bluuebunny/crossref_metadata_2025_split huggingface dataset:
J-Aggregates of meso- [2.2] Paracyclophanyl-BODIPY Dye for NIR-II Imaging
Authors: Liu Zhipeng , Li Kang , Duan Xingchen , Jiang Zhiyong , Ding Dan , Zhang Guo-qiang , Chen Yuncong 
Published: December 2020

Abstract
J-aggregation has been proved to be an efficient strategy for the development of fluorescent imaging agents in the second near-infrared (NIR-II, 1000–1700 nm) window. However, the design of NIR-II fluorescent J-aggregates is challenging due to the lack of suitable J-aggregation dyes. Herein, we report meso-[2.2]paracyclophanyl-3,5-bis-N,N-dimethylaminostyrl BODIPY (PCP-BDP2) as the first example of BODIPY dye with J-aggregation induced NIR-II fluorescence. PCP-BDP2 shows emission maximum at 795 nm in diluted solution and NIR-II emission at 1010 nm in the J-aggregation state. Mechanism studies reveal that the steric and conjugation effect of the PCP group on the BODIPY core plays key roles in the J-aggregation behavior and NIR-II fluorescence tuning. Notably, NIR-II emissive J-aggregates of PCP-BDP2 can be efficiently stabilized in the assembled nanoparticle. Taking advantage of high quantum yield and good photo-/chemo-stability, J-aggregates of PCP-BDP2 show high-resolution and long-term in vivo NIR-II imaging ability. Furthermore, J-aggregates of PCP-BDP2 can be utilized for lymph node imaging and fluorescence-guided surgery in the nude mouse, which demonstrates their potential clinical application. This study not only demonstrates BODIPY dye as a new J-aggregation platform for developing NIR-II imaging agents but also encourages further exploration on J-aggregation induced NIR-II emission of the other conventional organic dyes.
MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of haematopoietic stem cells
Authors: Wei Qiaozhi , Pinho Sandra , Dong Shuxian , Pierce Halley , Nakahara Fumio , Xu Jianing , Xu Chunliang , Boulais Philip , Zhang Dachuan , Maryanovich Maria , Cuervo Ana , Frenette Paul , Li Huihui 
Published: December 2020

Abstract
Haematopoietic stem cells (HSCs) tightly regulate their quiescence, proliferation, and differentiation to generate blood cells during the entire lifetime. The mechanisms by which these critical activities are balanced are still unclear. Here, we report that Macrophage-Erythroblast Attacher (MAEA, also known as EMP), a receptor thus far only identified in erythroblastic island1, is a membrane-associated E3 ubiquitin ligase subunit essential for HSC maintenance and lymphoid commitment. Maea is highly expressed in HSCs and its deletion in mice severely impairs HSC quiescence and function and leads to a lethal myeloproliferative syndrome. Mechanistically, we have found that the surface expression of several haematopoietic cytokine receptors (e.g. MPL, FLT3) is stabilised in the absence of Maea, thereby prolonging their intracellular signalling. This is associated with impaired autophagy flux in HSCs, but not in mature haematopoietic cells. Administration of receptor kinase inhibitor or autophagy-inducing compounds rescues the functional defects of Maea-deficient HSCs. These results suggest that MAEA provides E3 ubiquitin ligase activity, guarding HSC function by restricting cytokine receptor signalling via autophagy.
Cervical Epidural Electrical Stimulation Restores Voluntary Arm Control In Paralyzed Monkeys
Authors: Capogrosso Marco , Barra Beatrice , Conti Sara , Perich Matthew , Zhuang Katie , Schiavone Giuseppe , Fallegger Florian , Galan Katia , James Nicholas , Barraud Quentin , Delacombaz Maude , Kaeser Melanie , Rouiller Eric , Milekovic Tomislav , Lacour Stephanie , Bloch Jocelyne , Courtine Gregoire 
Published: December 2020

Abstract
Regaining arm motor control is critical for people with paralysis. Despite promising results on grasping, no technology could restore effective arm control. Here, we show that electrical stimulation of the cervical spinal cord enabled three monkeys with cervical spinal injury to execute functional arm movements. We designed an epidural interface that engaged surviving spinal circuits via the recruitment of large sensory afferents to produce movement. Simple stimulation bursts produced sustained joint movements which, triggered by movement-related intracortical signals, enabled monkeys with arm paralysis to perform an unconstrained, three-dimensional reach and grasp task. This restoration of voluntary motor control was enabled by the synergistic integration of spared descending commands and electrical stimulation within the spinal cord. The simplicity of this technology promises realistic clinical translation.
Mechanisms linking multi-year La Niña with preceding extreme El Niño
Authors: Iwakiri Tomoki , Watanabe Masahiro 
Published: December 2020

