bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-carbohydrate Dietary Pattern on Glycemic Outcomes Trial (ADEPT) among Individuals with Elevated Hemoglobin A1c:&nbsp;Study Protocol for a Randomized Controlled Trial
Authors: Dorans Kirsten S. , Bazzano Lydia A. , Qi Lu , He Hua , Appel Lawrence J. , Samet Jonathan M. , Chen Jing , Mills Katherine T. , Nguyen Bernadette T. , O'Brien Matthew J. , Uwaifo Gabriel I. , He Jiang 
Published: December 2020

Abstract
• Background: Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality globally. Strong evidence supports the importance of diet and other lifestyle factors in preventing T2DM. Among individuals with T2DM, low-carbohydrate diets lead to decreases in hemoglobin A1c (HbA1c). However, research on the effects of low-carbohydrate diets on glycemic outcomes among individuals not currently on glucose-lowering medications who have elevated HbA1c is limited.• Methods: The objective of this randomized controlled trial is to study the effect of a healthy low-carbohydrate diet achieved through behavioral intervention and key food supplementation compared with usual diet on HbA1c and other metabolic risk factors among individuals with HbA1c from 6.0 to 6.9% who are not on glucose-lowering medications. In this parallel trial, 150 participants will be randomized to the intervention or control group for 6 months. The healthy low-carbohydrate diet target is <40 grams of net carbohydrates during the first 3 months and <40 to 60 net grams for months 3 to 6. This diet is characterized by abundant unsaturated fat and protein, high-fiber foods such as non-starchy vegetables and nuts, and minimal refined carbohydrates. The primary outcome is the difference in HbA1c change from baseline to 6 months in the intervention compared with usual diet group. Secondary outcomes include differences between groups in 6-month changes in fasting glucose, systolic blood pressure, total-to high-density lipoprotein cholesterol ratio, and body weight. Exploratory outcomes include differences in 6-month changes in fasting insulin, homeostasis model assessment of insulin resistance, diastolic blood pressure, waist circumference, and 10-year cardiovascular disease risk. An intention-to-treat analysis will be used. • Discussion: We expect that the results from this study will lead to new approaches for developing and implementing dietary approaches (other than the most commonly used reduced fat diet) that will substantially reduce risk of cardiometabolic disease among adults with or at high risk of T2DM. The study intervention involves behavioural counselling and promotes consumption of dietary components thought to reduce risk of cardiometabolic disease and has expected applicability in clinical practice.• Trial registration: Clinicaltrials.gov registry: https://clinicaltrials.gov/ct2/show/NCT03675360. Registered on September 18, 2018 (prior to enrolment of the first participant).
Inhibiting BDNF/TrkB receptor improves resiniferatoxin-induced postherpetic neuralgia through decreasing ASIC3 signaling in dorsal root ganglia
Authors: Wei Xiang , Wang Lina , Hua Jie , Jin Xiao-hong , Ji Fuhai , Peng Ke , Zhou Bin , Yang Jianping , Meng Xiaowen 
Published: December 2020

Abstract
Background Postherpetic neuralgia (PHN) is a devastating complication after varicella-zoster virus infection. Brain-derived neurotrophic factor (BDNF) has been shown to participate in the pathogenesis of PHN. Tropomyosin receptor kinase B (TrkB), an endogenous high-affinity receptor of BDNF is abundantly expressed in primary sensory neurons. Acid-sensitive ion channel 3 (ASIC3) is involved in chronic neuropathic pain, but its relation with BDNF/TrkB during PHN is unclear. This study aimed to investigate whether BDNF/TrkB contributes to PHN through regulating ASIC3 signaling in dorsal root ganglia (DRGs). Methods Resiniferatoxin (RTX) was used to induce rat PHN models. Mechanical allodynia was assessed by measuring the paw withdrawal thresholds (PWTs). Thermal hyperalgesia was determined by measuring the paw withdrawal latencies (PWLs). We evaluated the effects of TrkB/ASIC3 signaling inhibition on the behavioral test, neuronal excitability and inflammatory response in rat models of PHN. ASIC3 short hairpin RNA (shRNA) transfection was used to investigate the effect of exogenous BDNF on inflammatory response in cultured PC-12 cells. Results RTX resulted in significant mechanical allodynia, upregulated the protein expression of BDNF, TrkB, ASIC3, TRAF6, nNOS and c-Fos, and increased neuronal excitability in DRGs. Inhibition of ASIC3 reversed the above-mentioned effects of RTX, except for BDNF and TrkB protein expression. In addition, inhibition of TrkB blocked RTX-induced mechanical allodynia, activation of ASIC3 signaling and hyperexcitability of neurons. RTX-induced activation of BDNF was found in both neurons and satellite glia cells in DRGs. Furthermore, exogenous BDNF activated ASIC3 signaling, increased NO level and enhanced IL-6, IL-1β, TNF-α level in PC-12 cells, which was blocked by shRNA-ASIC3 transfection. Conclusion These findings demonstrate that inhibiting BDNF/TrkB reduced inflammation, decreased neuronal hyperexcitability and improved mechanical allodynia through regulating ASIC3 signaling pathway in DRGs, which may provide a novel therapeutic target for patients with PHN.
HDAC6&nbsp;Inhibitors Sensitize Claudin-high Breast Cancer Cells to Cysteine Depletion via Activation of PKCγ&nbsp;Signaling
Authors: Alothaim Tahiyat , Charbonneau Morgan , Tang Xiaohu 
Published: December 2020

