bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibacterial wound dressing nanofibrous mats composed of cellulose acetate loaded with chitosan/erythromycin nanoparticles
Authors: Doostan Maryam , Maleki Hassan , Doostan Mahtab , Khoshnevisan Kamyar , Faridi-Majidi Reza , Arkan Elham
Published: July 2020

This study attempts to fabricate the antibacterial nanofibrous mats composed of cellulose acetate (CA) nanofibers loaded with erythromycin-chitosan nanoparticles (Ery-CS NPs) intended for infected wound dressing. The Ery-loaded CS NPs were prepared by ionic gelation process and then incorporated into the CA electrospun nanofibers (NFs). The characterization of the NPs and mats were investigated by using dynamic light scattering (DLS), scanning electron microscopy (SEM), Attenuated Total Reflection Fourier transform infrared (ATR-FTIR) to show the size distribution, morphology and surface chemistry along with other physiochemical properties including hydrophilicity property, porosity, and water absorption capacity. The antimicrobial activity and cell viability of fibroblast cells were also evaluated. The results indicated that Ery was loaded into CS NPs with high encapsulation efficiency (95%). The CA NFs (17%) incorporated with the Ery-CS NPs (12 wt%) displayed smooth homogenous morphology with 141.7 ± 91.7 nm average diameter. The relevant analyses revealed that the NPs incorporated in NFs and provided high water holding capacity with high porosity. Finally, Ery-CS NPs/CA mats were able to inhibit the growth of both Gram-positive and Gram-negative bacteria as well as showed no cytotoxic effect on the human dermal fibroblast cells. Overall, our findings concluded that the proposed system could be potentially applied as the proper antibacterial mats for infected wound dressing applications.
Integrated physiological and transcriptomic analyses responses to altitude stress in oat (Avena sativa L.)
Authors: Jinqiu YU , Bing Li , Guowen Cui , Tingting Song , Wenhua He , Lu Lian , Jinglei He , zelai KongLing , Yajun Chen
Published: July 2020

Background The oat is an annual gramineous forage grass with the remarkable ability to survive under various stressful environments. However, understanding the effects of high altitude stresses on oats is poor. Therefore, the physiological and the transcriptomic changes were analyzed at two sites with different altitudes, low (ca. 2,080 m) or high (ca. 2,918 m) respectively.Results It was indicated that oats at high altitude showed higher levels of antioxidant enzyme activities and significant decreases in the non-photochemical quenching coefficient,chlorophyll content and stomatal density. Furthermore, oat yields were severely suppressed at the high altitude. RNA-seq results showed that 11,639 differentially expressed genes were detected at both the low and the high altitudesin which 5,203 up-regulated and 6,436 down-regulated. GO and KEGG annotations suggested that many differentially expressed genes be involved in pathways of cellular processes, metabolic processes and plant-pathogen interactions. Furthermore, 125 differentially expressed genes encoding TFs were involved in signal transductions by regulating the resistance genes in oats at high altitude. Some differentially expressed genes related to pigment metabolisms and photosyntheses were differentially expressed suggesting that these genes probably play responsive and regulatory roles in oats under the high altitude stress. Meanwhile, 273 differentially expressed genes related to hormone signaling pathways were significantly enriched in gibberellin, auxin, jasmonic acid and abscisic acid pathways indicating that these genes participated in the processes of oats responding to high altitude stresses.Conclusion In summary, our study generated genome-wide transcript profile and may be useful for understanding the molecular mechanisms of Avena sativa L. in response to high altitude stresses.These new findings contribute to our deeper relevant researches on altitude stresses and further exploring new candidategenes for adapting plateau environment oat molecular breeding.
Comparison of Frontal Alpha Asymmetry Among Schizophrenia Patients, Major Depressive Disorder, and Healthy Controls
Authors: Jang Kuk-In , Lee Chany , Lee Sangmin , Huh Seung , Chae Jeong-Ho
Published: July 2020

Background
Electroencephalography (EEG) frontal alpha asymmetry (FAA) has been observed in several psychiatric disorders. However, dominance in left or right frontal alpha activity remains inconsistent in patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls. This study compared FAA among patients with MDD, schizophrenia, and healthy control.
Methods
We recruited 20 patients with MDD, 18 patients with schizophrenia, and 16 healthy individuals. The EEG alpha frequency ranged from 8.0 to 12.0 Hz. FAA was expressed as the difference between absolute power values in both the right and left electrodes in the alpha frequency range (common-log-transformed F4–F3 and F8–F7). Hamilton depression and anxiety rating scales were evaluated in patients with MDD. Positive and negative syndrome scales were evaluated in patients with schizophrenia.
Results
Patients with schizophrenia showed significantly lower left frontal lobe activity than healthy controls (FAA, schizophrenia vs. healthy: -0.10 ± 0.05 vs. -0.05 ± 0.05). There were no significant differences in FAA between patients with schizophrenia and MDD as well as between patients with MDD and healthy controls.
Conclusions
The present study suggests that frontal alpha asymmetry indicates a breaking neural activity in schizophrenia. Breaking rhythmic activity as a left-lateralized FAA can be a neuropathological attribute in patients with schizophrenia but lack of sample size and information such as medication and duration of illness, all of which could make it difficult generalize finding.
Distilling Nanoscale Heterogeneity of Amorphous Silicon using Tip-enhanced Raman Spectroscopy (TERS) via Multiresolution Manifold Learning
Authors: Yang Guang , Li Xin , Cheng Yongqiang , Wang Mingchao , Ma Dong , Sokolov Alexei , Kalinin Sergei , Veith Gabriel , Nanda Jagjit
Published: July 2020

