bluuebunny/crossref_metadata_2025 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

Background

Bowel 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).

Methods

A 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.

Results

Of 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.

Conclusion

In 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.
No Influence of Musicianship on the Effect of Contralateral Stimulation on Frequency Selectivity
Authors: Tarnowska Emilia , Wicher Andrzej , Moore Brian C. J.
Published: August 2020

The efferent system may control the gain of the cochlea and thereby influence frequency selectivity. This effect can be assessed using contralateral stimulation (CS) applied to the ear opposite to that used to assess frequency selectivity. The effect of CS may be stronger for musicians than for nonmusicians. To assess whether this was the case, psychophysical tuning curves (PTCs) were compared for 12 musicians and 12 nonmusicians. The PTCs were measured with and without a 60-dB sound pressure level (SPL) pink-noise CS, using signal frequencies of 2 and 4 kHz. The sharpness of the PTCs was quantified using the measure Q10, the signal frequency divided by the PTC bandwidth measured 10 dB above the level at the tip. Q10 values were lower in the presence of the CS, but this effect did not differ significantly for musicians and nonmusicians. The main effect of group (musicians vs. nonmusicians) on the Q10 values was not significant. Overall, these results do not support the idea that musicianship enhances contralateral efferent gain control as measured using the effect of CS on PTCs.
Development Signs in Healthy Toddlers in Different Stages of Toilet Training: Can They Help Define Readiness and Probability of Success?
Authors: Wyndaele Jean-Jacques , Kaerts Nore , Wyndaele Michel , Vermandel Alexandra
Published: August 2020

There is much uncertainty about when to start toilet training. Age cannot be a strict stand-alone criterion, as every child has its own pace of development. We observed toilet training (TT) related development signs (DS) in healthy toddlers and determined which can help to define the proper time to start TT and to predict success. The study group consisted of 269 healthy children, in different stages of TT: not started, during, and after completion. Sitting stable, picking up small objects, and spontaneously putting objects in containers were present in all children and had no predictive value. All other DS were significantly more present in those who had started and became more prevalent during completion of TT. Age had a significant association with 13/15 DS. Understanding and following instructions, and having a broader vocabulary were significantly more present when TT had been started. Dry during midday nap reached no significance.
Exploring the relationship between spatial morphology characteristics and scenic beauty preference of landscape open space unit by using point cloud data
Authors: Wang Yijing , Zlatanova Sisi , Yan Jinjin , Huang Ziqiao , Cheng Yuning
Published: August 2020

To explore the relationship between the objective morphological features and subjective scenic beauty preference of landscape open space units, this study improves the research method for morphology quantification, scenic beauty preference survey and relationship analysis. Fourteen morphology factors representing the features of boundary, domain and enclosure are quantified based on the point cloud data of 35 open space units. Scenic beauty evaluation is conducted online with dynamic panoramic photos. Principal component analysis is implemented to convert 14 correlated form factors into five principal components representing morphological principle. The multiple linear regression model explains the contribution of each principal component to scenic beauty preference values, showing a significance sequence of penetration, scale, naturalness, complexity and rhythm. The first three principal components have positive impacts on scenic beauty preference, while the last two principal components are negative. This work aims to reveal the regularity of public’s scenic beauty preference for open space morphology.
Hvalur hf: Commercial Hunter of Whales!
Authors: Ahmed Jashim Uddin , Faroque Anisur R. , Ahmed Asma , Anika Farzana Haque , Mamun Hasan A.
Published: August 2020

This case study is based on the only Icelandic commercial whaling (whale hunting) company, Hvalur hf. The majority of the meat from whale hunting is exported to Japan because consumption of whale meat is insignificant amongst the locals in Iceland. This case reflects on the challenges and controversies of Hvalur hf. It further focuses on the personality of Kristján Loftsson, CEO of Hvalur hf. Commercial whaling has been a major concern against Iceland. European Union has offered union membership to Iceland in order to stop the cruelty caused by whaling. The tourism sector of Iceland is hence at risk as whaling and whale watching coexists. Both of these are deemed to be major contributors to the economy of Iceland.
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

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

Although 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

Adaptive 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

Background

Pulmonary 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.

Methods

A 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.

Results

Three 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.