Abstract
IntroductionTriple-negative breast cancer (TNBC) is a highly malignant breast cancer type with poor prognosis and lacks effective therapy. TNBC is not responsive to targeted therapy for hormone receptors and often exhibit resistance to current chemotherapeutic agents. Targeting tumor metabolism is an emergent strategy to treat cancer. Therefore, identification of tumor metabolic deregulations and development of effective targeted therapies are urgently needed.MethodsWe performed the epigenetic compound library screening in claudin-high breast tumor cells and identified therapeutical sensitizers to overcome the drug resistance of targeted cysteine-dependence therapy. Gene expression profiling were generated to analyze signaling pathways induced by the combined tubacin and cysteine deprivation treatment. Specific inhibitors, shRNA, and CRISPR/Cas9 gene editing approaches were used to target cellular proteins HDAC6 and PKCγ and examine their roles in cell death. Cell viability, RT-qPCR, and Western blotting assays were performed in cysteine-independent tumor cells to examine the anticancer effects of combined tubacin and cysteine deprivation treatment. ResultsWe found that TNBC has differential death responses to cysteine deprivation and the cysteine-dependence of TNBC corelates with the expression levels of claudin genes in addition to the classical EMT markers. To overcome drug resistance in claudin-high/cysteine-independent breast tumor cells, HDAC6 inhibitors were identified by the epigenetic compound library screening as potent sensitizers that synergize with cysteine deprivation to eradicate cysteine-independent tumor cells. Unexpectedly, HDAC6 knockout did not recapitulate the HDAC6 inhibitors-mediated synthetic lethality, indicating that HDAC6 is not the actual target of HDAC6 inhibitors in this context. Transcriptomic profiling revealed that HDAC6 inhibitors synergizes with cysteine depletion to trigger a profound gene transcriptional program. Notably, a zinc-related gene response was observed to accompany with a prominent increase of labile zinc in cells during cell death. We further showed that activation of PKCγ signaling is required to interfere cellular zinc homeostasis and drive HDAC6 inhibitors-mediated cell death.ConclusionOur study demonstrated that HDAC6 inhibitors function as potent sensitizers to overcome the resistance of cysteine deprivation in claudin-high breast tumor cells. Identification of such sensitizers would make the targeted cysteine-dependence therapy applicable in various subtypes of breast cancer.
High BRCA1 Gene Expression Increases the Risk of Early Onset Distant Metastasis in ER+ Breast Cancers
Authors: Chang Hui-Ju , Yang Ueng-Cheng , Lai Mei-Yu , Chen Chen-Hsin , Fann Yang-Cheng 
Published: December 2020

