bluuebunny/crossref_metadata_2025 huggingface dataset:
What is the feasibility and observed effect of two implementation packages for stroke rehabilitation therapists implementing upper limb guidelines? A cluster controlled feasibility study
Authors: Jolliffe Laura , Hoffmann Tammy , Churilov Leonid , Lannin Natasha A
Published: May 2020

Background

Hand and arm activity after stroke improves with evidence-based rehabilitation. Therapists face known barriers when providing evidence-based rehabilitation and require support to implement guidelines. The aim of this study was to investigate the feasibility of two implementation packages on guideline adherence by occupational therapists and physiotherapists, and explore effect on patient upper limb outcomes.

Method

This was a non-randomised clustered feasibility study of occupational and physiotherapy rehabilitation services (n=3 inpatient and n=3 outpatient services). Services were allocated to one of three groups: (group A) facilitator-mediated implementation package, (group B) self-directed implementation package or (group C) usual care (control); we recruited n=1 inpatient and n=1 outpatient service per group. Outcomes of feasibility, adherence to guidelines (medical file audits) and patient upper limb impairment (Fugl-Meyer Upper Extremity Assessment), activity (Box and Block Test) and practice (minutes/week) were collected at baseline and after 3 months of intervention.

Results

29 therapists (8 in group A, 13 in groups B and 8 in group C) and 55 patients participated. Both the facilitator-mediated and the self-directed implementation packages were feasible to deliver in the rehabilitation setting. Therapists in group A improved with respect to guideline adherence (medical file audits; median within-group proportion difference of 0.29 (95% CI 0.22 to 0.36, p<0.0001) preintervention to postintervention). No significant within-group differences from baseline to postintervention were found in group B or group C, and no between-group differences were found for upper limb outcomes.

Conclusion

A facilitator-mediated package was acceptable to therapists working in stroke rehabilitation, and feasibility data suggest increased guideline uptake following implementation. An adequately powered study is planned to understand how to support therapists to provide evidence-based upper limb rehabilitation after stroke.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12619000596101).
Prompt recognition of infectious pulmonary tuberculosis is critical to achieving elimination goals: a retrospective cohort study
Authors: Heffernan Courtney , Barrie James , Doroshenko Alexander , Egedahl Mary Lou , Paulsen Catherine , Senthilselvan Ambikaipakan , Long Richard
Published: May 2020

Introduction

All pulmonary tuberculosis (PTB) cases are presumed to be infectious to some degree. This spectrum of infectiousness is independently described by both the acid-fast bacilli smear and radiographic findings. Smear-positive patients with chest radiographic findings that are typical for adult-type PTB are believed to be most infectious.

Hypothesis

Characterisation of the presumed most infectious PTB case is possible by reference to readily available clinical features and laboratory results.

Methods

Retrospective cohort study of adult, culture-positive PTB cases (151 smear-positive; 162 smear-negative) diagnosed between 1 January 2013 and 30 April 2017 in Canada. We describe cases according to demographic, clinical and laboratory features. We use multivariable multinomial logistic regression to estimate the relative risk ratio (RRR) with 95% CI of features associated with an outcome of smear-positive PTB, characterised by ‘typical’ chest radiograph findings.

Results

Being Canadian-born, symptomatic, having a subacute duration of symptoms and broad-spectrum antibiotic prescriptions were all more commonly associated with smear-positive than smear-negative disease (36% vs 20%; 95% vs 63%; 88% vs 54%; and 59% vs 28%, respectively). After combining smear status and radiographic features, we show that smear-positive patients with typical chest radiographs were younger, had a longer duration of symptoms (RRR 2.41; 95% CI 1.01 to 5.74 and 2.93; 95% CI 1.20 to 7.11, respectively) and were less likely to be foreign-born, or have a moderate to high-risk factor for reactivation (RRR 0.40; 95% CI 0.17 to 0.92 and 0.18; 95% CI 0.04 to 0.71, respectively) compared with smear-negative patients with atypical chest radiograph findings.

Conclusion

A clear picture of the presumed most infectious PTB case emerges from available historical and laboratory information; vigilance for this presentation by front-line providers will support elimination strategies aimed at reducing transmission.
Cytotoxic T-cell-related gene expression signature predicts improved survival in muscle-invasive urothelial bladder cancer patients after radical cystectomy and adjuvant chemotherapy
Authors: Eckstein Markus , Strissel Pamela , Strick Reiner , Weyerer Veronika , Wirtz Ralph , Pfannstiel Carolin , Wullweber Adrian , Lange Fabienne , Erben Philipp , Stoehr Robert , Bertz Simone , Geppert Carol Imanuel , Fuhrich Nicole , Taubert Helge , Wach Sven , Breyer Johannes , Otto Wolfgang , Burger Maximilian , Bolenz Christian , Keck Bastian , Wullich Bernd , Hartmann Arndt , Sikic Danijel
Published: May 2020

Background

Assessment of the immune status of muscle-invasive bladder cancer (MIBC) has previously shown to be prognostically relevant after treatment with curative intent. We conducted this study to develop a clinically applicable immune gene expression assay to predict prognosis and adjuvant chemotherapy benefit.