Abstract
El Niño/La Niña, characterized by anomalous sea surface temperature warming/cooling in the central-eastern equatorial Pacific, is a dominant interannual variability with irregularity, impacting worldwide weather and socioeconomics. The observed records show that La Niña often persists for more than two years, called “multi-year La Niña” which tends to accompany extreme El Niño in the preceding year; however, the physical linkage between them remains unclear. Here we show using reanalysis data that an extreme El Niño excites atmospheric conditions that favor the generation of the multi-year La Niña in subsequent years. Easterly wind anomalies along the northern off-equator in the Pacific during the decay phase of an extreme El Niño are crucial. They act to discharge ocean heat content (OHC) via an anomalous northward Ekman transport; the negative OHC anomaly is large enough to be restored by a single La Niña and, therefore, causes another La Niña to occur in the second year. Furthermore, analyses of the Coupled Model Intercomparison Project Phase 6 (CMIP6) models show that the occurrence frequencies of multi-year La Niña and extreme El Niño are highly correlated, supporting the abovementioned mechanism. Our results provide physical evidence that the increasing frequency of multi-year La Niña is explained by the increasing El Niño amplitude since the late 20th century.
Attitudes of Neurologists to Brain Death and Organ Donation in China: A Content Analysis
Authors: Wang Ping , Guo Yuji , Yin Gaohui , Li Mengzhen , Li Yan , Li Nan , Jin Suqin , Zhu Zhengyu , Ding Mao , Chu Bingcong , Wu Yijin , Ma Wen 
Published: December 2020

Abstract
Background: Between 2003 and 2009, there were approximately 20,000 brain deaths per million people per year in China.These cases represent an important source for organ donation. As it is neurologists who are primarily involved in determining brain death, their knowledge and attitude toward brain death and organ donation directly affects decisions of family members regarding organ donation.Methods: This qualitative study was conducted in 2019. Data on neurologists’ knowledge and attitudes towards brain death and organ donation were obtained from fifteen neurologists in the Departments of Neurology from Chinese hospitals using a content analysis approach as achieved in semi-structured interviews. Results: Overall, these neurologists conveyed a positive attitude toward organ donation after brain death. However, they noted the importance of considering and respecting the opinions of these patients’ families. From the data analysis, 4 themes and 12 categories were developed. The 4 themes included: 1) brain death organ donation as a good thing, 2) interacting with brain death patient’s family, 3) cultural influences on organ donation with brain death and 4) strategies to improve organ donation rates in patients with brain death.Conclusion: The results of this study have provided some new and important information regarding the knowledge and attitude of Chinese neurologists toward brain death and organ donation. Such information is critical for guiding government and health care systems in designing strategies to improve donation rates and decisions from brain death patients.
Novel Recombinant keratin Degrading Subtilisin Like Serine Alkaline Protease from Bacillus Cereus Isolated from Marine Hydrothermal Vent Crabs&nbsp;
Authors: Gurunathan Revathi , Huang Bin , Ponnusamy Vinoth Kumar , Hwang Jiang-Shiou , Dahms Hans-Uwe 
Published: December 2020

Abstract
Microbial secondary metabolites from extreme environments like hydrothermal vents are a promising source for industrial applications. In our study the protease gene from Bacillus cereus from shallow marine hydrothermal vents in the East China Sea was cloned, expressed and purified. The protein sequence of 38 kDa protease SLSP-k was retrieved from mass spectrometry and identified as a subtilisin serine proteinase. The novel SLSP-k is a monomeric protein with 38 amino acid signal peptides being active over wide pH (7–11) and temperature (40–80 ℃) ranges, with maximal hydrolytic activities at pH 10 and at 50 ℃ temperature. The hydrolytic activity is stimulated by Ca2+, Co2+, Mn2+, and DTT. It is inhibited by Fe2+, Cd2+, Cu2+, EDTA, and PMSF. The SLSP-k is stable in anionic, non- anionic detergents, and solvents. The ability to degrade keratin in chicken feather and hair indicate that the protein is suitable for waste management and value-added product synthesis as well as several research applications.
Stigma and Discrimination Towards HIV in Healthcare Workers in Shenzhen, China
Authors: Wang Li , Wang Wei , Zhu Na , Wang Jun , Chen Xiao , Luo Ya , Tang Wei 
Published: December 2020

