Miracle-dz/UniFAR-FTUs huggingface dataset:
The MathIOmica Toolbox: General Analysis Utilities for Dynamic Omics Datasets

MathIOmica is a package for bioinformatics, written in the Wolfram language, that provides multiple utilities to facilitate the analysis of longitudinal data generated from omics experiments, including transcriptomics, proteomics, and metabolomics data, as well as any generalized time series. MathIOmica uses Mathematica's notebook interface, wherein users can import longitudinal datasets, carry out quality control and normalization, generate time series, and classify temporal trends. MathIOmica provides spectral methods based on periodograms and autocorrelations for automatically detecting classes of temporal behavior and allowing the user to visualize collective temporal behavior, and also assess biological significance through Gene Ontology and pathway enrichment analyses. MathIOmica's time‐series classification methods address common issues including missing data and uneven sampling in measurements. As such, the software is ideally suited for the analysis of experimental data from individualized profiling of subjects, can facilitate analysis of data from the emerging field of individualized health monitoring, and can detect temporal trends that may be associated with adverse health events. In this article, we import a transcriptomics (RNA‐sequencing) dataset collected over multiple timepoints and generate time series for each transcript represented in the data. We classify the time series to identify classes of significant temporal trends (using autocorrelations). We assess statistical significance cutoffs in the classification by generating null distributions using randomly resampled time series. We then visualize the significant trends in heatmaps and assess biological significance using enrichment analyses. Finally, we visualize pathway results for statistically significant pathways of interest. © 2019 by John Wiley & Sons, Inc.
A Systematic Review and Meta-Analysis of Single-Incision Versus Multiport Laparoscopic Complete Mesocolic Excision Colectomy for Colon Cancer

Background. Our aim was to compare the emerging technique of single-incision laparoscopic surgery complete mesocolic excision (SILS CME) colectomy with the standard multiport laparoscopic CME (MPL CME) colectomy. Methods. MEDLINE (PubMed), Scopus, EMBASE, Ovid, and the Cochrane library were searched. Studies comparing the SILS CME with MPL CME in adults with colon adenocarcinoma were included. The Jadad and Newcastle Ottawa Scales were used to critically appraise the studies. The presence of statistical heterogeneity or publication bias was examined. Results. Seven studies (3 randomized) with a total number of 1344 patients were included (546 SILS CME and 798 MPL CME). No difference was found in anastomotic leakage (odds ratio [OR] = 0.79 [0.31 to 2.03]; P = .63), number of lymph nodes (weighted mean difference [WMD] = 0.85 [−0.97 to 2.66]; P = .36), hospital stay (WMD = 0.01 [−0.19 to 0.20]; P = .96), overall survival (hazard ratio [HR] = 1.19 [0.29 to 4.80]; P = .81), and disease-free survival (HR = 1.30 [0.30 to 5.61]; P = .72). Skin incision was shorter in SILS CME group (WMD = −3.02 [−3.25 to −2.80]; P < .00001) but with no difference in pain reported in postoperative day 1 (standardized mean difference [SMD] = −0.21 [−0.50 to 0.09]; P = .17) or day 2 (SMD = 0.16 [−0.52 to 0.84]; P = .64). Conclusions. SILS CME, although technically more demanding, has equivalent short- and long-term outcomes when compared with MPL CME. Potential benefits in cosmesis or postoperative pain need to be further explored by high-quality randomized controlled trials.
Reference value of 6-minute walk distance in patients with sub-acute stroke

ABSTRACT Background The 6-minute walk test (6MWT) has strong-to-moderate evidence to assess changes in walking distance for adults with neurologic conditions undergoing rehabilitation. However, the reference value of 6MWT distance according to walking ability and the cutoff value of walking independence in stroke patients in the rehabilitation unit has not been presented. Objectives To present the reference value of 6MWT distance depending on walking ability and determine the cutoff value of walking independence in stroke patients. Methods This cross-sectional observational study included 110 stroke patients admitted to the rehabilitation unit within 30 days from stroke onset. 6MWT was used to assess the walking ability at 30 days from stroke onset. Walking ability was classified using the Functional Ambulation Category (FAC). Reference value of 6MWT distance was presented for each walking ability according to FAC score. One-way analysis of variance was computed to investigate 6MWT distance according to walking ability. Receiver operating characteristic curve was used to identify the cutoff value of 6MWT for walking independence. Results 6MWT distances for each walking ability were as follows: FAC 2 was 141.8 m, FAC 3 was 224.5 m, FAC 4 was 352.6 m, and FAC 5 was 448.8 m (p < .001). Cutoff value of 6MWT for walking independence was 304 m (area under curve = 0.905, sensitivity of 0.833, specificity of 0.900). Conclusion 6MWT distance was found to be longer with better walking ability. A distance of 304 m during 6MWT might be useful for judging walking independence in stroke patients.
Return-to-Play and Rehabilitation Protocols following Cartilage Restoration Procedures of the Knee: A Systematic Review

