bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of key pathways and hub genes in the myogenic differentiation of pluripotent stem cell: A bioinformatics and experimental study
Authors: Fei Wenyong , Liu Mingsheng , Zhang Yao , Cao Shichao , Wang Xuanqi , Xie Bin , Wang Jingcheng 
Published: September 2020

Abstract
Background: The regeneration of muscle cells from stem cells is an intricate process and various genes are included in the process as myoD, mf5, mf6 etc. The key genes and pathways in the differentiating stages is various. Therefore, the differential expression of key genes after 4weeks of differentiation were investigated in our study.

Method: Three published gene expression profiles, GSE131125, GSE148994, GSE149055, about the comparisons of pluripotent stem cells to differentiated cells after 4 weeks were obtained from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (DEGs) were obtained for further analysis as proteinprotein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA analysis. After hub genes and key pathways were obtained, we manipulated in vitro cell research for substantiation as immunohistochemical staining and semi-quantitative analysis and quantitative real-time PCR.

Results: A total of 824 DEGs including 350 up-regulated genes and 474 down-regulated genes were identified in the three GSEs. 19 hub genes were identified from the PPI network. The GO and KEGG pathway analysis confirmed that myogenic differentiation at 4 weeks was strongly associated with pathway in cancer, PI3K pathway, actin cytoskeleton regulation and metabolic pathway, biosynthesis of antibodies and cell cycle. GSEA analysis indicated the differentiated cells were enriched in muscle cell development and myogenesis. Meanwhile, the core genes in each pathway were identified from the GSEA analysis. The in vitro cell research revealed that actin cytoskeleton and myoD were up-regulated after 4 weeks differentiation.

Conclusions: The research revealed the potential hub genes and key pathways after 4 weeks differentiation of stem cells which contribute to further study about the molecular mechanism of myogenesis regeneration. Paving a way for more accurate treatment for muscle dysfunction.
Choroidal Alterations of Sturge-Weber Syndrome Secondary Glaucoma and Non-glaucoma Port-wine Stain Patients Distinguished by Enhanced Depth Imaging Optical Coherence Tomography
Authors: Wu Yue , Huang Lulu , Liu Yixin , Xu Li , Guo Wenyi 
Published: September 2020

Abstract
Background: To evaluate the choroidal changes in Sturge-Weber syndrome (SWS) secondary glaucoma and non-glaucoma port-wine stain (PWS) patients by enhanced depth imaging optical coherence tomography (EDI-OCT).Methods: SWS and PWS patients who were over 3 years old and treated or screened at our ophthalmology department were included in the study. Baseline demographics, EDI-OCT and fundus photography data were collected from all patients.Results: Forty-six non-glaucoma PWS (NGPWS) patients and 35 SWS secondary glaucoma（SG）patients were included, with mean ages of 16.52±13.63 and 13.94±8.27 years, respectively (p>0.05). Among these patients, 2 exhibit bilateral PWS and unilateral glaucoma. Thus the two eyes of each person were divided into NGPWS group and SG group respectively. Twenty-one eyes had choroidal hemangiomas and 7 eyes had excessive thickening of the choroid without choroidal hemangiomas. Choroidal hemangiomas were only observed in ipsilateral eyes of SG patients. The choroidal thicknesses of the ipsilateral and contralateral eyes of NGPWS patients were 358.10±117.40 μm (45 eyes) and 288.20±79.04 μm (41 eyes), respectively (p<0.05). The choroidal thicknesses of the ipsilateral and contralateral eyes of SG patients were 511.40±242.10 μm (15 eyes) and 283.90±92.27 μm (29 eyes), respectively (p<0.05). Significant differences were found between the ipsilateral eyes of SWS and PWS patients (p<0.05). Six of 13 eyes (46%) with choroidal hemangiomas exhibited post-operative posterior segment complications. Conclusions: Non-glaucoma PWS and SWS secondary glaucoma patients had a thicker choroid in the ipsilateral eye. The trend was even more pronounced in SWS secondary glaucoma patients. Choroidal hemangiomas were only found in the ipsilateral eyes of SG. In addition, choroidal hemangioma was a risk factor for post-operative posterior segment complications in SWS patients.
Primary total hip arthroplasty using a short bone-conserving stem in young adult osteoporotic patients with Dorr type C femoral bone
Authors: Zhen Ping , Chang Yanfeng , Yue Heng , Chen Hui , Zhou Shenghu , Liu Jun , He Xiaole 
Published: September 2020

