bluuebunny/crossref_metadata_2025_split huggingface dataset:
Narrow H3K4me2 is required for chicken PGC formation
Authors: Zhang Chen , Zuo Qisheng , Wang Man , Chen Hao , He Nana , Jin Jing , Li Tingting , Jiang Jingyi , Yuan Xia , Li Jiancheng , Shi Xiang , Zhang Ming , Bai Hao , Zhang Yang , Xu Qi , Cui Hengmi , Chang Guobin , Song Jiuzhou , Sun Hongyan , Zhang Yani , Chen Guohong , Li Bichun 
Published: August 2020

AbstractThe development of primordial germ cells (PGCs) undergoes epigenetic modifications. The study of histone methylation in regulating PGCs is beneficial to understand the development and differentiation mechanism of germ stem cells. Notably, it provides a theoretical basis for directed induction and mass acquisition in vitro. However, little is known about the regulation of PGC formation by histone methylation. Here, we found the high enrichment of H3K4me2 in the blastoderm, genital ridges, and testis. Chromatin immunoprecipitation sequencing was performed and the results revealed that genomic H3K4me2 is dynamic in embryonic stem cells, PGCs, and spermatogonial stem cells. This trend was consistent with the H3K4me2 enrichment in the gene promoter region. Additionally, narrow region triggered PGC‐related genes (Bmp4, Wnt5a, and Tcf7l2) and signaling pathways (Wnt and transforming growth factor‐β). After knocking down histone methylase Mll2 in vitro and vivo, the level of H3K4me2 decreased, inhibiting Cvh and Blimp1 expression, then repressing the formation of PGCs. Taken together, our study revealed the whole genome map of H3K4me2 in the formation of PGCs, contributing to improve the epigenetic study in PGC formation and providing materials for bird gene editing and rescue of endangered birds.
Towards analyzing the potential of exosomes to deliver microRNA therapeutics
Authors: Giassafaki Lefki‐Pavlina N. , Siqueira Scheyla , Panteris Emmanuel , Psatha Konstantina , Chatzopoulou Fani , Aivaliotis Michalis , Tzimagiorgis Georgios , Müllertz Anette , Fatouros Dimitrios G. , Vizirianakis Ioannis S. 
Published: August 2020

AbstractExosome selectivity mechanisms underlying exosome–target cell interactions and the specific traits affecting their capability to communicate still remain unclear. Moreover, the capacity of exosomes to efficiently deliver their molecular cargos intracellularly needs precise investigation towards establishing functional exosome‐based delivery platforms exploitable in the clinical practice. The current study focuses on: (a) exosome production from normal MRC‐5 and Vero cells growing in culture, (b) physicochemical characterization by dynamic light scattering (DLS) and cryo‐transmission electron microscopy; (c) cellular uptake studies of rhodamine‐labeled exosomes in normal and cancer cells, providing to exosomes either “autologous” or “heterologous” cellular delivery environments; and (d) loading exogenous Alexa Fluor 488‐labeled siRNA into exosomes for the assessment of their delivering capacity by immunofluorescence in a panel of recipient cells. The data obtained thus far indicate that MRC‐5 and Vero exosomes, indeed exhibit an interesting delivering profile, as promising “bio‐shuttles,” being pharmacologically exploitable in the context of theranostic applications.
YEATS2 is a target of HIF1α and promotes pancreatic cancer cell proliferation and migration
Authors: Zeng Zhirui , Lei Shan , He Zhiwei , Chen Tengxiang , Jiang Jianxin 
Published: August 2020

AbstractHypoxia is involved in the development of pancreatic cancer (PC). The responses of hypoxia‐associated genes and their regulated mechanisms are largely unknown. In this study, through bioinformatic analysis and quantitative real‐time polymerase chain reaction, the YEATS domain containing 2 (YEATS2) was determined to be a key hypoxia‐associated gene. It was increased in PC cells under hypoxia, upregulated in PC tissues, and predicted poor outcome. YEATS2 inhibition decreased the proliferation and migration of PC cells under both normoxia and hypoxia in vitro as well as proliferation and metastasis in vivo. We found that hypoxia‐inducible factor 1α (HIF1α) regulated the expression of YEATS2 via binding to the hypoxia response element (HRE) of YEATS2 and coexpressed with YEATS2 in PC tissues. Overexpression of YEATS2 blocked the inhibitory effects of HIF1α silence on PC cell proliferation and migration under hypoxia. Collectively, our study revealed that YEATS2 is a target gene of HIF1α and promotes PC development under hypoxia.
Frail older adults show a distinct plasma microvesicle profile suggesting a prothrombotic and proinflammatory phenotype
Authors: Arauna Diego , Chiva‐Blanch Gemma , Padró Teresa , Fuentes Eduardo , Palomo Iván , Badimon Lina 
Published: August 2020