Patients and methods

Gene expression ofCD3Z,CD8AandCXCL9, immune cell (IC) populations including stromal tumor infiltrating lymphocytes (sTILs), T-cells, natural killer cells (NK-cells), macrophages, Programmed cell death protein 1 positive (PD-1) IC and tumor subtypes (MD Anderson Cancer Center/MDACC-approach) were assessed in 187 MIBC patients (Comprehensive Cancer Center Erlangen-EMN/CCC-EMN-cohort). A gene expression signature was derived by hierarchical-clustering and validated in The Cancer Genome Atlas (TCGA)-cohort. IC populations in the TCGA cohort were assessed via CIBERSORT. Benefit of platinum-containing adjuvant chemotherapy was assessed in a pooled cohort of 125 patients. Outcome measurements were disease specific survival, disease-free survival and overall survival.

Results

The gene expression signature ofCXCL9,CD3ZandCD8Acorrelates with quantitative amounts of specific IC populations and sTILs (CCC-EMN: ρ-range: 0.44–0.74; TCGA: ρ-range: 0.56–0.82) and allows stratification of three different inflammation levels (inflamed high, inflamed low, uninflamed). Highly inflamed tumors are preferentially basal subtype and show favorable 5-year survival rates of 67.3% (HR=0.27; CCC-EMN) and 55% (HR=0.41; TCGA). Uninflamed tumors are predominantly luminal subtypes and show low 5-year survival rates of 28% (CCC-EMN) and 36% (TCGA). Inflamed tumors exhibit higher levels of PD-1 and Programmed cell death 1 ligand 1 (PD-L1). Patients undergoing adjuvant platinum-based chemotherapy with ‘inflamed high’ tumors showed a favorable 5-year survival rate of 64% (HR=0.27; merged CCC-EMN and TCGA cohort).

Conclusion

The gene expression signature ofCD3Z,CD8AandCXCL9can assess the immune status of MIBC and stratify the survival of MIBC patients undergoing surgery and adjuvant platinum-based chemotherapy. Furthermore, the assay can identify patients with immunological hot tumors with particular high expression of PD-L1 potentially suitable for immunotherapy.
Optimized combinatorial pMHC class II multimer labeling for precision immune monitoring of tumor-specific CD4 T cells in patients
Authors: Rockinger Georg Alexander , Guillaume Philippe , Cachot Amélie , Saillard Margaux , Speiser Daniel E , Coukos Georges , Harari Alexandre , Romero Pedro J , Schmidt Julien , Jandus Camilla
Published: May 2020

Background

With immunotherapy gaining increasing approval for treatment of different tumor types, scientists rely on cutting edge methods for the monitoring of immune responses and biomarker development in patients. Due to the lack of tools to efficiently detect rare circulating human tumor-specific CD4 T cells, their characterization in patients still remains very limited.

Methods

We have used combinatorial staining strategies with peptide major histocompatibility complex class II (pMHCII) multimer constructs of different alleles to establish an optimized staining procedure for in vitro and direct ex-vivo visualization of tumor-specific CD4 T cells, in patient samples. Furthermore, we have generated reversible multimers to achieve optimal cell staining and yet disassemble prior to in vitro cell expansion, thus preventing activation induced cell death.

Results

We observed a vastly improved detection of tumor-specific, viral-specific and bacterial-specific cells with our optimization methods compared with the non-optimized staining procedure. By increasing the variety of fluorochromes used to label the pMHCII multimers, we were also able to increase the parallel detection of different specificities within one sample, including antigen-specific CD8 T cells. A decrease in cell viability was observed when using the full optimization method, but this was mitigated by the removal of neuraminidase and the use of reversible multimers.

Conclusion

This new optimized staining procedure represents an advance toward better detection and analysis of antigen-specific CD4 T cells. It should facilitate state-of-the art precision monitoring of tumor-specific CD4 T cells and contribute to accelerate the use and the targeting of these cells in cancer immunotherapy.
Quark structure of the $$\chi _{\mathrm{c}}(3P)$$ and X(4274) resonances and their strong and radiative decays
Authors: Ferretti J. , Santopinto E. , Anwar M. Naeem , Lu Yu
Published: May 2020

We calculate the masses of $$\chi _{\mathrm{c}}(3P)$$χc(3P) states with threshold corrections in a coupled-channel model. The model was recently applied to the description of the properties of $$\chi _{\mathrm{c}}(2P)$$χc(2P) and $$\chi _{\mathrm{b}}(3P)$$χb(3P) multiplets (Ferretti and Santopinto in Phys Lett B 789:550, 2019]. We also compute the open-charm strong decay widths of the $$\chi _{\mathrm{c}}(3P)$$χc(3P) states and their radiative transitions. According to our predictions, the $$\chi _{\mathrm{c}}(3P)$$χc(3P) states should be dominated by the charmonium core, but they may also show small meson-meson components. The X(4274) is interpreted as a $$c {{\bar{c}}}$$cc¯$$\chi _{\mathrm{c1}}(3P)$$χc1(3P) state. More information on the other members of the $$\chi _{\mathrm{c}}(3P)$$χc(3P) multiplet, as well as a more rigorous analysis of the X(4274)’s decay modes, are needed to provide further indications on the quark structure of the previous resonance.
Studying programming in the neuroage
Authors: Siegmund Janet , Peitek Norman , Brechmann André , Parnin Chris , Apel Sven
Published: May 2020

