bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mid-term results of revision surgery using double-trabecular metal cups alone or combined with impaction bone grafting for complex acetabular defects
Authors: Zhang Xianghong , Li Zhihong , Wang Wanchun , Liu Tang , Peng Weiqiu 
Published: August 2020

Abstract
Background
Revision surgery for complex acetabular defects is still technically challenging. In this study, we discussed and compared the clinical and radiological outcomes of revision surgery between two methods using double-trabecular metal (TM) cups alone or combined with impacting bone grafting (IBG).

Methods
The records of 18 patients (18 hips) who underwent revision surgery using double-trabecular metal (double-TM) cups between 2008 and 2016 were retrospectively reviewed. All the patients were diagnosed with Paprosky III acetabular defects. The acetabular defects were reconstructed by double-TM cups alone or in combination with IBG. We used the modified Harris Hip Score (mHHS), University of California, Los Angeles (UCLA), and Short Form 36 (SF-36) to evaluate the clinical outcomes. Pelvis plain X-ray was used to assess hip center of rotation (COR), abduction angle and anteversion angle of acetabular cup, and incorporation of the bone graft to host bone.

Results
The median follow-up time was 61.0 (IQR 56.0 to 65.8) months. No patients underwent re-revision for loosening or any other reasons. Complications included 3 patients (16.7%) with early dislocation and 3 patients (16.7%) with delayed wound healing. The average mHHS and UCLA preoperatively were 44.1 ± 4.0 (range 35 to 50) and 2.6 ± 0.7 (range 2 to 4), respectively and at the last follow-up were 73.7 ± 4.2 (range 68 to 85) and 7.3 ± 0.5 (range 7 to 8), respectively. The mean SF-36 scores at the last follow-up were improved significantly than preoperative scores, especially in bodily pain category (P < 0.05). The average limb-length discrepancy (LLD) decreased significantly from 24.2 ± 2.6 (range 20 to 32) mm preoperatively to 5.8 ± 1.8 (range 3 to 9) mm at the last follow-up, respectively. However, there was no significant difference between two methods at the last follow-up in terms of mHHS, UCLA, SF-36, LLD, and hip COR (P > 0.05). Radiographic evaluation demonstrated bone graft incorporation in all hips in the follow-up.

Conclusions
Defect reconstruction using double-TM cups alone or combined with IBG are practical and reliable treatment options for Paprosky III acetabular defects without pelvic discontinuity. Nevertheless, high postoperative complication rate, especially in terms of dislocation, remains a challenge.
The functional epigenetic landscape of aberrant gene expression in molecular subgroups of newly diagnosed multiple myeloma
Authors: Choudhury Samrat Roy , Ashby Cody , Tytarenko Ruslana , Bauer Michael , Wang Yan , Deshpande Shayu , Den Judith , Schinke Carolina , Zangari Maurizio , Thanendrarajan Sharmilan , Davies Faith E. , van Rhee Frits , Morgan Gareth J. , Walker Brian A. 
Published: August 2020

Abstract
Background
Multiple Myeloma (MM) is a hematological malignancy with genomic heterogeneity and poor survival outcome. Apart from the central role of genetic lesions, epigenetic anomalies have been identified as drivers in the development of the disease.

Methods
Alterations in the DNA methylome were mapped in 52 newly diagnosed MM (NDMM) patients of six molecular subgroups and matched with loci-specific chromatin marks to define their impact on gene expression. Differential DNA methylation analysis was performed using DMAP with a ≥10% increase (hypermethylation) or decrease (hypomethylation) in NDMM subgroups, compared to control samples, considered significant for all the subsequent analyses with p<0.05 after adjusting for a false discovery rate.

Results
We identified differentially methylated regions (DMRs) within the etiological cytogenetic subgroups of myeloma, compared to control plasma cells. Using gene expression data we identified genes that are dysregulated and correlate with DNA methylation levels, indicating a role for DNA methylation in their transcriptional control. We demonstrated that 70% of DMRs in the MM epigenome were hypomethylated and overlapped with repressive H3K27me3. In contrast, differentially expressed genes containing hypermethylated DMRs within the gene body or hypomethylated DMRs at the promoters overlapped with H3K4me1, H3K4me3, or H3K36me3 marks. Additionally, enrichment of BRD4 or MED1 at the H3K27ac enriched DMRs functioned as super-enhancers (SE), controlling the overexpression of genes or gene-cassettes.

Conclusions
Therefore, this study presents the underlying epigenetic regulatory networks of gene expression dysregulation in NDMM patients and identifies potential targets for future therapies.
Hospitalization for acute cerebellitis in children affected by varicella: how much does it cost?
Authors: Bozzola Elena , Guolo Stefano , Macchiarulo Giulia , Festa Lidia , Spina Giulia , Krzysztofiak Andrzej , Grandin Annalisa , Bozzola Mauro , Raponi Massimiliano , Villani Alberto 
Published: August 2020

Abstract
Background
Chickenpox is a highly contagious airborne disease caused by the varicella zoster virus. It is generally benign and self-limiting, but it may be responsible of life-threatening complications. Acute cerebellitis (AC) is the most common neurological complication and is associated with prolonged hospitalization in the acute phase (HAP).

Aim of the study
To estimate the costs of AC HAP in children affected by varicella.

Materials and methods
We retrospectively reviewed the medical records of a pediatric cohort hospitalized for chickenpox AC over a period of 15 years (from October 2003 to October 2018) and we analyzed acute care costs. For any patient the HAP has been calculated. The final value includes cost of hospital accommodation and management at the Pediatric and Infectious Diseases Unit. To this cost, the price of procedures (imaging, laboratory exams, medical and paramedical evaluations) and medical treatments was added.

Results
In the study period, 856 children had been hospitalized for varicella. Out of them, 65 met a diagnosis of AC and were included in the study. The hospitalization length was of 10 days (range 3–20 days). The median cost of HAP for each patient was of 5366 euro, with an average annual cost of 23,252 €. The most significant part of HAP is due to the cost of hospital accommodation and management at the Pediatric Infectious Diseases Unit, which was about € 537.78 for a single day.

Discussion
Although AC post-varicella is rare, its HAP cost is not negligible resulting in substantial economic burden. Vaccination would have probably prevented varicella and AC complication, avoiding hospitalization.

Conclusions
Financial studies are important for evaluate the cost saving in order to influence public funding decisions. Further studies are necessary to investigate the economic burden of the disease.
High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease patients after extubation: a multicenter, randomized controlled trial
Authors: Tan Dingyu , Walline Joseph Harold , Ling Bingyu , Xu Yan , Sun Jiayan , Wang Bingxia , Shan Xueqin , Wang Yunyun , Cao Peng , Zhu Qingcheng , Geng Ping , Xu Jun 
Published: August 2020

AbstractBackgroundHigh-flow nasal cannula (HFNC) oxygen therapy is being increasingly used to prevent post-extubation hypoxemic respiratory failure and reintubation. However, evidence to support the use of HFNC in chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure after extubation is limited. This study was conducted to test if HFNC is non-inferior to non-invasive ventilation (NIV) in preventing post-extubation treatment failure in COPD patients previously intubated for hypercapnic respiratory failure.MethodsCOPD patients with hypercapnic respiratory failure who were already receiving invasive ventilation were randomized to HFNC or NIV at extubation at two large tertiary academic teaching hospitals. The primary endpoint was treatment failure, defined as either resumption of invasive ventilation or switching to the other study treatment modality (NIV for patients in the NFNC group or vice versa).ResultsNinety-six patients were randomly assigned to the HFNC group or NIV group. After secondary exclusion, 44 patients in the HFNC group and 42 patients in the NIV group were included in the analysis. The treatment failure rate in the HFNC group was 22.7% and 28.6% in the NIV group—risk difference of − 5.8% (95% CI, − 23.8–12.4%,p = 0.535), which was significantly lower than the non-inferior margin of 9%. Analysis of the causes of treatment failure showed that treatment intolerance in the HFNC group was significantly lower than that in the NIV group, with a risk difference of − 50.0% (95% CI, − 74.6 to − 12.9%,p = 0.015). One hour after extubation, the mean respiratory rates of both groups were faster than their baseline levels before extubation (p < 0.050). Twenty-four hours after extubation, the respiratory rate of the HFNC group had returned to baseline, but the NIV group was still higher than the baseline. Forty-eight hours after extubation, the respiratory rates of both groups were not significantly different from the baseline. The average number of daily airway care interventions in the NIV group was 7 (5–9.3), which was significantly higher than 6 (4–7) times in the HFNC group (p = 0.006). The comfort score and incidence of nasal and facial skin breakdown of the HFNC group was also significantly better than that of the NIV group [7 (6–8) vs 5 (4–7),P < 0.001] and [0 vs 9.6%,p = 0.027], respectively.ConclusionAmong COPD patients with severe hypercapnic respiratory failure who received invasive ventilation, the use of HFNC after extubation did not result in increased rates of treatment failure compared with NIV. HFNC also had better tolerance and comfort than NIV.Trial registrationchictr.org(ChiCTR1800018530). Registered on 22 September 2018,http://www.chictr.org.cn/usercenter.aspx
Contiguous and stochastic CHH methylation patterns of plant DRM2 and CMT2 revealed by single-read methylome analysis
Authors: Harris Keith D. , Zemach Assaf 
Published: August 2020