Accurately identifying the local structural heterogeneity of complex, disordered amorphous materials such as amorphous silicon (a-Si) is crucial for accelerating technology development. However, short-range atomic ordering quantification and nanoscale spatial resolution over a large area on a-Si have remained major challenges and practically unexplored. We resolve phonon vibrational modes of a-Si at a lateral resolution of 20 nm by tip-enhanced Raman spectroscopy (TERS). To project the high dimensional TERS imaging to a low dimensional (i.e. 2D) manifold space and categorize a-Si structure, we developed a multiresolution manifold learning (MML) algorithm. It allows for quantifying average Si-Si distortion angle and the strain free energy at nanoscale without a human-specified threshold. The MML multiresolution feature allows for distilling local defects of ultra-low abundance (< 0.3%), presenting a new Raman mode at finer resolution grids. This work promises a general paradigm of resolving nanoscale structural heterogeneity and updating domain knowledge for highly disordered materials.
Skeletal Reorganization Divergence of N-Sulfonyl Ynamides
Authors: Zeng Linwei , Lin Yuxin , Li Jiaming , Sajiki Hironao , Cui Sunliang
Published: July 2020

Skeletal reorganization is a type of intriguing processes for their interesting mechanism, high atom-economy and synthetic versatility. Herein, we describe an unusual skeletal reorganization divergence of N-sulfonyl ynamides. Upon treatment with lithium diisopropylamine (LDA), the N-sulfonyl ynamides could undergo a skeletal reorganization to deliver thiete sulfones, while the additional use of DMPU would shift the process to furnish propargyl sulfonamides. Mechanistically, these processes are proposed to initiate from a lithiation/cyclization cascade, and the following ligand-dependent 1,3-sulfonyl migration or β-elimination would constitute the divergence. Therefore, this protocol not only represents a new skeletal reorganization mode, but also provides a facile access to privileged molecules from the easily accessible ynamides.
Complex lifestyle intervention among inactive older adults with elevated cardiovascular disease risk and obesity. A mixed-method, single-arm feasibility study for RESTART- a randomized controlled trial
Authors: Deraas Trygve , Hopstock Laila , Henriksen André , Morseth Bente , Sand Anne Sofie , Njølstad Inger , Pedersen Sigurd , Sagelv Edvard , Johansson Jonas , Grimsgaard Sameline
Published: July 2020

Background: Physical inactivity and obesity are global public health challenges. Older adults are important to target for prevention and management of disease and chronic conditions. However, many individuals struggle with maintaining increased physical activity (PA) and improved diet. This feasibility study provides the foundation for the RESTART trial, a randomized controlled trial (RCT) to test a complex intervention to facilitate favourable lifestyle changes older adults can sustain. The primary objective of this study was to investigate study feasibility (recruitment, adherence, side-effects and logistics) using an interdisciplinary approach.Methods: This mixed-method one-year prospective single-arm feasibility study was conducted in Tromsø, Norway from September 2017. We invited by mail randomly selected participants from the 7 th survey of the Tromsø Study (2015-16) aged 55-75 years with sedentary lifestyle, obesity and elevated cardiovascular risk. Participants attended a six-month complex lifestyle intervention program, comprising instructor-led high-intensive exercise and nutritionist- and psychologist-led counselling, followed by a six-month follow-up. All participants used a Polar activity tracker for daily activity monitoring during the intervention. Participants were interviewed three times throughout the study. Primary outcome was study feasibility measures.Results: We invited potential participants (n=75) by mail of which 27 % (n=20) agreed to participate. Telephone screening excluded four participants, and altogether 16 participants completed baseline screening.The intervention and test procedures of primary and secondary outcomes were feasible and acceptable for the participants. There were no exercise-induced injuries, indicating that the intervention program is safe. Participants experienced that the dietary and psychological counselling were delivered too early in the intervention and in too close proximity to the start of the exercise program. Minor logistic improvements were implemented throughout the intervention period.Conclusion: This study indicates that it is feasible to conduct a full-scale RCT of a multi- component randomised intervention trial, based on the model of the present study. No drop-outs due to exercise-induced injury indicates that the exercises were safe. While minor improvements in logistics were implemented during the intervention, we will improve recruitment and adherence strategies, rearrange schedule of intervention contents (exercise, diet and psychology) as well as improving the content of the dietary and behavioural counselling to maximize outcome effects in the RESTART protocol.
How Does Globalisation Affect COVID-19 Responses?
Authors: Bickley Steve J. , Chan Ho Fai , Skali Ahmed , Stadelmann David , Torgler Benno
Published: July 2020

Purpose

This paper examines the effects of globalisation on the pace of governments implementing international travel restrictions during the recent coronavirus pandemic.

Results

We find that more globalised countries experienced a longer delay in implementing international travel restriction policies with respect to the date of the first confirmed COVID-19 case. We also find that informational (a subcomponent of social globalisation) and political globalisation have the strongest effects on the observed delays in implementing international travel restriction policies in more globalised countries. Lastly, we do not find evidence that more globalised countries are more likely to adopt a more restrictive international travel policy as the first response to the pandemic.