Abstract
BackgroundDorr Type C femoral bone exhibits a wide, stovepipe-shaped femoral canal and thin cortices in the proximal femur. Dorr C bone combined with severe osteoporosis is an important challenge in primary hip arthroplasty. In this study, we assessed the effects of short metaphyseal fitting cementless stems on preformatted primary total hip arthroplasties in young adult osteoporotic patients with this femoral presentation.MethodsA total of 42 hip arthroplasties were performed in 35 young patients (range 20 to 36 years) using a short Tri-lock bone preservation metaphyseal-fitting cementless femoral component between 2012 and 2017. The mean age at surgery of the 27 male (33 hips) and 8 female (9 hips) patients was 27.5 years (range 20.3 to 35.8 years). The mean body mass index (BMI) was 20.2 kg/m 2 (range, 16.8-23.2 kg/m 2 ). According to Dorr’s criteria, all 42 femora were classified as type C bone and all femurs suffered from severe osteoporosis (Singh index≤3).ResultsThe mean follow-up period was 5.5 years (range 3.0 to 8.0 years). The clinical and functional results improved for the Harris hip score, WOMAC, and UCLA activity scores. The Harris Hip score improved from 48.0 ± 8.0 (range 38.0 to 61.0) preoperatively to 87.0 ± 9.0 (range 77.0 to 92.0) at 12 months after surgery and 91.0 ± 8.0 (range 85.0 to 98.0) at final follow-up. The preoperative UCLA activity score was 3.0 ± 0.5 points (range, 1.0-4.0 points), which significantly improved to 7.5 ± 0.7 points (range 6.0 to 8.0 points) at the final follow-up. No patient exhibited thigh pain at the final follow-up. The mean stem-to-canal fill percentages were 97% ± 2.1% (anteroposterior view at midstem). For stem alignment, 40 hips (95.2%) of the femoral stem were positioned neutrally to 3° of varus with reference to the femoral shaft axis. The remaining two were positioned at 4° varus to 4° valgus. Radiographic evaluation showed good osteointegration of the implants in follow-up.ConclusionsBased on the tapered-wedge design and proximal porous coating, the shortened tapered conventional stem can achieve reliable stability through neck filling and metaphyseal fixation, which does not depend on the isthmus hoop stress. This stem was suitable in severe osteoporotic patients with Type C bones in young adults who presented with a correspondingly straightened femoral canal with a wide isthmus and thin cortex.
Voluntary Exercise in Mesothelioma: Effects on Tumour Growth and Treatment Response in a Murine Model
Authors: FISHER Scott A , Peddle-McIntyre Carolyn J , Burton Kimberley , Newton Robert U , Marcq Elly , Lake Richard A , Nowak Anna K 
Published: September 2020

Abstract
Objective: There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogen‑induced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease development. However, there are limited studies investigating the ability of exercise to prevent or delay cancer, and exercise as a preventive strategy has never been assessed in models with a known carcinogen. We investigated the potential of voluntary exercise (VE) to delay development of asbestos related disease (ARD) in our well-characterised, asbestos induced MexTAg model of mesothelioma.Results: Asbestos exposed MexTAg mice were given continuous or delayed access to VE and ARD assessed over time. We found that the addition of VE did not affect ARD development in asbestos exposed MexTAg mice. However, non‑asbestos exposed, aged matched control mice participated in significantly more VE behaviours, suggesting subclinical development of ARD after asbestos exposure had a greater impact on VE participation than age alone. These data highlight the importance of model choice and the potential limitation that some pre‑clinical studies may not accurately represent the clinical paradigm, particularly in the context of prevention studies.
Apparent density, trypanosome infection rates and host preference of tsetse flies in the sleeping sickness endemic focus of Northwestern Uganda
Authors: Opiro Robert , Opoke Robert , Angwech Harriet , Nakafu Esther , Oloya Francis A. , Openy Geoffrey , Njahira Moses , Macharia Mercy , Echodu Richard , Malinga Geoffrey M. , Opiyo Elizabeth A. 
Published: September 2020