Abstract
BackgroundMore than 30% of ER+ breast cancer patients developed distant metastasis after adjuvant tamoxifen therapy. It has been shown that decreased BRCA1 protein function confers anti-estrogen “resistance.” Since the functional status of BRCA1 protein auto-regulates its own gene expression, BRCA1 transcript level should possibly be used to assess its active protein levels. Thus, it is interesting to explore the potential links between BRCA1 gene expression status and the prognosis of ER+ breast tumors.MethodsEarly-staged ER+ Breast cancer microarray samples were selected from the NCBI Gene Expression Omnibus (GEO) database. The aggressiveness of these tumors was evaluated based on molecular subtypes or patients’ distant metastasis-free survival (DMFS) time found in associated GEO datasets. In survival analysis, the optimal threshold to define high and low transcript levels was assessed by the logistic-accelerated failure time mixture regression model in a pooled data set, which simultaneously envisages the lifetime risk of distant metastasis and the distribution of the DMFS time from the surgery of a patient susceptible to distant metastasis. ResultsOn the basis of molecular subtyping, the relatively aggressive Luminal B tumor cells expressed significantly more BRCA1 transcripts than the less aggressive Luminal A tumor cells. This observation was supported by DMFS time analysis. When the upper 10% of the high BRCA1 expression patients was compared with the rest of the patients, the result was quite drastic. In patients susceptible to distant metastasis, the median onset time of distant metastasis for high BRCA1 expression group (2.2 years) was about one-fifth of the BRCA1 low expression group (10.5 years).Conclusions﻿High BRCA1 transcript level does not increase the incidence of distant metastasis, but increases the risk of early onset distant metastasis in ER+ breast cancers. As new therapeutic drugs have been developed for tumors with BRCA function loss, our findings suggest that BRCA1 gene expression test not only is useful for predicting patients’ outcome but also can be used in treatment decision.
Dynamic Analysis and Parametric Optimization of Telescopic Tubular Mast Applied on Solar Sail
Authors: Ji Chen-Yang , Liu Jin-Guo , Wu Chen-Chen , Zhao Peng-Yuan , Chen Ke-Li 
Published: December 2020

Abstract
The Telescopic Tubular Mast (TTM) has excellent performance and is widely used in aerospace. Reasonable parameter design and optimization can shorten development
cycle and improve performance for TTM. This paper designed a TTM driven by the bistable carbon reeled composite boom. The equivalent model of the TTM is established and simulated, which can be used as ex-tending structure for the solar sail. The work flow of the solar sail with the TTM is introduced. The natural frequency of the equivalent model and the segmented model is solved respectively using ABAQUS. The TTM under six different load conditions is analyzed. The influence of different factors on the vibration characteristics of the TTM is analyzed and the sensitivity analysis is carried out. Parameters including stiffness, natural frequency, mass and extension ratio are optimized using the multi-objective genetic optimization algorithm. According to the optimization results, the prototype was processed, and the experiment was completed with the equivalent load of solar sail. It provides a reference for the parametric design of the TTM.
Clinical Profiles of Osteoporotic Vertebral Compression Fractures: A Secondary Data Analysis of 358 Patients from a Prospective Clinical Study
Authors: Jin Huaijian , Ma Xiaoyuan , Liu Mingyong , Wang Zhong , Zhao Jianhua , Liu Peng 
Published: December 2020

Abstract
Background: For back pain patients with spine dysfunction, clinical profiles are crucial for clinicians to establish the diagnostic and therapeutic decision-making. The objectives of this study were (1) to outline the incident clinical findings and familiarize physicians with the clinical profiles of osteoporotic vertebral fractures (OVFs) and (2) to characterize patients with radiating pain (RP), spinal palpation tenderness (SPT), or axial spinal percussion pain (ASPP). Methods: This is a secondary data analysis of 358 patients from a prospective clinical study (November 1, 2016, to September 30, 2018) with particular focus on the incident RP, SPT, and ASPP. Predictive analyses for the incident RP, SPT and ASPP were done along the clinical profiles in 358 patients (284 females).Results: The cohort patients who complained of spinal movement-related pain performed a limited amplitude of movements with the purpose of avoiding the onset of back pain in daily life. Of the patients who had OVFs, 76 (21.2%) patients had RP, 197 (55.0%) patients had SPT, and 83 (23.2%) patients had ASPP. On multiple regression analysis, only patients with VFs located in T1–T9 or those who had a -2.5 ≤ T-score < -3.5 showed significantly higher incidences of RP, SPT, and ASPP (p < 0.05).Conclusion: Dynamic back pain and backache avoidance behavior are the typical clinical presentations of patients with OVFs. RP, SPT, and ASPP are nondeterministic incidents, indicating that avoidance is necessary with respect to cognitive bias in clinical practice.
miRNA-6087 Delivered by Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells, Inhibition of miR-6087 in Exosomes can Significantly Inhibit the Proliferation, Invasion and Migration of Tumor Cells.
Authors: Yang Xiaowei , Zhou Yibiao , Lai Qi , Huang Sheng , Liu Xuqiang , Hu Bolin , Dai Min , Zhang Bin 
Published: December 2020

