bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interstitial changes after reperfused myocardial infarction in swine: morphometric and genetic analysis
Authors: Rios-Navarro Cesar , Ortega Maria , Marcos-Garces Victor , Gavara Jose , de Dios Elena , Perez-Sole Nerea , Chorro Francisco J. , Bodi Vicente , Ruiz-Sauri Amparo 
Published: July 2020

Abstract
Background
Following myocardial infarction (MI), we aimed to characterize morphometric and genetic changes in extracellular matrix (ECM) components from ischemia onset until late phases after coronary reperfusion in necrotic and salvaged myocardium.

Results
Swine were divided into one control (n = 5) and three MI groups: 90-min of ischemia without reperfusion, or followed by 1-week or 1-month reperfusion (n = 5 per group). In samples from the necrotic and salvaged areas, ECM components were morphometrically quantified and mRNA levels of factors involved in ECM remodeling were evaluated. After 90-min of ischemia, fibronectin, laminin, and elastic fibers content as well as upregulated mRNA expression of tissue inhibitors of metalloproteinases (TIMP)1, TIMP2, TIMP3 and connective tissue growth factor increased in the necrotic and salvaged myocardium. In both reperfused MI groups, collagen-I, collagen-III, elastic fibers, glycosaminoglycans, laminin, and fibronectin levels heightened in the necrotic but not the salvaged myocardium. Moreover, mRNA expression of TIMP1, TIMP2 and TIMP3, as well as metalloproteinase-2 and metalloproteinase-9 heightened in the necrotic but not in the salvaged myocardium.

Conclusions
Matrix remodeling starts after ischemia onset in both necrotic and salvaged myocardium. Even if ECM composition from the salvaged myocardium was altered after severe ischemia, ECM makes a full recovery to normal composition after reperfusion. Therefore, rapid coronary reperfusion is essential not only to save cardiomyocytes but also to preserve matrix, thus avoiding impaired left ventricular remodeling.
Detection of leukemia gene fusions by targeted RNA-sequencing in routine diagnostics
Authors: Engvall Marie , Cahill Nicola , Jonsson Britt-Inger , Höglund Martin , Hallböök Helene , Cavelier Lucia 
Published: July 2020

AbstractBackgroundWe have evaluated an NGS-based method to detect recurrent gene fusions of diagnostic and prognostic importance in hematological malignancies. Our goal was to achieve a highly specific assay with a simple workflow, short turnaround time and low cost.MethodThe assay uses a commercially available anchored multiplex PCR panel for target enrichment and library preparation, followed by sequencing using a MiSeq instrument. The panel includes all recurrent gene fusions in AML and ALL and is designed to detect gene-specific fusions without prior knowledge of the partner sequence or specific break points. Diagnostic RNA samples from 27 cases with hematological malignancies encompassing 23 different transcript variants were analyzed. In addition, 12 cases from a validation cohort were assessed.ResultAll known fusion transcripts were identified with a high degree of confidence, with a large number of reads covering the breakpoints. Importantly, we could identify gene fusions where conventional methods had failed due to cryptic rearrangements or rare fusion partners. The newly-identified fusion partners were verified by RT-PCR and transcript-specific qPCR was designed for patient-specific follow-up. In addition, 12 cases were correctly assessed in a blind test, without prior knowledge of molecular cytogenetics or diagnosis.ConclusionIn summary, our results demonstrate that targeted RNA sequencing using anchored multiplex PCR can be implemented in a clinical laboratory for the detection of recurrent and rare gene fusions in hematological diagnostic samples.
The adipokine fatty-acid binding protein 4 and cardiac remodeling
Authors: von Jeinsen Beatrice , Ritzen Lisa , Vietheer Julia , Unbehaun Claudia , Weferling Maren , Liebetrau Christoph , Hamm Christian W. , Rolf Andreas , Keller Till 
Published: July 2020

Abstract
Background
Previous publications about the association between fatty-acid binding protein 4 (FABP4) and cardiac remodeling have reported different, both beneficial and harmful, associations. Aim of the present investigation was to evaluate the association of FABP4 with parameters of myocardial remodeling defined by cardiac magnetic resonance imaging (CMR).