Conclusions

The findings highlight the dynamic relationship between globalisation and protectionism when governments respond to significant global events such as a public health crisis.
Efficacy and Safety of CGRP Monoclonal Antibodies for the Prevention of Migraine Compared with Placebo: A Systematic Review and Meta-Analysis
Authors: Yi Xiaojing , Chen Yun , Chen Kun , Liu Mo , Yi Jiale , Hu Xiongwei , Wang Guibin
Published: July 2020

Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are a novel class of drugs for migraine that includes erenumab, fremanezumab, galcanezumab and eptinezumab. In clinical trials, CGRP mAbs have been reported to show good efficacy in the prevention of episodic migraines or chronic migraines. Our aim was to evaluate the efficacy and safety of CGRP monoclonal antibodies in this study.Methods: We systematically searched for randomized controlled trials in the PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. The primary outcome was overall mean change from baseline to end of treatment in the number of monthly migraine headache days (MMHDs). The secondary outcomes included 50% response rate, in the number of monthly headache days (MHDs), in the number of monthly headache hours (MHHs), and in the number of monthly acute migraine-specific medication days (MSMDs). The safety outcomes were evaluated in terms of reported adverse events. Results: Eighteen studies including 11,099 patients were included in the meta-analysis. The meta-analysis showed that CGRP mAbs exhibited a significant benefit in reducing the number of MMHDs compared to placebo (Episodic migraine: Std. MD -0.42, 95% CI -0.47 to -0.36; Chronic migraine: Std. MD -0.28, 95% CI -0.35 to -0.21). Similarly, CGRP mAbs were superior to placebo in the secondary outcomes of 50% response rate, MHDs, MHHs, and MSMDs. With respect to safety, serious adverse events and withdrawal due to adverse events were not significantly associated with CGRP mAbs. Fremanezumab was associated with a significantly higher incidence of any adverse event compared with placebo (RR 1.10, 95% CI 1.03 to 1.17). Galcanezumab was associated with significantly higher treatment-emergent adverse events compared with placebo (RR 1.11, 95% CI 1.04 to 1.17). Constipation and injection site pain were significantly higher with erenumab than placebo. Injection site erythema and injection site induration were significantly higher with fremanezumab than placebo. Upper respiratory tract infection, injection site erythema, injection site pruritus and injection site reaction were significantly higher with galcanezumab than placebo. Conclusions: This study confirms that CGRP mAbs are effective as preventive treatments for episodic migraines and chronic migraines. Adverse reactions at the injection site were associated with erenumab, fremanezumab and galcanezumab therapy. Constipation was more common with erenumab. The risk of upper respiratory tract infection was higher with galcanezumab.Systematic review registration: Our PROSPERO protocol registration number: CRD42019125928. Registered 26 November 2019.
Hospitalized COVID-19 Patients treated with Convalescent Plasma in a Mid-size City in the Midwest
Authors: Hartman William R , Hess Aaron S , Connor Joseph P
Published: July 2020

Background: SARS-CoV-2 and its associated disease, COVID-19, has infected over seven million people world-wide, including two million people in the United States. While many people recover from the virus uneventfully, a subset of patients will require hospital admission, some with intensive care needs including intubation, and mechanical ventilation. To date there is no cure and no vaccine is available. Passive immunotherapy by the transfusion of convalescent plasma donated by COVID-19 recovered patients might be an effective option to combat the virus, especially if used early in the course of disease. Here we report our experience of using convalescent plasma at a tertiary care center in a mid-size, midwestern city that did not experience an overwhelming patient surge.Methods: Hospitalized COVID-19 patients categorized as having Severe or Life-Threatening disease according to the Mayo Clinic Emergency Access Protocol were screened, consented, and treated with convalescent plasma collected from local donors recovered from COVID-19 infection. Clinical data and outcomes were collected retrospectively.Results: 31 patients were treated, 16 severe patients and 15 life-threatened patients. Overall mortality was 27% (4/31) but only patients with life-threatening disease died. 94% of transfused patients with severe disease avoided escalation to ICU care and mechanical ventilation. 67% of patients with life-threatening disease were able to be extubated. Most transfused patients had a rapid decrease in their respiratory support requirements on or about day 7 following convalescent plasma transfusion.Conclusion: Our results demonstrate that convalescent plasma is associated with reducing ventilatory requirements in patients with both severe and life-threatening disease, but appears to be most beneficial when administered early in the course of disease when patients meet the criteria for severe illness.
An evaluation of the effectiveness, facilitators and barriers of HIV Teen Clubs in achieving successful transition from teen to adult care in Blantyre, Malawi using the RE‐AIM Framework.
Authors: Galagade Jerome , Mwapasa Victor
Published: July 2020

