bluuebunny/crossref_metadata_2025_split huggingface dataset:
A primer in resilience status for German medical graduates - a necessary step in building an emotionally equipped healthcare workforce
Authors: Kiesewetter Jan , Huber Johanna 
Published: October 2020

Abstract
BackgroundResilience is a widely-used catchword in the last couple of years to describe the resistance to psychological strains of life, especially for the healthcare work force. The promises of resilience to burnout sound great and what we all would want: less health impairment despite stress, higher work satisfaction and last but not least higher work performance. However, little is known scientifically regarding the resilience status of the upcoming work-force. With our study we would like to investigate the resilience status of medical graduates from five medical schools within their first year after graduation. MethodsFor the identification of the resilience status we included the 5-point Likert 10-Item Connor-Davidson Resilience Scale, German Version in a graduate survey posted to 5 medical schools and over 1610 eligible participants of whom 610 (60% female) filled out at least parts of the survey. ResultsThe resilience status showed a mean resilience score of M = 37.1 (SD = 6.30). The score ranges from 3.22 (I am not easily discouraged by failure) to 4.26 (I am able to adapt to change). The item “I am able to handle unpleasant feeling” is interesting as one third of the participants did choose not to answer. Relationships to other constructs are presented in the article. ConclusionsThe study shows that the overall resilience status of medical graduates one year after their graduation is rather high, but subjectively they do not feel equivalently resilient for the different aspects they face in their job. Further research needs to see how trainings can provide medical students and professionals with the emotional coping skills that they lack in the moment.
Manufacturing and Banking Canine Adipose-Derived Mesenchymal Stem Cells for Veterinary Clinical Application
Authors: Luo Huina , Li Dongsheng , Chen Zhisheng , Wang Bingyun , Chen Shengfeng 
Published: October 2020

Abstract
BACKGROUND: Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications. RESULTS: After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. No adverse events were noted in two cases treated with intravenously AD-MSCs. CONCLUSION: Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use.
Gene expression profiling of orbital muscles in treatment-resistant ophthalmoplegic myasthenia gravis.
Authors: Europa Tarin A , Nel Melissa , Heckmann Jeannine M 
Published: October 2020

Abstract
Background: Unbiased in silico approaches applied to genome-wide data prioritized putative functional gene variants associating with treatment-resistant ophthalmoplegic myasthenia gravis (OP-MG). Although altered expression of genes harbouring these variants, or associated pathways, were shown in patient-derived transdifferentiated-myocyte models, gene expression in orbital-derived muscle was required to test the validity of the predictions. Methods: We sampled orbicularis oculi muscle (OOM) and one paralysed extraocular muscle (EOM) from six individuals with OP-MG during blepharoptosis and re-alignment surgeries, respectively. For controls, the OOMs were sampled from four individuals without myasthenia undergoing surgery for non-muscle causes of ptosis, and one non-paralysed EOM. Using a qPCR array, expression of 120 genes was compared between OP-MG and control OOMs, profiling putative “OP-MG” genes, genes in related biological pathways and genes reported to be dysregulated in MG cases or experimental MG models, and in EOMs of cases with strabismus. Normalization was performed with two stable reference genes. Differential gene expression was compared between OP-MG and control samples using the ΔΔCT method. Co-expression was analysed by pairwise correlation of gene transcripts to infer expression networks. Results: Overall, transcript levels were similar in OOMs and EOMs (p=0.72). In OOMs, significant downregulated expression of eight genes was observed in OP-MG cases compared with controls (>2-fold; p≤0.016), including TFAM, a mitochondrial transcription factor, and genes related to the following pathways: atrophy signalling; muscle regeneration and contraction; glycogen synthesis; and extracellular matrix remodelling. Several microRNAs, known to be highly expressed in EOMs, are predicted to regulate some of these genes. Co-expression analyses of gene-pairs suggested high interconnectedness of gene expression networks in OP-MG muscle, but not controls (r>0.96, p<0.01). Significant inverse directions of gene-pair correlations were noted in OP-MG vs controls OOM networks (r≥0.92, p<0.001) involving most OP-MG genes overlapping prominently with muscle atrophy/contractility and oxidative metabolism genes. Conclusions: The gene expression in orbital muscles derived from OP-MG individuals compared with normal controls, support the pathogenic hypothesis previously generated from whole genome sequence analyses. Repression of gene transcripts in OP-MG orbital muscle implicate tissue-specific regulatory mechanisms, which may inform future biomarker discovery approaches.
Thermally responsive poly(ethylene oxide)-based polyrotaxanes bearing hydrogen-bonding pillar [5] arene rings
Authors: Kato Kenichi , Onishi Katsuto , Maeda Koki , Yagyu Masafumi , Fa Shixin , Ichikawa Takahiro , Mizuno Motohiro , Kakuta Takahiro , Yamagishi Tada-aki , Ogoshi Tomoki 
Published: October 2020

Abstract
Poly(ethylene oxide)s (PEOs) are useful polymers with good water solubility, biological compatibility, and commercial availability. In this study, PEOs with various end groups were threaded into pillar[5]arene rings in a mixture of water and methanol to afford pseudopolyrotaxanes. Multiple hydrogen bonds between the pillar[5]arene rings and hydrophobic–hydrophilic interactions between the ethylene groups of the PEOs and the hydrophobic pillar[5]arenes are the driving forces to form the pseudopolyrotaxane structure. Corresponding polyrotaxanes were also constructed by capping COOH-terminated pseudopolyrotaxanes with bulky amines, in which multiple hydrogen bonds involving the pillar[5]arene OH groups were critically important to prevent de-threading. The number of threaded ring components could be rationally controlled in these materials, providing a simple and versatile method to tune the mechanical and thermal properties. Specifically, a polyrotaxane with a high-molecular-weight axle became elastic upon heating above the melting point of PEOs and exhibited temperature-dependent shape memory property, because of the topological confinement and cross-linking by hydrogen bonds.
Future river-flood damage increases under aggressive adaptations
Authors: Tanoue Masahiro , Taguchi Ryo , Alifu Haireti , Hirabayashi Yukiko 
Published: October 2020

Abstract
The risk of river flooding is expected to rise with climate change and socioeconomic development1-6, and therefore additional protection measures are required to reduce increased flood damage. Previous studies have investigated the effectiveness of adaptation measures to reduce flood risks7,8; however, there has been no evaluation of residual flood damage (RFD), which reflects the unavoidable increase in damage even under an aggressive adaptation strategy. Here, we evaluated RFD under several adaptation objectives. We found that China, India, Russia and countries in central Africa and Latin America can achieve a higher level of flood protection that will reduce RFD even under extreme scenarios. However, high RFD exceeding 0.1% of GDP remains, especially in eastern China, northern India, eastern Europe and central Africa. The high RFD are inevitable assuming the average construction period required for hard infrastructure (30 years), implying the need for immediate adaptation measures as well as soft adaptation.
Functional analysis of a monoclonal antibody reactive against anti-cluster A epitope obtained from a patient infected with HIV-1 CRF02_AG
Authors: Za Hasan Md , Kuwata Takeo , Takahama Shokichi , Yu Kaku , Biswas Shaswata , Matsumoto Kaho , Tamamura Hirokazu , Matsushita Shuzo 
Published: October 2020

Abstract
Background: Recent data suggest the importance of non-neutralizing antibodies (nnAbs) in the development of vaccines against HIV-1 because two types of nnAbs that recognize the coreceptor binding site (CoRBS) and inner domain cluster A mediate antibody-dependent cellular-cytotoxicity (ADCC) against HIV-1-infected cells. However, many studies have been conducted with nnAbs obtained from subtype B-infected individuals, with few studies in patients with non-subtype B infections. Results: We isolated a monoclonal antibody 1E5 from a CRF02_AG-infected individual and constructed two forms of antibody with constant regions of IgG1 or IgG3. The epitope of 1E5 belongs to cluster A, which consists of C1 and C2 of gp120, and 1E5 binds to 27 out of 35 strains (77%) across the subtypes. The 1E5 showed strong ADCC activity, especially in the form of IgG3 in the presence of small CD4-mimetic compounds (CD4mc) and anti-CoRBS antibody, but did not show any neutralizing activity even against the isolates with strong binding activities. The enhancement in the binding of A32, anti-cluster A antibody isolated from a patient with subtype B infection, was observed in the presence of 1E5 and the combination of both anti-cluster A antibodies enhanced ADCC activity. Conclusions: These results suggest that anti-cluster A antibodies that are induced in patients with different HIV-1 subtype infections have common functional modality and may have unexpected interactions. These data may have implications for vaccine development against HIV-1.
Universal scaling laws of keyhole stability and porosity in 3D printing of metals
Authors: Gan Zhengtao , Kafka Orion , Parab Niranjan , Zhao Cang , Fang Lichao , Heinonen Olle , Sun Tao , Liu Wing Kam 
Published: October 2020

Abstract
We leverage ultrahigh-speed synchrotron x-ray imaging and high-fidelity multiphysics modeling to identify strikingly simple yet universal scaling laws for keyhole stability and porosity in metal three-dimensional (3D) printing. The laws apply broadly and remain accurate for different materials, processing conditions, and printing machines. We define a new dimensionless number, the Keyhole number, to predict aspect ratio of a keyhole and the morphological transition from stable at low Keyhole number to chaotic at high Keyhole number. Furthermore, we discover inherent correlation between keyhole stability and porosity formation in metal 3D printing. By reducing the dimensions of the formulation of these challenging problems, the compact scaling laws will aid process optimization and defect elimination during metal 3D printing, and potentially lead to a quantitative predictive framework.
Differences in Assistive Technology Installed for People With Dementia Living at Home Who Have Wandering and Safety Risks
Authors: Curnow Eleanor , Rush Robert , Gorska Sylwia , Forsyth Kirsty 
Published: October 2020

Abstract
Background: Assistive Technology for people with dementia living at home is not meeting their care needs. Reasons for this may be due to limited understanding of variation in multiple characteristics of people with dementia including their safety and wandering risks, and how these affect their assistive technology requirements. To explore the possibility of grouping people with dementia according to data describing multiple person characteristics. Then to investigate the relationships between these groupings and installed Assistive Technology interventions.Methods: Partitioning Around Medoids cluster analysis was used to determine participant groupings based upon secondary data which described the person characteristics of 451 people with dementia with Assistive Technology needs. Relationships between installed Assistive Technology and participant groupings were then examined.Results: Two robust clustering solutions were identified within the person characteristics data. Relationships between the clustering solutions and installed Assistive Technology data indicate the utility of this method for exploring the impact of multiple characteristics on Assistive technology installations. Living situation and caregiver support influence installation of assistive technology more strongly than level of risk or cognitive impairment. People with dementia living alone received different AT from those living with others.Conclusions: Results suggest that caregiver support and the living situation of the person with dementia influence the type and frequency of installed Assistive Technology. Reasons for this include the needs of the caregiver themselves, the caregiver view of the participants’ needs, caregiver response to alerts, and the caregiver contribution to the assistive technology assessment and selection process. Selection processes should be refined to account for the needs and views of both caregivers and people with dementia. This will require additional assessor training, and the development of validated assessments for people with dementia who have additional impairments. Policies should support the development of services which provide a wider range of AT to facilitate interventions which are focused on the needs of the person with dementia.
Comprehensive genomic resources related to domestication and crop improvement traits in Lima bean
Authors: Garcia Tatiana , Duitama Jorge , Zullo Stephanie , Gil Juanita , Ariani Andrea , Dohle Sarah , Palkovic Antonia , Skeen Paola , Bermudez-Santana Clara , Debouck Daniel , Castillo Jaime Martinez , Gepts Paul , Chacón-Sánchez Maria 
Published: October 2020

Abstract
Lima bean (Phaseolus lunatus L.) is one of the five domesticated Phaseolus bean crops, which are essential sources of dietary proteins for human consumption. Compared to common bean (P. vulgaris), it shows a wider range of ecological adaptations along its distribution range from Mexico to Argentina. These adaptations and its phenotypic plasticity make Lima bean a promising crop for improving food security under predicted scenarios of climate change in Latin America and elsewhere. Lima bean is also an excellent model to study convergent evolution of the adaptive domestication syndrome due to its dual domestication in Mesoamerica and the Andes. Combining long and short read sequencing technologies with a dense genetic map from a biparental population, we obtained the first chromosome-level genome assembly for Lima bean. Annotation of 28,326 gene models showed high diversity among 1,917 genes with conserved domains related to disease resistance. Structural comparison across 21,180 orthologs with common bean revealed high genome synteny and two large intrachromosomal rearrangements. Speciation between P. lunatus and P. vulgaris occurred about six million years ago according to nucleotide evolution between these orthologs. Population genomic analysis of GBS data for 482 wild and domesticated accessions from the Mesoamerican and Andean gene pools provided novel evidence on population structure at a finer geographical scale. Results show that wild Lima bean is organized into six clusters with mostly non-overlapping distributions and that Mesomerican landraces can be further subdivided into three subclusters. A new wild cluster of diversity was found in the Colombian Andes and a separate genetic cluster was observed for Mesoamerican landraces of the Peninsula of Yucatan in Mexico. This study also documents genome wide patterns of selection and haplotype introgression events among gene pools. Analysis of RNA-seq data obtained from wild and domesticated accessions at two different pod developmental stages revealed 4,275 differentially expressed genes, which could be related to pod dehiscence and seed development. We expect that the present resources serve as a solid basis to achieve a comprehensive view of the degree of convergent evolution of Phaseolus species under domestication and provide new tools and information for breeding for climate change resiliency of different domesticated species.
Extracellular Superoxide Dismutase (EC-SOD) Regulates Gene Methylation and Cardiac Fibrosis During Chronic Hypoxic Stress
Authors: Rajgarhia Ayan , Ayyasola Kameshwar , Zaghloul Nahla , Re Jorge M. Lopez Da , Miller Edmund J. , Ahmed Mohamed 
Published: October 2020

Abstract
Background: Chronic hypoxic stress induces epigenetic modifications mainly DNA methylation in cardiac fibroblasts, inactivating tumor suppressor genes (RASSF1A), and activating kinases (ERK1/2) leading to fibroblast proliferation and cardiac fibrosis. The Ras/ERK signaling pathway is an intracellular signal transduction critically involved in fibroblast proliferation. RASSF1A functions through its effect on downstream ERK1/2. The antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), decreases oxidative stress from chronic hypoxia but it’s effects on these epigenetic changes has not been fully explored. Objectives: In-vitro model: Wild type C57B6 male mice (WT) and transgenic males with an extra copy of human hEC-SOD (TG) were housed in hypoxia (10% O2) for 21 days. Right ventricular tissue was studied for cardiac fibrosis markers using RT-PCR and Western Blot analyses. in-vitro model, downstream effects of RASSF-1 expression and methylation and its relation to ERK1/2, were studied using primary C57BL6 mouse cardiac fibroblast tissue culture.Results: There were significant increases in markers of cardiac fibrosis : Collagen 1, Alpha Smooth Muscle Actin (ASMA) and SNAIL, in the WT hypoxic animals as compared to the TG hypoxic group (p< 0.05). Expression of DNA methylation enzymes (DNMT 1,2) was significantly increased in the WT hypoxic mice as compared to the hypoxic TG mice (p<0.001). RASSF1A expression was significantly lower and ERK1/2 was significantly higher in hypoxia WT compared to the hypoxic TG group (p<0.05). Use of SiRNA to block RASSF1A gene expression in murine cardiac fibroblast tissue culture led to increased fibroblast proliferation (p<0.05). Methylation of RASSF1A promoter region was significantly reduced in the TG hypoxic group compared to the WT hypoxic group (0.59 vs 0.75 respectively). Conclusions: EC-SOD significantly attenuates RASSF1A gene methylation and can alleviate cardiac fibrosis induced by hypoxia.
Silencing Smad7 Potentiates BMP2-induced Chondrogenic Differentiation and Inhibits Endochondral Ossification in Human Synovial Derived Mesenchymal Stem Cells
Authors: xiao pengcheng , Zhu Zhenglin , Du Chengcheng , Zeng Yongsheng , Liao junyi , Cheng Qiang , Chen Hong , Zhao Chen , Huang Wei 
Published: October 2020

Abstract
Background: Cartilage injuries pose formidable challenges for effective clinical management. Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries. Bone morphogenetic protein 2 (BMP2) is a promising chondrogenic growth factors for transgene-enhanced cartilage tissue engineering. However the BMP2 is failed to maintain a stable chondrogenic phenotype as it also induces robust endochondral ossification. Recently, human synovial derived mesenchymal stem cells (hSMSCs) arouse interested through the poor differentiation potential into osteogenic lineage. Smad7, a protein to antagonizes TGF-β/BMP signaling pathway has been discovered significant in the endochondral ossification. In the present study ,we further explore the effect of downregulate Smad7 in BMP2-induced chondrogenic differentiation of hSMSCs. Methods: hSMSCs were isolated from synovium of human knee joint through adhesion growth. In vitro and in vivo chondrogenic differentiation models of hSMSCs were constructed . Transgenes of BMP2, silencing Smad7 and Smad7 were expressed by adenoviral vectors. The osteogenic differentiation was detected by alkaline phosphatase staining, alizarin red staining. The chondrogenic differentiation was detected by alcian blue staining. Gene expression was determined by reverse transcription and quantitative real-time PCR (RT-qPCR), Immunofluorescence and immunohistochemistry. The subcutaneous stem cell implantation model was established and evaluated by micro-CT , h＆e staining, alcian blue staining and immunohistochemistry assay.Results: Compared to other MSCs, hSMSCs performed less of capability to osteogenic differentiation. But the occurrence of endochondral ossification is still inevasible during BMP2 induced cartilage formation. We found that silencing Smad7 enhanced the BMP2-induced chondrogenic differentiation of hSMSCs in vitro. Also, it leading to much less of hypertrophic differentiation. The subcutaneous stem cells implantation assays demonstrated silencing Smad7 potentiates BMP2-induced cartilage formation and inhibits endochondral ossification. Conclusion: This study strongly suggests that application of hSMSCs , cell scaffolds and silencing Smad7 can potentiate BMP2-induced chondrogenic differentiation and inhibit endochondral ossification. Thus, inhibit the expression of Smad7 in BMP2-induced hSMSCs differentiation may be a new strategy for cartilage tissue engineering.