Methods
We investigated plasma FABP4 levels in 331 patients (71% men, mean age 63±13 years) with preserved left ventricular ejection fraction (LVEF ≥ 55%) who underwent a CMR examination. We used linear cox regression to investigate associations between FABP4 and left ventricular end-diastolic diameter (LVEDD), right ventricular end-diastolic diameter (RVEDD), relative wall thickness (RWT), left ventricular mass index (LVMI), and LVEF (unadjusted and adjusted for age, sex, body mass index, cardiac biomarkers, and comorbidities).

Results
FABP4 levels were associated with lower LVMI and higher NT-proBNP levels in an adjusted model. The inverse association between FABP4 and LVMI was more pronounced in lower FABP4 levels, whereas the positive association between FABP4 and NT-proBNP was more pronounced in relatively high NT-proBNP levels.

Conclusions
Possible beneficial and harmful associations between FABP4 and left ventricular size have been reported. Our results suggest a beneficial association with LVMI (more pronounced in lower FABP4 levels) but a harmful association with NT-proBNP (more pronounced in higher FABP4 levels). Therefore, our results might indicate a potential dose-dependent association of FABP4, but this observation needs further investigation in larger study samples.
The length of ribosomal binding site spacer sequence controls the production yield for intracellular and secreted proteins by Bacillus subtilis
Authors: Volkenborn Kristina , Kuschmierz Laura , Benz Nuka , Lenz Patrick , Knapp Andreas , Jaeger Karl-Erich 
Published: July 2020

Abstract
Background
Bacillus subtilis is widely used for the industrial production of recombinant proteins, mainly due to its high secretion capacity, but higher production yields can be achieved only if bottlenecks are removed. To this end, a crucial process is translation initiation which takes place at the ribosome binding site enclosing the Shine Dalgarno sequence, the start codon of the target gene and a short spacer sequence in between. Here, we have studied the effects of varying spacer sequence lengths in vivo on the production yield of different intra- and extracellular proteins.

Results
The shuttle vector pBSMul1 containing the strong constitutive promoter PHpaII and the optimal Shine Dalgarno sequence TAAGGAGG was used as a template to construct a series of vectors with spacer lengths varying from 4 to 12 adenosines. For the intracellular proteins GFPmut3 and β-glucuronidase, an increase of spacer lengths from 4 to 7–9 nucleotides resulted in a gradual increase of product yields up to 27-fold reaching a plateau for even longer spacers. The production of secreted proteins was tested with cutinase Cut and swollenin EXLX1 which were N-terminally fused to one of the Sec-dependent signal peptides SPPel, SPEpr or SPBsn. Again, longer spacer sequences resulted in up to tenfold increased yields of extracellular proteins. Fusions with signal peptides SPPel or SPBsn revealed the highest production yields with spacers of 7–10nt length. Remarkably, fusions with SPEpr resulted in a twofold lower production yield with 6 or 7nt spacers reaching a maximum with 10–12nt spacers. This pattern was observed for both secreted proteins fused to SPEpr indicating a dominant role also of the nucleotide sequence encoding the respective signal peptide for translation initiation. This conclusion was corroborated by RT qPCR revealing only slightly different amounts of transcript. Also, the effect of a putative alternative translation initiation site could be ruled out.

Conclusion
Our results confirm the importance of the 5′ end sequence of a target gene for translation initiation. Optimizing production yields thus may require screenings for optimal spacer sequence lengths. In case of secreted proteins, the 5′ sequence encoding the signal peptide for Sec-depended secretion should also be considered.
Constructing a novel expression system by specific activation of amylase expression pathway in Penicillium
Authors: Pi Changyu , Zhang Zhe , Xiang Boyu , Tian Hongwei , Liao Qinzhen , Chen Yu , Xia Liqiu , Hu Yibo , Hu Shengbiao 
Published: July 2020

Abstract
Background
Filamentous fungi have long been used as hosts for the production of proteins, enzymes and valuable products in various biotechnological applications. However, recombinant proteins are expressed with highly secreted host proteins when stronger promoters are used under inducing conditions. In addition, the efficiency of target protein expression can be limited by the application of constitutive promoters in recently developed filamentous fungal expression systems.