Background: High attrition is a major problem for Adolescent Living with HIV (ALHIV) transitioning from pediatric to adult care. Although the HIV Teen Club model has been shown to promote antiretroviral (ARV) adherence and viral suppression among ALHIV, its effect on promoting transitioning ALHIV from pediatric to adult care has not been formally evaluated. We sought to estimate the proportion of ALHIV enrolled in HIV Teen Clubs who successfully transitioned to adult care within six months of the expected transition time and assess health facilities’ fidelity in implementing HIV Teen Clubs’ adult care transition protocols and factors associated with successful transition to adult Care. Methods: From September 2018 to June 2019, we conducted a retrospective cohort study involving ALHIV attending HIV Teen Clubs in 14 primary health facilities in Blantyre, Malawi who had reached the recommended transition age of 18/19 years between July - December 2017. After obtaining consent, we reviewed their records to assess the proportion who successfully transitioned and also factors associated with transitioning. Checklist was used to ascertain fidelity of implementation of HIV Teen Club transition protocols. In-depth interviews were conducted with service providers (SP) in health facilities providing HIV Teen Club to get their perspectives on reasons for successful or unsuccessful transition.Results: Of the 131 eligible ALHIV enrolled in the study, only 6.9% (n=9) successfully transitioned to adult care within six months of the expected transition time. The overall fidelity in implementing adult care transition protocols in health facilities was medium. There was an association between implementation fidelity and ALHIV successful transition with 2 out of 3 health facilities with high implementation fidelity also successfully transitioning ALHIV into adult care. Successful ALHIV transitioning was associated with urban location of health facilities and ownership of the facilities by NGOs. SPs reported that lack of training in transitioning ALHIV, lack of clear guidelines, inadequate human resource and refusal of ALHIV to transition were some of the health system factors negatively influencing successful transition. Conclusions: Training and mentorship of SP in implementing transitioning protocols and adequately resourcing HIV teen clubs may improve their operations and facilitate successful transitioning.
Good clinical outcomes of patellofemoral arthroplasty for isolated patellofemoral osteoarthritis: a case-matched cohort comparative study of PFA with TKA
Authors: Wang Fei , Lin Wei , Chen Jia , Dai Yike , Niu Jinghui , Fan Chong Yi
Published: July 2020

Background: Severe isolated patellofemoral osteoarthritis is usually treated by total knee arthroplasty (TKA) in the majority of the world but patellofemoral arthroplasty (PFA) has been a viable alternative for many years although there have been concerns about implant longevity. The purpose of this research was to compare the clinical outcome of patients with isolated patellofemoral osteoarthritis who received PFA or TKA. Methods: From January 2015 to December 2017, 42 patients with isolated patellofemoral osteoarthritis who received PFA were included in the PFA group. In this period, a matched cohort of 42 patients with isolated patellofemoral osteoarthritis who received TKA (TKA group) was chosen for comparison. The results of the two groups were compared before surgery and at last follow-up using Tegner Activity Scale, Range of motion of the knee, Oxford Knee Score and Short Form 36 Health Survey. Differences were considered statistically significant at p < 0.05.Results: The mean follow-up time was 3.5 ± 0.3 and 3.4 ± 0.3 years in the PFA and TKA groups (p = 0.13), respectively. No significant difference in preoperative knee scores were found between the two groups (p > 0.05). However, postoperative, compared with Tegner Activity Scale, Range of motion, Oxford Knee Score and Short Form 36 Health Survey, the PFA group performed significantly better results (p < 0.05). The Kaplan-Meier implant survivorship with 95% confidence intervals was 94.12 % in the PFA group and 94.74% in the TKA group (p = 0.49).Conclusions: The patients with isolated patellofemoral osteoarthritis who underwent PFA had shown better clinical outcomes and higher quality of life. We believed that for the treatment of isolated patellofemoral osteoarthritis, the PFA was a less invasive procedure with improved patient satisfaction and range of motion at medium term follow-up.
Profile Of Children Referred To Primary Health Care Physiotherapy: A Longitudinal Observational Study In Norway
Authors: Evensen Kari Anne I , Sellæg Siw , Stræte Anne-Cath , Hansen Anne E. , Meisingset Ingebrigt
Published: July 2020

Background
Children are referred to primary care physiotherapy services for a variety of reasons, ranging from concerns for motor development to the need for extensive habilitation services. There is limited knowledge about their characteristics and outcome. The aim of this study was to describe the variation in baseline demographical and clinical characteristics as well as treatment outcome at follow-up six months after baseline.
Methods
Children referred to primary care physiotherapy in a municipality in Norway were invited to participate in this longitudinal observational study. The children’s demographics, causes of referral, functional diagnoses, influence on their daily activities, main goals and planned treatments were registered at baseline. Goal attainment and treatment compliance were registered at follow-up maximum six months after baseline.
Results
Baseline characteristics were registered for 148 children by the physiotherapist and for 101 (68.2%) children by their parents. Half of the children were referred from child health care centres due to concerns for motor development, asymmetry and orthopaedic conditions, and most of these children were below the age of one year. There was partly agreement between causes of referral and the physiotherapists’ functional diagnoses. The children’s daily activities were little affected by the problem or complaint for which they were referred. About a third of the children needed only examination. Follow-up data was registered for 64 children. The majority achieved their main treatment goal and the treatment was carried out as planned.
Conclusions
This study describes the profile of a broad spectrum of children referred to physiotherapy in primary health care in Norway. Our findings may guide further interdisciplinary collaboration and knowledge transfer between professionals involved in child health care with the goal to balance the use of resources to the need for physiotherapy.
Trial registration:
ClinicalTrials.gov Identifier: NCT03626389. Registered on August 13th 2018 (retrospectively registered).
Brockarchaeota, a novel archaeal lineage capable of methylotrophy
Authors: De Anda Valerie , Chen Lin-Xing , Dombrowski Nina , Hua Zhengshuang , Jiang Hong-Chen , Banfield Jillian , Li Wen-Jun , Baker Brett
Published: July 2020