Abstract
Background: African trypanosomiasis, caused by protozoa of the genus Trypanosoma and transmitted by the tsetse fly, is a serious parasitic disease of humans and animals. Reliable data on the vector distribution, feeding preference and the trypanosome species they carry is pertinent to planning sustainable control strategies.Methodology: We deployed 109 biconical traps in 10 villages in two districts of northwestern Uganda to obtain information on the apparent density, infection rates and blood meal sources of tsetse flies. A subset (272) of the collected samples was analyzed for detection of trypanosomes species and sub-species using a nested PCR protocol based on primers amplifying the Internal Transcribed Spacer (ITS) region of ribosomal DNA. 34 blood-engorged adult tsetse midguts were analyzed for blood meal sources by sequencing of the mitochondrial cytochrome c oxidase 1 (COI) and cytochrome b (cytb) genes. Results: Out of the 109 traps deployed, we captured 622 Glossina fuscipes fuscipes tsetse flies (269 males and 353 females). Apparent density (AD) ranged from 0.6 to 3.7 flies/trap/day in the two districts. 29 (10.7%) of the flies were infected with one or more trypanosome species. Infection rate was not significantly associated with neither age group (χ2 = 5.001, df=2, 0.082), sex of the fly (χ2 = 0.099, df = 1, p = 0.753), district of origin (χ2= 0.629, df = 1, p = 0.428) nor village (χ2= 9.252, df = 9, p = 0.414). Nested PCR revealed several species of trypanosomes: T. vivax (6.62%), T. congolense (2.57%), and T. brucei and T. simiae each at 0.73%. Blood meal analyses revealed five principal vertebrate hosts, namely, cattle (Bos taurus), humans (Homo sapiens), Nile monitor lizard (Varanus niloticus), African mud turtle (Pelusio schapini) and the African Savanna elephant (Loxodonta africana).Conclusion: We found a moderately high infection rate of 10.78%, with all infections attributed to trypanosome species that are causative agents for the animal disease only. However, more validation using large-scale passive and active screening of human and tsetse samples should be done. Cattle and humans appear to be the most important tsetse hosts in the region and should be considered in the design of interventions.
Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2
Authors: Dong Jianbo , Huang Betty , Wang Bo , Titong Allison , Kankanamalage Sachith Gallolu , Jia Zhejun , Wright Meredith , Parthasarathy Pannaga , Liu Yue 
Published: September 2020

Abstract
SARS-CoV-2 is a newly emergent coronavirus that causes COVID-19, which has adversely impacted human health and has led to a pandemic. There is an unmet need to develop therapies against SARS-CoV-2 due to its severity and lack of treatment options. A promising approach to combat COVID-19 is through the neutralization of SARS-CoV-2 by therapeutic antibodies. Previously, we described a strategy to rapidly identify and generate llama nanobodies (VHH) from naïve and synthetic humanized VHH phage libraries that specifically bind the S1 SARS-CoV-2 spike protein, and block the interaction to the ACE2 human receptor. In this study, we then used computer-aided designed and constructed multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs show favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19.
Uncomplicated falciparum malaria among schoolchildren in Bajil district of Hodeidah governorate, west of Yemen: Association with anaemia and underweight
Authors: Alwajeeh Talal S , Abdul-Ghani Rashad , Allam Amal F. , Farag Hoda F. , Khalil Safia S.M. , Shehab Amel Y. , El-Sayad Mona H. , Alharbi R.A. , Al Shaia S.R. , Azazy Ahmed A. 
Published: September 2020