Programming research has entered the Neuroage.
Contextual word representations
Authors: Smith Noah A.
Published: May 2020

Advances in how programs treat natural language words have a big impact in AI.
AI and accessibility
Authors: Morris Meredith Ringel
Published: May 2020

A discussion of ethical considerations.
Meltdown
Authors: Lipp Moritz , Schwarz Michael , Gruss Daniel , Prescher Thomas , Haas Werner , Horn Jann , Mangard Stefan , Kocher Paul , Genkin Daniel , Yarom Yuval , Hamburg Mike , Strackx Raoul
Published: May 2020

Lessons learned from Meltdown's exploitation of the weaknesses in today's processors.
The 'invisible' materiality of information technology
Authors: Borning Alan , Friedman Batya , Logler Nick
Published: May 2020

It's difficult to see the ecological impact of IT when its benefits are so blindingly bright.
Street lamps as a platform
Authors: Mühlhäuser Max , Meurisch Christian , Stein Michael , Daubert Jörg , Von Willich Julius , Riemann Jan , Wang Lin
Published: May 2020

Strategically augmented street lamps can become the key enabling technology in smart cities.
Communicate using the numbers 1, 2, 3, and more
Authors: Limoncelli Thomas A.
Published: May 2020

Leveraging expectations for better communication.
Commit to memory
Authors: Frazelle Jessie
Published: May 2020

Chipping away at Moore's Law.
Detecting/preventing infections, and moving instruction online
Authors: DeFranco Terrence , Roschelle Jeremy
Published: May 2020

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

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Terrence DeFranco suggests the Internet of Things could be keeping us safer, and Jeremy Roschelle airs issues related to online instruction.
Leveraging unlabeled data
Authors: Edwards Chris
Published: May 2020

Deep learning looks for better pretexts.
Hiring from the autism spectrum
Authors: Shein Esther
Published: May 2020

Companies increasingly are looking to hire people who are on the autism spectrum to fill IT roles.
Seeing through walls
Authors: Savage Neil
Published: May 2020

Artificial intelligence makes sense of radio signals to understand what someone in another room is doing.
An animating spirit
Authors: Savage Neil
Published: May 2020

ACM A.M. Turing Award recipients, Ed Catmull and Pat Hanrahan, overcame industry indifference to found Pixar and put their computer graphics expertise to work.
Attaining the third dimension
Authors: Hoffmann Leah
Published: May 2020

ACM A.M. Turing Award recipients Ed Catmull and Pat Hanrahan discuss how they helped to bring the power of three-dimensional imagery to computer graphics.
Data-driven algorithm design
Authors: Gupta Rishi , Roughgarden Tim
Published: May 2020

The best algorithm for a computational problem generally depends on the "relevant inputs," a concept that depends on the application domain and often defies formal articulation. Although there is a large literature on empirical approaches to selecting the best algorithm for a given application domain, there has been surprisingly little theoretical analysis of the problem.

We model the problem of identifying a good algorithm from data as a statistical learning problem. Our framework captures several state-of-the-art empirical and theoretical approaches to the problem, and our results identify conditions under which these approaches are guaranteed to perform well. We interpret our results in the contexts of learning greedy heuristics, instance feature-based algorithm selection, and parameter tuning in machine learning.
How to curtail oversensing in the home
Authors: Bolton Connor , Fu Kevin , Hester Josiah , Han Jun
Published: May 2020

Limiting sensitive information leakage via smart-home sensor data.
The Emerging Landscape of Edge Computing
Authors: Noghabi Shadi A. , Cox Landon , Agarwal Sharad , Ananthanarayanan Ganesh
Published: May 2020

Edge computing is a trending notion introduced a decade ago as a new computing paradigm for interactive mobile applications. The initial vision of the edge was a multi-tenant resource that will be used opportunistically for low-latency mobile applications. Despite that vision, we see in practice a different set of applications, driven by large-scale enterprises that have emerged and are driving realworld edge deployments today. In these applications, the edge is the primary place of storage and computation and, if network conditions allow, the cloud is opportunistically used alongside. We show how these enterprise deployments are driving innovation in edge computing. Enterprise-driven scenarios have a different motivation for using the edge. Instead of latency, the primary factors are limited bandwidth and unreliability of the network link to the cloud. The enterprise deployment layout is also unique: on-premise, single-tenant edges with shared, redundant outbound links. These previously unexplored characteristics of enterprise-driven edge scenarios open up a number of unique and exciting future research challenges for our community.
Strobe: Towards Low-Cost Soil Sensing Using Wi-Fi
Authors: Ding Jian , Chandra Ranveer
Published: May 2020

The knowledge of soil moisture and electrical conductivity (EC) is critical for a variety of agricultural applications. For example, precision irrigation, which refers to the variable application of water in different regions of the farm, depends on accurate soil moisture values at different depths. This technique helps reduce water use, and also reduces soil leaching and contamination of ground water by chemicals in fertilizers and other agricultural inputs. Soil EC is another key indicator of soil health. It has been shown to correlate very well with crop yield and plant nutrient availability, and the USDA recommends that farmers measure soil EC to determine soil treatment plans and management zones for Precision Agriculture [1].
eBP
Authors: Bui Nam , Pham Nhat , Truong Hoang , Nguyen Phuc , Xiao Jianliang , Deterding Robin , Dinh Thang , Vu Tam
Published: May 2020