Single carbon (C1) compounds such as methanol, methylamines and formaldehyde are ubiquitous in nature and they are large components of the carbon cycle. In anoxic environments C1-utilizing microbes (methylotrophs) play an important role in controlling global carbon degradation. Currently described anaerobic methylotrophs are limited to methanogenic archaea, acetogenic bacteria, and sulfate-reducing bacteria. Here, we report the first archaeal lineage outside of methanogenic taxa that are capable of anaerobic methylotrophy. Phylogenetic analyses suggest these archaea form a new phylum within the TACK superphylum, which we propose be named Brockarchaeota. A survey revealed Brockarchaeota are globally distributed in geothermal springs. Metabolic inference from 15 metagenome-assembled genomes from hot springs and deep-sea sediments indicates that Brockarchaeota are strict anaerobes. They contain a variety C1 metabolisms including the methanol and trimethylamine methyltransferases system, the ribulose bisphosphate pathway coupled with the non-oxidative pentoses phosphate pathway, and reductive glycine pathway. Brockarchaeota have an incomplete methyl-branch of the Wood-Ljungdahl pathway probably used for formaldehyde oxidation, since they lack several core genes involved in methanogenesis including methyl-CoM reductases. Brockarchaeota also appear to play an important role in the breakdown of plant-derived polysaccharides, especially cellulose, starch and xylan. Their broad distribution and their capacity to use both C1 compounds and complex polysaccharides via anaerobic metabolism suggest that the Brockarchaeota occupy previously overlooked roles in carbon cycling.
Dextrose 10% Drink is Superior than Sodium Dextrose in Increasing Blood Glucose and Sprint Speed in Soccer Players: a Double-Blinded Randomized Crossover Trial Study
Authors: Bukhari Agussalim , As’ad Suryani , Taslim Nurpudji A , Thaiyeb Mushawwir , Chrissander Ignatius Yuwanda , Pramudyo Febryan Agus
Published: July 2020

Background: Sports drink should be formulated to be effective in improving sports performance, but there is no standard of agreement about the most effective formulation. The diversity of situations in which these drinks are used for and the various factors might contribute to its specific efficacy. The main elements of a sports drink are water, sugar and salt. The major constituents which can be manipulated to alter the functional effects of sports drinks are the carbohydrate (CHO) concentration, type and the electrolyte content. The solution of either dextrose (D) 4-8 % or sodium dextrose (Na-D) are able to increase the blood glucose (BG). However, there are still no comparison about the differences in effects between solely D versus Na-D on soccer players. The aim of this study was to examine the effect of D supplementation on BG, VO2max, and sprint speed compared with Na-D. Method: We conducted a double-blinded crossover study of a 22 young male (19±1.1 years) soccer players, consumed either D or Na-D fluid. We compared pre and post data of BG, VO2max and sprint speed between D and Na-D group. The primary outcome was differences in ΔBG between D and Na-D group. Secondary outcomes were differences in ΔVO2max and Δsprint speed between D and Na-D group. Results: The mean BG level was higher in D compared with Na-D group [136±22.9 mg/dl vs 118±21.5 mg/dl] (p = 0.009). Mean differences of ΔBG of D (mean before and mean after) compared with ΔBG Na-D (mean before and mean after) is 16.8mg/dl (p = 0.001). The mean of sprint speed is faster in the D group [15.2±1.25 sec vs 15.9±1.61 sec] (p = 0.019), but we found no significant differences in VO2max between both groups [42.1±3.44 ml/min/kg vs 42.3±3.98 ml/min /kg] (p = 0.834). Conclusion: The present study demonstrated that D drink without added sodium has a large influence effect in increasing the BG level and sprint speed.Trial registration: ClinicalTrials, NCT04206579. Registered 20/12/2019 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04206579?term=NCT04206579&draw=2&rank=1
CXCL2 as a Prognostic Marker in Breast Cancer is Associated with Immune Infiltration and Regulated by miR-215
Authors: An Jia-Xiang , Chen Ying-Ying , Ma Zhao-Sheng , Yu Wen-Jie , Hu Jin-Xi , Cao Fei-Lin
Published: July 2020