Abstract
Introduction: To measure HIV-related stigma and discrimination (S&D) among health care facilities in Bao’an, Shenzhen to inform decision making regarding stigma-reduction intervention.Methods: A cross-sectional survey was conducted using a standardized measurement tool between October 2019 and January 2020 among 1235 staff randomly sampled from 18 public and private hospitals. Data relevant to respondents’ demographic information, drivers of HIV related S&D, enacted stigma, and stigma towards pregnant women living with HIV were collected for analysis.Results: Percentage of medical staff worrying occupational exposure to HIV infection when dressing wound, drawing blood and doing delivery are 82.8%, 82.1% and 81.9%, respectively. Gender, specialty, training and hospital funding are independent factors affecting health staff’s anxiety over infection. 75.2% respondents believe that people living with HIV (PLWH) should seek care exclusively from designated hospital specializing in infectious disease and more than 50% of health staff survey reported over-protective measures. Conclusion: S&D toward PLWH as well as its drivers are widely prevalent among health care facilities. Findings of this study highlight the importance of stigma-reduction interventions to ensure equal access to health care by PLWH.
Cpy(a/t)(q/w)e D-Hexapeptides Bind CUG Repeats and Rescue Phenotypes of Myotonic Dystrophy Myoblasts and A Drosophila Model of the Disease
Authors: Bargiela Ariadna , Artero Ruben , Estrada-Tejedor Roger , Rapisarda Anna , Garcia-España Enrique , Llamusi Beatriz , Perez-Alonso Manuel , Pont Isabel 
Published: December 2020

Abstract
In Myotonic Dystrophy type 1 (DM1), a non-coding CTG repeats rare expansion disease; toxic double-stranded RNA hairpins sequester the RNA-binding proteins Muscleblind-like 1 and 2 (MBNL1 and 2) and trigger other DM1-related pathogenesis pathway defects. In this paper, we characterize four D-amino acid hexapeptides identified together with abp1, a peptide previously shown to stabilize CUG RNA in its single-stranded conformation. With the generalized sequence cpy(a/t)(q/w)e, these related peptides improved three MBNL-regulated exon inclusions in DM1-derived cells. Subsequent experiments showed that these compounds generally increased the relative expression of MBNL1 and its nuclear-cytoplasmic distribution, reduced hyperactivated autophagy, and increased the percentage of differentiated (Desmin-positive) cells in vitro. All peptides rescued atrophy of indirect flight muscles in a Drosophila model of the disease, and partially rescued muscle function according to climbing and flight tests. Investigation of their mechanism of action supports that all four compounds can bind to CUG repeats with slightly different constant affinities, but binding did not strongly influence the secondary structure of the toxic RNA in contrast to abp1. Finally, molecular modeling suggests a detailed view of the interactions of peptide-CUG RNA complexes useful in the chemical optimization of compounds.
Influence of Perceived Baseline Contact on the Acceptability of a Personal Contact Intervention Among People Living With Dementia
Authors: Sullivan Danielle , Whynot Tynisha , Swindle Jennifer , Lee Heunjung , O'Rourke Hannah 
Published: December 2020

Abstract
Background: Living with dementia can be a lonely experience, undermining older adults’ quality of life. Evidence supports that personal contact interventions can address older adults’ loneliness. However, effects have been small to date, and little is known about how one’s perceptions of baseline contact may influence an intervention’s use and effects. The purpose of this study was to explore how baseline contact, as perceived by older adults living with dementia, may be associated with the acceptability of a personal contact intervention. Methods: This descriptive study was a secondary analysis of data that we collected from 15 people living with mild to moderate dementia in a long-term care home who participated in Connecting Today. Connecting Today is a personal contact intervention that involves 30 minutes of scheduled, unscripted interaction between persons living with dementia and a family member, friend or research assistant. Visits occurred for six weeks, face-to-face or by phone. We compared groups that perceived that they had high (i.e., weekly, n=8) versus low (i.e., monthly or unknown, n=7) contact at baseline to explore differences in acceptability. We measured perceived acceptability (adapted Treatment Perception and Preferences Questionnaire) and the amount and reasons reported for missing data and study withdrawal. Descriptive statistics were used to summarize the data, and proportions and frequencies were compared in tables and charts to explore differences between groups.Results: In visits one and two when there were little missing data, a larger proportion (85.7% to 100%) of low contact participants reported feeling better, that the visits helped them, and that the visits were easy ‘mostly’ or ‘a lot’, as compared to the high contact group (37.5% to 62.5%). Retention and attrition after visit two further supported that Connecting Today may be more acceptable for people with low perceived baseline contact: the majority of missing data (71%) and all study withdrawals were observed in the high contact group. Conclusions: Testing the hypotheses generated in this study about the influence of perceived baseline contact upon acceptability in larger feasibility and effectiveness studies will support development of tailored, theory-based personal contact interventions.
Eye-Color and Type-2 Diabetes Phenotype Prediction From Genotype Data Using Deep Learning Methods
Authors: Muneeb Muhammad , Henschel Andreas 
Published: December 2020

