bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of the Distraction Support in Intramedullary Nailing Treatment for Tibial Shaft Fracture: A Randomized Controlled Study
Authors: Yao Liwei , Mao Haijiao , Wu Zeting , Xu Dingli , Dong Wenwei
Published: December 2020

Purpose The aim of this study is to investigate the effectiveness of using a new distraction support in intramedullary nailing treatment for tibial shaft fracture.Methods: Patients at the trauma center who underwent the treatment for tibial shaft fractures from July 2013 to December 2018 were enrolled. The patients were randomized in control group(n=43) and distraction support(SD) group(n=42). All operations were performed by the same senior surgeon. The hospital day, blood loss, operative time, infect rate, delayed union rate and malalignment rate(p=0.68) were obtained for the evaluation.Results: 85 participants were recruited and all cases were achieved the acceptable reduction. The operative time was significantly shorter for DS group than control group (75.3 vs.90.4 p<0.001). Blood loss was significantly lower in the DS group compared to the control group(60.1vs.85.4 p=0.003) . There were no obvious difference about infect rate(p=0.98), delay union(p=0.45), hospital days(p=0.37) and malalignment rate(p=0.68) between the two groups.Conclusion: Distraction support was effective in intramedullary nailing surgery. The application of distraction support may be a useful method in our future work.
Individual Quality of Life and the Environment – Towards a Concept of Liveable Areas for Persons with Disabilities in Poland
Authors: Grabowska Izabela , Antczak Radosław , Zwierzchowski Jan , Panek Tomasz
Published: December 2020

BackgroundThe United Nations Convention on the Rights of Persons with Disabilities highlights the need to create proper socio-economic and political conditions for persons with disabilities, with a special focus on their immediate living conditions. According to the Convention, these conditions should be built to ensure that persons with disabilities have the potential to enjoy a high quality of life (QoL), and this principle is reflected in the notion of liveable areas. The crucial aspect of this framework is the relationship between the individual QoL and the environment, broadly understood as the socio-economic as well as the technical conditions in which persons with disabilities function.MethodsThe basic research problem was to assess the relationship between individual QoL for the population with disabilities as a dependent variable and liveability indicators as independent variables, controlling for individual characteristics. The study used a dataset from the EU-SILC (European Union Statistics on Income and Living Conditions) survey carried out in 2015 in Poland. The research concept involved several steps. First, we created a variable measuring the QoL for the entire population with disabilities. To measure the multidimensional QOL, we used Sen’s capability approach as a general concept, which was operationalised by the MIMIC (multiple indicators multiple causes) model. In the second step, we identified the liveability indicators available in the official statistics, and merged them with survey data. Finally, in the last step, we ran the regression analysis. We also checked the data for the nested structure.ResultsWe confirmed that environmental conditions, defined as all conditions focused on creating liveable areas, played a significant role in shaping the QoL of persons with disabilities, and that this relationship held even after controlling for the demographic characteristics of the respondents. Moreover, we found that in addition to the general environmental conditions, the conditions created especially for persons with disabilities affected the QoL of these individuals. ConclusionsThe results illustrate the need to strengthen policies aimed at promoting the QoL of persons with disabilities by creating access to community assets and services that can contribute to improving the life chances of this population.
Evaluation of A Novel Particle-Based Multi-Analyte Technology for the Detection of Anti-Fibrillarin Antibodies
Authors: Mahler Michael , Kim Grace , Roup Fabrece , Bentow Chelsea , Fabien Nicole , Goncalves David , Palterer Boaz , Fritzler Marvin J , Villalta Danilo
Published: December 2020

Objective: Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several anti-nuclear antibodies (ANA), including those in the classification criteria [anti-centromere, anti-topoisomerase I (Scl-70), anti-RNA Pol III]. However, the presence of less common antibodies such as anti-fibrillarin (U3-RNP), that generate a clumpy nucleolar pattern by HEp-2 indirect immunofluorescence assay (IFA, ICAP AC-9), are considered disease specific and are with clinical subsets of SSc, therefore playing a role in diagnosis and prognosis. A specific and sensitive anti-fibrillarin assay would be an important addition to serological diagnosis and evaluation of SSc. The goal of this study was to evaluate a new particle-based multi-analyte technology (PMAT) for the measurement of anti-fibrillarin antibodies Methods: A total of 149 patient samples were collected including 47 samples from France (Lyon and Paris, n=32) and Italy (Careggi Hospital, Florence, n=15) selected based on AC-9 HEp-2 IFA staining (>1:640, clumpy nucleolar pattern) and 102 non-SSc controls [inflammatory bowel disease (IBD) n=20, Sjögren’s syndrome (SjS) n=20, infectious disease (ID) n=7, systemic lupus erythematosus (SLE) n=17, rheumatoid arthritis (RA) n=17, and healthy individuals (HI) n=21]. All samples were tested on the anti-fibrillarin PMAT assay (research use only, Inova Diagnostics, USA). Additionally, the 47 anti-fibrillarin positive samples were also tested on PMAT assays for detecting other autoantibodies in ANA-associated rheumatic diseases (AARD). Anti-fibrillarin antibody data performed by fluorescence enzyme immunoassay (FEIA, Thermo Fisher, Germany) was available for 34 samples. Results: The anti-fibrillarin PMAT assay was positive in 31/32 (96.9%, France) and 12/15 (80.0 %, Italy) of samples preselected based on the AC-9 IIF pattern. Collectively, the PMAT assay showed 91.5% [95% Confidence Interval (CI): 80.1-96.6%] sensitivity with 100.0% (95% CI: 96.4-100.0%) specificity in non-SSc controls. Strong agreement was found between PMAT and FEIA with 100.0% positive qualitative agreement (34/34) and quantitative agreement (Spearman’s rho=0.89, 95% CI:0.77.9-0.95%, p<0.0001). Although most anti-fibrillarin positive samples were mono-specific (69.8%), some expressed additional antibodies (namely Scl-70, centromere, dsDNA, Ro52, Ro60, SS-B, Ribo-P, DFS70, and EJ). Conclusion: The new PMAT assay had high level of agreement to FEIA for the detection of anti-fibrillarin antibodies. Further studies are warranted to investigate the clinical associations and performance of the new method in combination with other critical markers in the SSc panel.
Study on Laser Powder Bed Fusion of Nickel-base Alloy: Scanning Strategy, Properties and Compression Properties
Authors: Qian Bo , Fan Hongri , Li Tengfei , Zhang Jianrui , Xi Jiangtao , Qiu Zhijun
Published: December 2020