Background: CXCL2 is a part of chemokine superfamily, which encodes secretory proteins involved in immune regulation and inflammation. The correlation between CXCL2 and prognosis of different cancers, tumor infiltrating lymphocytes are not clear. Methods: We analyzed the expression of CXCL2 and its effect on clinical prognosis through Oncomine database, Tumor Immune Estimation Resource (TIMER) website, Kaplan-Meier plotter, PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). TIMER and GEPIA were used to analyze the correlation between CXCL2 and the gene marker of immune infiltration. StarBase was used to predict the miRNA that may regulate CXCL2. The relationship between miR-532-5p and CXCL2 was detected by qRT-PCR. Kaplan-Meier plotter was used to evaluate the impact of miR-532-5p on clinical prognosis. Results: PrognoScan, Kaplan-Meier plotter and GEPIA database analysis showed that low expression of CXCL2 was associated with poor disease-specific survival time (DSS), relapse-free survival time (RFS) and overall disease survival (OS) in breast cancer patients. In addition, low expression of CXCL2 was associated with poor OS and RFS in patients with lymph node positive breast cancer. CXCL2 expression was positively correlated with the infiltration of B cells, CD4+T and CD8+T cells, neutrophils and dendritic cells (DCs) in BRCA, mainly in Luminal breast cancer. MiR-532-5p can directly regulate CXCL2 expression. High miR-532-5p expression is significantly correlated with HER2 negative, grade 2 and 3 and poor OS in patients with HER+ER- breast cancer. Conclusion: CXCL2 is closely related to the prognosis and immune infiltration level of breast cancer patients, it can be regulated by miR-532-5p.
Identification of Candidate Genes in Early-Stage Invasive Ductal Carcinoma Patients with High-Risk Mortality using 32 Genes Commonly Involved in Breast Cancer: A Retrospective Study
Authors: Hung Chih-Chiang , Huang Hsin-I , MOI SIN HUA
Published: July 2020

Background: Invasive ductal carcinoma (IDC) breast cancer is a heterogeneous disease characterized by multiple subtypes. Breast cancer survival is highly impacted by tumor burden, molecular subtypes, and gene profiles. Gene mutation is a type of genomic instability regarded as having a considerable effect on breast cancer prognosis. Using integrated survival analysis, this study identified candidate genes and a high-risk group of patients with early-stage IDC breast cancer to provide further understanding of the genetic characteristics associated with poor survival. Methods: The gene mutation profiles, baseline demographics, clinicopathological variables, and treatment characteristics of the early-stage breast cancer subpopulation were downloaded from an open access data platform. These data were analyzed for a total of 444 patients. In total, 32 genes commonly involved in breast cancer were listed, and the genes exhibiting significant differences (as estimated using the log-rank test) were selected as the candidate genes. Results: The patients were divided into control, low-risk, and high-risk groups according to their gene mutation profiles. The 5-year overall survival rates were 97.6%, 96.0%, and 68.2%, respectively. The high-risk group had a significantly higher risk of poor overall survival (adjusted hazard ratio = 9.94, 95% confidence interval = 2.24–44.20, P = 0.003) than the other groups and the low-risk group did not have a significantly higher risk of poor overall survival compared with controls. Conclusions: This study proposed an integrative approach for the identification of candidate genes for risk assessment of overall survival in these patients through typical survival analysis methods. The 10 candidate genes selected are particularly involved in cell-cycle processes, DNA repair, and drug resistance; their mutations were found to be generally associated with disease progression or therapeutic resistance, which is commonly associated with poor survival outcomes.
Exosome-Mediated siRNA pool Inhibits Axonal Growth Inhibitor in Cortical Neurons of Spinal Cord Injury in Rats
Authors: Liao Qi , Ming Jiang-Hua , Hu Ge-Liang
Published: July 2020

Background: As exosomes have been confirmed as a reservoir of siRNAs involved in certain diseases, the current study aims to investigate whether exosomal-siRNA could exert a protective role in spinal cord injury (SCI). Methods and Results: Exosomes in our experiment were isolated from lysosomal membrane-associated protein 2b (Lamp2b) overexpression HEK 293T cells, and purity of exosomes was characterized by the expression of CD9, CD47, and CD63 via western blot. Furthermore, the siRNA pool contains four siRNAs including siRNA-NgR, siRNA-LINGO-1, siRNA-Troy, and siRNA-PTEN was loaded to the exosomes, which indicated a significant role for the siRNA pool in reducing the expression of axon growth inhibitory factors. Upon the completion of loading into exosomes (exo-siRNA pool), the exo-siRNA pool was injected into primary cortical neurons of the SCI model in rats before cell proliferation and Rho expression were determined With the results revealed that purified addition could be applied to future experiments. The exo-siRNA pooled transfection caused downregulation of axon growth suppressors in primary cortical neurons including Nogo receptors (NgR), leucine-rich repeats and immunoglobulin domain-containing protein 1 (LINGO-1), Troy, and phosphatase and tenson homolog (PTEN). Cell proliferation and Rho expression of primary cortical neurons inhibited the expression of axonal growth inhibitors in rats with SCI by transfecting exogenous Sirna. Conclusion: This study confirmed that exosomes derived from Lamp2b overexpression HEK 293T cells facilitated both the recovery of functions and the survival of neurons when being loaded with the siRNA pool.
Anti-tumor effect of miR-1291 in colon cancer cells
Authors: Wang Jiaqi , Hirose Haruka , Yokoyama Yuhki , Ikeshima Ryo , Tsujimura Naoki , Bonkobara Saki , Takeda Koki , Hata Tsuyoshi , Inoue Akira , Hiraki Masayuki , Ohtsuka Masahisa , Nishida Naohiro , Takahashi Hidekazu , Haraguchi Naotsugu , Tanaka Shinji , Wu Xin , Mori Masaki , Yamamoto Hirofumi
Published: July 2020