Abstract
Background: Mesenchymal stem cells (hBMSCs) function in most of tumor microenvironment，including osteosarcoma,and interact with proximal cells. Here, in view of exosomes derived from hBMSCs, we studied the miRNA secreted from hBMSCs in the growth of human U2OS cells. Methods: hBMSCs were cultured in α-DMEM containing fetal bovine serum. After 48 hours, the cell culture supernatants containing the exosomes were harvested and exosome purification was performed by PEG-based vesicle enrichment. Osteosarcoma (U2OS) cells were treated with exosomes derived from hBMSCs enriched with or without miR-6087. Cell viability was measured by the scratch migration assay, Transwell invasion assay, and CCK-8 test. The expression of HSP70/ALIX and miR-6087 in exosomes was determined by western blotting and RT-PCR, respectively. Results: hBMSC-derived exosomes were found to play a key role in the U2OS cell growth. Inhibition of miR-6087 in exosomes can significantly inhibit the proliferation and invasion of tumor cells.Conclusion: This was the first time that we demonstrated that exosomes derived from hBMSCs have the power to suppress the growth of U2OS cells by downregulating miRNA-6087. Our research shows a new possibility for the way in which hBMSCs take part in tumor progression.
Designing a Sustainable Biofuel Supply Chain by Considering Carbon Policies: A Case Study in Iran
Authors: Zarrinpoor Naeme , Khani Aida 
Published: December 2020

Abstract
Background: Population growth and increasing the utilization of fossil fuels have increased carbon emissions and the global warming phenomenon with detrimental impacts on the human life and the environment. Therefore, finding a sustainable substitution for fossil fuels becomes a great challenge for all societies from all over the world. Renewable energies such as biofuels are the appropriate alternative to decrease environmental concerns.Methods: This study develops a multi-objective multi-period multi-echelon biofuel supply chain (BSC) from switch grass regarding economic, environmental and social aspects of the sustainability. For considering the environmental aspect, four carbon policies are taken into account; namely the carbon cap, the carbon tax, the carbon trade and the carbon offset. The fuzzy interactive programming method is implemented to solve the multi-objective model and the fuzzy best-worst method (FMWM) is applied for weighting social objective components.Results: To illustrate the applicability of the model, an actual case study in Iran is considered. It is revealed that different solutions are obtained for the location of switch grass resources, preprocessing centers, and bio-refineries under different carbon policies. Numerical results also demonstrate that biofuel production and transportation activities have a great share in carbon emissions and BSC costs. Applying the carbon cap policy in the proposed case study decreases the carbon emission over 14% in comparison to the basic situation. Moreover, implementing the carbon trade policy increases the total BSC profit about 11% in comparison to the basic situation. The carbon offset policy plays a significant role in improving social considerations compared with other policies. Overall, since three aspects of sustainability have appropriate values under the carbon trade policy, it can be concluded that this policy is the most appropriate policy.Conclusions: The proposed model can aid policy makers and governments to optimize the profitability of the BSC, the carbon emission reduction, and the social consideration, simultaneously.
Distinct symptoms and underlying comorbidities with latitude and longitude in COVID-19: A systematic review and meta-analysis
Authors: Tian Yong , Wu Qian , Li Honwei , Wu Qi , Xie Yi , Li Li , Chen Huaiyong 
Published: December 2020

Abstract
The coronavirus disease 2019 (COVID-19) pandemic is straining global health resources and the prevalence of severe disease appears to vary across countries. In accordance with PRISMA guidelines, we performed a systematic review and meta-analysis of clinical features and underlying medical conditions of COVID-19. Eighty-seven studies, involving 1,434,931 COVID-19 patients from the Americas, Asia, Europe, and Oceania, were included. Geographically, the rate of severity was highest in Asia (95% confidence interval [CI] 0.23‒0.30). The rates of comorbidities of COVID-19 patients in the Americas were significantly higher than those in Asia. Most Asian patients had fever (95%CI 0.70‒0.81), and most Oceanian patients had cough (95%CI 0.68‒0.70) as their prevalent symptom. Dyspnea was common in the Americas (95%CI 0.33‒0.64), Europe (95%CI 0.29‒0.64), and high latitude regions (95%CI 0.53‒0.82). European patients exhibited significantly high rates of loss of smell and taste (95%CI 0.60-0.97). In low-latitude regions, cancer (95%CI 14.50‒4.89) had the strongest correlation with illness severity. Comorbid diseases and clinical manifestations of severe COVID-19 patients vary substantially between latitudes and longitudes. Region-specific care should be considered to treat and improve the prognosis of COVID-19 patients.
Prediction of allergic diseases&nbsp;by measurement total IgE&nbsp;in umbilical cord&nbsp;blood levels: A 8 -year follow up study
Authors: Dib Ghazal , Doya Leen Jamel , Al-hakim Amal , Ismaeel Yazan , Motawej Hana Habib , Ismaeel Mayya 
Published: December 2020