Abstract
Background Malaria, malnutrition and anaemia are major public health problems in Yemen, with Hodeidah being the most malaria-afflicted governorate. To address the lack of relevant studies, this study was conducted to determine the prevalence of Plasmodium falciparum and its relation to nutritional status and haematological indices among schoolchildren in Bajil district of Hodeidah governorate, west of Yemen. Methods This cross-sectional study was conducted among 400 schoolchildren selected randomly from four schools in Bajil district. Data about demographic characteristics, risk factors and anthropometric measurements of age, height and weight were collected. Duplicate thick and thin blood films were prepared, stained with Giemsa and examined microscopically for malaria parasites. The density of P. falciparum asexual stages was estimated on thick films. EDTA-blood samples were examined for the haematological indices of haemoglobin (Hb) and blood cell counts. Results P. falciparum was prevalent among 8.0% (32/400) of schoolchildren with a mean parasite density of 244.3 299.3/µl of blood and most infections showing low-level parasitaemia, whereas Plasmodium vivax was detected in one child (0.25%). Residing near water collections was a significant independent predictor of falciparum malaria [adjusted odds ratio (AOR) = 2.6, 95.0% CI: 1.20–5.72; p = 0.016] in schoolchildren. Mild anaemia was prevalent among more than half of P. falciparum-infected schoolchildren and significantly associated with falciparum malaria (AOR = 5.8, 95.0% CI: 2.39–14.17; p <0.001), with a mean Hb concentration of 10.7 1.0 g/dL. Although the mean values of the total white blood cells, monocytes and platelets were significantly lower in infected than non-infected schoolchildren, they were within normal ranges. More than half of the children were malnourished, with stunting (39.3%) and underweight (36.0%) being the most prevalent forms of malnutrition; 6.3% of children were wasted. Underweight (AOR = 5.3, 95.0% CI: 2.09–13.62; p <0.001) but not stunting or wasting, was a significant predictor of falciparum malaria among schoolchildren. Conclusion Asymptomatic falciparum malaria is prevalent among schoolchildren in Bajil district of Hodeidah Governorate, with predominance of low parasitaemic infections and significant association with mild anaemia and underweight. Residence near water collection is a significant predictor of infection with falciparum malaria among schoolchildren. Further studies among children with severe malaria and those with high parasite densities are recommended.
Diagnostic value of 18F-FDG PET/MRI for staging in patients with ovarian cancer
Authors: Tsuyoshi Hideaki , Tsujikawa Tetsuya , Yamada Shizuka , Okazawa Hidehiko , Yoshida Yoshio 
Published: September 2020

Abstract
Purpose: To evaluate the diagnostic potential of PET/MRI with 18F-fluorodeoxyglucose (18F-FDG) in ovarian cancer.Materials and Methods: Participants comprised 103 patients with suspected ovarian cancer underwent pretreatment 18F-FDG PET/MRI, contrast-enhanced CT (ceCT) and pelvic dynamic contrast-enhanced MRI (ceMRI). Diagnostic performance of 18F-FDG PET/MRI and ceMRI for assessing the characterization and the extent of the primary tumor (T stage) and 18F-FDG PET/MRI and ceCT for assessing nodal (N stage) and distant (M stage) metastases was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. The McNemar test was employed for statistical analysis.Results: Accuracy for the characterization of suspected ovarian cancer was significantly better for 18F-FDG PET/MRI (92.5%) [95% confidence interval (CI) 0.841–0.950] than for ceMRI (80.6%) (95%CI 0.715–0.830) (p <0.05). Accuracy for T status was 96.4% (95%CI 0.964–0.964) and 92.9% (95%CI 0.929–0.929) for 18F-FDG PET/MRI and ceMRI/ceCT, respectively. Patient-based accuracies for N and M status were 100% (95%CI 0.883–1.000) and 100% (95%CI 0.884–1.000) for 18F-FDG PET/MRI and 85.2% (95%CI 0.758–0.852) and 30.8% (95%CI 0.188–0.308) for ceCT and M staging representing significant differences (p<0.01). Lesion-based sensitivity, specificity and accuracy for N status were 78.6% (95%CI 0.571–0.913), 95.7% (95%CI 0.932–0.972) and 93.9% (95%CI 0.893–0.966) for 18F-FDG PET/MRI and 42.9% (95%CI 0.240–0.581), 96.6% (95%CI 0.943–0.984) and 90.8% (95%CI 0.868–0.941) for ceCT. Conclusions: Use of 18F-FDG PET/MRI offers better sensitivity and specificity for the characterization and M staging than ceMRI and ceCT, and diagnostic value for T and N staging equivalent to ceMRI and ceCT, suggesting that 18F-FDG PET/MRI might represent a useful diagnostic alternative to conventional imaging modalities in ovarian cancer.
Mediastinal lymph node enlargement in idiopathic pulmonary fibrosis: relationships with disease progression and pulmonary function trends.
Authors: Sgalla Giacomo , Larici Anna Rita , Golfi Nicoletta , Calvello Mariarosaria , Farchione Alessandra , Ciello Annemilia Del , Varone Francesco , Iovene Bruno , Manfredi Riccardo , Richeldi Luca 
Published: September 2020