Background: Cancer stem cells (CSCs) are drug-tolerant and cause distant metastasis and recurrence in various cancers, including colorectal cancer (CRC). Thus, CSC-targeted therapy may be an effective curative approach in CRC. MiR-1291 has an anti-tumor effect in carcinoma of kidney, esophagus, pancreas, and prostate. However, there is no report about the effect of miR-1291 on CRC.Methods: In this study, we took CSC marker DCLK-1 as a target gene, and screened promising miRNAs that may suppress DCLK-1 by using TargetScan Human. We performed luciferase reporter assay, quantitative real-time PCR analysis, and Western blot analysis to verify the interaction between DCLK-1 and miR-1291 in CRC cells. We also confirmed the function of miR-1291 on cancer stemness by identifying the expression of Bmi1 and CD133 in CRC cells by quantitative real-time PCR analysis, Western blot analysis, and flow cytometric analysis, as well as performing sphere formation assay. We also explored the effect of miR-1291 on cell proliferation, invasion, and wound-healing, colony formation, and cell cycle regulation. Results: We found a 7-base seed sequence of miR-1291 that matches the 3’ UTR sequence of DCLK-1 using TargetScan Human. A luciferase reporter assay showed that miR-1291 directly bound the 3’ UTR sequence of DCLK-1 and suppressed its expression at both the mRNA and protein levels. In addition, miR-1291 suppressed CSC markers Bmi1 and CD133 as well as sphere formation ability in CRC cells. Moreover, miR-1291 significantly suppressed the proliferation, invasion, wound-healing, and colony formation capability of colon cancer cell lines. MiR-1291 caused altered expression of the cell cycle-regulatory proteins representatively, CDK inhibitors p21WAF1/CIP1 and p27KIP1. Conclusions: Taken together, these findings indicate that miR-1291 has an anti-tumor effect by modulating multiple functions, including, cancer stemness, cell cycle, and invasiveness. Our data suggest that miR-1291 could be a promising nucleic acid medicine against CRC.
Established fibrous peritoneal metastasis in an immunocompetent mouse model accurately reflects the real clinical immune microenvironment of gastric cancer
Authors: Fujimori Daisuke , Kinoshita Jun , Yamaguchi Takahisa , Nakamura Yusuke , Gunjigake Katsuya , Ohama Takashi , Sato Koichi , Yamamoto Masami , Tsukamoto Tetsuya , Nomura Sachiyo , Ohta Tetsuo , Fushida Sachio
Published: July 2020

Background Peritoneal metastasis (PM) in gastric cancer (GC) is characterized by diffusely infiltrating and proliferating cancer cells accompanied by extensive stromal fibrosis in the peritoneal space. The prognosis of GC with PM is still poor regardless of the various current treatments. In order to elucidate the cause of difficulties in PM treatment, we compared the tumor immune microenvironment (TME) in primary and PM lesions in GC. In addition, a PM model with fibrous stroma was constructed using immunocompetent mice to determine whether its TME was similar to that in patients. MethodsImmuno-histochemical analyses of infiltrating immune cells were performed in paired primary and PM lesions from 28 patients with GC. A C57BL/6J mouse model with PM was established using the mouse GC cell line YTN16 either with or without co-inoculation of mouse myofibroblast cell line LmcMF with a-SMA expression. The resected PM from each mouse model was analyzed the immunocompetent cells using immunohistochemistry.ResultsThe number of CD8+ cells was significantly lower in PM lesions than in primary lesions (P<0.01). Conversely, the number of CD163+ cells (M2 macrophages) was significantly higher in PM lesions than in primary lesions (P=0.016). Azan staining revealed that YTN16 and LmcMF co-inoculated tumors were more fibrous than tumor with YTN16 alone (P<0.05). Co-inoculated fibrous tumor also showed an invasive growth pattern and higher progression than tumor with YTN16 alone (P=0.045). Additionally, YTN16 and LmcMF co-inoculated tumors showed lower infiltration of CD8+ cells and higher infiltration of M2 macrophages than tumors with YTN16 alone (P<0.05, P<0.05). These results indicate that LmcMF plays as cancer-associated fibroblasts (CAFs) by crosstalk with YTN16 and CAFs contribute tumor progression, invasion, fibrosis, and immune suppression.ConclusionsThis model is the first immunocompetent mouse model to accurately reflect the TME of human clinical PM. By using this model, new treatment strategies for PM, such as anti-CAFs therapies, may be developed.
Evaluation of S2 Alar and Traditional S1 Pedicle Fixation for Severe Lumbar Spondylolisthesis in Different Bone Mineral Densities: A Finite Element Analysis
Authors: Wang Juehan , Chen Wei , Yang Xi , Zhu Ce , Ling Tingxian , Feng Ganjun , Song Yueming , Liu Limin
Published: July 2020