Abstract
Background: Genotype-Phenotype predictions are of great importance in genetics. These predictions can help to find genetic mutations causing variations in human beings. There are many approaches for finding the association which can be broadly categorized into two classes, statistical techniques, and machine learning. Statistical techniques are good for finding the actual SNPs causing variation where Machine Learning techniques are good where we just want to classify the people into different categories. In this article, we examined the Eye-color and Type-2 diabetes phenotype. The proposed technique is a hybrid approach consisting of some parts from statistical techniques and remaining from Machine learning. Results: The main dataset for Eye-color phenotype consists of 806 people. 404 people have Blue-Green eyes where 402 people have Brown eyes. After preprocessing we generated 8 different datasets, containing different numbers of SNPs, using the mutation difference and thresholding at individual SNP. We calculated three types of mutation at each SNP no mutation, partial mutation, and full mutation. After that data is transformed for machine learning algorithms. We used about 9 classifiers, RandomForest, Extreme Gradient boosting, ANN, LSTM, GRU, BILSTM, 1DCNN, ensembles of ANN, and ensembles of LSTM which gave the best accuracy of 0.91, 0.9286, 0.945, 0.94, 0.94, 0.92, 0.95, and 0.96 percent respectively. Stacked ensembles of LSTM outperformed other algorithms for 1560 SNPs with an overall accuracy of 0.96, AUC = 0.98 for brown eyes, and AUC = 0.97 for Blue-Green eyes. The main dataset for Type-2 diabetes consists of 107 people where 30 people are classified as cases and 74 people as controls. We used different linear threshold to find the optimal number of SNPs for classification. The final model gave an accuracy of 0.97 percent. Conclusion: Genotype-phenotype predictions are very useful especially in forensic. These predictions can help to identify SNP variant association with traits and diseases. Given more datasets, machine learning model predictions can be increased. Moreover, the non-linearity in the Machine learning model and the combination of SNPs Mutations while training the model increases the prediction. We considered binary classification problems but the proposed approach can be extended to multi-class classification.
Evaluation of Parents' Knowledge and Attitudes Regarding Self-Medication in the Dental Problems of Their Child During the COVID-19 Pandemic
Authors: Tunc Emine Sen , Aksoy Emre , Arslan Hatice , Kaya Zeynep 
Published: December 2020

Abstract
Background: Self-medication means taking medicine without consultation with any doctor or dentist and an important health issue, especially during the COVID-19 pandemic. The present study aims to evaluate the knowledge and attitudes of parents regarding self-medication in dental problems of their children during to COVID-19 pandemic in Northern Turkey. Methods: A cross-sectional survey was carried out in the pediatric dental clinic immediately after the COVID-19 lockdown ended. A total of 389 parents who agreed to participate in the study completed the questionnaire for three months. A structured questionnaire with 18 items was designed to collect information on the parents’ knowledge and attitudes regarding when, why, and how to use drugs and on their practices medicating children. Results: The majority of parents (n = 273; 70.2%) were practiced self-medication to their children's dental problems. Self-medication with a previous medication was usually preferred to their children by parents (n = 179; 62.2%). It was observed the analgesics practiced by parents (98%) were the most commonly used self-medication for their children's dental problems.Conclusion: New healthcare systems like tele-dentistry may be useful to overcome self-medication problems directed to children in unusual times that limit to reach healthcare providers such as pandemics.
Plasmon-Activated Water Decreases Vasculopathy in Orthotopic Allograft Transplantation Rats
Authors: Tsai Chien-Sung , Lin Yi-Wen , Shih Chun-Min , Tsai Yi-Ting , Huang Chun-Yao , Lin Shing-Jong , Li Chi-Yuan , Lin Cheng-Yen , Tseng Horng-Ta , Liu Yu-Chuan , Lin Feng-Yen 
Published: December 2020

