bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential susceptibility of Onchocerca volvulus microfilaria to ivermectin in two areas of contrasting history of mass drug administration in Cameroon: Relevance of microscopy and molecular techniques for the monitoring of skin microfilarial repopulation within six months of direct observed treatment
Authors: Abong Raphael Awah , Amambo Glory N. , Ndongmo Patrick W. Chounna , Njouendou Abdel Jelil , Manuel Ritter , Beng Amuam Andrew , Esum Mathias Eyong , Deribe Kebede , Cho Jerome Fru , Fombad Fanny Fri , Nji Theobald Mue , Enyong Peter Ivo , Poole Catherine B. , Pfarr Kenneth , Hoerauf Achim , Carlow Clotilde K.S. , Wanji Samuel 
Published: July 2020

Abstract
Background. Ivermectin is an excellent microfilaricide against Onchocerca volvulus. However, in some regions, long term use of ivermectin has resulted in sub-optimal responses to the treatment. More data to properly document the phenomenon in various contexts of ivermectin mass drug administration (IVM-MDA) is needed. Also, there is a need to accurately monitor a possible repopulation of skin by microfilariae following treatment. Skin snip microscopy is known to have a low sensitivity in individuals with light infections, which can be the case following treatment. This study was designed with two complementary objectives: (i) to assess the susceptibility of O. volvulus microfilariae to ivermectin in two areas undergoing IVM-MDA for different lengths of time, and (ii) to document the repopulation of skin by the O. volvulus microfilariae following treatment, using 3 independent diagnostic techniques.Method. Identified microfilaridermic individuals were treated with ivermectin and re-examined after 1, 3, and 6 months using microscopy, real-time PCR and LAMP assays. Susceptibility to ivermectin and trends in detecting reappearance of skin microfilariae were determined using three techniques. Microscopy was used as an imperfect gold standard to determine the performance of real-time PCR and LAMP.Results. In Bafia with over 20 years of IVM-MDA, 11/51 (21.6%) treated microfilaridemic participants where still positive for skin microfilariae after 1 month. In Melong, with 10 years of IVM-MDA, 2/29 (6.9%) treated participants were still positive. The microfilarial density reduction per skin biopsy within one month following treatment was significantly lower in participants from Bafia.In both study sites, the molecular techniques detected higher proportions of infected individuals than microscopy at all monitoring time points. LAMP demonstrated the highest levels of sensitivity and real-time PCR was found to have the highest specificity.Conclusion. Patterns in skin mirofilarial clearance and repopulation were established. O. volvulus worms from Bafia with higher number of annual MDA were less susceptible to ivermectin. Molecular assays displayed higher sensitivity in monitoring O. volvulus microfilaridemia within six months following treatment.
Monoclonal and polyclonal immunoglobulin G deposits on tubular basement membranes of native and pretransplant kidneys: A retrospective study
Authors: Sawada Anri , Okumi Masayoshi , Horita Shigeru , Tamura Tomomi , Taneda Sekiko , Ishida Hideki , Hattori Motoshi , Tanabe Kazunari , Nitta Kosaku , Honda Kazuho , Koike Junki , Nagashima Yoji , Shimizu Akira 
Published: July 2020

Abstract
The authors have withdrawn this preprint due to author disagreement.
Co-encapsulation of HNF4α Overexpressing UMSCs and Human Primary Hepatocytes Ameliorates Mouse Acute Liver Failure
Authors: Kong Defu , Xu Huiming , Chen Mo , Yu Yeping , Qian Yongbing , Qin Tian , Tong Ying , Xia Qiang , Hang Hualian 
Published: July 2020