Background: Lumbar spondylolisthesis is a common disease in older populations. The surgical treatment of spondylolisthesis has a history of more than 50 years, with L5-S1 screws widely used in clinical practice to reduce slippage and fusion. However, some patients with severe lumbar spondylolisthesis and osteoporosis could have complications, such as internal fixation rupture, S1 screw loosening, and incomplete slippage reduction. To better treat this kind of patient, sacral screw fixation is gradually becoming more common. Little is known about the biomechanical performance of L5-S2 alar internal fixation constructs after posterior lumbar interbody fusion. This study aimed to compare L5-S1 reduction and fixation methods and explore whether extending the fixation to include the S2 alar can significantly improve the stability of the internal fixation device. METHODS: Two kinds of validated finite element models of the L5-S1 segment were reconstructed via computed tomography images, including (1) the L5-S1 screw fixation model and (2) the L5-S2 alar fixation model. The inverse repair was performed using Geomagic software, the internal fixation device was drawn using Creo software, and the model parameters were set and analyzed using ANSYS Workbench software. Results: The average load of the L5-S2 alar internal fixation device was 86.9-111% higher than that of the L5-S1 fixation device when the internal bone of the S1 screw canal yielded. In the L5-S1 fixation model, the stress was concentrated in the tail of the S1 screw, and in the L5-S2 alar fixation model, the stress was concentrated in the titanium rod. In the L5-S2 alar fixation method, the internal deformation of the S1 screw track was scattered and uniform, while in the L5-S1 fixation method, local bone destruction in the front and back ends of the screw track was prone to occur due to the stress concentration. Conclusion: Extending fixation to the S2 wing can significantly improve internal fixation device stability and reduce the risk of intraoperative and postoperative fractures while avoiding injury to the sacroiliac joint, reducing the difficulty of surgery and the risk of injury to surrounding tissues. It is a reasonable plan for the treatment of moderate and severe lumbar spondylolisthesis with osteoporosis.
Treatment-Related Damage in Elderly-Onset ANCA Associated Vasculitis: Safety Outcome Analysis of Two Nationwide Prospective Cohort Studies
Authors: Sada Ken-ei , Ohashi Keiji , Asano Yosuke , Hayashi Keigo , Morishita Michiko , Watanabe Haruki , Matsumoto Yoshinori , Fujimoto Shouichi , Takasaki Yoshinari , Yamagata Kunihiro , Banno Shogo , Dobashi Hiroaki , Amano Koichi , Harigai Masayoshi , Arimura Yoshihiro , Makino Hirofumi
Published: July 2020

Background: It is not elucidated that treatment-related damage in elderly patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). Methods: Elderly (≥75 years of age) patients were enrolled from two nationwide prospective inception cohort studies. The primary outcome was 12-month treatment-related Vasculitis Damage Index (VDI) score. Secondary outcomes included serious infections within 6 months, total VDI score, remission, and relapse. Patient characteristics and outcomes were compared across three different initial glucocorticoid (GC) dose groups: high-dose, prednisolone (PSL) ≥ 0.8 mg/kg/day; medium-dose, 0.6 ≤ PSL < 0.8 mg/kg/day; and low-dose, PSL < 0.6 mg/kg/day. Results: Of the 179 eligible patients, the mean age was 80.0 years; 111 (62%) were female. The mean Birmingham Vasculitis Activity Score was 16.1. Myeloperoxidase-ANCA findings were positive in 168 (94%) patients, while proteinase3-ANCA findings were positive in 11 (6%). The low-dose group was older and had higher serum creatinine levels than the other groups. There were no statistically significant intergroup differences in remission or relapse, whereas serious infection developed more frequently in the high-dose (29 patients [43%]) than the low-dose (13 patients [22%]) or medium-dose (10 patients [19%]) groups (p = 0.0007). Frequent VDI items at 12 months included hypertension (19%), diabetes (13%), atrophy and weakness (13%), osteoporosis (8%), and cataracts (8%). Logistic regression analysis revealed that GC dose at 12 months (odds ratio, 1.14; 95% confidence interval, 1.00–1.35) was a predictor for diabetes.Conclusion: A reduced initial GC dose with rapid reduction might be required to ensure the safe treatment of elderly AAV patients.
Psychometric Properties of The Sub-Health Measurement Scale V1.0 for Assessing Suboptimal Health Status of Midwives: A Multi-Centre Cross-Sectional Study
Authors: Chen Xiao-Qian , Jiang Xiu-Min , Zheng Qing-Xiang , Huang Xin-Xin , Liu Gui-Hua , Pan Yu-Qing
Published: July 2020

Purpose Midwives with high work stress are prone to suboptimal health status (SHS). However, there is a lack of unified measurement standard for SHS. Sub-Health Measurement Scale V1.0 (SHMS V1.0) is a multidimensional inventory that has been proved to have adequate psychometric properties in other populations. Therefore, this study aimed to evaluate validity and reliability of SHMS V1.0 in midwives.Methods In this cross-sectional study, 842 midwives from 46 midwifery institutions completed the SHMS V1.0. Internal consistency and test-retest reliability of SHMS V1.0 were assessed with Cronbach's alpha and Pearson correlation coefficient. Project analysis and confirmatory factor analysis (CFA) were performed to assess construct validity. Concurrent validity of SHMS V1.0 was evaluated by Pearson correlation analysis with the 14-item Fatigue Scale (FS-14).Results The total Cronbach's alpha and test-retest reliability coefficient of SHMS V1.0 was 0.908 and 0.804, respectively. The correlation coefficients between each item and its corresponding dimension, and those between each dimension and its corresponding subscale were all greater than 0.4. The CFA supported the structure of SHMS V1.0 with strong factor loadings and excellent fit indexes in the first-order and modified second-order factor model. The concurrent validity for SHMS V1.0 showed large correlation with FS-14, but social subscale showed medium correlations with total fatigue, physical fatigue and mental fatigue. Conclusions The SHMS V1.0 is a valid and reliable instrument for measuring SHS for midwives. Given the severity and harmfulness of SHS in midwives, SHMS V1.0 is recommended as an important tool for clinical practice and research.