Abstract
Patients undergoing orthotopic allograft transplantation (OAT) will certainly suffer from vasculopathy. Although there are many immunosuppressive and immunomodulatory agents that are administered to patients, chronic rejection- induced vasculopathy cannot be entirely managed. Moreover, the implanted graft might become dysfunctional. In the past, we have used deionized reverse osmosis water (ROW) to stream via gold nanoparticles (AuNPs) at room temperature under powerful illumination, in order to prepare plasmon-activated water (PAW) with fewer hydrogen bonds. Compared to ROW, stable PAW can successfully remove free hydroxyl and 2,2-diphenyl-1-picrylhydrazyl radicals, and efficiently reduce lipopolysaccharide (LPS)-induced monocytes to release nitric oxide. Moreover, PAW can considerably induce the expression of the antioxidant gene Nrf2 in human gingival fibroblasts. Moreover, it might lower amyloid burden in mice with Alzheimer's disease. Furthermore, PAW decreased metastasis in mice grafted with Lewis lung carcinoma cells and boosted the overall survival in combination with cisplatin. Because of this possibility that PAW could prevent systemic disease, we aimed to evaluate the influence of PAW on OAT-induced vasculopathy. Here, we demonstrated that daily intake of PAW lowered the progression of vasculopathy in OAT-recipient ACI/NKyo rats by inhibiting collagen accumulation, proliferation of smooth muscle cells and fibroblasts, and T lymphocyte infiltration in the vessel wall. Moreover, the results showed reduced T and B lymphocytes, plasma cells, and macrophage activation in the spleen of the OAT-recipient ACI/NKyo rats that were administered PAW. Finally, in contrast to the control group, the OAT-recipient ACI/NKyo rats that were administered PAW exhibited higher mobilization and levels of circulating endothelial progenitor cells associated with vessel repair. Therefore, this study highlights the therapeutic roles of PAW in vasculopathy.
Identification of prognostic immune‐related gene signature associated with tumor microenvironment of colorectal cancer
Authors: Wang Yuanyuan , Li Wei , Jin Xiaojing , Jiang Xia , Guo Shang , Xu Fei , Su Xingkai , Wang Guiqi , Zhao Zengren , Gu Xiaosong 
Published: December 2020

Abstract
Background
The tumor microenvironment (TME) has significantly correlation with tumor occurrence and prognosis. Our study aimed to identify the prognostic immune-related genes (IRGs)in the tumor microenvironment of colorectal cancer (CRC).
Methods
Transcriptome and clinical data of CRC cases were downloaded from TCGA and GEO databases. Stromal score, immune score, and tumor purity were calculated by the ESTIMATE algorithm. Based on the scores, we divided CRC patients from the TCGA database into low and high groups, and the differentially expressed genes (DEGs) were identified. Immune-related genes (IRGs) were selected by venn plots. To explore underlying pathways, protein-protein interaction (PPI) networks and functional enrichment analysis were used. After utilizing LASSO Cox regression analysis, we finally established a multi-IRGs signature for predicting the prognosis of CRC patients. A nomogram consists of the thirteen-IRGs signature and clinical parameters was developed to predict the overall survival (OS). We investigated the association between prognostic validated IRGs and immune infiltrates by TIMER database.
Results
Gene expression profiles and clinical information of 1635 CRC patients were collected from the TCGA and GEO databases. Higher stromal score, immune score and lower tumor purity were observed positive correlation with tumor stage and poor OS. Based on stromal score, immune score and tumor purity, 1517 DEGs, 1296 DEGs, and 1892 DEGs were identified respectively. The 948 IRGs were screened by venn plots. A thirteen-IRGs signature was constructed for predicting survival of CRC patients. Nomogram with a C‐index of 0.769 (95%CI, 0.717–0.821) was developed to predict survival of CRC patients by integrating clinical parameters and thirteen‐IRGs signature. The AUC for 1‐, 3‐, and 5‐year OS were 0.789, 0.783 and 0.790, respectively. Results from TIMER database revealed that CD1B, GPX3 and IDO1 were significantly related with immune infiltrates.
Conclusions
In this study, we established a novel thirteen immune-related genes signature that may serve as a validated prognostic predictor for CRC patients, thus will be conducive to individualized treatment decisions.