bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Plasmodium vivax outbreak to elimination: lessons learnt from a retrospective analysis of data from Guantang
Authors: Yang Guo-Jing , Liu Ying , Shang Le-Yuan , Zhang Hong-Wei , Zhou Xiao-Nong , Penny Melissa A. , Smith Thomas A. 
Published: November 2020

Abstract
Background
Malaria was once a serious public health problem in China, with Plasmodium vivax the major species responsible for more than 90% of local transmission. Following significant integrated malaria control and elimination programmes, malaria burden declined, and since 2017 China has not recorded any indigenous case. To understand the historical malaria transmission patterns and epidemic characteristics in China and insights useful to guide P. vivax malaria control and elimination elsewhere, a retrospective study was carried out.

Methods
Historical data from a pilot study conducted in Guantang, Luyi in central China from 1971–1995, were digitized. The data included monthly numbers of reported cases, febrile cases, parasite carriage rates, the neonatal infection rate, and entomological data regarding Anopheles sinensis.

Results
Following 25 years of continuous integrated malaria control activities, malaria incidence in Guantang decreased from 4,333 cases per 10,000 in 1970 before integrated implementation to 0.23 cases per 10,000 in 1991, and no cases in 1992–1995. Some fluctuations in incidence were observed between 1977 and 1981. During the period parasite rates, antibody levels and the neonatal infection rate also decreased. The pattern of seasonality confirmed that P. vivax in Henan Province was primarily of the long incubation type (temperate) during non-transmission period. The findings retrospectively provide a scientific basis for the implementation of mass campaigns of liver stage hypnozoite clearance. Entomological studies indicated that An. sinensis was the only vector, and it preferred bovine to human hosts, predominantly biting and resting outdoors. Mosquito densities declined between 1971 and 1984.

Conclusion
The integrated malaria control approach in Guantang effectively controlled malaria and achieved elimination. Analysis of the effectiveness of the programme can provide guidance to other regions or countries with similar ecological settings aiming to move from malaria control to elimination. There is a potential challenge in the maintenance of non-transmission status owing to imported cases and the long dormancy of liver stage hypnozoites.
The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1α translation
Authors: Chen Liang-Yan , Wang Lian , Ren Yue-Xiang , Pang Zheng , Liu Yao , Sun Xiao-Dong , Tu Jian , Zhi Zheng , Qin Yan , Sun Li-Na , Li Jian-Ming 
Published: November 2020

Abstract
Background
Circular RNA (circRNAs) and hypoxia have been found to play the key roles in the pathogenesis and progression of cancer including colorectal cancer (CRC). However, the expressions and functions of the specific circRNAs in regulating hypoxia-involved CRC metastasis, and the circRNAs that are relevant to regulate HIF-1α levels in CRC remain elusive.

Methods
qRT-PCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circ-ERBIN. Function-based experiments were performed using circ-ERBIN overexpression and knockdown cell lines in vitro and in vivo, including CCK8, colony formation, EdU assay, transwell, tumor growth and metastasis models. Mechanistically, luciferase reporter assay, western blots and immunohistochemical stainings were performed.

Results
Circ-Erbin was highly expressed in the CRC cells and Circ-Erbin overexpression facilitated the proliferation, migration and metastasis of CRC in vitro and in vivo. Notably, circ-Erbin overexpression significantly promoted angiogenesis by increasing the expression of hypoxia induced factor (HIF-1α) in CRC. Mechanistically, circ-Erbin accelerated a cap-independent protein translation of HIF-1α in CRC cells as the sponges of miR-125a-5p and miR-138-5p, which synergistically targeted eukaryotic translation initiation factor 4E binding protein 1(4EBP-1).