Aiming at laser powder bed fusion of GH3536 nickel base alloy, the effects of different scanning strategies on microstructure, porosity and mechanical properties were explored. In the aspect of microstructure and micro hardness of the sample, three scanning strategies had little difference; in the aspect of macro mechanical properties of the sample, the slope subarea scanning was better than the helix and island scanning. On this basis, the slope subarea scanning was selected as the optimal scanning strategy to form the G-surface structure, and the compression performance of G-surface was studied. The results showed that: (1) the compression performance of G-surface structure was smaller than that of solid structure; while G-surface structure had a smooth compression curve, which indicated the good energy absorption characteristics; (2) with the increase of wall thickness, the mechanical performance of G-surface structure was also enhanced, while the energy absorption capacity was constantly reduced; (3) with the same wall thickness, the compression performance of sample in building direction (BD) is higher than that in horizontal direction (HD).
The Curcumin Analog (PAC) Has Anti-Oral Cancer Properties Through Impairing Pro-Survival Signaling Pathways and Activating the Cell Death Processes Apoptosis and Autophagy
Authors: Semlali Abdelhabib , Contant Camille Camille , Al-Otaibi Basem , Al-Jammaz Ibrahim , Chandad Fatiha
Published: December 2020

PAC (3,5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone), a novel bioactive curcumin analog, has been reported to have anticancer properties against various tumors. However, the anti-cancer effects of PAC on oral cavity squamous cell carcinoma (OC-SCC) were not studied yet. Our aim is to investigate the anti-oral cancer properties of PAC in vitro, and determine the molecular mechanisms underlying these effects. Viability assays including MTT and LDH were conducted to measure cell proliferation. Flow cytometry-based cytotoxicity assay was performed to detect autophagic cell death and oxidative stress markers. Western blotting was used for measuring protein expression/activation in apoptotic, autophagic and pro-carcinogenic cellular signaling pathways. We demonstrated that PAC preferentially and, in a dose, -dependent way kills oral cancer cells, but was not toxic to normal human gingival cells. PAC destabilizes cell-cycle distributions, inhibits the expression of oncogenes (cyclin D1) and that of cyclin-dependent kinase inhibitor (p21WAF1) is upregulated, increases the expression of p53 gene, and inhibits epithelial-mesenchymal transition markers in oral cancer cells. The PAC effect involve various signaling pathways including NF-κB, MAPK, Wnt, caspase-3/9 and PARP1. Finally, PAC demonstrated ability to induce autophagy, decrease production of reactive oxygen species (ROS), increase intracellular glutathione (GSH) activity, and reduce mitochondrial membrane potential in oral cancer cells. In conclusion, PAC inhibits the proliferation and increases the apoptosis and autophagy and oxidative stress of oral cancer cells. These effects involve ERK1/2, p38/JNK, NF-κB and Wnt cellular signaling pathways. Overall, our study suggests the potential use of PAC to treat oral cancer.
Monitoring Extinction Risk and Threats of the World’s Fishes based on the Sampled Red List Index
Authors: Miranda Rafael , Miqueleiz Imanol , Darwall William , Sayer Catherine , Dulvy Nicholas , Carpenter Kent , Polidoro Beth , Dewhurst-Richman Nadia , Pollock Caroline , Hilton-Taylor Craig , Freeman Robin , Collen Ben , Böhm Monika
Published: December 2020

Global biodiversity targets require us to identify species at risk of extinction and quantify status and trends of biodiversity. The Red List Index (RLI) tracks trends in the conservation status of entire species groups over time by monitoring changes in categories assigned to species. Here, we calculate this index for the world’s fishes in 2010, using a sampled approach to the RLI based on a randomly selected sample of 1,500 species, and also present RLI splits for freshwater and marine systems separately. We further compare specific traits of a worldwide fish list to our sample to assess its representativeness. Overall, 15.1% of species in the sample were estimated to be threatened with extinction, resulting in an sampled RLI of 0.914 for all species, 0.972 in marine and 0.860 in freshwater ecosystems. Our sample showed fishing as the principal threat for marine species, and pollution by agricultural and foresty effluents for freshwater fishes. The sampled list provides a robust representation for tracking trends in the conservation status of the world’s fishes, including disaggregated sampled indices for marine and freshwater fish. Reassessment and backcasting of this index is urgent to check the achievement of the commitments proposed in global biodiversity targets.
Green Coffee Extract Blockades Haloperidol-Induced Catalepsy and Contralateral Rotations Induced by Apomorphine After Unilateral 6-OHDA Lesion on Striatum
Authors: Molska Graziella , Paula-Freire Lyvia Izaura , Sakalem Marna , Köhn Daniele , Negri Giuseppina , Carlini Elisaldo , Mendes Fúlvio
Published: December 2020