AbstractIn a global context of advanced aging, geriatric diseases such as frailty syndrome face challenges in the search for biomarkers and preventive strategies. Frailty has been associated with atherothrombotic pathologies. Circulating microvesicles (cMVs), phospholipid‐rich vesicles with a size of 0.1–1.0 μm, have been shown to participate in atherothrombosis onset and progression. We have hypothesized that cMVs from platelets, and vascular and immune cells, are increased in frail older adults. To verify this, a prevalent‐case control study was designed with 28 frail older and 27 nonfrail older adults older than 64 years. Frailty was defined by Fried's phenotype. Total cMVs, annexin V positive (AV+)‐cMVs, and annexin V negative (AV−)‐cMVs derived from blood and vascular cells were measured by flow cytometry. In the analysis of total cMVs, the frail group presented higher levels of CD14+/CD142+ (p = .042), CD41a+/CD142+ (p = .041), and CD56+ (p = .025), CD14+cMVs (p = .043), and CD16+/CD14+ (p = .019) cMVs levels. Within the phosphatidylserine‐exposing cMVs (AV+), the frail group showed higher CD14+/AV+ (p = .044), CD9+/AV+ (p = .031), P2RY12+/AV+ (p = .028), and CD235a+/AV+ (p = .043) cMVs concentrations. Finally, within AV− cMVs, the frail group showed higher CD142+/CD41a+/AV− cMVs concentrations originated from platelets (p = .027), CD56+/AV− originated from natural killer cells (p = .022), and CD34+/AV− cMVs from hematopoietic stem cells (p = .037). In summary, frail older adults present higher concentrations of platelet‐, leukocyte‐, and hematopoietic cell‐derived cMVs compared to robust age‐matched older adults. These cMVs may be involved in the deregulation of the immune system, endothelial damage, and increased risk of thrombosis associated with frailty.
Congenitally corrected transposition and mitral atresia complicated by restrictive atrial septum
Authors: Pradhan Sarah , Strainic James 
Published: August 2020

AbstractCongenitally corrected transposition (ccTGA), also known as L‐transposition of the great arteries (L‐TGA), is a rare cardiac malformation accounting for approximately 0.05% of congenital heart disease, characterized by ventricular inversion, discordant ventriculo‐arterial connections with a normal visceroatrial relationship. It was first described by Baron Rokitansky in 1875, and prenatal sonographic diagnosis can be difficult. Symptomatology and clinical presentation of this malformation are related to the associated intracardiac defects. We report a rare case of severe, complex cardiac disease: prenatally diagnosed ccTGA with atrial restriction, mitral atresia, Ebsteinoid tricuspid valve, and severe pulmonary valve stenosis, who subsequently developed left pulmonary vein stenosis.
miR‐587 promotes cervical cancer by repressing interferon regulatory factor 6
Authors: Ren Yuefang , Dong Jie , He Pingya , Liang Yufei , Wu Lifang , Wang Jiajian , Chu Boliang 
Published: August 2020