Results
In this study, a novel expression system was constructed by using a Penicillium oxalium strain that has powerful protein secretion capability. The secretory background of the host was reduced by knocking out the Amy13A protein and utilizing the starch as a carbon source. The strong promoter amy15A(p) was further improved by overexpressing the transcription activator AmyR and deleting of putative repressor CreA. By using the native amylase Amy15A as a reporter, the efficiency of expression from the amy15A promoter was dramatically and specifically enhanced after redesigning the regulatory network of amylase expression.

Conclusions
Our researches clearly indicated that the triple-gene recombinant strain Δ13A-OamyR-ΔCreA, with the amy15A(p) promoter could be used as a suitable expression system especially for high-level and high-purity protein production.
Circ_0000190 suppresses gastric cancer progression potentially via inhibiting miR-1252/PAK3 pathway
Authors: Wang Gui-Jun , Yu Tian-Yu , Li Yan-Rong , Liu Yang-Jun , Deng Bei-Bei 
Published: July 2020

Abstract
Background
Gastric cancer is a serious malignant tumor associated with aberrant circular RNAs (circRNAs) expression. In this study, we aim to investigate the role and the underlying mechanism of circ_0000190, a circRNA in gastric cancer.

Methods
Circ_0000190 expression in vivo was examined in gastric cancer and adjacent normal tissues by RT-PCR. Circ_0000190 expression in gastric cancer cell lines was detected by FISH and RT-PCR. The role of the circRNA in gastric cancer cells was assessed by the analysis of cell viability, apoptosis, proliferation, cell cycle and migration. The potential effector of circ_0000190 was predicted by computational screen and validated by luciferase reporter assay. Furthermore, Mice model of human gastric cancer was established to observe the underlying mechanisms of circ_0000190.

Results
Circ_0000190 was down-regulated in gastric cancer tissues and cells, with a major location in cytoplasm. Circ_0000190 inhibited gastric cancer cell viability, proliferation and migration, and induced apoptosis and cell cycle arrest by regulating the expression of capase-3, p27 and cyclin D. In addition, the circRNA was validated as a sponge of miR-1252, which directly targeted PAK3. The effects of circ_0000190 on the cellular processes were blocked by miR-1252 mimics, which could be rescued after further overexpression of PAK3.

Conclusions
Circ_0000190 suppresses gastric cancer progression potentially via inhibiting miR-1252/PAK3 pathway, employing circ_0000190 might be a promising therapeutic strategy for the treatment of gastric cancer.
Molecular mechanisms of long non-coding RNAs in anaplastic thyroid cancer: a systematic review
Authors: Samimi Hilda , Sajjadi-Jazi Sayed Mahmoud , Seifirad Soroush , Atlasi Rasha , Mahmoodzadeh Habibollah , Faghihi Mohammad Ali , Haghpanah Vahid 
Published: July 2020

Abstract
Background
anaplastic thyroid cancer (ATC) is one of the most lethal and aggressive cancers. Evidence has shown that the tumorigenesis of ATC is a multistep process involving the accumulation of genetic and epigenetic changes. Several studies have suggested that long non-coding RNAs (lncRNAs) may play an important role in the development and progression of ATC. In this article, we have collected the published reports about the role of lncRNAs in ATC.

Methods
“Scopus”, “Web of Science”, “PubMed”, “Embase”, etc. were systematically searched for articles published since 1990 to 2020 in English language, using the predefined keywords.

Results
961 papers were reviewed and finally 33 papers which fulfilled the inclusion and exclusion criteria were selected. Based on this systematic review, among a lot of evidences on examining the function of lncRNAs in thyroid cancer, there are only a small number of studies about the role of lncRNAs and their molecular mechanisms in the pathogenesis of ATC.

Conclusions
lncRNAs play a crucial role in regulation of different processes involved in the development and progression of ATC. Currently, just a few lncRNAs have been identified in ATC that may serve as prognosis markers such as GAS5, MIR22HG, and CASC2. Also, because of the dysregulation of Klhl14-AS, HOTAIRM1, and PCA3 during ATC development and progression, they may act as therapeutic targets. However, for most lncRNAs, only a single experiment has evaluated the expression profile in ATC tissues/cells. Therefore, further functional studies and expression profiling is needed to resolve this limitation and identify novel and valid biomarkers.
Enhanced expression of microtubule-associated protein 7 functioned as a contributor to cervical cancer cell migration and is predictive of adverse prognosis
Authors: Tang Ning , Lyu Dan , Chang Jian-Fang , Liu Zhi-Tao , Zhang Yan , Liu Hai-Ping 
Published: July 2020

Abstract
Background
Cervical cancer (CC) is one of the most common female malignancies over the world. Microtubule-associated protein 7 (MAP7) belongs to the family of microtubule-associated proteins (MAPs) which involve in microtubule dynamics and are critical in several important cellular and intracellular activities. This study aimed to investigate the expression and potential role of MAP7 in CC.