Abstract
Background and objectivesEvidence of mediastinal Lymph Node Enlargement (LNE) on CT scan is a common finding in idiopathic pulmonary fibrosis (IPF). We sought to investigate whether the involvement of mediastinal lymph nodes is associated with accelerated disease progression, and explored the changes occurring in mediastinal lymph nodes during the radiological follow up of these patients.MethodsThis retrospective study included IPF patients referred to a single ILD centre in Italy. A consensus-based assessment of mediastinal LNE on chest CT scan was performed by two thoracic radiologists. Kaplan-Meier curves and multivariate Cox proportional hazards regression were used to assess hazard ratios for mortality and disease progression (defined as categorical FVC decline ≥10%). The annualized rates of change in functional parameters for each patient were calculated using mixed linear models.Results152 IPF patients were included in the analysis, of whom 135 (89%) received antifibrotic treatment for IPF during the study follow up. Patients having evidence of 3 or more enlarged mediastinal lymph nodes on baseline CT scan showed increased rates of mortality (HR 5.03, 95% CI 1.86-13.62, p≤0.001) and significant disease progression (HR 2.99, 95% CI 1.22-7.33, p=0.17) as compared to patients without LNE, after adjusting for GAP stage. Among 62 patients with LNE who underwent a follow up CT scan of the chest and received antifibrotic treatment, 57 (92%) maintained evidence mediastinal LNE over time.ConclusionsDiffuse mediastinal lymph node involvement predicts clinically meaningful functional deterioration in patients with IPF.
Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome
Authors: Pandolfi Laura , Tommaso Fossali , Vanessa Frangipane , Sara Bozzini , Monica Morosini , Maura D’Amato , Sara Lettieri , Mario Urtis , Alessandro Di Toro , Laura Saracino , Elena Percivalle , Stefano Tomaselli , Lorenzo Cavagna , Emanuela Cova , Francesco Mojoli , Paola Bergomi , Davide Ottolina , Daniele Lilleri , Guido Corsico Angelo , Eloisa Arbustini , Riccardo Colombo , Federica Meloni 
Published: September 2020

Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19. Methods: Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n=28) and to the Intermediate Medicine Ward (IMW) (n=5). We analyze the differential cell count, ultrastructure of cells and Interleukin(IL)6, 8 and 10 levels.Results: ICU patients showed a marked increase in neutrophils (1.24 x 105 ml-1 , 0.85-2.07), lower lymphocyte (0.97 x 105 ml-1, 0.024-0.34) and macrophages fractions (0.43 x 105 ml-1, 0.34-1.62) compared to IMW patients (0.095 x 105 ml-1, 0.05-0.73; 0.47 x 105 ml-1, 0.28-1.01 and 2.14 x 105 ml-1, 1.17-3.01, respectively) (p<0.01). Ultrastructural study of ICU patients BAL showed viral-like particles in cytopathic mononuclear cells and an extensive cytopathic damage in all cell lineages. Immunostaining with anti-viral capsid and spike antibodies specifically immunoreacted with BAL cells, mostly cytopathic ones. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p<0.01, IL8 p<0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p<0.1) or antivirals (p<0.05). Conclusions: Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.
The identification of a cannabinoid-like compound (adrenoyl-EA), in the flowers of a South African medicinal plant (Leonotis leonurus)
Authors: Hunter Ethan , Stander Marietjie , Kossmann Jens , Chakraborty Suparna , Prince Sharon , Peters Shaun , Loedolff Bianke 
Published: September 2020

Abstract
Objective Current global trends on natural therapeutics suggest an increasing market interest toward the use and discovery of new plant-derived therapeutic compounds, often referred to as traditional medicine (TM). The Cannabis industry is currently one such focal area receiving attention, owing to the occurrence of phytocannabinoids (pCBs) which have shown promise in health-promotion and disease prevention. However, the occurrence of pCBs in other plant species are often overlooked and rarely studied. Leonotis leonurus (L.) R. Br. is endemic to South Africa with a rich history of use in TM practices amongst indigenous people and, has been recorded to induce mild psychoactive effects akin to Cannabis. While the leaves have been well-reported to contain therapeutic phytochemicals, little information exists on the flowers. Consequently, as part of a larger research venture, we targeted the flowers of L. leonurus for the identification of potential pCB or pCB-like compounds.Results Flower extracts were separated and analyzed using high performance thin layer chromatography (HPTLC). A single pCB candidate was isolated from HPTLC plates and, using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), identified as 7,10,13,16-Docosatetraenoylethanolamine (adrenoyl-EA). Adrenoyl-EA is a known bioactive pCB-like compound reported to occur in only one other plant species, Tropaeolum tuberosum.