AbstractBackgroundInterferon regulatory factor 6 (IRF6) exhibits tumor‐suppressive functions in several cancer types. In the present study, the antitumor properties and related pathway mechanism of IRF6 were investigated in cervical cancer.MethodsForty‐one pairs of cervical cancer specimens and para‐carcinoma tissues were collected to evaluate IRF6 expression using immunohistochemical staining and miR‐587. The effects of miR‐587 and IRF6 on cervical cancer cell growth were explored by MTT assays and in a HeLa tumor xenograft mouse model. The migration and invasion of cervical cancer cells were monitored using transwell assays.ResultsIRF6 expression in cervical cancer specimens and cell lines was significantly reduced compared to that in the corresponding control group. In addition, IRF6 expression was negatively correlated with miR‐587 in cervical cancer tissues. Bioinformatics algorithms and luciferase assays revealed that IRF6 is a potential target of miR‐587, and miR‐587 mimic transfection led to a significant repression of IRF6 protein levels in cervical cancer cells. We also discovered that the antineoplastic properties of IRF6 could be reversed by overexpressing miR‐587 in cervical cancer cells. The up‐regulation of miR‐587 was correlated with poor overall survival in cervical cancer. In an in vivo experiment, miR‐587 silencing induced HeLa tumor growth inhibition, which was associated with the up‐regulation of IRF6 protein in the tumor.ConclusionsmiR‐587 post‐transcriptionally represses IRF6 protein expression to abrogate the antineoplastic activity of IRF6. The miR‐587/IRF6 signaling pathway plays a crucial role in the progression of cervical cancer and serves as a potential therapeutic target for the treatment of cervical cancer.
Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real‐world experience from HCV‐LALREAN cohort
Authors: Ridruejo Ezequiel , Piñero Federico , Mendizabal Manuel , Cheinquer Hugo , Wolff Fernando Herz , Anders Margarita , Reggiardo Virginia , Ameigeiras Beatriz , Palazzo Ana , Alonso Cristina , Schinoni María Isabel , Zuain María Grazia Videla , Tanno Federico , Figueroa Sebastián , Santos Luisa , Peralta Mirta , Soza Alejandro , Vistarini Cecilia , Adrover Raúl , Fernández Nora , Perez Daniela , Hernández Nelia , Estepo Claudio , Bruno Andres , Descalzi Valeria , Sixto Marcela , Borzi Silvia , Cocozzella Daniel , Zerega Alina , de Araujo Alexandre , Varón Adriana , Silva Marcelo ,   Latin American Liver Research Educational and Awareness Network (LALREAN)
Published: August 2020

AbstractIntroductionAlthough the effectiveness of direct‐acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real‐world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs.MethodsThis was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]).ResultsFrom 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full‐course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non‐SVR12 was 4.5% (95% CI, 3.5‐5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child‐Pugh score B OR, 2.09 (P = .06), Child‐Pugh C OR, 11.7 (P < .0001); and liver transplant (LT) recipient OR, 3.75 (P = .01).ConclusionIn this real‐life setting, higher DAA treatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time‐point of DAA treatment (NCT03775798; www.clinicaltrials.gov).
Distinguishing between COVID‐19 and influenza during the early stages by measurement of peripheral blood parameters
Authors: Chen Jiangnan , Pan Yong , Li Gangfeng , Xu Wenfang , Zhang Lihong , Yuan Shijin , Xia Yan , Lu Pei , Zhang Jun 
Published: August 2020

AbstractCoronavirus disease 2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus 2 infection. This study aims to examine the changes in peripheral blood parameters during the early stages of COVID‐19 and influenza. We analyzed the peripheral blood parameters of 169 COVID‐19 patients and 131 influenza patients during the early‐onset stage. Results from the patients with COVID‐19 were compared with those from healthy controls and influenza patients. In addition, results from patients with common and severe COVID‐19 were further compared. There were significant differences between COVID‐19 and influenza patients in terms of age, white blood cell count, platelet count, percentage of neutrophils, percentage of lymphocytes, percentage of monocytes, percentage of eosinophils, percentage of basophils, neutrophil, count and monocyte count. Two parameters (monocyte count and percentage of basophils) were combined to clarify the diagnostic efficacy of COVID‐19 and influenza and the area under the curve was found to be 0.772. Comparison of peripheral blood parameters from common COVID‐19, severe COVID‐19, and influenza patients revealed many differences during the early disease stages. The diagnostic formula developed by this study will be of benefit for physicians in the differentiation of COVID‐19 and influenza.
The effect of smoking on COVID‐19 severity: A systematic review and meta‐analysis
Authors: Reddy Rohin K. , Charles Walton N. , Sklavounos Alexandros , Dutt Atul , Seed Paul T. , Khajuria Ankur 
Published: August 2020