Conclusions
Our findings uncover a key mechanism for circ-Erbin mediated HIF-1α activation by miR-125a-5p-5p/miR-138-5p/4EBP-1 axis and circ-ERBIN is a potential target for CRC treatment.
Nanoparticle-complexed antimiRs for inhibiting tumor growth and metastasis in prostate carcinoma and melanoma
Authors: Kunz Manfred , Brandl Madeleine , Bhattacharya Animesh , Nobereit-Siegel Lars , Ewe Alexander , Weirauch Ulrike , Hering Doreen , Reinert Anja , Kalwa Hermann , Guzman Juan , Weigelt Katrin , Wach Sven , Taubert Helge , Aigner Achim 
Published: November 2020

AbstractBackgroundMiRNAs act as negative regulators of gene expression through target mRNA degradation or inhibition of its translation. In cancer, several miRNAs are upregulated and play crucial roles in tumorigenesis, making the inhibition of these oncomiRs an interesting therapeutic approach. This can be achieved by directly complementary single-stranded anti-miRNA oligonucleotides (antimiRs). A major bottleneck in antimiR therapy, however, is their efficient delivery. The nanoparticle formation with polyethylenimine (PEI) may be particularly promising, based on the PEI’s ability to electrostatically interact with oligonucleotides. This leads to their protection and supports delivery. In the present study, we explore for the first time PEI for antimiR formulation and delivery. We use the branched low molecular weight PEI F25-LMW for the complexation of different antimiRs, and analyse tumor- and metastasis-inhibitory effects of PEI/antimiR complexes in different tumor models.ResultsIn prostate carcinoma, transfection of antimiRs against miR-375 and miR-141 leads to tumor cell inhibition in 2D- and 3D-models. More importantly, an in vivo tumor therapy study in prostate carcinoma xenografts reveals anti-tumor effects of the PEI/antimiR complexes. In advanced melanoma and metastasis, we identify by a microRNA screen miR-150 as a particularly relevant oncomiR candidate, and validate this result in vitro and in vivo. Again, the systemic application of PEI/antimiR complexes inhibiting this miRNA, or the previously described antimiR-638, leads to profound tumor growth inhibition. These effects are associated with the upregulation of direct miRNA target genes. In a melanoma metastasis mouse model, anti-metastatic effects of PEI/antimiR treatment are observed as well.ConclusionsWe thus describe PEI-based complexes as efficient platform for antimiR therapy, as determined in two different tumor entities using in vivo models of tumor growth or metastasis. Our study also highlights the therapeutic relevance of miR-375, miR-141, miR-150 and miR-638 as target miRNAs for antimiR-mediated inhibition.
Generation of a novel human dermal substitute functionalized with antibiotic-loaded nanostructured lipid carriers (NLCs) with antimicrobial properties for tissue engineering
Authors: Chato-Astrain Jesús , Chato-Astrain Isabel , Sánchez-Porras David , García-García Óscar-Darío , Bermejo-Casares Fabiola , Vairo Claudia , Villar-Vidal María , Gainza Garazi , Villullas Silvia , Oruezabal Roke-Iñaki , Ponce-Polo Ángela , Garzón Ingrid , Carriel Víctor , Campos Fernando , Alaminos Miguel 
Published: November 2020

AbstractBackgroundTreatment of patients affected by severe burns is challenging, especially due to the high risk ofPseudomonasinfection. In the present work, we have generated a novel model of bioartificial human dermis substitute by tissue engineering to treat infected wounds using fibrin-agarose biomaterials functionalized with nanostructured lipid carriers (NLCs) loaded with two anti-Pseudomonasantibiotics: sodium colistimethate (SCM) and amikacin (AMK).ResultsResults show that the novel tissue-like substitutes have strong antibacterial effect onPseudomonascultures, directly proportional to the NLC concentration. Free DNA quantification, WST-1 and Caspase 7 immunohistochemical assays in the functionalized dermis substitute demonstrated that neither cell viability nor cell proliferation were affected by functionalization in most study groups. Furthermore, immunohistochemistry for PCNA and KI67 and histochemistry for collagen and proteoglycans revealed that cells proliferated and were metabolically active in the functionalized tissue with no differences with controls. When functionalized tissues were biomechanically characterized, we found that NLCs were able to improve some of the major biomechanical properties of these artificial tissues, although this strongly depended on the type and concentration of NLCs.ConclusionsThese results suggest that functionalization of fibrin-agarose human dermal substitutes with antibiotic-loaded NLCs is able to improve the antibacterial and biomechanical properties of these substitutes with no detectable side effects. This opens the door to future clinical use of functionalized tissues.
How effective are electronic cigarettes for reducing respiratory and cardiovascular risk in smokers? A systematic review
Authors: Goniewicz Maciej L. , Miller Connor R. , Sutanto Edward , Li Dongmei 
Published: November 2020

