determine their sensitivity, specificity and cutoff value.
Results

Clinical outcome analysis demonstrates marked improvements in patient-reported outcomes. The multivariate logistic regression analysis showed that when the postoperative LCEA was > 38°, adverse outcomes were much more likely. However, a Tönnis angle of -10°-0 was a protective factor. In addition, hips with fair or poor joint congruency were 7.794-fold more likely to develop negative outcomes. The ROC curve analysis showed that the optimal thresholds for the LCEA and Tönnis angles used to predict outcomes after PAO were 38.1° and − 9°, respectively. The patients with a postoperative LCEA < 38.1° had a success rate of 83%. In contrast, the success rate was 32% for patients with a postoperative LCEA > 38.1°. In addition, while the patients with a postoperative Tönnis angle of -9°-0 had a success rate of 70%, and those with a Tönnis angle of 0–10° had a success rate of 65%; the success rate of a Tönnis angle <-9° was only 10%.
Conclusions

Our results demonstrate marked improvements in patient-reported outcomes. Among hips with preoperative excellent or good joint congruency treated by experienced surgeons who obtain the proper postoperative LCEA and Tönnis angles, good patient-reported outcomes can be expected.
Resting-State Network Connectivity in Newly Diagnosed Drug-Naïve Parkinson’s Disease Patients With Mild Cognitive Impairment
Authors: Hou Yanbing , Wei Qianqian , Ou Ruwei , Zhang Lingyu , Yuan Xiaoqin , Gong Qiyong , Shang Huifang 
Published: April 2021

Abstract
Background: Cognitive impairment (CI) is one of the most frequent non-motor features in Parkinson's disease (PD). The frequency of mild cognitive impairment (MCI) was reported to exceed 40% in a large cohort of newly diagnosed PD patients.Method: Resting-state functional MRI (rs-fMRI) data was collected in 47 newly diagnosed drug-naïve PD patients (including 28 PD patients with MCI (PD-MCI subgroup) and 19 PD patients with cognitively unimpaired (PD-CU subgroup)) and 28 age- and sex-matched healthy controls (HCs). Independent component analysis (ICA) can decompose rs-fMRI data into resting state networks (RSNs). Brain intra- and inter-network alterations were investigated in RSNs among PD-MCI, PD-CU, and HCs groups.Results: Seven large-scale brain networks were extracted. The default mode network (DMN), visual network (VN) and sensorimotor network (SMN) were selectively vulnerable in the PD-MCI subgroup relative to the HC group. In PD-MCI patients, the reduced functional connectivity (FC) within the DMN was positively correlated with brief visuospatial memory test-revised (BVMT-R) scores (memory function); the reduced FC within the VN was positively correlated with clock copying test (CCT) scores (visuospatial function). In whole PD patients, the reduced FC within the SMN was negatively correlated with the Unified PD Rating Scale (UPDRS) part III scores. Moreover, FC between the SMN and limbic network, and between the ventral attention network (VAN) and VN were more prone to be damaged in PD patients.Conclusions: The DMN, VN and SMN were disrupted in PD-MCI patients. FC between the SMN and limbic network, and between the VAN and VN were also impaired in PD patients. The impaired intra- and inter-connectivity could provide further insights into the pathophysiological alterations of brain connectivity in newly diagnosed drug-naïve PD.
Prediction Dynamics of Malicious Objects in Internet of Things (IoT)
Authors: Saini Hemraj , Saini Dinesh Kumar , Mabrouk Anouar Ben , Tripathi Rajan , Gupta Punit 
Published: April 2021