Methods
The expression level of MAP7 in CC tissues and normal tissues were analyzed using the data obtained from The cancer genomes atlas (TCGA) and genotype-tissue expression (GTEx) databases. The prognostic value of MAP7 in patients with CC was analyzed by Kaplan–Meier analysis, Univariate and Multivariate analyses. Moreover, the influences of MAP7 expression alteration on the viability and motility of Caski, HeLa and C-33A cells was measured by CCK8 assay, colony formation assay, scratch assay, and transwell migration and invasion assays. Flow cytometry was conducted to determine cell apoptosis. Western blot was performed to evaluate the impact of MAP7 on the expression of apoptotic-related proteins as well as mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. In vivo tumorigenicity assay was performed to explore the influence of MAP7 on tumor growth.

Results
Up-regulation of MAP7 was observed in CC tissues and high MAP7 expression was positively correlated with worse prognosis. Multivariate analyses suggested that MAP7 expression can be served as an independent predictor for overall survival of patients with CC. Knockdown of MAP7 markedly suppressed Caski and HeLa cell viability, migration and invasion while notably induced cell apoptosis. Furthermore, depletion of MAP7 in Caski and HeLa cells elevated the expression levels of Active-caspase 3 and Bax, but declined the level of Bcl-2. Whilst, overexpression of MAP7 in C-33A cells presented the opposite outcomes. Additionally, knockdown of MAP7 significantly decreased the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) in Caski and HeLa cells, and overexpression of MAP7 increased their phosphorylation in C-33A cells, indicating that MAP7 may regulate the MAPK signaling pathway in CC cells. In vivo assays revealed that knockdown of MAP7 remarkably repressed the growth of CC tumors.

Conclusion
The results of the present study suggest that MAP7 functions as a promoter during the occurrence and progression of CC, and that MAP7 may serve as a promising therapeutic target in CC.
Global mapping of interventions to improve the quality of life of patients with cardiovascular diseases during 1990–2018
Authors: Tran Bach Xuan , Nghiem Son , Afoakwah Clifford , Ha Giang Hai , Doan Linh Phuong , Nguyen Thao Phuong , Le Tuan Thanh , Latkin Carl A. , Ho Cyrus S. H. , Ho Roger C. M. 
Published: July 2020

Abstract
Background
Cardiovascular diseases (CVDs) have been the global health problems that cause a substantial burden for the patients and the society. Assessing the Quality of Life (QOL) of CVD patients is critical in the effectiveness evaluation of CVD treatments as well as in determining potential areas for enhancing health outcomes. Through the adoption of a combination of bibliometric approach and content analysis, publications trend and the common topics regarding interventions to improve QOL of CVD patients were searched and characterized to inform priority setting and policy development.

Methods
Bibliographic data of publications published from 1990 to 2018 on interventions to improve QOL of CVD patients were retrieved from Web of Science. Network graphs illustrating the terms co-occurrence clusters were created by VOSviewer software. Latent Dirichlet Allocation approach was adopted to classify papers into major research topics.

Results
A total of 6457 papers was analyzed. We found a substantial increase in the number of publications, citations, and the number of download times of papers in the last 5 years. There has been a rise in the number of papers related to intervention to increase quality of life among patients with CVD during 1990–2018. Conventional therapies (surgery and medication), and psychological, behavioral interventions were common research topics. Meanwhile, the number of papers evaluating economic effectiveness has not been as high as that of other topics.

Conclusions
The research areas among the scientific studies emphasized the importance of interdisciplinary and inter-sectoral approaches in both evaluation and intervention. Future research should be a focus on economic evaluation of intervention as well as interventions to reduce mental issues among people with CVD.
Psychometric characteristics of the Iranian Caregiver Burden Inventory (CBI) in caregivers of elderly patients with Alzheimer
Authors: Shafiezadeh Akram , Heravi-Karimooi Majideh , Mirzaee Amin , Rejeh Nahid , Sharif Nia Hamid , Montazeri Ali 
Published: July 2020

Abstract
Background
It is essential to better understand the caregiving burden and its determinants to support caregivers. The aim of this study was to test the validity and reliability (internal consistency) of the caregiver burden inventory (CBI) in Iranian caregivers of elderly patients with Alzheimer.

