bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does the Source of Mesenchymal Stem Cell Have an Effect in the Management of Osteoarthritis of the Knee? Meta-Analysis of Randomized Controlled Trials
Authors: Jeyaraman Madhan , Muthu Sathish , Ganie Parvez Ahmad 
Published: August 2020

Study Design Meta-analysis. Objectives To compare the efficacy and safety of bone marrow(BM)–derived mesenchymal stem cell(MSCs) and adipose-derived(AD) MSCs in the management of osteoarthritis of knee from randomized controlled trials(RCTs) available in the literature. Materials and Methods We conducted electronic database searche from PubMed, Embase, and Cochrane Library till May 2020 for RCTs analyzing the efficacy and safety of MSCs in management of osteoarthritis of knee. Visual Analog Score(VAS) for Pain, Western Ontario McMaster Universities Osteoarthritis Index(WOMAC), Lysholm Knee Scale(Lysholm), Whole-Organ Magnetic Resonance Imaging Score(WORMS), Knee Osteoarthritis Outcome Score(KOOS), and adverse events were the outcomes analyzed. Analysis was performed in R platform using OpenMeta[Analyst] software. Results Nineteen studies involving 811 patients were included for analysis. None of the studies compared the source of MSCs for osteoarthritis of knee and results were obtained by pooled data analysis of both sources. At 6 months, AD-MSCs showed significantly better VAS( P<0.001, P=0.069) and WOMAC( P=0.134, P=0.441) improvement than BM-MSCs, respectively, compared to controls. At 1 year, AD-MSCs outperformed BM-MSCs compared to their control in measures like WOMAC( P=0.007, P=0.150), KOOS( P<0.001; P=0.658), and WORMS( P<0.001, P=0.041), respectively. Similarly at 24 months, AD-MSCs showed significantly better Lysholm score( P=0.037) than BM-MSCs( P=0.807) although VAS improvement was better with BM-MSCs at 24 months( P<0.001). There were no significant adverse events with either of the MSCs compared to their controls. Conclusion Our analysis establishes the efficacy, safety, and superiority of AD-MSC transplantation, compared to BM-MSC, in the management of osteoarthritis of knee from available literature. Further RCTs are needed to evaluate them together with standardized doses.
Can adjuncts to bowel preparation for colonoscopy improve patient experience and result in superior bowel cleanliness? A systematic review and meta‐analysis
Authors: Kamran Umair , Abbasi Abdullah , Tahir Imran , Hodson James , Siau Keith 
Published: August 2020

BackgroundBowel preparation for colonoscopy is often poorly tolerated due to poor palatability and adverse effects. This can negatively impact on the patient experience and on the quality of bowel preparation. This systematic review and meta‐analysis was carried out to assess whether adjuncts to bowel preparation affected palatability, tolerability and quality of bowel preparation (bowel cleanliness).MethodsA systematic search strategy was conducted on PubMed, MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to identify studies evaluating adjunct use for colonoscopic bowel preparation. Studies comparing different regimens and volumes were excluded. Specific outcomes studied included palatability (taste), willingness to repeat bowel preparation, gastrointestinal adverse events and the quality of bowel preparation. Data across studies were pooled using a random‐effects model and heterogeneity assessed using I 2 ‐statistics.ResultsOf 467 studies screened, six were included for analysis (all single‐blind randomised trials; n  = 1187 patients). Adjuncts comprised citrus reticulata peel, orange juice, menthol candy drops, simethicone, Coke Zero and sugar‐free chewing gum. Overall, adjunct use was associated with improved palatability (mean difference 0.62, 95% confidence interval 0.29–0.96, p  < 0.001) on a scale of 0–5, acceptability of taste (odds ratio 2.75, 95% confidence interval: 1.52–4.95, p  < 0.001) and willingness to repeat bowel preparation (odds ratio 2.92, 95% confidence interval: 1.97–4.35, p  < 0.001). Patients in the adjunct group reported lower rates of bloating (odds ratio 0.48, 95% confidence interval: 0.29–0.77, p  = 0.003) and vomiting (odds ratio 0.47, 95% confidence interval 0.27–0.81, p  = 0.007), but no difference in nausea (p  = 0.10) or abdominal pain (p  = 0.62). Adjunct use resulted in superior bowel cleanliness (odds ratio 2.52, 95% confidence interval: 1.31–4.85, p  = 0.006). Heterogeneity varied across outcomes, ranging from 0% (vomiting) to 81% (palatability), without evidence of publication bias. The overall quality of evidence was rated moderate.ConclusionIn this meta‐analysis, the use of adjuncts was associated with better palatability, less vomiting and bloating, willingness to repeat bowel preparation and superior quality of bowel preparation. The addition of adjuncts to bowel preparation may improve outcomes of colonoscopy and the overall patient experience.
Use of increasing the number of biopsy cores in proportion to prostate size on prostate cancer diagnosis
Authors: Morokuma Futoshi , Sadashima Eiji , Chikamatsu Soutaro , Nakamura Tomoya , Hayakawa Yusuke , Tokuda Noriaki 
Published: August 2020

Objectives: This study aimed to determine the value of changing the number of biopsy cores in proportion to the size of the prostate in patients who had initial transperineal prostate biopsies. Materials and methods: This study included 470 patients who underwent an initial transperineal prostate biopsy. The number of biopsy cores was changed according to the value of the product of the vertical and horizontal diameters of the largest horizontal section of the prostate on transrectal ultrasonography (TRUS). Biopsies were classified into five groups: 12 cores, 14 cores, 18 cores, 20 cores, and 24 cores. Predictive factors for positive biopsy were studied with logistic regression analyses. Results: Variables that were significantly associated with positive biopsy were age, prostate-specific antigen density (PSAD), prostate volume (Pvol), and number of biopsy cores in univariate analysis. Age, PSAD, and Pvol were independent predictors in multivariate analysis. There was no significant difference in the number of biopsy cores, and it was not an independent predictor. Conclusions: Changing the number of biopsy cores according to the area of the largest horizontal section of the prostate on TRUS had no significant impact in detecting prostate cancer. However, further research is required to confirm this conclusion. Level of evidence: Level 2b.
Cell-specific expression of ENACα gene by FOXA1 in the glucocorticoid receptor pathway
Authors: Chung Young Sun , Jin Hong Lan , Jeong Kwang Won 
Published: August 2020

Introduction: The glucocorticoid receptor (GR) is one of the most widely studied ligand-dependent nuclear receptors. The combination of transcriptional regulatory factors required for the expression of individual genes targeted by GR varies across cell types; however, the mechanisms underlying this cell type–specific regulation of gene expression are not yet clear. Methods: Here, we investigated genes regulated by GR in two different cell lines, A549 and ARPE-19, and examined how gene expression varied according to the effect of pioneer factors using RNA-seq and RT-qPCR. Results: Our RNA-seq results identified 19 and 63 genes regulated by GR that are ARPE-19-specific and A549-specific, respectively, suggesting that GR induces the expression of different sets of genes in a cell type–specific manner. RT-qPCR confirmed that the epithelial sodium channel ( ENACα) gene is an ARPE-19 cell-specific GR target gene, whereas the FK506 binding protein 5 ( FKBP5) gene was A549 cell-specific. There was a significant decrease in ENACα expression in FOXA1-deficient ARPE-19 cells, suggesting that FOXA1 might function as a pioneer factor enabling the selective expression of ENACα in ARPE-19 cells but not in A549 cells. Conclusion: These findings indicate that ENACα expression in ARPE-19 cells is regulated by FOXA1 and provide insights into the molecular mechanisms of cell type–specific expression of GR-regulated genes.
LncRNA ADAMTS9-AS2 in osteosarcoma inhibits cell proliferation and enhances paclitaxel sensitivity by suppressing microRNA-130a-5p
Authors: Ren Xiaoqiang , Cai Jingwei , Wang Yongheng , Zhu Xingren , Qian Jun , Han Cailing , Chen Xiaohui 
Published: August 2020

Introduction: Long noncoding RNA ADAMTS9-AS2 (lncRNA ADAMTS9-AS2) has critical function in tumor growth and drug resistance of various cancers. However, the role and mechanism of lncRNA ADAMTS9-AS2 in osteosarcoma (OS) is still unclear. Methods: The expression of lncRNA ADAMTS9-AS2 and MicroRNAs-130a-5p (miR-130a-5p) was detected by real-time polymerase chain reaction (RT-qPCR) experiment. In addition, we used the plasmids transfection to construct the lncRNA ADAMTS9-AS2 overexpressed OS cell lines. Subsequently, the cell proliferation ability and the sensitivity to paclitaxel (PTX) in OS cells upon up-regulating lncRNA ADAMTS9-AS2 expression were analyzed via CCK-8 assay, while Western blotting experiment was performed to detect the regulatory mechanism. Results: We found that lncRNA ADAMTS9-AS2 was down-regulated in OS tissues, and the OS patients with lncRNA ADAMTS9-AS2 downexprssion were usually accompanied with a poor prognosis. Subsequently, we discovered that up-regulation of lncRNA ADAMTS9-AS2 inhibited cell proliferation and increased the sensitivity to PTX in OS cells. Interestingly, the Western blot results showed that overexpression of lncRNA ADAMTS9-AS2 could lead to PTEN expression increased, with PI3K and p-AKT expression decreased, indicating that lncRNA ADAMTS9-AS2 could increase the OS cell sensitivity to PTX via regulating PTEN-PI3K/AKT pathway. Furthermore, we identified MicroRNAs-130a-5p (miR-130a-5p) as the downstream target gene of lncRNA ADAMTS9-AS2, which was further confirmed by the luciferase reporter assay. More importantly, our data revealed that miR-130a-5p mimics could partly reverse the influence on cell proliferation and drug sensitivity induced by lncRNA ADAMTS9-AS2 overexpression. Conclusion: LncRNA ADAMTS9-AS2 exerts its anti-carcinogenesis function by sponging miR-130a-5p, which might be a new therapeutic target for OS treatment.
Arthroscopic Suture Fixation With Autograft Augmentation Reconstruction for Delayed Tibial Avulsion Fractures of the Posterior Cruciate Ligament
Authors: Bi Mingguang , Zhao Chen , Chen Jihang , Hong Zheping , Wang Zhen , Gan Kaifeng , Tong Yu , Bi Qing 
Published: August 2020

Background: The optimal surgical treatment of delayed avulsion fractures of the posterior cruciate ligament (PCL) is still controversial. Purpose: To evaluate the clinical results of arthroscopic suture fixation of tibial avulsion fractures of the PCL with autograft augmentation reconstruction. Study Design: Case series; Level of evidence, 4. Methods: From January 2013 to February 2017, we treated 15 patients with delayed tibial avulsion fractures of the PCL arthroscopically through posteromedial and posterolateral portals. The PCL and avulsion bone fragment were fixed with No. 2 nonabsorbable FiberWire sutures that were pulled out through a single tibial bone tunnel and fixed on a small Endobutton. Concomitantly, anatomic PCL augmentation reconstruction was performed, and the graft was pulled out through the same tunnel and fixed with an interference screw. Knee stability was assessed using the posterior drawer test, and the side-to-side difference was determined using a KT-1000 arthrometer with 134 N of posterior force at 30° of knee flexion. The International Knee Documentation Committee (IKDC) 2000 subjective form and Lysholm scale were used to evaluate clinical outcomes at follow-up. Overall, 12 patients were enrolled for analysis. The mean follow-up period was 34.4 months (range, 26-49 months). Results: At the final follow-up, 2 patients encountered 10° terminal flexion limitations. All patients had negative posterior drawer test results. The KT-1000 arthrometer side-to-side difference was significantly decreased from 8.25 ± 1.96 mm preoperatively to 1.08 ± 0.86 mm at the last follow-up ( P < .001). The mean IKDC and Lysholm scores, respectively, increased from 54.67 ± 7.13 and 53.50 ± 7.90 preoperatively to 91.13 ± 3.78 and 94.25 ± 3.32 at the final follow-up ( P < .001 for both). Conclusion: Arthroscopic suture fixation with autograft augmentation reconstruction for delayed tibial avulsion fractures of the PCL showed good clinical stability and function in this study.
Exposure of plasminogen and a novel plasminogen receptor, Plg-RKT, on activated human and murine platelets
Authors: Whyte Claire S. , Morrow Gael B. , Baik Nagyung , Booth Nuala A. , Jalal Mohammed M. , Parmer Robert J. , Miles Lindsey A. , Mutch Nicola J. 
Published: August 2020