Abstract
Background: Acute liver failure (ALF) is a complicated condition that is characterized by global hepatocyte death and often requires immediate liver transplantation. However, this therapy is limited by shortage of donor organs. Mesenchymal stem cells (MSCs) and hepatocytes are two attractive sources of cell-based therapies to treat ALF. The combined transplantation of hepatocytes and MSCs is considered to be more effective for the treatment of ALF than single-cell transplantation. We have previously demonstrated that HNF4α-overexpressing human umbilical cord MSCs (HNF4α-UMSCs) promoted the expression of hepatic-specific genes. In addition, microencapsulation allows exchange of nutrients, forming a protective barrier to the transplanted cells. Moreover, encapsulation of hepatocytes improves the viability and synthetic ability of hepatocytes and circumvents immune rejection. This study aimed to investigate the therapeutic effect of microencapsulation of hepatocytes and HNF4α-UMSCs in ALF mice.Methods: Human hepatocytes and UMSCs were obtained separately from liver and umbilical cord , followed by co-encapsulation and transplantation into mice by intraperitoneal injection. LPS/D-gal was used to induce ALF by intraperitoneal injection 24 h after transplantation. In addition, Raw 264.7cells (a macrophage cell line) were used to elucidate the effect of HNF4α-UMSCs-hepatocyte microcapsules on polarization of macrophages. The protein chip was used to define the important paracrine factors in the conditioned mediums (CMs) of UMSCs and HNF4α-UMSCs and investigate the possible mechanism of HNF4α-UMSCs for the treatment of ALF in mice.Results: HNF4α-UMSCs can enhance the function of primary hepatocytes in alginate–poly-L-lysine–alginate (APA) microcapsules. The co-encapsulation of both HNF4α-UMSCs and hepatocytes achieved better therapeutic effects in ALF mice by promoting M2 macrophage polarization and reducing inflammatory response t mainly mediated by the paracrine factor HB-EGF secreted byHNF4α-UMSCs.Conclusions: The present study confirms that the co-encapsulation of HNF4α-UMSC and hepatocytes could exert therapeutic effect on ALF mainly by HB-EGF secreted by HNF4α-UMSCs and provides a novel strategy for the treatment of ALF.
Association of human cytomegalovirus (HCMV) neutralizing antibodies with antibodies to the HCMV glycoprotein complexes
Authors: Shibamura Miho , Yoshikawa Tomoki , Yamada Souichi , Inagaki Takuya , Nguyen Phu Hoang Anh , Fujii Hikaru , Harada Shizuko , Fukushi Shuetsu , Oka Akira , Mizuguchi Masashi , Saijo Masayuki 
Published: July 2020

Abstract
Background: Human cytomegalovirus (HCMV) causes asymptomatic infections, but also causes congenital infections when women were infected with HCMV during pregnancy, and life-threatening diseases in immunocompromised patients. To better understand the mechanism of the neutralization activity against HCMV, the association of HCMV NT antibody titers was assessed with the antibody titers against each glycoprotein complex (gc) of HCMV. Methods: Sera collected from 78 healthy adult volunteers were used. HCMV Merlin strain and HCMV clinical isolate strain 1612 were used in the NT assay with the plaque reduction assay, in which both the MRC-5 fibroblasts cells and the RPE-1 epithelial cells were used. Glycoprotein complex of gB, gH/gL complexes (gH/gL/gO and gH/gL/UL128-131A [PC]) and gM/gN were selected as target glycoproteins. 293FT cells expressed with gB, gM/gN, gH/gL/gO, or PC, were prepared and used for the measurement of the antibody titers against each gc in an indirect immunofluorescence assay (IIFA). The correlation between the IIFA titers to each gc and the HCMV-NT titers was evaluated.Results: There were no significant correlations between gB-specific IIFA titers and the HCMV-NT titers in epithelial cells or between gM/gN complex-specific IIFA titers and the HCMV-NT titers. On the other hand, there was a statistically significant positive correlation between the IIFA titers to gH/gL complexes and HCMV-NT titers.Conclusions: The data suggest that the gH/gL complexes might be the major target to induce NT activity against HCMV.
Neural defects caused by total and Wnt1-Cre mediated ablation of p120ctn in mice
Authors: Pieters Tim , Sanders Ellen , Tian Huiyu , Hengel Jolanda van , Roy Frans Van 
Published: July 2020