Abstract
Presently, the Internet of Things (IoT) is playing an important role in data gathering and submitting information to different data analysis engines for most of the real-world applications. However, IoT applications have a danger of information theft or manipulation by malicious attacks which lead to a wrong conclusion or result. Therefore, malicious attacks are to be taken care of by using some means like prediction dynamics of malicious objects in IoT. In this manuscript, the behavior of malicious objects in the IoT network is studied with the help of two deterministic models. These models are working like the pre-predator model in IoT networks where prey consists of infected and uninfected nodes, whereas, the predator consists of malicious objects. Besides, the time delay is not much real in the spread of infection in networks due to the chaotic nature of the malicious object's outbursts, and therefore, these models are explored with delay differential equation modeling. Stochastic behavior of malicious objects in real dynamics of transmission of malicious objects makes things worse. Therefore, the study of proposed models in absence of anti-malicious software as well as in presence of anti-malicious software is carried out. Threshold conditions are characterized by the reproductive number and the system is identified as in an asymptotically stable state to help the fast recovery from malicious objects which helps to model the behavior of malicious objects spread in the real environment like IoT.
Understand the role of exosomal miRNA in the development of breast cancer in patients with chronic HBV infection
Authors: Xie Wenjun , Chen Chun , Lin Qiang , Li Huashui 
Published: April 2021

Abstract
Background: Female chronic hepatitis B patients has shown a higher incidence of breast cancer with poorer prognosis, compared to the non-infected female patients. A significant difference in miRNAs expression in serum exosomes has been identified between female patients with chronic HBV infection and non-infected female. Whether this difference could contribute to the differential incidence and development of breast cancer in these female patients has not been fully understood.Methods: Information of exosomal expression of miRNAs (expression profiles of GSE33857) were acquired from the Gene Expression Omnibus (GEO) database. Targeted genes of this miRNAs and the differentially expressed genes of breast cancer in GEPIA V2.0 database was used to obtain the differentially expressed genes (DEGs). Four analytic methods were performed, including functional annotation, protein-protein interaction (PPI) network and module construction, the clinical pathologic parameters analysis, alongsides prognosis analysis.Results: In the serum exsomes, expression of miR-1237-3p and miR-363-3p were down-regulated whilst expression of miR-100-5p, miR-125b-5p, miR-1260a, miR-1287-5p, miR-148a-3p, miR-885-5p and miR-99a-5p were up-regulated in female chronic hepatitis B (CHB) patients. 228 up-regulated genes and 641 down-regulated genes were selected as DEGs. The DEGs involved in several biological processes ranging from cellular response to hormone stimulus. According to the main enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was the pathways in cancer. Our analysis revealed that among the hub genes, CXCL11 was up-regulated and CXCL12, GNG2, LPAR1, GPR17, CXCL1, ADCY5, ADCY3, CX3CL1, S1PR1 were down-regulated. These genes expression levels were verified in UALCAN, Oncomine and HPA database. High expression level of CXCL11 and low expression levels of CXCL12, LPAR1, ADCY3 and CX3CL1 were positively correlated with some clinical pathological parameters that predicted worse prognosis. Kaplan-Meier (K-M) plotter analysis revealed that these genes that showed a low expression level were positively correlated with poor prognosis of breast cancer, and the high expression genes were negatively correlated with poor prognosis of breast cancer.Conclusion: This bioinformatics analysis study explored the mechanisms of chronic HBV related occurrence and development of breast cancer by changing the expression of miRNAs of serum exosomes. It provided novel directions and therapeutic strategy for chronic HBV infection associated occurrence and development of breast cancer in female patients.
Novel biological implication of a strictly monomorphic GCC repeat in the human PRKACB gene
Authors: Khamse Safoura , Jafarian Zahra , Bozorgmehr Ali , Tavakoli Mostafa , Iranian Hossein Afshar , Keshavarz Maryam , Moayedi Razieh , Ohadi Mina 
Published: April 2021

Abstract
Across human protein-coding genes, PRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) contains one of the longest GCC-repeats, and is predominantly expressed in the brain. Here we studied this STR in 300 human subjects, consisting of late-onset neurocognitive disorder (NCD) (N = 150) and controls (N = 150). We also studied the impact of this STR on the three-dimensional structure of DNA. While the PRKACB GCC-STR was strictly monomorphic at 7-repeats, we detected two 7/8 genotypes only in the NCD group. In comparison to all other lengths, (GCC)7 had the least effect on the three-dimensional structure of DNA, evidenced by minimal divergence between 0 and 7-repeats (divergence score = 0.04) and significant divergence between 0 and 8 repeats (divergence score = 0.50). A similar inert effect to the GCC-repeat was not detected in other classes of STRs such as GA and CA repeats. In conclusion, we report monomorphism of an exceptionally long GCC repeat in the PRKACB gene in human, its inert effect on DNA structure, and divergence in two cases of late-onset NCD. This is the first indication of natural selection for an exceptionally long monomorphic GCC-repeat, which probably evolved to function as an “epigenetic knob”, without changing the regional DNA structure.
Comparative Epidemiology and Outcomes among Trauma Patients transported by Private and Formal Pre-hospital Care Modes in Kigali, Rwanda
Authors: NZABANDORA Jean Paul , Bilal Saadiyah , Jing Ling , Henry Michael B. , Beeman Aly , Mbanjumucyo Gabin , Rosenberg Noah , Nyinawankusi Jeanne D’Arc , Sharma Vinay , Ndebwanimana Vincent , Muragizi Jean , Aluisio Adam R. 
Published: April 2021

Abstract
IntroductionInjuries account for approximately five million deaths worldwide and have high burdens in low- and middle-income countries, where pre-hospital systems are being developed to improve acute injury care. This study compares the characteristics and outcomes between trauma patients transported by formal emergency medical services (EMS), known as Service d’Aide Medicale Urgente, and by private transport to the emergency department (ED) at the Centre Hospitalier Universitaire de Kigali (CHUK) in Rwanda.MethodsThis retrospective cohort study analysed a random sample of trauma patients from of the CHUK ED presenting between 1 August 2015 and 30 July 2016. Non-trauma patients and transferred patients were excluded. The primary outcomes were ED and inpatient dispositions and outcome characteristics of: admission, length of stay (LOS), mortality. Descriptive analyses were performed and differences in outcomes assessed based on transport modalities via Pearson Chi-Squared or Fisher’s Exact tests.ResultsThere were 556 trauma patients analysed, of which 87.1% were transported by private transport and the remainder by EMS. The median age was 28 years (IQR:18-39), 52.1% had serious injuries, based on the triage system at CHUK. Common mechanisms of injury included road traffic crashes (62.7%) and falls (17.1%). Median inpatient LOS for private transport patients was 7 days (IQR:3-16 days), compared to 9.5 days for EMS patients (IQR:4-18 days) (p=0.301). There was a significant relationship between ED disposition and transport method (p=0.005), with a higher number of admissions among EMS-transported patients. The observed mortality of EMS and privately transported patients were not significant different, however there were a higher percentage of deaths in the ED and inpatient setting among those who were privately transported. ConclusionWhile mortality and hospital LOS between EMS and private transport patients were not statistically significantly different, this may not reflect a lack of clinical significance. Future research will be needed to continue to assess the EMS utilisation rate, quality and impact on patient-centred outcomes and should include studies that prospectively investigate larger samples of patients to better evaluate the effects of EMS trauma care in Rwanda.
Calculating the water dissipation of buildings in urban areas based on global nighttime light data
Authors: Gao Han , Liu Jiahong , Mei Chao , Hao Wang , Shao Weiwei , Liu Chuang 
Published: April 2021

Abstract
Urban water dissipation is increasing gradually as urbanization progresses. Urban water dissipation mainly includes the dissipation of water in buildings and natural water evapotranspiration. Previous studies have mainly focused on calculating natural evapotranspiration in urban areas and have overlooked the dissipation of water in buildings under the influence of strong human-related water use activities. In this paper, the concept of building water dissipation (BWD) was proposed to describe the phenomenon that water dissipation occurs inside buildings. Moreover, a BWD calculation model was established and applied to calculate global building water dissipation. To reveal the specific water dissipation inside buildings, it is necessary to obtain the urban building floor area first. This paper proposed a new method to calculate the urban building floor area based on global nighttime light data obtained from NPP-VIIRS. Taking the floor area results into the BWD calculation model, the global building water dissipation in urban areas was found to be 127 billion m3 in 2015. The vast building water dissipation that occurs in urban areas mostly results from rapidly developing economies and intense human activities. The results provide a basic understanding of the nexus between water resources and the energy-heat island effect in urban areas.