Diagnosing hypertension or hemodialysis requires patients to carry a blood pressure (BP) monitoring device for 24 hours. Th erefore, wearing the wrist/arm-based BP monitoring device, in this case, has a signifi cant impact on users' daily activities. To address the problem, we developed eBP, an ear-worn device that measures blood pressure from inside the ear. Th rough the evaluation of 35 subjects, eBP can achieve the average error of 1.8 mmHg for systolic BP and -3.1 mmHg for diastolic BP with the standard deviation error of 7.2 mmHg and 7.9 mmHg, respectively.
The Responsibility Not to Veto Revisited under the Theory of ‘Consequential Jus Cogens’
Authors: Essawy Rana M.
Published: May 2020

In this article, I argue that contemporary international law imposes an obligation upon the UN Security Council permanent members to refrain from using their veto repeatedly in ways that impede the Council from acting against violations of peremptory norms. This obligation not to veto emanates from the duty to cooperate to end violations of peremptory norms as enshrined in Article 41(1) of the International Law Commission Articles on State Responsibility. For this purpose, I demonstrate that the duty to cooperate itself possesses a peremptory character under the theory of ‘consequential jus cogens’, whereby effects of jus cogens norms are themselves peremptory. In doing so, this article contributes to the ongoing debates concerning the legal nature of the effects of jus cogens norms by showing that the theory of ‘consequential jus cogens’ is an application of the generally accepted maxim accessorium sequitur principale and thus forms part of positive international law.
Pirfenidone alleviates pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways
Authors: Lv Qun , Wang Jianjun , Xu Changqing , Huang Xuqing , Ruan Zhaoyang , Dai Yifan
Published: May 2020

Background

Pirfenidone (PFD) is effective for pulmonary fibrosis (PF), but its action mechanism has not been fully explained. This study explored the signaling pathways involved in anti-fibrosis role of PFD, thus laying a foundation for clinical application.

Methods

Pulmonary fibrosis mice models were constructed by bleomycin (BLM), and TGF-β1 was used to treat human fetal lung fibroblasts (HLFs). Then, PFD was added into treated mice and cells alone or in combination with β-catenin vector. The pathological changes, inflammatory factors levels, and Collagen I levels in mice lung tissues were assessed, as well as the activity of HLFs was measured. Levels of indices related to extracellular matrix, epithelial-mesenchymal transition (EMT), Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways were determined in tissues or cells.

Results

After treatment with BLM, the inflammatory reaction and extracellular matrix deposition in mice lung tissues were serious, which were alleviated by PFD and aggravated by the addition of β-catenin. In HLFs, PFD reduced the activity of HLFs induced by TGF-β1, inhibited levels of vimentin and N-cadherin and promoted levels of E-cadherin, whereas β-catenin produced the opposite effects to PFD. In both tissues and cells, Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways were activated, which could be suppressed by PFD.

Conclusions

PFD alleviated pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways, which might further improve the action mechanism of anti-fibrosis effect of PFD.
Sensitivity of censored data analysis to determine the characteristic value of structural timber
Authors: Pang Sung-Jun , Lee Hyeon-Jeong , Ahn Kyung-Sun , Oh Jung-Kwon
Published: May 2020

In structural timber tests, unintended failure mechanisms occur frequently in specimens and their results are called censored data. There are two censored data analysis: censored maximum likelihood estimation (CMLE) and Kaplan–Meier (KM) method. In this study, the precision of the censored data analysis was investigated to determine the characteristic value, 5th percentile value, of the structural timber. The results show that (1) the 5th percentile value was underestimated by ordinary data analysis methods; maximum likelihood estimation (MLE) and Order statistics. (2) CMLE with 30% lower tail censored data and KM method provided much more precise 5th percentile value. (3) The amount of under-measurement (5 MPa, 10 MPa, and 15 MPa in this simulation study) did not show significant effect on the 5th percentile determination in CMLE and KM method, but the proportion of censored data (percentage of unintended failure specimen; 10%, 20%, 30%, and 40%) affected the determination of 5th percentile value. (4) CMLE with 30% lower tail censored data and KM method showed good agreement in case that the data included unintended failure data up to 20%.
Persistent post-traumatic headache: a migrainous loop or not? The clinical evidence
Authors:   On behalf of the European Headache Federation School of Advanced Studies (EHF-SAS), Labastida-Ramírez Alejandro , Benemei Silvia , Albanese Maria , D’Amico Antonina , Grillo Giovanni , Grosu Oxana , Ertem Devrimsel Harika , Mecklenburg Jasper , Fedorova Elena Petrovna , Řehulka Pavel , di Cola Francesca Schiano , Lopez Javier Trigo , Vashchenko Nina , MaassenVanDenBrink Antoinette , Martelletti Paolo
Published: May 2020

Background

Headache is a common complication of traumatic brain injury. The International Headache Society defines post-traumatic headache as a secondary headache attributed to trauma or injury to the head that develops within seven days following trauma. Acute post-traumatic headache resolves after 3 months, but persistent post-traumatic headache usually lasts much longer and accounts for 4% of all secondary headache disorders.

Main body

The clinical features of post-traumatic headache after traumatic brain injury resemble various types of primary headaches and the most frequent are migraine-like or tension-type-like phenotypes. The neuroimaging studies that have compared persistent post-traumatic headache and migraine found different structural and functional brain changes, although migraine and post-traumatic headache may be clinically similar. Therapy of various clinical phenotypes of post-traumatic headache almost entirely mirrors the therapy of the corresponding primary headache and are currently based on expert opinion rather than scientific evidence. Pharmacologic therapies include both abortive and prophylactic agents with prophylaxis targeting comorbidities, especially impaired sleep and post-traumatic disorder. There are also effective options for non-pharmacologic therapy of post-traumatic headache, including cognitive-behavioral approaches, onabotulinum toxin injections, life-style considerations, etc.

Conclusion

Notwithstanding some phenotypic similarities, persistent post-traumatic headache after traumatic brain injury, is considered a separate phenomenon from migraine but available data is inconclusive. High-quality studies are further required to investigate the pathophysiological mechanisms of this secondary headache, in order to identify new targets for treatment and to prevent disability.
Study on the Color Compensation Effect of Composite Orange-Red Quantum Dots in WLED Application
Authors: Hu Xiaoyue , Xie Yangyang , Geng Chong , Xu Shu , Bi Wengang
Published: May 2020

Quantum dots (QDs) as emerging light-converting materials show the advantage of enhancing color quality of white light-emitting diode (WLED). However, WLEDs employing narrow-emitting monochromic QDs usually present unsatisfactory color rendering in the orange region. Herein, composite orange-red QDs (composite-QDs) are developed through mixing CdSe/ZnS-based orange QDs (O-QDs) and red QDs (R-QDs) to compensate the orange-red light for WLEDs. We investigated the effect of self-absorption and fluorescence resonance energy transfer (FRET) process in composite-QDs on the spectral controllability and fluorescent quenching in WLEDs. The concentration and donor/acceptor ratios were also taken into account to analyze the FRET efficiency and help identify suitable composite-QDs for color compensation in the orange-red light region. As the result, the optimized composite-QDs effectively improve the color rendering index of the WLED compared with monochromatic QDs.
Effects of cryopreservation and long-term culture on biological characteristics and proteomic profiles of human umbilical cord-derived mesenchymal stem cells
Authors: Fu Xufeng , Xu Bo , Jiang Jiang , Du Xing , Yu Xiaoli , Yan Yaping , Li Shanshan , Inglis Briauna Marie , Ma Huiming , Wang Hongyan , Pei Xiuying , Si Wei
Published: May 2020

Background

Human umbilical cord-derived MSCs (hUC-MSCs) have been identified as promising seeding cells in tissue engineering and clinical applications of regenerative medicine due to their advantages of simple acquisition procedure and the capability to come from a young tissue donor over the other MSCs sources. In clinical applications, large scale production is required and optimal cryopreservation and culture conditions are essential to autologous and allogeneic transplantation in the future. However, the influence of cryopreserved post-thaw and long-term culture on hUC-MSCs remains unknown, especially in terms of specific protein expression. Therefore, biological characteristics and proteomic profiles of hUC-MSCs after cryopreserving and long-term culturing were investigated.

Methods

Firstly, hUC-MSCs were isolated from human umbilical cord tissues and identified through morphology, surface markers and tri-lineage differentiation potential at passage 3, and then the biological characteristics and proteomic profiles were detected and compared after cryopreserving and long-term culturing at passage 4 and continuously cultured to passage 10 with detection occurring here as well. The proteomic profiles were tested by using the isobaric tags for relative and absolute quantification (iTRAQ) labeling technique and differential protein were confirmed by mass spectrometry.

Results

The results showed no significant differences in phenotypes including morphology, surface marker and tri-lineage differentiation potential but have obvious changes in translation level, which is involved in metabolism, cell cycle and other pathways.

Conclusion

This suggests that protein expression may be used as an indicator of hUC-MSCs security testing before applying in clinical settings, and it is also expected to provide the foundation or standardization guide of hUC-MSCs applications in regenerative medicine.
Identification of TUBB2A by quantitative proteomic analysis as a novel biomarker for the prediction of distant metastatic breast cancer
Authors: Shin Dongyoon , Park Joonho , Han Dohyun , Moon Ji Hye , Ryu Han Suk , Kim Youngsoo
Published: May 2020

Background

Metastasis of breast cancer to distal organs is fatal. However, few studies have identified biomarkers that are associated with distant metastatic breast cancer. Furthermore, the inability of current biomarkers, such as HER2, ER, and PR, to differentiate between distant and nondistant metastatic breast cancers accurately has necessitated the development of novel biomarker candidates.

Methods

An integrated proteomics approach that combined filter-aided sample preparation, tandem mass tag labeling (TMT), high pH fractionation, and high-resolution MS was applied to acquire in-depth proteomic data from FFPE distant metastatic breast cancer tissues. A bioinformatics analysis was performed with regard to gene ontology and signaling pathways using differentially expressed proteins (DEPs) to examine the molecular characteristics of distant metastatic breast cancer. In addition, real-time polymerase chain reaction (RT-PCR) and invasion/migration assays were performed to validate the differential regulation and function of our protein targets.

Results

A total of 9441 and 8746 proteins were identified from the pooled and individual sample sets, respectively. Based on our criteria, TUBB2A was selected as a novel biomarker candidate. The metastatic activities of TUBB2A were subsequently validated. In our bioinformatics analysis using DEPs, we characterized the overall molecular features of distant metastasis and measured differences in the molecular functions of distant metastatic breast cancer between breast cancer subtypes.

Conclusions

Our report is the first study to examine the distant metastatic breast cancer proteome using FFPE tissues. The depth of our dataset allowed us to discover a novel biomarker candidate and a proteomic characteristics of distant metastatic breast cancer. Distinct molecular features of various breast cancer subtypes were also established. Our proteomic data constitute a valuable resource for research on distant metastatic breast cancer.
Data-based RNA-seq simulations by binomial thinning
Authors: Gerard David
Published: May 2020

Background

With the explosion in the number of methods designed to analyze bulk and single-cell RNA-seq data, there is a growing need for approaches that assess and compare these methods. The usual technique is to compare methods on data simulated according to some theoretical model. However, as real data often exhibit violations from theoretical models, this can result in unsubstantiated claims of a method’s performance.

Results

Rather than generate data from a theoretical model, in this paper we develop methods to add signal to real RNA-seq datasets. Since the resulting simulated data are not generated from an unrealistic theoretical model, they exhibit realistic (annoying) attributes of real data. This lets RNA-seq methods developers assess their procedures in non-ideal (model-violating) scenarios. Our procedures may be applied to both single-cell and bulk RNA-seq. We show that our simulation method results in more realistic datasets and can alter the conclusions of a differential expression analysis study. We also demonstrate our approach by comparing various factor analysis techniques on RNA-seq datasets.

Conclusions

Using data simulated from a theoretical model can substantially impact the results of a study. We developed more realistic simulation techniques for RNA-seq data. Our tools are available in the R package on the Comprehensive R Archive Network:https://cran.r-project.org/package=seqgendiff.
PACVr: plastome assembly coverage visualization in R
Authors: Gruenstaeudl Michael , Jenke Nils
Published: May 2020

Background

Plastid genomes typically display a circular, quadripartite structure with two inverted repeat regions, which challenges automatic assembly procedures. The correct assembly of plastid genomes is a prerequisite for the validity of subsequent analyses on genome structure and evolution. The average coverage depth of a genome assembly is often used as an indicator of assembly quality. Visualizing coverage depth across a draft genome is a critical step, which allows users to inspect the quality of the assembly and, where applicable, identify regions of reduced assembly confidence. Despite the interplay between genome structure and assembly quality, no contemporary, user-friendly software tool can visualize the coverage depth of a plastid genome assembly while taking its quadripartite genome structure into account. A software tool is needed that fills this void.

Results

We introduce ’PACVr’, an R package that visualizes the coverage depth of a plastid genome assembly in relation to the circular, quadripartite structure of the genome as well as the individual plastome genes. By using a variable window approach, the tool allows visualizations on different calculation scales. It also confirms sequence equality of, as well as visualizes gene synteny between, the inverted repeat regions of the input genome. As a tool for plastid genomics, PACVr provides the functionality to identify regions of coverage depth above or below user-defined threshold values and helps to identify non-identical IR regions. To allow easy integration into bioinformatic workflows, PACVr can be invoked from a Unix shell, facilitating its use in automated quality control. We illustrate the application of PACVr on four empirical datasets and compare visualizations generated by PACVr with those of alternative software tools.

Conclusions

PACVr provides a user-friendly tool to visualize (a) the coverage depth of a plastid genome assembly on a circular, quadripartite plastome map and in relation to individual plastome genes, and (b) gene synteny across the inverted repeat regions. It contributes to optimizing plastid genome assemblies and increasing the reliability of publicly available plastome sequences. The software, example datasets, technical documentation, and a tutorial are available with the package at https://cran.r-project.org/package=PACVr.
A novel investigation of the effect of iterations in sliding semi-landmarks for 3D human facial images
Authors: Nazri Azree , Agbolade Olalekan , Yaakob Razali , Ghani Abdul Azim , Cheah Yoke Kqueen
Published: May 2020

Background

Landmark-based approaches of two- or three-dimensional coordinates are the most widely used in geometric morphometrics (GM). As human face hosts the organs that act as the central interface for identification, more landmarks are needed to characterize biological shape variation. Because the use of few anatomical landmarks may not be sufficient for variability of some biological patterns and form, sliding semi-landmarks are required to quantify complex shape.

Results

This study investigates the effect of iterations in sliding semi-landmarks and their results on the predictive ability in GM analyses of soft-tissue in 3D human face. Principal Component Analysis (PCA) is used for feature selection and the gender are predicted using Linear Discriminant Analysis (LDA) to test the effect of each relaxation state. The results show that the classification accuracy is affected by the number of iterations but not in progressive pattern. Also, there is stability at 12 relaxation state with highest accuracy of 96.43% and an unchanging decline after the 12 relaxation state.

Conclusions

The results indicate that there is a particular number of iteration or cycle where the sliding becomes optimally relaxed. This means the higher the number of iterations is not necessarily the higher the accuracy.
Substitution matrix based color schemes for sequence alignment visualization
Authors: Kunzmann Patrick , Mayer Benjamin E. , Hamacher Kay
Published: May 2020

Background

Visualization of multiple sequence alignments often includes colored symbols, usually characters encoding amino acids, according to some (physical) properties, such as hydrophobicity or charge. Typically, color schemes are created manually, so that equal or similar colors are assigned to amino acids that share similar properties. However, this assessment is subjective and may not represent the similarity of symbols very well.

Results

In this article we propose a different approach for color scheme creation: We leverage the similarity information of a substitution matrix to derive an appropriate color scheme. Similar colors are assigned to high scoring pairs of symbols, distant colors are assigned to low scoring pairs. In order to find these optimal points in color space a simulated annealing algorithm is employed.

Conclusions

Using the substitution matrix as basis for a color scheme is consistent with the alignment, which itself is based on the very substitution matrix. This approach allows fully automatic generation of new color schemes, even for special purposes which have not been covered, yet, including schemes for structural alphabets or schemes that are adapted for people with color vision deficiency.
RintC: fast and accuracy-aware decomposition of distributions of RNA secondary structures with extended logsumexp
Authors: Takizawa Hiroki , Iwakiri Junichi , Asai Kiyoshi
Published: May 2020

Background

Analysis of secondary structures is essential for understanding the functions of RNAs. Because RNA molecules thermally fluctuate, it is necessary to analyze the probability distributions of their secondary structures. Existing methods, however, are not applicable to long RNAs owing to their high computational complexity. Additionally, previous research has suffered from two numerical difficulties: overflow and significant numerical errors.

Result

In this research, we reduced the computational complexity of calculating the landscape of the probability distribution of secondary structures by introducing a maximum-span constraint. In addition, we resolved numerical computation problems through two techniques: extended logsumexp and accuracy-guaranteed numerical computation. We analyzed the stability of the secondary structures of 16S ribosomal RNAs at various temperatures without overflow. The results obtained are consistent with previous research on thermophilic bacteria, suggesting that our method is applicable in thermal stability analysis. Furthermore, we quantitatively assessed numerical stability using our method..

Conclusion

These results demonstrate that the proposed method is applicable to long RNAs..
VADR: validation and annotation of virus sequence submissions to GenBank
Authors: Schäffer Alejandro A. , Hatcher Eneida L. , Yankie Linda , Shonkwiler Lara , Brister J. Rodney , Karsch-Mizrachi Ilene , Nawrocki Eric P.
Published: May 2020

Background

GenBank contains over 3 million viral sequences. The National Center for Biotechnology Information (NCBI) previously made available a tool for validating and annotating influenza virus sequences that is used to check submissions to GenBank. Before this project, there was no analogous tool in use for non-influenza viral sequence submissions.

Results

We developed a system called VADR (Viral Annotation DefineR) that validates and annotates viral sequences in GenBank submissions. The annotation system is based on the analysis of the input nucleotide sequence using models built from curated RefSeqs. Hidden Markov models are used to classify sequences by determining the RefSeq they are most similar to, and feature annotation from the RefSeq is mapped based on a nucleotide alignment of the full sequence to a covariance model. Predicted proteins encoded by the sequence are validated with nucleotide-to-protein alignments using BLAST. The system identifies 43 types of “alerts” that (unlike the previous BLAST-based system) provide deterministic and rigorous feedback to researchers who submit sequences with unexpected characteristics. VADR has been integrated into GenBank’s submission processing pipeline allowing for viral submissions passing all tests to be accepted and annotated automatically, without the need for any human (GenBank indexer) intervention. Unlike the previous submission-checking system, VADR is freely available (https://github.com/nawrockie/vadr) for local installation and use. VADR has been used for Norovirus submissions since May 2018 and for Dengue virus submissions since January 2019. Since March 2020, VADR has also been used to check SARS-CoV-2 sequence submissions. Other viruses with high numbers of submissions will be added incrementally.

Conclusion

VADR improves the speed with which non-flu virus submissions to GenBank can be checked and improves the content and quality of the GenBank annotations. The availability and portability of the software allow researchers to run the GenBank checks prior to submitting their viral sequences, and thereby gain confidence that their submissions will be accepted immediately without the need to correspond with GenBank staff. Reciprocally, the adoption of VADR frees GenBank staff to spend more time on services other than checking routine viral sequence submissions.
Subcellular location prediction of apoptosis proteins using two novel feature extraction methods based on evolutionary information and LDA
Authors: Du Lei , Meng Qingfang , Chen Yuehui , Wu Peng
Published: May 2020

Background

Apoptosis, also called programmed cell death, refers to the spontaneous and orderly death of cells controlled by genes in order to maintain a stable internal environment. Identifying the subcellular location of apoptosis proteins is very helpful in understanding the mechanism of apoptosis and designing drugs. Therefore, the subcellular localization of apoptosis proteins has attracted increased attention in computational biology. Effective feature extraction methods play a critical role in predicting the subcellular location of proteins.