Conclusions

PF 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

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.
Machine learning models predicting multidrug resistant urinary tract infections using “DsaaS”
Authors: Mancini Alessio , Vito Leonardo , Marcelli Elisa , Piangerelli Marco , De Leone Renato , Pucciarelli Sandra , Merelli Emanuela
Published: August 2020

Background

The scope of this work is to build a Machine Learning model able to predict patients risk to contract a multidrug resistant urinary tract infection (MDR UTI) after hospitalization. To achieve this goal, we used different popular Machine Learning tools. Moreover, we integrated an easy-to-use cloud platform, called DSaaS (Data Science as a Service), well suited for hospital structures, where healthcare operators might not have specific competences in using programming languages but still, they do need to analyze data as a continuous process. Moreover, DSaaS allows the validation of data analysis models based on supervised Machine Learning regression and classification algorithms.

Results

We used DSaaS on a real antibiotic stewardship dataset to make predictions about antibiotic resistance in the Clinical Pathology Operative Unit of the Principe di Piemonte Hospital in Senigallia, Marche, Italy. Data related to a total of 1486 hospitalized patients with nosocomial urinary tract infection (UTI). Sex, age, age class, ward and time period, were used to predict the onset of a MDR UTI. Machine Learning methods such as Catboost, Support Vector Machine and Neural Networks were utilized to build predictive models. Among the performance evaluators, already implemented in DSaaS, we used accuracy (ACC), area under receiver operating characteristic curve (AUC-ROC), area under Precision-Recall curve (AUC-PRC), F1 score, sensitivity (SEN), specificity and Matthews correlation coefficient (MCC). Catboost exhibited the best predictive results (MCC 0.909; SEN 0.904; F1 score 0.809; AUC-PRC 0.853, AUC-ROC 0.739; ACC 0.717) with the highest value in every metric.

Conclusions

the predictive model built with DSaaS may serve as a useful support tool for physicians treating hospitalized patients with a high risk to acquire MDR UTIs. We obtained these results using only five easy and fast predictors accessible for each patient hospitalization. In future, DSaaS will be enriched with more features like unsupervised Machine Learning techniques, streaming data analysis, distributed calculation and big data storage and management to allow researchers to perform a complete data analysis pipeline. The DSaaS prototype is available as a demo at the following address: https://dsaas-demo.shinyapps.io/Server/
Data integration by fuzzy similarity-based hierarchical clustering
Authors: Ciaramella Angelo , Nardone Davide , Staiano Antonino
Published: August 2020

Background

High throughput methods, in biological and biomedical fields, acquire a large number of molecular parameters or omics data by a single experiment. Combining these omics data can significantly increase the capability for recovering fine-tuned structures or reducing the effects of experimental and biological noise in data.

Results

In this work we propose a multi-view integration methodology (named FH-Clust) for identifying patient subgroups from different omics information (e.g., Gene Expression, Mirna Expression, Methylation). In particular, hierarchical structures of patient data are obtained in each omic (or view) and finally their topologies are merged by consensus matrix. One of the main aspects of this methodology, is the use of a measure of dissimilarity between sets of observations, by using an appropriate metric. For each view, a dendrogram is obtained by using a hierarchical clustering based on a fuzzy equivalence relation with Łukasiewicz valued fuzzy similarity. Finally, a consensus matrix, that is a representative information of all dendrograms, is formed by combining multiple hierarchical agglomerations by an approach based on transitive consensus matrix construction. Several experiments and comparisons are made on real data (e.g., Glioblastoma, Prostate Cancer) to assess the proposed approach.

Conclusions

Fuzzy logic allows us to introduce more flexible data agglomeration techniques. From the analysis of scientific literature, it appears to be the first time that a model based on fuzzy logic is used for the agglomeration of multi-omic data. The results suggest that FH-Clust provides better prognostic value and clinical significance compared to the analysis of single-omic data alone and it is very competitive with respect to other techniques from literature.
Transcriptome analysis provides new insights into the transcriptional regulation of methyl jasmonate-induced flavonoid biosynthesis in pear calli
Authors: Premathilake Apekshika T. , Ni Junbei , Shen Jiaqi , Bai Songling , Teng Yuanwen
Published: August 2020

Background

Flavonoid biosynthesis is strongly influenced by phytohormones. For example, methyl jasmonate (MeJA) enhances the flavonoid accumulation in pear. However, the molecular mechanism underlying the MeJA-induced flavonoid biosynthesis in pear is largely uncharacterized. Therefore, the transcriptome of pear calli treated with MeJA was analyzed to elucidate the mechanism regulating MeJA-mediated flavonoid biosynthesis.

Results

The application of exogenous MeJA significantly enhanced flavonoid accumulation, especially anthocyanin, in pear calli. A weighted gene co-expression network analysis identified the differentially expressed genes associated with MeJA-induced flavonoid biosynthesis. The MeJA treatment upregulated the expression of the flavonoid biosynthesis pathway structural genes (PcCHS, PcCHI, PcF3H, PcDFR, PcANS, PcANR2a, and PcLAR1). The MYB family members were the main transcription factors regulating the MeJA-induced flavonoid biosynthesis, but the bHLH, AP2-EREBP, NAC, WRKY, and TIFY families were also involved. In addition to PcMYB10, which is a known positive regulator of anthocyanin biosynthesis in pear, several novel MYB candidates that may regulate flavonol and proanthocyanidin biosynthesis were revealed. Yeast two-hybrid and bimolecular fluorescence complementation assays demonstrated that PcMYB10 and PcMYC2 can directly interact with each other and bind to JAZ repressors (PcJAZ1 and PcJAZ2).

Conclusions

The PcMYB10–PcMYC2 molecular complex is likely involved in the regulation of jasmonate-mediated flavonoid biosynthesis at the transcript level. The data generated in this study may clarify the transcriptional regulatory network associated with the MeJA-induced flavonoid accumulation in pear calli and provide a solid foundation for future studies.
A systematic review and meta-analysis comparing the effect of aquatic and land exercise on dynamic balance in older adults
Authors: Kim Youngwook , Vakula Michael N. , Waller Benjamin , Bressel Eadric
Published: August 2020

Background

Balance impairments are the leading causes of falls in older adults. Aquatic-based exercises have been broadly practiced as an alternative to land-based exercises; however, the effects on dynamic balance have not been comprehensively reviewed and compared to land exercises. Thus, the purpose of this systematic review and meta-analysis was to compare the effectiveness of aquatic exercises (AE) to land exercises (LE) on dynamic balance in older adults.

Methods

Electronic databases (PubMed, MEDLINE, CINAHL, SPORTDiscus, psycINFO), from inception to November 2019, were searched. Studies met the following eligibility criteria: Randomized controlled trials, English language, older adults aged 65 years or older, a minimum of one AE and LE group, at least one assessment for dynamic balance. For the meta-analysis, the effect sizes of dynamic balance outcomes were calculated using a standardized mean difference (SMD) and a 95% confidence interval (CI).

Results

A total of 11 trials met the inclusion criteria, and 10 studies were eligible for the meta-analysis. The meta-analysis presented that older adults in AE groups demonstrated comparable enhancements in dynamic steady-state balance (SMD = − 0.24; 95% CI, −.81 to .34), proactive balance (SMD = − 0.21; 95% CI, −.59 to .17), and balance test batteries (SMD = − 0.24; 95% CI, −.50 to .03) compared with those in LE groups.

Conclusions

AE and LE have comparable impacts on dynamic balance in older adults aged 65 years or older. Thus, this review provides evidence that AE can be utilized as a reasonable alternative to LE to improve dynamic balance and possibly reduce the risk of falls.
Can broad-spectrum multinutrients treat symptoms of antenatal depression and anxiety and improve infant development? Study protocol of a double blind, randomized, controlled trial (the ‘NUTRIMUM’ trial)
Authors: Bradley Hayley A. , Campbell Siobhan A. , Mulder Roger T. , Henderson Jaqueline M. T. , Dixon Lesley , Boden Joseph M. , Rucklidge Julia J.
Published: August 2020

Background

Untreated antenatal depression and anxiety can be associated with short and long term health impacts on the pregnant woman, her infant and the rest of the family. Alternative interventions to those currently available are needed. This clinical trial aims to investigate the efficacy and safety of a broad-spectrum multinutrient formula as a treatment for symptoms of depression and anxiety in pregnant women and to determine the impact supplementation has on the general health and development of the infant.

Methods

This randomised, controlled trial will be conducted in Canterbury, New Zealand between April 2017 and June 2022. One hundred and twenty women aged over 16 years, between 12 and 24 weeks gestation and who score ≥ 13 on the Edinburgh Postnatal Depression Scale (EPDS) will be randomly assigned to take the intervention (n = 60) or an active control formula containing iodine and riboflavin (n = 60) for 12 weeks. After 12 weeks, participants can enter an open-label phase until the birth of their infant and naturalistically followed for the first 12 months postpartum. Infants will be followed until 12 months of age. Randomisation will be computer-generated, with allocation concealment by opaque sequentially numbered envelopes. Participants and the research team including data analysts will be blinded to group assignment. The EPDS and the Clinical Global Impressions Scale of Improvement (CGI-I) will be the maternal primary outcome measures of this study and will assess the incidence of depression and anxiety and the improvement of symptomatology respectively. Generalized linear mixed effects regression models will analyse statistical differences between the multinutrient and active control group on an intent-to-treat basis. A minimum of a three-point difference in EPDS scores between the groups will identify clinical significance. Pregnancy outcomes, adverse events and side effects will also be monitored and reported.

Discussion

Should the multinutrient formula be shown to be beneficial for both the mother and the infant, then an alternative treatment option that may also improve the biopsychosocial development of their infants can be provided for pregnant women experiencing symptoms of depression and anxiety.

Trial registration

Trial ID: ACTRN12617000354381; prospectively registered at Australian New Zealand Clinical Trials Registry on 08/03/2017.
Risk of mini-mental state examination (MMSE) decline in the elderly with type 2 diabetes: a Chinese community-based cohort study
Authors: Zhao Lei , Han Chao , Zheng Zheng , Xiu Shuang Ling , Chan Piu
Published: August 2020

Background

We aimed to investigate the correlation of factors involved in the change of Mini-Mental State Examination (MMSE) and type 2 diabetes in the elderly.

Methods

This study was a secondary analysis of a prospective cohort study. Type 2 diabetes patients aged > 55 years were recruited and assigned into three groups based on their glycated hemoglobin (HbA1c) levels: HbA1c < 7, 7% ≤ HbA1c < 8% and HbA1c ≥8%. MMSE decline was considered the endpoint. Factors related to MMSE decline were identified by univariate and multivariate regression analyses.

Results

Altogether, 1519 subjects were included, 883 in the Low group, 333 in the Median group, and 303 in the High group. Age ≥ 75 years, education below elementary school level, not participating in seminars or consultation on healthcare, physical activity less than 30 min/day, cerebrovascular disease history, MMSE score at baseline, and HBA1c ≥8% were associated with cognitive decline by univariate and multivariate analysis. When the other factors were adjusted for, HBA1c ≥8% was independently associated with the severity of cognitive decline (β = 0.58, 95%CI:0.06–1.11, P = 0.029) and the occurrence of cognitive decline (odds ratio (OR) = 1.55, 95%CI:1.13–2.12, P = 0.007).

Conclusions

In elderly patients with type 2 diabetes, HbA1c ≥8% is an independent factor for cognitive decline and is also associated with the severity of the cognitive decline.
Using routine health information data for research in low- and middle-income countries: a systematic review
Authors: Hung Yuen W. , Hoxha Klesta , Irwin Bridget R. , Law Michael R. , Grépin Karen A.
Published: August 2020

Background

Routine health information systems (RHISs) support resource allocation and management decisions at all levels of the health system, as well as strategy development and policy-making in many low- and middle-income countries (LMICs). Although RHIS data represent a rich source of information, such data are currently underused for research purposes, largely due to concerns over data quality. Given that substantial investments have been made in strengthening RHISs in LMICs in recent years, and that there is a growing demand for more real-time data from researchers, this systematic review builds upon the existing literature to summarize the extent to which RHIS data have been used in peer-reviewed research publications.

Methods

Using terms ‘routine health information system’, ‘health information system’, or ‘health management information system’ and a list of LMICs, four electronic peer-review literature databases were searched from inception to February 202,019: PubMed, Scopus, EMBASE, and EconLit. Articles were assessed for inclusion based on pre-determined eligibility criteria and study characteristics were extracted from included articles using a piloted data extraction form.

Results

We identified 132 studies that met our inclusion criteria, originating in 37 different countries. Overall, the majority of the studies identified were from Sub-Saharan Africa and were published within the last 5 years. Malaria and maternal health were the most commonly studied health conditions, although a number of other health conditions and health services were also explored.

Conclusions

Our study identified an increasing use of RHIS data for research purposes, with many studies applying rigorous study designs and analytic methods to advance program evaluation, monitoring and assessing services, and epidemiological studies in LMICs. RHIS data represent an underused source of data and should be made more available and further embraced by the research community in LMIC health systems.
Assessing and decomposing inequality of opportunity in access to child health and nutrition in sub-Saharan Africa: evidence from three countries with low human development index
Authors: Sanoussi Yacobou , Ahinkorah Bright Opoku , Banke-Thomas Aduragbemi , Yaya Sanni
Published: August 2020

Background

Inequality of opportunity in health and nutrition is a major public health issue in the developing regions. This study analyzed the patterns and extent of inequality of opportunity in health and nutrition among children under-five across three countries sub-Saharan Africa with low Human development index (HDI).

Methods

We used data from the Multiple Indicator Cluster Survey of the Democratic Republic of Congo (20,792 households, 21,756 women aged 15 to 49 and 21,456 children under five), Guinea Bissau (6601 households, 10,234 women aged 15–49 and 7573 children under five) and Mali (11,830 households, 18,409 women in 15–49 years and 16,468 children under five) to compute the human opportunity index (HOI) and the dissimilarity index (D-index). Secondly, the Shapley decomposition method was used to estimate the relative contribution of circumstances that are beyond the control of children under-five and affecting their development outcomes in later life stages.

Results

The study revealed that children belonging to the most favorable group had higher access rates for immunization (93.64%) and water and sanitation facilities (73.59%) in Guinea Bissau. In Congo DR, the access rate was high for immunization (93.9%) for children in the most favorable group. In Mali, access rates stood at 6.56% for children in the most favorable group. In Guinea Bissau, the inequality of opportunity was important in access to health services before and after delivery (43.85%). In Congo DR, the inequality of opportunity was only high for the immunization composite indicator (83.79%) while in Mali, inequality of opportunity was higher for access to health services before and after delivery (41.67%).

Conclusion

The results show that there are efforts in some places to promote access to health and nutrition services in order to make access equal without distinction linked to the socio-economic and demographic characteristics in which the children live. However, the inequalities of opportunity observed between the children of the most favorable group and those of the least favorable group, remain in general at significant levels and call on government of these countries to implement policies taking them into account.
Finding the optimal control level of intraoperative blood pressure in no tourniquet primary total knee arthroplasty combine with tranexamic acid: a retrospective cohort study which supports the enhanced recovery strategy
Authors: Wang Hao-Yang , Yuan Ming-cheng , Pei Fu-Xing , Zhou Zong-Ke , Liao Ren
Published: August 2020

Background

With the use of tranexamic acid and control of the blood pressure during the operation, total knee arthroplasty (TKA) without tourniquet can be achieved. There is no exact standard for the control level of blood pressure during no tourniquet TKA. We explored the optimal level of blood pressure control during no tourniquet TKA surgery with the use of tranexamic acid in this study.

Methods

Patients underwent TKA were divided into three groups: the mean intraoperative systolic blood pressure in group A was < 90 mmHg, 90–100 mmHg in group B, > 100 mmHg in group C. Total blood loss (TBL), intraoperative blood loss, hidden blood loss, transfusion rate, maximum hemoglobin drop, operation time, and postoperative hospitalization days were recorded.

Results

Two hundred seventy-eight patients were enrolled, 82 in group A, 105 in group B, and 91 in group C. Group A (663.3 ± 46.0 ml) and group B (679.9 ± 57.1 ml) had significantly lower TBL than group C (751.7 ± 56.2 ml). Group A (120.2 ± 18.7 ml) had the lowest intraoperative blood loss than groups B and C. Group C (26.0 ± 4.1 g/l) had the largest Hb change than groups A and B. Group A (62.3 ± 4.7 min) had the shortest operation time. The incidence rate of postoperative hypotension in group A (8, 9.8%) was significantly greater than groups B and C. No significant differences were found in other outcomes.

Conclusion

The systolic blood pressure from 90 to 100 mmHg was the optimal strategy for no tourniquet primary TKA with tranexamic acid.
Two rare cases of acute myeloid leukemia with t(8;16)(p11.2;p13.3) and 1q duplication: case presentation and literature review
Authors: Liu Meng , Ren Yuan , Wang Xianfu , Lu Xianglan , Li Ming , Kim Young Mi , Li Shibo , Zhang Lijun
Published: August 2020

Background

Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. The identification and understanding of chromosomal abnormalities are important for the diagnosis and management of AML patients. Compared with recurrent chromosomal translocations in AML, t(8;16)(p11.2;p13.3) can be found in any age group but is very rare and typically associated with poor prognosis.

Methods

Conventional cytogenetic studies were performed among 1,824 AML patients recorded in our oncology database over the last 20 years. Fluorescence in situ hybridization (FISH) was carried out to detect the translocation fusion. Array comparative genome hybridization (aCGH) was carried out to further characterize the duplication of chromosomes.

Results

We identified three AML patients with t(8;16)(p11.2;p13.3) by chromosome analysis. Two of the three patients, who harbored an additional 1q duplication, were detected by FISH and aCGH. aCGH characterized a 46.7 Mb and 49.9 Mb gain in chromosome 1 at band q32.1q44 separately in these two patients. One patient achieved complete remission (CR) but relapsed 3 months later. The other patient never experienced CR and died 2 years after diagnosis.

Conclusion

A 1q duplication was detected in two of three AML patients with t(8;16)(p11.2;p13.3), suggesting that 1q duplication can be a recurrent event in AML patients with t(8;16). In concert with the findings of previous studies on similar patients, our work suggests that 1q duplication may also be an unfavorable prognostic factor of the disease.