Abstract
Background p120 catenin (p120ctn) is an important component in the cadherin-catenin cell adhesion complex because it stabilizes cadherin-mediated intercellular junctions. Outside these junctions, p120ctn is actively involved in the regulation of small GTPases of the Rho family, in actomyosin dynamics and in transcription regulation. We and others reported that loss of p120ctn in mouse embryos results in an embryonic lethal phenotype, but the exact developmental role of p120ctn during brain formation has not been reported. Results We combined floxed p120ctn mice with Del-Cre or Wnt1-Cre mice to deplete p120ctn from either all cells or specific brain and neural crest cells. Complete loss of p120ctn in mid-gestation embryos resulted in an aberrant morphology, including growth retardation, failure to switch from lordotic to fetal posture, and defective neural tube formation and neurogenesis. By expressing a wild-type p120ctn from the ROSA26 locus in p120ctn-null mouse embryonic stem cells, we could partially rescue neurogenesis. To further investigate the developmental role of p120ctn in neural tube formation, we generated conditional p120ctn fl/fl ;Wnt1Cre knockout mice. p120ctn deletion in Wnt1-expressing cells resulted in neural tube closure defects (NTDs) and craniofacial abnormalities. These defects could not be correlated with misregulation of brain marker genes or cell proliferation. In contrast, we found that p120ctn is required for proper expression of the cell adhesion components N-cadherin, E-cadherin and β-catenin, and of actin-binding proteins cortactin and Shroom3 at the apical side of neural folds. This region is of critical importance for closure of neural folds. Surprisingly, the lateral side of mutant neural folds showed loss of p120ctn, but not of N-cadherin, β-catenin or cortactin. Conclusions These results indicate that p120ctn is required for neurogenesis and neurulation. Elimination of p120ctn in cells expressing Wnt1 affects neural tube closure by hampering correct formation of specific adhesion and actomyosin complexes at the apical side of neural folds. Collectively, our results demonstrate the crucial role of p120ctn during brain morphogenesis.
Analysis of Six Chloroplast Genomes Provides Insight into the Evolution of Chrysosplenium (Saxifragaceae)
Authors: Wu Zhihua , Liao Rui , Yang Tiange , Dong Xiang , Lan Deqing , Qin Rui , Liu Hong 
Published: July 2020

Abstract
Background: Chrysosplenium L. (Saxifragaceae) is a genus of plants widely distributed in Northern Hemisphere and usually found in moist, shaded valleys and mountain slopes. This genus is ideal for studying plant adaptation to low-light conditions. Although some progress has been made in the systematics and biogeography of Chrysosplenium, its chloroplast genome evolution remains to be investigated. Results: To fill this gap, we sequenced the chloroplast genomes of six Chrysosplenium species and analyzed their genome structure, GC content, and nucleotide diversity. Moreover, we performed a phylogenetic analysis and calculated non-synonymous (Ka) /synonymous (Ks) substitution ratios using the combined protein-coding genes of 29 species within Saxifragales and two additional species as outgroups, as well as a pair-wise estimation for each gene within Chrysosplenium. Compared with the outgroups in Saxifragaceae, the six Chrysosplenium chloroplast genomes had lower GC contents; they also had conserved boundary regions and gene contents, as only the rpl32 gene was lost in four of the Chrysosplenium chloroplast genomes. Phylogenetic analyses suggested that the Chrysosplenium separated to two major clades (the opposite group and the alternate group). The selection pressure estimation (Ka/Ks ratios) of genes in the Chrysosplenium species showed that matK and ycf2 were subjected to positive selection.Conclusion: This study provides genetic resources for exploring the phylogeny of Chrysosplenium and sheds light on plant adaptation to low-light conditions. The lower average GC content and the lacking gene of rpl32 indicated selective pressure in their unique habitats. Different from results previously reported, our selective pressure estimation suggested that the genes related to photosynthesis (such as ycf2) were under positive selection at sites in the coding region.
Hemodynamics during the 10-Minute NASA Lean Test: Evidence of circulatory decompensation in a subset of ME/CFS patients
Authors: Lee Jihyun , Vernon Suzanne D , Jeys Patricia , Ali Weam , Campos Andrea , Unutmaz Derya , Yellman Brayden , Bateman Lucinda 
Published: July 2020