Results

In this paper, we proposed two novel feature extraction methods based on evolutionary information. One of the features obtained the evolutionary information via the transition matrix of the consensus sequence (CTM). And the other utilized the evolutionary information from PSSM based on absolute entropy correlation analysis (AECA-PSSM). After fusing the two kinds of features, linear discriminant analysis (LDA) was used to reduce the dimension of the proposed features. Finally, the support vector machine (SVM) was adopted to predict the protein subcellular locations. The proposed CTM-AECA-PSSM-LDA subcellular location prediction method was evaluated using the CL317 dataset and ZW225 dataset. By jackknife test, the overall accuracy was 99.7% (CL317) and 95.6% (ZW225) respectively.

Conclusions

The experimental results show that the proposed method which is hopefully to be a complementary tool for the existing methods of subcellular localization, can effectively extract more abundant features of protein sequence and is feasible in predicting the subcellular location of apoptosis proteins.
Bio-semantic relation extraction with attention-based external knowledge reinforcement
Authors: Li Zhijing , Lian Yuchen , Ma Xiaoyong , Zhang Xiangrong , Li Chen
Published: May 2020

Background

Semantic resources such as knowledge bases contains high-quality-structured knowledge and therefore require significant effort from domain experts. Using the resources to reinforce the information retrieval from the unstructured text may further exploit the potentials of such unstructured text resources and their curated knowledge.

Results

The paper proposes a novel method that uses a deep neural network model adopting the prior knowledge to improve performance in the automated extraction of biological semantic relations from the scientific literature. The model is based on a recurrent neural network combining the attention mechanism with the semantic resources, i.e., UniProt and BioModels. Our method is evaluated on the BioNLP and BioCreative corpus, a set of manually annotated biological text. The experiments demonstrate that the method outperforms the current state-of-the-art models, and the structured semantic information could improve the result of bio-text-mining.

Conclusion

The experiment results show that our approach can effectively make use of the external prior knowledge information and improve the performance in the protein-protein interaction extraction task. The method should be able to be generalized for other types of data, although it is validated on biomedical texts.
Aligning functional network constraint to evolutionary outcomes
Authors: Wollenberg Valero Katharina C.
Published: May 2020

Background

Functional constraint through genomic architecture is suggested to be an important dimension of genome evolution, but quantitative evidence for this idea is rare. In this contribution, existing evidence and discussions on genomic architecture as constraint for convergent evolution, rapid adaptation, and genic adaptation are summarized into alternative, testable hypotheses. Network architecture statistics from protein-protein interaction networks are then used to calculate differences in evolutionary outcomes on the example of genomic evolution in yeast, and the results are used to evaluate statistical support for these longstanding hypotheses.

Results

A discriminant function analysis lent statistical support to classifying the yeast interactome into hub, intermediate and peripheral nodes based on network neighborhood connectivity, betweenness centrality, and average shortest path length. Quantitative support for the existence of genomic architecture as a mechanistic basis for evolutionary constraint is then revealed through utilizing these statistical parameters of the protein-protein interaction network in combination with estimators of protein evolution.

Conclusions

As functional genetic networks are becoming increasingly available, it will now be possible to evaluate functional genetic network constraint against variables describing complex phenotypes and environments, for better understanding of commonly observed deterministic patterns of evolution in non-model organisms. The hypothesis framework and methodological approach outlined herein may help to quantify the extrinsic versus intrinsic dimensions of evolutionary constraint, and result in a better understanding of how fast, effectively, or deterministically organisms adapt.
The features of polyglutamine regions depend on their evolutionary stability
Authors: Mier Pablo , Andrade-Navarro Miguel A.
Published: May 2020

Background

Polyglutamine regions (polyQ) are one of the most studied and prevalent homorepeats in eukaryotes. They have a particular length-dependent codon usage, which relates to a characteristic CAG-slippage mechanism. Pathologically expanded tracts of polyQ are known to form aggregates and are involved in the development of several human neurodegenerative diseases. The non-pathogenic function of polyQ is to mediate protein-protein interactions via a coiled-coil pairing with an interactor. They are usually located in a helical context.

Results

Here we study the stability of polyQ regions in evolution, using a set of 60 proteomes from four distinct taxonomic groups (Insecta, Teleostei, Sauria and Mammalia). The polyQ regions can be distinctly grouped in three categories based on their evolutionary stability: stable, unstable by length variation (inserted), and unstable by mutations (mutated). PolyQ regions in these categories can be significantly distinguished by their glutamine codon usage, and we show that the CAG-slippage mechanism is predominant in inserted polyQ of Sauria and Mammalia. The polyQ amino acid context is also influenced by the polyQ stability, with a higher proportion of proline residues around inserted polyQ. By studying the secondary structure of the sequences surrounding polyQ regions, we found that regarding the structural conformation around a polyQ, its stability category is more relevant than its taxonomic information. The protein-protein interaction capacity of a polyQ is also affected by its stability, as stable polyQ have more interactors than unstable polyQ.

Conclusions

Our results show that apart from the sequence of a polyQ, information about its orthologous sequences is needed to assess its function. Codon usage, amino acid context, structural conformation and the protein-protein interaction capacity of polyQ from all studied taxa critically depend on the region stability. There are however some taxa-specific polyQ features that override this importance. We conclude that a taxa-driven evolutionary analysis is of the highest importance for the comprehensive study of any feature of polyglutamine regions.