AbstractCytosine methylome data is commonly generated through next-generation sequencing, with analyses averaging methylation states of individual reads. We propose an alternative method of analysing single-read methylome data. Using this method, we identify patterns relating to the mechanism of two plant non-CG-methylating enzymes, CMT2 and DRM2. CMT2-methylated regions show higher stochasticity, while DRM2-methylated regions have higher variation among cells. Based on these patterns, we develop a classifier that predicts enzyme activity in different species and tissues. To facilitate further single-read analyses, we develop a genome browser, SRBrowse, optimised for visualising and analysing sequencing data at single-read resolution.
The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation
Authors: Kosti Adam , de Araujo Patricia Rosa , Li Wei-Qing , Guardia Gabriela D. A. , Chiou Jennifer , Yi Caihong , Ray Debashish , Meliso Fabiana , Li Yi-Ming , Delambre Talia , Qiao Mei , Burns Suzanne S. , Lorbeer Franziska K. , Georgi Fanny , Flosbach Markus , Klinnert Sarah , Jenseit Anne , Lei Xiufen , Sandoval Carolina Romero , Ha Kevin , Zheng Hong , Pandey Renu , Gruslova Aleksandra , Gupta Yogesh K. , Brenner Andrew , Kokovay Erzsebet , Hughes Timothy R. , Morris Quaid D. , Galante Pedro A. F. , Tiziani Stefano , Penalva Luiz O. F. 
Published: August 2020

Abstract
Background
RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in RBP expression and function are often observed in cancer and influence critical pathways implicated in tumor initiation and growth. Identification and characterization of oncogenic RBPs and their regulatory networks provide new opportunities for targeted therapy.

Results
We identify the RNA-binding protein SERBP1 as a novel regulator of glioblastoma (GBM) development. High SERBP1 expression is prevalent in GBMs and correlates with poor patient survival and poor response to chemo- and radiotherapy. SERBP1 knockdown causes delay in tumor growth and impacts cancer-relevant phenotypes in GBM and glioma stem cell lines. RNAcompete identifies a GC-rich region as SERBP1-binding motif; subsequent genomic and functional analyses establish SERBP1 regulation role in metabolic routes preferentially used by cancer cells. An important consequence of these functions is SERBP1 impact on methionine production. SERBP1 knockdown decreases methionine levels causing a subsequent reduction in histone methylation as shown for H3K27me3 and upregulation of genes associated with neurogenesis, neuronal differentiation, and function. Further analysis demonstrates that several of these genes are downregulated in GBM, potentially through epigenetic silencing as indicated by the presence of H3K27me3 sites.

Conclusions
SERBP1 is the first example of an RNA-binding protein functioning as a central regulator of cancer metabolism and indirect modulator of epigenetic regulation in GBM. By bridging these two processes, SERBP1 enhances glioma stem cell phenotypes and contributes to GBM poorly differentiated state.
Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose
Authors: Kołaczkowski Bartłomiej M. , Schaller Kay S. , Sørensen Trine Holst , Peters Günther H. J. , Jensen Kenneth , Krogh Kristian B. R. M. , Westh Peter 
Published: August 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 twofold larger for the triple deficient enzyme. Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed 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.
Contrasted transmission efficiency of Zika virus strains by mosquito species Aedes aegypti, Aedes albopictus and Culex quinquefasciatus from Reunion Island
Authors: Gomard Yann , Lebon Cyrille , Mavingui Patrick , Atyame Célestine M. 
Published: August 2020

Abstract
Background
Zika virus (ZIKV) is a mosquito-borne flavivirus that recently emerged in the South Pacific islands and Americas where unprecedented outbreaks were reported. Although Aedes aegypti is considered to be the main vector for ZIKV, other mosquito species have been shown to be potential vectors and differences in vector competence with respect to mosquito strain and ZIKV strain have been demonstrated. In this study we compared the vector competence of three mosquito species Aedes albopictus, Ae. aegypti and Culex quinquefasciatus from Reunion Island for three ZIKV strains.

Methods
Five mosquito strains (2 strains of Ae. albopictus, 1 of Ae. aegypti and 2 of Cx. quinquefasciatus) were exposed to three ZIKV strains: one African strain (Dak84) and two Asian strains (PaRi_2015 and MAS66). The vector competence parameters (infection rate, dissemination efficiency and transmission efficiency) and viral loads were examined at 14 and 21 days post-infection.

Results
The two Cx. quinquefasciatus strains did not become infected and were therefore unable to either disseminate or transmit any of the three ZIKV strains. Aedes albopictus and Ae. aegypti strains were poorly competent for the two Asian ZIKV strains, while both mosquito species displayed higher infection rates, dissemination and transmission efficiencies for the African ZIKV Dak84 strain. However, this African ZIKV strain was better transmitted by Ae. aegypti as compared to Ae. albopictus.