AbstractVarious comorbidities represent risk factors for severe coronavirus disease 2019 (COVID‐19). The impact of smoking on COVID‐19 severity has been previously reported in several meta‐analyses limited by small sample sizes and poor methodology. We aimed to rigorously and definitively quantify the effects of smoking on COVID‐19 severity. MEDLINE, Embase, CENTRAL, and Web of Science were searched between 1 December 2019 and 2 June 2020. Studies reporting smoking status of hospitalized patients with different severities of disease and/or at least one clinical endpoint of interest (disease progression, intensive care unit admission, need for mechanical ventilation, and mortality) were included. Data were pooled using a random‐effects model. This study was registered on PROSPERO: CRD42020180920. We analyzed 47 eligible studies reporting on 32 849 hospitalized COVID‐19 patients, with 8417 (25.6%) reporting a smoking history, comprising 1501 current smokers, 5676 former smokers, and 1240 unspecified smokers. Current smokers had an increased risk of severe COVID‐19 (risk ratios [RR]: 1.80; 95% confidence interval [CI]: 1.14‐2.85; P = .012), and severe or critical COVID‐19 (RR: 1.98; CI: 1.16‐3.38; P = .012). Patients with a smoking history had a significantly increased risk of severe COVID‐19 (RR: 1.31; CI: 1.12‐1.54; P = .001), severe or critical COVID‐19 (RR: 1.35; CI: 1.19‐1.53; P < .0001), in‐hospital mortality (RR: 1.26; CI: 1.20‐1.32; P < .0001), disease progression (RR: 2.18; CI: 1.06‐4.49; P = .035), and need for mechanical ventilation (RR: 1.20; CI: 1.01‐1.42; P = .043). Patients with any smoking history are vulnerable to severe COVID‐19 and worse in‐hospital outcomes. In the absence of current targeted therapies, preventative, and supportive strategies to reduce morbidity and mortality in current and former smokers are crucial.
Asymmetric least‐squares baseline algorithm with peak screening for automatic processing of the Raman spectra
Authors: Korepanov Vitaly I. 
Published: August 2020

AbstractThe signal in Raman spectroscopy has three components: vibrational bands, noise, and luminescence. Although the noise can be easily separated from the Raman bands either by a variety of algorithms or by adjusting the measurement conditions, to distinguish between the luminescence and the Raman peaks is a challenging task. Even though a number of algorithms have been proposed for this purpose, most of them show poor performance when applied to broad overlapping Raman bands with extended tails. A practical example of such a case can be found in many carbon‐based nanoscale materials with some degree of disorder, where the two close‐lying D and G bands dominate the spectrum. Conventional asymmetric least‐squares algorithms generate a baseline with penalizing the second derivative of the baseline itself. Instead, the approach suggested in the present work is based on an assumption that the vibrational bands can be “detected” and “masked” by their first and second derivatives of the raw spectrum. This makes it possible to handle the broad tails and superimposed bands very efficiently. The proposed algorithm was compared to several state‐of‐the‐art approaches including original and recently proposed ALS implementations, wavelet‐transform, and morphological algorithms. The “quality” of different algorithms was quantitatively estimated by adding random smooth curves to the spectrum. It was found that among the tested approaches, the peak‐screened ALS algorithm shows the best separation of the broad superimposed Raman peaks from the smooth random baselines. The Python code of the algorithm is provided.
An investigation of comparative substitution behavior of bifunctional trans‐platinum(II) complexes with symmetric and asymmetric alkylamine ligands
Authors: Olusegun Moses Ariyo , Reddy Desigan , Jaganyi Deogratius 
Published: August 2020

AbstractThis study was undertaken to investigate the comparative substitution behavior of mononuclear trans‐platinum(II) complexes with symmetric and asymmetric amine ligands. The rate of substitution of the aqua moeities from the complexes trans‐[Pt(NH3)2(H2O)2](ClO4)2 (tPt), trans‐[Pt(NH3)(NH2C2H5)(H2O)2](ClO4)2 (tPt2H2O), trans‐[Pt(NH3)(NH2C3H7)(H2O)2](ClO4)2 (tPt3H2O), [trans‐Pt(OH2)2(NH2CH3)2](ClO4)2 (tPtM), and [trans‐Pt(OH2)2{NH2CH(CH3)2}2](ClO4)2 (tPtR), by three nucleophiles, namely thiourea (TU), 1,3‐dimethylthiourea (DMTU), and 1,1,3,3‐tetramethylthiourea (TMTU) was studied under pseudo–first‐order conditions as a function of concentration and temperature by stopped‐flow spectrophotometry. All the substitution reactions of each of the trans‐platinum(II) complexes proceeds by a stepwise mechanism involving rate‐determining substitution of the first aqua ligand followed by a fast second substitution step, without any intermediates formed. The reactions were second order overall (rate = kobs[complex] where kobs = k2[nucleophile]), first order in both [complex] and [nucleophile]. The reactivity of the complexes was essentially governed by both steric and electronic factors. Comparing the second‐order rate constants for the substitution reactions of the mononuclear diaqua trans‐platinum(II) complexes with the thiourea‐based nucleophiles, the observed trend follows: tPt > tPt2H2O > tPtM > tPt3H2O > tPtR. This reactivity trend is consistent with the pKa values obtained for the first deprotonation step. The reactivity of the nucleophiles with the complexes decreases with an increase in steric demand in the following order: TU > DMTU > TMTU. The low positive values of activation enthalpy and large negative values of activation entropy indicate an associative mechanism of substitution in all the complexes. The computational modeling using density functional theory calculations was employed to provide theoretical interpretation of kinetic data.
Pressure abnormalities in patients with Zenker's diverticulum using pharyngeal high‐resolution manometry
Authors: Rosen Sarah P. , Jones Corinne A. , Hoffman Matthew R. , Knigge Molly A. , McCulloch Timothy M. 
Published: August 2020