Objective The purpose of this study is to systematically review the literature and to evaluate the reported rehabilitation protocols, return-to-play guidelines, and subsequent rates of return to play following cartilage restoration procedures in the knee. Design MEDLINE, EMBASE, and the Cochrane Library were searched according to the PRISMA guidelines to find studies on cartilage restoration procedures in the knee, including (1) microfracture (Mfx), (2) osteochondral autograft transfer (AOT), (3) osteochondral allograft implantation (OCA), and (4) autologous chondrocyte implantation (ACI). Studies were included if they reported return-to-play data or rehabilitation protocols. Results Overall, 179 studies fit our inclusion criteria, with 48 on Mfx, 34 on AOT, 54 on OCA, and 51 on ACI. The rate of return to play was reported as high as 88.2% with AOT, and as low as 77.2% following OCA, with rates of return to play at the same/higher level as high as 79.3% with AOT, and as low as 57.3% following ACI. The average reported time of return to play was as low as 4.9 months with AOT, and as high as 11.6 months following ACI. Conclusions The majority of patients are able to return to play following cartilage restoration procedures in the knee, regardless of surgical procedure utilized. However, while the rate of return to play at the same level was similar to the overall rate of return following AOT, there was a large number of patients unable to return to the same level following Mfx, OCA, and ACI. Additionally, there is wide variety in the rehabilitation protocols, and scant literature on return-to-play protocols.
Gamma-glutamyl transpeptidase-to-platelet ratio and the fibrosis-4 index in predicting hepatitis B virus-related hepatocellular carcinoma development in elderly chronic hepatitis B patients in China

Abstract Gamma-glutamyl transpeptidase-to-platelet ratio (GPR) and fibrosis-4 (FIB-4) index have been reported to be useful predictors in predicting hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients. However, their predictive performances on HCC development have not been validated in elderly patients. Thus, the aim of this study was to evaluate the predictive values of the GPR and FIB-4 index on HCC in elderly CHB patients with in China. Between January 2007 and December 2016, 1011 CHB patients older than 60 years were enrolled in the study, and their data were retrospectively analyzed. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal cutoff points of GPR and the FIB-4 index. Cumulative HCC incidence rates were calculated by the Kaplan–Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to detect risk factors for HCC development. The prediction performances of GPR and FIB-4 index were compared based on time-dependent ROC analyses. After a median follow-up of 6.8 (interquartile range 3.9–8.4) years, 39 (3.9%) patients developed HCC. The ROC analysis of GPR and the FIB-4 index at the 5-year time point revealed that the optimal cutoff point was 0.23 for GPR and 4.15 for the FIB-4 index. When stratified by low and high GPR values and FIB-4 indices, the patients’ subgroups showed significantly different cumulative incidences of HCC. The multivariate analysis revealed that high GPR (hazard ratio [HR] 4.224; 95% confidence interval [CI] 1.891–9.434, P < .001) was an independent risk factor for HCC development, whereas a high FIB-4 index was not (HR 0.470; 95% CI 0.212–1.043; P = .063). In the time-dependent ROC analysis, GPR showed higher area under curve (AUC) values than the FIB-4 index did at all time points and reached statistical significance at the 5-, 7-, and 10-year time points (GPR vs FIB-4 index, AUC 0.725 vs 0.549 at 5 years, P = .005; GPR vs FIB-4 index, AUC 0.733 vs 0.578 at 7 years, P = .001; GPR vs FIB-4 index, AUC 0.837 vs 0.475 at 10 years, P < .001). In conclusion, our study suggests GPR is superior to the FIB-4 index in predicting HCC development in elderly CHB patients in China.
Gingival crevicular fluid response to protocols of non-surgical periodontal therapy: A longitudinal evaluation

Context and Aim: Gingival crevicular fluid (GCF) volume reflects the level of periodontal inflammation. This secondary analysis aimed to evaluate the GCF volume in patients submitted to non-surgical periodontal therapies under a split-mouth design. Materials and Methods: GCF volume of 25 participants (47.24 ± 6.47 years) with moderate-to-severe chronic periodontitis was collected at Days 0, 30, 60, 90, 120, 270, and 450. The participants were submitted to three different non-surgical therapies randomly assigned per quadrant [GI: supragingival control (Supra) as only intervention (one quadrant); GII: Supra plus scaling and root planing (SRP) on Day 0 (two quadrants); GIII: Supra on Day 0 and SRP 30 days later (one quadrant)]. During treatment (0–60 days) and maintenance (90–450 days) participants were submitted to supragingival plaque control reinforcements. GCF volumes were analyzed after logarithmic transformation (log10) and linear models were used for intra- and inter-group comparisons, considering the data dependence. Results: Baseline GCF volumes were similar between groups (GI: 0.39 ± 0.22 μl; GII: 0.42 ± 0.26 μl; GIII: 0.41 ± 0.14 μl;P > 0.05). At Day 60, GCF volumes were significantly reduced (GI: 0.20 ± 0.13 μl; GII: 0.18 ± 0.11 μl; GIII: 0.22 ± 0.13 μl; P < 0.001), without inter-groups differences. These results were maintained along maintenance period (P > 0.05). Even in sites bleeding on probing (BOP) + the means of GCF volume did not differ between groups (P > 0.05). Conclusions: All therapies determined reductions on the GCF volume along time. Supragingival plaque control modulated the subgingival area during the study, reinforcing the importance of this control over the subgingival inflammatory response.
Common activation mechanism of class A GPCRs

Class A G-protein-coupled receptors (GPCRs) influence virtually every aspect of human physiology. Understanding receptor activation mechanism is critical for discovering novel therapeutics since about one-third of all marketed drugs target members of this family. GPCR activation is an allosteric process that couples agonist binding to G-protein recruitment, with the hallmark outward movement of transmembrane helix 6 (TM6). However, what leads to TM6 movement and the key residue level changes of this movement remain less well understood. Here, we report a framework to quantify conformational changes. By analyzing the conformational changes in 234 structures from 45 class A GPCRs, we discovered a common GPCR activation pathway comprising of 34 residue pairs and 35 residues. The pathway unifies previous findings into a common activation mechanism and strings together the scattered key motifs such as CWxP, DRY, Na+ pocket, NPxxY and PIF, thereby directly linking the bottom of ligand-binding pocket with G-protein coupling region. Site-directed mutagenesis experiments support this proposition and reveal that rational mutations of residues in this pathway can be used to obtain receptors that are constitutively active or inactive. The common activation pathway provides the mechanistic interpretation of constitutively activating, inactivating and disease mutations. As a module responsible for activation, the common pathway allows for decoupling of the evolution of the ligand binding site and G-protein-binding region. Such an architecture might have facilitated GPCRs to emerge as a highly successful family of proteins for signal transduction in nature.
EZH2 enhances expression of CCL5 to promote recruitment of macrophages and invasion in lung cancer

EZH2 (enhancer of zeste homolog 2) regulates epigenetic gene silencing and functions as critical regulators in various tumor progression. Macrophages infiltration promotes cancer development via stimulating tumor cell migration and invasion. However, the effect of EZH2 on macrophages infiltration, cell invasion, and migration of lung cancer remains to be investigated. In this study, we found that knockdown of EZH2 inhibited macrophages chemotaxis and decreased chemokine ligand 5 (CCL5). Wound‐healing and transwell assays results showed that migration and invasion of lung cancer cells was inhibited by EZH2 deletion. Moreover, EZH2 overexpression increased CCL5 expression. Loss‐of functional assay indicated that the promotion ability of EZH2 on macrophages chemotaxis was inhibited by CCL5 knockdown. Mechanistically, the promotion ability of EZH2 on cell migration and invasion of lung cancer was also inhibited by CCL5 knockdown. The in vivo subcutaneous xenotransplanted tumor model also revealed that silence of EZH2 suppressed lung cancer metastasis and macrophages infiltration via regulation of CCL5. In conclusion, our findings indicated that EZH2 promoted lung cancer metastasis and macrophages infiltration via upregulation of CCL5, which might be the underlying mechanism of EZH2‐induced lung cancer cell progression.
Effect of light intensity on survival, growth and physiology of rohu, Labeo rohita (Cyprinidae) fry

Abstract Purpose: Light intensity is one of the important environmental factors that have strong influence on larviculture. Culture of fish at high intensity of light generates harmful radicals in the body that can compromise their health and production. The present study aims to evaluate the effect of various light intensities on the physiology of rohu Labeo rohita fry. Materials and Methods: Rohu fry (13.56 ± 0.4 mg) were exposed at five different light intensities: 0.17 ± 0.005 (Lc, control), 1.45 ± 0.23 (L1), 2.69 ± 0.47 (L2), 3.93 ± 0.72 (L3) and 5.06 ± 0.95 Wm−2 (L4). After 90 days of culture, rohu were harvested. Results and Conclusions: A 2-5% mortality of rohu was recorded in L3 and L4 treatments. The average weight and specific growth rate were significantly (p < .05) higher in Lc treatment compared to others. The light intensity and swimming activity of rohu showed direct relationship, whereas, light intensity showed inverse relation with nitric oxide synthase and reduced glutathione levels. Significantly (p < .05) higher glutathione S-transferase and glutathione peroxidase activies were found in rohu exposed at L4 treatment. Higher light intensities resulted in oxidative stress in the muscles of rohu. Thiobarbituric acid reactive substances, carbonyl protein and heat shock protein 70 were significantly (p < .05) higher in rohu exposed at L4 compared to other treatments. Exposure of rohu fry to intense light resulted into physiological stress and immunosupression.
The Current Status and the Perspectives of Nutrition Survey.

The Korea National Health and Nutrition Examination Survey is a nationwide health survey in Korea. This survey is composed of three parts: the Health Interview Survey, the Health Examination Survey, and the Nutrition Survey. The aim of this study was to refine the nutrition survey system in the Korean National Health and Nutrition Examination Survey (KNHANES). Based on the literature review, we summarized international survey systems and the limitations of the current system in Korea and proposed an improved system. We suggested the following: 1) A government agency which will be exclusively responsible for KNHANES overall is needed. 2) The current short-term nutrition survey should be a year-round survey. 3) The objectives of this survey should be written with more clarity and detail. 4) Biochemical measures in relation to nutritional status should be added. 5) The budget to set up various databases in the nutrition survey should be increased. 6) Various other issues should be addressed, including the definition of raw data (i.e., whether nutrient intake data per day is raw data), ethical issues in survey techniques, and strategies to produce evidence for the public using this survey data. Not all suggestions could be adopted in the short-term, but should be integrated into long-term goals for survey system improvement.
FOXO1 regulates developmental lymphangiogenesis by upregulating CXCR4 in the mouse-tail dermis

ABSTRACT Lymphangiogenesis plays important roles in normal fetal development and postnatal growth. However, its molecular regulation remains unclear. Here, we have examined the function of forkhead box protein O1 (FOXO1) transcription factor, a known angiogenic factor, in developmental dermal lymphangiogenesis using endothelial cell-specific FOXO1-deficient mice. FOXO1-deficient mice showed disconnected and dilated lymphatic vessels accompanied with increased proliferation and decreased apoptosis in the lymphatic capillaries. Comprehensive DNA microarray analysis of the causes of in vivo phenotypes in FOXO1-deficient mice revealed that the gene encoding C-X-C chemokine receptor 4 (CXCR4) was the most drastically downregulated in FOXO1-deficient primary lymphatic endothelial cells (LECs). CXCR4 was expressed in developing dermal lymphatic capillaries in wild-type mice but not in FOXO1-deficient dermal lymphatic capillaries. Furthermore, FOXO1 suppression impaired migration toward the exogenous CXCR4 ligand, C-X-C chemokine ligand 12 (CXCL12), and coordinated proliferation in LECs. These results suggest that FOXO1 serves an essential role in normal developmental lymphangiogenesis by promoting LEC migration toward CXCL12 and by regulating their proliferative activity. This study provides valuable insights into the molecular mechanisms underlying developmental lymphangiogenesis. Summary: The transcription factor FOXO1 contributes to developing hierarchical lymphangiogenesis in the mouse-tail dermis by transcribing the CXCR4 chemokine receptor and controlling CXCL12-dependent cell migration and proliferation in lymphatic endothelium.
Identification of TMC1 as a relatively common cause for nonsyndromic hearing loss in the Saudi population

Hearing loss (HL) is the most common sensory disorder worldwide and genetic factors contribute to approximately half of congenital HL cases. HL is subject to extensive genetic heterogeneity, rendering molecular diagnosis difficult. Mutations of the transmembrane channel‐like 1 (TMC1) gene cause hearing defects in humans and mice. The precise function of TMC1 protein in the inner ear is unknown, although it is predicted to be involved in functional maturation of cochlear hair cells. TMC1 mutations result in autosomal recessive (DFNB7/11) and sometimes dominant (DFNA36) nonsyndromic HL. Mutations in TMC1 are responsible for a significant portion of HL, particularly in consanguineous populations. To evaluate the importance of TMC1 mutations in the Saudi population, we used a combination of autozygome‐guided candidate gene mutation analysis and targeted next generation sequencing in 366 families with HL previously shown to lack mutations in GJB2. We identified 12 families that carried five causative TMC1 mutations; including three novel (c.362+3A > G; c.758C > T [p.Ser253Phe]; c.1396_1398delACC [p.Asn466del]) and two reported mutations (c.100C > T [p.Arg34Ter]; c.1714G > A [p.Asp572Asn]). Each of the identified recessive mutation was classified as severe, by both age of onset and severity of HL. Similarly, consistent with the previously reported dominant variant p.Asp572Asn, the HL phenotype was progressive. Eight families in our cohort were found to share the pathogenic p.Arg34Ter mutation and linkage disequilibrium was observed between p.Arg34Ter and SNPs investigated. Our results indicate that TMC1 mutations account for about 3.3% (12/366) of Saudi HL cases and that the recurrent TMC1 mutation p.Arg34Ter is likely to be a founder mutation.
Modulating Macrophage Phenotype by Sustained MicroRNA Delivery Improves Host‐Implant Integration

Biomedical implant failure due to the host's response remains a challenging problem. In particular, the formation of the fibrous capsule is a common barrier for the normal function of implants. Currently, there is mounting evidence indicating that the polarization state of macrophages plays an important role in effecting the foreign body reaction (FBR). This opens up a potential avenue for improving host‐implant integration. Here, electrospun poly(caprolactone‐co‐ethyl ethylene phosphate) nanofiber scaffolds are utilized to deliver microRNAs (miRs) to induce macrophage polarization and modulate FBR. Specifically, C57BL/6 mice that are treated with M2‐inducing miRs, Let‐7c and miR‐124, display relatively thinner fibrous capsule formation around the scaffolds at both Week 2 and 4, as compared to treatment with M1‐inducing miR, Anti‐Let‐7c. Histological analysis shows that the density of blood vessels in the scaffolds are the highest in miR‐124 treatment group, followed by Anti‐Let‐7c and Let‐7c treatment groups. Based on immunohistochemical quantifications, these miR‐encapsulated nanofiber scaffolds are useful for localized and sustained delivery of functional miRs and are able to modulate macrophage polarization during the first 2 weeks of implantation to result in significant alteration in host‐implant integration at longer time points.
Cellular perspectives for improving mesophyll conductance

Summary After entering the leaf, CO2 faces an intricate pathway to the site of photosynthetic fixation embedded within the chloroplasts. The efficiency of CO2 flux is hindered by a number of structural and biochemical barriers which, together, define the ease of flow of the gas within the leaf, termed mesophyll conductance. Previous authors have identified the key elements of this pathway, raising the prospect of engineering the system to improve CO2 flux and, thus, to increase leaf photosynthetic efficiency. In this review, we provide a perspective on the potential for improving the individual elements that contribute to this complex parameter. We lay particular emphasis on generation of the cellular architecture of the leaf which sets the initial boundaries of a number of mesophyll conductance parameters, incorporating an overview of the molecular transport processes which have been proposed as major facilitators of CO2 flux across structural boundaries along the pathway. The review highlights the research areas where future effort might be invested to increase our fundamental understanding of mesophyll conductance and leaf function and, consequently, to enable translation of these findings to improve the efficiency of crop photosynthesis.