Conclusions
Our results show that both Ae. albopictus and Ae. aegypti, from Reunion Island, are more likely to be competent for ZIKV in contrast to Cx. quinquefasciatus which appeared refractory to all tested ZIKV strains. This improves our understanding of the role of mosquito species in the risk of the ZIKV emergence on Reunion Island.
COVID19 antibody detection using lateral flow assay tests in a cohort of convalescent plasma donors
Authors: Ragnesola Brett , Jin Daniel , Lamb Christopher C. , Shaz Beth H. , Hillyer Christopher D. , Luchsinger Larry L. 
Published: August 2020

Abstract
Objective
COVID19 has caused a global and ongoing pandemic. The need for population seroconversion data is apparent to monitor and respond to the pandemic. Using a lateral flow assay (LFA) testing platform, the seropositivity in 63 New York Blood Center (NYBC) Convelescent Plasma (CP) donor samples were evaluated for the presence of COVID19 specific IgG and IgM.

Results
CP donors showed diverse antibody result. Convalescent donor plasma contains SARS-CoV-2 specific antibodies. Weak antibody bands may identify low titer CP donors. LFA tests can identify antibody positive individuals that have recovered from COVID19. Confirming suspected cases using antibody detection could help inform the patient and the community as to the relative risk to future exposure and a better understanding of disease exposure.
Genome-wide methylation patterns predict clinical benefit of immunotherapy in lung cancer
Authors: Kim Jeong Yeon , Choi Jung Kyoon , Jung Hyunchul 
Published: August 2020

Abstract
Background
It is crucial to unravel molecular determinants of responses to immune checkpoint blockade (ICB) therapy because only a small subset of advanced non-small cell lung cancer (NSCLC) patients responds to ICB therapy. Previous studies were concentrated on genomic and transcriptomic markers (e.g., mutation burden and immune gene expression). However, these markers are not sufficient to accurately predict a response to ICB therapy.

Results
Here, we analyzed DNA methylomes of 141 advanced NSCLC samples subjected to ICB therapy (i.e., anti-programmed death-1) from two independent cohorts (60 and 81 patients from our and IDIBELL cohorts). Integrative analysis of patients with matched transcriptome data in our cohort (n = 28) at pathway level revealed significant overlaps between promoter hypermethylation and transcriptional repression in nonresponders relative to responders. Fifteen immune-related pathways, including interferon signaling, were identified to be enriched for both hypermethylation and repression. We built a reliable prognostic risk model based on eight genes using LASSO model and successfully validated the model in independent cohorts. Furthermore, we found 30 survival-associated molecular interaction networks, in which two or three hypermethylated genes showed significant mutual exclusion across nonresponders.

Conclusions
Our study demonstrates that methylation patterns can provide insight into molecular determinants underlying the clinical benefit of ICB therapy.
Mouse CD146+ muscle interstitial progenitor cells differ from satellite cells and present myogenic potential
Authors: Mierzejewski Bartosz , Grabowska Iwona , Jackowski Daniel , Irhashava Aliksandra , Michalska Zuzanna , Stremińska Władysława , Jańczyk-Ilach Katarzyna , Ciemerych Maria Anna , Brzoska Edyta 
Published: August 2020

AbstractBackgroundThe skeletal muscle regeneration relays on the satellite cells which are stem cells located between basal lamina and plasmalemma of muscle fiber. In the injured muscles, the satellite cells become activated, start to proliferate, and then differentiate into myoblasts, which fuse to form myotubes and finally myofibers. The satellite cells play the crucial role in the regeneration; however, other cells present in the muscle could also support this process. In the present study, we focused on one population of such cells, i.e., muscle interstitial progenitor cells.MethodsWe used the CD146 marker to identify the population of mouse muscle interstitial cells. We analyzed the expression of selected markers, as well as clonogenic, myogenic, adipogenic, and chondrogenic potential in vitro. Simultaneously, we analyzed satellite cell-derived myoblasts and bone marrow-derived mesenchymal stem/stromal cells that allowed us to pinpoint the differences between these cell populations. Moreover, we isolated CD146+ cells and performed heterotopic transplantations to follow their in vivo differentiation.ResultsMouse muscle CD146+ interstitial progenitor cells expressed nestin and NG2 but not PAX7. These cells presented clonogenic and myogenic potential both in vitro and in vivo. CD146+ cells fused also with myoblasts in co-cultures in vitro. However, they were not able to differentiate to chondro- or adipocytes in vitro. Moreover, CD146+ cells followed myogenic differentiation in vivo after heterotopic transplantation.ConclusionMouse CD146+ cells represent the population of mouse muscle interstitial progenitors that differ from satellite cell-derived myoblasts and have clonogenic and myogenic properties.