AbstractObjectivesZenker's diverticulum is associated with reduced cricopharyngeal compliance and abnormal intrabolus pressure. However, it is unclear how the pharynx compensates for these deficits. Developments in manometric technology have improved our ability to capture pharyngeal pressure events. This study aims to describe the pharyngeal‐upper esophageal sphincter (UES) pressure profile during swallowing in patients with Zenker's diverticulum.MethodsHigh‐resolution manometry was performed on 11 patients with symptomatic Zenker's diverticulum and 11 age‐ and sex‐matched healthy controls during 10 mL liquid swallowing tasks. Pharyngeal and UES pressure magnitudes, durations, and integrals were compared between patients and controls using independent t tests. Other manometric parameters, including residual UES pressure at the time of maximum tongue base pressure and pharyngeal‐UES pressure gradient, were also evaluated. A case example using three‐dimensional high‐resolution manometry is presented.ResultsCompared with healthy controls, patients with Zenker's diverticulum exhibited pressure abnormalities in the UES region. While baseline and pre‐opening maximum pressures were not different, residual pressures were elevated (P = .001). Pharyngeal‐UES pressure gradients did not differ between the two groups.ConclusionThis study used high‐resolution manometry to characterize pharyngeal pressure dynamics in patients with Zenker's diverticulum. The changes occurring at the cricopharyngeus appear to result in persistent UES pressurization during UES opening, rather than high tonic resting pressure. Pharyngeal‐UES pressure gradients, critical to bolus passage, were also preserved in this patient population.Level of Evidence3b.
Differential Impact of Extended Criteria Donors After Brain Death or Circulatory Death in Adult Liver Transplantation
Authors: Pandya Keval , Sastry Vinay , Panlilio Mara T. , Yip Terry C. F. , Salimi Shirin , West Claire , Virtue Susan , Wells Mark , Crawford Michael , Pulitano Carlo , Strasser Simone I. , McCaughan Geoffrey W. , Majumdar Avik , Liu Ken 
Published: August 2020

Using grafts from extended criteria donors (ECDs) and donation after circulatory death (DCD) donors is a strategy to address organ shortage in liver transplantation (LT). We studied the characteristics and outcomes of ECD and DCD grafts. We retrospectively studied consecutive adults who underwent deceased donor LT between 2006 and 2019. ECD was defined using modified Eurotransplant criteria. Our primary outcomes were graft and patient survival. A total of 798 grafts were used for LT, of which 93.1% were donation after brain death (DBD; 59.9% were also ECD) and 6.9% were DCD grafts (49.1% were also ECD). Among DBD graft recipients, donors having >33% liver steatosis or 3 ECD criteria resulted in poorer graft survival. Otherwise ECD graft recipients had similar graft and patient survival compared with non‐ECD graft recipients. DCD graft recipients also had similar patient survival compared with DBD recipients. However, DCD grafts from an ECD appeared to have worse outcomes. DCD graft recipients experienced higher rates of early allograft dysfunction (50.9% versus 24.7%; P < 0.001) and ischemic biliopathy (16.4% versus 1.5%; P < 0.001) compared with DBD graft recipients. Use of DBD grafts from ECDs did not impact outcomes unless there was significant donor steatosis or 3 Eurotransplant criteria were met. DCD graft recipients have similar patient survival compared with DBD graft recipients as long as the donor was not an ECD. We recommend that DBD donors with 3 or more ECD features or >33% steatosis and DCD donors with any ECD features be used with caution in adult LT.