Abstract
Background
Electronic cigarettes (e-cigarettes) are widely promoted as harm-reduction products for smokers, and smokers commonly perceive them as less harmful than combustible cigarettes. One of the key questions regarding public health consequences of e-cigarettes is the magnitude of harm reduction achievable by smokers who switch from combustible cigarettes to e-cigarettes. We conducted a systematic literature review of epidemiological studies that estimated odds of respiratory and cardiovascular outcomes among former smokers who use e-cigarettes compared to current smokers.

Methods
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We searched the PubMed and Embase databases in September 2020 to identify epidemiological studies that compared odds of cardiovascular and respiratory outcomes among former smokers who transitioned to e-cigarettes relative to odds among current smokers not using e-cigarettes (current exclusive smokers). We included studies that provided direct estimates of relevant odds ratios (ORs). We also included studies where indirect estimates of relevant ORs could be calculated based on published results. Two reviewers independently extracted data and conducted quality appraisals.

Results
Six population-based studies with sample sizes ranging from 19,475 to 161,529 respondents met review inclusion criteria, five of which were cross-sectional and one longitudinal. Three studies reported respiratory outcomes and three reported cardiovascular outcomes. ORs of respiratory outcomes (including chronic obstructive pulmonary disease, chronic bronchitis, emphysema, asthma, and wheezing) in former smokers who transitioned to e-cigarettes versus current exclusive smokers were below 1.0, ranging from 0.58 (95%CI 0.36–0.94) to 0.66 (95%CI 0.50–0.87; all p < 0.05). All ORs for cardiovascular outcomes (including stroke, myocardial infarction, and coronary heart disease) did not differ significantly from 1.0.

Conclusion
Though our review included a small number of studies, it provided consistent results. Former smokers who transitioned to e-cigarettes showed ~ 40% lower odds of respiratory outcomes compared to current exclusive smokers. Switching from smoking to e-cigarette does not appear to significantly lower odds of cardiovascular outcomes. Since the utility of cross-sectional studies for causal inference remains limited, both randomized controlled trials and prospective cohort studies are needed to better evaluate contributions of e-cigarettes as harm reduction tools for smokers.
Individual quality of life in spousal ALS patient-caregiver dyads
Authors: Galvin Miriam , Gavin Tommy , Mays Iain , Heverin Mark , Hardiman Orla 
Published: November 2020

Abstract
Background
Quality of life is a basic goal of health and social care. The majority of people with Amyotrophic Lateral Sclerosis (ALS) are cared for at home by family caregivers. It is important to recognize the factors that contribute to quality of life for individuals to better understand the lived experiences in a condition for which there is currently no curative treatment.

Aim
To explore individual quality of life of people with ALS and their informal caregivers over time.

Methods
Over three semi-structured home interviews, 28 patient-caregiver dyads provided information on a range of demographic and clinical features, psychological distress, caregiver burden, and individual quality of life. Quality of life data were analysed using quantitative and qualitative methods with integration at the analysis and interpretation phases.

Results
Individual Quality of Life was high for patients and caregivers across the interviews series, and higher among patients than their care partners at each time point. Family, hobbies and social activities were the main self-defined contributors to quality of life. The importance of health declined relative to other areas over time. Friends and finances became less important for patients, but were assigned greater importance by caregivers across the illness trajectory. Psychological distress was higher among caregivers. Caregiver burden consistently increased.

Conclusion
The findings from this study point to the importance of exploring and monitoring quality of life at an individual level. Self-defined contributory factors are relevant to the individual within his/her context. As an integrated outcome measure individual quality of life should be assessed and monitored as part of routine clinical care during the clinical encounter. This can facilitate conversations between health care providers, patients and families, and inform interventions and contribute to decision support mechanisms. The ascertainment of self-defined life quality, especially in progressive neurodegenerative conditions, mean health care professionals are in a better position to provide person-centred care.
Establishment of an immortalized stromal cell line derived from human Endometriotic lesion
Authors: Huang Zhi-Xiong , Wu Rong-Feng , Mao Xiao-Mei , Huang Shao-Min , Liu Tian-Tian , Chen Qiong-Hua , Chen Qing-Xi 
Published: November 2020

Abstract
Background
Endometriosis is a benign gynecological disease with obviously feature of estrogen-dependence and inflammatory response. The applications of primary endometriotic stromal cells in research of endometriosis are restricted for short life span, dedifferentiation of hormone and cytokine responsiveness. The objective of this study was to establish and characterize immortalized human endometriotic stromal cells (ihESCs).