Abstract
Background. Lightheadedness, fatigue, weakness, heart palpitations, cognitive dysfunction, muscle pain, and exercise intolerance are some of the symptoms of orthostatic intolerance (OI). There is substantial comorbidity of OI in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome). The 10-minute NASA Lean Test (NLT) is a simple, point-of-care method that can aid ME/CFS diagnosis and guide management and treatment of OI. The objective of this study was to understand the hemodynamic changes that occur in ME/CFS patients during the 10-minute NLT. Methods. A total of 150 ME/CFS patients and 75 age, gender and race matched healthy controls (HCs) were enrolled. We recruited 75 ME/CFS patients who had been sick for less than 4 years (<4 ME/CFS) and 75 ME/CFS patients sick for more than 10 years (>10 ME/CFS). The 10-minute NLT involves measurement of blood pressure and heart rate while resting supine and every minute for 10 minutes while standing with shoulder-blades on the wall for a relaxed stance. Spontaneously reported symptoms are recorded during the test. ANOVA and regression analysis were used to test for differences and relationships in hemodynamics, symptoms and upright activity between groups.Results. At least 5 minutes of the 10-minute NLT were required to detect hemodynamic changes. The <4 ME/CFS group had significantly higher heart rate and abnormally narrowed pulse pressure compared to >10 ME/CFS and HCs. The <4 ME/CFS group experienced significantly more OI symptoms compared to >10 ME/CFS and HCs. The circulatory decompensation observed in the <4 ME/CFS group was not related to age or medication use. Conclusions. Circulatory decompensation characterized by increased heart rate and abnormally narrow pulse pressure was identified in a subgroup of ME/CFS patients who have been sick for <4 years. This suggests inadequate ventricular filling from low venous pressure. The 10-minute NLT can be used to diagnose and treat the circulatory decompensation in this newly recognized subgroup of ME/CFS patients. The >10 ME/CFS group had less pronounced hemodynamic changes during the NLT possibly from adaptation and compensation that occurs over time. The 10-minute NLT is a simple and clinically useful point-of-care method that can be used for early diagnosis of ME/CFS and help guide OI treatment.
Sphingomyelin(d35:1) as a novel predictor for lung adenocarcinoma recurrence after a radical surgery: a case-control study
Authors: Takanashi Yusuke , Funai Kazuhito , Sato Shumpei , Kawase Akikazu , Tao Hong , Takahashi Yutaka , Sugimura Haruhiko , Setou Mitsutoshi , Kahyo Tomoaki , Shiiya Norihiko 
Published: July 2020

Abstract
Background: To improve the postoperative prognosis of patients with lung cancer, predicting the recurrence high-risk patients is needed for the efficient application of adjuvant chemotherapy. However, predicting lung cancer recurrence after a radical surgery is difficult even with conventional histopathological prognostic factors, thereby a novel predictor should be identified. As lipid metabolism alterations are known to contribute to cancer progression, we hypothesized that lung adenocarcinomas with high recurrence risk contain candidate lipid predictors. This study aimed to identify candidate lipid predictors for the recurrence of lung adenocarcinoma after a radical surgery.Methods: Frozen tissue samples of primary lung adenocarcinoma obtained from patients who underwent a radical surgery were retrospectively reviewed. Recurrent and non-recurrent cases were assigned to recurrent (n = 10) and non-recurrent (n = 10) groups, respectively. Extracted lipids from frozen tissue samples were subjected to liquid chromatography-tandem mass spectrometry analysis. The average total lipid levels of the non-recurrent and recurrent groups were compared. Candidate predictors were screened by comparing the folding change and P-value of t-test in each lipid species between the recurrent and non-recurrent groups.Results: The average total lipid level of the recurrent group was 1.65 times higher than that of the non-recurrent group (P < 0.05). A total of 203 lipid species were increased (folding change, ≥2; P < 0.05) and 4 lipid species were decreased (folding change, ≤0.5; P < 0.05) in the recurrent group. Among these candidates, increased sphingomyelin (SM)(d35:1) in the recurrent group was the most prominent candidate predictor, showing high performance of recurrence prediction (AUC, 9.1; sensitivity, 1.0; specificity, 0.8; accuracy, 0.9).Conclusion: We propose SM(d35:1) as a novel candidate predictor for lung adenocarcinoma recurrence. Our finding can contribute to precise recurrence prediction and qualified postoperative therapeutic strategy for lung adenocarcinomas.Abbreviations: AUC, area under the ROC curve; ROC, receiver operating characteristic.
Nasal decolonization of Staphylococcus aureus and the risk of surgical site infection after surgery: a meta-analysis
Authors: Tang Jia , Hui Jiangjin , Ma Jing , Chen Mingquan 
Published: July 2020