Epidemiological studies have shown an inverse association between coffee consumption and the development of Parkinson’s disease (PD). The present investigation aimed to evaluate the effects of caffeine and green (non-roasted) coffee extract in experimental models of PD. The effects of the oral treatment with green coffee extracts (CE, Coffea arabica 100 or 400 mg/kg) and caffeine (31.2 mg/kg) were evaluated on the catalepsy induced by haloperidol in mice and unilateral 6-OHDA lesion of medial forebrain bundle (MFB) or striatum in rats. Also, the in vitro antioxidant activity and the monoamine levels in the striatum were investigated. CE presented a mild antioxidant activity and administration decreased the catalepsy index. CE at the dose of 400 mg/kg induced ipsilateral rotations 14 days after the lesion. However, the 30-day CE and caffeine treatments did not interfere with the animals’ rotation after apomorphine or methamphetamine challenges in animals with MFB lesion, nor on monoamines levels. Furthermore, CE and caffeine were effective in inhibiting the asymmetry between ipsilateral and contralateral rotations induced by methamphetamine and apomorphine in animals with lesion in the striatum but did not avoid the monoamines depletion. These results suggest a pro-dopaminergic action of CE, although its mechanism remains unclear.
The Impact of Inequalities and Health Expenditure on Mortality Due to Oral and Oropharyngeal Cancer: A 20-Year Trend Analysis
Authors: Cunha Amanda , Bigoni Alessandro , Antunes José , Hugo Fernando
Published: December 2020

Objectives: To assess the magnitude and trend of mortality rates due to oral (OC) and oropharyngeal cancer (OPC) in the 133 Intermediate Geographic Regions (IGR) of Brazil between 1996 and 2018 and to analyze its association with sociodemographic variables and provision of health services. It also aims to compare the trend of mortality from neoplasms that have been reported as associated with HPV (OPC) with the trend of neoplasms that have been reported as not associated with HPV (OC). Methods: We obtained mortality data from the Mortality Information System in Brazil and analyzed the trends using the Prais-Winsten method. Then, we assessed the relationship between mortality trends and socioeconomic, health spending, and health services provision variables. Results: The median of the APC of the country’s mortality rates was 0.63% for OC and 0.83% for OPC. Trends in mortality in the IGRs correlated significantly with the Human Development Index and government expenditure on ambulatory health care and hospitalizations. Conclusions: Mortality from both types of cancer decreased in those IGR in which the government spent more on health and in the more socioeconomically developed ones. This study found no epidemiological evidence that HPV plays the leading etiological factor in OPC in Brazil.
Spatio-temporally targeted in-situ electroporation of mammalian cells through SiO2 thin-film capacitive microelectrodes
Authors: Maschietto Marta , Maschio Marco Dal , Girardi Stefano , Vassanelli Stefano
Published: December 2020

Electroporation is a widely used non-viral technique for the delivery of molecules, including nucleic acids, into cells. Recently, electronic microsystems that miniaturize the electroporation machinery have been developed as a new tool for genetic manipulation of cells in vitro, by integrating metal microelectrodes in the culture substrate and enabling electroporation in-situ. We report that non-faradic SiO2 thin film-insulated microelectrodes can be used for reliable and spatially selective in-situ electroporation of mammalian cells. CHO-K1 and SH-SY5Y cell lines and primary neuronal cultures were electroporated by application of short and low amplitude voltage transients leading to cell electroporation by capacitive currents. We demonstrate reliable delivery of DNA plasmids and exogenous gene expression, accompanied by high spatial selectivity and cell viability. Finally, we show that SiO2 thin film-insulated microelectrodes support a double and serial transfection of the targeted cells.
A Fibular Notch Approach for the Treatment of Ankle Fractures Involving the Distal Tibial Plafond
Authors: Liu Tong , Cheng Yiheng , Qu Wenqing
Published: December 2020

BACKGROUND: Although several approaches have been used for the treatment of complex ankle fractures, there are still some ankle fractures which can not obtain ideal intraoperative exposure with these traditional approaches. The purpose of this study was to present an innovative fibular notch approach in detail for the treatment of ankle fractures involving the distal tibial plafond and to present a series of patients with either functional or radiographic outcomes.METHODS: Between March 2015 and October 2018, 22 patients with distal tibial plafond fractures with concomitant fibular and distal tibiofibular syndesmosis injuries were treated through a fibular notch approach. The details of the surgical technique were reviewed from the operative notes. Relevant data were reviewed from the medical records. The quality of fractures and syndesmosis reduction was examined using CT scans, and lateral stability of the ankle was assessed by physical examination and stress radiographs. The American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS) score was implemented for clinical functional assessment.RESULTS: All surgeries were successfully performed via the fibular notch approach as the primary approach. Postoperative radiography revealed satisfying restoration of all fractures and syndesmosis; however, CT scans showed mild malreduction with a gap of less than 2 mm in 4 fractures and a step-off of less than 2 mm in 1 fracture. No significant soft tissue complications occurred except for one case of delayed wound healing. All fractures healed with an average time of 17.3±3.6 weeks. Mild posttraumatic osteoarthritis (PTOA) was present in 4 patients. All patients achieved lateral stability of the ankle except one patient with distal syndesmosis instability. The average ankle range of motion was 55.0 degrees. The average AOFAS score was 88.8.CONCLUSIONS: The fibular notch approach is a safe and reliable approach for the treatment of specific ankle fractures involving the distal tibial plafond. This approach provides excellent direct visualization of the fragments and articular surface without significantly increasing iatrogenic injuries. Satisfactory radiographic and clinical results were observed, and further clinical and anatomical studies are recommended to ascertain the feasibility of this approach in the treatment of complex distal tibial fractures.
Analyses of the pericyte transcriptome in ischemic skeletal muscles
Authors: Teng Yuan-chi , Porfírio-Sousa Alfredo , Ribeiro Giulia , Arend Marcela , Meirelles Lindolfo , Chen Elizabeth , Rosa Daniela , Han Sang
Published: December 2020

Background
Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic therapies are becoming a real therapeutic approach to treat CLI. Pericytes are cells that surround vascular endothelial cells to reinforce vessel integrity and regulate local blood pressure and metabolism. In the past decade, researchers also found that pericytes may function as stem or progenitor cells in the body, showing the potential to differentiate into several cell types. We investigated the gene expression profiles of pericytes during the early stages of limb ischemia, as well as the alterations in pericyte subpopulations to better understand the behavior of pericytes under ischemic conditions.
Methods
In this study, we used a hindlimb ischemia model to mimic CLI in C57/BL6 mice and explore the role of pericytes in regeneration. To this end, muscle pericytes were isolated at different time points after the induction of ischemia. The phenotypes and transcriptomic profiles of the pericytes isolated at these discrete time points were assessed using flow cytometry and RNA sequencing.
Results
Ischemia triggered proliferation and migration and upregulated the expression of myogenesis-related transcripts in pericytes. Furthermore, the transcriptomic analysis also revealed that pericytes induce or upregulate the expression of a number of cytokines with effects on endothelial cells, leukocyte chemoattraction, or the activation of inflammatory cells.
Conclusions
Our findings provide a database that will improve our understanding of skeletal muscle pericyte biology under ischemic conditions, which may be useful for the development of novel pericyte-based cell and gene therapies.
A Merged Molecular Representation Learning for Molecular Properties Prediction with a Web-based Service
Authors: Kim Hyunseob , Lee Jeongcheol , Ahn Sunil , Lee Jongsuk
Published: December 2020

Deep learning has brought a dramatic development in molecular property prediction which is crucial in the field of drug discovery. Various methods such as fingerprint, SMILES, graphs have been proposed for representing molecules. Recently, unlabeled molecule data is used to improve performance for various pre-training methods. The main challenge of molecular properties predictions is designing a data representation and model that can show good performance for various datasets. However, performance deviation due to scarcity of dataset exists in constructing the model. We propose a new self-supervised method to learn the characteristics and structures of molecules by integrating existing methods. The key of our model is learning structures with matrix embedding and learning logics that can infer descriptors via QED prediction. As a result, our method improves the generalization of the data and achieves the best average performance by benchmarking downstream tasks. Moreover, we develop a web-based fine-tuning service to utilize our model on various tasks.
Breast Surgery on the Post-operative Well-being of Women: A Prospective Evaluation
Authors: Ranieri Jessica , Guerra Federica , Giacomo Dina Di
Published: December 2020

Background. Mammoplasty is the most common surgery that is used for both breast augmentation in healthy women (aesthetic plastic) and breast reconstruction (disease-related plastic) in women who have been diagnosed with and surgically treated for regional breast cancer with radical mastectomy (MRM). When compared to breast reconstruction surgery, aesthetic breast surgery is perceived to result in more favourable aesthetic outcomes.. This study aimed to examine the long-term effects of mammoplasty on the psychological adaptation of women.Methods. A total of 44 30–50-year-old women participated in this study. They were divided into two groups based on the type of breast surgery that they had undergone (augmentation surgery [AS] vs. reconstruction surgery [RS]) and the time that had elapsed since their surgery (≤ 3 years vs. > 3 years). Results. Our findings suggest that the psychological well-being of women who undergo AS declines over time. The women who had undergone AS ≤ 3 and > 3 years earlier did not differ in any of the indicators of emotional functioning. The only exception was their level of satisfaction with their breasts. We examined the impact of mammoplasty on the satisfaction levels and well-being of women who had undergone RS (after MRM). As expected, they were less satisfied with their breasts than those who belonged to the AS group However, this was true only among those who had undergone their surgery ≤ 3 years earlier.Conclusions. In conclusion, our findings underscore the need to provide psychological support to those who have undergone AS and RS. To shorten the adaptation process and enhance their mental well-being, personalised psychological interventions should be provided.
Leveraging Lean Research Principles to Engage Caregivers to Improve Child Undernutrition: a Case Example in Kolkata, India.
Authors: Mallory Kristen , Miller Mikaela A. , Brahmachari Rittika , Mitra Namrata , Abel-Rahman Susan
Published: December 2020

Background: For social purpose organizations (SPOs), decisions on which programs to scale are driven by information that often falls short of the gold-standard randomized control trial (RCT). This article offers a case study of how lean research, lean experimentation and lean impact principles can be leveraged by SPOs to inform strategic decision-making.Methods: Through two Phases of iterative experimentation, Children International assessed the feasibility and effectiveness of at-home anthropometric evaluation [mid-upper arm circumference Z-score (MUACz) tape] and nutritional support [supplementary foods (SupF)] to influence caregiver engagement and improve children’s nutritional status compared to centralized interventions. Body Mass Index Z-scores (BMIz) at baseline and completion of each Phase were collected along with semi-structured survey and focus group discussion data. Results: Phase I enrolled 37 caregiver/child dyads (17 MUACz, 20 control). The group receiving MUACz tapes reported ease of use for the intervention and a trend towards improved nutrition outcomes. The findings informed the design of Phase II, which enrolled 88 caregiver/child dyads across four groups (20 control, 21 MUACz, 27 SupF, 20 MUACz + SupF). Phase II uncovered low satisfaction with supplementary food and modest overall impact of the interventions despite favorable perceptions of changes in children’s overall health and higher levels of caregiver engagement addressing child nutritional needs. Conclusions: Lean approaches allow SPOs to innovate within the constraints of their organizations, and provide practical platforms to co-create and test evidence-based solutions with the populations they serve. Lean process and a lean mindset allowed the team to rapidly respond with at-home nutrition implementation strategies when faced with the emerging COVID-19 pandemic. Lean approaches can provide a framework to guide teams towards new solutions even during the most unpredictable and unprecedented times.
An Integrative Multi-omics Approach Reveals New Central Nervous System Pathway Alterations in Alzheimer’s Disease
Authors: Clark Christopher , Dayon Loïc , Masoodi Mojgan , Bowman Gene L , Popp Julius
Published: December 2020

Background: Multiple pathophysiological processes have been described in Alzheimer’s disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood, however. We tested the hypothesis that cerebrospinal fluid (CSF) integrative multi-omics analysis highlights novel interacting pathway alterations in AD.Methods: We performed multi-level CSF omics in a well-characterized cohort of older adults including subjects with normal cognition, mild cognitive impairment, and mild dementia. Proteomics, metabolomics, lipidomics, one-carbon metabolism, and neuroinflammation related molecules were analysed applying Elastic-net regression and Multi-Omics Factor Analysis followed by pathway enrichment. Multivariate analysis was used to select best predictive models of AD pathology and cognitive decline.Results: Multi-omics integration identified five major dimensions of heterogenicity explaining the variance within the cohort and differentially associated with AD . Further analysis exposed multiple interactions between single ‘omics modalities and distinct multi-omics molecular signatures differentially related to amyloid pathology, neuronal injury, and tau hyperphosphorylation. Enrichment pathway analysis revealed overrepresentation of the hemostasis, immune response and extracellular matrix signalling pathways in association with AD. Further, combinations of four selected molecules significantly improved prediction of both AD (protein 14-3-3 zeta/delta, clusterin, interleukin-15, and transgelin-2) and cognitive decline (protein 14-3-3 zeta/delta, clusterin, cholesteryl ester 27:1 16:0 and monocyte chemoattractant protein-1). Conclusions: Applying an integrative multi-omics approach we confirmed previously reported associations with AD pathology and report new molecular and pathways alterations. These findings are relevant for the development of personalized diagnosis and treatment approaches in AD.
Dexmedetomidine postconditioning attenuates cerebral ischemia following asphyxia cardiac arrest through down-regulation of apoptosis and neuroinflammation in rats
Authors: Fan Dan , Li GuangQian , Qian Lei , Gu Pan
Published: December 2020

Background and Purpose Neuroprotection strategies after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) remain key areas of basic and clinical research. This study was designed to investigate the neuroprotective effects of dexmedetomidine following resuscitation and potential mechanisms. Methods Anesthetized rats underwent 6-minute asphyxia-based cardiac arrest and resuscitation, after which the experimental group received a single intravenous dose of dexmedetomidine (25μg/kg). Neurological outcomes and ataxia were assessed after the return of spontaneous circulation. The serum levels and brain expression of inflammation markers was examined, and apoptotic cells were quantified by TUNEL staining. Results Neuroprotection was enhanced by dexmedetomidine post-conditioning after the return of spontaneous circulation. This enhancement was characterized by the promotion of survival, neurological function scores and coordination. In addition, dexmedetomidine post-conditioning attenuated the serum levels of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α at 2h, as well as interleukin (IL)-6 at 2, 24, and 48h. TUNEL staining showed that the number of apoptotic cells in the dexmedetomidine post-conditioning group was significantly reduced compared with in the control group. Further western blot analysis indicated that dexmedetomidine markedly reduced the levels of caspase-3 and nuclear factor-kappa B (NF-κB) in the brain. Conclusions Dexmedetomidine post-conditioning had a neuroprotective effect against cerebral injury following asphyxia-induced cardiac arrest and improved the survival rate. The mechanism was associated with the down-regulation of apoptosis and neuroinflammation.
Shared Decision Making in Pregnancy in Inflammatory Bowel Disease: Design of a Patient Orientated Decision Aid
Authors: Williams Astrid-Jane , Karimi Neda , Chari Radha , Connor Susan , De Vera Mary A , Dieleman Levinus A , Hansen Tawnya , Ismond Kathleen , Khurana Rshmi , Kingston Dawn , O’Connor Katie , Sadowski Daniel C , Fang-Hwa Flora , Wine Eytan , Leung Yvette , Huang Vivian
Published: December 2020

Objective: Research has indicated a lack of disease-specific reproductive knowledge among patients with Inflammatory Bowel Disease (IBD) and this has been associated with increased “voluntary childlessness”. Furthermore, a lack of knowledge may contribute to inappropriate medication changes during or after pregnancy. Decision aids have been shown to support decision making in pregnancy as well as in multiple other chronic diseases. A published decision aid for pregnancy in IBD has not been identified, despite the benefit of pre-conception counselling and patient desire for a decision support tool. Development and feasibility testing of a decision aid encompassing reproductive decisions in the setting of IBDMethods:The International Patient Decision Aid Standards were implemented in the development of the Pregnancy in IBD Decision Aid (PIDA). A multi-disciplinary steering committee was formed. Patient and clinician focus groups were conducted to explore themes of importance in the reproductive decision-making processes in IBD. A PIDA prototype was designed and tested for feasibility.Results:Issues considered of importance to patients and clinicians encountering decisions regarding pregnancy in the setting of IBD included fertility, conception timing, inheritance, medications, infant health, impact of surgery, contraception, nutrition and breastfeeding. Decisions relating to conception and medications were chosen as the current focus of PIDA, however content inclusion was broad to support use across preconception, pregnancy and post-partum phases. Favourable and constructive user feedback was received. Conclusions:The novel development of a decision aid for use in pregnancy and IBD was supported by initial user testing.
Prognostic Implications of Lymphocyte/C-Reactive Protein Ratio With Tumor-Infiltrating Lymphocytes in Resected Intrahepatic Cholangiocarcinoma
Authors: Miyazaki Katsuki , Morine Yuji , Imura Satoru , Ikemoto Tetsuya , Saito Yu , Yamada Shinichiro , Tokuda Kazunori , Okikawa Shohei , Yamashita Shoko , Oya Takeshi , Tsuneyama Koichi , Shimada Mitsuo
Published: December 2020

BackgroundLymphocyte/C-reactive protein (CRP) ratio (LCR), is a promising prognostic factor that can reflect tumor inflammation and systemic patient condition. The aim of this study was to investigate whether preoperative LCR can be a prognostic factor for post-surgical outcomes among patients with intrahepatic cholangiocarcinoma (IHCC). We also investigated the relationship between LCR and tumor infiltrating lymphocytes (TILs) to clarify whether systemic host immune parameters reflect local tumor immunity.MethodsWe enrolled 45 patients who had undergone hepatectomy for IHCC. Patients were divided into low LCR and high LCR groups, according to reactive operating characteristic curve (Cut-off value: 8836). We analyzed their overall survival (OS) and disease-free survival (DFS) with respect to LCR and other clinicopathological factors. We also investigated stromal TILs and numbers of CD8+ TILs in surgical specimens, and the relationship between LCR and TILs.ResultsTwenty-one patients (46.7%) were associated with low LCR. Low LCR was significantly correlated with older age, high CRP and advanced disease stage, and was a prognostic factor for OS and DFS. And multivariate analysis revealed that low LCR was an independent prognostic factor for worse OS (HR: 2.81 P<0.04). Regarding the relationship between LCR and local tumor immunity, while LCR and levels for stromal TILs were significantly related, LCR and levels for CD8+ TILs were significantly related. ConclusionsPreoperative LCR levels could predict the post-surgical prognosis of patients with IHCC, and reflected numbers of intra-tumoral CD8+ TILs.Trial registrationThis study was approved by Tokushima University Hospital ethics committee and with the approval of corresponding regulatory agencies, and all the experiments were carried out in accordance with the approved guidelines (Tokushima Clinical Trial Management System Number; 3215). All the patients involved in this study signed informed consent forms and agreed to participate.
Primary pulmonary invasive mucinous adenocarcinoma with sigmoid colon metastasis:a case report and literature review
Authors: Fang Jian , hu hui juan , cao hong
Published: December 2020

Background: Invasive mucinous carcinoma is a very rare tumor. The colonic metast-asis of IMA is more infrequent. So far, no literatures are published. Case presentation: We report a case of a patient with invasive mucinous adenocarci-noma. After serial months of chemitherapy, the sigmoid colonic metastasis was detected.Conclusions: Symptoms and CT findings can initially be subtle, histological examination remains the gold standard for the definitive diagnosis. Patients with high grade primary lung cancer may have gastrointestinal metastases, therefore their gastrointestinal should be examined to allow early detection and treatment.
A Phase 1 Study of SHR6390, A Cyclin-dependent Kinase 4/6 Inhibitor in Patients with Advanced Breast Cancer
Authors: Zhang Pin , Xu Binghe , Gui Lin , Wang Wenna , Xiu Meng , Zhang Xiao , Sun Guilan , Zhu Xiaoyu , Zou Jianjun
Published: December 2020

Background: SHR6390 is a novel inhibitor of cyclin-dependent kinase 4/6 which demonstrated promising anti-tumor potency in preclinical models. This first-in-human study was conducted to evaluate the tolerability, pharmacokinetics, safety, and preliminary antitumor activity of SHR6390 in patients with advanced breast cancer (ABC).Methods: In this open-label, phase 1 study, patients who had failed standard therapy were enrolled to receive oral SHR6390 in 3 + 3 dose-escalation pattern at doses of 25−175 mg. Eligible patients were given a single-dose of SHR6390 in week 1, followed by once daily continuous doses for three weeks, and one week off in 28-day cycles. Based on the tolerability, pharmacokinetics, and activity data revealed from the dose-escalation phase, three dose cohorts were selected to expand to 8−10 patients. The primary endpoints were maximum tolerated dose (MTD) and pharmacokinetics. Results: Between Apr 15, 2016 and Dec 21, 2018, 40 patients were enrolled; all were diagnosed of hormone receptor-positive and HER2-negative ABC. SHR6390 100 mg, 125 mg, and 150 mg cohorts were expanded to 10 patients. No dose limiting toxicity was observed and the MTD was not reached. Adverse events (AEs) of grade 3 or 4 were observed in 22 (55.0%) of 40 patients, being neutropenia (52.5%), leukopenia (35.0%), thrombocytopenia (5.0%), and hypertension (2.5%). No serious AEs were reported. At the doses of 50−175 mg, steady state areas under the concentration-time curve and peak concentration increased almost proportionally with dose. The disease control rate (DCR) was 62.5% (25/40, 95% CI: 45.8−77.3). Two patients (5%; 125 mg and 150 mg cohorts) achieved partial response, with responses lasting 169 and 356+ days, respectively. Among the three expansion cohorts, the 150 mg cohort had the numerically highest DCR of 80.0% (95% CI: 44.4‒97.5) and longest median progression-free survival of 8.4 months (95% CI: 2.1‒not reached).Conclusions: SHR6390 showed acceptable safety profile and dose-dependent plasma exposure in patients with ABC. The recommended phase 2 dose was 150 mg. Preliminary evidence of clinical activity was observed, which warrants further validation.Trial registration: ClinicalTrials.gov identifier: NCT02684266. Registered Feb 17, 2016. https://clinicaltrials.gov/ct2/show/NCT02684266.
Engineering Oleaginous Yeast Rhodosporidium Toruloides for Overproduction of Fatty Acid Ethyl Esters
Authors: Zhang Yang , Peng Jie , Zhao Huimin , Shi Shuobo
Published: December 2020

BackgroundProduction of biofuels and green chemicals by microbes is currently of great interest due to the increasingly limited reserves of fossil fuels. Biodiesel, especially fatty acid ethyl esters (FAEEs), is considered as an attractive alternative because of its similarity with petrodiesel and compatibility with existing infrastructures. Cost-efficient bio-production of FAEEs requires a highly lipogenic production host that is suitable for large-scale fermentation. As a non-model oleaginous yeast that can be cultured to an extremely high cell density and accumulate over 70 % biomass as lipids, Rhodosporidium toruloides represents an attractive host for FAEEs production. ResultsWe first constructed the FAEE biosynthetic pathways in R. toruloides by introducing various wax ester synthase genes from different sources, and the bifunctional wax ester synthase /acyl-CoA-diacyglycerol acyltransferase (WS/DGAT) gene from Acinetobacter baylyi was successfully expressed, leading to a production of 826 mg/L FAEEs in shake-flask fermentation. We then mutated this bifunctional enzyme to abolish the DGAT activity, and further improved the titer to 1.02 g/L. Finally, by fed-batch fermentation in a 1-L fermenter, the titer of FAEEs reached 9.2 g/L. It is worth mentioning that most of the produced FAEEs were secreted out of the cell, which should greatly reduce the cost of downstream processing.ConclusionWe achieved the highest FAEEs production in yeast with a final titer of 9.2 g/L and demonstrated that the engineered R. toruloides has the potential to serve as a platform strain for efficient production of fatty acid derived molecules.
Predictors for County Level Variations in Initial 4-week COVID-19 Incidence and Case Fatality Risk in the United States
Authors: Khose Swapnil , Chan Hei Kit , Wang Henry E. , Moore Justin Xavier
Published: December 2020

While studies indicate differences in incidence and case fatality risk of COVID-19, few efforts have shed light on regional variations in the intensity of initial community spread. We conducted a nationwide study using county-level data on COVID-19 from Center for Systems Science and Engineering at Johns Hopkins University. We characterized intensity of initial community COVID-19 attack by calculating the incidence and case fatality risk (CFR) for the first 4-week period of COVID-19 spread in each county. We used multivariate multilevel multinomial logistic regression to estimate the association of county-level characteristics with COVID-19 incidence and CFR. Of 3,143 counties, we included 1,052 with at least 100 reported cases on June 1st. Median incidence was 193.4 per 100,000 population (IQR: 94.2-397.5). Median case fatality risk was 3.6% (IQR: 1.4–7.3). Median age, rural population, population density, lower education, uninsured population, obesity, COPD prevalence were positively associated, while population, female sex, races (Asian, white), higher education, excessive drinking were negatively associated with initial COVID-19 incidence. Median age, female sex, Asian race, population density, higher education, excessive drinking, Intensive Care Unit beds, airborne infection isolation rooms were positively associated, while Hispanic ethnicity, lower education, obesity (paradox), uninsured population were negatively associated with initial COVID-19 CFR.
Developing a Tailored Implementation Action Plan for a Suicide Prevention Clinical Intervention in an Australian Mental Health Service: A Qualitative Study Using the EPIS Framework.
Authors: Zbukvic Isabel , Rheinberger Demee , Rosebrock Hannah , Lim Jaclyn , McGillivray Lauren , Mok Katherine , Stamate Eve , McGill Katie , Shand Fiona , Torok Michelle , Moullin Joanna C
Published: December 2020

Background: Tailoring implementation strategies to local contexts is a promising approach to supporting implementation and sustainment of evidence-based practices in health settings. While there is increasing research on tailored implementation of mental health interventions, implementation research on suicide prevention interventions is limited. This study aimed to evaluate implementation and subsequently develop a tailored action plan to support implementation, sustainment and scale-up of an evidence-based suicide prevention intervention - Collaborative Assessment and Management of Suicidality (CAMS) - in an Australian public mental health service.Methods: This study took place within a larger randomised stepped-wedge design suicide prevention trial. Approximately 150 mental health staff working within a regional and remote community Local Health District in Australia were trained in CAMS. Semi-structured interviews and focus groups with frontline staff and clinical leaders were conducted to examine barriers and facilitators to using CAMS. Data were analysed using a reflexive thematic analysis approach and mapped to the Exploration, Preparation, Implementation and Sustainment (EPIS) framework. This was followed by stakeholder engagement to design a tailored implementation action plan based on a ‘tailored blueprint’ methodology.Results: A total of 22 barriers to implementing CAMS were identified. Based on the perceived impact on implementation fidelity and the feasibility of addressing identified barriers, six barriers were prioritised for addressing through an implementation plan. These barriers were mapped to evidence-based implementation strategies and, in collaboration with local health district staff, goals and actionable steps for each strategy were generated. This information was combined into a tailored implementation plan to support the sustainable use of CAMS as part of routine care within this mental health service. Conclusions: This study provides an example of a collaborative approach to tailoring strategies for implementation on a large scale. Novel insights were obtained into the challenges of evaluating the implementation process and barriers to implementing an evidence-based suicide prevention treatment approach within a geographically large and varied mental health service in Australia.Trial registration: This study was conducted as part of the LifeSpan suicide prevention trial. Trial registration for LifeSpan in Australia New Zealand Clinical Trials Register, ID: ACTRN12617000457347. Prospectively registered on 28 March 2017.
Comparative Study of Trajectory Tracking Control for Automated Vehicles via Model Predictive Control and Robust H-infinity State Feedback Control
Authors: Yang Kai , TANG Xiaolin , Qin Yechen , Huang Yanjun , Wang Hong , Pu Huayan
Published: December 2020

A comparative study of model predictive control (MPC) schemes and robust A state feedback control (RSC) method for trajectory tracking, is proposed in this paper. Both MPC-based and RSC-based tracking controllers are designed on the basis of a 3-DOF vehicle model, including longitudinal, lateral and yaw motions. The main objective of this paper is to compare both controllers’ performance in tracking expected trajectory under different scenarios. Therefore, three cases, namely, verification test, double lane change test and curve test, were built in Carsim-Simulink joint platform. The simulation results indicate that MPC controller performed better in terms of accuracy and responding time under well driving conditions. However, in the test of double lane change manoeuvre where the road adhesion was set as 0.2, the maximum velocity RSC can execute was 14m/s, while that for MPC was 10m/s. In addition, in the curve test, the maximum velocity MPC can carry out was only 9m/s and that for RSC was 12m/s. In conclusion, RSC was robust and stable when the driving conditions was worse, while MPC was prone to be unstable.
Mapping Regional Forest Management Units: A Road-based Framework in Southeastern Coastal Plain and Piedmont
Authors: Yang Di , Fu Chiung-Shiuan
Published: December 2020

Management practices are one of the most important factors affecting forest structure and function. Landowners in southern United States manage forests using appropriately sized areas, to meet management objectives that include economic return, sustainability, and esthetic enjoyment. Road networks spatially designate the socio-environmental elements for the forests, which represented and aggregated as forest management units. Road networks are widely used for managing forests by setting logging roads and firebreaks. We propose that common types of forest management are practiced in road-delineated units that can be determined by remote sensing satellite imagery coupled with crowd-sourced road network datasets. Satellite sensors do not always capture road-caused canopy openings, so it is difficult to delineate ecologically relevant units based only on satellite data. By integrating citizen-based road networks with the National Land Cover Database, we mapped road-delineated management units across the regional landscape and analyzed the size frequency distribution of management units. We found the road-delineated units smaller than 0.5 Ha comprised 64% of the number of units, but only 0.98% of the total forest area. We also applied a statistical similarity test (Warren’s Index) to access the equivalency of road-delineated units with forest disturbances by simulating a serious of neutral landscapes. The outputs showed that the whole southeastern U.S. has the probability of road-delineated unit of 0.44 and production forests overlapped significantly with disturbance areas with an average probability of 0.50.