Methods
The endometriotic samples were from a patient with ovarian endometriosis and the primary endometriotic stromal cells were isolated from the endometriotic tissues. The primary cells were infected by lentivirus to establish telomerase reverse transcriptase (hTERT)-induced immortalized cells. Quantification of mRNA and proteins was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot. CCK-8 assay and EdU labeling assay were assigned to assess the growth of ihESCs. Karyotype assay was performed to detect the chromosomes of ihESCs. Colony formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities.

Results
ihESCs continuously overexpressed hTERT via infection of lentivirus and significant extended the life span reaching 31 passages. The morphology, proliferation and karyotype of ihESCs remained unchanged. The expression of epithelial-mesenchymal transition (EMT) markers, estrogen-metabolizing proteins and estrogen/progesterone receptors (ERs and PRs) were unaltered. Furthermore, the treatment of estrogen increased the proliferation and EMT of ihESCs. Lipopolysaccharides (LPS) and IL-1β remarkably induced inflammatory response. The clonogenesis ability of ihESCs was consistent with primary cells, which were much lower than Ishikawa cells. In addition, nude mouse tumorigenicity assay demonstrated that ihESCs were unable to trigger tumor formation.

Conclusion
This study established and characterized an immortalized endometriotic stromal cell line that exhibited longer life span and kept the cellular morphology and physiological function as the primary cells. The immortalized cells remained normal feedback to estrogen and inflammatory response. Moreover, the immortalized cells were not available with tumorigenic ability. Therefore, ihESCs would be serviceable as in vitro cell tool to investigate the pathogenesis of endometriosis.
Incidence of thromboembolism in patients with COVID-19: a systematic review and meta-analysis
Authors: Boonyawat Kochawan , Chantrathammachart Pichika , Numthavaj Pawin , Nanthatanti Nithita , Phusanti Sithakom , Phuphuakrat Angsana , Niparuck Pimjai , Angchaisuksiri Pantep 
Published: November 2020

Abstract
Background
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the incidence of thromboembolism has been increasingly reported. The aim of this systematic review was to explore the incidence of venous and arterial thromboembolism among COVID-19 patients requiring hospitalization.

Methods
Medline, Embase, Scopus, and grey literature were searched until June 2020. Observational studies reported on the incidence of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) or arterial thromboembolism (ATE) were included. The pool incidences and their 95% confidence intervals (CI) were calculated using the random-effects model.

Results
A total of 36 studies were included. In the intensive care unit (ICU) setting, the pooled incidence of VTE was 28% (95% CI, 22–34%). Subgroups based on compression ultrasound (CUS) screening revealed a higher incidence of DVT in the CUS screening group than in the no CUS screening group (32% [95% CI, 18–45%] vs. 6% [95% CI, 4–9%]). The pooled incidence of ATE in ICU was 3% (95% CI, 2–5%). In the non-ICU setting, the pooled incidence of VTE was 10% (95% CI, 6–14%,).

Conclusions
The incidence of VTE in COVID-19 patients was higher in the ICU setting than in the non-ICU setting, and also significantly higher in studies that incorporated the CUS screening protocol. The incidence of ATE in the ICU setting was low. VTE prophylactic measures should be given to all hospitalized patients diagnosed with COVID-19.
Synergistic effects of EMPs and PMPs on pulmonary vascular leakage and lung injury after ischemia/reperfusion
Authors: Zhang Jie , Zhu Yu , Wu Yue , Yan Qing-Guang , Peng Xiao-Yong , Xiang Xin-Ming , Xue Ming-Ying , Li Qing-Hui , Liu Liang-Ming , Li Tao 
Published: November 2020

Abstract
Background
Vascular leakage is an important pathophysiological process of critical conditions such as shock and ischemia–reperfusion (I/R)-induced lung injury. Microparticles (MPs), including endothelial cell-derived microparticles (EMPs), platelet-derived microparticles (PMPs) and leukocyte-derived microparticles (LMPs), have been shown to participate in many diseases. Whether and which of these MPs take part in pulmonary vascular leakage and lung injury after I/R and whether these MPs have synergistic effect and the underlying mechanism are not known.