Abstract
Allergic diseases in children have increased significantly in recent years and now affect up to 35% of children. This study aimed to investigate the total IgE level in newborn’s umbilical cord blood and its association with the development of allergic diseases during 8 years. Methods: In cross-sectional study included 500 infants who were born in the obstetrics department at Tishreen and Al-Assad University Hospitals during the period 2007-2015. Questionnaires were administered after the birth of the infant included gender, gestational age, birth weight, mode and season of delivery, smoking during pregnancy, family history of the allergic diseases, and umbilical cord blood was obtained for measurement of total immunoglobulin E (IgE) levels. We followed the newborns for eight years through clinical examination to investigate the development of allergic diseases. Results: Of 500 newborns, 214 (42.8%) were classified as having high total immunoglobulin E in umbilical cord blood. We followed 143 of 214 newborns for 8 years. There was an allergic family history in 51.7% of newborns. During the following period, the allergic diseases developed in 76.22% of the children with high total immunoglobulin E in umbilical cord blood. Allergic symptoms in children varied between nasal allergy in 19.6% of children, skin allergy (Eczema and urticarial)in 25.2% of children, childhood asthma in 31.5% of children. The rate of development of allergic symptoms in the presence of two factors (family history and high total immunoglobulin E in umbilical cord blood) was 51.7%. Conclusion: We found a high Prevalence of allergic diseases in children with high total immunoglobulin E in umbilical cord blood. The Current study could be used as a preventative strategy to reduce the risk of allergic diseases by predictive of subsequent
A qualitative study to identify critical attributes and attribute-levels for a Discrete Choice Experiment on oral Pre-Exposure Prophylaxis (PrEP) delivery among young people in Cape Town and Johannesburg, South Africa.
Authors: Dietrich Janan Janine , Atujuna Millicent , Tshabalala Gugulethu , Hornschuh Stefanie , Mulaudzi Mamakiri , Koh Michelle , Ahmed Nadia , Muhumuza Richard , Ssemata Andrew , Otwombe Kennedy , Bekker Linda-Gail , Seeley Janet , Martinson Neil Alexander , Terris-Prestholt Fern , Fox Julie 
Published: December 2020

Abstract
Background The uptake and adherence of daily oral PrEP has been poor in high-risk populations in South Africa including young people. We used qualitative research methods to explore user preferences for daily and on-demand oral PrEP use among young South Africans, and to inform the identification of critical attributes and attribute-levels for quantitative analysis of user preferences, i.e. a discrete choice experiment (DCE). MethodsData were collected between September and November 2018 from eight group discussions and 20 in-depth interviews with young people 13 to 24 years in Cape Town and Johannesburg. Using a convenience sampling strategy, participants were stratified by sex and age. Interviewers used a semi-structured interview guide to discuss several attributes (dosing regimen, location, costs, side effects, and protection period) for PrEP access and use. Groups discussions and in-depth interviews were audio-recorded, transcribed verbatim and translated to English. We used framework analysis to explore context-specific attributes and attribute-levels for delivering oral PrEP in South Africa. The adolescent community advisory board, expert and study team opinions were consulted for the final DCE attributes and levels. ResultsWe enrolled 74 participants who were 51% (n=38/74) male, had a median age of 18.5 [Interquartile range=16-21.25] years, 91% (n=67/74) identified as heterosexual and 49% (n=36/74) had not completed 12th grade education. Using the qualitative data, we identified five candidate attributes including (1) dosing regimen, (2) location to get PrEP, (3) cost, (4) route of administration and (5) frequency. After discussions with experts and the study team, we revised the DCE to include the following five attributes and levels: dosing regime: daily, and on-demand PrEP; location: private pharmacy, public clinic, mobile clinic, ATM); cost: free-of-charge, R50 (~2GBP), R265 (~12GBP); side effects: nausea, headache, rash; and duration of protection: fulltime protection versus when PrEP is used). ConclusionsThere is limited literature on qualitative research methods describing the step-by-step process of developing a DCE for PrEP in adolescents, especially in resource-constrained countries. We provide the process followed for the DCE technique to understand user preferences for daily and on-demand oral PrEP among young people in South Africa.