Abstract
Plasminogen activation rates are enhanced by cell surface binding. We previously demonstrated that exogenous plasminogen binds to phosphatidylserine-exposing and spread platelets. Platelets contain plasminogen in their α-granules, but secretion of plasminogen from platelets has not been studied. Recently, a novel transmembrane lysine-dependent plasminogen receptor, Plg-RKT, has been described on macrophages. Here, we analyzed the pool of plasminogen in platelets and examined whether platelets express Plg-RKT. Plasminogen content of the supernatant of resting and collagen/thrombin-stimulated platelets was similar. Pretreatment with the lysine analog, ε-aminocaproic acid, significantly increased platelet-derived plasminogen (0.33 vs 0.08 nmol/108 platelets) in the stimulated supernatant, indicating a lysine-dependent mechanism of membrane retention. Lysine-dependent, platelet-derived plasminogen retention on thrombin and convulxin activated human platelets was confirmed by flow cytometry. Platelets initiated fibrinolytic activity in fluorescently labeled plasminogen-deficient clots and in turbidimetric clot lysis assays. A 17-kDa band, consistent with Plg-RKT, was detected in the platelet membrane fraction by western blotting. Confocal microscopy of stimulated platelets revealed Plg-RKT colocalized with platelet-derived plasminogen on the activated platelet membrane. Plasminogen exposure was significantly attenuated in thrombin- and convulxin-stimulated platelets from Plg-RKT−/− mice compared with Plg-RKT+/+ littermates. Membrane exposure of Plg-RKT was not dependent on plasminogen, as similar levels of the receptor were detected in plasminogen−/− platelets. These data highlight Plg-RKT as a novel plasminogen receptor in human and murine platelets. We show for the first time that platelet-derived plasminogen is retained on the activated platelet membrane and drives local fibrinolysis by enhancing cell surface–mediated plasminogen activation.
Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents
Authors: Roeker Lindsey E. , Dreger Peter , Brown Jennifer R. , Lahoud Oscar B. , Eyre Toby A. , Brander Danielle M. , Skarbnik Alan , Coombs Catherine C. , Kim Haesook T. , Davids Matthew , Manchini Steven T. , George Gemlyn , Shah Nirav , Voorhees Timothy J. , Orchard Kim H. , Walter Harriet S. , Arumainathan Arvind K. , Sitlinger Andrea , Park Jae H. , Geyer Mark B. , Zelenetz Andrew D. , Sauter Craig S. , Giralt Sergio A. , Perales Miguel-Angel , Mato Anthony R. 
Published: August 2020

AbstractAlthough novel agents (NAs) have improved outcomes for patients with chronic lymphocytic leukemia (CLL), a subset will progress through all available NAs. Understanding outcomes for potentially curative modalities including allogeneic hematopoietic stem cell transplantation (alloHCT) following NA therapy is critical while devising treatment sequences aimed at long-term disease control. In this multicenter, retrospective cohort study, we examined 65 patients with CLL who underwent alloHCT following exposure to ≥1 NA, including baseline disease and transplant characteristics, treatment preceding alloHCT, transplant outcomes, treatment following alloHCT, and survival outcomes. Univariable and multivariable analyses evaluated associations between pre-alloHCT factors and progression-free survival (PFS). Twenty-four-month PFS, overall survival (OS), nonrelapse mortality, and relapse incidence were 63%, 81%, 13%, and 27% among patients transplanted for CLL. Day +100 cumulative incidence of grade III-IV acute graft-vs-host disease (GVHD) was 24%; moderate-severe GVHD developed in 27%. Poor-risk disease characteristics, prior NA exposure, complete vs partial remission, and transplant characteristics were not independently associated with PFS. Hematopoietic cell transplantation–specific comorbidity index independently predicts PFS. PFS and OS were not impacted by having received NAs vs both NAs and chemoimmunotherapy, 1 vs ≥2 NAs, or ibrutinib vs venetoclax as the line of therapy immediately pre-alloHCT. AlloHCT remains a viable long-term disease control strategy that overcomes adverse CLL characteristics. Prior NAs do not appear to impact the safety of alloHCT, and survival outcomes are similar regardless of number of NAs received, prior chemoimmunotherapy exposure, or NA immediately preceding alloHCT. Decisions about proceeding to alloHCT should consider comorbidities and anticipated response to remaining therapeutic options.
Human NK cells prime inflammatory DC precursors to induce Tc17 differentiation
Authors: Clavijo-Salomon Maria A. , Salcedo Rosalba , Roy Soumen , das Neves Rodrigo X. , Dzutsev Amiran , Sales-Campos Helioswilton , Borbely Karen Steponavicius-Cruz , Silla Lucia , Orange Jordan S. , Mace Emily M. , Barbuto José A. M. , Trinchieri Giorgio 
Published: August 2020

AbstractAdaptive immune responses are acknowledged to evolve from innate immunity. However, limited information exists regarding whether encounters between innate cells direct the generation of specialized T-cell subsets. We aim to understand how natural killer (NK) cells modulate cell-mediated immunity in humans. We found that human CD14+CD16− monocytes that differentiate into inflammatory dendritic cells (DCs) are shaped at the early stages of differentiation by cell-to-cell interactions with NK cells. Although a fraction of monocytes is eliminated by NK-cell–mediated cytotoxicity, the polarization of interferon-γ (IFN-γ) at the NKp30-stabilized synapses triggers a stable IFN-γ signature in surviving monocytes that persists after their differentiation into DCs. Notably, NK-cell–instructed DCs drive the priming of type 17 CD8+ T cells (Tc17) with the capacity to produce IFN-γ and interleukin-17A. Compared with healthy donors, this cellular network is impaired in patients with classical NK-cell deficiency driven by mutations in the GATA2 gene. Our findings reveal a previously unrecognized connection by which Tc17-mediated immunity might be regulated by NK-cell–mediated tuning of antigen-presenting cells.
Characterisation of pulmonary function trajectories: results from a Brazilian cohort
Authors: Weber Priscila , Menezes Ana Maria Baptista , Gonçalves Helen , Perez-Padilla Rogelio , Jarvis Deborah , de Oliveira Paula Duarte , Wehrmeister Fernando César 
Published: August 2020

BackgroundPulmonary function (PF) trajectories are determined by different exposures throughout the life course. The aim of this study was to investigate characteristics related to PF trajectories from 15 to 22 years in a Brazilian cohort.MethodsA birth cohort study (1993 Pelotas Birth Cohort) was conducted with spirometry at 15, 18 and 22 years. PF trajectories were built based on z-score of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio using a group-based trajectory model. Associations with exposures reported from perinatal to 22 years were described.ResultsThree trajectories, low (LT), average (AT) and high (HT) were identified in 2917 individuals. Wealthiest individuals belonged to the HT of FEV1(p=0.023). Lower maternal pregestational body mass index (BMI) (22.4±0.2; p<0.001 and 22.1±0.14; p<0.001) and lower birth weight (3164.8±25.4; p=0.029 and 3132.3±19.4; p=0.005) were related to the LT of FEV1and FVC. Mother's smoking exposure during pregnancy (37.7%; p=0.002), active smoking at ages 18 and 22 years (20.1% and 25.8%; p<0.001) and family history of asthma (44.8%; p<0.001) were related to the LT of FEV1/FVC. Wheezing, asthma and hospitalisations due to respiratory diseases in childhood were related to the LT of both FEV1and FEV1/FVC. Higher BMIs were related to the HT of FEV1and FVC at all ages.ConclusionsPF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.
OscoNet: inferring oscillatory gene networks
Authors: Cutillo Luisa , Boukouvalas Alexis , Marinopoulou Elli , Papalopulu Nancy , Rattray Magnus 
Published: August 2020

Abstract
Background
Oscillatory genes, with periodic expression at the mRNA and/or protein level, have been shown to play a pivotal role in many biological contexts. However, with the exception of the circadian clock and cell cycle, only a few such genes are known. Detecting oscillatory genes from snapshot single-cell experiments is a challenging task due to the lack of time information. Oscope is a recently proposed method to identify co-oscillatory gene pairs using single-cell RNA-seq data. Although promising, the current implementation of Oscope does not provide a principled statistical criterion for selecting oscillatory genes.

Results
We improve the optimisation scheme underlying Oscope and provide a well-calibrated non-parametric hypothesis test to select oscillatory genes at a given FDR threshold. We evaluate performance on synthetic data and three real datasets and show that our approach is more sensitive than the original Oscope formulation, discovering larger sets of known oscillators while avoiding the need for less interpretable thresholds. We also describe how our proposed pseudo-time estimation method is more accurate in recovering the true cell order for each gene cluster while requiring substantially less computation time than the extended nearest insertion approach.

Conclusions
OscoNet is a robust and versatile approach to detect oscillatory gene networks from snapshot single-cell data addressing many of the limitations of the original Oscope method.