Methods
Using hemorrhage/transfusion (Hemo/Trans) and aorta abdominalis occlusion-induced I/R rat models, the role of EMPs, PMPs and LMPs and the mechanisms in pulmonary vascular leakage and lung injury were observed.

Results
The concentrations of EMPs, PMPs and LMPs were significantly increased after I/R. Intravenous administration of EMPs and PMPs but not LMPs induced pulmonary vascular leakage and lung injury. Furthermore, EMPs induced pulmonary sequestration of platelets and promoted more PMPs production, and played a synergistic effect on pulmonary vascular leakage. MiR-1, miR-155 and miR-542 in EMPs, and miR-126 and miR-29 in PMPs, were significantly increased after hypoxia/reoxygenation (H/R). Of which, inhibition of miR-155 in EMPs and miR-126 in PMPs alleviated the detrimental effects of EMPs and PMPs on vascular barrier function and lung injury. Overexpression of miR-155 in EMPs down-regulated the expression of tight junction related proteins such as ZO-1 and claudin-5, while overexpression of miR-126 up-regulated the expression of caveolin-1 (Cav-1), the trans-cellular transportation related protein such as caveolin-1 (Cav-1). Inhibiting EMPs and PMPs production with blebbistatin (BLE) and amitriptyline (AMI) alleviated I/R induced pulmonary vascular leakage and lung injury.

Conclusions
EMPs and PMPs contribute to the pulmonary vascular leakage and lung injury after I/R. EMPs mediate pulmonary sequestration of platelets, producing more PMPs to play synergistic effect. Mechanically, EMPs carrying miR-155 that down-regulates ZO-1 and claudin-5 and PMPs carrying miR-126 that up-regulates Cav-1, synergistically mediate pulmonary vascular leakage and lung injury after I/R.

Graphic abstract
The COX-2-derived PGE2 autocrine contributes to bradykinin-induced matrix metalloproteinase-9 expression and astrocytic migration via STAT3 signaling
Authors: Lee Tsong-Hai , Liu Pei-Shan , Tsai Ming-Ming , Chen Jiun-Liang , Wang Su-Jane , Hsieh Hsi-Lung 
Published: November 2020

Abstract
Background
The matrix metalloproteinase-9 (MMP-9) is up-regulated by several proinflammatory mediators in the central nervous system (CNS) diseases. Increasing reports show that MMP-9 expression is an inflammatory biomarker of several CNS disorders, including the CNS inflammation and neurodegeneration. Bradykinin (BK) is a common proinflammatory mediator and elevated in several brain injury and inflammatory disorders. The raised BK may be detrimental effects on the CNS that may aggravate brain inflammation through MMP-9 up-regulation or cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production in brain astrocytes. However, the relationship between BK-induced MMP-9 expression and COX-2-derived PGE2 release in brain astrocytes remains unclear.

Methods
Herein we used rat brain astrocytes (RBA) to investigate the role of the COX-2/PGE2 system in BK-induced MMP-9 expression. We used zymographic, RT-PCR, EIA, and Western blotting analyses to confirm that BK induces MMP-9 expression via a COX-2/PGE2-dependent pathway.

Results
Our results show activation of native COX-2 by BK led to PGE2 production and release. Subsequently, PGE2 induced MMP-9 expression via PGE2 receptor (EP)-mediated c-Src, Jak2, ERK1/2, and then activated signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, up-regulation of MMP-9 by BK via the pathway may promote astrocytic migration.

Conclusion
These results demonstrated that a novel autocrine pathway for BK-induced MMP-9 protein expression is mediated through activation of STAT3 by native COX-2/PGE2-mediated c-Src/Jak2/ERK cascades in brain astrocytes.