Abstract
Aim: To assess the effects of nasal decontamination on preventing surgical site infections (SSIs) in people who are Staphylococcus aureus carriers undergoing different types of surgeries and diverse measures of decolonization. Methods: Relevant randomized controlled trials (RCTs) were identified through systematic searches of the PubMed, Embase, Web of science, and the Cochrane Library databases. The risk ratios (RRs) and 95% confidence intervals (CIs) were calculated and the effects model was chosen according to the heterogeneity. Subgroup analyses were performed according to different types of surgeries and measures of decolonization that Staphylococcus aureus carriers were applied.Results: Twenty RCTs published between 1996 and 2019 involving 10526 patients were included. Pooled results showed that the overall SSIs and pulmonary surgery SSIs presented with a statistical difference in measures of nasal decontamination (RR=0.59 and 0.47, respectively, both p<0.01). However, the associations between nasal decolonization and increased risks of SSIs in orthopedics surgery or cardiovascular surgery remained insignificant in studies. As for the diverse measures of nasal decontamination, 50% used mupirocin, 15% used chlorhexidine, 30% used different types of antimicrobial drugs, and 5% use others. The SSIs rate were decreased after chlorhexidine (RR=0.474, 95% CI: 0.259-0.864), while no significant difference was shown in the use of mupirocin (RR=0.871, 95% CI: 0.544-1.394).Conclusion: It seems that nasal decolonization of Staphylococcus aureus may be associated with a reduction of SSIs in these patients, especially in patients who have been administered by pulmonary surgeries or treated with chlorhexidine.
Systematic modification of N-glycosylation sites in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose
Authors: Kołaczkowski Bartłomiej Maciej , Schaller Kay S. , Sørensen Trine Holst , Peters Günther H. J. , Jensen Kenneth , Krogh Kristian B. R. M. , Westh Peter 
Published: July 2020

Abstract
Background: Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation. For many years, Trichoderma reesei Cel7A (TrCel7A) has served as a model to understand structure-function relationships of processive cellobiohydrolases. The architecture of TrCel7A includes an N-glycosylated catalytic domain, which is connected to a carbohydrate-binding module through a flexible, O-glycosylated linker. Depending on the fungal expression host, glycosylation can vary not only in glycoforms, but also in site occupancy, leading to a complex pattern of glycans, which can affect the enzyme’s stability and kinetics. Results: Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WTAo and WTTr) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glycAo and ΔN-glycTr). Also, we expressed single N-glycosylation site deficient mutants TrCel7A (N45QAo, N270QAo, N384QAo). The TrCel7A enzymes were studied by steady-state kinetics under both substrate- and enzyme-saturating conditions using different cellulosic substrates. The Michaelis constant (KM) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs value on some substrates. The ability of the enzyme to combine productively with sites on the cellulose surface followed a similar pattern on all tested substrates. Thus, site density (number of sites per gram cellulose) was 30-60 % higher for the single deficient variants compared to the WT, and about two-fold larger for the triple deficient enzyme. Molecular dynamic simulation of the N-glycan mutants TrCel7A reveled higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384. Conclusions: The kinetic changes of TrCel7A imposed by removal of N-linked glycans reflected modifications of substrate accessibility. The presence of N-glycans with extended structures increased KM and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation. This knowledge could be applied to modify enzyme glycosylation to engineer enzyme with higher activity on the insoluble substrates.