Methods
A cross sectional study was conducted to translate and validate the CBI in Iran. The structural validity of the scale was evaluated by exploratory factor analysis. The concurrent validity was tested correlating the CBI scores with the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI) scores. The internal consistency reliability was assessed using the Cronbach’s alpha coefficient.

Results
In total, we enrolled 315 caregivers of elderly patients with Alzheimer disease (79% women, mean age 56.5 ± 13.9). The structural validity of the CBI as assessed by exploratory factor analysis indicated three factors (emotional/psychological, time-dependence and physical burden) that jointly explained 45.21% of the total variance observed. The Pearson correlation coefficient for the relationship between the scores obtained on the Caregiver Burden Inventory and the BAI and the BDI were 0.69 and 0.49 respectively, confirming the concurrent validity. The Cronbach’s alpha for the CBI was 0.91 ranging from 0.78 to 0.92 for its subscales.

Conclusion
Used in clinical practice and research, the CBI was verified to be a proper multidimensional instrument for evaluating the burden in caregivers of elderly patients with Alzheimer disease.
The effect of growth hormone supplementation in poor ovarian responders undergoing IVF or ICSI: a meta-analysis of randomized controlled trials
Authors: Yang Peiwen , Wu Ruxing , Zhang Hanwang 
Published: July 2020

Abstract
Purpose
The aim of this meta-analysis was to evaluate the effect of growth hormone (GH) supplementation in poor responders undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).

Methods
PubMed, MEDLINE and Cochrane Library databases were searched for the identification of relevant randomized controlled trials. Outcome measures were live birth rate, clinical pregnancy rate, miscarriage rate, cycle cancelation rate, number of retrieved oocytes and total dose of gonadotropin.

Results
Fifteen randomized controlled trails (RCTs) involving 1448 patients were eligible for the analysis. GH supplementation improved live birth rate (RR, 1.74; 95% CI, 1.19–2.54), clinical pregnancy rate (RR, 1.65; 95% CI, 1.31–2.08) and retrieved oocytes number (SMD, 0.72; 95% CI, 0.28–1.16), while reducing cancelled cycles rate (RR, 0.62; 95% CI, 0.44–0.85) and dose of Gonadotropin (SMD,-1.05 95% CI, − 1.62 - -0.49) for poor ovarian response patients. Besides, there was no significant difference in the miscarriage rate between GH group and control group.

Conclusions
Based on the limited available evidence, growth hormone supplementation seems to improve IVF/ICSI outcomes for poor ovarian responders. Further randomized controlled trials with large sample sizes are required to clarify the effect of GH adjuvant therapy in the treatment of women with poor ovarian response.
A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease
Authors: Holden Sean , Maksoud Rebekah , Eaton-Fitch Natalie , Cabanas Hélène , Staines Donald , Marshall-Gradisnik Sonya 
Published: July 2020

Abstract
Background
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) present with a constellation of symptoms including debilitating fatigue that is unrelieved by rest. The pathomechanisms underlying this illness are not fully understood and the search for a biomarker continues, mitochondrial aberrations have been suggested as a possible candidate. The aim of this systematic review is to collate and appraise current literature on mitochondrial changes in ME/CFS/SEID patients compared to healthy controls.

Methods
Embase, PubMed, Scopus and Medline (EBSCO host) were systematically searched for articles assessing mitochondrial changes in ME/CFS/SEID patients compared to healthy controls published between January 1995 and February 2020. The list of articles was further refined using specific inclusion and exclusion criteria. Quality and bias were measured using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies.

Results
Nineteen studies were included in this review. The included studies investigated mitochondrial structural and functional differences in ME/CFS/SEID patients compared with healthy controls. Outcomes addressed by the papers include changes in mitochondrial structure, deoxyribonucleic acid/ribonucleic acid, respiratory function, metabolites, and coenzymes.

Conclusion
Based on the included articles in the review it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID.